Perilla frutescens leaf extracts alleviate acute lung injury in mice by inhibiting KAT2A.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) can lead to respiratory failure and even death. KAT2A is a key target to suppress the development of inflammation. A herb, perilla frutescens, is an effective treatment for pulmonary inflammatory diseases with anti-inflammatory effects; however, its mechanism of action remains unclear. AIM OF THE STUDY: The purpose of this study was to investigate the therapeutic effect and underlying mechanism of perilla frutescens leaf extracts (PLE), in the treatment of ALI by focusing on its ability to treat inflammation. MATERIALS AND METHODS: In vivo and in vitro models of ALI induced by LPS. Respiratory function, histopathological changes of lung, and BEAS-2B cells damage were assessed upon PLE. This effect is also tested under conditions of KAT2A over expression and KAT2A silencing. RESULTS: PLE significantly attenuated LPS-induced histopathological changes in the lungs, improved respiratory function, and increased survival rate from LPS stimuation background in mice. PLE remarkably suppressed the phosphorylation of STAT3, AKT, ERK (1/2) and the release of cytokines (IL-6, TNF-α, and IL-1ß) induced by LPS via inhibiting the expression of KAT2A. CONCLUSIONS: PLE has a dose-dependent anti-inflammatory effect by inhibiting KAT2A expression to suppress LPS-induced ALI n mice. Our study expands the clinical indications of the traditional medicine PLE and provide a theoretical basis for clinical use of acute lung injury.

Prognostic Value of Quantitative Flow Ratio Combined with SYNTAX Scores I/II in Multivessel Coronary Artery Disease: A Small-Sample, Single-Center Study.

Background: A fractional flow reserve (FFR)-fixed-SYNTAX score could decrease the number of high-risk patients. This study explored the prognostic value of non-invasive quantitative flow ratio (QFR)-fixed-SYNTAX I/II scores in multivessel disease patients. Methods: This was a single-center, small-sample, observational study. Multivessel coronary disease patients were enrolled and finished a 1-year follow-up. SYNTAX scores I/II and functional SYNTAX scores I/II based on QFR (cut-off value of 0.85) were calculated for all patients. The composite occurrence of cardiac deaths, any myocardial infarction, or ischemia-driven revascularization were analyzed using a different score system. Results: A total of 160 patients were stratified into risk groups based on a different scoring system. FSS (functional SYNTAX score) and FSSII (functional SYNTAX score II) reduce the radio of high-risk major adverse cardiovascular events (MACEs), transforming the patients from high-risk to medium- and low-risk. Furthermore, FSSII (hazard ratio (HR): 1.069, 95% CI: 1.025-1.115, p = 0.002) showed a better relationship with MACEs than the other score systems. After recalculating SSII, the survival-free ratio stratified by FSSII decreased from 38.46% to 27.27% in the high-risk group and increased from 84.09% to 86.05% in the low-risk group. Conclusions: FSS or FSSII could decrease the number of high-risk patients compared to SYNTAX score (SS) and FSS. SYNTAX II score (SSII) and FSSII showed a better predictive ability than other scoring systems for under-risk stratification.

Analyzing nutrition risks and blood biomarkers in hospitalized patients with tuberculosis: Insights from a 2020 hospital-based study.

BACKGROUND: There exists a bidirectional relationship between tuberculosis (TB) and nutrition, wherein they mutually influence and interact causally. However, current guidance for providing nutrition support to individuals diagnosed with TB remains inadequate, leading to a significant gap in comprehensive patient care. This study aims to assess the nutrition status of patients with TB and endeavors to provide insights into early nutrition interventions for individuals vulnerable to TB-associated malnutrition. METHODS: Data from 2204 newly admitted patients at Beijing Chest Hospital in 2020 were collected, with 1735 patients with confirmed TB aged ≥18 years after exclusions. Patient data, encompassing diagnosis and results from routine blood tests and biochemical analyses conducted on the day after admission, were gathered using the electronic medical records system. Nutrition risk screening was conducted using the Nutritional Risk Screening 2002 (NRS 2002) tool, and questionnaire-based assessments were administered. Statistical analyses were performed using SPSS 17.0 software. RESULTS: Among 1735 patients with TB, the occurrence rate of nutrition risk was 74.58%. Factors such as age ≥65 years, sputum smear positivity for TB, and concurrent illnesses significantly increased the occurrence rate of nutrition risk. Nutrition risk among patients with TB exhibited negative correlations with parameters such as body weight, hemoglobin, and serum albumin level while showing positive correlations with white blood cell count and C-reactive protein, among others. CONCLUSION: The occurrence rate of nutrition risk among patients with TB at Beijing Chest Hospital was notably high, particularly among older individuals, those with sputum smear positivity, and those with concurrent illnesses.

The short-term outcomes and risk factors of post-myocardial infarction ventricular septal rupture: a multi-center retrospective Study.

OBJECTIVES: Post-myocardial infarction ventricular septal rupture (PIVSR) is one of the most severe types of mechanical complications after acute myocardial infarction (AMI) with high mortality and poor prognosis. The risk factors for short-term mortality of patients with PIVSR may be not widely recognized. We aimed to assess the prevalence and short-term mortality risk predictors of PIVSR. METHODS: A total of 62 patients with a diagnosis of PIVSR were admitted to three top general public hospitals in Chongqing, China. Clinical characteristics and short-term outcomes of patients with PIVSR were compared. Predictors of PIVSR were assessed using logistic regression analysis. RESULTS: Mean age was 70.7 ± 10.7 years (38.7% female). The overall in-hospital mortality of PIVSR remained high (71%). Most (47/62) of the patients were in Killip class III or IV at the time of rupture diagnosis. Logistic regression analysis revealed that white blood cell count (WBC, OR 1.619, 95% CI 1.172-2.237, P = 0.005), cardiogenic shock (OR 47.706, 95%CI 2.859-795.945, P = 0.007) and left ventricular ejection fraction (LVEF, OR 0.803, 95%CI 0.689-0.936, P = 0.009) were independent risk factors of in-hospital early mortality. The nomogram developed for predicting the risk of short-term mortality showed a robust discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.956 (95%CI 0.912-1.000). CONCLUSION: The short-term mortality of PIVSR remained high. WBC, cardiogenic shock, and LVEF were the independent predictive factors of short-term mortality. Our nomogram might be used to predict early mortality of patients with PIVSR.

The increased tendency for anemia in traditional Chinese medicine deficient body constitution is associated with the gut microbiome.

Background: Constitution is a valuable part of traditional Chinese medicine theory; it is defined as the internal foundation for the occurrence, development, transformation and outcome of diseases, and has its characteristic gut microbiota. Previous study showed that deficiency constitution was related to lower Hb counts. However, no research has examined how alterations in the gut microbiome induced by deficiency constitution may increase the tendency for anemia. Methods: We used a multiomics strategy to identify and quantify taxonomies and compounds found under deficient constitution individuals and further explore the possible pathological factors that affect red blood cell indices. Results: ① People with deficient constitution showed lower hemoglobin (Hb), more Firmicutes, less Bacteroidetes, and higher α diversity. ② We identified Escherichia coli, Clostridium bolteae, Ruminococcus gnavus, Streptococcus parasanguinis and Flavonifractor plautii as potential biomarkers of deficient constitution. ③ Slackia piriformis, Clostridium_sp_L2_50 and Bacteroides plebeius were enriched in balanced-constitution individuals, and Parabacteroides goldsteinii was the key bacterial marker of balanced constitution. ④ Flavonifractor plautii may be a protective factor against the tendency for anemia among deficient individuals. ⑤ Ruminococcus gnavus may be the shared microbe base of deficiency constitution-related the tendency for anemia. ⑥ The microorganism abundance of the anaerobic phenotype was lower in deficient constitution group. ⑦ Alterations in the microbiome of deficient-constitution individuals were associated with worse health status and a greater risk of anemia, involving intestinal barrier function, metabolism and immune responses, regulated by short-chain fatty acids and bile acid production. Conclusion: The composition of the gut microbiome was altered in people with deficient constitution, which may explain their poor health status and tendency toward anemia.

Chronic kidney diseases and inflammation research: a bibliometric analysis.

Background: Chronic kidney diseases (CKD) is a severe public health problem. This study aimed to explore the field of inflammation-related research in CKD from a bibliometric perspective. Methods: Relevant literature published between 2004 and 2023 were searched from the Web of Science database. The bibliometric analysis were performed to summarize countries, institutions, authors, journals and keywords using VOSviewer and CiteSpace. Results: A total of 9,287 publications on CKD and inflammation were included. Publications were mainly from the United States, China, Italy, Germany, and Japan. The findings revealed that the United States had the highest number of publications in this field, followed by China. There is strong collaboration between the two countries. The most productive institutions included the University of California system and the US Department of Veterans Affairs. Research hotspots primarily focused on inflammation mechanisms, biomarkers, and interventions. Conclusion: This study revealed the basic knowledge structure and provided a comprehensive insight into the research field of CKD and inflammation through bibliometric methods. Future studies should focus on early diagnosis, prevention, and treatment strategies of CKD, and explore more inflammation associated biomarkers and therapeutic targets for CKD.

Increased Intestinal Inflammation and Permeability in Glaucoma.

Objective: Evidence suggests that dysbiosis of the gut microbiota plays a pivotal role in the development of glaucoma. This dysbiosis is commonly associated with chronic intestinal inflammation and increased intestinal permeability. However, the understanding of intestinal inflammation and permeability in glaucoma remains insufficient. This study aims to investigate the potential relationship between fecal inflammation and permeability markers and glaucoma. Methods: We recruited 114 glaucoma patients and 75 healthy controls. Levels of fecal lactoferrin (Lf) and alpha-1 antitrypsin (AAT) were quantified using enzyme linked immunosorbent assay (ELISA) to compare both biomarkers between groups and across different severity grades of glaucoma. Logistic regression analysis was used to assess the association between these fecal biomarkers and glaucoma. The severity of glaucoma was assessed based on the mean deviation (MD) in the visual field. Results: In this study, we observed elevated levels of fecal Lf and AAT in glaucoma patients. The proportion of glaucoma patients with abnormal fecal Lf levels (≥ 7.25 µg/g) was significantly higher than that of the controls (p = 0.012). A positive correlation was noted between fecal Lf and AAT (rho = 0.20, p = 0.006). After adjusting for age and sex, multivariable logistic regression analysis indicated that both fecal Lf (OR = 1.11, 95% CI: 1.01-1.21, p = 0.026) and AAT (OR = 1.01, 95% CI: 1.01-1.02, p < 0.001) positively correlated with glaucoma. These biomarkers might reflect glaucoma severity, with significant differences in fecal Lf levels observed between moderate and severe stages, but not in the early stage. Furthermore, increasing levels of fecal AAT correlated with greater severity of glaucomatous injury and a larger vertical cup-to-disc ratio (VCDR) (p < 0.05). Conclusion: This study suggests an increase in intestinal inflammation and permeability in glaucoma, further indicating the importance of the 'gut-retina axis' in the pathogenesis of the disease and potentially offering new therapeutic avenues.

Inhibition of hepatitis B virus through PPAR-JAK/STAT pathway modulation by electroacupuncture and tenofovir disoproxil fumarate combination therapy.

BACKGROUND: Acupuncture combined with nucleos(t)ide analogues (NAs) has shown promise in treating chronic hepatitis B (CHB), though mechanisms remain unclear. This study evaluates the antiviral effects of combining acupuncture with NAs against hepatitis B virus (HBV) and explores underlying mechanisms. METHODS: The HBV-infected mouse model, established using the high-pressure hydrodynamic method, was divided into three groups: normal saline (NS), tenofovir disoproxil fumarate (TF), and electroacupuncture combined with TF (E_T), n = 6. Antiviral effects were assessed by monitoring HBV DNA, HBsAg, and HBeAg levels weekly. Mechanistic insights were gained via transcriptomics, metabolomics, and 16S rDNA sequencing, validated by WB, PCR, and flow cytometry. RESULTS: Serum HBV DNA levels decreased by 1.98 log10 IU/mL in TF and 2.2 log10 IU/mL in E_T groups compared to NS. Serum HBeAg decreased by 10.61 % in TF and 35.75 % in E_T, while HBsAg decreased by 7.38 % and 37.58 %, respectively. Multi-omics indicated E_T modulates the PPAR pathway, upregulates taurine and all-trans-retinoic acid, and increases gut microbiota like Bacteroides and Blautia. E_T also enhanced tight junction proteins (ZO-1, Occludin, Claudin-4), improving intestinal barrier integrity. Mechanistically, E_T inhibited the PGC-1α/PPAR-α/SIRT1 pathway, reducing PGC-1α, PPAR-α, SIRT1, RXRα, and HNF4α, while promoting JAK/STAT signaling via IFN-γ, p-JAK1, p-JAK2, p-STAT1, IRF8, and suppressing SOCS-1. CONCLUSION: E_T more effectively inhibited HBV replication, showing superior antigen inhibition, particularly HBsAg, than TF alone. This may be due to PPAR-JAK/STAT pathway regulation, suggesting E_T as a potential adjuvant therapy for CHB, especially in achieving a functional cure.

Pancreatic Cancer Cell-derived Migrasomes Promote Cancer Progression by Fostering an Immunosuppressive Tumor Microenvironment.

Pancreatic cancer is distinguished by an immunosuppressive tumor microenvironment (TME) that facilitates cancer progression. The assembly of the TME involves numerous contributing factors. Migrasomes, recently identified as cellular organelles in migrating cells, play a pivotal role in intercellular signaling. However, research into their involvement in cancers remains nascent. Thus far, whether pancreatic cancer cells generate migrasomes and their potential role in TME formation remains unexplored. In this study, it was found that both murine and human pancreatic cancer cells could indeed generate migrasomes, termed pancreatic cancer cell-derived migrasomes (PCDMs), which actively promote cancer progression. Moreover, utilizing chemokine antibody arrays and quantitative mass spectrometry analysis, we observed significant differences between the chemokines, cytokines, and proteins present in PCDMs compared to their originating cell bodies. Notably, PCDMs exhibited an enrichment of immunosuppression-inducing factors. Furthermore, macrophages could directly uptake PCDMs, leading to the expression of high levels of M2-like markers and secretion of tumor-promoting factors. PCDM-induced macrophages played a pivotal role in inhibiting T cell proliferation and activation partially through ARG-1. In summary, this study provides compelling evidence that pancreatic cancer cells generate migrasomes, which play a crucial role in promoting tumor progression by contributing to an immunosuppressive TME. The exploration of migrasomes as a therapeutic target could pave the way for the development of tailored immunotherapies for pancreatic cancer.

Integrated volatile metabolome and transcriptome analyses provide insights into the warm aroma formation elicited by methyl jasmonate in carrot root.

Carrot is a highly significant vegetable cultivated worldwide and possesses a unique aroma with abundant edible and medicinal values. However, it remains largely unknown whether jasmonic acid could regulate aroma formation in carrot. Here, an integrated analysis of the volatile metabolome and transcriptome of carrot roots exposed to different concentrations of methyl jasmonate (MeJA) was performed. The results revealed 1,227 volatile organic compounds and 972 differential accumulated metabolites, with terpenes representing the largest portion. MeJA treatment evidently increased the relative odor activity values as well as the accumulation of most volatile compounds. In addition, 4,787 differentially expressed genes were identified and subjected to function enrichment analysis, indicating a role of terpene biosynthesis and metabolism in response to MeJA application. A network consisting of 4,680 transcription factor-structural pairs that showed highly significant positive correlations was constructed, which may be utilized as genetic targets for examining terpene accumulation and aroma formation elicited by methyl jasmonate. The results from the present work substantially improved our understanding of MeJA-mediated aroma formation in carrot.

Design, synthesis, and mechanism study of novel tetrahydroisoquinoline derivatives as antifungal agents.

In screening for natural-derived fungicides, a series of 32 novel tetrahydroisoquinoline derivatives were designed and synthesized based on tetrahydroisoquinoline alkaloids. Their structures were verified by 1H NMR, 13C NMR, HRMS, and single X-ray crystal diffraction analysis. Most of the target products exhibited medium to excellent antifungal activity against 6 phytopathogenic fungi in vitro at a concentration of 50 mg/L. Interestingly, compounds A13 and A25 with EC50 values of 2.375 and 2.251 mg/L against A. alternate were similar to boscalid (EC50 = 1.195 mg/L). The in vivo experiments revealed that A13 presented 51.61 and 70.97% protection activities against A. alternate at the dosage of 50 and 100 mg/L, respectively, which were equal to that of boscalid (64.52 and 77.42%). SDH enzyme assays and molecular docking studies indicated that compound A13 may act on SDH. In addition, the SEM analysis showed that compound A13 could strongly damage the mycelium morphology. These results revealed that A13 may be a promising lead compound for the development of natural-derived fungicides.

Family burden and psychological distress among Chinese caregivers of elderly people with dementia: a moderated mediation model.

BACKGROUND: Although the Stress-Coping Model (SCM) has been widely used to explain the coping process of individuals facing stressful situations, its applicability to caregivers of elderly people with dementia (PwD) in China needs to be further investigated. Furthermore, the role of external resources in caregivers stress coping is not yet clear. Therefore, our study aimed to investigated the mediating and moderating mechanisms between family burden and psychological distress in PwD caregivers based on the SCM. METHODS: A cross-sectional study, with 193 pairs of PwD and caregivers completed the self-designed questionnaire, Family Burden Scale of Disease, Kessler Psychological Distress Scale, General Self-Efficacy Scale, Simplified Coping Style Question, The Family Adaptation and Cohesion Evaluation Scales II-CV and Social Support Rating Scale. Partial least squares-structural equation modeling (PLS-SEM) analyzed the mediating and moderating effects. RESULTS: Family burden positively correlated with psychological distress; the chain mediation effects of self-efficacy and positive coping between family burden and psychological distress was significant; the interaction term (family function_positive coping) did not but (social support_positive coping) had a significant positive impact on psychological distress. CONCLUSIONS: The findings provides a practical basis for the use of SCM in informal caregivers of elderly PwD, assists understanding the mechanism of the relationship between family burden and psychological distress. And it supplies new perspectives for reducing the negative psychological health status and a theoretical basis for designing interventions for caregivers.

Capacity analysis of short-distance continuous diversion areas on mountainous urban expressways.

The short-distance continuous diversion area plays a crucial role within mountainous urban expressway systems, significantly enhancing the efficiency of specialized road sections through capacity analysis. This study develops a capacity calculation model tailored to the diversion area's unique characteristics and principal capacity-influencing factors. Initially, the research focuses on a specific short-distance continuous diversion area of a mountainous urban expressway, employing video trajectory tracking technology to gather trajectory data. This data serves as the basis for analyzing road and traffic characteristics. Subsequently, the model computes the capacity influenced by eight variables, including diversion point spacing and deceleration lane length, using VISSIM simulation experiments. A gray correlation analysis identifies key factors, which guide the establishment of the model's fundamental structure through two-factor surface fitting results. Mathematical statistical methods are then applied to resolve the model's parameters, culminating in a robust capacity calculation model. The findings reveal that diversion point spacing, along with primary and secondary diversion ratios, significantly influence capacity. Notably, the capacity exhibits a marked quadratic polynomial relationship with the primary diversion ratio and diversion point spacing, and a linear relationship with the secondary diversion ratio. The model's validity is confirmed through a case study at the diversion area north of Huacun Interchange in Chongqing Municipality, where the discrepancy between calculated and actual capacities is under 5%, underscoring the model's high accuracy. These results offer valuable theoretical and methodological support for the planning, design, and traffic management of diversion areas.

Pulmonary delivery of forsythin-phospholipid complexes improves the lung anti-inflammatory efficacy in mice by enhancing dissolution and lung tissue affinity.

Forsythin, currently in phase II clinical trials in China for the treatment of the common cold and influenza, faces challenges in achieving adequate lung drug exposure due to its limited dissolution and permeability, thereby restricting its therapeutic efficacy. The objective of this work was to formulate a forsythin-phospholipid complex (FPC) to enhance its dissolution properties and lung affinity with a particular view to improving pulmonary drug exposure and anti-inflammatory response. The results revealed that forsythin reacted with dipalmitoyl-phosphatidylcholine to form a stable, nanosized FPC suspension. This formulation significantly improved the in vitro drug's dissolution, cellular uptake, and lung affinity compared to its uncomplexed form. Intratracheal administration of FPC in a mouse model of acute lung injury induced by lipopolysaccharide (LPS) resulted in a substantial increase in drug exposure to lung tissues (39.6-fold) and immune cells in the epithelial lining fluid (198-fold) compared to intraperitoneal injection. In addition, FPC instillation exhibited superior local anti-inflammatory effects, leading to improved survival rates among mice with LPS-induced acute respiratory distress syndrome, outperforming both instilled forsythin and injected FPC. Overall, this work demonstrated the potential of phospholipid complexes as a viable option for developing inhalation products for drugs with limited solubility and permeability properties.

Impact of pesticides exposure and type 2 diabetes risk: a systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis of observational studies that assessed the relationship between pesticides exposure and type 2 diabetes. We also examined the presence of heterogeneity and biases across the available studies. METHODS: We conducted a comprehensive literature search of peer-reviewed studies published from 2011 to 2023, without language limitations. A random-effects model was employed to calculate the overall odds ratio (OR) and its corresponding 95% confidence interval (CI). RESULTS: We included 19 studies (n = 12 case-control and n = 7 cross-sectional) for a total of 45,813 participants in our analysis. Our findings revealed a notable correlation between pesticide exposure and type 2 diabetes (non-specific definition) when not limiting pesticide types (OR: 1.19, 95% CI: 1.11-1.28). Subgroup analysis identified associations between pyrethroid (OR: 1.17, 95% CI: 1.05-1.30) and type 2 diabetes, as well as between organochlorine (OR: 1.26, 95% CI: 1.11-1.43) and type 2 diabetes. However, no statistically significant association was observed between herbicide exposure and the onset of type 2 diabetes (OR: 1.26, 95% CI: 0.91-1.75). In the elderly group, pesticide exposure significantly heightened the risk of type 2 diabetes (OR: 1.25, 95% CI: 1.14-1.38), with no statistically significant heterogeneity among studies (I2 = 14.2%, p = 0.323). CONCLUSIONS: Pesticide (organochlorine and pyrethroid) exposure constitutes a risk factor for type 2 diabetes.

Comparison of protein immobilization methods with covalent bonding on paper for paper-based enzyme-linked immunosorbent assay.

In this study, two methods were examined to optimize the immobilization of antibodies on paper when conducting a paper-based enzyme-linked immunosorbent assay (P-ELISA). Human IgG, as a test-capture protein, was immobilized on paper via the formation of Schiff bases. Aldehyde groups were introduced onto the surface of the paper via two methods: NaIO4 and 3-aminopropyltriethoxysilane (APTS) with glutaraldehyde (APTS-glutaraldehyde). In the assay, horseradish peroxidase-conjugated anti-human IgG (HRP-anti-IgG) binds to the immobilized human IgG, and the colorimetric reaction of 3,3',5,5'-tetramethylbenzyzine (TMB) produces a blue color in the presence of H2O2 and HRP-anti-IgG as a model analyte. The immobilization of human IgG, the enzymatic reaction conditions, and the reduction of the chemical bond between the paper surface and immobilized human IgG all were optimized in order to improve both the analytical performance and the stability. In addition, the thickness of the paper was examined to stabilize the analytical signal. Consequently, the APTS-glutaraldehyde method was superior to the NaIO4 method in terms of sensitivity and reproducibility. Conversely, the reduction of imine to amine with NaBH4 proved to exert only minimal influence on sensitivity and stability, although it tended to degrade reproducibility. We also found that thick paper was preferential when using P-ELISA because a rigid paper substrate prevents distortion of the paper surface that is often caused by repeated washing processes.

Targeting osteoblastic 11ß-HSD1 to combat high-fat diet-induced bone loss and obesity.

Excessive glucocorticoid (GC) action is linked to various metabolic disorders. Recent findings suggest that disrupting skeletal GC signaling prevents bone loss and alleviates metabolic disorders in high-fat diet (HFD)-fed obese mice, underpinning the neglected contribution of skeletal GC action to obesity and related bone loss. Here, we show that the elevated expression of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), the enzyme driving local GC activation, and GC signaling in osteoblasts, are associated with bone loss and obesity in HFD-fed male mice. Osteoblast-specific 11ß-HSD1 knockout male mice exhibit resistance to HFD-induced bone loss and metabolic disorders. Mechanistically, elevated 11ß-HSD1 restrains glucose uptake and osteogenic activity in osteoblast. Pharmacologically inhibiting osteoblastic 11ß-HSD1 by using bone-targeted 11ß-HSD1 inhibitor markedly promotes bone formation, ameliorates glucose handling and mitigated obesity in HFD-fed male mice. Taken together, our study demonstrates that osteoblastic 11ß-HSD1 directly contributes to HFD-induced bone loss, glucose handling impairment and obesity.

Establishing a critical phosphorus dilution curve for potato in semi-arid regions based on a Bayesian analysis.

Phosphorus (P) fertilizer use efficiency in potato production is relatively low in semi-arid regions, wasting P resources and increasing environmental risks. Therefore, improving P use efficiency (PUE) is critical for sustainable potato production. The critical P dilution curve (CPDC) and P nutrition index (PNI) have proven to be robust diagnostic tools for assessing crop P status and aiding in improving P fertilizer management. Several potato CPDCs have been established, however, few studies have been conducted to establish a CPDC for potato (Solanum tuberosum L.) under ridge planting with drip irrigation, a planting pattern that has been increasingly adopted in semi-arid regions. In addition, the different CPDCs established using the conventional Jestus statistical model cannot discriminate the true variability across scenarios or have become linked to estimation errors. Therefore, the objectives of this study were to (1) establish a potato CPDC based on a Bayesian statistical method and (2) evaluate the relationship between potato yield and PNI. Three years of field experiments with five levels of P2O5 application (0, 80, 160, 240, 320 kg ha-1) were conducted in Inner Mongolia, China. No significant differences were found between CPDCs across the year × site for the assessed scenarios, and thus, a generic CPDC for potatoes in the region was derived as Pc = 0.616 DM-0.296, and it can be used to calculate the PNI. Further analysis showed that at each growth stage, the PNI exhibits a significant plateauing linear relationship with relative potato tuber yield. Thus, it provides a standard for diagnosing the P nutritional status in potatoes and lays a robust foundation for precise P recommendations in the region.

The Influence of Exposure to Inorganic Arsenic and Other Arsenic Species on Early Renal Impairment Among Young Adults in Taiwan.

Chronic kidney disease (CKD) poses a significant global public health challenge, with environmental toxins potentially contributing to its prevalence. In Taiwan, where arsenic (As) contamination is endemic in certain areas of the country, assessing its impact on renal health is crucial due to the country's high rates of unexplained CKD. This cross-sectional study assessed associations between urinary As species and early renal impairment biomarkers-the microalbumin-to-creatinine ratio (ACR) and ß2-microglobulin (B2MG)-in 248 young Taiwanese adults (aged 20‒29 years). We measured urinary As species (including arsenite [As3+], arsenate [As5+], monomethylarsonic acid [MMA], and dimethylarsinic acid [DMA]) and early renal impairment biomarkers (urinary microalbumin and B2MG levels). Median concentrations of urinary As3+, As5+, MMA, DMA, inorganic As (iAs), and the sum of inorganic and methylated As species (iSumAs) were 1.43, 1.02, 3.79, 31.53, 2.82, and 68.29 µg/g creatinine (Cre.), respectively. We also evaluated the first methylation ratio (FMR) and the second methylation ratio (SMR). After adjusting for potential confounding factors, a multivariate linear regression showed significant associations between urinary As5+ (ß= 0.299, p= 0.002), iAs, and B2MG (ß= 0.281, p= 0.013) concentrations. A generalized additive model (GAM) revealed non-linear relationships among As5+, iAs, and B2MG concentrations. Moreover, there were elevated risks associated with the highest tertile of B2MG concentrations compared to the highest tertile of urinary As5+ (odds ratio [OR]= 2.366, 95% confidence interval [CI]: 1.196 - 4.682), MMA (OR= 1.917, 95% CI: 1.002 - 3.666), DMA (OR= 1.952, 95% CI: 1.015 - 3.753), and iSumAs (OR= 2.302, 95% CI: 1.182 - 4.483). These results indicated that exposure to As was associated with early renal impairment, particularly evidenced by increased urinary B2MG concentrations.

eIF6 deficiency regulates gut microbiota, decreases systemic inflammation, and alleviates atherosclerosis.

Altered composition of the gut microbiota affects immunity and metabolism. This study previously found that eIF6 gene knockdown changes the composition of the intestinal flora in the eIF6 gene knockdown mouse model. Lactobacillus acidophilus is significantly increased in the model. This study was designed to investigate the role of L. acidophilus in the pathogenesis of atherosclerosis. Transcriptomic data from 117 patients with coronary artery disease (CAD) and 79 healthy individuals were obtained. ApoE-/- and ApoE-/-/eIF6+/- mice on normal chow diet or a high-fat diet were treated for 16 weeks; eIF6 deficiency was evaluated atherosclerosis. ApoE-/- mice on normal chow diet or a high-fat diet were treated with L. acidophilus by daily oral gavage for 16 weeks. Moreover, one group was treated with lipopolysaccharide at 12 weeks. The levels of eIF6, RNASE3, and RSAD2 were notably higher in the patients with CAD than in the healthy individuals. eIF6 deficiency altered the composition of gut microbiota. eIF6 deficiency reduced the atherosclerotic lesion formation in ApoE-/-/eIF6+/- mice compared with the ApoE-/- mice. The microbial sequencing and metabolomics analysis demonstrated some beneficial bacterial (L. acidophilus, Ileibacterium, and Bifidobacterium) and metabolic levels significantly had deference in ApoE-/-/eIF6+/- mice compared with the ApoE-/- mice. Correlational studies indicated that L. acidophilus had close correlations with low-density lipoprotein cholesterol, lesion area, and necrotic area. L. acidophilus inhibited high-fat diet-induced inflammation and atherosclerotic lesion, increasing the expression of tight junction proteins (ZO-1 and claudin-1) and reducing the gut permeability. However, lipopolysaccharide reversed the protective effect of L. acidophilus against atherosclerosis. eIF6 deficiency protected against atherosclerosis by regulating the composition of gut microbiota and metabolites. L. acidophilus attenuated atherosclerotic lesions by reducing inflammation and increasing gut permeability.IMPORTANCEeIF6 deficiency modulates the gut microbiota and multiple metabolites in atherosclerotic ApoE-/- mice. L. acidophilus was reduced in the gut of atherosclerotic ApoE-/- mice, but administration of Lactobacillus acidophilus reversed intestinal barrier dysfunction and vascular inflammation. Our findings suggest that targeting individual species is a beneficial therapeutic strategy to prevent inflammation and atherosclerosis.