[Treatment of proximal phalangeal fracture with miniature combined external fixator].

OBJECTIVE: To investigate the clinical effect of limited open reduction treatment of proximal phalangeal fracture with miniature external fixator combined with small incision. METHODS: Between January 2020 and December 2022, 29 patients with proximal phalangeal fracture were treated with micro external fixator combined with small incision in fracture plane, including 23 males and 6 females, aged from 19 to 62 years old with an average of (36.2±21.0) years old. Five patients with open phalangeal fracture were treated with stageⅠsurgery, 24 cases of closed phalangeal fracture were treated with elective surgery. At the 6 month follow-up, the curative effect was evaluated according to the total active flexion scale (TAFS) of the American Hand Surgery Association. The fracture healing, nail path, local soft tissue healing, and complications were observed. RESULTS: All the 29 patients were followed up for 6 to 10 months with an average of(8.3±2.1) months, 3 patients had delayed fracture healing, 1 patient had distal skin numbness, symptoms were relieved after nutritional nerve treatment, no external fixator broken nails, no infection, the nail path and small incision healing was good, bone healing was achieved at the end of follow-up. Fracture healing time ranged from 10 to 24 with an average of (13.7±3.1) weeks. Six months after operation, according to the TAFS standard, 19 cases (227.68±4.23) were excellent, 7 cases (203.86±14.32) were good, and 3 cases (170.33±7.32) were poor. CONCLUSION: The micro-combined external fixator combined with limited incision with small incision can be used in the treatment of proximal phalangeal fracture. The operation is simple and beneficial to early functional exercise, small extensor tendon irritation, convenient second-stage removal, and high rate of excellent and good functional score in recovery period.

Prognostic value of the advanced lung cancer inflammation index in intrahepatic cholangiocarcinoma.

INTRODUCTION: The advanced lung cancer inflammation index (ALI), which combines inflammation and nutrition data, was recently proposed as a prognostic biomarker. We assessed the impact of ALI on overall survival (OS) among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC). METHODS: Patients who underwent surgery for ICC were identified from an international cohort. ALI was calculated as body-mass index (BMI)∗albumin/neutrophil-to-lymphocyte ratio; patients were categorized into "low-" and "high-ALI" using log-rank statistics. The impact of ALI on OS was compared against other inflammatory markers (i.e., neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], systemic immune inflammation index [SII = platelets∗NLR]) using Harrell's Concordance index (C-index) and the Akaike Information Criterion (AIC). To minimize intergroup differences, propensity score matching was employed. RESULTS: Among 1045 patients, more than one-half of individuals underwent major hepatectomy (n = 582, 55.7 %), median tumor size was 5.5 cm (IQR, 3.8-7.8), and median ALI was 38.9 (IQR 26.5-57.2). On multivariate analysis, low ALI was an independent risk factor for worse OS (HR 1.21, 95 % CI 1.01-1.46; p = 0.04). Patients with low ALI had worse 5-year OS (36.9 % vs. 49.9 %; p < 0.001), which remained significant after PSM (36.9 % vs. 41.3 %; p = 0.039). ALI had a comparable discriminatory ability compared with NLR, PLR, and SII (C-index: 0.646 vs. 0.644 vs. 0.640 vs. 0.641, respectively), yet had a lower AIC (5475.31 vs. 5546.80 vs. 5550.45 vs. 5548.62, respectively) suggesting slightly better model fit and accuracy. CONCLUSIONS: ALI was an independent predictor of OS among patients undergoing surgery for ICC. Nutritional and inflammatory markers should be incorporated into predictive models to improve prognostic stratification.

High strength "breathable" glycosilicone/Aloe vera polysaccharide-based gel dressing for efficient wound repair.

Medical wound dressings are effective in protecting wounds, maintaining moisture, creating an optimal healing environment and accelerating wound healing. However, their deficiencies in mechanical properties, adhesion and prevention of adhesion to the wound bed have been identified as limiting factors for their therapeutic efficacy in wound healing. To address these issues, we prepared glycosilicone gel dressings consisting of hydrophobic polysiloxanes and highly hydrophilic polysaccharides via ester exchange and silicone hydrogen addition reactions. Silicone gel dressings exhibit skin-like "respiratory" properties, with good permeability to O2 and CO2. Additionally, elongation and other important parameters are similar to those of the skin, which provides a foundation for the application of silicone gels in the field of wound dressings. The introduction of Aloe vera polysaccharide (AP) results in the glycosilicone gel exhibiting certain mechanical properties, including a tensile strength of 0.35 MPa and an adhesion force of 10 N/m. Furthermore, a mouse model of total skin defect demonstrated that the wound healing rate of the mice on the 12th day was 98 %, which effectively promotes wound healing. Consequently, the glycosilicone gel is anticipated to be an optimal wound dressing.

A Novel Liver Metastasis Score for Patients Undergoing Surgical Resection of Gastroenteropancreatic Neuroendocrine Tumors: A Multi-institutional Study.

BACKGROUND: Liver metastasis impacts survival in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs); however, current guidelines lack consensus on post-resection surveillance and adjuvant therapy. A comprehensive risk stratification tool is needed to guide personalized management. OBJECTIVE: We aimed to develop and validate a predictive model for liver metastasis risk after surgical resection of GEP-NETs that incorporates pathological factors and adjuvant therapy. METHODS: Patients with GEP-NETs who underwent surgical resection with curative intent at three major Chinese hospitals (2010-2022) were identified. Univariable and multivariable Cox regression analysis identified independent risk factors of liver metastasis. The liver metastasis score (LMS) was developed using weighted risk factors and validated by tenfold cross-validation. RESULTS: Among the 724 patients included in the analytic cohort, liver metastasis occurred in 66 patients (9.1%) at a median of 36 months; patients with liver metastasis had a worse 5-year overall survival (no liver metastasis 63.6% vs. liver metastasis 95.8%; p < 0.001). Independent predictors were Ki-67 index (hazard ratio [HR] 10.36 for Ki-67 3-20%, HR 18.30 for Ki-67 >20%, vs. <3%), vascular invasion (HR 5.03), lymph node metastases (HR 2.24), and lack of adjuvant therapy (HR 3.03). The LMS demonstrated excellent discrimination (C-index 0.888) and stratified patients into low, intermediate, and high-risk relative to 5-year risk of liver metastasis: 2.9%, 20.8%, and 49.7%, respectively (p < 0.001). CONCLUSIONS: The novel LMS effectively predicted the risk of liver metastasis after surgical resection of GEP-NETs. This validated model can help guide personalized surveillance and adjuvant treatment strategies, potentially improving outcomes for high-risk patients.

Clinical care guidance in patients with diabetes and metabolic dysfunction-associated steatotic liver disease: A joint consensus.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting >30% of the global population. Metabolic dysregulation, particularly insulin resistance and its subsequent manifestation as type 2 diabetes mellitus, serves as the fundamental pathogenesis of metabolic liver disease. Clinical evidence of the recent nomenclature evolution is accumulating. The interaction and impacts are bidirectional between MASLD and diabetes in terms of disease course, risk, and prognosis. Therefore, there is an urgent need to highlight the multifaceted links between MASLD and diabetes for both hepatologists and diabetologists. The surveillance strategy, risk stratification of management, and current therapeutic achievements of metabolic liver disease remain the major pillars in a clinical care setting. Therefore, the Taiwan Association for the Study of the Liver (TASL), Taiwanese Association of Diabetes Educators, and Diabetes Association of the Republic of China (Taiwan) collaboratively completed the first guidance in patients with diabetes and MASLD, which provides practical recommendations for patient care.

An Injection Molded SlipChip with Self-Sampling for Integrated Point-of-Care Testing of Human Papilloma Virus.

High-risk human papillomavirus (HPV) screening is crucial for cervical cancer prevention. However, laboratory-based nucleic acid amplification tests (NAATs) require costly equipment, designated lab space, and skilled personnel. Additionally, cervical swabs collected by healthcare professionals can be inconvenient, uncomfortable, and reduce privacy, limiting broader application and patient compliance. A SlipChip-based Integrated Point-of-Care (SIPOC) system featuring an injection-molded SlipChip is presented with preloaded reagents for nucleic acid extraction and a portable four-channel real-time quantitative PCR instrument for detection. This system incorporates a self-sampling method that allows participants to collect their own vaginal swabs, with the ß-Globin gene as a control. After testing 130 participants for HPV-16 and HPV-18, 97.7% of the self-collected samples are valid. Among valid samples, 25 tested positive for HPV-16 and 9 for HPV-18. Compared to Roche's standard HPV PCR test, the SIPOC system shows 100% positive predictive value (PPV) for both HPV-16 and HPV-18 and negative predictive values (NPVs) of 99.0% and 99.1%, respectively. This system is promising for HPV screening in resource-limited settings and adaptable for other point-of-care NAAT applications, including home testing.

Upfront surgery for intrahepatic cholangiocarcinoma: Prediction of futility using artificial intelligence.

OBJECTIVE: We sought to identify patients at risk of "futile" surgery for intrahepatic cholangiocarcinoma using an artificial intelligence (AI)-based model based on preoperative variables. METHODS: Intrahepatic cholangiocarcinoma patients who underwent resection between 1990 and 2020 were identified from a multi-institutional database. Futility was defined either as mortality or recurrence within 12 months of surgery. Various machine learning and deep learning techniques were used to develop prediction models for futile surgery. RESULTS: Overall, 827 intrahepatic cholangiocarcinoma patients were included. Among 378 patients (45.7%) who had futile surgery, 297 patients (78.6%) developed intrahepatic cholangiocarcinoma recurrence and 81 patients (21.4%) died within 12 months of surgical resection. An ensemble model consisting of multilayer perceptron and gradient boosting classifiers that used 10 preoperative factors demonstrated the highest accuracy, with areas under receiver operating characteristic curves of 0.830 (95% confidence interval 0.798-0.861) and 0.781 (95% confidence interval 0.707-0.853) in the training and testing cohorts, respectively. The model displayed sensitivity and specificity of 64.5% and 80.0%, respectively, with positive and negative predictive values of 73.1% and 72.7%, respectively. Radiologic tumor burden score, serum carbohydrate antigen 19-9, and direct bilirubin levels were the factors most strongly predictive of futile surgery. The artificial intelligence-based model was made available online for ease of use and clinical applicability (https://altaf-pawlik-icc-futilityofsurgery-calculator.streamlit.app/). CONCLUSION: The artificial intelligence ensemble model demonstrated high accuracy to identify patients preoperatively at high risk of undergoing futile surgery for intrahepatic cholangiocarcinoma. Artificial intelligence-based prediction models can provide clinicians with reliable preoperative guidance and aid in avoiding futile surgical procedures that are unlikely to provide patients long-term benefits.

Study of the Characteristics of Ba0.6Sr0.4Ti1-xMnxO3-Film Resistance Random Access Memory Devices.

In this study, Ba0.6Sr0.4Ti1-xMnxO3 ceramics were fabricated by a novel ball milling technique followed by spin-coating to produce thin-film resistive memories. Measurements were made using field emission scanning electron microscopes, atomic force microscopes, X-ray diffractometers, and precision power meters to observe, analyze, and calculate surface microstructures, roughness, crystalline phases, half-height widths, and memory characteristics. Firstly, the effect of different sintering methods with different substitution ratios of Mn4+ for Ti4+ was studied. The surface microstructural changes of the films prepared by the one-time sintering method were compared with those of the solid-state reaction method, and the effects of substituting a small amount of Ti4+ with Mn4+ on the physical properties were analyzed. Finally, the optimal parameters obtained in the first part of the experiment were used for the fabrication of the thin-film resistive memory devices. The voltage and current characteristics, continuous operation times, conduction mechanisms, activation energies, and hopping distances of two types of thin-film resistive memory devices, BST and BSTM, were measured and studied under different compliance currents.

Customizing Ionic Liquids Functionalized MOFs Composites with Hydrophobic Interface for Electrochemical CO2 Reduction.

The electrochemical carbon dioxide reduction reaction (CO2RR) to generate feedstocks for chemical products (e.g., carbon monoxide, CO) offers a highly attractive method for achieving the closure of the carbon cycle. Ionic liquids (ILs)-functionalized Cu-based catalyst Cu2O-HKUST-1/IL1/PTFE was developed, configuring metal-organic frameworks(MOFs) based materials with high adsorption and multiple active sites. The modified electrocatalysts exhibited high specific surface area, strong CO2 adsorption capacity, abundant active sites, and fast charge transfer rate. The nucleophilic active site of deprotonation at the C2 site in imidazole ILs further improved the selectivity of proton migration and CO product generation, which was verified through DFT calculations for the low Gibbs free energy of the generated intermediate interactions. In addition, the hydrophobic interface constructed by PTFE facilitated the inhibition of the hydrogen evolution reaction (HER) and significantly improved the efficiency of CO2 electroreduction. The Cu2O-HKUST-1/IL1/PTFE catalyst manifested a high C1 Faraday efficiency (FE) up to 96.5% and in particular 92.7% for FECO at -1.7 V vs RHE. The present work provides an efficient strategy for configuring ILs-functionalized MOFs-based materials with good hydrophobic interfaces to enhance the efficiency of CO2 electroreduction to C1 products.

Immobilization of laccase on mesoporous metal organic frameworks for efficient cross-coupling of ethyl ferulate.

Laccases act as green catalysts for oxidative cross-coupling of phenolic antioxidnt compounds, but low stability and non-recyclability limit its application. To address that, metal-organic frameworks Cu-BTC and Cr-MOF were synthesized as supports to immobilize the efficient laccase from Cerrena sp. HYB07. The Brunauer-Emmett-Teller surface area of Cu-BTC and Cr-MOF were 1213.2 and 907.1 m2/g, respectively. The two carriers respectively presented pore diameters of 1.2-10 nm and 1.4-12 nm as octahedron, indicating nano-scale mesoporosity. These Cu-BTC and Cr-MOF carriers could adsorb laccase with enzyme loading of 1933.2 and 1564.4 U/g carrier, respectively. The stability and organic solvent tolerance of Cu-BTC-laccase and Cr-MOF-laccase were both obviously improved compared to free laccase. Thermal inactivation kinetics showed that both the two immobilized laccases displayed lower thermal inactivation rate constants. Importantly, the Cu-BTC-laccase and Cr-MOF-laccase both showed much higher activity for cross-coupling of ethyl ferulate than free laccase, which had 2.5-fold higher cross-coupling efficiency than that by free laccase. The ethyl ferulate coupling product was also analyzed by mass spectroscopy and the synthesis pathway of ethyl ferulate dimer was proposed. The cross coupling of ethyl ferulate required the formation of radical intermediates of ethyl ferulate generated by laccase mediated oxidation. This work paved the way for MOFs immobilized laccase for cross coupling of antioxidant phenols.

Development and Validation of a Predictive Risk Score for Blood Transfusion in Patients Undergoing Curative-Intent Surgery for Intrahepatic Cholangiocarcinoma.

BACKGROUND AND OBJECTIVES: Among patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC), perioperative bleeding requiring blood transfusion is a common complication, yet preoperative identification of patients at risk for transfusion remains challenging. The objective of this study was to develop a preoperative risk score for blood transfusion requirement during surgery for ICC. METHODS: Patients undergoing curative-intent liver surgery for ICC (1990-2020) were identified from a multi-institutional database. A predictive model was developed and validated. An easy-to-use risk calculator was made available online. RESULTS: Among 1420 patients, 300 (21.1%) received an intraoperative transfusion. Independent predictors of transfusion included severe preoperative anemia (OR = 1.65, 95% CI 1.10-2.47), T2 category or higher (OR = 2.00, 95% CI 1.36-3.02), positive lymph nodes (OR = 1.75, 95% CI 1.32-2.32) and major resection (OR = 2.56, 95%CI 1.85-3.58). Receipt of blood transfusion significantly correlated with worse outcomes. The model showed good discriminative ability in both training (AUC = 0.68, 95% CI 0.66-0.72) and bootstrapping validation (C-index = 0.67, 95% CI 0.65-0.70) cohorts. An online risk calculator of blood transfusion requirement was developed (https://catalano-giovanni.shinyapps.io/TransfusionRisk). CONCLUSIONS: Intraoperative blood transfusion was significantly associated with poor postoperative outcomes among patients undergoing surgery for ICC. The identification of patients at high risk of transfusion could improve perioperative patient care and blood resources allocation.

In-situ DRIFTS insights into the evolution of surface functionality of biochar upon thermal air oxidation.

Biochar surface functionality is crucial for its application. Herein, the evolution of biochar surface functionality upon thermal air oxidation (TAO) was investigated in-situ by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and thermogravimetric analysis (TGA). The results show that, although the surface functionality of biochar is remarkably changed during TAO at the initial low temperature range, the biochar weight is still stable in the initial low temperature range, suggesting the chemisorption of O2 as intermediate oxygenated functional groups (OFGs) on biochar surface. Moreover, the evolution of biochar surface functionality upon TAO is highly affected on its preparation temperature and intrinsic minerals. Specifically, biochar produced at a high temperature is more resistant to TAO, and more favorable for the formation of ketone groups during TAO. While the biochars prepared at low or medium temperatures show a remarkable formation of carboxyl/lactone groups upon TAO, and the maximum temperature for the formation of carboxyl/lactone groups can be achieved at 400 °C. It's worth noting that the intrinsic minerals in biochar catalyze the TAO reaction, resulting in a much higher mass loss of biochar upon TAO. Furthermore, with the catalysis of intrinsic minerals, TAO is more suitable for enhancing the performance of biochar with intrinsic minerals. These results facilitate the design of engineered biochar via TAO for enhanced applications.

Hepatic portal venous gas after ingesting glyphosate: A case report and literature review.

Background: Glyphosate is a widely used herbicide. Clinical presentations of glyphosate intoxication show variation, but hepatic portal venous gas(HPVG) caused by glyphosate poisoning is rarely reported. Herein, we report a rare case of ominous HPVG after ingesting glyphosate. HPVG, which used to be an ominous abdominal radiologic sign, is associated with numerous underlying abdominal pathologies, ranging from benign conditions that require no invasive treatment to potentially lethal diseases that necessitate prompt surgical intervention. Case summary: A young woman who ingested 100 mL glyphosate 6-h prior was admitted to the emergency intensive care unit. Before admission to our hospital, the patient was administered gastric lavage treatment with 10000 mL of normal saline in the local hospital. After 14 h, her laboratory examinations showed systemic inflammatory response syndrome and multiple organ dysfunction syndrome, while the condition deteriorated. Computed tomography of the abdomen showed multilinear air densities in the portal vein, hepatic branches, and mesenteric vessels, intestinal obstruction, and intestinal necrosis. Septic shock and a severe abdominal infection were diagnosed. The patient was treated conservatively as they could not tolerate surgery and, after 20 h died of septic shock. Conclusion: We reviewed 289 cases of "hepatic portal venous gas" in PUBMED and analyzed the etiology and treatment of HPVG accompanied by the underlying pathology. We concluded that HPVG is a radiological sign associated with various diseases, and the prognosis mainly depends on the underlying cause and clinical condition. As glyphosate may erode the digestive tract, attention should be paid to the volume, pressure, and speed of gastric lavage in treating glyphosate poisoning to avoid fatal complications such as HPVG. Abdominal symptoms need to be closely observed, and changes in the early onset of the condition in clinical practice need to be responded to promptly.

Calcium modulates the tethering of BCOR-PRC1.1 enzymatic core to KDM2B via liquid-liquid phase separation.

Recruitment of non-canonical BCOR-PRC1.1 to non-methylated CpG islands via KDM2B plays a fundamental role in transcription control during developmental processes and cancer progression. However, the mechanism is still largely unknown on how this recruitment is regulated. Here, we unveiled the importance of the Poly-D/E regions within the linker of BCOR for its binding to KDM2B. Interestingly, we also demonstrated that these negatively charged Poly-D/E regions on BCOR play autoinhibitory roles in liquid-liquid phase separation (LLPS) of BCORANK-linker-PUFD/PCGF1RAWUL. Through neutralizing negative charges of these Poly-D/E regions, Ca2+ not only weakens the interaction between BCOR/PCGF1 and KDM2B, but also promotes co-condensation of the enzymatic core of BCOR-PRC1.1 with KDM2B into liquid-like droplet. Accordingly, we propose that Ca2+ could modulate the compartmentation and recruitment of the enzymatic core of BCOR-PRC1.1 on KDM2B target loci. Thus, our finding advances the mechanistic understanding on how the tethering of BCOR-PRC1.1 enzymatic core to KDM2B is regulated.

A Single-Cell Metabolic Profiling Characterizes Human Aging via SlipChip-SERS.

Metabolic dysregulation is a key driver of cellular senescence, contributing to the progression of systemic aging. The heterogeneity of senescent cells and their metabolic shifts are complex and unexplored. A microfluidic SlipChip integrated with surface-enhanced Raman spectroscopy (SERS), termed SlipChip-SERS, is developed for single-cell metabolism analysis. This SlipChip-SERS enables compartmentalization of single cells, parallel delivery of saponin and nanoparticles to release intracellular metabolites and to realize SERS detection with simple slipping operations. Analysis of different cancer cell lines using SlipChip-SERS demonstrated its capability for sensitive and multiplexed metabolic profiling of individual cells. When applied to human primary fibroblasts of different ages, it identified 12 differential metabolites, with spermine validated as a potent inducer of cellular senescence. Prolonged exposure to spermine can induce a classic senescence phenotype, such as increased senescence-associated ß-glactosidase activity, elevated expression of senescence-related genes and reduced LMNB1 levels. Additionally, the senescence-inducing capacity of spermine in HUVECs and WRL-68 cells is confirmed, and exogenous spermine treatment increased the accumulation and release of H2O2. Overall, a novel SlipChip-SERS system is developed for single-cell metabolic analysis, revealing spermine as a potential inducer of senescence across multiple cell types, which may offer new strategies for addressing ageing and ageing-related diseases.

Photodynamic Therapy Using RGD-Functionalized Quantum Dots Elicit a Potent Immune Response in a Syngeneic Mouse Model of Pancreatic Cancer.

Purpose: Photodynamic therapy (PDT) induces anti-tumor immune responses by triggering immunogenic cell death in tumor cells. Previously, we demonstrated that novel QDs-RGD nanoparticles exhibited high efficiency as photosensitizers in the treatment of pancreatic cancer. However, the underlying mechanism of the anti-tumor immune effects induced by the photosensitizer remains unknown. This study assessed the anticancer immune effect of QDs-RGD, as well as the conventional photosensitizer chlorine derivative, YLG-1, for comparison, against pancreatic cancer in support of superior therapeutic efficacy. Methods: The pancreatic cancer cell line, Panc02, was used for in vitro studies. C57BL/6 mice bearing pancreatic cancer cell-derived xenografts were generated for in vivo studies to assess the anti-tumor effects of QDs-RGD-PDT and YLG-1-PDT. The immunostimulatory ability of both photosensitizers was examined by measuring the expression of damage-associated molecular patterns (DAMP), such as calreticulin (CRT), assessing dendritic cell (DC) maturation, and analyzing cytokine expression. The specific immunity of QDs-RGD and YLG-1-PDT on distant tumor were determined by combining PDT with anti-CTLA-4 antibody. Results: QDs-RGD-PDT and YLG-1-PDT significantly inhibited pancreatic cancer cell growth in a dose- and time-dependent manner. While both photosensitizers significantly promoted CRT release, DC maturation, and interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) expression, QDs-RGD exerted a stronger immunostimulatory effect than YLG-1. Combination treatment with QDs-RGD and CTLA-4 blockade was able to significantly inhibit the growth of distant tumors. Conclusion: QDs-RGD is a novel and effective PDT strategy for treating pancreatic tumors by inducing anti-tumor immune responses.

The functional role of m6A demethylase ALKBH5 in cardiomyocyte hypertrophy.

Cardiomyocyte hypertrophy is a major outcome of pathological cardiac hypertrophy. The m6A demethylase ALKBH5 is reported to be associated with cardiovascular diseases, whereas the functional role of ALKBH5 in cardiomyocyte hypertrophy remains confused. We engineered Alkbh5 siRNA (siAlkbh5) and Alkbh5 overexpressing plasmid (Alkbh5 OE) to transfect cardiomyocytes. Subsequently, RNA immunoprecipitation (RIP)-qPCR, MeRIP-qPCR analysis and the dual-luciferase reporter assays were applied to elucidate the regulatory mechanism of ALKBH5 on cardiomyocyte hypertrophy. Our study identified ALKBH5 as a new contributor of cardiomyocyte hypertrophy. ALKBH5 showed upregulation in both phenylephrine (PE)-induced cardiomyocyte hypertrophic responses in vitro and transverse aortic constriction (TAC)/high fat diet (HFD)-induced pathological cardiac hypertrophy in vivo. Knockdown or overexpression of ALKBH5 regulated the occurrence of hypertrophic responses, including the increased cardiomyocyte surface areas and elevation of the hypertrophic marker levels, such as brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP). Mechanically, we indicated that ALKBH5 activated JAK2/STAT3 signaling pathway and mediated m6A demethylation on Stat3 mRNA, but not Jak2 mRNA, resulting in the phosphorylation and nuclear translocation of STAT3, which enhances the transcription of hypertrophic genes (e.g., Nppa) and ultimately leads to the emergence of cardiomyocytes hypertrophic growth. Our work highlights the functional role of ALKBH5 in regulating the onset of cardiomyocyte hypertrophy and provides a potential target for hypertrophic heart diseases prevention and treatment. ALKBH5 activated JAK2/STAT3 signaling pathway and mediated m6A demethylation on Stat3 mRNA, but not Jak2 mRNA, resulting in the phosphorylation and nuclear translocation of STAT3, which enhances the transcription of hypertrophic genes (e.g., Nppa) and ultimately leads to the emergence of cardiomyocytes hypertrophic growth.

Preoperative frailty as a key predictor of short- and long-term outcomes among octogenarians undergoing hepatectomy for hepatocellular carcinoma: a multicenter comprehensive analysis.

BACKGROUND: When considering hepatectomy for elderly HCC patients, it's essential to assess surgical safety and survival benefits. This study investigated the impact of preoperative frailty, assessed with the Clinical Frailty Scale (CFS), on outcomes for octogenarians undergoing HCC hepatectomy. METHODS: A retrospective cohort study of octogenarians who had hepatectomy for HCC between 2010 and 2022 at 16 hepatobiliary centers was conducted. Patients were categorized as frail or non-frail based on preoperative CFS, with frailty defined as CFS ≥5. The primary endpoints were overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS), with perioperative outcomes as secondary endpoints. RESULTS: Among 240 octogenarians, 105 were characterized as being frail. Frail patients had a higher incidence of postoperative 30-day morbidity and postoperative 30-day and 90-day mortality versus non-frail patients. Meanwhile, 5-year OS, RFS and CSS among frail patients were lower compared with non-frail patients. Univariable and multivariable analysis revealed that preoperative frailty was an independent risk factor of postoperative 30-day morbidity (OR: 2.060), OS (HR: 2.384), RFS (HR: 2.190) and CSS (HR: 2.203). CONCLUSION: Preoperative frailty, as assessed by the CFS, was strongly associated with both short-term outcomes and long-term survival among octogenarians undergoing hepatectomy for HCC. Incorporating frailty assessment into the preoperative evaluation may help optimize patient selection and perioperative care.

Hydrothermal Valorization of Biosugars with Heterogeneous Catalysts: Advances, Catalyst Deactivation, Mitigation Strategies and Perspectives.

Sustainable production of valuable biochemicals and biofuels from lignocellulosic biomass necessitates the development of durable and high-performance catalysts. To assist the next-stage catalyst design for hydrothermal treatment of biosugars, this paper provides a critical review of (1) recent advances in biosugar hydrothermal valorization using heterogeneous catalysts, (2) the deactivation process of catalysts based on recycling tests of representative biosugar hydrothermal treatments, (3) state-of-the-art understandings of the deactivation mechanisms of heterogeneous catalysts, and (4) strategies for preparing durable catalysts and the regeneration of deactivated catalysts. Based on the review, challenges and perspectives are proposed. Some remarkable achievements in heterogeneous catalysis of biosugars are highlighted. The understanding of catalyst durability needs to be further enhanced based on full examination of the catalytic performance based on the conversion of substrates, the yield, and selectivity of products. Further, a full examination of the physiochemical changes based on multiple characterization techniques is required to eclucidate the relationships between treatment variables and catalyst durability. Collectively, a clear understanding of the relationships between chemical reaction pathways, treatment variables, and the physiochemistry of catalysts is encouraged to be gained to advise the development of heterogeneous catalysts for long-term and efficient hydrothermal upgrading of biosugars.

Isoliquiritigenin attenuates myocardial ischemia reperfusion through autophagy activation mediated by AMPK/mTOR/ULK1 signaling.

BACKGROUND: Ischemia reperfusion (IR) causes impaired myocardial function, and autophagy activation ameliorates myocardial IR injury. Isoliquiritigenin (ISO) has been found to protect myocardial tissues via AMPK, with exerting anti-tumor property through autophagy activation. This study aims to investigate ISO capacity to attenuate myocardial IR through autophagy activation mediated by AMPK/mTOR/ULK1 signaling. METHODS: ISO effects were explored by SD rats and H9c2 cells. IR rats and IR-induced H9c2 cell models were established by ligating left anterior descending (LAD) coronary artery and hypoxia/re-oxygenation, respectively, followed by low, medium and high dosages of ISO intervention (Rats: 10, 20, and 40 mg/kg; H9c2 cells: 1, 10, and 100 µmol/L). Myocardial tissue injury in rats was assessed by myocardial function-related index, HE staining, Masson trichrome staining, TTC staining, and ELISA. Autophagy of H9c2 cells was detected by transmission electron microscopy (TEM) and immunofluorescence. Autophagy-related and AMPK/mTOR/ULK1 pathway-related protein expressions were detected with western blot. RESULTS: ISO treatment caused myocardial function improvement, and inhibition of myocardial inflammatory infiltration, fibrosis, infarct area, oxidative stress, CK-MB, cTnI, and cTnT expression in IR rats. In IR-modeled H9c2 cells, ISO treatment lowered apoptosis rate and activated autophagy and LC3 fluorescence expression. In vivo and in vitro, ISO intervention exhibited enhanced Beclin1, LC3II/LC3I, and p-AMPK/AMPK levels, whereas inhibited P62, p-mTOR/mTOR and p-ULK1(S757)/ULK1 protein expression, activating autophagy and protecting myocardial tissues from IR injury. CONCLUSION: ISO treatment may induce autophagy by regulating AMPK/mTOR/ULK1 signaling, thereby improving myocardial IR injury, as a potential candidate for treatment of myocardial IR injury.