Sulfur dioxide inhibits mast cell degranulation by sulphenylation of galectin-9 at cysteine 74.

Objectives: Mast cell (MC) degranulation is a key process in allergic reactions and inflammatory responses. Aspartate aminotransferase 1 (AAT1)-derived endogenous sulfur dioxide (SO2) is an important regulator of MC function. However, the mechanism underlying its role in MC degranulation remains unclear. This study aimed to investigate the mechanism by which endogenous SO2 controlled MC degranulation. Methods: HMC-1 and Rat basophilic leukemia cell MC line (RBL-2H3) were used in the cell experiments. SO2 content was detected by in situ fluorescent probe. MC degranulation represented by the release rate of MC ß-hexosaminidase was determined using a colorimetric assay. Sulfenylation of galectin-9 (Gal-9) in MCs and purified protein was detected using a biotin switch assay. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the exact sulfenylation sites of Gal-9 by SO2. Animal models of passive cutaneous anaphylaxis (PCA) and hypoxia-driven pulmonary vascular remodeling were used to investigate the effect of SO2 on mast cell activation in vivo. Site-directed mutation of Gal-9 was conducted to confirm the exact site of SO2 and support the significance of SO2/Gal-9 signal axis in the regulation of MC degranulation. Results: Degranulation was increased in AAT1-knockdowned MCs, and SO2 supplementation reversed the increase in MC degranulation. Furthermore, deficiency of endogenous SO2 contributed to IgE-mediated degranulation in vitro. Besides, SO2 inhibited IgE-mediated and hypoxia-driven MC degranulation in vivo. Mechanistically, LC-MS/MS analysis and site-directed mutation results showed that SO2 sulfenylated Gal-9 at cysteine 74. Sulfenylation of the 74th cysteine of Gal-9 protein was required in the SO2-inhibited MC degranulation under both physiological and pathophysiological conditions. Conclusion: These findings elucidated that SO2 inhibited MC degranulation via sulfenylating Gal-9 under both physiological and pathophysiological conditions, which might provide a novel treatment approach for MC activation-related diseases.

Phase separation of RNF214 promotes the progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and the expression and function of an uncharacterized protein RNF214 in HCC are still unknown. Phase separation has recently been observed to participate in the progression of HCC. In this study, we investigated the expression, function, and phase separation of RNF214 in HCC. We found that RNF214 was highly expressed in HCC and associated with poor prognosis. RNF214 functioned as an oncogene to promote the proliferation, migration, and metastasis of HCC. Mechanically, RNF214 underwent phase separation, and the coiled-coil (CC) domain of RNF214 mediated its phase separation. Furthermore, the CC domain was necessary for the oncogenic function of RNF214 in HCC. Taken together, our data favored that phase separation of RNF214 promoted the progression of HCC. RNF214 may be a potential biomarker and therapeutic target for HCC.

Comparative Studies on Full Dehydrogenation of Dodecahydro-N-Ethylcarbazole on Pd(111) and Ni(111) Surfaces: Mechanism and Catalytic Enhancement.

Dodecahydro-N-ethylcarbazole (12H-NEC) is regarded as the most promising liquid organic hydrogen carrier for hydrogen storage and transportation. Understanding the mechanism of 12H-NEC dehydrogenation and developing cost-effective catalysts are significant. Pd is a high-performance catalyst for 12H-NEC but is not cost-effective, and Ni is just the opposite. How to understand the whole process of full dehydrogenation and improve the performance of Ni become two key questions. Herein, we systematically investigated the mechanism of the full dehydrogenation of 12H-NEC on Pd(111) and Ni(111) for the first time. By calculating all the barriers in the whole dehydrogenation process, we identified that 3H-NEC to 2H-NEC is the rate-determining step and Ni is catalytically less effective than Pd, which is attributed to its narrower d-band distribution and a 0.32 eV higher d-band center than that of Pd. To improve the performance of Ni, we further introduced dopants of Au, Ag, Cu, Pd, Pt, Ru, Rh, Zn, and Al. We found that Ag doping brings a downshift of the d-band center from -1.29 to -1.67 eV and reduces the barrier of 4H-NEC to NEC from 0.94 to 0.76 eV. This study provides new insights into the catalytic mechanism and performance-tuning strategy to help future experimental synthesis.

Recycled Cathodes in Rechargeable Aqueous Batteries as Ready-Made Electrodes for Oxygen Evolution Catalysis.

The development of a low-cost and efficient oxygen evolution reaction (OER) electrode is of critical importance for water electrolysis technologies. The general approach to achieving a high-efficiency OER electrode is to regulate catalytic material structures by synthetic control. Here we reported an orthogonal approach to obtaining the OER electrode without intentional design and synthesis, namely, recycling MnO2 cathodes from failed rechargeable aqueous batteries and investigating them as ready-made catalytic electrodes. The recycled MnO2 cathode showed very little Zn2+ storage capacity but surprisingly high OER activity with a low overpotential of 307 mV at 10 mA cm-2 and a small Tafel slope of 77.9 mV dec-1, comparable to the state-of-the-art RuO2 catalyst (310 mV, 86.9 mV dec-1). In situ electrochemical and theoretical studies jointly revealed that the accelerated OER kinetics of the recycled MnO2 electrode was attributed to the enlarged active surface area of MnO2 and optimized electronic structure of Mn sites. This work suggests failed battery cathodes as successful catalysis electrodes for sustainable energy development.

A new tau dephosphorylation-targeting chimera for the treatment of tauopathies.

Abnormal accumulation of hyperphosphorylated tau protein plays a pivotal role in a collection of neurodegenerative diseases named tauopathies, including Alzheimer's disease (AD). We have recently conceptualized the design of hetero-bifunctional chimeras for selectively promoting the proximity between tau and phosphatase, thus specifically facilitating tau dephosphorylation and removal. Here, we sought to optimize the construction of tau dephosphorylating-targeting chimera (DEPTAC) and obtained a new chimera D14, which had high efficiency in reducing tau phosphorylation both in cell and tauopathy mouse models, while showing limited cytotoxicity. Moreover, D14 ameliorated neurodegeneration in primary cultured hippocampal neurons treated with toxic tau-K18 fragments, and improved cognitive functions of tauopathy mice. These results suggested D14 as a cost-effective drug candidate for the treatment of tauopathies.

Factors associated with blood donation among college and university students in Wuhan, China: structural equation model.

BACKGROUND: College and university students were an important population group of blood donors, especially in the current situation of tight blood supply. This study aimed to investigate the current status and determinants of blood donation among this population group in Wuhan using a structural equation model. METHODS: We conducted a cross-sectional study involving 12 colleges and universities in Wuhan, China, including 5168 students. Sociodemographic characteristics, health status, knowledge about blood donation, and attitude toward blood donation were treated as latent variables, with blood donation as the observed variable. Confirmatory factor analysis was conducted using the Mplus 8.0 statistical software application, followed by the establishment of a structural equation model to assess the relationships that exist between these variables. RESULTS: The overall blood donation rate among college and university students was 24.71%. The established model indicated that sociodemographic characteristics, health status, knowledge about blood donation, and attitude toward blood donation showed significant positive effects (0.135, 0.056, 0.321, and 0.389, respectively) on blood donation, among them, the direct effects were 0.076, -0.110, 0.143, and 0.389, respectively (P < 0.01). Additionally, sociodemographic characteristics, health status, and knowledge about blood donation had indirectly affected blood donation through the mediating effect of attitude towards blood donation. Their effects on attitude towards blood donation were 0.099, 0.243, and 0.468, respectively. (P < 0.01). The model could explain explained 22.22% of the variance in blood donation behavior among college and university students in Wuhan. CONCLUSION: Blood donation among college and university students in Wuhan was associated with sociodemographic characteristics, health status, knowledge about blood donation, and attitude towards blood donation, with attitude being the primary influencing factor. Tailored recruitment strategies for blood donation among students should prioritize initiatives aimed at enhancing knowledge about blood donation and fostering positive attitudes toward it.

Interface Engineering of the Cu1.5Mn1.5O4/CeO2 Heterostructure for Highly Efficient Electrocatalytic Nitrate Reduction to Ammonia.

The electrochemical nitrate reduction reaction (NO3RR) is considered a sustainable technology to convert the nitrate pollutants to ammonia. However, developing highly efficient electrocatalysts is necessary and challenging given the slow kinetics of the NO3RR with an eight-electron transfer process. Here, a Cu1.5Mn1.5O4 (CMO)/CeO2 heterostructure with rich interfaces is designed and fabricated through an electrospinning and postprocessing technique. Benefiting from the strong coupling between CMO and CeO2, the optimized CMO/CeO2-2 catalyst presents excellent NO3RR performance, with NH3 Faraday efficiency (FE) up to 93.07 ± 1.45% at -0.481 V vs reversible hydrogen electrode (RHE) and NH3 yield rate up to 48.06 ± 1.32 mg cm-2 h-1 at -0.681 V vs RHE. Theoretical calculations demonstrate that the integration of CeO2 with CMO modulates the adsorption/desorption process of the reactants and intermediates, showing a reduced energy barrier in the rate determination step of NO* to N* and achieving an outstanding NO3RR performance.

The Gene Rearrangement and Transcriptional Regulation of Non B Cell-Derived Immunoglobulin.

Traditionally, immunoglobulin (Ig) expression has been attributed solely to B cells/plasma cells with well-documented and accepted regulatory mechanisms governing Ig expression in B cells. Ig transcription is tightly controlled by a series of transcription factors. However, increasing evidence has recently demonstrated that Ig is not only produced by B cell lineages but also by various types of non-B cells (non-B-Ig). Under physiological conditions, non-B-Ig not only exhibits antibody activity but also regulates cellular biological activities (such as promoting cell proliferation, adhesion, and cytoskeleton protein activity). In pathological conditions, non-B-Ig is implicated in the development of various diseases including tumour, kidney disease, and other immune-related disorders. The mechanisms underline Ig gene rearrangement and transcriptional regulation of Ig genes in non-B cells are not fully understood. However, existing evidence suggests that these mechanisms in non-B cells differ from those in B cells. For instance, non-B-Ig gene rearrangement occurs in an RAG-independent manner; and Oct-1 and Oct-4, rather than Oct-2, are required for the transcriptional regulation of non-B derived Igs. In this chapter, we will describe and compare the mechanisms of gene rearrangement and expression regulation between B-Ig and non-B-Ig.

The Expression of Non B Cell-Derived Immunoglobulins.

Although V(D)J recombination and immunoglobulin (Ig) production are traditionally recognised to occur only in B lymphocytes and plasma cells, the expression of Igs in non-lymphoid cells, which we call non B cell-derived Igs (non B Igs), has been documented by growing studies. It has been demonstrated that non B-Igs can be widely expressed in most cell types, including, but not limited to, epithelial cells, cardiomyocytes, hematopoietic stem/progenitor cells, myeloid cells, and cells from immune-privileged sites, such as neurons and spermatogenic cells. In particular, malignant tumour cells express high level of IgG. Moreover, different from B-Igs that mainly localised on the B cell membrane and in the serum and perform immune defence function mainly, non B-Igs have been found to distribute more widely and play critical roles in immune defence, maintaining cell proliferation and survival, and promoting progression. The findings of non B-Igs may provide a wealthier breakthrough point for more therapeutic strategies for a wide range of immune-related diseases.

Unlocking Efficient Hydrogen Production: Nucleophilic Oxidation Reactions Coupled with Water Splitting.

Electrocatalytic water splitting driven by sustainable energy is a clean and promising water-chemical fuel conversion technology for the production of high-purity green hydrogen. However, the sluggish kinetics of anodic oxygen evolution reaction (OER) pose challenges for large-scale hydrogen production, limiting its efficiency and safety. Recently, the anodic OER has been replaced by a nucleophilic oxidation reaction (NOR) with biomass as the substrate and coupled with a hydrogen evolution reaction (HER), which has attracted great interest. Anode NOR offers faster kinetics, generates high-value products, and reduces energy consumption. By coupling NOR with hydrogen evolution reaction, hydrogen production efficiency can be enhanced while yielding high-value oxidation products or degrading pollutants. Therefore, NOR-coupled HER hydrogen production is another new green electrolytic hydrogen production strategy after electrolytic water hydrogen production, which is of great significance for realizing sustainable energy development and global decarbonization. This review explores the potential of nucleophilic oxidation reactions as an alternative to OER and delves into NOR mechanisms, guiding future research in NOR-coupled hydrogen production. It assesses different NOR-coupled production methods, analyzing reaction pathways and catalyst effects. Furthermore, it evaluates the role of electrolyzers in industrialized NOR-coupled hydrogen production and discusses future prospects and challenges. This comprehensive review aims to advance efficient and economical large-scale hydrogen production.

Unfolding the mysteries of heterogeneity from a high-resolution perspective: integration analysis of single-cell multi-omics and spatial omics revealed functionally heterogeneous cancer cells in ccRCC.

The genomic landscape of clear cell renal cell carcinoma (ccRCC) has a considerable intra-tumor heterogeneity, which is a significant obstacle in the field of precision oncology and plays a pivotal role in metastasis, recurrence, and therapeutic resistance of cancer. The mechanisms of intra-tumor heterogeneity in ccRCC have yet to be fully established. We integrated single-cell RNA sequencing (scRNA-seq) and transposase-accessible chromatin sequencing (scATAC-seq) data from a single-cell multi-omics perspective. Based on consensus non-negative matrix factorization (cNMF) algorithm, functionally heterogeneous cancer cells were classified into metabolism, inflammatory, and EMT meta programs, with spatial transcriptomics sequencing (stRNA-seq) providing spatial information of such disparate meta programs of cancer cells. The bulk RNA sequencing (RNA-seq) data revealed high clinical prognostic values of functionally heterogeneous cancer cells of three meta programs, with transcription factor regulatory network and motif activities revealing the key transcription factors that regulate functionally heterogeneous ccRCC cells. The interactions between varying meta programs and other cell subpopulations in the microenvironment were investigated. Finally, we assessed the sensitivity of cancer cells of disparate meta programs to different anti-cancer agents. Our findings inform on the intra-tumor heterogeneity of ccRCC and its regulatory networks and offers new perspectives to facilitate the designs of rational therapeutic strategies.

Epidemiological and genomic characteristics of global blaNDM-carrying Escherichia coli.

BACKGROUND: Escherichia. coli is the most frequent host for New Delhi metallo-ß-lactamase (NDM) which hydrolyzes almost all ß-lactams except aztreonam. The worldwide spread of blaNDM-carrying E. coli heavily threatens public health. OBJECTIVE: This study aimed to explore the global genomic epidemiology of blaNDM- carrying E. coli isolates, providing information for preventing the dissemination of such strains. METHODS: Global E. coli genomes were downloaded from NCBI database and blaNDM was detected using BLASTP. Per software was used to extract meta information on hosts, resources, collection data, and countries of origin from GenBank. The sequence types (STs) and distribution of antimicrobial resistance gene (ARG) were analyzed by CLC Workbench; Plasmid replicons, serotypes and virulence genes (VFs) were analyzed by submitting the genomes to the websites. Statistical analyses were performed to access the relationships among ARGs and plasmid replicons. RESULTS: Until March 2023, 1,774 out of 33,055 isolates collected during 2003-2022 were found to contain blaNDM in total. Among them, 15 blaNDM variants were found with blaNDM-5 (74.1%) being most frequent, followed by blaNDM-1 (16.6%) and blaNDM-9 (4.6%). Among the 213 ARGs identified, 27 blaCTX-M and 39 blaTEM variants were found with blaCTX-M-15 (n = 438, 24.7%) and blaTEM-1B (n = 1092, 61.6%) being the most frequent ones, respectively. In addition, 546 (30.8%) plasmids mediated ampC genes, 508 (28.6%) exogenously acquired 16 S rRNA methyltransferase encoding genes and 262 (14.8%) mcr were also detected. Among the 232 distinct STs, ST167 (17.2%) were the most prevalent. As for plasmids, more than half of isolates contained IncFII, IncFIB and IncX3. The VF terC, gad, traT and iss as well as the serotypes O101:H9 (n = 231, 13.0%), O8:H9 (n = 115, 6.5%) and O9:H30 (n = 99, 5.6%) were frequently observed. CONCLUSIONS: The study delves into the intricate relationship between plasmid types, virulence factors, and ARGs, which provides valuable insights for clinical treatment and public health interventions, and serves as a critical resource for guiding future research, surveillance, and implementation of effective strategies to address the challenges posed by blaNDM-carrying E. coli. The findings underscore the urgent need for sustained global collaboration, surveillance efforts, and antimicrobial stewardship to mitigate the impact of these highly resistant strains on public health.

[Accuracy and clinical efficacy of robot-assisted transiliac-transsacral screw placement for posterior pelvic ring fractures].

OBJECTIVE: To explore accuracy and clinical effect of robot-assisted implantation of sacroiliac penetrating screw in orthopedic surgery for posterior pelvic ring fracture. METHODS: The clinical data of 24 patients with posterior pelvic ring fracture treated with robot-assisted sacroiliac penetration screws from August 2022 to August 2023 were retrospectively analyzed, including 10 males and 14 females; aged from 21 to 73 years old with an average of (49.29±14.48) years old;according to Tile pelvic fractures, 13 patients were type B and 11 were type C. The effect of screw placement was evaluated according to Gras criteria based on postoperative CT scan results. At the final follow-up, fracture healing was evaluated according to Matta score, and functional recovery was evaluated by Majeed score. RESULTS: All patients were followed up for 3 to 13 months with an average of (6.00±3.28) months. Totally 36 sacroiliac penetrating screws, 18 S1 penetrating screws, 18 S2 penetrating screws were inserted, a total of 29 were excellent and 7 good according to Gras standard. Screw adjustment times was 0.00 (0.00, 0.75) times. At the final follow-up, Matta score was excellent in 18 patients, 5 good and 1 moderate, and the maximum displacement distance was 2.55 (0.00, 5.65) mm. Majeed score was 84.37±8.38, 15 patients were excellent, 7 good and 2 moderate. CONCLUSION: Robot could accurately and safely assist in the placement of sacroiliac joint screws for the treatment of posterior pelvic ring fractures, and promote postoperative functional recovery of patients.

Assessing leaf physiological traits in response to flooding among dominant riparian herbs along the Three Gorges Dam in China.

Dams worldwide have significantly altered the composition of riparian forests. However, research on the functional traits of dominant herbs experiencing flooding stress due to dam impoundment remains limited. Given the high plasticity of leaf traits and their susceptibility to environmental influences, this study focuses on riparian herbs along the Three Gorges Hydro-Fluctuation Zone (TGHFZ). Specifically, it investigates how six leaf physiological traits of leading herbs-carbon, nitrogen, phosphorus, and their stoichiometric ratios-adapt to periodic flooding in the TGHFZ using cluster analysis, one-way analysis of variance (ANOVA), multiple comparisons, Pearson correlation analysis, and principal component analysis (PCA). We categorized 25 dominant herb species into three plant functional types (PFTs), noting that species from the same family tended to fall into the same PFT. Notably, leaf carbon content (LCC) exhibited no significant differences across various PFTs or altitudes. Within riparian forests, different PFTs employ distinct adaptation strategies: PFT-I herbs invest in structural components to enhance stress resistance; PFT-II, mostly comprising gramineous plants, responds to prolonged flooding by rapid growth above the water; and PFT-III, encompassing nearly all Compositae and annual plants, responds to prolonged flooding with vigorous rhizome growth and seed production. Soil water content (SWC) emerges as the primary environmental factor influencing dominant herb growth in the TGHFZ. By studying the response of leaf physiological traits in dominant plants to artificial flooding, we intend to reveal the survival mechanisms of plants under adverse conditions and lay the foundation for vegetation restoration in the TGHFZ.

[Effects of acupuncture on fecal short-chain fatty acids and TLR4/MyD88/NF-κB signaling pathway in spontaneously hypertensive rats].

OBJECTIVE: To observe the effects of acupuncture on blood pressure, fecal short-chain fatty acids (SCFAs) and toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway in spontaneously hypertensive rats (SHR), and to explore the mechanism of acupuncture for anti-hypertension. METHODS: Twenty-four male SHR of SPF grade were randomly divided into a model group, a western medication group, an acupuncture group and a sham acupuncture group, with 6 rats in each group, and 6 male Wistar-Kyoto rats were selected as the blank group additionally. Hydrochlorothiazide solution was given by gavage in the western medication group; acupuncture was applied at bilateral "Renying" (ST 9) and "Zusanli" (ST 36) in the acupuncture group, 20 min a time; acupuncture was applied at the non-meridian and non-acupoint points close to bilateral "Renying" (ST 9) and "Zusanli" (ST 36) in the sham acupuncture group, 20 min a time. The intervention was adopted once a day for 4 weeks continuously in each group. The systolic blood pressure (SBP) of the caudal artery was measured before intervention and after 1, 2, 3 and 4 weeks of intervention. After intervention, the morphology of colonic tissue was observed by HE staining; the fecal level of SCFAs was detected by gas chromatography; the serum levels of interleukin (IL)-6, IL-1ßand tumor necrosis factor-α (TNF-α) were detected by ELISA; the protein expression of TLR4, MyD88 and NF-κB p65 in the mesenteric artery was detected by Western blot. RESULTS: Compared with the blank group, in the model group, the SBP was increased (P<0.05), significant pathological changes could be found in the colonic tissue, the fecal SCFAs level was decreased (P<0.05), the serum levels of IL-6, IL-1ß and TNF-α were increased (P<0.05), the protein expression of TLR4, MyD88 and NF-κB p65 in the mesenteric artery was increased (P<0.05). Compared with the model group, the SBP after 2, 3 and 4 weeks of intervention was decreased (P<0.05), the serum levels of IL-6, IL-1ß and TNF-α were decreased (P<0.05) in the acupuncture group and the western medication group; the mucosal epithelium of colonic tissue was intact, the number of intestinal glands was abundant, the fecal SCFAs level was increased (P<0.05), and the protein expression of TLR4, MyD88 and NF-κB p65 in the mesenteric artery was decreased (P<0.05) in the acupuncture group. Compared with the sham acupuncture group, the SBP after 2, 3 and 4 weeks of intervention was decreased (P<0.05), the fecal SCFAs level was increased (P<0.05), the serum levels of IL-6, IL-1ß and TNF-α were decreased (P<0.05), the protein expression of TLR4, MyD88 and NF-κB p65 in the mesenteric artery was decreased (P<0.05) in the acupuncture group. CONCLUSION: Acupuncture at bilateral "Renying" (ST 9) and "Zusanli" (ST 36) can effectively play an anti-hypertensive role in SHR. Its mechanism may be related to regulating fecal SCFAs level and inhibiting the TLR4/MyD88/NF-κB signaling pathway.

The relationship between organizational support, professional quality of life, decent work, and professional well-being among nurses: a cross-sectional study.

BACKGROUND: Nurses often face challenges such as inadequate welfare protection, injustice, and workplace adversity including violence, bullying, and sexual harassment. In this context, providing sufficient support to nurses is crucial for the promotion of their professional well-being. This study examines the direct and indirect effects of perceived organizational support on nurses' well-being, particularly highlighting the mediating roles of professional quality of life and the perception of decent work. METHODS: A cross-sectional survey design was employed in this study. Convenience sampling was used to survey 792 nurses from five tertiary A-grade hospitals in Shanxi Province in January 2024. Data collection tools included a custom demographic survey, the Perceived Organizational Support Scale, Professional Quality of Life Scale, Decent Work Perception Scale, and Nurse Occupational Well-being Questionnaire. Descriptive statistics, correlation analysis, and mediation effect analyses were performed. RESULTS: The findings demonstrate that perceived organizational support has a direct impact on nurses' occupational well-being (ß = 0.323, p < 0.001). Additionally, professional quality of life and the perception of decent work play chain mediating roles between perceived organizational support and nurses' well-being (ß = 0.019, BootLLCI = 0.010, BootULCI = 0.030). CONCLUSIONS: This study highlighted the importance of organizational support in enhancing nurses' well-being. Professional quality of life and decent work were key mediators. Healthcare institutions should prioritize support measures to improve nurses' well-being. Future research should explore additional mediators and mechanisms to develop effective strategies for nursing policymakers and administrators.

Growth characteristics of HCT116 xenografts lacking asparagine synthetase vary according to sex.

BACKGROUND: Sex-related differences in colorectal (CRC) incidence and mortality are well-documented. However, the impact of sex on metabolic pathways that drive cancer growth is not well understood. High expression of asparagine synthetase (ASNS) is associated with inferior survival for female CRC patients only. Here, we used a CRISPR/Cas9 technology to generate HCT116 ASNS-/- and HCT 116 ASNS+/+ cancer cell lines. We examine the effects of ASNS deletion on tumor growth and the subsequent rewiring of metabolic pathways in male and female Rag2/IL2RG mice. RESULTS: ASNS loss reduces cancer burden in male and female tumor-bearing mice (40% reduction, q < 0.05), triggers metabolic reprogramming including gluconeogenesis, but confers a survival improvement (30 days median survival, q < 0.05) in female tumor-bearing mice alone. Transcriptomic analyses revealed upregulation of G-protein coupled estrogen receptor (GPER1) in tumors from male and female mice with HCT116 ASNS-/- xenograft. Estradiol activates GPER1 in vitro in the presence of ASNS and suppresses tumor growth. CONCLUSIONS: Our study indicates that inferior survival for female CRC patients with high ASNS may be due to metabolic reprogramming that sustains tumor growth. These findings have translational relevance as ASNS/GPER1 signaling could be a future therapeutic target to improve the survival of female CRC patients.

Solid state preparation of carbon-supported Pt2Ca nanoparticles for the oxygen reduction reaction.

Pt2Ca nanoparticles with a mean size diameter of 6 nm can be prepared by heating K2PtCl6, CaH2, carbon black and KCl at 400-500 °C. A mechanism study suggests that the formation of the Pt2Ca phase at moderate temperature is enabled by the fast ion transport via the vacancies in the KCl-CaH2 solid solution. The Pt2Ca nanoparticles exhibit high performance for the oxygen reduction reaction in acid due to optimal adsorption energy of the oxygen intermediate.

Mendelian randomization evidence for the causal effect of mental well-being on healthy aging.

Mental well-being relates to multitudinous lifestyle behaviours and morbidities and underpins healthy aging. Thus far, causal evidence on whether and in what pattern mental well-being impacts healthy aging and the underlying mediating pathways is unknown. Applying genetic instruments of the well-being spectrum and its four dimensions including life satisfaction, positive affect, neuroticism and depressive symptoms (n = 80,852 to 2,370,390), we performed two-sample Mendelian randomization analyses to estimate the causal effect of mental well-being on the genetically independent phenotype of aging (aging-GIP), a robust and representative aging phenotype, and its components including resilience, self-rated health, healthspan, parental lifespan and longevity (n = 36,745 to 1,012,240). Analyses were adjusted for income, education and occupation. All the data were from the largest available genome-wide association studies in populations of European descent. Better mental well-being spectrum (each one Z-score higher) was causally associated with a higher aging-GIP (ß [95% confidence interval (CI)] in different models ranging from 1.00 [0.82-1.18] to 1.07 [0.91-1.24] standard deviations (s.d.)) independent of socioeconomic indicators. Similar association patterns were seen for resilience (ß [95% CI] ranging from 0.97 [0.82-1.12] to 1.04 [0.91-1.17] s.d.), self-rated health (0.61 [0.43-0.79] to 0.76 [0.59-0.93] points), healthspan (odds ratio [95% CI] ranging from 1.23 [1.02-1.48] to 1.35 [1.11-1.65]) and parental lifespan (1.77 [0.010-3.54] to 2.95 [1.13-4.76] years). Two-step Mendelian randomization mediation analyses identified 33 out of 106 candidates as mediators between the well-being spectrum and the aging-GIP: mainly lifestyles (for example, TV watching and smoking), behaviours (for example, medication use) and diseases (for example, heart failure, attention-deficit hyperactivity disorder, stroke, coronary atherosclerosis and ischaemic heart disease), each exhibiting a mediation proportion of >5%. These findings underscore the importance of mental well-being in promoting healthy aging and inform preventive targets for bridging aging disparities attributable to suboptimal mental health.

Molecular Characteristics of Salmonella Spp. Responsible for Bloodstream Infections in a Tertiary Hospital in Nanjing, China, 2019-2021.

Objective: To investigate the clinical and molecular characteristics of Salmonella spp. causing bloodstream infections (BSIs) in our hospital. Methods: We studied 22 clinical Salmonella isolates from BSIs and 16 from non-BSIs, performing antimicrobial susceptibility testing (AST) and whole genome sequencing (WGS). The analysis included serovars, antibiotic resistance genes (ARGs), virulence factors (VFs), sequence types (STs), plasmid replicons, and genetic relationships. We also assessed pathogenicity of the isolates causing BSIs through growth, biofilm formation, and anti-serum killing assays. Results: WGS analysis identified 13 Salmonella serovars, with four responsible for BSIs. S. Enteritidis was the most prevalent serovar, involved in 19 (50.0%) cases. BSIs were caused by 17S. Enteritidis, two S. Typhimurium, two S. Munster and one S. Diguel. Of the 38 isolates, 27 (71.1%) exhibited high resistance to ampicillin, and 24 (63.2%) to ampicillin/sulbactam. Thirty-six types of ARGs were identified, with blaTEM-1B (n = 25, 65.8%) being the most frequent. Ten plasmid replicons were found; the combination of IncFIB(S)-IncFII(S)-IncX1 was the most common in S. Enteritidis (94.7%). Fifteen STs were identified, among which ST11 was the most prevalent and clonally disseminated, primarily responsible for BSIs. A total of 333 different VFs were detected, 177 of which were common across all strains. No significant differences were observed between the BSI and non-BSI isolates in terms of resistance rates, ARGs, plasmid replicons, and VFs, except for seven VFs. No strong pathogenicity was observed in the BSI-causing isolates. Conclusion: BSIs were predominantly caused by clonally disseminated S. Enteritidis ST11, the majority of which carried multiple ARGs, VFs and plasmid replicons. This study provides the first data on clonally disseminated S. Enteritidis ST11 causing BSIs, highlighting the urgent need for enhanced infection control measures.