A nomogram model for early recurrence of HBV-related hepatocellular carcinomas after radical hepatectomy.

Background: To identify the risk factors and construct a predictive model for early recurrence of hepatitis B virus(HBV-)- related hepatocellular carcinomas(HCCs) after radical resection. Data and methods: A total of 465 HBV-related HCC patients underwent radical resections between January 1, 2012 and August 31, 2018.Their data were collected through the inpatient information management system of the First Affiliated Hospital of University of Science and Technology of China. Survival and subgroup analyses of early recurrence among male and female patients were performed using Kaplan-Meier curves. The independent risk factors associated with early postoperative tumor recurrence were analyzed using multivariate Cox proportional hazards regression model. Based on these independent risk factors, a risk function model for early recurrence was fitted, and a column chart for the prediction model was drawn for internal and external validation. Results: A total of 181 patients developed early recurrences, including 156 males and 25 females. There was no difference in the early recurrence rates between males and females. Tumor diameters>5cm, microvascular invasion and albumin level<35 g/L were independent risk factors for early recurrence. A nomogram for the early recurrence prediction model was drawn; the areas under the curve for the model and for external verification were 0.638 and 0.655, respectively. Conclusion: Tumor diameter>5 cm, microvascular invasion, and albumin level<35 g/L were independent risk factors for early recurrence. The prediction model based on three clinical indicators could predict early recurrence, with good discrimination, calibration, and extrapolation.

A systematic review and meta-analysis comparing the impact of tenofovir and entecavir on the prognosis of hepatitis B virus-related hepatocellular carcinoma patients undergoing liver resection.

Background: Tenofovir (TDF) and entecavir (ETV) are highly effective and well-tolerated nucleos(t)ide analogs commonly prescribed for hepatitis B virus (HBV) treatment. Yet, it is unclear whether survival outcomes differ for HBV-related hepatocellular carcinoma (HCC) patients treated with ETV and TDF. Thus, this meta-analysis aimed to compare the prognostic effectiveness of ETV and TDF in HBV-related HCC patients. Methods: We comprehensively searched four databases, PubMed, Web of Science, Embase, and the Cochrane Library, to identify pertinent studies utilizing keywords "entecavir," "tenofovir," "hepatocellular carcinoma," and "liver resection." Our primary outcomes of interest encompassed overall survival (OS), recurrence-free survival (RFS), early recurrence, and late recurrence. The statistical effect size for these measures was expressed in terms of hazard ratios (HRs). Results: Our search yielded 10 studies encompassing 11 datasets involving 7,400 patients. Our meta-analysis revealed that patients treated with TDF achieved better OS (HR = 0.53; 95% confidence interval [CI] = 0.40-0.70, p < 0.0001), RFS (HR = 0.68; 95% CI = 0.57-0.80; p < 0.0001), early recurrence (HR = 0.80; 95% CI = 0.67-0.94; p < 0.0077), and late recurrence (HR = 0.64; 95% CI = 0.43-0.97; p = 0.0368). We detected publication bias potentially affecting OS but not RFS. Conclusion: Our findings demonstrated that TDF outperformed ETV regarding RFS for HBV-related HCC patients. However, to bolster the evidence and establish more conclusive conclusions, further validation via extensive and high-quality randomized controlled trials is essential. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD 42024542579.

Effects of Bifidobacterium animalis subsp. lactis BB-12 and yogurt on mice during oral antibiotic administration.

Probiotics have the potential to prevent disruptions to normal gastrointestinal function caused by oral antibiotic use. In this study, we examined the capacity of Bifidobacterium animalis subspecies lactis BB-12 (BB-12) and yogurt, separately and combined, to mitigate the effects of the antibiotic amoxicillin-clavulanate (AMC) on the gut microbiota and metabolomes of C57BL/6 J mice. Male and female mice were administered either BB-12, yogurt, BB-12 in yogurt, or saline for 10 days concurrent with the inclusion of AMC in the drinking water. Male mice exposed to AMC exhibited significant reductions (p<0.05) in body weight over the course of the study compared to sham (no AMC) controls whereas no such effects were observed for female mice. AMC administration resulted in rapid alterations to the intestinal microbiota in both sexes irrespective of BB-12 or yogurt treatment, including significant (p<0.05) losses in bacterial cell numbers and changes in microbial alpha-diversity and beta-diversity in the feces and cecal contents. The effects of AMC on the gut microbiota were observed within one day of administration and the bacterial contents continued to change over time, showing a succession marked by rapid reductions in Muribaculaceae and Lachnospiraceae and temporal increases in proportions of Acholeplasmataceae (day 1) and Streptococcaceae and Leuconostocaceae (day 5). By day 10 of AMC intake, high proportions of Gammaproteobacteria assigned as Erwiniaceae or Enterobacteriaceae (average of 63 %), were contained in the stools and were similarly enriched in the cecum. The cecal contents of mice given AMC harbored significantly reduced concentrations of (branched) short-chain fatty acids (SCFA), aspartate, and other compounds, whereas numerous metabolites, including formate, lactate, and several amino acids and amino acid derivatives were significantly enriched. Despite the extensive impact of AMC, starting at day 7 of the study, the body weights of male mice given yogurt or BB-12 (in saline) with AMC were similar to the healthy controls. BB-12 (in saline) and yogurt intake was associated with increased Streptococcaceae and both yogurt and BB-12 resulted in lower proportions of Erwiniaceae in the fecal and cecal contents. The cecal contents of mice fed BB-12 in yogurt contained levels of formate, glycine, and glutamine that were equivalent to the sham controls. These findings highlight the potential of BB-12 and yogurt to mitigate antibiotic-induced gut dysbiosis.

Can adjuvant immune checkpoint inhibitors improve the long-term outcomes of hepatocellular carcinoma with high-risk recurrent factors after liver resection? A meta-analysis and systematic review.

Background: Administering adjuvant therapy following liver resection is crucial for patients with hepatocellular carcinoma (HCC) exhibiting high-risk recurrence factors. Immune checkpoint inhibitors (ICIs) are effective against unresectable HCC; however, their effectiveness and safety for this specific patient group remain uncertain. Methods: We conducted an extensive literature search across four scholarly databases to identify relevant studies. Our primary endpoints were overall survival (OS), recurrence-free survival (RFS), and adverse events (AEs). OS and RFS were quantified using hazard ratios (HRs), whereas the 1-, 2-, and 3-year OS and RFS rates were expressed as risk ratios (RRs). Additionally, the incidence of AEs was calculated. Results: Our meta-analysis included 11 studies (N = 3,219 patients), comprising two randomized controlled trials (RCTs) and nine retrospective studies. Among these, eight studies reported HRs for OS, showing a statistically significant improvement in OS among patients receiving adjuvant ICIs (HR, 0.60; 95% confidence interval [CI], 0.45-0.80; p < 0.0001). All included studies reported HRs for RFS, indicating a favorable impact of adjuvant ICIs (HR, 0.62; 95% CI, 0.52-0.73; p < 0.0001). Moreover, aggregated data demonstrated improved 1- and 2-year OS and RFS rates with adjuvant ICIs. The incidence rate of AEs of any grade was 0.70 (95% CI, 0.49-0.91), with grade 3 or above AEs occurring at a rate of 0.12 (95% CI, 0.05-0.20). Conclusion: Adjuvant ICI therapy can enhance both OS and RFS rates in patients with HCC exhibiting high-risk recurrence factors, with manageable AEs. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails PROSPERO, identifier CRD42023488250.

Investigating Milk Fat Globule Structure, Size, and Functionality after Thermal Processing and Homogenization of Human Milk.

Human milk provides bioactive compounds such as milk fat globules (MFGs), which promote brain development, modulate the immune system, and hold antimicrobial properties. To ensure microbiological safety, donor milk banks apply heat treatments. This study compares the effects of heat treatments and homogenization on MFG's physicochemical properties, bioactivity, and bioavailability. Vat pasteurization (Vat-PT), retort (RTR), and ultra-high temperature (UHT) were performed with or without homogenization. UHT, RTR, and homogenization increased the colloidal dispersion of globules, as indicated by increased zeta potential. The RTR treatment completely inactivated xanthine oxidase activity (a marker of MFG bioactivity), whereas UHT reduced its activity by 93%. Interestingly, Vat-PT resulted in less damage, with 28% activity retention. Sialic acid, an important compound for brain health, was unaffected by processing. Importantly, homogenization increased the in vitro lipolysis of MFG, suggesting that this treatment could increase the digestibility of MFG. In terms of color, homogenization led to higher L* values, indicating increased whiteness due to finer dispersion of the fat and casein micelles (and thus greater light scattering), whereas UHT and RTR increased b* values associated with Maillard reactions. This study highlights the nuanced effects of processing conditions on MFG properties, emphasizing the retention of native characteristics in Vat-PT-treated human milk.

Precisely modulating the chromatin tracker via substituent engineering: reporting pathological oxidative stress during mitosis.

An in-depth understanding of cancer-cell mitosis presents unprecedented advantages for solving metastasis and proliferation of tumors, which has aroused great interest in visualizing the behavior via a luminescence tool. We developed a fluorescent molecule CBTZ-yne based on substituent engineering to acquire befitting lipophilicity and electrophilicity for anchoring lipid droplets and the nucleus, in which the low polarity environment and nucleic acids triggered a "weak-strong" fluorescence and "short-long" fluorescence-lifetime response. Meaningfully, CBTZ-yne visualized chromatin condensation, alignment, pull-push, and separation as well as lipid droplet dynamics, for the first time, precisely unveiling the asynchronous cellular mitosis processes affected by photo-generation reactive oxygen species according to the subtle change of fluorescence-lifetime. Our work suggested a new guideline for tracking the issue of the proliferation of malignant tumors in photodynamic therapy.

Comparison of liver resection and radiofrequency ablation in long-term survival among patients with early-stage hepatocellular carcinoma: a meta-analysis of randomized trials and high-quality propensity score-matched studies.

BACKGROUND: Whether radiofrequency ablation (RFA) and liver resection (LR) are comparable treatments for early-stage hepatocellular carcinoma (HCC) is controversial. We conducted this study to provide ample clinical evidence for the argument. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify randomized controlled trials (RCTs) and propensity score-matched (PSM) studies that compared long-term outcomes of both RFA and LR for patients with early-stage HCC. The hazard ratios (HRs) with 95% confidence intervals (95% CI) of overall survival (OS) and disease-free survival (DFS) were calculated. RESULTS: Thirty-six studies consisting of six RCTs and 30 PSM studies were included in this study, and a total of 7384 patients were involved, with 3694 patients being treated with LR and 3690 patients with RFA. Meta-analysis showed that LR provided better OS and DFS than RFA (HR: 1.22, 95% CI: 1.13-1.31; HR: 1.56, 95% CI: 1.39-1.74, respectively). A sensitivity analysis indicated that the results were stable. For the subgroup of patients with BCLC 0 stage, RFA and LR resulted in similar OS and DFS. For the subgroup of patients with single tumor sizes less than 3 cm, RFA reached similar OS (HR: 1.19, 95% CI: 0.90-1.58) but worse DFS compared with LR (HR: 1.45, 95% CI: 1.11-1.90). For the subgroup of ablation margin larger than 0.5 cm, LR still resulted in better OS than RFA (HR: 1.29, 95% CI: 1.09-1.53); while the ablation margin was larger than 1 cm, both RFA and LR resulted in similar OS. The modality of RFA was also a factor that affected results. Subgroup analysis showed that patients receiving ultrasound-guided RFA had worse OS and DFS than LR (HR: 1.24, 95% CI: 1.14-1.36; HR: 1.44, 95% CI: 1.25-1.66, respectively). CONCLUSIONS: Meta-analysis showed that LR provided better OS and DFS for patients with early-stage HCC. However, RFA and LR had similar effects on long-term survival in patients with BCLC 0 stage HCC. RFA and LR probably had similar effects on OS in patients with solitary HCC less than 3 cm or when the ablation margin was larger than 1 cm which need more studies to confirm. The effects of different modalities of RFA on long-term survival are needed for further assessment.

Effect of intermittent Pringle maneuver on perioperative outcomes and long-term survival following liver resection in patients with hepatocellular carcinoma: a meta-analysis and systemic review.

BACKGROUND: Intermittent Pringle maneuver (IPM) is commonly used to control bleeding during liver resection. IPM can cause ischemia-reperfusion injury, which may affect the prognosis of patients with hepatocellular carcinoma (HCC). The present meta-analysis was conducted to evaluate the effect of IPM use on perioperative outcomes and long-term survival in patients with HCC. METHODS: A systemic literature search was performed in the PubMed, Embase, Web of Science, and Cochrane Library databases to identify randomized controlled trials and retrospective studies that compared the effect of IPM with no Pringle maneuver during liver resection in patients with HCC. Hazard ratio (HR), risk ratio, standardized mean difference, and their 95% confidence interval (CI) values were calculated based on the type of variables. RESULTS: This meta-analysis included nine studies comprising one RCT and eight retrospective studies and involved a total of 3268 patients. Perioperative outcomes, including operation time, complications, and length of hospital stay, except for blood loss, were comparable between the two groups. After removing the studies that led to heterogeneity, the results showed that IPM was effective in reducing blood loss. Five studies reported overall survival (OS) and disease-free survival (DFS) data and eight studies reported perioperative outcomes. No significant difference in OS and DFS was observed between the two groups (OS: HR, 1.01; 95% CI, 0.85-1.20; p = 0.95; DFS: HR, 1.01; 95% CI, 0.88-1.17; p = 0.86). CONCLUSION: IPM is a useful technique to control blood loss during liver resection and does not affect the long-term survival of patients with HCC.

Does perioperative allogeneic blood transfusion worsen the prognosis of patients with hepatocellular carcinoma? A meta-analysis of propensity score-matched studies.

Background: Allogeneic blood transfusion is required in a part of liver resection. The effect of allogeneic blood transfusion on the prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. To investigate whether perioperative allogeneic blood transfusion (PBT) affects the long-term prognosis of patients with HCC, we conducted a meta-analysis that included only propensity score-matched (PSM) studies. Methods: The Cochrane Library, Embase, PubMed, and Web of Science databases were systematically searched to identify PSM studies that compared the long-term outcomes of allogeneic blood transfusion in resected HCC patients. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated. Results: This meta-analysis included 9 PSM studies with 12 datasets involving 2476 patients. Lower OS and RFS in HCC patients receiving allogeneic blood transfusion were observed than those in patients not receiving blood transfusion (OS: hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.10-1.64; p < 0.01; RFS: HR, 1.29; 95% CI, 1.07-1.56; p < 0.01). Subgroup analysis revealed that among patients with BCLC A HCC, those receiving allogeneic blood transfusion had lower OS and RFS (OS: HR, 2.27; 95% CI, 1.61-3.21; RFS: HR, 2.11; 95% CI, 1.30-3.41). OS and RFS were similar in both groups of patients with BCLC B and C HCC. Conclusion: The receipt of perioperative allogeneic blood transfusion is associated with a decrease in OS and RFS. These results seem to be reliable for patients in BCLC stage A. But more high-quality research is needed to confirm this conclusion.

Impact of milk secretor status on the fecal metabolome and microbiota of breastfed infants.

Maternal secretor status has been shown to be associated with the presence of specific fucosylated human milk oligosaccharides (HMOs), and the impact of maternal secretor status on infant gut microbiota measured through 16s sequencing has previously been reported. None of those studies have confirmed exclusive breastfeeding nor investigated the impact of maternal secretor status on gut microbial fermentation products. The present study focused on exclusively breastfed (EBF) Indonesian infants, with exclusive breastfeeding validated through the stable isotope deuterium oxide dose-to-mother (DTM) technique, and the impact of maternal secretor status on the infant fecal microbiome and metabolome. Maternal secretor status did not alter the within-community (alpha) diversity, between-community (beta) diversity, or the relative abundance of bacterial taxa at the genus level. However, infants fed milk from secretor (Se+) mothers exhibited a lower level of fecal succinate, amino acids and their derivatives, and a higher level of 1,2-propanediol when compared to infants fed milk from non-secretor (Se-) mothers. Interestingly, for infants consuming milk from Se+ mothers, there was a correlation between the relative abundance of Bifidobacterium and Streptococcus, and between each of these genera and fecal metabolites that was not observed in infants receiving milk from Se- mothers. Our findings indicate that the secretor status of the mother impacts the gut microbiome of the exclusively breastfed infant.

Expanding the toolset of fluorescent covalent staining of biological samples by labeling carboxylate and phosphate groups.

Recently, fluorescent covalent staining methods have been developed for visualization of anatomical structures in cells and tissues. Coupled with expansion microscopy, these stains revealed various ultrastructural details. However, the covalently stainable chemical groups have been limited to amines, carbohydrates, and thiols. Here, we developed procedures for covalently labeling tissues for carboxylate and phosphate groups, utilizing carbodiimide crosslinker chemistry. In porcine kidney tissues, the carboxylate and phosphate stain provides 1.8-4.8-fold higher signal intensity than those from the three existing stains. In cancer cells, such stain allows 2-8-fold more accurate identification of nucleoli than the amine stain. In expansion microscopy samples, such stain reveals a variety of sub-cellular structures in tissues when combined with the amine stain. Such stain also allows imaging of lipid-based structures in cultured cells. With these advantages, this new covalent staining method further expands the toolset for fluorescent visualization of histology.

Efficacy of transarterial therapy combined with first-line tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: a network meta-analysis.

BACKGROUND: Transarterial therapies, including transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), and selective internal radiation therapy, combined with first-line tyrosine kinase inhibitors (TKIs) are considered the standard therapy for unresectable hepatocellular carcinoma. However, inconsistent results have been reported in various studies assessing different combinations of targeted agents. METHODS: A network meta-analysis (NMA) was performed by including 23 randomized controlled trials (RCTs) with 6175 patients to investigate the efficiency of transarterial therapies in combination with different TKIs. Outcomes of interest included overall survival (OS), progression-free survival (PFS), time to progression (TTP), and tumor objective response rate (ORR). A random-effects consistency model was used in this Bayesian NMA. Hazard ratio and odd risks with a 95% credible interval were calculated and agents were ranked based on ranking probability. RESULTS: HAIC showed maximal OS and TTP and TACE plus lenvatinib showed maximal PFS, ORR, and disease control rate (DCR). HAIC and TACE plus lenvatinib were ranked highest based on their respective parameters, which were OS for HAIC and PFS, ORR, and DCR for TACE plus lenvatinib. CONCLUSION: HAIC and TACE plus lenvatinib were relatively better choice for unresectable hepatocellular carcinoma. However, owing to the lack of statistically significant OS benefits among most agents, other agents should be considered as potential alternatives for unresectable hepatocellular carcinoma.

Advances in Small Molecules of Flavonoids for the Regulation of Gluconeogenesis.

Hyperglycemia resulting from over-gluconeogenesis is a prominent feature of type 2 diabetes mellitus (T2DM). Therefore, it is very important to reduce glucose output, especially liver glucose output, and maintain blood glucose homeostasis in the treatment of T2DM. It has been found that small molecules of natural flavonoids are able to act on various targets in the gluconeogenic pathways, interfering with rate-limiting enzyme activity or regulating the cascade of hormonal signaling and affecting all levels of transcription factors by limiting the transport of non-sugar substrates. As a result, gluconeogenesis is inhibited. Literature indicated that gluconeogenesis regulated by flavonoids could be divided into two pathways, namely the pre-translational pathway and the pro-translational pathway. The pre-translational pathway mainly interferes with the signaling pathway and transcription factors in gluconeogenesis and inhibits RNA transcription and the expression of gluconeogenic genes, while the post-translational pathway mainly regulates the transport of nonglucose substrates and directly inhibits four rate-limiting enzymes. This review describes the effects of small flavonoid molecules on different targets and signaling pathways during gluconeogenesis, as well as relevant validation methods, in the hope of providing references for similar studies and promoting the development of anti-diabetic drugs.

Efficacy analysis of hybrid operating room-based laparoscopic cholecystectomy combined with intraoperative endoscopic retrograde cholangiopancreatography in the treatment of cholelithiasis combined with choledocholithiasis - A case-control study.

Objective: The objective is to compare the therapeutic effects of laparoscopic cholecystectomy (LC) combined with intraoperative endoscopic retrograde cholangiopancreatography (ERCP) in hybrid operating room and ERCP + LC under traditional conditions in the treatment of cholelithiasis and choledocholithiasis. Materials and Methods: Data of 82 patients with cholelithiasis complicated with choledocholithiasis treated by our centre from November 2018 to March 2021 were retrospectively analysed. Amongst them, 40 patients treated with LC combined with intraoperative ERCP in a hybrid operating room were placed into Group A, and 42 patients treated with ERCP first followed by LC under traditional conditions were placed into Group B. The differences in operative time, intraoperative blood loss, surgical success rate, stone clearance rate, pain score, exhaust time, ambulation time, post-operative complications, length of hospital stay, hospitalisation cost and other indicators between the two groups were compared. Results: There were no significant differences in operative time, intraoperative blood loss, surgical success rate and stone clearance rate between the two groups (P > 0.05), while there were significant differences in post-operative pain score, exhaust time, ambulation time, length of hospital stay, hospitalisation cost and complications (P < 0.05). Conclusion: LC combined with intraoperative ERCP in hybrid operating room for the treatment of cholelithiasis combined with choledocholithiasis has a better therapeutic effect than traditional ERCP followed by LC, which is worthy of further popularization. Notably, the reasonable selection should be made based on patients' own conditions and hospital facilities.

Does adjuvant hepatic artery infusion chemotherapy improve patient outcomes for hepatocellular carcinoma following liver resection? A meta-analysis.

BACKGROUND: Adjuvant hepatic artery infusion chemotherapy (HAIC) has been shown to be beneficial to the patient outcomes in hepatocellular carcinoma (HCC). METHODS: Randomized controlled trials (RCTs) and non-RCTs were identified from six databases up to January 26, 2023. Patient outcomes were assessed using overall survival (OS) and disease-free survival (DFS). Data were presented as hazard ratios (HR, 95% confidence intervals, or CIs). RESULTS: The present systematic review included 2 RCTs and 9 non-RCTs with a total of 1290 cases. Adjuvant HAIC improved OS (HR of 0.69; 95% CI of 0.56-0.84; p < 0.01) and DFS (HR of 0.64; 95% CI of 0.49-0.83; p < 0.01). Subgroup analysis showed that HCC patients with portal vein invasion (PVI) or microvascular invasion (MVI) benefit from adjuvant HAIC in terms of OS ((HR of 0.43; 95% CI of 0.19-0.95; p < 0.01) and (HR of 0.43; 95% CI of 0.19-0.95; p = 0.0373), respectively) and DFS ((HR of 0.38; 95% CI of 0.21-0.69; p < 0.01) and (HR of 0.73; 95% CI of 0.60-0.88; p = 0.0125), respectively). Adjuvant HAIC with the oxaliplatin-based approach significantly improved OS (HR of 0.60; 95% CI of 0.36-0.84; p = 0.02) and (HR of 0.59; 95% CI of 0.43-0.75; p < 0.01), respectively). CONCLUSION: This meta-analysis demonstrated that postoperative adjuvant HAIC was beneficial in HCC patients with PVI and MVI. It remains unclear whether HAIC can improve the survival outcome in all HCC patients after hepatic resection.

Hepatocyte-derived extracellular vesicles miR-122-5p promotes hepatic ischemia reperfusion injury by regulating Kupffer cell polarization.

Ischemia reperfusion injury remains a major barrier to liver transplantation, especially using grafts from donation after circulatory death, and it is also a pressing issue to be solved in clinical practice. Kupffer cell polarization toward a proinflammatory M1 phenotype is an early trigger of liver ischemia-reperfusion injury. However, the molecular mechanism regulating Kupffer cell polarization has not yet been fully elucidated. We induced liver ischemia reperfusion injury in mice and obtained samples from patients undergoing liver transplantation, serum and hepatocytes-derived extracellular vesicles were isolated by differential ultracentrifugation. Kupffer cell polarization was examined by flow cytometry and immunofluorescence histochemistry. RNA-seq was conducted to detect the differentially expressed miRNAs in extracellular vesicles. The role and mechanism of exosomal miR-122-5p in liver ischemia-reperfusion injury were determined both in vitro and in vivo. We identified ischemia reperfusion induced extracellular vesicles as a major cause of hepatic inflammation and tissue damage using adoptive transfer and release inhibition. The study also demonstrated that hepatocyte-derived exosomal miR-122-5p mediates liver ischemia reperfusion injury by polarizing Kupffer cell via PPARδ down-regulation and NF-κB pathway activation using profiling and functional analysis. Moreover, inhibiting miR-122-5p with antagomir suppressed Kupffer cell M1 polarization and attenuated liver ischemia reperfusion injury. Overall, our study demonstrated that hepatocyte-derived exosomal miR-122-5p played a critical role in promoting hepatic ischemia reperfusion injury through modulating PPARδ signaling and NF-κB pathway to introduce M1 polarization of Kupffer cell. Inhibition of miR-122-5p exhibited a protective effect against liver ischemia reperfusion injury, suggesting a potential therapeutic target for liver transplantation.

Mechanism of Interlaminar Strengthening and Toughening of Al/CFRP/Al Composite Laminates.

To solve the problem of easy delamination of the interface of Al/CFRP/Al laminate (CFRP, carbon fiber composite; Al, aluminum), a method of constructing high strength and toughness at the interface is proposed. The effects of adding resin and carbon nanotubes at the interface on the shear, flexural strength and impact resistance of Al/CFRP/Al laminates are studied. Experimental results show that gullies and micropores can be formed on the surface of aluminum after pretreatment, and the contact area between aluminum and matrix can be increased. After resin is added to the Al/CFRP interface, the shear strength between layers and the bending strength and impact resistance of laminates are improved. Mixing carbon nanotubes into the added resin will further improve the mechanical properties of laminates. On the basis of strengthening and toughening the Al/CFRP interface, the carbon nanotubes added between the CFRP layers can strengthen and toughen the resin at the interface, which enhances the bending strength and impact resistance of the laminates. When the resin between the layers breaks, the carbon nanotubes will be pulled off and pulled out to resist the damage of the resin, and the carbon nanotubes at the end of the crack can hinder the propagation of the cracks.

Effect of grazing exclusion on emission of greenhouse gases and soil organic carbon turnover in alpine shrub meadow.

Grazing exclusion (GE) is a management option used widely to restore degraded grassland and improve grassland ecosystems. However, the impacts of GE on soil properties and greenhouse gas emissions of alpine shrub meadow are still unclear, especially long-term GE of more than ten years. To fill part of this gap, we examined the effects of long-term GE of alpine shrub meadow on soil nutrients, soil properties, greenhouse gas emissions (CO2 and CH4) and soil organic carbon (SOC) turnover. When compared to grazed grassland (GG), long-term GE resulted in: 1) greater SOC, nitrogen (N), and phosphorous (P) content, especially in the 20-30 cm soil layer; 2) greater soil C:N, C:P and N:P ratios in the 20-30 cm depth; 3) greater soil CO2, but lesser CH4 emission during the growing season; and 4) much faster SOC turnover time (0-30 cm). GE of more than ten years can increase grassland C reserves and improve the C sequestration capacity of the ecosystem. Results from this study can have important implications in developing future grassland management policies on soil nutrient balances, restoration of degraded grassland and controlling shrub expansion.

Comparison of the effects of lenvatinib and sorafenib on survival in patients with advanced hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND AND AIM: The first-line systemic therapy for advanced hepatocellular carcinoma (HCC) involves the use of sorafenib and lenvatinib. The present meta-analysis attempted to compare the therapeutic safety and effectiveness of the two drugs in advanced HCC. METHODS: The library databases of Cochrane, Embase, PubMed, and Web of Science were systematically searched to identify eligible studies comparing the long-term outcomes of sorafenib and lenvatinib use in advanced HCC patients. Overall survival (OS) was considered the primary endpoint, whereas the progression-free survival (PFS), severe adverse events (AEs), objective response rate (ORR), and disease control rate (DCR) were considered the secondary endpoints. RESULTS: The present systematic review included 8 nonrandomized studies and 1 randomized controlled trial, comprising a total of 1, 914 cases. OS in patients receiving lenvatinib was better than that in patients receiving sorafenib [hazard ratio (HR): 1.23; 95% confidence interval (CI): 1.04-1.45]. Additionally, patients who received lenvatinib exhibited better PFS, ORR, and DCR (HR: 0.89, 95% CI: 0.79-0.99), [odds ratio (OR: 7.50, 95% CI: 4.43-12.69)], (OR: 7.50, 95% CI: 4.43-12.69), but higher incidences of AEs than those receiving sorafenib (OR: 1.28, 95% CI: 1.08-1.53). CONCLUSION: Lenvatinib is superior to sorafenib in treating unresectable HCC patients.

Me-Better Drug Design Based on Nevirapine and Mechanism of Molecular Interactions with Y188C Mutant HIV-1 Reverse Transcriptase.

In this paper, the Y188C mutant HIV-1 reverse transcriptase (Y188CM-RT) target protein was constructed by homology modeling, and new ligands based on nevirapine (NVP) skeleton were designed by means of fragment growth. The binding activity of new ligands to Y188CM-RT was evaluated by structural analysis, ADMET prediction, molecular docking, energy calculation and molecular dynamics. Results show that 10 new ligands had good absorbability, and their binding energies to Y188CM-RT were significantly higher than those of wild-type HIV-1 reverse transcriptase(wt). The binding mode explained that fragment growth contributed to larger ligands, leading to improved suitability at the docking pocket. In the way of fragment growth, the larger side chain with extensive contact at terminal is obviously better than substituted benzene ring. The enhancement of docking activity is mainly due to the new fragments such as alkyl chains and rings with amino groups at NVP terminal, resulting in a large increase in hydrophobic bonding and the new addition of hydrogen bonding or salt bonding. This study is expected to provide reference for the research on non-nucleoside reverse transcriptase inhibitors resistance and AIDS treatment.