Narcissism, perfectionism, and self-promoting behavior on social networking sites among university students in Pakistan / Narcisismo, perfeccionismo y comportamiento de autopromoción en sitios de redes sociales entre estudiantes universitarios en Pakistán

Existe un debate considerable en la literatura sobre cómo el narcisismo predice diversos comportamientos asociados con la utilidad de los sitios de redes sociales, pero los investigadores han prestado menos atención a explorar los mediadores potenciales de esta relación. Con base en la literatura existente, anticipamos que el narcisismo predice comportamientos de autopromoción en los sitios de redes sociales. El estudio actual también investigó el papel mediador del perfeccionismo multidimensional entre el narcisismo y el comportamiento de autopromoción. Se recopiló un total de 605 cuestionarios completos de estudiantes de universidades de Rawalpindi e Islamabad, Pakistán, mediante un muestreo conveniente. El estudio utilizó el Inventario de Personalidad Narcisista (Ames et al., 2006), un cuestionario de desarrollo propio sobre comportamiento de autopromoción en sitios de redes sociales y la Escala de Perfeccionismo Multidimensional (Hewitt et al., 1991). Los hallazgos indicaron que las mujeres en comparación con los hombres y las solteras en comparación con las casadas obtuvieron puntuaciones más altas en narcisismo. Los niveles educativos más altos se asociaron con tasas más altas de narcisismo. Los resultados también sugieren que el narcisismo se correlaciona con el perfeccionismo orientado a uno mismo y, más significativamente, con el narcisismo orientado a los demás. El perfeccionismo orientado a uno mismo y a los demás medió significativamente la relación entre el narcisismo y el comportamiento de autopromoción en los sitios de redes sociales.(AU)

There is considerable debate in the literature about how narcis-sism predicts various behaviors associated with the utility of social net-working sites, but researchers have paid less attention to exploring the po-tential mediators of this relationship.Based on the existing literature, we anticipated that narcissism predicts self-promoting behaviors on social networking sites. The current study also investigated the mediating role of multidimensional perfectionismbetween narcissism and self-promoting behavior. A total of 605 complete questionnaires weregathered fromstu-dents from universities from Rawalpindi and Islamabad, Pakistan using convenient sampling. The study used Narcissistic Personality Inventory (Ames et al., 2006), self-developed Self-promoting Behavior on social net-working sites questionnaire, and the Multidimensional Perfectionism Scale (Hewitt et al., 1991). Findings indicated that females as compared to males and single as comparedto married individuals scored higher on narcissism. Higher educational levels were associated with higher rates of narcissism. The results also suggestthat narcissism correlated with self-oriented per-fectionism, and more significantlywith others-oriented narcissism. Self-oriented and others-oriented perfectionism significantly mediated the rela-tionship between narcissism and self-promoting behavior on social net-working sites.(AU)

METTL3-mediated NDUFB5 m6A modification promotes cell migration and mitochondrial respiration to promote the wound healing of diabetic foot ulcer.

BACKGROUND: Diabetic foot ulcer (DFU) is the most devastating complication of diabetes mellitus (DM) and plays a major role in disability and death in DM patients. NADH: ubiquinone oxidoreductase subunit B5 (NDUFB5) plays an important role in maintaining mitochondrial respiration, but whether it is involved in regulating the progression of advanced glycation end products (AGEs)-mediated DFU is still unclear. METHODS: Firstly, the role of AGEs on cell viability, migration, and mitochondrial respiration in human umbilical vein endothelial cells (HUVECs) was explored in vitro. Next, NDUFB5 expression was detected in human samples and AGEs-treated HUVECs, and NDUFB5's effect on AGEs-induced HUVECs injury and skin wound in diabetic mice was further clarified. In addition, the role of m6A modification mediated by methyltransferase-like 3 (METTL3) in regulating NDUFB5 expression and AGEs-induced HUVECs injury was investigated. RESULTS: NDUFB5 promoted cell viability, migration, and mitochondrial respiration in AGEs-treated HUVECs, whereas mitochondrial fusion promoter M1 facilitated cell viability, migration, and mitochondrial oxiadative respiration in NDUFB5 knockdown HUVECs. Meanwhile, NDUFB5 promotes skin wound healing in diabetic mice. Besides, METTL3-mediated m6A modification and insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) enhanced NDUFB5 expression in HUVECs. Furthermore, METTL3 promoted cell viability, migration, and mitochondrial respiration in AGEs-treated HUVECs by increasing NDUFB5. CONCLUSION: METTL3-mediated NDUFB5 m6A modification inhibits AGEs-induced cell injury in HUVECs. METTL3 and NDUFB5 might serve as potential targets for DFU therapy in the future.

Internal Superwettability Inversion of a COF-Encapsulated Melamine Sponge Prepared by a One-Step Synthesis at Room Temperature.

Superwettable materials have been attracting attention due to their unique properties, showing great application prospects in a variety of fields including oil-water separation. Herein, a kind of covalent organic framework (COF)-encapsulated melamine sponge (MS) capable of internal superwettability inversion is prepared by a one-step synthesis at room temperature. COF is produced in situ on the skeleton of MS, which is favorable for practical application, and the prepared COF-encapsulated sponge (MS@COF) exhibits superhydrophobicity (water contact angle of about 157.0°) due to the rough surface provided by the micro/nanostructure of COF. More importantly, MS@COF displays reversibly superhydrophilicity by simple prewetting, achieving superwettability inversion conveniently, unlike the previous switchable materials that rely on external conditions. This facile intrinsic superwettability inversion greatly enriches the application prospects of this kind of smart sponge.

Carotid revascularisation versus medical treatment for asymptomatic carotid artery stenosis.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To compare the safety and efficacy of carotid revascularisation plus best medical treatment with best medical treatment alone in people with asymptomatic carotid artery stenosis.

Causal relationship between bone mineral density and intervertebral disc degeneration: a univariate and multivariable mendelian randomization study.

BACKGROUND: Although previous studies have suggested a possible association between bone mineral density (BMD) and intervertebral disc degeneration (IDD), the causal relationship between them remains unclear. Evidence from accumulating studies indicates that they might mutually influence one another. However, observational studies may be affected by potential confounders. Meanwhile, Mendelian randomization (MR) study can overcome these confounders to assess causality. OBJECTIVES: This Mendelian randomization (MR) study aimed to explore the causal effect of bone mineral density (BMD) on intervertebral disc degeneration (IDD). METHODS: Summary data from genome-wide association studies of bone mineral density (BMD) and IDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran's Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. Multivariate MR (MVMR) analyses used multivariable inverse variance-weighted methods to individually and jointly adjust for four potential confounders, body mass index (BMI), Type2 diabetes, hyperthyroidism and smoking. A reverse MR analysis was conducted to assess potential reverse causation. RESULTS: In the univariate MR analysis, femoral neck bone mineral density (FNBMD), heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) had a direct causal effect on intervertebral disc degeneration (IDD) [FNBMD-related analysis: OR(95%CI) = 1.17 (1.04 to 1.31), p = 0.008, eBMD-related analysis: OR(95%CI) = 1.06 (1.01 to 1.12), p = 0.028, LSBMD-related analysis: OR(95%CI) = 1.20 (1.10 to 1.31), p = 3.38E-7,TB BMD-related analysis: OR(95%CI) = 1.20 (1.12 to 1.29), p = 1.0E-8]. In the MVMR analysis, it was revealed that, even after controlling for confounding factors, heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) still maintained an independent and significant causal association with IDD(Adjusting for heel bone mineral density: beta = 0.073, OR95% CI = 1.08(1.02 to 1.14), P = 0.013; Adjusting for lumbar spine bone mineral density: beta = 0.11, OR(95%CI) = 1.12(1.02 to 1.23), P = 0.03; Adjusting for total body bone mineral density: beta = 0.139, OR95% CI = 1.15(1.06 to 1.24), P = 5.53E - 5). In the reverse analysis, no evidence was found to suggest that IDD has an impact on BMD. CONCLUSIONS: The findings from our univariate and multivariable Mendelian randomization analysis establish a substantial positive causal association between BMD and IDD, indicating that higher bone mineral density may be a significant risk factor for intervertebral disc degeneration. Notably, no causal effect of IDD on these four measures of bone mineral density was observed. Further research is required to elucidate the underlying mechanisms governing this causal relationship.

The antibodies against the A137R protein drive antibody-dependent enhancement of African swine fever virus infection in porcine alveolar macrophages.

African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a highly contagious disease that can kill up to 100% of domestic pigs and wild boars. It has been shown that the pigs inoculated with some ASF vaccine candidates display more severe clinical signs and die earlier than do pigs not immunized. We hypothesize that antibody-dependent enhancement (ADE) of ASFV infection may be caused by the presence of some unidentified antibodies. In this study, we found that the ASFV-encoded structural protein A137R (pA137R) can be recognized by the anti-ASFV positive sera, indicating that the anti-pA137R antibodies are induced in the ASFV-infected pigs. Interestingly, our results demonstrated that the anti-pA137R antibodies produced in rabbits or pigs enhanced viral replication of different ASFV strains in primary porcine alveolar macrophages (PAMs), the target cells of ASFV. Mechanistic investigations revealed that anti-pA137R antibodies were able to promote the attachment of ASFV to PAMs and two types of Fc gamma receptors (FcγRs), FcγRII and FcγRIII, mediated the ADE of ASFV infection. Taken together, anti-pA137R antibodies are able to drive ASFV ADE in PAMs. These findings shed new light on the roles of anti-ASFV antibodies and have implications for the pathophysiology of the disease and the development of ASF vaccines.

Accurately deciphering spatial domains for spatially resolved transcriptomics with stCluster.

Spatial transcriptomics provides valuable insights into gene expression within the native tissue context, effectively merging molecular data with spatial information to uncover intricate cellular relationships and tissue organizations. In this context, deciphering cellular spatial domains becomes essential for revealing complex cellular dynamics and tissue structures. However, current methods encounter challenges in seamlessly integrating gene expression data with spatial information, resulting in less informative representations of spots and suboptimal accuracy in spatial domain identification. We introduce stCluster, a novel method that integrates graph contrastive learning with multi-task learning to refine informative representations for spatial transcriptomic data, consequently improving spatial domain identification. stCluster first leverages graph contrastive learning technology to obtain discriminative representations capable of recognizing spatially coherent patterns. Through jointly optimizing multiple tasks, stCluster further fine-tunes the representations to be able to capture complex relationships between gene expression and spatial organization. Benchmarked against six state-of-the-art methods, the experimental results reveal its proficiency in accurately identifying complex spatial domains across various datasets and platforms, spanning tissue, organ, and embryo levels. Moreover, stCluster can effectively denoise the spatial gene expression patterns and enhance the spatial trajectory inference. The source code of stCluster is freely available at https://github.com/hannshu/stCluster.

Rapid and Amplification-free Nucleic Acid Detection with DNA Substrate-Mediated Autocatalysis of CRISPR/Cas12a.

To enable rapid and accurate point-of-care DNA detection, we have developed a single-step, amplification-free nucleic acid detection platform, a DNA substrate-mediated autocatalysis of CRISPR/Cas12a (DSAC). DSAC makes use of the trans-cleavage activity of Cas12a and target template-activated DNA substrate for dual signal amplifications. DSAC employs two distinct DNA substrate types: one that enhances signal amplification and the other that negatively modulates fluorescent signals. The positive inducer utilizes nicked- or loop-based DNA substrates to activate CRISPR/Cas12a, initiating trans-cleavage activity in a positive feedback loop, ultimately amplifying the fluorescent signals. The negative modulator, which involves competitor-based DNA substrates, competes with the probes for trans-cleaving, resulting in a signal decline in the presence of target DNA. These DNA substrate-based DSAC systems were adapted to fluorescence-based and paper-based lateral flow strip detection platforms. Our DSAC system accurately detected African swine fever virus (ASFV) in swine's blood samples at femtomolar sensitivity within 20 min. In contrast to the existing amplification-free CRISPR/Dx platforms, DSAC offers a cost-effective and straightforward detection method, requiring only the addition of a rationally designed DNA oligonucleotide. Notably, a common ASFV sequence-encoded DNA substrate can be directly applied to detect human nucleic acids through a dual crRNA targeting system. Consequently, our single-step DSAC system presents an alternative point-of-care diagnostic tool for the sensitive, accurate, and timely diagnosis of viral infections with potential applicability to human disease detection.

Perturbation of METTL1-mediated tRNA N7- methylguanosine modification induces senescence and aging.

Cellular senescence is characterized by a decrease in protein synthesis, although the underlying processes are mostly unclear. Chemical modifications to transfer RNAs (tRNAs) frequently influence tRNA activity, which is crucial for translation. We describe how tRNA N7-methylguanosine (m7G46) methylation, catalyzed by METTL1-WDR4, regulates translation and influences senescence phenotypes. Mettl1/Wdr4 and m7G gradually diminish with senescence and aging. A decrease in METTL1 causes a reduction in tRNAs, especially those with the m7G modification, via the rapid tRNA degradation (RTD) pathway. The decreases cause ribosomes to stall at certain codons, impeding the translation of mRNA that is essential in pathways such as Wnt signaling and ribosome biogenesis. Furthermore, chronic ribosome stalling stimulates the ribotoxic and integrative stress responses, which induce senescence-associated secretory phenotype. Moreover, restoring eEF1A protein mitigates senescence phenotypes caused by METTL1 deficiency by reducing RTD. Our findings demonstrate that tRNA m7G modification is essential for preventing premature senescence and aging by enabling efficient mRNA translation.

Recent progress in on-surface synthesis of nanoporous graphene materials.

Nanoporous graphene (NPG) materials are generated by removing internal degree-3 vertices from graphene and introducing nanopores with specific topological structures, which have been widely explored and exploited for applications in electronic devices, membranes, and energy storage. The inherent properties of NPGs, such as the band structures, field effect mobilities and topological properties, are crucially determined by the geometric structure of nanopores. On-surface synthesis is an emerging strategy to fabricate low-dimensional carbon nanostructures with atomic precision. In this review, we introduce the progress of on-surface synthesis of atomically precise NPGs, and classify NPGs from the aspects of element types, topological structures, pore shapes, and synthesis strategies. We aim to provide a comprehensive overview of the recent advancements, promoting interdisciplinary collaboration to further advance the synthesis and applications of NPGs.

Stabilization of TGF-ß Receptor 1 by a Receptor-Associated Adaptor Dictates Feedback Activation of the TGF-ß Signaling Pathway to Maintain Liver Cancer Stemness and Drug Resistance.

Dysregulation of the transforming growth factor-ß (TGF-ß) signaling pathway regulates cancer stem cells (CSCs) and drug sensitivity, whereas it remains largely unknown how feedback regulatory mechanisms are hijacked to fuel drug-resistant CSCs. Through a genome-wide CRISPR activation screen utilizing stem-like drug-resistant properties as a readout, the TGF-ß receptor-associated binding protein 1 (TGFBRAP1) is identified as a TGF-ß-inducible positive feedback regulator that governs sensitivity to tyrosine kinase inhibitors (TKIs) and promotes liver cancer stemness. By interacting with and stabilizing the TGF-ß receptor type 1 (TGFBR1), TGFBRAP1 plays an important role in potentiating TGF-ß signaling. Mechanistically, TGFBRAP1 competes with E3 ubiquitin ligases Smurf1/2 for binding to TGFΒR1, leading to impaired receptor poly-ubiquitination and proteasomal degradation. Moreover, hyperactive TGF-ß signaling in turn up-regulates TGFBRAP1 expression in drug-resistant CSC-like cells, thereby constituting a previously uncharacterized feedback mechanism to amplify TGF-ß signaling. As such, TGFBRAP1 expression is correlated with TGFΒR1 levels and TGF-ß signaling activity in hepatocellular carcinoma (HCC) tissues, as well as overall survival and disease recurrence in multiple HCC cohorts. Therapeutically, blocking TGFBRAP1-mediated stabilization of TGFBR1 by selective inhibitors alleviates Regorafenib resistance via reducing CSCs. Collectively, targeting feedback machinery of TGF-ß signaling pathway may be an actionable approach to mitigate drug resistance and liver cancer stemness.

Effects of recreational team sports on the metabolic health, body composition and physical fitness parameters of overweight and obese populations: A systematic review.

This systematic review aims to provide a summary of the results from individual studies that specifically focused on overweight or obese populations, regardless of age or sex. The goal is to determine the effects of structured recreational team sports interventions (TSG) on metabolic health, body composition and physical fitness parameters when compared to passive or active control groups. This study adhered to the PRISMA guidelines for reporting a systematic review. A thorough examination of relevant literature was conducted on November 06, 2023, using three prominent databases: PubMed, Scopus, and the Web of Science. Inclusion criteria considered overweight (e.g., BMI 25.0-29.9 kg/m2) and obese (e.g., BMI > 30 kg/m2) populations exposed to training interventions using recreational team sports, while the comparator group consisted of the same populations not exposed to exercise (passive controls) or exposed to alternative training methods. The primary outcomes of interest were metabolic health parameters (glucose, waist circumference, blood pressure, cholesterol, triglycerides), body composition (e.g., fat mass, lean mass), as well as physical fitness parameters (e.g., aerobic fitness, muscular fitness). Only studies with two- or multi-arm designs, whether randomized or not, were eligible for inclusion. The PEDro scale was used to assess the methodological bias of the included studies. Out of the initial 275 titles retrieved, we deemed ten eligible for our study. In terms of body composition, TSG demonstrated a significant decrease in body mass index across three studies (-2.3 to -5.1%) and a significant reduction in waist circumference in four studies (-4.6% to -8.4%). Regarding blood pressure, TSG exhibited a significant decrease in systolic blood pressure in two studies (-3.9% to -8.3%), while diastolic blood pressure showed a significant decrease in only one study (-7.3%). Cholesterol levels saw a significant decrease in TSG in three studies (-7.0% to -9.7%), and triglyceride levels showed a significant reduction in four studies (-16.4% to -20.1%). In terms of aerobic fitness, TSG demonstrated within-group improvements in the field-based tests in three studies (8.1% to 79.0%), and within-group improvements in maximal oxygen uptake in four studies (6.5% to 31.0%), with significant favoring of TSG in most studies. Overall, TSG demonstrated significant benefits for overweight and obese populations compared to the control group, particularly in terms of improvements in body mass index, systolic blood pressures, cholesterol and triglyceride levels, and aerobic fitness. Future research ought to concentrate on tailoring responses to varying training volumes on an individualized basis.

Differential expression profiles and functional prediction of circular RNAs in lung cancer patients with chronic obstructive pulmonary disease: a pilot study.

Chronic obstructive pulmonary disease (COPD), characterized by clinical sub-phenotypes such as emphysema (E) and chronic bronchitis (CB), is associated with a greater risk of lung cancer (LC). This study aimed to assess the expression patterns of circRNA and their potential functional involvement in LC patients with COPD. A circRNA microarray was used to characterize differentially expressed circRNAs (DEcircRNAs) profiles. A total of 176, 240, 163, and 243 DEcircRNAs were identified in comparisons between CB vs. LC patients (Con), E vs. Con, E vs. CB, and CBE vs. Con, respectively. DEcircRNAs in all comparison groups were primarily associated with immune-related GO terms and were also enriched in immune and inflammatory pathways. In total, 49 DEcircRNAs were significantly correlated with the infiltration of multiple immune cells. Among them, hsa-MROH9_0001 and hsa-RP11-35J10_0013 were positively and negatively correlated with plasma cells and T-cell CD4 memory resting cells, respectively; these two DEcircRNA-sponged miRNAs have good diagnostic performance. WGCNA identified six key circRNAs associated with CB progression. The expression patterns of hsa-MROH9_0001 and circRNA_21729 in E and CB groups were confirmed by RT-qPCR. In conclusion, we reported circRNA profiles and the findings demonstrated that hsa-MROH9_0001 and circRNA_21729 may be potential therapeutic targets for LC with COPD.

Impact of Molecular Chlorine Production from Aerosol Iron Photochemistry on Atmospheric Oxidative Capacity in North China.

Elevated levels of atmospheric molecular chlorine (Cl2) have been observed during the daytime in recent field studies in China but could not be explained by the current chlorine chemistry mechanisms in models. Here, we propose a Cl2 formation mechanism initiated by aerosol iron photochemistry to explain daytime Cl2 formation. We implement this mechanism into the GEOS-Chem chemical transport model and investigate its impacts on the atmospheric composition in wintertime North China where high levels of Cl2 as well as aerosol chloride and iron were observed. The new mechanism accounts for more than 90% of surface air Cl2 production in North China and consequently increases the surface air Cl2 abundances by an order of magnitude, improving the model's agreement with observed Cl2. The presence of high Cl2 significantly alters the oxidative capacity of the atmosphere, with a factor of 20-40 increase in the chlorine radical concentration and a 20-40% increase in the hydroxyl radical concentration in regions with high aerosol chloride and iron loadings. This results in an increase in surface air ozone by about 10%. This new Cl2 formation mechanism will improve the model simulation capability for reactive chlorine abundances in the regions with high emissions of chlorine and iron.

Selective N-functionalization of Arylhydrazines with Primary Alcohols and Acids under PPh3/DDQ System.

We present a PPh3/DDQ-mediated regiospecific selective N-functionalization of arylhydrazines with primary benzylic alcohols and aryl carboxylic acids for the synthesis of N1-benzyl arylhydrazines and N2-acyl arylhydrazines, respectively. This metal- and base-free approach features very short reaction times (about 10 min), broad substrate scope, good functional group tolerance, and mild reaction conditions. Furthermore, N1-benzlated products have also been successfully applied to the concise synthesis of N-substituted indoles and anticancer drug MDM2 inhibitor.

Harnessing the Missing Spectral Correlation for Metasurface Inverse Design.

A long-held tenet in computer science asserts that the training of deep learning is analogous to an alchemical furnace, and its "black box" signature brings forth inexplicability. For electromagnetic metasurfaces, the related intelligent applications also get stuck into such a dilemma. Although the past 5 years have witnessed a proliferation of deep learning-based works across complex photonic scenarios, they neglect the already existing but untapped physical laws. Here, the intrinsic correlation between the real and imaginary parts of the spectra are revealed using Kramers-Kronig relations, which is then mimicked by bidirectional information flow in neural network space. Such consideration harnesses the missing spectral connection to extract crucial features effectively. The bidirectional recurrent neural network is benchmarked in metasurface inverse design and compare it with a fully-connected neural network, unidirectional recurrent neural network, and attention-based transformer. Beyond the improved accuracy, the study examines the intermediate information products and physically explains why different network structures yield different performances. The work offers explicable perspectives to utilize physical information in the deep learning field and facilitates many data-intensive research endeavors.

Enhanced Thermally Activated Delayed Fluorescence by Sole Coordination: From an Organic Molecule to Its Zinc Complex.

A BPAPTPyC organic molecule containing a sandwich structural chromophore is designed and synthesized to produce blue thermally activated delayed fluorescence (TADF). The chromophore is composed of two di(4-tert-butylphenyl)amino donors and one inserted terpyridyl acceptor hitched at positions 1, 8, and 9 of a single carbazole via the p-phenylene group, in which the multiple space π-π interactions between the donor and acceptor enable the molecule to possess the TADF feature with a high energy emission at 470 nm but a low photoluminescence quantum yield (PLQY) and a small proportion of the delayed component. In contrast, the corresponding Zn(BPAPTPyC)Cl2 complex has a high PLQY and a short lifetime with a red-shifted emission due to the enhanced rigidity and electron accepting ability of the terpyridyl group from coordination. A solution-processed organic light-emitting diode (OLED) based on the complex achieves a maximum external quantum efficiency (EQE) of 17.9% with an emission peak at 585 nm, while an OLED of the organic molecule produces blue emission with a maximum EQE of 2.7%.

Phage-displayed heptapeptide sequence conjugation significantly improves the specific targeting ability of antimicrobial peptides against Staphylococcus aureus.

Broad-spectrum antibacterial drugs often lack specificity, leading to indiscriminate bactericidal activity, which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration. In this study, we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure-function relationship through one-factor modification. SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S. aureus. Moreover, SFK2 showed excellent biocompatibility in mice and piglet, and demonstrated significant therapeutic efficacy against S. aureus infection. In conclusion, our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S. aureus, providing a theoretical basis for developing targeted antimicrobial peptides.

In vitro anticancer study of novel curcumin derivatives via targeting PI3K/Akt/p53 signaling pathway.

Four new series of curcumin derivatives bearing NO-donating moiety were synthesized via etherification, nucleophilic substitution, and Knoevenagel condensation etc. The cytotoxicity activity of curcumin derivatives against five human tumor cell lines (A549, Hela, HepG2, MCF-7 and HT-29) and two normal cell lines (LO-2 and HK-2) has been studied. The results showed that compound 6a could inhibit the proliferation of MCF-7 cells remarkably and exhibit low toxicity to normal cells. Also, the underlying mechanism in vitro of compound 6a on MCF-7 was investigated. It has been found that compound 6a induced G2/M arrest and apoptosis of MCF-7 in a dose-dependent manner. Compound 6a-induced the fluorescence changes of ROS in MCF-7 cells confirmed the occurrence of apoptosis. Western Blot suggested that compound 6a decreased the expression of PI3K, as well as increased the expression of p53, cleaved caspase-9 and cleaved caspase-3. Furthermore, molecular docking revealed that compound 6a could bind well at active site of PI3K (3zim) with total score 9.59. Together, compound 6a, a potential PI3K inhibitor, may inhibit the survival of MCF-7 cells via interfering with PI3K/Akt/p53 pathway.

Mapping the distribution of Nipah virus infections: a geospatial modelling analysis.

BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.