Pericentriolar material 1 promotes intestinal inflammation in ulcerative colitis by activating NLRP3/gasdermin D-mediated macrophage pyroptosis.

Excessive proinflammatory cytokine release induced by pyroptosis plays a vital role in intestinal mucosal inflammation in ulcerative colitis (UC). Several pyroptosis-related factors are regulated by the centrosome. Pericentriolar material 1 (PCM1) is a primary component of centriolar satellites that is present as cytoplasmic granules around the centrosome. Our previous study revealed that PCM1 was highly expressed in UC patients, but the role of PCM1 in UC remains unknown. This study aimed to elucidate the role of PCM1 in the development of UC, especially the mechanism in pyroptosis process of UC. Clinical mucosal sample and dextran sulfate sodium (DSS)-induced colitis mouse were used to reveal the association between PCM1 and intestinal inflammation. Intestinal epithelial cell-specific PCM1-knockout mice were constructed to determine the role of PCM1 in colitis. Finally, PCM1 RNA interference and overexpression assays in THP1 cells were employed to study the molecular mechanisms of PCM1 in inflammatory responses and pyroptosis. We found that PCM1 expression was upregulated in the colonic mucosa of UC patients and positively correlated with inflammatory indicators. PCM1 expression was elevated in DSS-induced colitis mice and was reduced after methylprednisolone treatment. In the DSS colitis model, intestinal-specific PCM1-knockout mice exhibited milder intestinal inflammation and lower pyroptosis levels than wild-type mice. In cell level, PCM1 exerted a proinflammatory effect by activating the NLRP3 inflammasome and triggering subsequent gasdermin D-mediated pyroptosis to release IL-1ß and IL-18. In conclusion, PCM1 mediates activation of the NLRP3 inflammasome and gasdermin D-dependent pyroptosis, ultimately accelerating intestinal inflammation in UC. These findings revealed a previously unknown role of PCM1 in initiating intestinal mucosal inflammation and pyroptosis in UC, and this factor is expected to be a regulator in the complex inflammatory network of UC.

Hydrogen Sulfide in Musculoskeletal Diseases: Molecular Mechanisms and Therapeutic Opportunities.

SIGNIFICANCE: Musculoskeletal diseases seriously affect global health, but their importance is greatly underestimated. These diseases often afflict the elderly, leading to disability, paralysis, and other complications. Hydrogen sulfide (H2S) plays an important role in the occurrence and development of musculoskeletal diseases, which may have potential ther-apeutic significance for these diseases. RECENT ADVANCES: Recently, it has been found that many musculoskeletal diseases, such as osteoporosis, periodontitis, muscle atrophy, muscle ischemia-reperfusion injury, mus-cle contraction under high fever, arthritis, and disc herniation, can be alleviated by sup-plementing H2S. H2S may be conducive to the development of multiple myeloma. The mechanism of H2S effect on the musculoskeletal system has been elucidated. A variety of H2S donors and nano-delivery systems provide prospects for H2S-based therapies. CRITICAL ISSUES: Related research remains at the level of cell or animal experiments, and clinical research is lacking. The role of H2S in more musculoskeletal disorders remains largely unknown. The importance of musculoskeletal diseases has not been widely con-cerned. Targeted delivery of H2S remains a challenging task. FUTURE DIRECTION: Develop therapeutic drugs for musculoskeletal diseases based on H2S and test their safety, efficacy, and tolerance. Explore the combination of current musculo-skeletal disease drugs with H2S releasing components to improve efficacy and avoid side effects. Carry out relevant clinical trials to verify the possibility of its widespread use.

A comprehensive prognostic and immunological implications of PFKP in pan-cancer.

BACKGROUND: Phosphofructokinase P (PFKP) is a key rate-limiting enzyme in glycolysis, playing a crucial role in various pathophysiological processes. However, its specific function in tumors remains unclear. This study aims to evaluate the expression and specific role of PFKP across multiple tumor types (Pan-cancer) and to explore its potential clinical significance as a therapeutic target in cancer treatment. METHODS: We analyzed the expression of PFKP, immune cell infiltration, and patient prognosis across various cancers using data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we conducted a series of experiments in lung cancer cells, including Western blot, CCK-8 assay, colony formation assay, transwell migration assay, scratch wound healing assay, LDH release assay, and flow cytometry, to evaluate the impact of PFKP on tumor cells. RESULTS: PFKP was found to be highly expressed in most cancers and identified as a prognostic risk factor. Elevated PFKP expression is associated with poorer clinical outcomes, particularly in lung adenocarcinoma (LUAD). Receiver operating characteristic (ROC) curve analysis indicated that PFKP can effectively differentiate between cancerous and normal tissues. The expression of PFKP in most tumors showed significant correlations with tumor mutational burden (TMB), microsatellite instability (MSI), immune score, and immune cell infiltration. In vitro experiments demonstrated that PFKP overexpression promotes lung cancer cell proliferation and migration while inhibiting apoptosis, whereas PFKP deficiency results in the opposite effects. CONCLUSION: PFKP acts as an oncogene involved in tumorigenesis and may influence the immune microenvironment within the tumor. Our findings suggest that PFKP could serve as a potential biomarker for predicting prognosis and the efficacy of immunotherapy in tumors.

Chronic intermittent hypoxia triggers cardiac fibrosis: Role of epididymal white adipose tissue senescent remodeling?

AIM: Obstructive sleep apnea (OSA) is a growing health problem affecting nearly 1 billion people worldwide. The landmark feature of OSA is chronic intermittent hypoxia (CIH), accounting for multiple organ damage, including heart disease. CIH profoundly alters both visceral white adipose tissue (WAT) and heart structure and function, but little is known regarding inter-organ interaction in the context of CIH. We recently showed that visceral WAT senescence drives myocardial alterations in aged mice without CIH. Here, we aimed at investigating whether CIH induces a premature visceral WAT senescent phenotype, triggering subsequent cardiac remodeling. METHODS: In a first experiment, 10-week-old C57bl6J male mice (n = 10/group) were exposed to 14 days of CIH (8 h daily, 5%-21% cyclic inspired oxygen fraction, 60 s per cycle). In a second series, mice were submitted to either epididymal WAT surgical lipectomy or sham surgery before CIH exposure. Finally, we used p53 deficient mice or Wild-type (WT) littermates, also exposed to the same CIH protocol. Epididymal WAT was assessed for fibrosis, DNA damages, oxidative stress, markers of senescence (p16, p21, and p53), and inflammation by RT-qPCR and histology, and myocardium was assessed for fibrosis and cardiomyocyte hypertrophy. RESULTS: CIH-induced epididymal WAT remodeling characterized by increased fibrosis, oxidative stress, DNA damage response, inflammation, and increased expression of senescent markers. CIH-induced epididymal WAT remodeling was associated with subtle and early myocardial interstitial fibrosis. Both epididymal WAT surgical lipectomy and p53 deletion prevented CIH-induced myocardial fibrosis. CONCLUSION: Short-term exposure to CIH induces epididymal WAT senescent remodeling and cardiac interstitial fibrosis, the latter being prevented by lipectomy. This finding strongly suggests visceral WAT senescence as a new target to mitigate OSA-related cardiac disorders.

Mid-term outcomes of different treatments of internal iliac artery in endovascular aneurysm repair.

OBJECTIVE: To evaluate the mid-term outcomes of different treatment strategies for the internal iliac artery (IIA) during EVAR. METHODS: This was a retrospective study. All patients undergoing EVAR, who required treatment of at least one side of IIA from January 2013 to July 2022 in a single center, were included. According to the different treatment strategies for IIA, the patients were divided into UP (unilateral preservation), BP (bilateral preservation) and BE (bilateral embolization) groups. The primary outcomes included buttock claudication, bowel ischemia and iliac-related reintervention. Then patients who underwent IIA reconstruction were divided into IPG (iliac parallel stent graft) and IBG (iliac branch stent graft) groups according to the reconstruction technique. The primary outcomes included endoleak, iliac branch occlusion and iliac-related reintervention. RESULTS: A total of 237 patients were included, including 167 in the UP group, 9 in the BP group and 61 in the BE group. The mean follow-up time was 39.0 ± 27.7, 50.0 ± 22.1 and 25.8 ± 18.9 months in UP, BP and BE groups, respectively. Thirty cases (12.7%) of buttock claudication occurred, and it was significantly higher in the BE group than the UP group (26.2% vs. 7.8%, p < 0.001). There were no significant differences in the other follow-up outcomes among three groups. The K-M analysis indicated that the patients in the BE group had a lower survival rate than those in the other two groups (p = 0.024). 24 patients underwent IIA reconstruction, including 8 in the IPG group and 16 in the IBG group. The endoleak in the IBG group was significantly lower than that in the IPG group (0% vs. 25.0%, p = 0.041). The iliac-related reintervention, iliac occlusion and mortality were similar between the two groups. CONCLUSION: Overall it is beneficial for patients to preserve at least one side of IIA during EVAR as much as possible. Compared with IPG, IBG might be more applicable for IIA reconstruction.

Safety evaluation of extracorporeal shockwave lithotripsy for pancreatic stones: Experience based on a large chronic pancreatitis cohort.

BACKGROUND: The safety of extracorporeal shock wave lithotripsy for pancreatic stones (P-ESWL) and adverse events were not evaluated and classified within large sample population. This study aimed to evaluate the safety and classify the adverse events of P-ESWL based on a large sample cohort. METHODS: This is an observational study based on the large prospective chronic pancreatitis (CP) cohort. Patients with painful pancreatic stones over 5 mm who underwent P-ESWL between March 2011 and June 2018 at Shanghai Changhai Hospital were included. Adverse events after P-ESWL including complications and transient adverse events (TAEs) were recorded. Risk factors of adverse events were analyzed through univariable and multivariable logistics regression analysis. Sensitivity analysis was conducted to test the stability of the study. RESULTS: Totally 2,071 patients underwent 5,002 sessions of P-ESWL were included. The overall complication rate and TAEs rate after all P-ESWL procedures were 5.2% and 20.9%. The complications and TAEs rate decreased obviously within the first 6 sessions. Several independent risk factors for adverse events after P-ESWL were identified. Sensitivity analysis suggested the stability of the results. CONCLUSIONS: P-ESWL is a safe treatment for pancreatic stones. Multiple P-ESWL sessions did not increase the complications and TAEs rate. ClincialTrials.gov number, NCT05916547.

On the equivalence of demagnetization tensors as discrete cell size approaches zero in three-dimensional space.

The calculation of the demagnetization field is crucial in various disciplines, including magnetic resonance imaging and micromagnetics. A standard method involves discretizing the spatial domain into finite difference cells and using demagnetization tensors to compute the field. Different demagnetization tensors can result in contributions from adjacent cells that do not approach zero, nor do their differences, even as the cell size decreases. This work demonstrates that in three-dimensional space, a specific set of magnetization tensors produces the same total demagnetization field as the Cauchy principal value when the cell size approaches zero. Additionally, we provide a lower bound for the convergence speed, validated through numerical experiments.

Organic Matter Enrichment in Jurassic Hydrocarbon Source Rocks from the Turpan-Hami Basin: Insights from Organic and Elemental Geochemistry.

Petroleum can be generated by thermal cracking of organic matter within sediments, and the organic matter within sediments plays the dominant role in determining oil and gas generation. Organic matter within sediments is characterized by various sources, such as sapropelic organic matter from algal, microbial, and planktonic organisms and humic organic matter from higher plants. Paleo-productivity, terrestrial influx, and depositional environments could obviously influence the enrichment processes of the organic matter within sediments. Organic and elemental geochemical proxies can investigate the sedimentary process and reflect the enrichment characteristics of organic matter. In this study, hydrocarbon source rocks from the Shuixigou Group were collected from the Taibei Sag of the Turpan-Hami Basin, rock-eval pyrolysis was conducted, and stable carbon isotope composition of organic carbon and major and trace element distributions were measured. Based on this, the type and maturation of organic matter, paleo-productivity, terrestrial influx, and depositional paleo-environments were investigated. The results show that the Jurassic hydrocarbon source rocks are characterized by type III kerogen and are in the oil-window stage of maturation. The depositional paleo-environments of hydrocarbon source rocks in different formations are not remarkably different. The water bodies have freshwater oxidizing environments, and the paleo-climatic characteristics are warm and humid. However, the paleo-productivity of samples from the lower Jurassic Sangonghe Formation is higher than samples from other formations. Overall, the organic matter enrichment in Jurassic hydrocarbon source rocks of the Turpan-Hami Basin could be mutually controlled by the paleo-productivity and depositional paleo-environments. The results of this study could provide theoretical insight into deep petroleum exploration and resource evaluation in the Turpan-Hami Basin.

Dimensionally Extending from 1D MX-Chain to Ladder and Nanotube Systems: Structural and Electronic properties.

Molecular one-dimensional (1D) electron systems have attracted much attention due to their unique electronic state, physical and chemical properties derived from high-aspect-ratio structures. Among 1D materials, mixed-valence halogen-bridged transition-metal chain complexes (MX-chains) based on coordination assemblies are currently of particular interest because their electronic properties, such as mixed-valence state and band gap, can be controlled by substituting components and varying configurations. In particular, chemistry has recently noted that dimensionally extending MX-chains through organic rung ligands can introduce and modulate electronic coupling of metal atoms between chains, i.e., interchain interactions. In this review, for the first time, we highlight the recent progress on MX systems from the viewpoint of dimensionally extending from 1D chain to ladder and nanotube, mainly involving structural design and electronic properties. Overall, dimensional extension can not only tune the electronic properties of MX-chain, but also build the unique platform for studying transport dynamics in confined space, such as proton conduction. Based on these features, we envision that the MX-chain systems provide valuable insights into deep understanding of 1D electron systems, as well as the potential applications such as nanoelectronics.

Men with a history of commercial heterosexual contact play essential roles in the transmission of HIV-1 CRF55_01B from men who have sex with men to the general population in Guangxi, China.

Background: There is increasing focus on HIV-1 CRF55_01B in China. However, there is limited information regarding the dissemination of CRF55_01B across different regions and populations in Guangxi. This study was performed to elucidate the evolutionary history of the introduction and dissemination of CRF55_01B in Guangxi. Methods: Molecular network and phylogenetic analyses were used to investigate the transmission characteristics of CRF55_01B in China. The analyses particularly focused on the cross-provincial spatial and temporal transmission patterns between Guangdong Province and Guangxi, as well as the transmission dynamics among different regions and populations within Guangxi. Results: In total, 2226 partial pol sequences of CRF55_01B strains sampled from 2007 to 2022 were collected, including 1895 (85.09%) sequences from Guangdong, 199 (8.94%) sequences from Guangxi, and 172 (7.59%) sequences from other provinces of China. Most people living with HIV in Guangxi were infected with HIV-1 through heterosexuals (52.76%). Among these, 19.10% had a history of commercial heterosexual contact (CHC) and 15.58% had a history of non-marital non-commercial heterosexual contact (NMNCHC). Overall, 1418 sequences were identified in the molecular network. Notably, the sequences from Guangdong Province were most closely linked to those from Guangxi. Phylogenetic analysis showed that CRF55_01B was first introduced from Shenzhen City to Nanning City around 2007. Subsequently, CRF55_01B established local transmission within Guangxi, with Nanning City serving as the transmission center from 2008 to 2017. After 2017, the CRF55_01B strain spread to other regions of Guangxi. Men who have sex with men (MSM) and men with a history of CHC have played a significant role in the transmission of CRF55_01B among different populations in Guangxi. Conclusions: This study provides evidence on the transmission trajectory of CRF55_01B among different regions and populations in Guangxi. Given the bridging role of men with a history of CHC in the dissemination of CRF55_01B from MSM to the general population, it is imperative to enhance surveillance among key populations to mitigate the secondary transmission of HIV-1.

Association between sidedness and survival among chemotherapy refractory metastatic colorectal cancer patients treated with trifluridine/tipiracil or regorafenib.

BACKGROUND: The impact of sidedness on survival of later-line treatment in patients with metastatic colorectal cancer (mCRC) is undetermined. This study aimed to investigate the association between sidedness and survival among chemotherapy refractory patients with mCRC treated with trifluridine/tipiracil (TAS-102) or regorafenib or both. PATIENTS AND METHODS: Patients with mCRC treated with TAS-102 or regorafenib between 2015 and 2020 was retrospectively collected. Patients were stratified into TAS-102 first and regorafenib first, then subdivided into TAS-102 followed by regorafenib (T-R) and regorafenib followed by TAS-102 (R-T) groups. The oncologic outcomes were presented with time-to-treatment failure (TTF) and overall survival (OS). RESULTS: After matching, 376 TAS-102 patients and 376 regorafenib patients were included for outcomes comparison. TTF had insignificant differences while OS was significantly different between TAS-102 and regorafenib groups. Median TTF and OS were 1.9 months versus 2.0 months (P = .701) and 9.1 months versus 7.0 months (P = .008) in TAS-102 and regorafenib, respectively. The OS benefits were consistent regardless primary tumor location. Subgroup analysis with 174 T-R patients and 174 R-T patients was investigated for treatment sequences. TTF and OS had significant differences in both groups. Median TTF and OS were 8.5 months versus 6.3 months (P = .001) and 14.4 months versus 12.6 months (P = .035) in T-R and R-T groups, respectively. The TTF and OS benefits were persisted regardless primary tumor location. CONCLUSION: TAS-102 first provided a better survival benefit in chemotherapy refractory patients with mCRC across all sidedness. Further prospective studies are warranted to validate our conclusions.

Application of 'CDC- Public Security Bureau-NGO' Joint Prevention and Control Mechanism Allied AIDS prevention and control in Guigang, Guangxi.

BACKGROUND: HIV/AIDS has emerged as a nationwide epidemic and has taken the forefront position as the primary infectious killer of adults in China. The control and prevention of the disease have been hampered by a weak link in the form of heterosexual transmission. However, conventional intervention measures have demonstrated suboptimal efficacy in reducing the incidence of new HIV infections. In light of the current epidemiological characteristics, we have developed and executed an innovative intervention model known as the Joint Prevention and Control Mechanism of the 'CDC-Public Security Bureau-NGO'. The purpose of this research is to assess the impact of this model on the AIDS awareness, HIV infection rates, sexual behavior, and associated factors among female sex workers and elderly clients. Through the provision of robust evidence of the efficacy of this innovative model, we seek to advocate for its implementation in future interventions. METHODS: The research design of this study incorporates both a serial cross-sectional study and time-series analysis from 2014 to 2021, including a 4-year traditional intervention (2014-2017) and the 4-year 'CDC-Public Security Bureau-NGO' innovative intervention (2018-2021), was conducted to evaluate the effects of the new intervention. The GM(1, 1) model was performed to predict the proportion of HIV infection without implementing the innovative intervention in 2018-2021; P and C values were used to evaluate the performance of the model. Mann-Kendall test and descriptive methods were used to analyzed the trend of traditional and innovative interventions models on HIV positive detection rate in FSWs and elderly clients. RESULTS: The condom usage rates during the last commercial sexual encounter for FSWs and elderly clients improved from 74.9% and 9.1%, respectively, to 96.9% and 28.1%. (P < 0.05), newly reported cases of HIV have decreased by 15.56% yearly and the HIV positive detection rate among middle-aged and elderly people has dropped by 14.47%. The innovative intervention model has significantly reduced the HIV infection rates. CONCLUSIONS: The 'CDC-Public Security Bureau-NGO' innovative intervention has achieved beneficial effects on HIV/AIDS prevention and control and provides a good reference for Guangxi, China.

Long-term clinical outcomes of extracorporeal shockwave lithotripsy and endoscopic retrograde cholangiopancreatography for pancreatic duct stone treatment in patients with chronic pancreatitis.

BACKGROUND AND AIMS: Extracorporeal shock wave lithotripsy for pancreatic stones (P-ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) are the preferred therapeutic approaches for painful chronic pancreatitis (CP) with pancreatic stones. This study aimed to report the short- and long-term outcomes following P-ESWL and ERCP in a large cohort with CP. METHODS: Patients with painful CP and pancreatic stones >5 mm in size, who underwent P-ESWL and subsequent ERCP between March 2011 and June 2018, were included in this retrospective-prospective mixed observational study. The total stone clearance rates were recorded. All patients were followed up until the end of March 2024, with the visual analogue scale (VAS) for pain, pain type, quality-of-life scores and other relevant information recorded. RESULTS: A total of 2071 patients underwent P-ESWL, and 93.1% of them subsequently underwent ERCP during the study period. Patients were followed up for an average of 11.8 years from the onset of CP and 6.7 years from the first P-ESWL procedure. Complete stone clearance was achieved in 73.7% of the patients. At the end of the follow-up period, 70.1% of the patients achieved complete pain remission. Significant pain type conversion and lower VAS scores were observed in the patients after treatment. Quality-of-life scores and body mass indices increased after P-ESWL and ERCP. CONCLUSIONS: P-ESWL and ERCP are effective and minimally invasive treatments for pancreatic stones in patients with painful CP. Most patients achieved complete pain relief, and pain-type conversion was common after treatment. (ClinicalTrials.gov: NCT05916547).

Scutellaria baicalensis Polysaccharide-Mediated Green Synthesis of Smaller Silver Nanoparticles with Enhanced Antimicrobial and Antibiofilm Activity.

Silver nanoparticles (AgNPs) have attracted widespread attention in multidrug-resistant bacterial infections. However, the application of AgNPs synthesized by conventional methods is restricted by its high costs, toxicity, and poor stability. Herein, a water-soluble polysaccharide (Scutellaria baicalensis polysaccharide, SBP) rich in reducing sugars was used as both the reductant and stabilizer to greenly synthesize spherical AgNPs@SBP with smaller particle sizes (11.18 ± 2.50 nm) and higher negative zeta potential (-23.05 ± 2.76 mV), which was favorable to enhance its antimicrobial activity and improve pH and thermal stability. Besides, SBP facilitated the adhesion and penetration of AgNPs@SBP to methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Escherichia coli (CREC), thus significantly enhancing its antibacterial activity (increased by 32-fold and 64-fold, respectively). Likewise, AgNPs@SBP at a low concentration (7.8 µg/mL) could effectively penetrate and inhibit nearly 90% of MRSA and CREC biofilm formation. Antimicrobial mechanism studies showed that AgNPs@SBP could lead to more severe cell membrane damage and genetic material leakage by upregulating reactive oxygen species and depolarizing mitochondrial membrane potential, ultimately resulting in the apoptosis of bacteria. Overall, the wrapping of SBP significantly enhanced the antibacterial and antibiofilm activity of AgNPs, which possessed great potential in the prevention and treatment of multidrug-resistant bacterial infections.

HIV knowledge, sexual attitudes, and PrEP-Eligible behaviors among college students in Southwest China: a cross-sectional study.

BACKGROUND: There is an increasing number of human immunodeficiency virus (HIV) reported cases among students in Southwest China. However, the data on HIV/sex-related knowledge, attitude toward sex, sexual behaviors, and correlates of pre-exposure prophylaxis (PrEP)-eligible behaviors among college students in this area is still limited. This study aimed to assess the prevalence of HIV/sex-related knowledge, sexual attitudes, sexual behaviors, and factors associated with PrEP-eligible behaviors among college students. METHOD: An online survey from 2020 to 2021 based on a multistage stratified and cluster sampling method was conducted among college students in Southwest China, and a well-designed questionnaire collected data. Propensity score matching (PSM), logistic, and log-binomial regression were used to identify the determinants of PrEP-eligible behaviors. RESULT: A total of 108,987 students participated in the survey, and 92,946 provided valid responses. 91.6% (85,145/92,946) had good HIV-related knowledge, while only 26.0% (24,137/92,946) reported awareness of sex-related knowledge. Furthermore, more than half of the participants (64.5%) held negative stances towards engaging in "one-night stand", and 58.9% (617/1,047) reported PrEP-eligible behaviors. Log-binomial regression analysis indicated that unaware of HIV-related knowledge (aPR = 1.66, 95% CI:1.22-2.26, P = 0.001), not discussing about sex with their parent(s) (aPR = 1.16, 95% CI:1.01-1.33, P = 0.021), not receiving sex-related education in school(aPR = 1.24, 95% CI: 1.07-1.45, P = 0.005), not participating in HIV/AIDS prevention activities in the past year (aPR = 1.32, 95%CI:1.09-1.60, P = 0.004), experiencing forced sex (aPR = 2.08, 95% CI: 1.19-3.63, P = 0.010), and having the drug abuse (aPR = 22.21, 95% CI:5.59-88.31, P < 0.001) were significantly associated with increased odds of PrEP-eligible behaviors. CONCLUSION: College students in Southwest China exhibited suboptimal HIV/sex-related knowledge, received limited sex education, reported conservative attitudes towards casual sex, and significant PrEP-eligible behaviors. These findings suggest that sexually experienced college students who were unaware of HIV-related knowledge, lacked sex education, experienced forced sex, and reported drug abuse were the key individuals for evaluating eligibility for PrEP initiation, and interventions aimed at increasing awareness of HIV/sex-related knowledge, promoting participation in sex education, addressing issues related to forced sex and tackling drug abuse could contribute to reducing the incidence of PrEP-eligible behaviors among college students.

Green manuring combined with zeolite reduced nitrous oxide emissions in maize field by targeting microbial nitrogen transformations.

Green manure is a crucial strategy for increasing cereal yield and mitigating environmental burden while reducing chemical N fertilizer. To effectively tackle climate change, finding ways to reduce nitrous oxide (N2O) emissions from green manuring systems is vital. Herein, field and 15N labeled microcosm experiments were arranged to investigate the effect and mechanisms of green manuring and zeolite application on N2O emission. Both experiments comprised four treatments: conventional chemical N (N100), 70 % chemical N (N70), N70 with green manure (N70 + CV), and N70 + CV combined with zeolite (N70 + CV + Z). Compared with N100, both N70 + CV and N70 + CV + Z maintained maize yield, cumulative N2O emissions decreased by 37.7 % and 34.9 % in N70 + CV + Z in 2022-yr and 2023-yr, and by 12.8 % in N70 + CV in 2022-yr. Moreover, the reduction of N2O emission primarily occurred after incorporating green manure. The N100 and N70 + CV demonstrated a similar transformed proportion of chemical N to N2O (i.e., 4.9 % and 4.7 %) while reducing it to 2.7 % in N70 + CV + Z. Additionally, a mere 0.7 % of green manure N was transformed to N2O in both N70 + CV and N70 + CV + Z treatments. Compared with N100, both N70 + CV and N70 + CV + Z decreased the relative abundances of ammonia oxidation microbes, increased denitrifier and the ratios of (nirK + nirS)/nosZ and norBC/nosZ. Furthermore, compared with N70 + CV, N70 + CV + Z decreased the relative abundances of N2O-producer and the ratios of (nirK + nirS)/nosZ and norBC/nosZ in denitrification. These findings revealed that the reduction of N2O emissions resulting from green manure replaced chemical N was mainly due to weakened nitrification, while zeolite reduced N2O emissions attributed to enhanced conversion of N2O to N2. Moreover, certain key N-cycling functional bacteria, such as Phycisphaerae, Rubrobacteria, and Thermoflexia, were positively correlated with N2O emission. In contrast, Dehalococcoidia, Gammaproteobacteria, and Betaproteobacteria were negatively correlated with N2O emission. This investigation uncovered the underlying mechanisms for effectively reducing N2O emissions through green manuring combined with zeolite.

SEC16A Variants Predispose to Chronic Pancreatitis by Impairing ER-to-Golgi Transport and Inducing ER Stress.

Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next-generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26-2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67-4.50) and in a biobank meta-analysis (OR, 1.16; 95% CI, 1.04-1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9-edited HEK293T cell lines show that loss-of-function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/- mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein-stimulated pancreatitis models, Sec16a+/- mice display heightened pancreatic inflammation and fibrosis compared to wild-type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.