Rationally designed febuxostat-based hydroxamic acid and its pH-Responsive nanoformulation elicits anti-tumor activity.

Attempts to furnish antitumor structural templates that can prevent the occurrence of drug-induced hyperuricemia spurred us to generate xanthine oxidase inhibitor-based hydroxamic acids and anilides. Specifically, the design strategy involved the insertion of febuxostat (xanthine oxidase inhibitor) as a surface recognition part of the HDAC inhibitor pharmacophore model. Investigation outcomes revealed that hydroxamic acid 4 elicited remarkable antileukemic effects mediated via HDAC isoform inhibition. Delightfully, the adduct retained xanthine oxidase inhibitory activity, though xanthine oxidase inhibition was not the underlying mechanism of its cell growth inhibitory effects. Also, compound 4 demonstrated significant in-vivo anti-hyperuricemic (PO-induced hyperuricemia model) and antitumor activity in an HL-60 xenograft mice model. Compound 4 was conjugated with poly (ethylene glycol) poly(aspartic acid) block copolymer to furnish pH-responsive nanoparticles (NPs) in pursuit of circumventing its cytotoxicity towards the normal cell lines. SEM analysis revealed that NPs had uniform size distributions, while TEM analysis ascertained the spherical shape of NPs, indicating their ability to undergo self-assembly. HDAC inhibitor 4 was liberated from the matrix due to the polymeric nanoformulation's pH-responsiveness, and the NPs demonstrated selective cancer cell targeting ability.

Association Between Social Vulnerability and Gastrointestinal Cancer Mortality in the United States Counties.

Background and Aims: Social determinants of health contribute to disparities in gastrointestinal (GI) cancer mortality between individuals in the US. Their effects on count-level mortality rates remain uncertain. We aimed to assess the association between county social vulnerability and GI cancer mortality. Methods: In this ecological study (2016-2020), we obtained US county Social Vulnerability Index (SVI) from the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry and age-adjusted mortality rates (AAMRs) for GI cancers from Centers for Disease Control and Prevention WONDER (Wide-Ranging Online Data for Epidemiological Research). SVI ranges from 0 to 1, with higher indices indicating greater vulnerability. We presented AAMRs by quintiles of SVIs. We used Poisson regression through generalized estimating equation to calculate rate ratios (RRs) and 95% confidence intervals (CIs) for GI cancer mortality by quintiles of SVI. Results: There were 799,968 deaths related to GI cancers from 2016 to 2020, resulting in an AAMR (95% CI) of 39.9 (41.4-51.2) deaths per 100,000 population. The largest concentration of counties with greater SVI and GI cancer mortality was clustered in the southern US. Counties with greater SVI had higher mortality related to all GI cancers (RRQ5 vs Q1, 1.19 [95% CI, 1.14-1.24]), gastric cancer (1.58 [1.48-1.69]), liver cancer (1.54 [1.36-1.73]), and colorectal cancer (RRQ5 vs Q1, 1.23 [95% CI, 1.15-1.31]). RRs for overall GI cancers were greater among individuals <45 years (1.24 [1.15-1.32]), men (1.22 [1.16-1.27]), Hispanic individuals (1.33 [1.18-1.50]), and rural counties (1.21 [1.14-1.27]) compared with their counterparts. Conclusion: Socially disadvantaged counties face a disproportionately high burden of GI cancer mortality in the US. Targeted public health interventions should aim to address social inequities faced by underserved communities.

Developmental trajectories of professional preparedness among senior nursing students during clinical placement: A longitudinal study.

BACKGROUND: Newly graduated nurses' lack of professional competence is associated with inadequate preparation during their clinical placement as nursing students. Clinical placement is a critical stage in the development of nursing students' professional preparedness. However, research on the trajectory of nursing students' professional preparedness during clinical placement has not yielded findings with the same specificity. OBJECTIVES: The aim of this study is to estimate differences in professional preparedness levels at different clinical placement stages, to identify distinct patterns of professional preparedness trajectories during clinical placement, and to evaluate predictors of these trajectory group memberships. DESIGN: A quantitative longitudinal study. SETTINGS: Participants were recruited on a voluntary basis using convenience sampling at a tertiary hospital in Nanning, China. PARTICIPANTS: 224 senior nursing students were initially invited to participate in the study. A total of 178 nursing students successfully completed the follow-up assessments at baseline, as well as at 1 month, 4 months, and 8 months into their clinical placement. METHODS: Participants completed four online surveys, during which their professional preparedness level was measured using the Perceived Professional Preparedness questionnaire for senior nursing students. Professional preparedness scores at different time points were compared using one-way repeated measures ANOVA and latent growth model. Group-based trajectory model was applied to identify professional preparedness trajectories. Multiple logistic regression was adopted to determine the predictors of trajectory group memberships. RESULTS: The entire sample of Senior nursing students experienced a significant increase in professional preparedness during clinical placement. The best-fitting group-based trajectory model delineated three distinct trajectories: low-slowly increase trajectory (27.53 % of sample), moderate-rapidly increase trajectory (47.19 % of sample) and a high-stably increase trajectory (25.28 % of sample). Male, good and excellent academic performance, and very high degree of professional interest are the predictors of the moderate-rapidly increase trajectory. While male, good and excellent academic performance, high and very high degree of professional interest and participating in medical-related part-time employment are the predictors of the high-stable increase trajectory. CONCLUSIONS: Senior nursing students exhibit different levels of professional preparedness throughout their clinical placement. Simultaneously, three different trajectories were identified among the sample of nursing students. Therefore, in future research, greater attention should be directed towards the professional preparedness levels of nursing students with different trajectories, and early identification and targeted interventions should be prioritized.

Fitness implications of low-temperature storage for Eocanthecona furcellata (Hemiptera: Pentatomidae).

Exploring the impact of low-temperature storage on the fitness of natural enemy insects is crucial for practical field applications because this parameter directly influences their potential for population growth and effective pest control. Eocanthecona furcellata (Wolff) (Hemiptera: Pentatomidae) is widely used in biological pest control. This study aimed to identify optimal storage stages, temperatures, and durations for E. furcellata to produce high-quality individuals for practical use. The quality of E. furcellata after storage was evaluated by assessing parameters such as predatory capacity and fecundity, along with age-stage, two-sex life table. The findings revealed that the adult stage was the optimal storage form for E. furcellata, and the most favorable temperature for storage was 12 °C. Adult females had the highest predatory ability after 15 days of storage at 12 °C. Although survival rates declined with prolonged storage, they remained above 50% after 30 days, and longevity, fecundity, and predatory capacity of surviving individuals remained comparable to those of individuals in the control group (rearing at a constant temperature of 26 °C without low-temperature storage). The effects of low-temperature storage extended to the F1 generation of E. furcellata, which exhibited maximum mean longevity, fecundity, net reproductive rate, and mean generation time as well as fastest population growth after 30 days of storage at 12 °C. These results can be used to achieve optimal low-temperature storage conditions for E. furcellata production, particularly for extending its shelf life.

[Simultaneous determination of 61 hormones in water by solid phase extraction-ultra performance liquid chromatography-tandem mass spectrometry].

Concerns over the emergence of steroid hormones as pollutants in water have grown. Steroid hormone compounds present challenges in the simultaneous detection of total residual hormones owing to their analogous structures and diverse types. In this study, we established a rapid and high-throughput continuous online method based on solid phase extraction (SPE) coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the simultaneous determination of 61 hormone components, including 48 glucocorticoids, 1 mineralocorticoid, 4 androgens, and 8 progesterones, in water. Various SPE columns were investigated to assess their extraction efficiency for enriching and purifying target compounds in a large sample volume (1 L). An HC-C18 SPE column was selected because of its superior performance. Acetonitrile was used as a washing solution during SPE to ensure that the majority of the tested substances achieved recoveries exceeding 70% and effectively avoid interferences from water-soluble components. Various C8 and C18 columns were tested, and the optimal HPLC conditions for hormone retention were established. We systematically evaluated different UPLC columns and mobile phases, including methanol-water and acetonitrile-water systems with 0.1% formic acid added to the aqueous phase. The optimized UPLC conditions were as follows: BEH C18 column (100 mm×2.1 mm, 1.7 µm); column temperature, 40 ℃; flow rate, 0.3 mL/min; injection volume, 5 µL; mobile phase A: 0.1% formic acid aqueous phase; mobile phase B: acetonitrile. Gradient elution was performed as follows: 0-0.5 min, 30%B; 0.5-15.0 min, 30%B-75%B; 15.0-18.0 min, 75%B-98%B; 18.0-19.0 min, 98%B; 19.0-19.1 min, 98%B-30%B; 19.1-20.0 min, 30%B. Both positive- and negative-ion modes were explored in the UPLC-MS/MS experiment to obtain the full scan of the parent ions, and positive mode was finally selected for electrospray ionization (ESI). Two product ions exhibiting strong signals and minimal interference were selected for quantitative and qualitative ion analyses, using an external standard method for quantification. MS/MS was performed in positive-ion (ESI+) mode with multiple reaction monitoring (MRM) scanning. The MS/MS parameters were as follows: atomizing gas pressure, 379 kPa; curtain air pressure, 241 kPa; spray voltage, 5500 V; desolvation temperature, 550 ℃; collision exit voltage (CXP), 13 V; intake voltage (EP), 10 V; and residence time of each ion pair, 0.5 ms. Other instrument settings, such as the collision energy and declustering voltage, were also optimized. The 61 hormones exhibited excellent linear relationships within their corresponding concentration ranges, with correlation coefficients greater than 0.99. The method detection limits (MDLs) were in the range of 0.05-1.50 ng/L. The average recoveries of the 61 hormones across three spiked levels ranged from 62.3% to 125.2%, with relative standard deviations (RSDs, n=6) of 1.1%-10.5%. Using this method, we successfully detected 10 hormone components (cortisone, fluticasone propionate, ciclesonide, betamethasone dipropionate, clobetasone butyrate, diflucortolone valerate, halobetasol propionate, isoflupredone, difluprednate, and hydroxyprogesterone caproate) in various surface water and groundwater samples collected from the Taihu Basin region. The SPE-UPLC-MS/MS method presented in this paper is simple, highly sensitivity, and exceptionally accurate. Thus, it exhibits promising potential for tracing targeted hormone residues in water and will be of great value in monitoring and ensuring water safety. Finally, a regional analysis was conducted on the hormone levels in water, and suggestions were made for the targeted treatment of hormone residues in future sewage treatment processes.

Supplementation with Bifidobacterium animalis subsp. lactis MH-022 for remission of motor impairments in a 6-OHDA-induced Parkinson's disease rat model by reducing inflammation, reshaping the gut microbiome, and fostering specific microbial taxa.

Inflammation significantly influences the degeneration of dopaminergic neurons in Parkinson's disease (PD), which is potentially intensified by associated gut dysbiosis. The therapeutic potential of probiotics, due to their antioxidant, anti-inflammatory, and gut microbiota modulatory properties, is explored herein as a means to improve gut health and influence the gut-brain-microbiota axis in the context of PD. In this study, we investigated the role and possible mechanism of Bifidobacterium animalis subsp. lactis MH-022 (B. lactis MH-022) supplementation in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Findings demonstrated that B. lactis MH-022 supplementation markedly ameliorated motor deficits, preserved dopaminergic neurons, enhanced the antioxidant capacity, and mitigated inflammation through restoring mitochondrial function. Furthermore, B. lactis MH-022 supplementation significantly altered the gut microbiota composition, augmenting the production of short-chain fatty acids and promoting the proliferation of beneficial bacterial taxa, thereby reinforcing their anti-inflammatory properties. Correlation analyses established strong associations between specific bacterial taxa and improvements in motor function, antioxidant levels, and reductions in inflammation markers. These insights emphasize the therapeutic potential of B. lactis MH-022 in modulating diverse aspects of PD, particularly highlighting its role in reducing inflammation, restoring mitochondrial function, enhancing antioxidant capacity, and reshaping the gut microbiota. This multifaceted approach underscores the probiotic's potential in reducing neuroinflammation and protecting dopaminergic neurons, thus offering a promising avenue for PD treatment.

Age-stratified risk of suicide in patients with schizophrenia.

OBJECTIVES: Schizophrenia is associated with an increased risk of suicide. Few studies have investigated the risk of suicide across different ages, likely due to limitations around sample size. METHODS: From the National Health Insurance Research Database in Taiwan, this study identified 195,787 patients with schizophrenia from January 1, 2000, to December 31, 2019. During the study period, 3848 patients died from suicide. We calculated the standardized mortality ratio (SMR) for suicide stratified by age. In this age-stratified, nested case-control study, risk set sampling was used to match each case with 4 living controls by age, sex, and the year of the first diagnosis with schizophrenia. Conditional logistic regression was used for estimating age-stratified risk profiles. RESULTS: The SMR was the highest in the <25 years age group (52.8) and inversely correlated with age. Unemployment was associated with an increased risk of suicide in the 25 to 34, 35 to 44, 45 to 54, and 55 to 64 years age groups. Depressive and sleep disorders before suicide were more common among suicide cases with schizophrenia than among controls across all age groups. Drug-induced and alcohol-induced mental disorders were significantly associated with suicide but were observed only in the age group younger than 54. Heart disease, pneumonia, and moderate or severe renal disease were risk factors for suicide in the age groups less than 65. CONCLUSIONS: The risk factors for suicide differ by age. This study's findings can be used to optimize health-care interventions for preventing suicide in patients with schizophrenia.

Angong Niuhuang Wan ameliorates LPS-induced cerebrovascular edema by inhibiting blood‒brain barrier leakage and promoting the membrane expression of AQP4.

Introduction: Angong Niuhuang Wan (AGNHW), developed during the Qing dynasty (18th century) for the treatment of consciousness disturbances caused by severe infections, has been used to treat brain edema caused by ischemia‒reperfusion. However, it remains unclear whether AGNHW can ameliorate vascular-origin brain edema caused by lipopolysaccharides (LPS). This study explored the ameliorative effects of AGNHW on LPS-induced cerebrovascular edema in mice, as well as the potential underlying mechanisms. Methods: A cerebrovascular edema model was established in male C57BL/6N mice by two intraperitoneal injections of LPS (15 mg/kg), at 0 and 24 h. AGNHW was administered by gavage at doses of 0.2275 g/kg, 0.455 g/kg, and 0.91 g/kg, 2 h after LPS administration. In control mice, normal saline (NS) or AGNHW (0.455 g/kg) was administered by gavage 2 h after intraperitoneal injection of NS. The survival rate, cerebral water content, cerebral venous FITC-dextran leakage, Evans blue extravasation, and expression of vascular endothelial cadherin (VE-cadherin), zonula occludens-1 (ZO-1), claudin-5, phosphorylated caveolin-1 (CAV-1), and cytomembrane and cytoplasmic aquaporin 1 (AQP1) and aquaporin 4 (AQP4) were evaluated. The cerebral tissue phosphoproteome, blood levels of AGNHW metabolites, and the relationships between these blood metabolites and differentially phosphorylated proteins were analyzed. Results: AGNHW inhibited the LPS-induced decrease in survival rate, increase in cerebral water content, decrease in VE-Cadherin expression and increase in phosphorylated CAV-1 (P-CAV-1). AGNHW treatment increased the expression of AQP4 on astrocyte membrane after LPS injection. AGNHW also inhibited the LPS-induced increases in the phosphorylation of 21 proteins, including protein kinase C-α (PKC-α) and mitogen-activated protein kinase 1 (MAPK1), in the cerebral tissue. Eleven AGNHW metabolites were detected in the blood. These metabolites might exert therapeutic effects by regulating PKC-α and MAPK1. Conclusion: AGNHW can ameliorate cerebrovascular edema caused by LPS. This effect is associated with the inhibition of VE-Cadherin reduction and CAV-1 phosphorylation, as well as the upregulation of AQP4 expression on the astrocyte membrane, following LPS injection.

Fungal Infections in Hospitalized Patients of Systemic Lupus Erythematosus: A United States Nationwide Cohort Analysis.

Introduction/objective Immunosuppressive therapy is the cornerstone of management in patients with systemic lupus erythematosus (SLE). Patients on immunosuppressive therapy are at increased risk of developing opportunistic fungal infections. We conducted this analysis to describe the epidemiology, including incidence, risk factors, and outcomes, of fungal infections in hospitalized patients with SLE in the United States. Method A retrospective cohort study was performed by analyzing the National Inpatient Sample (NIS) 2016-2020 for all patients with a discharge diagnosis of SLE and fungal infections, including histoplasmosis, pneumocystosis, cryptococcosis, aspergillosis, and blastomycosis, as a primary or secondary diagnosis via ICD-10 (International Classification of Diseases 10th Revision) codes. Frequencies, demographics, and trends were determined and compared between hospitalized patients with SLE and those without SLE. STATA version 17 was used for data analysis. A p-value of ≤0.05 was considered statistically significant. Results In hospitalized SLE patients, there were lower odds of developing fungal infections in females (odds ratio (OR): 0.63 (95% confidence interval (CI): 0.49-0.80)) and higher odds in Hispanic (OR: 1.52 (95% CI: 1.16-1.98) and Asian (OR: 1.78 (95% CI: 1.15-2.75) populations. Steroid use (OR: 1.96 (95% CI: 1.58-2.42)), concomitant HIV infection(OR: 22.39 (95% CI: 16.06-31.22)), and the presence of leukemias (OR: 3.56 (95% CI: 1.67-7.59)) and lymphomas (OR: 3.29 (95% CI: 1.78-6.09)) in hospitalized SLE patients were significant predictors of fungal infection (p < 0.01). There were differences in the incidence of fungal infections based on geographical areas in the US, with blastomycosis being more common in the Midwest. From 2016 to 2020, there was a decline in the incidence rate of hospitalization per 100,000 for non-SLE patients with fungal infections (10.7 per 100,000 hospitalizations in 2016 versus 9.6 per 100,000 hospitalizations in 2020), whereas this rate remained steady for the SLE cohort (0.1 per 100,000 hospitalizations in 2016 versus 0.2 per 100,000 hospitalizations in 2020). Conclusions Hospitalized patients with SLE are at an increased risk of developing fungal infections, and this risk is increased further in patients who are males, are on steroid therapy, and have HIV or leukemia and lymphomas. Further studies can be done to explain the increased risk of fungal infections associated with these patient characteristics.

Sarcopenia is associated with short- and long-term mortality in patients with acute-on-chronic liver failure.

BACKGROUND: While sarcopenia is recognized as a predictor of mortality in cirrhosis, its influence on acute-on-chronic liver failure (ACLF) remains uncertain. Despite multiple studies examining the impact of sarcopenia on short-term mortality in patients with ACLF, the sample size of these studies was limited, and their outcomes were inconsistent. Therefore, this study aimed to explore the impact of sarcopenia on both short- and long-term mortality in patients with ACLF. METHODS: This retrospective cohort study included 414 patients with ACLF that were treated between January 2016 and September 2022. Sarcopenia was diagnosed based on the measurement of the skeletal muscle index at the third lumbar vertebra (L3-SMI). Subsequently, the patients were divided into sarcopenia and non-sarcopenia groups. We analysed the basic clinical data of the two groups. Multivariate Cox proportional analysis was used to analyse short-term (28 days) and long-term (1 year and overall) mortality rates. RESULTS: A total of 414 patients were included, with a mean age of 52.88 ± 13.41 years. Among them, 318 (76.8%) were male, and 239 (57.7%) had sarcopenia. A total of 280 (67.6%) patients died during the study period. Among them, 153 patients died within 28 days (37%) and 209 patients died within 1 year (50.5%). We found that the 28-day, 1-year and overall mortality rates in the sarcopenia group were significantly higher than those in the non-sarcopenia group (37% vs. 22.3%, P < 0.01; 50.5% vs. 34.9%, P < 0.01; and 67.6% vs. 53.1%, P < 0.01, respectively). Multivariate Cox regression analysis revealed that sarcopenia was significantly associated with increased mortality. The hazard ratios for sarcopenia were 2.05 (95% confidence interval [CI] 1.41-3.00, P < 0.01) for 28-day mortality, 1.81 (95% CI 1.29-2.54, P < 0.01) for 1-year mortality and 1.82 (95% CI 1.30-2.55, P < 0.01) for overall mortality. In addition, muscle density and international normalized ratio were associated with short- and long-term mortality. CONCLUSIONS: Sarcopenia is associated with both short- and long-term mortality in patients with ACLF. Therefore, regular monitoring for sarcopenia is important for these patients.

Racial and ethnic disparities in gallbladder cancer: A two-decade analysis of incidence and mortality rates in the US.

BACKGROUND: Gallbladder cancer (GBC) is an aggressive malignancy that is usually diagnosed at a late stage. Prior data showed increasing incidence of GBC in the US. However, little is known about race/ethnic-specific incidence and mortality trends of GBC per stage at diagnosis. Therefore, we aimed to conduct a time-trend analysis of GBC incidence and mortality rates categorized by race/ethnicity and stage-at-diagnosis. METHODS: Age-adjusted GBC incidence and mortality rates were calculated using SEER*Stat software from the United States Cancer Statistics database (covers ~98% of US population between 2001 and 2020) and NCHS (covers ~100% of the US population between 2000 and 2020) databases, respectively. Race/Ethnic groups were Non-Hispanic-White (NHW), Non-Hispanic-Black (NHB), Hispanic, Non-Hispanic-Asian/Pacific-Islander (NHAPI), and Non-Hispanic-American-Indian/Alaska-Native (NHAIAN). Stage-at-diagnoses were all stages, early, regional, and distant stages. Joinpoint regression was used to generate time-trends [annual percentage change (APC) and average APC (AAPC)] with parametric estimations and a two-sided t-test (p-value cut-off 0.05). RESULTS: 76,873 patients were diagnosed with GBC with decreasing incidence rates in all races/ethnicities except NHB who experienced an increasing trend between 2001 and 2014 (APC = 2.08, p < 0.01) and plateauing afterward (APC = -1.21, p = 0.31); (AAPC = 1.03, p = 0.03). Among early-stage tumors (9927 patients), incidence rates were decreasing only in Hispanic (AAPC = -4.24, p = 0.006) while stable in other races/ethnicities (NHW: AAPC = -2.61, p = 0.39; NHB: AAPC = -1.73, p = 0.36). For regional-stage tumors (29,690 patients), GBC incidence rates were decreasing only in NHW (AAPC = -1.61, p < 0.001) while stable in other races/ethnicities (NHB: AAPC = 0.73, p = 0.34; Hispanic: AAPC = -1.58, p = 0.24; NHAPI: AAPC = -1.22, p = 0.07). For distant-stage tumors (31,735 patients), incidence rates were increasing in NHB (AAPC = 2.72, p < 0.001), decreasing in Hispanic (AAPC = -0.64, p = 0.04), and stable in NHW (AAPC = 0.07, p = 0.84) and NHAPI (AAPC = 0.79, p = 0.13). There were 43,411 deaths attributed to GBC with decreasing mortality rates in all races/ethnicities except NHB who experienced a stable trend (AAPC = 0.25, p = 0.25). CONCLUSION: Nationwide data over the last two decades show that NHB patients experienced increasing GBC incidence between 2001 and 2014 followed by stabilization of the rates. This increase was driven by late-stage tumors and occurred in the first decade. NHB also experienced non-improving GBC mortality, compared to other race and ethnic groups who had decreasing mortality. This can be due to lack of timely-access to healthcare leading to delayed diagnosis and worse outcomes. Future studies are warranted to investigate contributions to the revealed racial and ethnic disparities, especially in NHB, to improve early detection.

Portable loop-mediated isothermal amplification device with spectrometric detection for rapid pathogen identification.

With the rise in extreme weather due to global warming, coupled with globalization facilitating the spread of infectious diseases, there's a pressing need for portable testing platforms offering simplicity, low cost, and remote transmission, particularly beneficial in resource-limited and non-urban areas. We have developed a portable device using loop-mediated isothermal amplification (LAMP) with spectrometric detection to identify Salmonella Typhimurium DNA. The device utilizes the LinkIt 7697 microcontroller and a microspectrometer to capture and transmit spectral signals in real-time, allowing for improved monitoring and analysis of the reaction progress. We built a hand-held box containing a microspectrometer, thermoelectric cooler, ultraviolet LED, disposable reaction tube, and homemade thermal module, all powered by rechargeable batteries. Additionally, we conducted thorough experiments to ensure temperature accuracy within 1 °C under thermal control, developed a heating module with a LinkIt 7697 IoT development board to heat the DNA mixture to the reaction temperature within 3 min, and integrated foam insulation and a 3D-printed frame to enhance the device's thermal stability. We successfully demonstrated the amplification of Salmonella Typhimurium DNA with an impressive sensitivity of 2.83 × 10-4 ng/µL. A remote webpage interface allows for monitoring the temperature and fluorescence during the LAMP process, improving usability. This portable LAMP device with real-time detection offers a cost-effective solution for detecting Salmonella Typhimurium in food products. Its unique design and capabilities make it a promising tool for ensuring food safety.

Polystyrene microplastics facilitate renal fibrosis through accelerating tubular epithelial cell senescence.

Microplastics (MPs), emerging contaminants, are easily transported and enriched in the kidney, suggesting the kidney is susceptible to the toxicity of MPs. In this study, we explored the toxicity of MPs, including unmodified polystyrene (PS), negative-charged PS-SO3H, and positive-charged PS-NH2 MPs, in mice models for 28 days at a human equivalent concentration. The results showed MPs significantly increased levels of UREA, urea nitrogen (BUN), creatinine (CREA), and uric acid (UA) levels in serum and white blood cells, protein, and microalbumin in urine. In the kidney, MPs triggered persistent inflammation and renal fibrosis, which was caused by the increased senescence of tubular epithelial cells. Moreover, we identified the critical role of the Klotho/Wnt/ß-catenin signaling pathway in the process of MPs induced senescence of tubular epithelial cells, promoting the epithelial-mesenchymal transformation of epithelial cells. MPs supported the secretion of TGF-ß1 by senescent epithelial cells and induced the activation of renal fibroblasts. On the contrary, restoring the function of Klotho can alleviate the senescence of epithelial cells and reverse the activation of fibroblasts. Thus, our study revealed new evidence between MPs and renal fibrosis, and adds an important piece to the whole picture of the plastic pollution on people's health.

T cell receptor repertoire deciphers anti-tuberculosis immunity.

T cell induced cellular immunity is considered to be extremely important for the control of tuberculosis (TB). T cell receptor (TCR), the key component responsible for the specificity and clustering of T cells, holds the potential to advance our understanding of T cell immunity against TB infection. This review systematically expounded the study progressions made in the field of TB-relevant TCRs based on single cell sequencing together with GLIPH2 technology and initiated a comparison of the T cell distribution between peripheral blood and infected organs. We divided clonal expanded T cell clones into recirculation subsets and local subsets to summarize their distinctions in clonal abundance, TCR sequences and antigenic specificity. Notably, local expansion appears to drive the primary variances in T cell subsets between these two contexts, indicating the necessity for further exploration into the functions and specificity of local subsets.

Modifiable Risk Factors in Hispanic Adults With Gastric Cancer in the United States.

BACKGROUND: Hispanics make up 19% of the U.S. population and are experiencing rising rates of cancer, primarily due to an increase in infection-related cancers (gastric, hepatic, cervical) and advanced cancers secondary to delayed screening (colorectal, cervical, breast). There is an increased incidence of gastric cancer (associated with infection, obesity, alcohol, and tobacco use) in Hispanics, especially at a young age, highlighting the need to consider ethnicity as a risk factor. METHODS: This study utilized the 2016-2019 National Inpatient Sample database to examine all patients admitted with gastric cancer. Individuals were stratified by race, age, and comorbidities, including modifiable risk factors that are associated with gastric cancer. RESULTS: There were 5,785 (7.44%) patients aged 18-44, 28,370 (36.49%) aged 45-64, and 43,590 (56.07%) over 65 years of age. Notably, 34.3% of the youngest group were Hispanic, contrasted with 19.7% and 12.9% in the older groups, respectively. Younger Hispanic patients showed a higher prevalence of H. pylori infection (8.6%) compared with older Hispanics (3.6% in the middle age group and 2.1% in the oldest, p<0.01). There was a high prevalence of obesity, tobacco use, and gastric ulcers in this cohort. Other risk factors such as alcohol use and gastric polyps were present at a lesser prevalence. CONCLUSIONS: This study reveals that Hispanic patients tend to have a younger age of onset of gastric cancer, coupled with an increased incidence of H. pylori infection at a younger age. This finding underscores the potential benefit of H. pylori screening among asymptomatic young Hispanics with the aim of reducing gastric cancer morbidity and mortality in this population.

Esophageal cancer mortality disparities between Black and White adults in the United States, 1999-2020: insights from CDC-WONDER.

BACKGROUND AND AIM: Esophageal cancer significantly contributes to US cancer mortality, with notable racial disparities. This study aims to provide updated esophageal cancer mortality trends among Black and White adults from 1999 to 2020. METHODS: CDC-WONDER was used to identify Black and White adults in the United States from 1999 to 2020. We calculated age-standardized mortality rates, absolute rate differences, and rate ratios to compare the mortality differences between these populations. RESULTS: From 1999 to 2020 in the United States, there were 303 267 esophageal cancer deaths, with significant racial disparities. The age-adjusted mortality rate for Black adults fell from 6.52 to 2.62 per 100 000, while for White adults, it declined from 4.19 to 3.97 per 100 000, narrowing the racial mortality gap. Gender-wise, the study showed a decrease in the mortality rate from 3.31 to 2.29 per 100 000 in Black women, but an increase from 1.52 to 1.99 per 100 000 in White women. Among young men, the rate dropped in Black men from 12.82 to 6.26 per 100 000 but rose in White men from 9.90 to 10.57 per 100 000. Regionally, Black adults in the Midwest and South initially had higher mortality rates than Whites, but this gap reduced over time. By 2020, Black men had lower mortality rates across all regions. CONCLUSIONS: Over the last two decades, age-adjusted esophageal cancer mortality decreased in Black adults but stabilized in White adults, reflecting distinct cancer trends and risk factors. The study highlights the importance of tailored public health strategies for healthcare access and risk factor management.

Rescue of nucleus pulposus cells from an oxidative stress microenvironment via glutathione-derived carbon dots to alleviate intervertebral disc degeneration.

The senescence of nucleus pulposus (NP) cells (NPCs), which is induced by the anomalous accumulation of reactive oxygen species (ROS), is a major cause of intervertebral disc degeneration (IVDD). In this research, glutathione-doped carbon dots (GSH-CDs), which are novel carbon dot antioxidant nanozymes, were successfully constructed to remove large amounts of ROS for the maintenance of NP tissue at the physical redox level. After significantly scavenging endogenous ROS via exerting antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant capacity, GSH-CDs with good biocompatibility have been demonstrated to effectively improve mitochondrial dysfunction and rescue NPCs from senescence, catabolism, and inflammatory factors in vivo and in vitro. In vivo imaging data and histomorphological indicators, such as the disc height index (DHI) and Pfirrmann grade, demonstrated prominent improvements in the progression of IVDD after the topical application of GSH-CDs. In summary, this study investigated the GSH-CDs nanozyme, which possesses excellent potential to inhibit the senescence of NPCs with mitochondrial lesions induced by the excessive accumulation of ROS and improve the progression of IVDD, providing potential therapeutic options for clinical treatment.

Emerging perfluoroalkyl substances retard skeletal growth by accelerating osteoblasts senescence via ferroptosis.

Due to the persistent nature and significant negative impacts of perfluorooctanoic acid (PFOA) on human health and other organisms, the emergence of new PFOA alternatives, such as perfluoro (2-methyl-3-oxhexanoic) acid (GenX) and perfluoro-3,6,9-trioxyundecanoic acid (PFO3TDA), have drawn significant attention. However, the toxic effects of PFOA and its substitutes on bones remain limited. In this study, we administered different concentrations of PFOA, GenX, and PFO3TDA via gavage to 3-week-old male BALB/C mice for four weeks. X-ray and micro-CT scans revealed shortening of the femur and tibia and significant reduction in bone density. Additionally, PFOA, GenX, and PFO3TDA promoted osteoblast senescence and impaired osteogenic capabilities. This was characterized by a decrease in the expression of osteogenesis-related genes (OCN, ALP, Runx2, etc.) and an increase in the expression of aging and inflammation-related factors (p16INK4a, P21, MMP3, etc). Furthermore, RNA sequencing revealed activation of the ferroptosis pathway in PFOA-treated osteoblasts, characterized by notable lipid peroxidation and excessive iron accumulation. Finally, by inhibiting the ferroptosis pathway with ferrostatin-1 (Fer-1), we effectively alleviated the senescence of MC3T3-E1 cells treated with PFOA, GenX, and PFO3TDA, and improved their osteogenic capabilities. Therefore, our study provides a new therapeutic insight into the impact of PFOA and its substitutes on bone growth and development.

Antipsychotic medications and severe sepsis in schizophrenia: A nested case-control study.

BACKGROUND: Sepsis constitutes a condition that involves life-threatening organ dysfunction induced by severe infection. This nested case-control study investigated risk factors for severe sepsis and whether antipsychotic use is associated with severe sepsis risk in patients with schizophrenia, a topic that has not been comprehensively explored in previous studies. METHODS: We selected 39,432 patients with schizophrenia aged between 15 and 65 years from Taiwan's Psychiatric Inpatient Medical Claims database for the period 2000-2012. The case group comprised patients with severe sepsis after their first psychiatric admission (n = 1382). The case and control groups were randomly matched (1:4) by age, sex and first psychiatric admission (year) and finally comprised 1382 and 5528 individuals, respectively. We employed multivariable conditional logistic regression to identify (1) risk factors (physical illnesses and nonpsychiatric medications) and (2) antipsychotic-severe sepsis associations. RESULTS: Higher numbers of psychiatric admissions and physical illnesses such as delirium, cerebrovascular disease and cancer were significantly associated with a higher risk of severe sepsis. Furthermore, severe sepsis was associated with the use of antithrombotic agents, systemic corticosteroids and agents targeting the renin-angiotensin system. Clozapine (adjusted risk ratio = 1.65) and quetiapine (adjusted risk ratio = 1.59) use were associated with an increased risk of severe sepsis. The use of more than one antipsychotic drug could further increase this risk. CONCLUSION: Several physical illnesses and nonpsychiatric medications increase the risk of severe sepsis in patients with schizophrenia. Specifically, clozapine or quetiapine use significantly increased the risk of severe sepsis in these patients.

Effect of Jianpi Shengxue Tablet on Iron Metabolism and Nutritional Status in Patients with Renal Anemia: A Prospective, Randomized, Open, Parallel Controlled and Multicenter Clinical Study.

OBJECTIVE: This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia. METHODS: A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups. Patients in the control group were treated with polysaccharide-iron complex, and those in the experimental group were administered Jianpi Shengxue tablet. After 8 weeks of continuous treatment, the therapeutic outcomes regarding anemia were compared between the two groups. RESULTS: After treatment, the red blood cell (RBC) count, hematocrit (HCT), reticulocyte percentage (RET), ferritin (SF), serum iron (SI), transferrin saturation (TSAT), and serum albumin (ALB) all increased (P<0.01), and the clinical symptom score and total iron binding capacity decreased (P<0.01) in the experimental group. Moreover, the improvements in RBC, HCT, RET, SF, SI, TAST, ALB, and clinical symptoms (fatigue, anorexia, dull skin complexion, numbness of hands and feet) in the experimental group were significantly greater than those in the control group (P<0.05). The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group (P<0.01). CONCLUSION: The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia, leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.