Circulating cell-free DNA methylation-based multi-omics analysis allows early diagnosis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5-year survival rate of 7.2% in China. However, effective approaches for diagnosis of PDAC are limited. Tumor-originating genomic and epigenomic aberration in circulating free DNA (cfDNA) have potential as liquid biopsy biomarkers for cancer diagnosis. Our study aims to assess the feasibility of cfDNA-based liquid biopsy assay for PDAC diagnosis. In this study, we performed parallel genomic and epigenomic profiling of plasma cfDNA from Chinese PDAC patients and healthy individuals. Diagnostic models were built to distinguish PDAC patients from healthy individuals. Cancer-specific changes in cfDNA methylation landscape were identified, and a diagnostic model based on six methylation markers achieved high sensitivity (88.7% for overall cases and 78.0% for stage I patients) and specificity (96.8%), outperforming the mutation-based model significantly. Moreover, the combination of the methylation-based model with carbohydrate antigen 19-9 (CA19-9) levels further improved the performance (sensitivity: 95.7% for overall cases and 95.5% for stage I patients; specificity: 93.3%). In conclusion, our findings suggest that both methylation-based and integrated liquid biopsy assays hold promise as non-invasive tools for detection of PDAC.

Metabolite and transcriptome analyses reveal the effects of salinity stress on the biosynthesis of proanthocyanidins and anthocyanins in grape suspension cells.

Proanthocyanidins (PAs) and anthocyanins are flavonoids that contribute to the quality and health benefits of grapes and wine. Salinity affects their biosynthesis, but the underlying mechanism is still unclear. We studied the effects of NaCl stress on PA and anthocyanin biosynthesis in grape suspension cells derived from berry skins of Vitis vinifera L. Cabernet Sauvignon using metabolite profiling and transcriptome analysis. We treated the cells with low (75 mM NaCl) and high (150 mM NaCl) salinity for 4 and 7 days. High salinity inhibited cell growth and enhanced PA and anthocyanin accumulation more than low salinity. The salinity-induced PAs and anthocyanins lacked C5'-hydroxylation modification, suggesting the biological significance of delphinidin- and epigallocatechin-derivatives in coping with stress. The genes up-regulated by salinity stress indicated that the anthocyanin pathway was more sensitive to salt concentration than the PA pathway, and WGCNA analysis revealed the coordination between flavonoid biosynthesis and cell wall metabolism under salinity stress. We identified transcription factors potentially involved in regulating NaCl dose- and time-dependent PA and anthocyanin accumulation, showing the dynamic remodeling of flavonoid regulation network under different salinity levels and durations. Our study provides new insights into regulator candidates for tailoring flavonoid composition and molecular indicators of salt stress in grape cells.

A rapid and sensitive fluorescent chromatography with cloud system for MPXV point-of-care diagnosis.

Monkeypox (mpox) is spreading around the world, and its rapid diagnosis is of great significance. In the present study, a rapid and sensitive fluorescent chromatography assisted with cloud system was developed for point-of-care diagnosis of mpox. To screen high affinity antibodies, nanoparticle antigen AaLS-A29 was generated by conjugating A29 onto scaffold AaLS. Immunization with AaLS-A29 induced significantly higher antibody titers and monoclonal antibodies were generated with the immunized mice. A pair of monoclonal antibodies, MXV 14 and MXV 15, were selected for fluorescence chromatography development. The Time-Resolved Fluorescence Immunoassay (TRFIA) was used to develop the chromatography assay. After optimization of the label and concentration of antibodies, a sensitive TRFIA assay with detection limit of 20 pg/mL and good repeatability was developed. The detection of the surrogate Vaccinia virus (VACA) strain Tian Tan showed that the TRFIA assay was more sensitive than the SYBR green I based quantitative PCR. In real samples, the detection result of this assay were highly consistent with the judgement of Quantitative Real-Time PCR (Concordance Rate = 90.48%) as well as the clinical diagnosis (Kappa Value = 0.844, P < 0.001). By combining the portable detection and online cloud system, the detection results could be uploaded and shared, making this detection system an ideal system for point-of-care diagnosis of mpox both in field laboratory and outbreak investigation.

Phloretic acid requires the insulin/IGF-1 pathway and autophagy to enhance stress resistance and extend the lifespan of Caenorhabditis elegans.

Objective: In humans, aging is associated with increased susceptibility to most age-related diseases. Phloretic acid (PA), a naturally occurring compound found in Ginkgo biloba and Asparagus, exhibits has potential as an anti-aging agent and possesses antioxidant, anti-inflammatory, and immunomodulatory properties. This study aimed to investigate the effects of PA on longevity and stress resistance in Caenorhabditis elegans (C.elegans) and the mechanisms that underlie its effects. Methods: First, we examined the effects of PA on lifespan and healthspan assay, stress resistance and oxidative analysis, lipofuscin levels. Second, we examined the insulin/insulin-like pathway, mitochondria, autophagy-related proteins, and gene expression to explain the possible mechanism of PA prolonging lifespan. Results: Our findings demonstrated that PA dose-dependently extended the C.elegans lifespan, with 200 µM PA showing the greatest effect and increased the C.elegans lifespan by approximately 16.7%. PA enhanced motility and the pharyngeal pumping rate in senescent C.elegans while reducing the accumulation of aging pigments. Further investigations revealed that daf-16, skn-1, and hsf-1 were required for mediating the lifespan extension effect of PA in C.elegans since its impact was suppressed in mutant strains lacking these genes. This suggests that PA activates these genes, leading to the upregulation of downstream genes involved in stress response and senescence regulation pathways. Furthermore, PA did not extend the lifespan of the RNAi atg-18 and RNAi bec-1 but it attenuated SQST-1 accumulation, augmented autophagosome expression, upregulated autophagy-related gene expression, and downregulated S6K protein levels. These findings suggest that the potential life-extending effect of PA also involves the modulation of the autophagy pathway. Conclusion: These findings results highlight the promising anti-aging effects of PA and warrant further investigation into its pharmacological mechanism and medicinal development prospects.

ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways. / ELABELA衍生肽ELA13通过抑制Smad和ERK信号通路减轻肾纤维化.

Kidney fibrosis is an inevitable result of various chronic kidney diseases (CKDs) and significantly contributes to end-stage renal failure. Currently, there is no specific treatment available for renal fibrosis. ELA13 (amino acid sequence: RRCMPLHSRVPFP) is a conserved region of ELABELA in all vertebrates; however, its biological activity has been very little studied. In the present study, we evaluated the therapeutic effect of ELA13 on transforming growth factor-ß1 (TGF-ß1)-treated NRK-52E cells and unilateral ureteral occlusion (UUO) mice. Our results demonstrated that ELA13 could improve renal function by reducing creatinine and urea nitrogen content in serum, and reduce the expression of fibrosis biomarkers confirmed by Masson staining, immunohistochemistry, real-time polymerase chain reaction (RT-PCR), and western blot. Inflammation biomarkers were increased after UUO and decreased by administration of ELA13. Furthermore, we found that the levels of essential molecules in the mothers against decapentaplegic (Smad) and extracellular signal-regulated kinase (ERK) pathways were reduced by ELA13 treatment in vivo and in vitro. In conclusion, ELA13 protected against kidney fibrosis through inhibiting the Smad and ERK signaling pathways and could thus be a promising candidate for anti-renal fibrosis treatment.

The feasibility of left ventricular strain and strain rate for evaluating patients with risk factors of sudden cardiac death in hypertrophic cardiomyopathy by Feature-tracking Cardiac Magnetic Resonance.

Sudden cardiac death (SCD) represents the most severe complication of hypertrophic cardiomyopathy (HCM). However, the relationship between strain, strain rate, and risk factors in SCD risk stratification remains elusive. The study aimed to assess the attenuation of strain and strain rate in HCM by feature-tracking cardiac magnetic resonance (FT-CMR). All strain and strain rates were obtained automatically by FT, with manual adjustment of endocardial and epicardial borders. Strain indicators included left ventricular (LV) global longitudinal (GLS), circumferential (GCS), radial strain (GRS), peak diastolic-longitudinal (PD-LSR), circumferential (PD-CSR), and radial strain rate (PD-RSR). Patients were categorized into high and low-risk groups for SCD based on the 2020 American Heart Association/American College (AHA/ACC) HCM Risk-SCD model. The correlation between strain/strain rate and SCD risk factors was assessed via Spearman correlation analysis. Furthermore, a multivariate logistic regression analysis was conducted to explore the factors that influence SCD risk in HCM patients. A total of 105 HCM patients were analyzed in this study, including 38 patients in the high-risk group, and 67 patients in the low-risk group. Compared to the low-risk group, the high-risk group exhibited significantly worse strain and strain rate (p<0.001). Furthermore, both circumferential and radial strain as well as strain rate exhibited meaningful associations with risk factors for SCD. Additionally, GRS emerged as an independent risk factor for predicting heightened SCD risk in HCM patients (p<0.001). In conclusion, LV strain and strain rate based on FT-CMR can be evaluated for SCD risk and are strongly associated with SCD risk factors.

Characterization of chemical and sensory properties of Cabernet Sauvignon and Marselan wines made by flash détente technique.

This study aimed to characterize the sensory profiles of wines produced using the flash détente (FD) technique and to identify the flavor compounds contributing to the sensory characteristics. The FD technique was applied to two major grape varieties, Cabernet Sauvignon and Marselan, from the Changli region of China to produce high-quality wines with aging potential. Compared to the traditional macerated wines, the FD wines showed greater color intensity, mainly due to the higher levels of anthocyanins. Regarding the aroma characteristics, FD wines were found to have a more pronounced fruitness, especially fresh fruit note, which was due to the contribution of higher concentration of esters. Concurrently, FD wines showed an increased sweet note which was associated with increased lactones and furanones. In addition, FD wines exhibited reduced green and floral notes due to lower levels of C6 alcohols and C13-norisoprenoids. With regard to mouthfeel, FD wines presented greater astringency and bitterness, which was due to the higher levels of phenolics. The total concentration of condensed tannins and condensed tannins for each degree of polymerization was considerably higher in FD wines due to the strong extraction of the FD technique. A significant increase in grape-derived polysaccharides and glycerol was also found in FD wines, contributing to a fuller body. This study contributed to an increase in the knowledge of the Changli region and demonstrated that the FD technique could be applied to the wine production in this region to address the negative impacts of rainfall in individual vintages.

Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration.

PURPOSE: GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown. METHODS: Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays. A short hairpin RNA lentivirus was used to knock down GPX8, and the main signaling pathways were investigated using transcriptome sequencing and a phosphorylated kinase array. The sphere formation assays, cloning-formation assays and cell migration assays were used to evaluate the stemness and migration ability of HCC cells. Identifying the GPX8-interacting proteins was accomplished through immunoprecipitation and protein mass spectrometry. RESULTS: The GPX8 protein levels were downregulated in HCC patients. Low expression of GPX8 protein was related to early recurrence and poor prognosis in HCC patients. GPX8 knockdown could enhance the stemness and migration ability of HCC cells. Consistently, Based on transcriptome analysis, multiple signaling pathways that include the PI3K-AKT and signaling pathways that regulate the pluripotency of stem cells, were activated after GPX8 knockdown. The downregulation of GPX8 could increase the expression of the tumor stemness markers KLF4, OCT4, and CD133. The in vivo downregulation of GPX8 could also promote the subcutaneous tumor-forming and migration ability of HCC cells. MK-2206, which is a small-molecule inhibitor of AKT, could reverse the tumor-promoting effects both in vivo and in vitro. We discovered that GPX8 and the 71-kDa heat shock cognate protein (Hsc70) have a direct interaction. The phosphorylation of AKT encouraged the translocation of Hsc70 into the nucleus and the expression of the PI3K p110 subunit, thereby increasing the downregulation of GPX8. CONCLUSION: The findings from this study demonstrate the anticancer activity of GPX8 in HCC by inactivating the Hsc70/AKT pathway. The results suggest a possible therapeutic target for HCC.

Local magnesium sulfate administration ameliorates nociception, peripheral inflammation, and spinal sensitization in a rat model of incisional pain.

OBJECTIVE: Postoperative pain remains one of the most common complaints after surgery, and appropriate treatments are limited. METHODS: We therefore investigated the effect of the anti-nociceptive properties of magnesium sulfate (MgSO4), an N-methyl-D-aspartate (NMDA) receptor antagonist, on incision-induced postoperative pain and peripheral and central nervous system inflammation. RESULTS: We found that local MgSO4 administration dose-dependently increases paw withdrawal latency, indicating reduced peripheral postoperative pain. Furthermore, MgSO4 inhibited the expression of interleukin-1ß (IL-1ß) and inducible nitric oxide synthase (iNOS) and phosphorylation of the NMDA receptor NR1 subunit in injured paw tissue and significantly attenuated microglial and astrocytic activation in the ipsilateral lumbar spinal cord dorsal horn. CONCLUSION: Locally administered MgSO4 has potential for development as an adjunctive therapy for preventing central nociceptive sensitization.

The molecular characteristics of recurrent/metastatic HPV-positive head and neck squamous cell carcinoma: A systematic review of the literature.

OBJECTIVES: About 17% of patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC), which is mainly comprised of oropharyngeal SCC (OPSCC), will experience disease recurrence, which is often considered incurable when manifested at a metastatic and/or recurrent stage. We conducted a critical qualitative systematic review. Our objectives were to provide an overview of the molecular landscape of recurrent/metastatic HPV-positive HNSCC as well as novel molecular biomarkers. DESIGN: A literature review was conducted to identify studies reporting on the molecular characteristics of recurrent/metastatic HPV-positive HNSCC, novel molecular biomarkers and treatment options. The reviews of abstracts, full articles, and revision of the included studies, followed by data extraction and quality assessment were performed by three independent assessors. All primary literature, such as retrospective, prospective, and clinical trials as well as basic research studies were considered, and the final search was conducted at the end of February 2023. The level of evidence was rated using the guidelines published by the Oxford Centre for Evidence-based Medicine and quality was assessed using the Newcastle-Ottawa Scale criteria. RESULTS AND CONCLUSIONS: The literature search resulted in the identification of 1991 articles. A total of 181 full articles were screened, and 66 articles were included in this analysis. Several studies reported that recurrent/metastatic HPV-positive HNSCC had higher rates of TP53 mutation and were genomically similar to HPV-negative HNSCC. The detection of circulating tumour tissue-modified HPV DNA (ctHPVDNA) as a specific biomarker has shown promising results for monitoring treatment response and recurrence in the subset of HPV-positive HNSCC. In addition, evidence for targeted therapy in recurrent/metastatic HPV-positive HNSCC has emerged, including agents that inhibit overexpressed EGFR. Studies of combination immunotherapy are also underway. Our review outlines the latest evidence on the distinct molecular profiles of recurrent/metastatic HPV-positive HNSCC as well as the clinical potential of ctHPVDNA testing in routine practice. More controlled and longitudinal studies are needed to identify additional molecular targets and to assess the performance and benefits of novel molecular biomarkers in clinical practice.

Risk Factors and Clinical Characterization of Cardiovascularand Cerebrovascular Events in Elderly Hemodialysis Patients.

INTRODUCTION: The purpose of this study was to assess the risk factors and clinical characteristics of cardiovascular and cerebrovascular events in elderly hemodialysis patients. METHODS: Elderly patients undergoing hemodialysis (HD) at Deqing County People's Hospital in Zhejiang, China, from May 2020 to May 2023 were enrolled in this study. They were divided into two groups depending on the occurrence of cardiovascular or cerebrovascular events: the case group and the control group. RESULTS: A total of 106 patients were enrolled in this study. Among them, 49 patients experienced cardiovascular or cerebrovascular events, resulting in an incidence rate of 46.23%. According to whether cardiovascular or cerebrovascular events occurred, 57 patients were assigned to the control group, and 49 patients were assigned to the case group. Comparing the basic information and clinical indicators of the two groups, significant differences were observed in patients with hypertensive nephropathy and diabetic nephropathy (P < .05). There were also significant differences in dialysis duration, smoking history, systolic and diastolic blood pressures, uric acid, blood glucose, total cholesterol (TC), lowdensity lipoprotein cholesterol (TG), C-reactive protein (CRP), and PTH (parathyroid hormone) levels and platelet-to-lymphocyte ratio (PLR), between the two groups (P < .05). Multivariate logistic regression analysis revealed that longer dialysis duration, higher systolic and diastolic blood pressures, elevated uric acid, TC, TG, LDL-C, PTH, and blood glucose levels, smoking history, elevated PLR, and CRP were independent risk factors for cardiovascular and cerebrovascular events. The ROC curve showed that these risk factors predicted cardiovascular and cerebrovascular events in patients. CONCLUSION: Patients with underlying diseases such as hypertensive or diabetic nephropathy are more likely to experience cardiovascular and cerebrovascular events. Longer dialysis duration, higher systolic and diastolic blood pressures, elevated uric acid, TC, TG, LDL-C, PTH and blood glucose levels, and boosted inflammatory reaction are risk factors for these events among elderly HD patients. The purpose of this study is to provide practical guidelines for clinical treatment. Comprehensive measures such as active intervention of risk factors, rational drug use and regular examination should be taken to improve the overall health level to the greatest extent for elderly patients with high-risk HD. DOI: 10.52547/ijkd.7877.

Human Adipose-derived Mesenchymal Stem Cells Colonize and Promote Healing of Leprosy Ulcer by Inducing Neuro-vascularization.

Leprosy ulcer is a chronic and recurrent disease resulting from nerve injury. While existing treatments partially facilitate ulcer healing, they exhibit limited ability to address localized nerve repair, leading to a risk of recurrence. Moreover, there is a dearth of animal models to evaluate the preclinical efficacy and safety of novel therapeutic approaches. Over the years, adipose-derived mesenchymal stem cells have been extensively employed in regenerative medicine as an optimal cell therapy source for fostering skin ulcer healing. They have also demonstrated the capacity to enhance nerve regeneration in vitro experiments and clinical trials. In this study, we established a NU/NU mouse foot pad leprosy ulcer model, transplanted human adipose-derived stem cells (hADSCs) into leprosy ulcers via local injection, and conducted subsequent follow-up. Our findings revealed that hADSCs persisted in the leprosy ulcer and facilitated healing process. In this respect, gross observation and histological analysis revealed increased granular formation, collagen synthesis, and re-epithelialization in the local ulcer area. RNA-Seq data revealed that the upregulated differential genes resulting from the transplantation intervention were not only enriched in pathways related to re-epithelialization and collagen synthesis but also contributed to local nerve regeneration. Furthermore, immunofluorescence assays revealed the increased expression of angiogenesis markers CD31 and VEGFa, cell proliferation markers Ki67 and TGF-ß, and nerve regeneration markers ß3-tubulin, SOX10, NGF, and NT-3. These results underscore the potential of hADSCs in promoting the healing of leprosy ulcers and offer valuable preclinical data for their prospective clinical application.

Efficacy of Electroacupuncture Combined with Chinese Herbal Medicine on Pain Intensity for Chronic Sciatica Secondary to Lumbar Disc Herniation: Study Protocol for a Randomised Controlled Trial.

Purpose: Chinese herbal medicine and electroacupuncture (EA) have been used to control pain for many decades in China. We aim to explore the efficacy of intervening patients whose discogenic sciatica symptoms lasting longer than 3 months with these conservative treatments. Patients and Methods: This is a single-center, parallel-group, patient-unblinded Randomized Controlled Trial (RCT) with blinded outcome assessment and statistician. One hundred and twenty-four patients will be assigned randomly into 2 groups including conservative treatment group (Shenxie Zhitong capsule combined with EA treatment) and Nonsteroidal Anti-inflammatory Drugs (Nonsteroidal Anti-inflammatory Drugs, NSAIDs) control group (Celecoxib) in a 1:1 ratio. The trial involves a 4-week treatment along with follow-up for 6 months. The primary outcome is the leg pain intensity measured by the visual analogue scale (VAS) at 6 months after randomization. Secondary outcomes include leg pain intensity at other time points, back pain intensity, leg pain and back pain frequency, functional status, quality of life, return to work status and satisfaction of patients. Adverse events will also be recorded. Strengths and Limitations of This Study: Through this study, we want to observe the efficacy of electroacupuncture combined with Chinese herbal medicine on pain intensity for chronic sciatica secondary to Lumbar Disc Herniation. If the final results are favorable, it is expected to be a safe, economical, and effective treatment for patients. The study design has the following limitations: the setup of control group was less than perfect; patients and doctors could not be blinded in this trial; we skipped the feasibility study. We have tried our best to minimize adverse impacts. Trial Registration: ChiCTR2300070884 (Chinese Clinical Trial Registry, http://www.chictr.org.cn, registered on 25th April 2023).

Use of patient-reported experience and outcome measures within the colorectal cancer care continuum: a scoping review.

OBJECTIVE: Patient-reported outcome measures (PROM) are frequently adopted to evaluate colorectal cancer (CRC) care, but the use of patient-reported experience measures (PREM) appears to be underdeveloped and not widely validated. This scoping review aims to understand the contexts for deployment of PREMs in CRC care, reliability of measures, gaps in current use of PREMs, and how PREMs are associated with PROMs when deployed together. METHODS: Four scientific databases (PubMed, CINAHL, PsycINFO, Scopus) were systematically searched from January 2011 to December 2023. Observational or interventional studies involving quantitative or mixed methodology with samples consisting CRC patients undergoing screening, treatment, or cancer surveillance and utilizing at least one PREM as an exposure or outcome were included. RESULTS: The initial search resulted in 10,400 records. Only 13 relevant studies (consisting of 17,105 participants) met the eligibility criteria. Utilization of PREMs was heterogenous across our sample and the CRC care continuum, and about half of the studies (53.8%) evaluated the relationship between PREMs and PROMs. PREM usage across the CRC care continuum largely focused on treatment/survivorship. Better care experience was positively associated with improved patient-reported outcomes. CONCLUSIONS: Future work in CRC PREM development should focus on (1) establishing validated measures that aim to either capture disease/treatment-specific granularity or capitalize on applicability across care settings, (2) localizing novel or existing PREMs to consider different cultural contexts in healthcare, and (3) benchmarking associations between PREMs, PROMs, and other outcomes of interest. IMPLICATIONS FOR CANCER SURVIVORS: Individuals progressing through the CRC care continuum often undergo a multitude of procedures from detection and diagnosis to treatment and surveillance. The establishment of validated PREMs specific to CRC would help to benchmark and further improve the quality of care received-which should translate to better patient-reported outcomes-and serve as process indicators for institutions and providers to maintain rigorous health service delivery standard for CRC survivors.

The characteristics of polysaccharide composition of red wines in China: Effects of grape varieties, origins and winemaking techniques.

In this work, the polysaccharide profile of different grapes and red wines in China was studied and the influences of two common winemaking techniques on the components of wine were analyzed. The soluble polysaccharide content in the skins of native grape species in China (non-Vitis vinifera grapes) was significantly higher than that of Vitis vinifera species, while the terroir effect on V. vinifera varieties was limited. The combination of the enzyme preparation and the addition of mannoproteins (MPs) at the beginning of alcoholic fermentation (MP1 + E) could increase the contents of MPs and acid polysaccharides (APS) compared to the control wines. Meanwhile, better color characteristics and higher level of anthocyanin derivatives were observed. However, MP1 + E treatment reduced the content of polysaccharides rich in arabinose and galactose (PRAGs) due to enzymatic hydrolysis. The study will provide useful information for winemakers to regulate the wine polysaccharide profile.

Clinical efficacy of probiotics in the treatment of alcoholic liver disease: a systematic review and meta-analysis.

Objective: Alcoholic liver disease (ALD) is a liver damage disease caused by long-term heavy drinking. Currently, there is no targeted pharmaceutical intervention available for the treatment of this disease. To address this, this paper evaluates the efficacy and safety of probiotic preparation in treating ALD through conducting a meta-analysis, and provides a valuable insight for clinical decision-making. Methods: A systematic search was conducted across databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, Wanfang, and CBM from the inception dates to October 15, 2023, to identify clinical randomized controlled trials on probiotic preparations in the treatment of ALD. After the literature underwent screening, data extraction, and quality assessment, RevMan 5.3 and Stata 14.2 were employed for data analysis and processing. Results: A total of 9 randomized controlled trials fulfilled the inclusion criteria. The results of the meta-analysis showed that probiotic preparation could significantly improve the liver function of patients with alcoholic liver disease compared with the control group. Probiotic intervention led to a significant reduction in the levels of alanine aminotransferase (MD=-13.36,95%CI:-15.80,-10.91;P<0.00001),aspartate aminotransferase (MD=-16.99,95%CI:-20.38,-13.59;P<0.00001),γ-glutamyl transpeptidase (MD=-18.79,95% CI:-28.23,-9.34; P<0.0001). Concurrently, the level of serum albumin (MD=0.19,95% CI:0.02,0.36;P=0.03) was increased. Furthermore, probiotic intervention could also modulate the composition of intestinal flora in patients with alcoholic liver disease, leading to an augmentation in Bifidobacteria and a reduction in Escherichia coli. However, in patients with alcoholic liver disease, probiotic intervention showed no significant effects on total bilirubin (MD=-0.01,95% CI:-0.17,0.15;P=0.91), tumor necrosis factor-α (MD=0.03,95% CI:-0.86,0.92;P=0.94) and interleukin-6 (MD=-5.3,95% CI:-16.04,5.45;P=0.33). Conclusion: The meta-analysis indicates that probiotics can improve liver function in alcoholic liver disease, reduce inflammatory responses, regulate intestinal flora, which have potential value in the treatment of alcoholic liver disease. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023472527.

Lattice dynamics and heat transport in zeolitic imidazolate framework glasses.

The glassy state of zeolitic imidazolate frameworks (ZIFs) has shown great potential for energy-related applications, including solid electrolytes. However, their thermal conductivity (κ), an essential parameter influencing thermal dissipation, remains largely unexplored. In this work, using a combination of experiments, atomistic simulations, and lattice dynamics calculations, we investigate κ and the underlying heat conduction mechanism in ZIF glasses with varying ratios of imidazolate (Im) to benzimidazolate (bIm) linkers. The substitution of bIm for Im tunes the node-linker couplings but exhibits only a minor impact on the average diffusivity of low-frequency lattice modes. On the other hand, the linker substitution induces significant volume expansion, which, in turn, suppresses the contributions from lattice vibrations to κ, leading to decreased total heat conduction. Furthermore, spatial localization of internal high-frequency linker vibrations is promoted upon substitution, reducing their mode diffusivities. This is ascribed to structural deformations of the bIm units in the glasses. Our work unveils the detailed influences of linker substitution on the dual heat conduction characteristics of ZIF glasses and guides the κ regulation of related hybrid materials in practical applications.

Structures and bonding characteristics of KCl(H2O)n clusters with n = 1-10 based on density functional theory.

Aqueous inorganic salt solutions play a prominent role in both physiological and chemical experiments, and significant attention has been directed toward understanding the mechanisms underlying salt dissolution. In our effort to elucidate the hydration process of potassium chloride, we employed a comprehensive genetic algorithm to explore the structures of KCl(H2O)n (n = 1-10). A series of stable structures were identified by high-level ab initio optimization and single-point energy calculations with a zero-point energy correction. An analysis of the probability distribution of KCl(H2O)1-10 revealed that clusters with high probability at low temperatures exhibit reduced probabilities at higher temperatures, while others become more prevalent. When n = 1-9, the contact ion pair configurations or partially dissociated structures dominate in the system, and the probability distribution plot shows that the proportion of the solvent-separated ion pair (SSIP) structures of KCl(H2O)n is very small, while the SSIP configuration in KCl(H2O)10 becomes a stable structure with increasing temperature. The results from natural bond orbital analysis reveal a stronger interaction between chloride ions and water molecules. These findings provide valuable insights for a more comprehensive understanding of the intricacies of potassium chloride dissolution in water.

FeP-Based Nanotheranostic Platform for Enhanced Phototherapy/Ferroptosis/Chemodynamic Therapy.

Ferroptosis is an iron-dependent and lipid peroxides (LPO)-overloaded programmed damage cell death, induced by glutathione (GSH) depletion and glutathione peroxide 4 (GPX4) inactivation. However, the inadequacy of endogenous iron and reactive oxygen species (ROS) restricts the efficacy of ferroptosis. To overcome this obstacle, a near-infrared photo-responsive FeP@PEG NPs is fabricated. Exogenous iron pool can enhance the effect of ferroptosis via the depletion of GSH and further regulate GPX4 inactivation. Generation of ·OH derived from the Fenton reaction is proved by increased accumulation of lipid peroxides. The heat generated by photothermal therapy and ROS generated by photodynamic therapy can enhance cell apoptosis under near-infrared (NIR-808 nm) irradiation, as evidenced by mitochondrial dysfunction and further accumulation of lipid peroxide content. FeP@PEG NPs can significantly inhibit the growth of several types of cancer cells in vitro and in vivo, which is validated by theoretical and experimental results. Meanwhile, FeP@PEG NPs show excellent T2-weighted magnetic resonance imaging (MRI) property. In summary, the FeP-based nanotheranostic platform for enhanced phototherapy/ferroptosis/chemodynamic therapy provides a reliable opportunity for clinical cancer theranostics.

Impact of preoperative antiviral therapy on the prognosis of hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: For chronic hepatitis B virus (HBV) infection patients, increasing evidence has demonstrated the effectiveness of expanding the indications and applicable population for antiviral therapy. However, the expanded indication of antiviral therapy for hepatocellular carcinoma (HCC) remains to be further explored. METHODS: 196 HBV-related HCC patients who received radical hepatectomy and nucleos(t)ide analogues (NAs) therapy at Sichuan Provincial People's Hospital were enrolled in this study. HCC recurrence, overall survival (OS), early virological (VR) and biochemical responses (BR) of patients were compared between different NAs therapy and the use of anti-programmed cell death protein 1 (PD-1) therapy. RESULTS: NAs therapy at different timing of surgery was a strong independent risk factor for postoperative recurrence and overall mortality of HBV-related HCC patients. Furthermore, in HCC patients who received postoperative anti-PD-1 therapy, patients with HBV DNA < 1000 copy/mL had significantly better recurrence-free survival (RFS) and OS than those with HBV DNA ≥ 1000 copy/mL (HR: 7.783; P = 0.002; HR: 6.699; P < 0.001). However, the differences of RFS and OS rates between entecavir group and tenofovir disoproxil fumarate group were not statistically significant. Similar results were also observed in the rates of early VR, BR and combined VR and BR. CONCLUSION: Timely and reasonable preoperative NAs therapy showed clinical benefit in improving the prognosis of patients with HBV-related HCC, even in the case of normal alanine aminotransferase (ALT) level and negative hepatitis e antigen (HBeAg). Furthermore, a possible synergistic effect between antiviral therapy and anti-PD-1 therapy was founded and need further verification.