Clinically used drug arsenic trioxide targets XIAP and overcomes apoptosis resistance in an organoid-based preclinical cancer model.

Drug resistance in tumor cells remains a persistent clinical challenge in the pursuit of effective anticancer therapy. XIAP, a member of the inhibitor of apoptosis protein (IAP) family, suppresses apoptosis via its Baculovirus IAP Repeat (BIR) domains and is responsible for drug resistance in various human cancers. Therefore, XIAP has attracted significant attention as a potential therapeutic target. However, no XIAP inhibitor is available for clinical use to date. In this study, we surprisingly observed that arsenic trioxide (ATO) induced a rapid depletion of XIAP in different cancer cells. Mechanistic studies revealed that arsenic attacked the cysteine residues of BIR domains and directly bound to XIAP, resulting in the release of zinc ions from this protein. Arsenic-XIAP binding suppressed the normal anti-apoptosis functions of BIR domains, and led to the ubiquitination-dependent degradation of XIAP. Importantly, we further demonstrate that arsenic sensitized a variety of apoptosis-resistant cancer cells, including patient-derived colon cancer organoids, to the chemotherapy drug using cisplatin as a showcase. These findings suggest that targeting XIAP with ATO offers an attractive strategy for combating apoptosis-resistant cancers in clinical practice.

Longitudinal association between Body mass index (BMI), BMI trajectories and the risk of frailty among older adults: A systematic review and meta-analysis of prospective cohort studies.

OBJECTIVE: We aimed to determine whether BMI categories and BMI trajectories were longitudinally associated with frailty in older adults via systematic review and meta-analysis of prospective cohort studies. METHOD: 3 databases (PubMed/MEDLINE, EMBASE and Web of Science) were systematically searched from inception to 8 September 2023. Two independent reviewers extracted data and appraised study quality. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Data were pooled using random-effects models. RESULTS: 7 prospective cohort studies with 23043 participants were included in final BMI categories analyses, and 3 studies included BMI trajectory(23725 individuals). Compared with normal weight, we found a positive association between obesity (odds ratios(OR) = 1.74, 95 % confidence interval (CI): 1.21-2.51, P = 0.003), underweight (OR = 1.70, 95 % CI: 1.13-2.57, P = 0.011) and frailty in older adults. In middle age subgroup, compared with normal weight, OR of 2.21 (95 % CI: 1.44-3.38;I2 = 0 %) for overweight and OR of 5.20 (95 % CI: 2.56-10.55; I2 = 0 %) for obesity were significantly associated with frailty. In old age subgroup, compared with normal weight, only OR of 1.41 (95 % CI: 1.13-1.77; I2 = 65 %) for obesity was significantly associated with frailty. The results of BMI trajectories found that decreasing BMI (OR = 3.25, 95 % CI: 2.20-4.79, P < 0.0001) and consistently high BMI (OR = 3.66, 95 % CI: 2.03-6.61, P < 0.0001) increase the risk of frailty compared to consistently normal or overweight. CONCLUSION: Overweight and obesity in middle age were associated with significantly higher frailty in older adults, while obesity and underweight in old age were associated with relatively higher frailty in older adults. Early weight control may be beneficial for old age.

Chinese characters carry special anatomical connotations.

In the domain of anatomy, some Chinese characters in anatomical terms possess distinctive morphological significance. Chinese characters evolved from pictographic characters, with some of these pictographs being created by ancient people based on their own body structure. This implies that the comprehension and depiction of the human body structure have been integral since the inception of Chinese characters, and this knowledge has been passed down and developed through the continued inheritance of Chinese characters. Even today, certain characters retain the appearance to reflect the shape of the human body structure. By examining the characters related to vertebrae, cranial fontanel and heart, we can find the unique and enduring link between Chinese characters and the fields of anatomy as well as Chinese traditional medicine.

Early patient-reported outcomes after robotic-assisted versus video-assisted thoracoscopic lobectomy.

BACKGROUND: Robotic-assisted thoracoscopic surgery (RATS) can achieve traditional clinical outcomes comparable to those of video-assisted thoracoscopic surgery (VATS). However, patient-reported outcomes (PROs) during the early period after RATS and VATS remain unclear. This study aimed to utilize longitudinal electronic PRO (ePRO) assessments to evaluate symptom burden and functional status between these approaches from patients' perspective. METHODS: This study comprised patients who underwent lobectomy via RATS or VATS for non-small cell lung cancer. We collected multiple-time-point PROs data from the prospective longitudinal study via an ePRO system. Symptom severity and function status were assessed using the perioperative symptom assessment for patients undergoing lung surgery and were analyzed between groups using linear mixed-effects models. RESULTS: Of the 164 patients, 42 underwent RATS and 122 underwent VATS. After propensity score matching (PSM), 42 RATS and 84 VATS exhibited similar baseline characteristics. During the 7-day postoperative period, participants underwent RATS reported milder pain (p = 0.014), coughing (p < 0.001), drowsiness (p = 0.001), and distress (p = 0.045) compared with those underwent VATS. Moreover, participants in RATS group showed less functional interference with walking (p < 0.001) and general activity (p < 0.001). RATS exhibited a shorter postoperative hospitalization (p = 0.021) but higher hospital cost (p < 0.001). Meanwhile, short-term clinical outcomes of operative time, dissected lymph node stations, chest tube drainage, and postoperative complication rates were comparable. CONCLUSION: PROs are important metrics for assessing patients' recovery after lobectomy. Compared with VATS, RATS may induce less symptom burden and better functional status for patients in the early postoperative period.

Functional and Genetic Analyses Unveil the Implication of CDC27 in Hemifacial Microsomia.

Hemifacial microsomia (HFM) is a rare congenital genetic syndrome primarily affecting the first and second pharyngeal arches, leading to defects in the mandible, external ear, and middle ear. The pathogenic genes remain largely unidentified. Whole-exome sequencing (WES) was conducted on 12 HFM probands and their unaffected biological parents. Predictive structural analysis of the target gene was conducted using PSIPRED (v3.3) and SWISS-MODEL, while STRING facilitated protein-to-protein interaction predictions. CRISPR/Cas9 was applied for gene knockout in zebrafish. In situ hybridization (ISH) was employed to examine the spatiotemporal expression of the target gene and neural crest cell (NCC) markers. Immunofluorescence with PH3 and TUNEL assays were used to assess cell proliferation and apoptosis. RNA sequencing was performed on mutant and control embryos, with rescue experiments involving target mRNA injections and specific gene knockouts. CDC27 was identified as a novel candidate gene for HFM, with four nonsynonymous de novo variants detected in three unrelated probands. Structural predictions indicated significant alterations in the secondary and tertiary structures of CDC27. cdc27 knockout in zebrafish resulted in craniofacial malformation, spine deformity, and cardiac edema, mirroring typical HFM phenotypes. Abnormalities in somatic cell apoptosis, reduced NCC proliferation in pharyngeal arches, and chondrocyte differentiation issues were observed in cdc27-/- mutants. cdc27 mRNA injections and cdkn1a or tp53 knockout significantly rescued pharyngeal arch cartilage dysplasia, while sox9a mRNA administration partially restored the defective phenotypes. Our findings suggest a functional link between CDC27 and HFM, primarily through the inhibition of CNCC proliferation and disruption of pharyngeal chondrocyte differentiation.

Evaluation of hemostatic, anti-inflammatory, wound healing, skin irritation and allergy, and antimicrobial properties of active fraction from the ethanol extract of Chromolaena odorata (L.) R.M. King & H. Rob.

ETHNOPHARMACOLOGICAL RELEVANCE: Chromolaenaodorata (L.) R.M. King & H. Rob, a perennial herb, has been traditionally utilized as a herbal remedy for treating leech bites, soft tissue wounds, burn wounds, skin infections, and dento-alveolitis in tropical and subtropical regions. AIM OF THE STUDY: The present study was to analyze the active fraction of C. odorata ethanol extract and investigate its hemostatic, anti-inflammatory, wound healing, and antimicrobial properties. Additionally, the safety of the active fraction as an external preparation was assessed through skin irritation and allergy tests. MATERIALS AND METHODS: The leaves and stems of C. odorata were initially extracted with ethanol, followed by purification through AB-8 macroporous adsorption resin column chromatography to yield different fractions. These fractions were then screened for hemostatic activity in mice and rabbits to identify the active fraction. Subsequently, the hemostatic effect of the active fraction was assessed through the bleeding time of the rabbit ear artery in vivo and the coagulant time of rabbit blood in vitro. The anti-inflammatory activity of the active fraction was tested on mice ear edema induced by xylene and rat paw edema induced by carrageenin. Furthermore, the active fraction's promotion effect on wound healing was evaluated using a rat skin injury model, and skin safety tests were conducted on rabbits and guinea pigs. Lastly, antimicrobial activities against two Gram-positive bacteria (G+, Staphylococcus aureus and S. epidermidis) and three Gram-negative bacteria (G-, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were determined using the plate dilution method. RESULTS: The ethanol extract of C. odorata leaves and stems was fractionated into 30%, 60%, and 90% ethanol eluate fractions. These fractions demonstrated hemostatic activity, with the 30% ethanol eluate fraction (30% EEF) showing the strongest effect, significantly reducing bleeding time (P < 0.05). A concentration of 1.0 g/mL of the 30% EEF accelerated cutaneous wound healing in rats on the 3rd, 6th, and 9th day post-operation, with the healing effect increasing over time. No irritation or allergy reactions were observed in rabbits and guinea pigs exposed to the 30% EEF. Additionally, the 30% EEF exhibited mild inhibitory effect on mice ear and rat paw edema, as well as antimicrobial activity against tested bacteria, with varying minimal inhibitory concentration (MIC) values. CONCLUSIONS: The 30% EEF demonstrated a clear hemostatic effect on rabbit bleeding time, a slight inhibitory effect on mice ear edema and rat paw edema, significant wound healing activity in rats, and no observed irritation or allergic reactions. Antibacterial activity was observed against certain clinically isolated bacteria, particularly the G- bacteria. This study lays the groundwork for the potential development and application of C. odorata in wound treatment.

Cytochrome P450 SmCYP78A7a positively functions in eggplant response to salt stress via forming a positive feedback loop with SmWRKY11.

Accumulating salinity in soil critically affected growth, development, and yield in plant. However, the mechanisms of plant against salt stress largely remain unknown. Herein, we identified a gene named SmCYP78A7a, which encoded a cytochrome P450 monooxygenase and belonged to the CYP78A sub-family, and its transcript level was significantly up-regulated by salt stress and down-regulated by dehydration stress. SmCYP78A7a located in the endoplasmic reticulum. Silencing of SmCYP78A7a enhanced susceptibility of eggplant to salt stress, and significantly down-regulated the transcript levels of salt stress defense related genes SmGSTU10 and SmWRKY11 as well as increased hydrogen peroxide (H2O2) content and decreased catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) enzyme activities. In addition, SmCYP78A7a transient expression enhanced eggplant tolerance to salt stress. By chromatin immunoprecipitation PCR (ChIP-PCR), luciferase reporter assay, and electrophoretic mobility shift assay (EMSA), SmWRKY11 activated SmCYP78A7a expression by directly binding to the W-box 6-8 (W-box 6, W-box 7, and W-box 8) within SmCYP78A7a promoter to confer eggplant tolerance to salt stress. In summary, our finds reveal that SmCYP78A7a positively functions in eggplant response to salt stress via forming a positive feedback loop with SmWRKY11, and provide a new insight into regulatory mechanisms of eggplant to salt stress.

Effect of COVID-19 on the characteristics and outcome of patients who have otitis media with effusion: a case-control study.

BACKGROUND: Few studies have examined the otologic symptoms of Coronavirus disease 2019 (COVID-19). The objective of this study was to identify the effect of COVID-19 on the characteristics and outcomes of patients who have otitis media with effusion (OME). METHODS: This case-control study compared the characteristics and outcomes of OME patients who did or did not have COVID-19. A total of 65 patients with previous COVID-19 and 40 patients who did not have COVID-19 (controls) were enrolled from October 1, 2022 to January 31, 2023 at a single institution in China. Demographics, medical histories, morbidities, hearing test results, treatments, and outcomes of the two groups were compared. RESULTS: The COVID-19 group had significantly better outcomes from OME than the control group, with higher rates of complete resolution (64.6% vs. 30%) and improvement (30.8% vs. 17.5%), and a lower rate of persistent OME (4.6% vs. 52.5%). Previous COVID-19 was independently associated with a more favorable OME outcome in three multivariate logistic regression models. The COVID-19 group also had a greater improvement in hearing threshold based on air-bone gap measurements. CONCLUSION: The outcomes of OME patients who had previous COVID-19 were generally good, in that most patients responded well to treatment and achieved complete resolution or improvement within one month.

Efficacy of Magnesium Sulfate and Labetalol in the Treatment of Pregnancy-Induced Hypertension and Its Effect on Anxiety and Depression: A Retrospective Cohort Study.

Background: In this study, the effect of magnesium sulfate and labetalol in treating pregnancy-induced hypertension (PIH) and its influence on anxiety and depression in patients are observed, and new ideas for treating anxiety and depression in PIH are introduced. Methods: A retrospective cohort study was conducted to select patients with PlH diagnosed from July 2020 to July 2023 from Affiliated Hospital of Electronic Science and Technology University and Chengdu Women' s and Children's Central Hospital in Chengdu of Sichuan Province. The changes in blood pressure, Edinburgh Postnatal Depression Scale (EPDS), and generalized anxiety disorder 7 (GAD-7) in patients with hypertensive pregnancy were collected and analyzed. Results: In our investigation, 219 patients completed the study, and 36.1% (79/219) of them developed anxiety and depression. According to whether the patients were treated with magnesium sulfate and labetalol, 49 cases were assigned to the magnesium sulfate and labetalol treatment (MSLT) group, and 30 cases were assigned to the conventional treatment (CT) group. Edinburgh Postnatal Depression Scale scores and GAD-7 scores in the MSLT group were significantly lower than those in the CT group, indicating that magnesium sulfate and labetalol can improve anxiety and depression in hypertensive patients during pregnancy. The difference was statistically significant (P < .05). According to the changes in systolic blood pressure, the clinical efficacy of patients was evaluated, and no significant difference in efficacy existed between the MSLT and CT groups. Conclusion: Magnesium sulfate and labetalol can control the blood pressure of patients with PIH and indirectly improve anxiety and depression in patients with PIH, thereby introducing new ideas for the treatment of PIH accompanied by anxiety and depression.

A Compact-Sized Fully Self-Powered Wireless Flowmeter Based on Triboelectric Discharge.

Flow sensing exhibits significant potential for monitoring, controlling, and optimizing processes in industries, resource management, and environmental protection. However, achieving wireless real-time and omnidirectional sensing of gas/liquid flow on a simple, self-contained device without external power support has remained a formidable challenge. In this study, a compact-sized, fully self-powered wireless sensing flowmeter (CSWF) is introduced with a small size diameter of down to less than 50 mm, which can transmit real-time and omnidirectional wireless signals, as driven by a rotating triboelectric nanogenerator (R-TENG). The R-TENG triggers the breakdown discharge of a gas discharge tube (GDT), which enables flow rate wireless sensing through emitted electromagnetic waves. Importantly, the performance of the CSWF is not affected by the R-TENG's varied output, while the transmission distance is greater than 10 m. Real-time wireless remote monitoring of wind speed and water flow rate is successfully demonstrated. This research introduces an approach to achieve a wireless, self-powered environmental monitoring system with a diverse range of potential applications, including prolonged meteorological observations, marine environment monitoring, early warning systems for natural disasters, and remote ecosystem monitoring.

[Study on mechanism of icariin-induced ferroptosis in HepG2 hepatoma carcinoma cells through PPARG/FABP4/GPX4 pathway].

The aim of this study was to explore the mechanism of icaritin-induced ferroptosis in hepatoma HepG2 cells. By bioinformatics screening, the target of icariin's intervention in liver cancer ferroptosis was selected, the protein-protein interaction(PPI) network was constructed, the related pathways were focused, the binding ability of icariin and target protein was evaluated by molecular docking, and the impact on patients' survival prognosis was predicted and the clinical prediction model was built. CCK-8, EdU, and clonal formation assays were used to detect cell viability and cell proliferation; colorimetric method and BODIPY 581/591 C1 fluorescent probe were used to detect the levels of Fe~(2+), MDA and GSH in cells, and the ability of icariin to induce HCC cell ferroptosis was evaluated; RT-qPCR and Western blot detection were used to verify the mRNA and protein levels of GPX4, xCT, PPARG, and FABP4 to determine the expression changes of these ferroptosis-related genes in response to icariin. Six intervention targets(AR, AURKA, PPARG, AKR1C3, ALB, NQO1) identified through bioinformatic analysis were used to establish a risk scoring system that aids in estimating the survival prognosis of HCC patients. In conjunction with patient age and TNM staging, a comprehensive Nomogram clinical prediction model was developed to forecast the 1-, 3-, and 5-year survival of HCC patients. Experimental results revealed that icariin effectively inhibited the activity and proliferation of HCC cells HepG2, significantly modulating levels of Fe~(2+), MDA, and lipid peroxidation ROS while reducing GSH levels, hence revealing its potential to induce ferroptosis in HCC cells. Icariin was found to diminish the expression of GPX4 and xCT(P<0.01), inducing ferroptosis in HCC cells, potentially in relation to inhibition of PPARG and FABP4(P<0.01). In summary, icariin induces ferroptosis in HCC cells via the PPARG/FABP4/GPX4 pathway, providing an experimental foundation for utilizing the traditional Chinese medicine icariin in the prevention or treatment of HCC.

Synthesis of Organopolysilazane Nanoparticles as Lithium-Ion Battery Anodes with Superior Electrochemical Performance via the Two-Step Stöber Method.

The Stöber method, a widely utilized sol-gel technique, stands as a green and reliable approach for preparing nanostructures on a large scale. In this study, we employed an enhanced Stöber method to synthesize organopolysilazane nanoparticles (OPSZ NPs), utilizing polysilazane oligomers as the primary precursor material and ammonia as the catalytic agent. By implementing a two-step addition process, control over crucial parameters facilitated the regulation of the nanoparticle size. Generally, maintaining relatively low concentrations of organopolysilazane and catalyst while adjusting the water/acetonitrile ratio can effectively enhance the surface energy of the organopolysilazane, resulting in the uniform formation of small spherical particles. The average particle size of the synthesized OPSZ NPs is about 140 nm, which were monodispersed and characterized by scanning electron microscopy, transmission electron microscopy, and dynamic light scattering. Furthermore, the composition of OPSZ NPs after pyrolysis was confirmed as SiC2.054N0.206O1.631 with 5.44 wt % free carbon structure by X-ray diffraction and energy-dispersive X-ray spectroscopy. Notably, the electrochemical performance assessment of SiCNO NPs as potential electrode materials for lithium-ion batteries exhibited promising outcomes. Specifically, at 1 A g-1 current density, the specific capacity is 585.45 mA h g-1 after 400 cycles, and the minimum capacity attenuation per cycle is only 0.1076 mA h g-1 (0.0172% of the original capacity), which indicates excellent energy storage capacity and cycle stability. In summary, this research contributes to the development of advanced anode materials for next-generation energy storage systems, marking a stride toward sustainable energy solutions.

Solanum aculeatissimum and Solanum torvum chloroplast genome sequences: a comparative analysis with other Solanum chloroplast genomes.

BACKGROUND: Solanum aculeatissimum and Solanum torvum belong to the Solanum species, and they are essential plants known for their high resistance to diseases and adverse conditions. They are frequently used as rootstocks for grafting and are often crossbred with other Solanum species to leverage their resistance traits. However, the phylogenetic relationship between S. aculeatissimum and S. torvum within the Solanum genus remains unclear. Therefore, this paper aims to sequence the complete chloroplast genomes of S. aculeatissimum and S. torvum and analyze them in comparison with 29 other previously published chloroplast genomes of Solanum species. RESULTS: We observed that the chloroplast genomes of S. aculeatissimum and S. torvum possess typical tetrameric structures, consisting of one Large Single Copy (LSC) region, two reverse-symmetric Inverted Repeats (IRs), and one Small Single Copy (SSC) region. The total length of these chloroplast genomes ranged from 154,942 to 156,004 bp, with minimal variation. The highest GC content was found in the IR region, while the lowest was in the SSC region. Regarding gene content, the total number of chloroplast genes and CDS genes remained relatively consistent, ranging from 128 to 134 and 83 to 91, respectively. Nevertheless, there was notable variability in the number of tRNA genes and rRNAs. Relative synonymous codon usage (RSCU) analysis revealed that both S. aculeatissimum and S. torvum preferred codons that utilized A and U bases. Analysis of the IR boundary regions indicated that contraction and expansion primarily occurred at the junction between SSC and IR regions. Nucleotide polymorphism analysis and structural variation analysis demonstrated that chloroplast variation in Solanum species mainly occurred in the LSC and SSC regions. Repeat sequence analysis revealed that A/T was the most frequent base pair in simple repeat sequences (SSR), while Palindromic and Forward repeats were more common in long sequence repeats (LSR), with Reverse and Complement repeats being less frequent. Phylogenetic analysis indicated that S. aculeatissimum and S. torvum belonged to the same meristem and were more closely related to Cultivated Eggplant. CONCLUSION: These findings enhance our comprehension of chloroplast genomes within the Solanum genus, offering valuable insights for plant classification, evolutionary studies, and potential molecular markers for species identification.

HOXB9 promotes osteosarcoma cell survival and malignancy under glucose starvation via upregulating SPP1 expression.

Homeobox B9 (HOXB9) has been shown to play a critical role in several tumors. However, the precise biological mechanisms and functions of HOXB9 in osteosarcoma remain largely unknown. In this study, we found that HOXB9 was increased upon glucose starvation. Elevated HOXB9 suppressed osteosarcoma cell death and supported cell growth and migration under glucose starvation. Further mechanistic studies demonstrated that HOXB9 directly bound to the promoter of secreted phosphoprotein 1 (SPP1) and transcriptionally upregulated SPP1 expression which then led cell death decrease and cell growth increase under glucose deprivation environment. Clinically, HOXB9 was significantly upregulated in osteosarcoma compared with normal tissues and increase of HOXB9 expression was positively associated with the elevation of SPP1 in osteosarcoma. Overall, our study illustrates that HOXB9 contributes to malignancy in osteosarcoma and inhibits cell death through transcriptional upregulating SPP1 under glucose starvation.

Cyano modified triphenylmethyl radical skeletons: higher stability and efficiency.

We introduced cyano groups to replace chlorine atoms in the tris(2,4,6-trichlorophenyl)methyl (TTM) radical skeleton, resulting in two cyano-modified TTM skeletons. The incorporation of cyano groups effectively suppresses nonradiative transition processes and lowers the frontier molecular orbital energy levels compared to those of the TTM radical. Consequently, enhanced photoluminescence quantum efficiency (PLQE) and a shift towards longer-wavelength emission in solution were achieved. Furthermore, the cyano-modified TTM skeletons exhibited improved stabilities. The development of these two skeletons adds diversity to stable organic luminescent radical skeletons.

Lymphatic endothelial cell-mediated accumulation of CD177+Treg cells suppresses antitumor immunity in human esophageal squamous cell carcinoma.

Regulatory T (Treg) cells are critical in shaping an immunosuppressive microenvironment to favor tumor progression and resistance to therapies. However, the heterogeneity and function of Treg cells in esophageal squamous cell carcinoma (ESCC) remain underexplored. We identified CD177 as a tumor-infiltrating Treg cell marker in ESCC. Interestingly, expression levels of CD177 and PD-1 were mutually exclusive in tumor Treg cells. CD177+ Treg cells expressed high levels of IL35, in association with CD8+ T cell exhaustion, whereas PD-1+ Treg cells expressed high levels of IL10. Pan-cancer analysis revealed that CD177+ Treg cells display increased clonal expansion compared to PD-1+ and double-negative (DN) Treg cells, and CD177+ and PD-1+ Treg cells develop from the same DN Treg cell origin. Importantly, we found CD177+ Treg cell infiltration to be associated with poor overall survival and poor response to anti-PD-1 immunotherapy plus chemotherapy in ESCC patients. Finally, we found that lymphatic endothelial cells are associated with CD177+ Treg cell accumulation in ESCC tumors, which are also decreased after anti-PD-1 immunotherapy plus chemotherapy. Our work identifies CD177+ Treg cell as a tumor-specific Treg cell subset and highlights their potential value as a prognostic marker of survival and response to immunotherapy and a therapeutic target in ESCC.

Accessing Benzoazepine Derivatives via Photoinduced Radical Relay Formal [5 + 2] Reaction of Amide/Alkyne Enabled by Palladium Catalysis.

A novel class of alkyne-tethered amides facilitates an unprecedented photoinduced palladium-catalyzed radical relay formal [5 + 2] reaction. This innovative strategy allows for the rapid construction of diverse fused benzoazepine structures, yielding structurally novel and compelling compounds. With a broad substrate scope and excellent functional group tolerance, the methodology synthesizes biologically active compounds. Notably, the resulting tricyclic benzo[b]azepines offer diversification opportunities through simple transformations. DFT calculations elucidate a seven-membered ring closure mechanism involving the alkenyl radical and Pd(I) rebound alongside a concerted metalation-deprotonation (CMD) process.

Ca2+/Calmodulin-Dependent Protein Kinase II Enhances Retinal Ganglion Cell Survival But Suppresses Axon Regeneration after Optic Nerve Injury.

Neuroprotection after injury or in neurodegenerative disease remains a major goal for basic and translational neuroscience. Retinal ganglion cells (RGCs), the projection neurons of the eye, degenerate in optic neuropathies after axon injury, and there are no clinical therapies to prevent their loss or restore their connectivity to targets in the brain. Here we demonstrate a profound neuroprotective effect of the exogenous expression of various Ca2+/calmodulin-dependent protein kinase II (CaMKII) isoforms in mice. A dramatic increase in RGC survival following the optic nerve trauma was elicited by the expression of constitutively active variants of multiple CaMKII isoforms in RGCs using adeno-associated viral (AAV) vectors across a 100-fold range of AAV dosing in vivo. Despite this neuroprotection, however, short-distance RGC axon sprouting was suppressed by CaMKII, and long-distance axon regeneration elicited by several pro-axon growth treatments was likewise inhibited even as CaMKII further enhanced RGC survival. Notably, in a dose-escalation study, AAV-expressed CaMKII was more potent for axon growth suppression than the promotion of survival. That diffuse overexpression of constitutively active CaMKII strongly promotes RGC survival after axon injury may be clinically valuable for neuroprotection per se. However, the associated strong suppression of the optic nerve axon regeneration demonstrates the need for understanding the intracellular domain- and target-specific CaMKII activities to the development of CaMKII signaling pathway-directed strategies for the treatment of optic neuropathies.

Prevalence of cigarette use and addiction among Chinese females by age and province: Findings from nationwide China Health Literacy Survey during 2018-19.

BACKGROUND: The prevalence of cigarette smoking among women is significantly different from that of men, however, cigarette use by women is little known. The study aims to describe cigarette use prevalence and patterns among Chinese females by age and province. METHODS: This study was based on the 2018 China Health Literacy Survey (2018 CHLS), a nationally representative cross-sectional study, and our analysis included 43,319 female participants aged 20-69 with valid data. The prevalence of cigarette use was estimated overall by sociodemographic factors and weighted based on the census population data. The logistic regression model was conducted to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the risk factors associated with cigarette use and dependency. RESULTS: In China, the estimated female current cigarette use prevalence was 1.85%, with over half of the population suffering from tobacco dependence (7.34 million). Jilin Province has the highest cigarette prevalence among women (10.59%), while Fujian Province has the lowest (0.27%). Participants over 60 years old (aOR=1.61, 95%CI=1.20-2.14), single (aOR=1.54, 95%CI=1.07-2.21), with primary education (aOR=1.93, 95%CI=1.47-2.52) were more likely to smoke. The age of smoking initiation among women intergenerational advanced, and compared to the cigarette users without tobacco dependence, those who have tobacco dependence start smoking earlier in all age groups (25.69 years vs. 19.36 years, p<0.001). CONCLUSIONS: The cigarette use prevalence among Chinese women was 1.85%, and there are significant differences among provinces. We noted a trend of women initiating smoking at increasingly younger ages, particularly among those with tobacco dependence.

Nutrition Status Plays a partial Mediation Role in the relationship between number of Teeth and Frailty: A Cross-sectional Multi-center Study.

Introduction Although the relationship between the number of teeth and frailty has been extensively studied, the mediating role of nutrition status in the association between the number of teeth and frailty remains to be clarified. Methods A number of 6664 participates lived in the communities of West China were analyzed in our study. Physical frailty was determined based on the phenotype established by Fried. Nutrition status was evaluated using the Mini Nutrition Assessment-Short Form (MNA-SF) scale. Multiple linear regression was employed to evaluate the direct relationships between the number of teeth, nutrition, and frailty. Mediation models and structural equation model (SEM) pathway analysis were used to test the mediating role of nutrition status in the relationship between the number of teeth and frailty. Results Among the 6664 participants aged over 50 years old, the prevalence of frailty was 6.2%. Multiple linear regression analysis showed a significant total relationship between the number of teeth (ß = -0.359, 95% CI: -0.473 to -0.244, p < 0.001) and frailty. After adjusting for MNA-SF scores, the relationship between the number of teeth and frailty remained significant (ß= -0.327, 95% CI: -0.443 to -0.211, p < 0.001), indicating a partial mediating effect of nutrition. Mediation analysis verified that nutrition partially mediated the relationship between the number of teeth and frailty (indirect effect estimate = -0.0121, bootstrap 95% CI: -0.0151 to -0.0092; direct effect estimate = -0.0874, bootstrap 95% CI: -0.1086 to -0.0678) in the fully adjusted model. This mediating effect occurred through influencing weight loss, low level of physical activity, and debility. Structural equation model (SEM) framework pathway analysis confirmed the association between the number of teeth, nutrition, and frailty. Conclusions Our findings demonstrated that frailty was correlated with the number of teeth and poorer nutritional status, with nutrition partially mediating the correlation between the number of teeth and frailty. Our results supported early nutritional evaluation and intervention in oral health to decrease the risk of frailty.