p39 Affects Myelin Formation in Cerebral Ischemic Injury.

Stroke is a significant public health issue, and research has consistently focused on studying the mechanisms of injury and identifying new targets. As a CDK5 activator, p39 plays a crucial role in various diseases. In this article, we will explore the role and mechanism of p39 in cerebral ischemic injury. We measured the level of p39 using western blot and QPCR at various time points following cerebral ischemia-reperfusion (I/R) injury. The results indicated a significant reduction in the level of p39. TTC staining and behavioral results indicate that the knockout of p39 (p39KO) provides neuroprotection in the short-term. Interestingly, the behavioral dysfunction in p39KO mice was exacerbated after the repair phase of I/R. Further study revealed that this deterioration may be due to demyelination induced by elevated p35 levels. In summary, our study offers profound insights into the significance of p39 in both the acute and repair stages of ischemic injury recovery and a theoretical foundation for future therapeutic drug exploration.

Oridonin ameliorates ocular surface inflammatory responses by inhibiting the NLRP3/caspase-1/GSDMD pyroptosis pathway in dry eye.

Chronic inflammation is one of the central drivers in the development of dry eye disease (DED), in which pyroptosis induced by the NLRP3/caspase-1/gasdermin D (GSDMD) pathway plays a key role. This pathway has become a major target for the treatment of a variety of inflammatory disorders. Oridonin (Ori) is a naturally occurring substance with anti-inflammatory properties obtained from Rabdosia rubescens. Whether Ori can exert an anti-inflammatory effect on DED, and its anti-inflammatory mechanism of action, are still unknown. This experiment is intended to investigate the impact of Ori on the hyperosmolarity-induced NLRP3/caspase-1/GSDMD pyroptosis pathway in immortalized human corneal epithelial (HCE-T) cells, as well as its efficacy and mechanism of action on ocular surface injury in DED mice. Our study showed that Ori could inhibit hyperosmotic-induced pyroptosis through the NLRP3/caspase-1/GSDMD pathway in HCE-T cells, and similarly, Ori inhibited the expression of this pathway in DED mice. Moreover, Ori was protective against hyperosmolarity-induced HCE-T cell damage. In addition, we found that the morphology and number of HCE-T cells were altered under culture conditions of various osmolarities. With increasing osmolarity, the proliferation, migration, and healing ability of HCE-T cells decreased significantly, and the expression of N-GSDMD was elevated. In a mouse model of DED, Ori application inhibited the expression of the NLRP3/caspase-1/GSDMD pyroptosis pathway, improved DED signs and injury, decreased corneal sodium fluorescein staining scores, and increased tear volume. Thus, our study suggests that Ori has potential applications for the treatment of DED, provides potential novel therapeutic approaches to treat DED, and provides a theoretical foundation for treating DED using Ori.

Remodeling of tumor microenvironment by extracellular matrix protein 1a differentially regulates ovarian cancer metastasis.

We previously reported that extracellular matrix protein 1 isoform a (ECM1a) promotes epithelial ovarian cancer (EOC) through autocrine signaling by binding to cell surface receptors αXß2. However, the role of ECM1a as a secretory molecule in the tumor microenvironment is rarely reported. In this study, we constructed murine Ecm1-knockout mice and human ECM1a-knockin mice and further generated orthotopic or peritoneal xenograft tumor models to mimic the different metastatic stages of EOC. We show that ECM1a induces oncogenic metastasis of orthotopic xenograft tumors, but inhibits early-metastasis of peritoneal xenograft tumors. ECM1a remodels extracellular matrices (ECM) and promotes remote metastases by recruiting and transforming bone marrow mesenchymal stem cells (BMSCs) into platelet-derived growth factor receptor beta (PDGFRß+) cancer-associated fibroblasts (CAFs) and facilitating the secretion of angiopoietin-like protein 2 (ANGPTL2). Competing with ECM1a, ANGPTL2 also binds to integrin αX through the P1/P2 peptides, resulting in negative effects on BMSC differentiation. Collectively, this study reveals the dual functions of ECM1a in remodeling of TME during tumor progression, emphasizing the complexity of EOC phenotypic heterogeneity and metastasis.

Metabolomics Simultaneously Derives Benchmark Dose Estimates and Discovers Metabolic Biotransformations in a Rat Bioassay.

Benchmark dose (BMD) modeling estimates the dose of a chemical that causes a perturbation from baseline. Transcriptional BMDs have been shown to be relatively consistent with apical end point BMDs, opening the door to using molecular BMDs to derive human health-based guidance values for chemical exposure. Metabolomics measures the responses of small-molecule endogenous metabolites to chemical exposure, complementing transcriptomics by characterizing downstream molecular phenotypes that are more closely associated with apical end points. The aim of this study was to apply BMD modeling to in vivo metabolomics data, to compare metabolic BMDs to both transcriptional and apical end point BMDs. This builds upon our previous application of transcriptomics and BMD modeling to a 5-day rat study of triphenyl phosphate (TPhP), applying metabolomics to the same archived tissues. Specifically, liver from rats exposed to five doses of TPhP was investigated using liquid chromatography-mass spectrometry and 1H nuclear magnetic resonance spectroscopy-based metabolomics. Following the application of BMDExpress2 software, 2903 endogenous metabolic features yielded viable dose-response models, confirming a perturbation to the liver metabolome. Metabolic BMD estimates were similarly sensitive to transcriptional BMDs, and more sensitive than both clinical chemistry and apical end point BMDs. Pathway analysis of the multiomics data sets revealed a major effect of TPhP exposure on cholesterol (and downstream) pathways, consistent with clinical chemistry measurements. Additionally, the transcriptomics data indicated that TPhP activated xenobiotic metabolism pathways, which was confirmed by using the underexploited capability of metabolomics to detect xenobiotic-related compounds. Eleven biotransformation products of TPhP were discovered, and their levels were highly correlated with multiple xenobiotic metabolism genes. This work provides a case study showing how metabolomics and transcriptomics can estimate mechanistically anchored points-of-departure. Furthermore, the study demonstrates how metabolomics can also discover biotransformation products, which could be of value within a regulatory setting, for example, as an enhancement of OECD Test Guideline 417 (toxicokinetics).

Fosfenopril Attenuates Inflammatory Response in Diabetic Dry Eye Models by Inhibiting the TLR4/NF-κB/NLRP3 Signaling Pathway.

Purpose: The purpose of this study was to investigate the involvement of the TLR4/NF-κB/NLRP3 signaling pathway and its underlying mechanism in diabetic dry eye. Methods: Two models of diabetic dry eye were established in high glucose-induced human corneal epithelial (HCE-T) cells and streptozotocin (STZ)-induced C57BL/6 mice, and the TLR4 inhibitor fosfenopril (FOS) was utilized to suppress the TLR4/NF-κB/NLRP3 signaling pathway. The expression changes in TLR4, NF-κB, NLRP3, and IL-1ß, and other factors were detected by Western blot and RT‒qPCR, the wound healing rate was evaluated by cell scratch assay, and the symptoms of diabetic mice were evaluated by corneal sodium fluorescein staining and tear secretion assay. Results: In the diabetic dry eye model, the transcript levels of TLR4, NF-κB, NLRP3, and IL-1ß were raised, and further application of FOS, a TLR4 inhibitor, downregulated the levels of these pathway factors. In addition, FOS was found to be effective in increasing the wound healing rate of high glucose-induced HCE-T cells, increasing tear production, and decreasing corneal fluorescence staining scores in diabetic mice, as measured by cell scratch assay, corneal sodium fluorescein staining assay, and tear production. Conclusions: The current study found that the TLR4/NF-κB/NLRP3 signaling pathway regulates diabetic dry eye in an in vitro and in vivo model, and that FOS reduces the signs of dry eye in diabetic mice, providing a new treatment option for diabetic dry eye.

Effects of ultraviolet C on the quality and aroma volatile in peach fruit during postharvest storage.

The study investigated the impact of UV-C irradiation on peach fruit quality during postharvest storage, with a focus on aroma changes and the mechanisms involving lipoxygenase metabolism. Results showed that UV-C irradiation at a dosage of 1.5 kJ/m2 was found to preserve the quality attributes of peach fruit during ambient storage, as evidenced by high flesh firmness, inhibition of weight loss and respiration rate, as well as high values of L* and ascorbic acid. Meanwhile, UV-C irradiation led to an increase in the contents of aroma-related volatiles, particularly esters and lactones, compared to non-irradiated fruit. Our results suggested that the enhanced emission of aroma-related volatiles in UV-C irradiated peach fruit was linked to elevated levels of unsaturated fatty acids. Besides, UV-C induced the expressions and activities of enzymes in the lipoxygenase pathway, thus promoting the synthesis of esters and lactones, which contribute to the enhanced aroma in peach fruit.

Worldwide trend in research on Candida albicans and cancer correlations: a comprehensive bibliometric analysis.

Objective: Candida albicans (C. albicans), an opportunistic pathogen, is implicated in the carcinogenesis of various cancers, thereby significantly impacting human health. This study conducts an in-depth analysis of the prevailing research dynamics concerning the relationship between C. albicans and cancer over the past decade, offering a comprehensive overview of the knowledge structure and emerging focal points in this field through bibliometric scrutiny. Methods: A methodical quantitative and visual scrutiny of pertinent literature from the Web of Science Core Collection (WoSCC) spanning the previous decade was carried out employing VOS Viewer and CiteSpace software. Results: From January 1, 2014, to January 1, 2024, a comprehensive corpus of 1,259 articles was delineated. Prominent research institutions included the Egyptian Knowledge Bank, Cairo University, and King Saud University. The top three prolific countries were the United States, China, and India. Among the authors, Mohamed, Gehad G., Mahmoud, Walaa H., and Netea, Mihai G., emerged as the most prolific, with Pfaller, Ma being distinguished as the most frequently cited author. The journal Molecules published the highest number of articles, while PLoS One had the highest citation count. Nature had the highest impact factor. The research focal points in this field encompassed the interactions between C. albicans and cancer, the correlation with oral cancer, the underlying mechanisms of C. albicans carcinogenic potential, as well as antifungal and anticancer therapies. Conclusion: This investigation constitutes a pioneering bibliometric analysis elucidating the trends and advancements in research regarding the correlation between C. albicans and cancer. Said analyses uncover the prevailing research focal points and trends, offering insightful guidance for subsequent inquiry in this domain. Systematic review registration: https://www.webofscience.com/wos/woscc/summary/df33afba-f843-41e8-b932-cb3678eb8243-e92e7316/relevance/1.

The impact of internet use and cognitive conflict on farmer IPM technology adoption: evidence from China.

BACKGROUND: Integrated pest management (IPM) plays a crucial role in protecting agricultural environments and enhancing the quality of agricultural products. However, a major challenge in China is the conflicting understanding of IPM among farmers, leading to low adoption rates. This undermines farmers' ability to control pests and diseases while increasing risks to agricultural quality and safety. This study aimed to investigate the impact of cognitive conflicts on farmers' adoption of IPM in kiwifruit farms in Shaanxi and Sichuan provinces. Additionally, the study explored the moderating role of internet use in the relationship between cognitive conflicts and farmer adoption of IPM. Data were collected from 686 kiwifruit farms through field surveys in 2018. The binary Probit model and moderating effect models were used to assess the influence of internet use and cognitive conflict on farmer adoption of IPM. RESULTS: The study found that cognitive conflicts significantly hindered farmers' adoption of IPM. Higher levels of cognitive conflict were associated with lower likelihoods of adopting IPM. Internet use and frequency had positive effects on farmer adoption of IPM, promoting its implementation. Moreover, internet use and frequency helped alleviate the inhibitory effect of cognitive conflicts on farmer adoption IPM. CONCLUSION: This research enhances our understanding of cognitive conflicts among farmers when promoting IPM and provides viable strategies to improve the effectiveness of public sector promotion and stimulate farmers' willingness to adopt IPM. It emphasizes the importance of addressing cognitive conflicts and utilizing internet resources to enhance IPM adoption among kiwifruit growers in China. © 2024 Society of Chemical Industry.

Unraveling the determinants of antibiotic resistance evolution in farmland under fertilizations.

Organic fertilization is a major driver potentiating soil antibiotic resistance in farmland. However, it remains unclear how bacterial antibiotic resistance evolves in fertilized soils and even spreads to crops. Compared with no fertilizer and commercial fertilizer treatments, organic fertilizers markedly increased the abundance of soil antibiotic resistance genes (ARGs) but the relatively weaker transfer of resistance genes from soil to crops. The introduction of organic fertilizers enriches the soil with nutrients, driving indigenous microorganisms towards a K-strategy. The pH, EC, and nutrients as key drivers influenced the ARGs abundance. The neutral (pH 7.2), low salt (TDS 1.4 %) and mesotrophic (carbon content 3.54 g/L) habitats similar to the soil environment conditioned by organic fertilizers. These environmental conditions clearly prolonged the persistence of resistant plasmids, and facilitated their dissemination to massive conjugators soil microbiome but not to plant endophytes. This suggested that organic fertilizers inhibited the spread of ARGs to crops. Moreover, the composition of conjugators showed differential selection of resistant plasmids by endophytes under these conditions. This study sheds light on the evolution and dissemination of antibiotic resistance in farmlands and can aid in the development of antimicrobial resistance control strategies in agriculture.

Corrigendum: Intelligent diagnosis of the severity of disease conditions in COVID-19 patients based on the LASSO method.

[This corrects the article DOI: 10.3389/fpubh.2024.1302256.].

Synergistic Catalysis of SO42-/TiO2-CNT for the CO2 Desorption Process with Low Energy Consumption.

To address the issue of high energy consumption associated with monoethanolamine (MEA) regeneration in the CO2 capture process, solid acid catalysts have been widely investigated due to their performance in accelerating carbamate decomposition. The recently discovered carbon nanotube (CNT) catalyst presents efficient catalytic activity for bicarbonate decomposition. In this paper, bifunctional catalysts SO42-/TiO2-CNT (STC) were prepared, which could simultaneously catalyze carbamate and bicarbonate decomposition, and outstanding catalytic performance has been exhibited. STC significantly increased the CO2 desorption amount by 82.3% and decreased the relative heat duty by 46% compared to the MEA-CO2 solution without catalysts. The excellent stability of STC was confirmed by 15 cyclic absorption-desorption experiments, showing good practical feasibility for decreasing energy consumption in an industrial CO2 capture process. Furthermore, associated with the results of experimental characterization and theoretical calculations, the synergistic catalysis of STC catalysts via proton and charge transfer was proposed. This work demonstrated the potential of STC catalysts in improving the efficiency of amine regeneration processes and reducing energy consumption, contributing to the design of more effective and economical catalysts for carbon capture.

Shared and distinct electroencephalogram microstate abnormalities across schizophrenia, bipolar disorder, and depression.

BACKGROUND: Microstates of an electroencephalogram (EEG) are canonical voltage topographies that remain quasi-stable for 90 ms, serving as the foundational elements of brain dynamics. Different changes in EEG microstates can be observed in psychiatric disorders like schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD). However, the similarities and disparatenesses in whole-brain dynamics on a subsecond timescale among individuals diagnosed with SCZ, BD, and MDD are unclear. METHODS: This study included 1112 participants (380 individuals diagnosed with SCZ, 330 with BD, 212 with MDD, and 190 demographically matched healthy controls [HCs]). We assembled resting-state EEG data and completed a microstate analysis of all participants using a cross-sectional design. RESULTS: Our research indicates that SCZ, BD, and MDD exhibit distinct patterns of transition among the four EEG microstate states (A, B, C, and D). The analysis of transition probabilities showed a higher frequency of switching from microstates A to B and from B to A in each patient group compared to the HC group, and less frequent transitions from microstates A to C and from C to A in the SCZ and MDD groups compared to the HC group. And the probability of the microstate switching from C to D and D to C in the SCZ group significantly increased compared to those in the patient and HC groups. CONCLUSIONS: Our findings provide crucial insights into the abnormalities involved in distributing neural assets and enabling proper transitions between different microstates in patients with major psychiatric disorders.

Pore walls as high-way for efficient bulk charge transfer in porous SrTiO3 single crystals boosting photocatalytic overall water splitting.

Suppressing carrier recombination in bulk and facilitating carrier transfer to surface via rational structure design is of great significance to improve solar-to-H2 conversion efficiency. We demonstrate a facile hydrothermal method to synthesize porous SrTiO3 single crystals (SrTiO3-P) with exposed (001) facets by introducing carbon spheres as templates. The obviously increased surface photovoltage and photocurrent response indicate that the interconnected pore walls act as enormous charge transfer "highways", accelerating carrier transport from bulk to surface. Furthermore, the absence of grain boundaries and high crystallinity could also lower the carrier recombination rate. Thus, the SrTiO3-P photocatalyst loaded with Rh/Cr2O3 as cocatalyst exhibits 1.5 times higher overall water splitting activity than that of solid SrTiO3, with gas evolution rate of 19.99 µmol h-1 50 mg-1 for H2 and 11.37 µmol h-1 50 mg-1 for O2. Additionally, SrTiO3-P also shows superior stability without any decay during cycling testing. This work provides a new insight into designing efficient multicomponent photocatalysts with a single-crystal porous structure.

Nicotine inhalant via E-cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF-TrkB signalling in traumatic brain injury.

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) causes lifelong physical and psychological dysfunction in affected individuals. The current study investigated the effects of chronic nicotine exposure via E-cigarettes (E-cig) (vaping) on TBI-associated behavioural and biochemical changes. EXPERIMENTAL APPROACH: Adult C57/BL6J male mice were subjected to controlled cortical impact (CCI) followed by daily exposure to E-cig vapour for 6 weeks. Sensorimotor functions, locomotion, and sociability were subsequently evaluated by nesting, open field, and social approach tests, respectively. Immunoblots were conducted to examine the expression of mature brain-derived neurotrophic factor (mBDNF) and associated downstream proteins (p-Erk, p-Akt). Histological analyses were performed to evaluate neuronal survival and neuroinflammation. KEY RESULTS: Post-injury chronic nicotine exposure significantly improved nesting performance in CCI mice. Histological analysis revealed increased survival of cortical neurons in the perilesion cortex with chronic nicotine exposure. Immunoblots revealed that chronic nicotine exposure significantly up-regulated mBDNF, p-Erk and p-Akt expression in the perilesion cortex of CCI mice. Immunofluorescence microscopy indicated that elevated mBDNF and p-Akt expression were mainly localized within cortical neurons. Immunolabelling of Iba1 demonstrated that chronic nicotine exposure attenuated microglia-mediated neuroinflammation. CONCLUSIONS AND IMPLICATIONS: Post-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions.

Association between serum sodium trajectory and mortality in patients with acute kidney injury: a retrospective cohort study.

INTRODUCTION: Dysnatremia is strongly associated with poor prognosis in acute kidney injury (AKI); however, the impact of sodium trajectories on the prognosis of patients with AKI has not yet been well elucidated. This study aimed to assess the association between sodium trajectories in patients with AKI and mortality at 30-day and 1-year follow-up. METHODS: This retrospective cohort study used data from Medical Information Mart for Intensive Care (MIMIC)-IV database, and patients diagnosed with AKI within 48 h after admission were enrolled. Group-based trajectory models (GBTM) were applied to map the developmental course of the serum sodium fluctuations. Kaplan-Meier survival curve was used to compare differences in mortality in AKI patients with distinct serum sodium trajectories. Hazard ratios (HRs) were calculated to determine the association between trajectories and prognosis using Cox proportional hazard models. RESULTS: A total of 9,314 AKI patients were enrolled. Three distinct sodium trajectories were identified including: (i) stable group (ST, in which the serum sodium levels remained relatively stable, n = 4,935; 53.0%), (ii) descending group (DS, in which the serum sodium levels declined, n = 2,994; 32.15%) and (iii) ascending group (AS, in which the serum sodium levels were elevated, n = 1,383; 14.85%). There was no significant difference in age and gender distribution among the groups. The 30-day mortality rates were 7.9% in ST, 9.5% in DS and 16.6% in AS (p < 0.001). The results of 1-year mortality rates were similar (p < 0.001). In adjusted analysis, patients in the DS (HR = 1.22, 95% confidence interval [CI], 1.04-1.43, p = 0.015) and AS (HR = 1.68, 95% CI, 1.42-2.01, p = 0.013) groups had higher risks of 30-day mortality compared to those in the ST group. CONCLUSION: In patients with AKI, the serum sodium trajectories were independently associated with 30-day and 1-year mortality. Association between serum sodium level trajectories and prognosis in patients with AKI deserve further study.

[An early warning model for sepsis complicated with acute respiratory distress syndrome based on synthetic minority oversampling technique algorithm].

OBJECTIVE: To explore the independent risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis, establish an early warning model, and verify the predictive value of the model based on synthetic minority oversampling technique (SMOTE) algorithm. METHODS: A retrospective case-control study was conducted. 566 patients with sepsis who were admitted to Jinan People's Hospital from October 2016 to October 2022 were enrolled. General information, underlying diseases, infection sites, initial cause, severity scores, blood and arterial blood gas analysis indicators at admission, treatment measures, complications, and prognosis indicators of patients were collected. The patients were grouped according to whether ARDS occurred during hospitalization, and the clinical data between the two groups were observed and compared. Univariate and binary multivariate Logistic regression analysis were used to select the independent risk factors of ARDS during hospitalization in septic patients, and regression equation was established to construct the early warning model. Simultaneously, the dataset was improved using the SMOTE algorithm to build an enhanced warning model. Receiver operator characteristic curve (ROC curve) was drawn to validate the prediction efficiency of the model. RESULTS: 566 patients with sepsis were included in the final analysis, of which 163 developed ARDS during hospitalization and 403 did not. Univariate analysis showed that there were statistically significant differences in age, body mass index (BMI), malignant tumor, blood transfusion history, pancreas and peripancreatic infection, gastrointestinal tract infection, pulmonary infection as the initial etiology, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, albumin (Alb), blood urea nitrogen (BUN), mechanical ventilation therapy, septic shock and length of intensive care unit (ICU) stay between the two groups. Binary multivariate Logistic regression analysis showed that age [odds ratio (OR) = 3.449, 95% confidence interval (95%CI) was 2.197-5.414, P = 0.000], pulmonary infection as the initial etiology (OR = 2.309, 95%CI was 1.427-3.737, P = 0.001), pancreas and peripancreatic infection (OR = 1.937, 95%CI was 1.236-3.035, P = 0.004), septic shock (OR = 3.381, 95%CI was 1.890-6.047, P = 0.000), SOFA score (OR = 9.311, 95%CI was 5.831-14.867, P = 0.000) were independent influencing factors of ARDS during hospitalization in septic patients. An early warning model was established based on the above risk factors: P1 = -4.558+1.238×age+0.837×pulmonary infection as the initial etiology+0.661×pancreas and peripancreatic infection+1.218×septic shock+2.231×SOFA score. ROC curve analysis showed that the area under the ROC curve (AUC) of the model for ARDS during hospitalization in septic patients was 0.882 (95%CI was 0.851-0.914) with sensitivity of 79.8% and specificity of 83.4%. The dataset was improved based on the SMOTE algorithm, and the early warning model was rebuilt: P2 = -3.279+1.288×age+0.763×pulmonary infection as the initial etiology+0.635×pancreas and peripancreatic infection+1.068×septic shock+2.201×SOFA score. ROC curve analysis showed that the AUC of the model for ARDS during hospitalization in septic patients was 0.890 (95%CI was 0.867-0.913) with sensitivity of 85.3% and specificity of 79.1%. This result further confirmed that the early warning model constructed by the independent risk factors mentioned above had high predictive performance. CONCLUSIONS: Risk factors for the occurrence of ARDS during hospitalization in patients with sepsis include age, pulmonary infection as the initial etiology, pancreatic and peripancreatic infection, septic shock, and SOFA score. Clinically, the probability of ARDS in patients with sepsis can be assessed based on the warning model established using these risk factors, allowing for early intervention and improvement of prognosis.

Efficacy and safety of Qushi Huayu, a traditional Chinese medicine, in patients with nonalcoholic fatty liver disease in a randomized controlled trial.

BACKGROUND: The effective treatment of non-alcoholic fatty liver disease (NAFLD) is an unmet medical need. Qushi Huayu (QSHY) is an empirical herbal formula with promising effects in NAFLD rodent models and a connection to gut microbiota regulation. HYPOTHESIS/PURPOSE: This study aimed to evaluate the effects of QSHY in patients with NAFLD through a multicenter, randomized, double-blind, double-dummy clinical trial. STUDY DESIGN: A total of 246 eligible patients with NAFLD and liver dysfunction were evenly divided to receive either QSHY and Dangfei Liganning capsule (DFLG) simulant or QSHY simulant and DFLG (an approved proprietary Chinese medicine for NAFLD in China) for 24 weeks. The primary outcomes were changes in liver fat content, assessed using vibration-controlled transient elastography, and serum alanine aminotransferase (ALT) levels from baseline to Week 24. RESULTS: Both QSHY and DFLG led to reductions in liver fat content and liver enzyme levels post-intervention (p < 0.05). Compared to DFLG, QSHY treatment improved ALT (ß, -0.128 [95 % CI, -0.25, -0.005], p = 0.041), aspartate transaminase (ß, -0.134 [95 % CI, -0.256 to -0.012], p = 0.032), and fibrosis-4 score (ß, -0.129 [95 % CI, -0.254 to -0.003], p = 0.044) levels. QSHY markedly improved gut dysbiosis compared to DFLG, with changes in Escherichia-Shigella and Bacteroides abundance linked to its therapeutic effect on reducing ALT. Patients with a high ALT response after QSHY treatment showed superior reductions in peripheral levels of phenylalanine and tyrosine, along with an elevation in the related microbial metabolite p-Hydroxyphenylacetic acid. CONCLUSION: Our results demonstrate favorable clinical potential for QSHY in the treatment of NAFLD.

Yogurt Prevents Colorectal Tumorigenesis in ApcMin/+ Mice.

SCOPE: Yogurt consumption is related to a decreased risk of colorectal cancer (CRC), but whether such association is causal remains unclear. Patients with familial adenomatous polyposis (FAP) are at increased risk of CRC development. Here, the study investigates the efficacy of yogurt for intestinal polyposis chemoprevention in ApcMin/+ mice, a preclinical model for human FAP. METHODS AND RESULTS: A 10-week yogurt supplementation (15 g kg-1) in ApcMin/+ mice significantly reduces the intestinal polyp number (6.50 ± 0.97 versus 1.80 ± 0.49; p < 0.001) compared to controls. 16S rRNA gene-based microbiota analysis suggests that yogurt supplementation may greatly modulate the gut microbiome composition, especially in the relative abundance of Lactobacillus and Bifidobacterium. Importantly, the fecal concentration of d-lactate (d-Lac, 0.39 ± 0.04 µmol g-1 versus 8.14 ± 0.62 µmol g-1; p < 0.001) is boosted by yogurt, while oral administration with d-Lac (125 or 250 mg kg-1) reduces the polyp number by 71.43% or 77.14% (p < 0.001), respectively. The study also observes that d-Lac does not affect cell viability and anchorage-independence in CRC cells, but it greatly suppresses epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation in preneoplastic cells. Mechanistically, it demonstrates that d-Lac may attenuate epithelial cell transformation by targeting PI3K/AKT/ß-catenin axis. CONCLUSION: Yogurt protects against intestinal polyposis in ApcMin/+ mice, and d-Lac may partially account for the chemopreventive effects above.

What are the differences in paraspinal muscle morphometry among degenerative spondylolisthesis patients, isthmic spondylolisthesis patients, and healthy individuals? A propensity score matching analysis.

PURPOSE: To compare the morphometry of paraspinal muscles in patients with degenerative spondylolisthesis (DS), isthmic spondylolisthesis (IS), and healthy individuals. METHODS: Thirty-seven pairs of DS patients were selected using propensity score matching with IS patients, while 37 healthy individuals matched for age, sex, and BMI were selected as controls. The relative cross-sectional area (rCSA), and relative functional cross-sectional area (rfCSA) of paraspinal muscles were measured, and the degree of fatty infiltration (FI) was calculated. Based on occupational differences, the patients were also divided into worker and farmer groups, and the same measurements were taken on them. RESULTS: At the L3/L4 level, the multifidus (MF) FI was greater in the DS and IS groups than in the control group, the erector spinae (ES) rfCSA was higher in the IS group than in the DS and control groups. At the L4/L5 level, MF rfCSA was smaller in the DS and IS groups than in the control group; ES rfCSA was higher in the IS group than in the DS and control groups. At the L5/S1 level, MF rfCSA was smaller in the DS and IS groups than in the control group; ES rfCSA was higher in the IS group than in the DS group. At the L3/L4, L4/L5 level, MF rfCSA were higher in the worker group than in the farmer group (p < 0.05). CONCLUSION: The morphological changes in paraspinal muscles in patients with DS were dominated by selective atrophy of the MF, while in patients with IS, the morphological changes in paraspinal muscle showed selective atrophy of the MF accompanied by compensatory hypertrophy of the ES. The surgeon should consider the morphological differences in paraspinal muscle between different types of lumbar spondylolisthesis when establishing the appropriate surgical program.

Risk factors and their association network for young adults' suicidality: a cross-sectional study.

BACKGROUND: Understanding the intricate influences of risk factors contributing to suicide among young individuals remains a challenge. The current study employed interpretable machine learning and network analysis to unravel critical suicide-associated factors in Chinese university students. METHODS: A total of 68,071 students were recruited between Sep 2016 and Sep 2020 in China. Students reported their lifetime experiences with suicidal thoughts and behaviors, categorized as suicide ideation (SI), suicide plan (SP), and suicide attempt (SA). We assessed 36 suicide-associated factors including psychopathology, family environment, life events, and stigma. Local interpretations were provided using Shapley additive explanation (SHAP) interaction values, while a mixed graphical model facilitated a global understanding of their interplay. RESULTS: Local explanations based on SHAP interaction values suggested that psychoticism and depression severity emerged as pivotal factors for SI, while paranoid ideation strongly correlated with SP and SA. In addition, childhood neglect significantly predicted SA. Regarding the mixed graphical model, a hierarchical structure emerged, suggesting that family factors preceded proximal psychopathological factors, with abuse and neglect retaining unique effects. Centrality indices derived from the network highlighted the importance of subjective socioeconomic status and education in connecting various risk factors. CONCLUSIONS: The proximity of psychopathological factors to suicidality underscores their significance. The global structures of the network suggested that co-occurring factors influence suicidal behavior in a hierarchical manner. Therefore, prospective prevention strategies should take into account the hierarchical structure and unique trajectories of factors.