A Shared Receptor Suggests a Common Ancestry between an Insecticidal Bacillus thuringiensis Cry Protein and an Anti-Cancer Parasporin.

Cry toxins, produced by the bacterium Bacillus thuringiensis, are of significant agronomic value worldwide due to their potent and highly specific activity against various insect orders. However, some of these pore-forming toxins display specific activity against a range of human cancer cells whilst possessing no known insecticidal activity; Cry41Aa is one such toxin. Cry41Aa has similarities to its insecticidal counterparts in both its 3-domain toxic core structure and pore-forming abilities, but how it has evolved to target human cells is a mystery. This work shows that some insecticidal Cry toxins can enhance the toxicity of Cry41Aa against hepatocellular carcinoma cells, despite possessing no intrinsic toxicity themselves. This interesting crossover is not limited to human cancer cells, as Cry41Aa was found to inhibit some Aedes-active Cry toxins in mosquito larval assays. Here, we present findings that suggest that Cry41Aa shares a receptor with several insecticidal toxins, indicating a stronger evolutionary relationship than their divergent activities might suggest.

Resurgence of influenza with increased genetic diversity of circulating viruses during the 2022-2023 season.

Introduction. After two seasons of absence and low circulation, influenza activity increased significantly in the winter of 2022-2023. This study aims to characterize virological and epidemiological aspects of influenza infection in Bulgaria during the 2022-2023 season and perform a phylogenetic/molecular analysis of the hemagglutinin (HA) and neuraminidase (NA) sequences of representative influenza strains.Hypothesis/Gap Statement. Influenza A and B viruses generate new genetic groups/clades each season, replacing previously circulating variants. This results in increased antigenic distances from current vaccine strains. Strengthening existing influenza surveillance is essential to meet the challenges posed by the co-circulation of influenza and SARS-CoV-2.Methodology. We tested 2713 clinical samples from patients with acute respiratory illnesses using a multiplex real-time RT-PCR kit (FluSC2) to detect influenza A/B and Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2) simultaneously. Representative Bulgarian influenza strains were sequenced at the WHO Collaborating Centres in London, UK, and Atlanta, USA.Results. Influenza virus was detected in 694 (25.6 %) patients. Of these, 364 (52.4 %), 213 (30.7 %) and 117 (16.9 %) were positive for influenza A(H1N1)pdm09, A(H3N2) and B/Victoria lineage virus, respectively. HA genes of the 47 influenza A(H1N1)pdm09 viruses fell into clades 5a.2. and 5a.2a.1 within the 6B.5A.1A.5a.2 group. Twenty-seven A(H3N2) viruses belonging to subclades 2b, 2a.1, 2a.1b and 2a.3a.1 within the 3C.2a1b.2a.2 group were analysed. All 23 sequenced B/Victoria lineage viruses were classified into the V1A.3a.2 group. We identified amino acid substitutions in HA and NA compared with the vaccine strains, including several substitutions in the HA antigenic sites.Conclusion. The study's findings showed genetic diversity among the influenza A viruses and, to a lesser extent, among B viruses, circulating in the first season after the lifting of anti-COVID-19 measures.

Heterologous Expression and Biochemical Characterization of a Novel Lytic Polysaccharide Monooxygenase from Chitinilyticum aquatile CSC-1.

Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes that catalyze the oxidative cleavage of recalcitrant polysaccharides. There are limited reports on LPMOs capable of concurrently catalyzing the oxidative cleavage of both cellulose and chitin. In this study, we identified and cloned a novel LPMO from the newly isolated bacterium Chitinilyticum aquatile CSC-1, designated as CaLPMO10. When using 2, 6-dimethylphenol (2, 6-DMP) as the substrate, CaLPMO10 exhibited optimal activity at 50 °C and pH 8, demonstrating good temperature stability at 30 °C. Even after a 6 h incubation at pH 8 and 30 °C, CaLPMO10 retained approximately 83.03 ± 1.25% residual enzyme activity. Most metal ions were found to enhance the enzyme activity of CaLPMO10, with ascorbic acid identified as the optimal reducing agent. Mass spectrometry analysis indicated that CaLPMO10 displayed oxidative activity towards both chitin and cellulose, identifying it as a C1/C4-oxidized LPMO. CaLPMO10 shows promise as a key enzyme for the efficient utilization of biomass resources in future applications.

The Affective Charge of Sulphur and Salt in Working with Compulsion.

The author presents a long analysis of a patient, Giulia, whose obstinate will to achieve evokes the workings of alchemical sulphur at its fieriest and a dread of its coniunctio with alchemical salt. Jung's description of these symbols in Mysterium Coniunctionis offers a useful imaginal perspective to clinical work in the area of compulsion and its possible transformations. Right from the start, the analytic relationship appeared to be mirrored and affected by this alchemical perspective. However, it was only after much time, uncertainty and emotional endurance that a fuller psychological experience of sulphur and salt could be accessed, allowing the analysis to take a more imaginative and mercurial turn. In the course of his work with Giulia the author has witnessed and experienced a range of intense affects-the many colours that the combustion of sulphur can generate-whether on the verge of unstoppable creation or ruthless destruction, often of archetypal intensity. This experience has been lived through and has undergone a transformative relation with salt, which until then had lived a dissociated existence in the fixed trauma of the compulsion and in a nocturnal underworld of tears.

L'auteur présente la longue analyse d'une patiente, Giulia, dont la volonté obstinée de réussir fait penser à l'activité du soufre alchimique à son point le plus ardent et à la crainte terrible de son coniunctio avec le sel alchimique. La description que fait Jung de ces symboles dans Mysterium Coniunctionis fournit une perspective imaginale qui est utile pour le travail clinique dans le domaine de la compulsion et de ses transformations possibles. Dès le début, la relation analytique semblait être reflétée et affectée par cette perspective alchimique. Cependant, ce fut seulement après beaucoup de temps, d'incertitude et d'endurance émotionnelle qu'une expérience psychologique plus complète du soufre et du sel a pu être atteinte, ce qui a permis à l'analyse de prendre une tournure plus imaginative et plus mercurienne. Durant son travail avec Giulia l'auteur a été témoin et a éprouvé un éventail d'affects intenses ­ les multiples couleurs que la combustion du souffre peut générer ­ que ce soit au bord d'une création irrésistible ou d'une destruction impitoyable, souvent d'une intensité archétypale. Cette expérience a été traversée et a subi une relation transformative avec le sel, qui jusqu'alors avait vécu une existence dissociée dans le traumatisme figé de la compulsion et dans les enfers nocturnes des larmes.

El autor presenta un largo análisis de una paciente, Giulia, cuya obstinada voluntad de logro evoca el funcionamiento del azufre alquímico en su forma más ardiente y el temor a su coniunctio con la sal alquímica. La descripción que Jung hace de estos símbolos en Mysterium Coniunctionis ofrece una perspectiva imaginal útil para el trabajo clínico en el ámbito de la compulsión y sus posibles transformaciones. Desde el principio, la relación analítica pareció reflejarse y verse afectada por esta perspectiva alquímica. Sin embargo, fue sólo después de mucho tiempo, incertidumbre y resistencia emocional que pudo accederse a una más plena experiencia psicológica de azufre y sal, lo cual permitió que el análisis tomara un giro más imaginativo y mercurial. En el transcurso de su trabajo con Giulia, el autor ha sido testigo y ha experimentado una gama de intensas emociones ­los múltiples colores que puede generar la combustión del azufre­, ya sea al borde de una creación imparable o de una destrucción despiadada, a menudo de intensidad arquetípica. Esta experiencia pudo ser atravesada y ha experimentado una relación transformadora con la sal, la cual hasta entonces había vivido una existencia disociada en la fijeza compulsiva del trauma y en un submundo nocturno de lágrimas.

[Clinical effects of transesophageal echocardiography in different surgical methods for nephrectomy combined with Mayo â ¢-â £ vena tumor thrombectomy].

OBJECTIVE: To analyze the clinical effects of intraoperative transesophageal echocardiography (TEE) in different surgical methods for nephrectomy combined with Mayo Ⅲ-Ⅳ inferior vena cave (IVC) tumor thrombectomy. METHODS: In the study, 28 patients who did surgery of nephrectomy and Mayo Ⅲ-Ⅳ IVC thrombectomys in Peking University Third Hospital from 2022 January to 2024 February were included. Of the 28 patients, 16 patients did robotic surgery, 2 patients did laparoscopic surgery, and 10 patients did open surgery. All patients' clinical data were collected. RESULTS: Intra-operative TEE was used in 9 robotic surgeries, of which 7 cases showed image changes compared with preoperative image results. Intraoperative TEE indicated that tumor thrombus entered the right atrium in 2 cases, showed that tumor thrombus grade rose from Mayo Ⅲ to Mayo Ⅳ in 2 cases, and indicated that tumor thrombus adhered to IVC wall in 3 cases. All of these surgical plans were timely adjusted. Intra-operative TEE was used in 6 cases of open surgery, and 4 cases of them showed Mayo grade changes compared with preoperative image results. Intraoperative TEE indicated that tumor thrombus adhered to the IVC wall in 3 cases, and tumor thrombus adhered to the IVC wall with thrombus in one case. The surgical plans were adjusted, and the tumor thrombus was left or segmentally removed. Laparoscopic surgery did not use intraoperative TEE. The effects of intraoperative TEE included: the combination of exploration and TEE monitoring was used in open surgery, and tumor thrombus removal process was fully monitored by intraoperative TEE in the robotic surgery. Intraoperative TEE real-time monitored circulatory status and cardiac function changes. CONCLUSION: In different surgical methods for nephrectomy combined with Mayo Ⅲ-Ⅳ tumor thrombectomy, intraoperative TEE can re-determine the tumor thrombus grade and degree of tumor thrombus adhered to IVC, track the tumor thrombus removal process in real-time, and monitor circulatory status and cardiac function changes. Intraoperative TEE plays an important role in different surgical methods, but its clinical application is still insufficient. Intraoperative TEE is recommended to such type of surgeries.

Could tocilizumab be used in familial Mediterranean Fever? A systematic review.

INTRODUCTION: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine is the primary treatment, around 10% of FMF patients do not respond to it, necessitating alternative therapies. Biologic treatments, such as interleukin-1ß (IL-1ß), TNF-α, and interleukin-6 (IL-6) inhibitors, have been considered. However, the accessibility and cost of IL-1ß inhibitors may limit their use in certain regions. Tocilizumab (TCZ), an IL-6 receptor inhibitor, offers an alternative, but its efficacy in FMF is not well-documented. OBJECTIVE: To evaluate the efficacy and safety of tocilizumab in the treatment of FMF. METHODS: Following PRISMA guidelines, we identified 237 articles on the use of TCZ in FMF. RESULTS: After selection, 14 articles were included: 2 double-blind RCTs, 2 retrospective studies, and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in pediatric FMF. CONCLUSION: This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1ß inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors.

The ReCoDe addiction research consortium: Losing and regaining control over drug intake-Findings and future perspectives.

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.

Elucidating molecular mechanism and chemical space of chalcones through biological networks and machine learning approaches.

We developed a bio-cheminformatics method, exploring disease inhibition mechanisms using machine learning-enhanced quantitative structure-activity relationship (ML-QSAR) models and knowledge-driven neural networks. ML-QSAR models were developed using molecular fingerprint descriptors and the Random Forest algorithm to explore the chemical spaces of Chalcones inhibitors against diverse disease properties, including antifungal, anti-inflammatory, anticancer, antimicrobial, and antiviral effects. We generated and validated robust machine learning-based bioactivity prediction models (https://github.com/RatulChemoinformatics/QSAR) for the top genes. These models underwent ROC and applicability domain analysis, followed by molecular docking studies to elucidate the molecular mechanisms of the molecules. Through comprehensive neural network analysis, crucial genes such as AKT1, HSP90AA1, SRC, and STAT3 were identified. The PubChem fingerprint-based model revealed key descriptors: PubchemFP521 for AKT1, PubchemFP180 for SRC, PubchemFP633 for HSP90AA1, and PubchemFP145 and PubchemFP338 for STAT3, consistently contributing to bioactivity across targets. Notably, chalcone derivatives demonstrated significant bioactivity against target genes, with compound RA1 displaying a predictive pIC50 value of 5.76 against HSP90AA1 and strong binding affinities across other targets. Compounds RA5 to RA7 also exhibited high binding affinity scores comparable to or exceeding existing drugs. These findings emphasize the importance of knowledge-based neural network-based research for developing effective drugs against diverse disease properties. These interactions warrant further in vitro and in vivo investigations to elucidate their potential in rational drug design. The presented models provide valuable insights for inhibitor design and hold promise for drug development. Future research will prioritize investigating these molecules for mycobacterium tuberculosis, enhancing the comprehension of effectiveness in addressing infectious diseases.

Comparison of Efficacy of Autologous Platelet Rich Plasma Therapy With 5% Topical Minoxidil Spray in Treating Alopecia Areata: A Head-to-Head Assessment of Novel Approaches.

BACKGROUND: Alopecia areata (AA) remains one of the most challenging afflictions encountered in dermatology clinics. It is characterized by an autoimmune-mediated inflammatory process of and around hair follicles, causing reversible, non-scarring hair loss. With the ongoing search for optimal treatment strategies, the potentially positive role of autologous platelet-rich plasma (PRP) therapy as well as minoxidil has been reported in various studies; however, the comparison of the two treatment modalities is largely underexplored. This research aims to compare and assess the effectiveness of intralesional PRP with topical minoxidil therapy in AA to identify efficacious management options amongst the newly described treatment modalities. METHODOLOGY: The research work was conducted over four months and included 40 (31 males and 9 females) patients suffering from alopecia areata. They were divided into Group A, which was administered monthly autologous PRP injections, while Group B was given daily topical 5% minoxidil therapy. In group A, four treatments of PRP were given, each one month apart. While in group B, daily topical minoxidil spray was administered for the same duration. The alopecia areata severity grade was recorded by employing the "Severity of Alopecia Tool" (SALT) scoring system. The pre- and post-treatment SALT scores were noted and compared at each monthly visit. RESULTS: The study comprised nine (22.5%) female and 31 (77.5%) male patients. At the beginning of the study and after one month of treatment, the difference in the SALT score was not statistically significant between the two groups, suggesting that both interventions had similar effects during the early stages of the treatment. At two months, a statistically significant difference emerged (p-value 0.037), indicating that a more significant fall in the SALT score was observed with autologous PRP treatment compared to topical minoxidil. After four months, a highly significant difference was noted between the two groups (p-value <0.0001), implying that intralesional PRP therapy led to a far more significant decrease in the SALT score compared to topical minoxidil therapy. CONCLUSION: Monthly intralesional autologous PRP therapy for four months manifests better outcomes in alopecia areata than daily 5% topical minoxidil therapy.

Characterizing disparities in receipt of palliative care for Asian Americans, Native Hawaiians, and Pacific Islanders with metastatic cancer in the United States.

PURPOSE: Palliative care plays essential roles in cancer care. However, differences in receipt among individuals identifying as Asian American, Native Hawaiian, and Other Pacific Islanders (AA&NHPI) with cancer are not well-characterized, especially when these diverse groups are disaggregated. We characterized disparities in receipt of palliative care among AA&NHPI patients with AJCC Stage IV prostate, breast, or lung cancer. METHODS: We performed multivariable logistic regressions were performed in this retrospective cohort analysis, using deidentified data from the National Cancer Database (NCDB) of patients diagnosed with AJCC analytic group stage IV breast, lung, or prostate cancer (2004-2018) who were White or of Asian Indian/Pakistani, Chinese, Filipino, Hawaiian, Hmong, Japanese, Kampuchean, Korean, Laotian, Other Pacific Islander, Thai, or Vietnamese descent. We conducted multivariable logistic regression analyses in a retrospective cohort study using deidentified data from the National Cancer Database (NCDB). The study included patients diagnosed with AJCC analytic group Stage IV breast, lung, or prostate cancer between 2004 and 2018, who were White or identified as Asian Indian/Pakistani, Chinese, Filipino, Hawaiian, Hmong, Japanese, Kampuchean, Korean, Laotian, Other Pacific Islander, Thai, or Vietnamese descent. Adjusted odds ratios and 95% confidence intervals of receiving palliative care were measured when comparing White vs. AA&NHPI patients as one cohort and White vs. disaggregated AA&NHPI patients, adjusting for clinical, socioeconomic, and demographic covariates. RESULTS: Among 775,289 individuals diagnosed with cancer (median age: 68 years), no significant differences in palliative care receipt were observed between White patients and aggregated AA&NHPI patients among patients with prostate, breast, or lung cancer. However, disaggregated analyses revealed reduced palliative care receipt for breast cancer patients of Asian Indian/Pakistani descent (AOR 0.75, 95% CI, 0.60-0.94, P = 0.011) and for lung cancer patients of Chinese, Vietnamese, Thai, and Asian Indian/Pakistani descent compared to White patients (Chinese AOR 0.88, [0.81-0.94], P = 0.001; Vietnamese AOR 0.89, [0.80 to 0.99], P = 0.032; Thai AOR 0.64, [0.44-0.92], P = 0.016; Asian Indian/Pakistani AOR 0.83, [0.74-0.93], P = 0.001). Palliative care was greater for patients of Japanese and Hawaiian descent with prostate cancer (Japanese AOR 1.92, [1.32-2.75], P = 0.001; Hawaiian AOR 2.09, [1.20-3.66], P = 0.009), breast cancer (Japanese AOR 1.72, [1.21-2.43], P = 0.001; Hawaiian AOR 1.70, [1.08-2.67], P = 0.021), and lung cancer (Japanese AOR 1.92, [1.70-2.17], P < 0.001; Hawaiian AOR 2.95, [2.5-3.5], P < 0.001), as well as patients of Other Pacific Islander descent with lung cancer (AOR 1.62, [1.34-1.96], P < 0.001). CONCLUSIONS AND RELEVANCE: Our findings demonstrate disparities in receipt of palliative care upon disaggregation of diverse AA&NHPI groups, the need for disaggregated research and targeted interventions that address the unique cultural, socioeconomic, and healthcare system barriers to palliative care receipt.

Genome-wide DNA methylation profile and its function in regulating Vip3Aa tolerance in fall armyworm (Spodoptera frugiperda).

BACKGROUND: Vegetative insecticidal proteins (Vips) are widely used in pest management, but Vip tolerance poses a significant threat. DNA methylation plays important roles in regulating the response of biological organisms to environmental stress, and it may also regulate fall armyworm (FAW, Spodoptera frugiperda) Vip3Aa tolerance. RESULTS: In this study, a DNA methylation map was developed for FAW, and its function in regulating FAW Vip3Aa tolerance was explored. The FAW genome-wide DNA methylation map showed that exons were preferred regions for DNA methylation and housekeeping genes were highly methylated. FAW was screened using Vip3Aa for ten generations, and bioassays indicated that Vip3Aa tolerance increased trans-generationally. A comparison of DNA methylation maps between Vip3Aa-tolerant and -susceptible strains showed that gene body methylation was positively correlated with gene expression level. FAW exhibits significant variation in DNA methylation among individuals, and Vip3Aa screening induces epigenetic variation based on DNA methylation. Moreover, the study demonstrated that a reduction in methylation density within the gene body of a 3'5'-cyclic nucleotide phosphodiesterase gene resulted in decreased expression and increased tolerance of FAW to Vip3Aa, which was validated through RNA interference experiments. CONCLUSION: The DNA methylation map and mechanism of Vip3Aa tolerance improve our understanding of DNA methylation and its function in Lepidoptera and provide a new perspective for developing pest management strategies. © 2024 Society of Chemical Industry.

Assessing the conservation value of cemeteries to urban biota worldwide.

Cemeteries are key urban green spaces with multifaceted societal and ecological importance. Their biodiversity is shaped by unique environmental and cultural factors. They can potentially protect rare and endangered species, yet their conservation value compared with other urban green spaces remains largely unexplored. We sought to fill this gap by systematically reviewing literature to investigate the conservation value of cemeteries relative to other urban green spaces (botanical gardens, institutional premises, natural remnants, and parks) by comparing species richness and proportions of native and unique species. We analyzed data from 70 papers covering 50 cities in 27 countries with linear and binomial mixed-effects models at both site and city level. Cemetery conservation value was similar to urban parks, except for the proportion of unique species, for which parks had significantly higher proportions (21.9% vs. 14.2%, p < 0.001). Cemeteries hosted slightly higher proportions of native species at the city level than botanical gardens (99.7% vs. 99.6%, p < 0.001) and institutional green spaces (96.3% vs. 94.1%, p = 0.034) and proportions comparable to parks and natural remnants (p > 0.05). They also had similar or higher values than institutional premises in species richness and unique species proportions (p > 0.05) and a higher site-level proportion of native species (p < 0.001). In contrast, species richness (slopes = -0.11 and -0.25, respectively) and unique species proportions (4.4% and 6.9%, respectively, p < 0.001 for both) were lower in cemeteries than in remnants of natural areas and in botanical gardens. The conservation value of cemeteries and parks was similar for animals, but parks had a higher value for plants. Overall, cemeteries were generally at least as valuable as some other green spaces for urban biodiversity and mostly native biota. Their religious and cultural significance suggests they will remain intact in the long term; thus, it is essential to prioritize and further promote their biodiversity in conservation and sustainable urban design plans.

Análisis del valor de conservación que tienen los cementerios para la biota urbana a nivel mundial Resumen Los cementerios son espacios urbanos verdes con una importancia social y ecológica multifacética. Su biodiversidad está moldeada por factores ambientales y culturales únicos. Los cementerios tienen el potencial para proteger especies raras y en peligro, pero su valor de conservación sigue sin ser explorado cuando se compara con otros espacios urbanos verdes. Buscamos llenar este vacío con una revisión sistemática de la bibliografía para investigar el valor de conservación de los cementerios en relación a otros espacios urbanos verdes (jardines botánicos, sedes institucionales, remanentes naturales y parques) al comparar la riqueza de especies y la proporción de especies nativas y únicas. Analizamos con modelos lineales y binomiales de efectos mixtos a nivel de sitio y de ciudad los datos de 70 artículos enfocados en 50 ciudades de 27 países. El valor de conservación de los cementerios fue similar al de los parques urbanos, excepto para la proporción de especies únicas, para la cual los parques tuvieron una proporción significativamente más alta (21.9% vs. 14.2%, p<0.001). A nivel de ciudad, los cementerios albergaron una proporción ligeramente mayor de especies nativas en comparación con los jardines botánicos (99.7% vs. 99.6%, p<0.001) y las sedes institucionales (96.3% vs. 94.1%, p = 0.034) y tuvieron una proporción comparable a los parques y los remanentes naturales (p>0.05). Los cementerios también tuvieron un valor similar o mayor a los espacios verdes institucionales en cuanto a riqueza de especies y proporción de especies únicas (p>0.05) y una proporción mayor a nivel de sitio de especies nativas (p<0.001). Al contrario, la riqueza de especies (pendientes = ­0.11 y ­0.25, respectivamente) y la proporción de especies únicas (4.4% y 6.9%, respectivamente, p<0.001 para ambas) fueron menores en los cementerios que en los remanentes de las áreas naturales y en los jardines botánicos. El valor de conservación de los cementerios y los parques fue similar para los animales, pero los parques tuvieron un valor mayor para las plantas. En general, los cementerios fueron al menos tan valiosos como otros espacios verdes para la biodiversidad urbana y casi toda la biota nativa. El significado religioso y cultural que tienen los cementerios sugiere que seguirán intactos a largo plazo; por ello, es esencial priorizar y promover aún más su biodiversidad en la conservación y en los planes de diseño urbano sustentable.

Unleashing the Neurotherapeutic Potential: The Crucial Role of miR-206-3p in Facilitating Hsp90aa1-Mediated Central Nervous System Injuries During Heat Stroke.

This study aims to explore the molecular mechanisms of miR-206-3p in regulating Hsp90aa1 and its involvement in the central nervous system (CNS) injury in heat stroke. Weighted gene co-expression network analysis (WGCNA) was performed on the GSE64778 dataset of heat stroke to identify module genes most closely associated with disease characteristics. Through the selection of key genes and predicting upstream miRNAs using RNAInter and miRWalk databases, the regulatory relationship between miR-206-3p and Hsp90aa1 was determined. Through in vitro experiments, various methods, including bioinformatics analysis, dual-luciferase reporter gene assay, RIP experiment, and RNA pull-down experiment, were utilized to validate this regulatory relationship. Furthermore, functional experiments, including CCK-8 assay to test neuron cell viability and flow cytometry to assess neuron apoptosis levels, confirmed the role of miR-206-3p. Transmission electron microscopy, real-time quantitative PCR, DCFH-DA staining, and ATP assay were employed to verify neuronal mitochondrial damage. Heat stroke rat models were constructed, and mNSS scoring and cresyl violet staining were utilized to assess neural functional impairment. Biochemical experiments were conducted to evaluate inflammation, brain water content, and histopathological changes in brain tissue using H&E staining. TUNEL staining was applied to detect neuronal apoptosis in brain tissue. RT-qPCR and Western blot were performed to measure gene and protein expression levels, further validating the regulatory relationship in vivo. Bioinformatics analysis indicated that miR-206-3p regulation of Hsp90aa1 may be involved in CNS injury in heat stroke. In vivo, animal experiments demonstrated that miR-206-3p and Hsp90aa1 co-localized in neurons of the rat hippocampal CA3 region, and with prolonged heat stress, the expression of miR-206-3p gradually increased while the expression of Hsp90aa1 gradually decreased. Further in vitro cellular mechanism validation and functional experiments confirmed that miR-206-3p could inhibit neuronal cell viability and promote apoptosis and mitochondrial damage by targeting Hsp90aa1. In vivo, experiments confirmed that miR-206-3p promotes CNS injury in heat stroke. This study revealed the regulatory relationship between miR-206-3p and Hsp90aa1, suggesting that miR-206-3p could regulate the expression of Hsp90aa1, inhibit neuronal cell viability, and promote apoptosis, thereby contributing to CNS injury in heat stroke.

Microstructural Characterization, Tribological and Corrosion Behavior of H111 Hot-Rolled AA5754 after Homogenization and Aging.

In this study, the microstructural properties, wear resistance, and corrosion behavior of H111 hot-rolled AA5754 alloy before heat treatment, after homogenization, and after aging were examined. The microstructure was mainly composed of the scattered forms of black and gray contrast particles on the matrix and precipitations were observed at the boundaries of the grain. The as-rolled material exhibited a dense pancake-shaped grain structure, which is typical of as-rolled material. Observation along the L-direction did not yield distinct demarcations among the grains and was not uniformly distributed, with precipitates at the grain boundary. When they aged, there was a parallel increase in fine and huge black and gray contrast particles in the zone. Therefore, it could be stated that the amount of fine grains increased due to the rise in the homogenization process. The rolled base metal with the grain orientation was found to be parallel to the rolling direction. On the other hand, the coarse grains were clearly observed in the aging heat-treatment condition. The grains had an elongated morphology consistent with the rolling process of the metal before the heat-treatment process. The aged alloy had the highest hardness with a value of 86.83 HB; the lowest hardness was seen in the alloy before heat treatment with a value of 68.67 HB. The weight loss and wear rate of this material at the end of 10,000 m were, respectively, 1.01 × 10-3 g and 5.07 × 10-9 g/Nm. It was observed that the alloy had the highest weight loss and worst wear resistance before heat treatment. Weight loss and wear rates at the end of 10,000 m were, respectively, 3.42 × 10-3 g and 17.08 × 10-9 g/Nm. According to these results, the friction coefficients during wear were parallel and the material with the lowest friction coefficient after aging was 0.045. While the alloys corroded after aging showed more weight loss, the alloys corroded before heat treatment exhibited better corrosion behavior. Among the alloys, the least weight loss after 24 h was observed in the alloy that was corroded before heat treatment and this value was 0.69 × 10-3 mg/dm2. The highest weight loss was observed in the aged alloy with a value of 1.37 × 10-3 mg/dm2. The alloy before heat treatment, which corroded after casting, showed the lowest corrosion rate with a value of 0.39 × 10-3 mg/(dm2·day) after 72 h. The alloy that was corroded before heat treatment showed the best corrosion behavior by creating a corrosion potential of 1.04 ± 1.5 V at a current density of -586 ± 0.04 µA/cm2. However, after aging, the corroded alloy showed the worst corrosion behavior with a corrosion potential of 5.16 ± 3.3 V at a current density of -880 ± 0.01 µA/cm2.

Comparison between Mechanical Properties and Joint Performance of AA 2024-T351 Aluminum Alloy Welded by Friction Stir Welding, Metal Inert Gas and Tungsten Inert Gas Processes.

The aim of this work is to study joining Al 2024-T3 alloy plates with different welding procedures. Aluminum alloy AA 2024-T351 is especially used in the aerospace industry. Aluminum plates are welded by the TIG and MIG fusion welding process, as well as by the solid-state welding process, friction stir welding (FSW), which has recently become very important in aluminum and alloy welding. For welding AA2024-T35 with MIG and TIG fusion processes, the filler material ER 4043-AlSi5 was chosen because of reduced cracking. Different methods were used to evaluate the quality of the produced joints, including macro- and microstructure evaluation, in addition to hardness and tensile tests. The ultimate tensile strength (UTS) of the FSW sample was found to be 80% higher than that of MIG and TIG samples. The average hardness value of the weld zone of metal for the MIG- and TIG-produced AA2024-T3511 butt joints showed a significant decrease compared to the hardness of the base metal AA2024-T351 by 50%, while for FSW joints, in the nugget zone, the hardness is about 10% lower relative to the base metal AA2024-T3511.

Molecular Dynamics Simulation of Salt Diffusion in Constituting Phosphazene-based Polymer Electrolyte.

A growing demand to visualize polymer models in liquid poses a computational challenge in molecular dynamics (MD) simulation, as this requires emerging models under suitable force fields to capture the underlying molecular behaviour accurately. In our present study, we have employed TIP3P potential on water and all atomistic optimized potentials for liquid simulations force fields to study the liquid electrolyte behavior of phosphazene-based polymer by considering its potential use in lithium-ion polymer batteries. We have explored the polymer's local structure, chain packing, wettability, and hydrophobic tendencies against the silicon surface using a combination of a pseudocontinuum model in MD simulation, and surface-sensitive sum frequency generation (SFG) vibrational spectroscopy. The finding yields invaluable insights into the molecular architecture of phosphazene. This approach identifies the importance of hydrophobic interactions with air and hydrophilic units with water molecules in understanding the behavior and properties of phosphazene-based polymers at interfaces, contributing to its advancements in materials science. The MD study uniquely captures traces of the polymer-ion linkage, which is observed to become more pronounced with the increase in polymer weight fraction. The theoretical observation of this linkage's influence on lithium-ion diffusion motion offers valuable insights into the fundamental physics governing the behavior of atoms and molecules within phosphazene-based polymer electrolytes in aqueous environments. Further these predictions are corroborated in the molecular-level depiction at the air-aqueous interface, as evidenced from the OH-oscillator strength variation measured by the SFG spectroscopy. The fundamental findings from this study open new avenues for utilizing MD simulation as a versatile methodology to gain profound insights into intermolecular interactions of polymer. It could be useful in the application of biomedical and energy-related research, such as polymer lithium-ion batteries, fuel cells, and organic solar cells.

Characterization of a novel AA16 lytic polysaccharide monooxygenase from Thermothelomyces thermophilus and comparison of biochemical properties with an LPMO from AA9 family.

Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes which are categorized in the CAZy database under auxiliary activities families AA9-11, 13, 14-17. Secreted by various microorganisms, they play a crucial role in carbon recycling, particularly in fungal saprotrophs. LPMOs oxidize polysaccharides through monooxygenase/peroxygenase activities and exhibit peroxidase and oxidase activities, with variations among different families. AA16, a newly identified LPMO family, is noteworthy due to limited studies on its members, thus rendering the characterization of AA16 enzymes vital for addressing controversies around their functions. This study focused on heterologous expression and biochemical study of an AA16 LPMO from Thermothelomyces thermophilus (formerly known as Myceliophthora thermophila), namely MtLPMO16A. Substrate specificity evaluation of MtLPMO16A showed oxidative cleavage of hemicellulosic substrates and no activity on cellulose, accompanied by a strong oxidase activity. A comparative analysis with an LPMO from AA9 family explored correlations between these families, while MtLPMO16A was shown to boost the activity of some AA9 family LPMOs. The results offer new insights into the AA16 family's action mode and microbial hemicellulose decomposition mechanisms in nature.

Loneliness and global cognitive functioning in racially and ethnically diverse US midlife and older adults.

Introduction: Few studies have examined the association of loneliness and cognitive functioning in the US. We used two common measures of loneliness and examined their association in a large sample of US Black, Latino, and White adults (ages ≥ 50). Methods: We analyzed Wave 3 of the National Social Life, Health, and Aging Project (N = 2,757). We examined loneliness using one item from the CES-D and the Felt Loneliness Measure (NFLM); cognitive functioning was assessed using the Montreal Cognitive Assessment (MoCA) tool, where higher scores indicated better functioning. We used weighted ordinary least squares regressions to examine the effects of loneliness (CES-D loneliness and NFLM in separate models) on MoCA scores. In exploratory analyses, we examined if these relationships varied by race and ethnicity. We adjusted all models for sociodemographic and other salient factors (e.g., chronic disease, depressive symptoms, living alone). Results: Mean age was 63.49 years, 52% were female, and 9% were Black and 6% Latino persons. Approximately 54% endorsed feeling lonely on at least one measure; 31% (CES-D) and 46% (NFLM). The relationship between loneliness measures was positive and significant, X 2 (1, N = 2,757) = 435.493 p < 0.001. However, only 40% of lonely individuals were identified as lonely on both assessments. CES-D loneliness was inversely (߈ = -0.274, p = 0.032) associated with MoCA scores and this association did not vary by race and ethnicity. Greater NFLM loneliness was positively associated (߈ = 0.445, p < 0.001) with higher MoCA scores for Latino participants only. Discussion: Loneliness appears to be an important predictor of cognitive functioning. However, the association of loneliness and cognitive functioning varied when using the CES-D loneliness item or the NFLM. Future work is needed to understand how loneliness and its clinically relevant dimensions (social, emotional, existential, chronicity) relate to global and individual cognitive domains. Research is needed with racially and ethnically diverse midlife and older adults, particularly to understand our counterintuitive finding for Latino participants. Finally, findings also support the need for research on interventions to prevent cognitive decline targeting loneliness.

The Public Understanding of Analytical Psychology.

In 1960, Jung lamented psychology's limited impact on global fate. Although Fordham tried to reassure him that Jungians were promoting his work, Jung was looking from the other end of the telescope, seeing the need to rescue humanity from its one-sidedness that would ultimately lead to nuclear conflict. Astronomical evidence, such as the Fermi paradox, echoes Jung's concerns about likely self-destruction. Rather than promoting Jungian ideas to interested groups, the imperative lies in identifying crucial messages for global survival and engaging the public in them. Science provides some useful lessons because its concerted efforts over centuries led to the gradual integration of scientific thinking into the public psyche. These lessons suggest that, to cross the border from the Jungian to wider public domain, compromises are necessary, such as simplifying messages and making engagement enchanting and practical. Analytical psychology's task goes beyond one individual, group, or even generation, and a debate is needed to begin to form a consensus on the way ahead. Some initial suggestions are made for adopting terminology the public can relate to, focusing on the transcendent function as the main vehicle to overcome one-sidedness and conflict, and using figures like Nelson Mandela to demonstrate practical application.

En 1960 Jung se désolait du faible impact de la psychologie sur le destin global. Bien que Fordham ait essayé de le rassurer, lui disant que les Jungiens faisaient la promotion de son travail, Jung regardait les choses d'un point de vue différent. Il voyait le besoin de sauver l'humanité de sa partialité, partialité qui l'amènerait en fin de compte au conflit nucléaire. Les indices venant de l'astronomie, comme le paradoxe de Fermi, font écho aux préoccupations de Jung concernant une probable autodestruction. Plutôt que de promouvoir les idées jungiennes à des groupes de personnes intéressées, l'impératif serait d'identifier des messages cruciaux pour la survie globale et de mobiliser le public avec de tels messages. La science fournit des leçons utiles parce que ses efforts d'ensemble sur une durée de plusieurs siècles ont apporté l'intégration progressive du penser scientifique dans la psyché publique. Ces leçons suggèrent que ­ pour traverser la frontière entre le monde Jungien et un domaine public plus large ­ des compromis sont nécessaires, tels que de simplifier les messages et de rendre l'implication séduisante et réaliste. La tâche de la psychologie analytique va au­delà d'un individu, d'un groupe, ou même d'une génération, et nous avons besoin d'un débat afin de commencer à élaborer un consensus sur le chemin devant nous. Quelques suggestions initiales sont faites pour adopter une terminologie à laquelle le public puisse s'identifier, se concentrant sur la fonction transcendante comme véhicule principal pour surmonter la partialité et le conflit, et utilisant des personnalités telles Nelson Mandela pour démontrer l'utilité pratique.

En 1960, Jung se lamentaba del limitado impacto de la psicología en el destino global. Aunque Fordham intentó asegurarle que los Junguianos estaban promoviendo su trabajo, Jung mirando desde el otro extremo del telescopio, estaba viendo la necesidad de rescatar a la humanidad de su unilateralidad que, en última instancia, conduciría al conflicto nuclear. La evidencia astronómica, como la paradoja de Fermi, refleja las preocupaciones de Jung sobre la probable autodestrucción. En lugar de promover las ideas de Jung entre los grupos interesados, el imperativo reside en identificar los mensajes cruciales para la supervivencia global e implicar al público en ellos. La ciencia ofrece algunas lecciones útiles porque sus esfuerzos concertados durante siglos condujeron a la integración gradual del pensamiento científico en la psique pública. Estas lecciones sugieren que, para cruzar la frontera de lo Junguiano a un dominio público más amplio, son necesarios compromisos, como simplificar los mensajes y hacer que el compromiso sea encantador y práctico. La tarea de la psicología analítica va más allá de un individuo, grupo o incluso generación, y es necesario un debate para empezar a formar un consenso sobre el camino a seguir. Se hacen algunas sugerencias iniciales para adoptar una terminología con la que el público pueda identificarse, centrándose en la función trascendente como vehículo principal para superar la unilateralidad y el conflicto, y utilizando figuras como Nelson Mandela para demostrar la aplicación práctica.

Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: Results from the Phase 3 randomized, controlled trial (THRIVE-AA1).

BACKGROUND: Alopecia areata (AA) is a hair loss disorder that can seriously impact quality of life. Janus kinase (JAK) inhibitors, including deuruxolitinib, have previously demonstrated significant hair regrowth in AA. OBJECTIVE: The Phase 3 THRIVE-AA1 randomized, double-blinded, placebo-controlled trial (NCT04518995) evaluated safety and efficacy of the oral JAK1/JAK2 inhibitor deuruxolitinib in adult patients with AA. METHODS: Patients aged 18-65 years with ≥50% hair loss were randomized to deuruxolitinib 8 mg BID, deuruxolitinib 12 mg BID, or placebo for 24 weeks. The primary endpoint was percentage of patients achieving Severity of Alopecia Tool (SALT) score ≤20. A key secondary endpoint was percentage of satisfaction of hair patient-reported outcome (SPRO) responders. RESULTS: Significantly higher proportions of patients taking deuruxolitinib met the primary endpoint (8 mg 29.6%; 12 mg 41.5% versus placebo 0.8%). Both deuruxolitinib doses achieved significant improvements in all secondary endpoints versus placebo, including SPRO (8 mg 42.1%; 12 mg 53.0% versus placebo 4.7%). Most treatment-emergent adverse events were mild or moderate, consistent with other oral JAK inhibitors. LIMITATIONS: Further studies are required to understand longer-term safety, efficacy, and impact of treatment cessation. CONCLUSION: Both doses of deuruxolitinib were effective for hair regrowth. Patient satisfaction aligned with hair growth.