Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population: A prospective, multicenter, randomized, two-stage study.

BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.

CD36 restricts lipid-associated macrophages accumulation in white adipose tissues during atherogenesis.

Visceral white adipose tissues (WAT) regulate systemic lipid metabolism and inflammation. Dysfunctional WAT drive chronic inflammation and facilitate atherosclerosis. Adipose tissue-associated macrophages (ATM) are the predominant immune cells in WAT, but their heterogeneity and phenotypes are poorly defined during atherogenesis. The scavenger receptor CD36 mediates ATM crosstalk with other adipose tissue cells, driving chronic inflammation. Here, we combined the single-cell RNA sequencing technique with cell metabolic and functional assays on major WAT ATM subpopulations using a diet-induced atherosclerosis mouse model (Apoe-null). We also examined the role of CD36 using Apoe/Cd36 double-null mice. Based on transcriptomics data and differential gene expression analysis, we identified a previously undefined group of ATM displaying low viability and high lipid metabolism and labeled them as "unhealthy macrophages". Their phenotypes suggest a subpopulation of ATM under lipid stress. We also identified lipid-associated macrophages (LAM), which were previously described in obesity. Interestingly, LAM increased 8.4-fold in Apoe/Cd36 double-null mice on an atherogenic diet, but not in Apoe-null mice. The increase in LAM was accompanied by more ATM lipid uptake, reduced adipocyte hypertrophy, and less inflammation. In conclusion, CD36 mediates a delicate balance between lipid metabolism and inflammation in visceral adipose tissues. Under atherogenic conditions, CD36 deficiency reduces inflammation and increases lipid metabolism in WAT by promoting LAM accumulation.

Cannabidiol enhances socially transmitted food preference: a role of acetylcholine in the mouse basal forebrain.

RATIONALE AND OBJECTIVE: Rodents acquire food information from their conspecifics and display a preference for the conspecifics' consumed food. This social learning of food information from others promotes the survival of a species, and it is introduced as the socially transmitted food preference (STFP) task. The cholinergic system in the basal forebrain plays a role in the acquisition of STFP. Cannabidiol (CBD), one of the most abundant phytocannabinoids, exerts its therapeutic potential for cognitive deficits through versatile mechanisms of action, including its interaction with the cholinergic system. We hypothesize a positive relationship between CBD and STFP because acetylcholine (ACh) is involved in STFP, and CBD increases the ACh levels in the basal forebrain. MATERIALS AND METHODS: Male C57BL/6J mice were trained to acquire the STFP task. We examined whether CBD affects STFP memory by administering CBD (20 mg/kg, i.p.) before the STFP social training. The involvement of cholinergic system in CBD's effect on STFP was examined by knockdown of brain acetylcholinesterase (AChE), applying a nonselective muscarinic antagonist SCO (3 mg/kg, i.p.) before CBD treatment, and measuring the basal forebrain ACh levels in the CBD-treated mice. RESULTS: We first showed that CBD enhanced STFP memory. Knockdown of brain AChE also enhanced STFP memory, which mimicked CBD's effect on STFP. SCO blocked CBD's memory-enhancing effect on STFP. Our most significant finding is that the basal forebrain ACh levels in the CBD-treated mice, but not their control counterparts, were positively correlated with mice's STFP memory performance. CONCLUSION: This study indicates that CBD enhances STFP memory in mice. Specifically, those which respond to CBD by increasing the muscarinic-mediated ACh signaling perform better in their STFP memory.

van der Waals-bonded graphene clusters enhance thermal conductivity of phase-change materials for advanced thermal energy management.

Organic phase-change materials possess immense application potential, but their low thermal conductivity (≤0.5 W m-1 K-1) severely limits the thermal energy charge/discharge rate, impeding their practical implementation in the field of advanced energy. While incorporating thermally conductive fillers into the phase-change matrix can address this issue, achieving a thermal conductivity exceeding 10 W m-1 K-1 at a filler content below 30 vol% remains challenging, attributed to the absence of a well-designed filler interface and structure. Herein, a strategy for developing planar graphene clusters and subsequently integrating them with phase-change microcapsules to fabricate composites using compression molding was demonstrated. The proposed graphene clusters are formed by closely aligned and overlapping graphene sheets that bond together through van der Waals forces, resulting in a significant decrease in junction thermal resistance within the composites. Combining this interface design with compression-induced construction of a highly oriented structure, the composites achieved a remarkable thermal conductivity of 103 W m-1 K-1 with ≈29 vol% filler addition, enhancing the thermal energy charge/discharge rate by over two orders of magnitude. Furthermore, we demonstrated that the composites possess the essential enthalpy values, competent strength, and ease of shaping, making them applicable across various domains of thermal energy management.

Unveiling the shield: Troglitazone's impact on epilepsy-induced nerve injury through ferroptosis inhibition.

BACKGROUND: Epilepsy is a widespread central nervous system disorder with an estimated 50 million people affected globally. It is characterized by a bimodal incidence peak among infants and the elderly and is influenced by a variety of risk factors, including a significant genetic component. Despite the use of anti-epileptic drugs (AEDs), drug-refractory epilepsy develops in about one-third of patients, highlighting the need for alternative therapeutic approaches. AIMS: The primary aim of this study was to evaluate the neuroprotective effects of troglitazone (TGZ) in epilepsy and to explore the potential mechanisms underlying its action. METHODS: We employed both in vitro and in vivo models to assess TGZ's effects. The in vitro model involved glutamate-induced toxicity in HT22 mouse hippocampal neurons, while the in vivo model used kainic acid (KA) to induce epilepsy in mice. A range of methods, including Hoechst/PI staining, CCK-8 assay, flow cytometry, RT-PCR analysis, Nissl staining, scanning electron microscopy, and RNA sequencing, were utilized to assess various parameters such as cellular damage, viability, lipid-ROS levels, mitochondrial membrane potential, mRNA expression, seizure grade, and mitochondrial morphology. RESULTS: Our results indicate that TGZ, at doses of 5 or 20 mg/kg/day, significantly reduces KA-induced seizures and neuronal damage in mice by inhibiting the process of ferroptosis. Furthermore, TGZ was found to prevent changes in mitochondrial morphology. In the glutamate-induced HT22 cell damage model, 2.5 µM TGZ effectively suppressed neuronal ferroptosis, as shown by a reduction in lipid-ROS accumulation, a decrease in mitochondrial membrane potential, and an increase in PTGS2 expression. The anti-ferroptotic effect of TGZ was confirmed in an erastin-induced HT22 cell damage model as well. Additionally, TGZ reversed the upregulation of Plaur expression in HT22 cells treated with glutamate or erastin. The downregulation of Plaur expression was found to alleviate seizures and reduce neuronal damage in the mouse hippocampus. CONCLUSION: This study demonstrates that troglitazone has significant therapeutic potential in the treatment of epilepsy by reducing epileptic seizures and the associated brain damage through the inhibition of neuronal ferroptosis. The downregulation of Plaur expression plays a crucial role in TGZ's anti-ferroptotic effect, offering a promising avenue for the development of new epilepsy treatments.

Association of Myostatin With Complications and Cognition in Lung Cancer Patients With Sarcopenia.

INTRODUCTION: The risk of surgery and postoperative complications increases greatly in frail older patients with sarcopenia. The purpose of this study is to explore the correlation between myostatin (MSTN) levels and cognitive function and postoperative pulmonary complications (PPCs) in older patients undergoing thoracoscopic lobectomy and to determine whether MSTN could be used to predict the risk of postoperative complications and cognitive impairment. METHODS: A prospective observational study was conducted at the First Affiliated Hospital of Bengbu Medical College, China, between January 2023 and June 2023. The risk factors of PPCs and postoperative cognitive impairment were studied using backward stepwise logistic regression analysis. The independent factors were formed into a linear regression equation to construct a risk score model for each patient. The 122 patients who participated in the study were divided into two groups, a low-level group and a high-level group, based on an MSTN level cut-off; the preoperative MSTN cut-off values was 25.55 ng/mL for cognitive dysfunction and 22.29 ng/mL for PPCs. The PPCs and cognitive function of the groups were compared. RESULTS: Preoperative MSTN was confirmed as a risk factor for postoperative cognitive dysfunction and PPCs. After surgery, the proportion of patients with cognitive impairment in the high-level group was significantly higher than in the low-level group (P < 0.001). In the high-level group, the incidence of respiratory tract infections was 17.9% higher (P = 0.021), hypoxaemia was 20.5% higher (P = 0.001) and respiratory failure was 14.4% higher (P = 0.012) than in the low-level group. In addition, a high level of MSTN increased the length of hospital stay (P < 0.001) and decreased the Barthel Index score (P < 0.001). CONCLUSIONS: The study findings suggest that MSTN could be used as an index to predict complications and cognitive impairment after thoracoscopic lobectomy in older patients with sarcopenia and to provide evidence for reducing postoperative cognitive impairment and PPCs.

The safety and efficacy of indobufen or aspirin combined with clopidogrel in patients with acute myocardial infarction after percutaneous coronary intervention.

Currently, the standard treatment for patients who have undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (MI) involves dual antiplatelet therapy (DAPT) with a combination of aspirin and a potent P2Y12 receptor inhibitor. However, the potential benefits of aspirin were partially constrained by the intolerance of some patients. The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.This retrospective study was conducted at a single center and utilized propensity score matching. The enrollment spanned from January 2019 to June 2022, incorporating patients with AMI after PCI. The participants were categorized into two groups based on discharged prescriptions: the aspirin DAPT group and the indobufen DAPT group. The primary endpoint focused on net adverse clinical event (NACE), defined as a composite outcome, including cardiac death, recurrence of MI, definite or probable stent thrombosis (ST), target lesion revascularization (TLR), ischemic stroke and Bleeding Academic Research Consortium (BARC) criteria type 2, 3, or 5. All the patients underwent a one-year follow-up period.A total of 1451 patients were enrolled in this study, with 258 assigned to the indobufen DAPT group and 1193 to the aspirin DAPT group. Following 1:1 propensity score matching, 224 patients were retained in each group. In the indobufen DAPT group, 58 individuals (25.9%) experienced the primary endpoint within one year, compared to 52 individuals (23.2%) in the aspirin DAPT group (HR 1.128, 95% CI 0.776-1.639, p = .527). Specifically, no significant differences were observed in either the efficacy endpoint (MACCE, 20.1% vs. 14.7%, HR 1.392, 95% CI 0.893-2.170, p = .146) or the safety endpoint (BARC 2,3 or 5, 8.04% vs. 10.30%, HR 0.779, p = .427). These findings remained consistent at 1, 3, or 6 months. Additionally, the incidence of gastrointestinal symptoms were significantly lower in indobufen DAPT group compared to the aspirin DAPT group (7.1% vs. 14.3%, p = .022).Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.

What is the context? Currently, the standard treatment for patients who have undergone percutaneous coronary intervention following acute myocardial infarction involves dual antiplatelet therapy with a combination of aspirin and a potent P2Y12 receptor inhibitor.However, the potential benefits of aspirin were partially constrained by the intolerance of some patients.The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.What is new? While both American and European clinical guidelines recommend the use of indobufen as an alternative treatment for patients who cannot tolerate aspirin, there exists a limited body of research on this subject.Our research is the first to address this gap by comparing the efficacy and safety of indobufen and aspirin in patients with AMI.Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.What is the impact? These findings might pave the way for further exploration of alternatives to aspirin in patients with AMI.

Revealing Different Pathways for Influenza A Virus To Reach Microtubules after Endocytosis by Quantum Dot-Based Single-Virus Tracking.

Actin- and microtubule (MT)-based transport systems are essential for intracellular transport. During influenza A virus (IAV) infection, MTs provide long tracks for virus trafficking toward the nucleus. However, the role of the actin cytoskeleton in IAV entry and especially the transit process is still ambiguous. Here, by using quantum dot-based single-virus tracking, it was revealed that the actin cytoskeleton was crucial for the virus entry via clathrin-mediated endocytosis (CME). After entry via CME, the virus reached MTs through three different pathways: the virus (1) was driven by myosin VI to move along actin filaments to reach MTs (AF); (2) was propelled by actin tails assembled by an Arp2/3-dependent mechanism to reach MTs (AT); and (3) directly reached MTs without experiencing actin-related movement (NA). Therefore, the NA pathway was the main one and the fastest for the virus to reach MTs. The AT pathway was activated only when plenty of viruses entered the cell. The viruses transported by the AF and AT pathways shared similar moving velocities, durations, and displacements. This study comprehensively visualized the role of the actin cytoskeleton in IAV entry and transport, revealing different pathways for IAV to reach MTs after entry. The results are of great significance for globally understanding IAV infection and the cellular endocytic transport pathway.

Simultaneous Mapping of the Nanoscale Organization and Redox State of Extracellular Space in Living Brain Tissue.

The spatial organization characteristics and redox status of the extracellular space (ECS) are crucial in the development of brain diseases. However, it remains a challenge to simultaneously capture dynamic changes in microstructural features and redox states at the submicron level within the ECS. Here, we developed a reversible glutathione (GSH)-responsive nanoprobe (RGN) for mapping the spatial organization features and redox status of the ECS in brain tissues with nanoscale resolution. The RGN is composed of polymer nanoparticles modified with GSH-responsive molecules and amino-functionalized methoxypoly(ethylene glycol), which exhibit exceptional single-particle brightness and excellent free diffusion capability in the ECS of brain tissues. Tracking single RGNs in acute brain slices allowed us to dynamically map spatial organizational features and redox levels within the ECS of brain tissues in disease models. This provides a powerful super-resolution imaging method that offers a potential opportunity to study the dynamic changes in the ECS microenvironment and to understand the physiological and pathological roles of the ECS in vivo.

Oxidized LDL regulates efferocytosis through the CD36-PKM2-mtROS pathway.

Macrophage efferocytosis, the process by which phagocytes engulf and remove apoptotic cells (ACs), plays a critical role in maintaining tissue homeostasis. Efficient efferocytosis prevents secondary necrosis, mitigates chronic inflammation, and impedes atherosclerosis progression. However, the regulatory mechanisms of efferocytosis under atherogenic conditions remain poorly understood. We previously demonstrated that oxidized LDL (oxLDL), an atherogenic lipoprotein, induces mitochondrial reactive oxygen species (mtROS) in macrophages via CD36. In this study, we demonstrate that macrophage mtROS facilitate continual efferocytosis through a positive feedback mechanism. However, oxLDL disrupts continual efferocytosis by dysregulating the internalization of ACs. This disruption is mediated by an overproduction of mtROS. Mechanistically, oxLDL/CD36 signaling promotes the translocation of cytosolic PKM2 to mitochondria, facilitated by the chaperone GRP75. Mitochondrial PKM2 then binds to Complex III of the electron transport chain, inducing mtROS production. This study elucidates a novel regulatory mechanism of efferocytosis in atherosclerosis, providing potential therapeutic targets for intervention. SUMMARY: Macrophages clear apoptotic cells through a process called efferocytosis, which involves mitochondrial ROS. However, the atherogenic oxidized LDL overstimulates mitochondrial ROS via the CD36-PKM2 pathway, disrupting continual efferocytosis. This finding elucidates a novel molecular mechanism that explains defects in efferocytosis, driving atherosclerosis progression.

Predicting the Risk of Postoperative Delirium in Elderly Patients Undergoing Hip Arthroplasty: Development and Assessment of a Novel Nomogram.

OBJECTIVE: To construct and internally validate a nomogram that predicts the likelihood of postoperative delirium in a cohort of elderly individuals undergoing hip arthroplasty. METHODS: Data for a total of 681 elderly patients underwent hip arthroplasty were retrospectively collected and divided into a model (n = 477) and a validation cohort (n = 204) according to the principle of 7:3 distribution temporally. The assessment of postoperative cognitive function was conducted through the utilization of The Confusion Assessment Method (CAM). The nomogram model for postoperative cognitive impairments was established by a combination of Lasso regression and logistic regression. The receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) were used to evaluate the performance. RESULTS: The nomogram utilized various predictors, including age, body mass index (BMI), education, preoperative Barthel Index, preoperative hemoglobin level, history of diabetes, and history of cerebrovascular disease, to forecast the likelihood of postoperative delirium in patients. The area under the ROC curves (AUC) for the nomogram, incorporating the aforementioned predictors, was 0.836 (95% CI: 0.797-0.875) for the training set and 0.817 (95% CI: 0.755-0.880) for the validation set. The calibration curves for both sets indicated a good agreement between the nomogram's predictions and the actual probabilities. CONCLUSION: The use of this novel nomogram can help clinicians predict the likelihood of delirium after hip arthroplasty in elderly patients and help prevent and manage it in advance.

Association of whole blood copper, zinc, calcium, magnesium, and iron with non-alcoholic fatty liver disease in overweight and obese children. / å ¨è¡€é“œã€é”Œã€é’™ã€é•ã€é“ä¸Žè¶ é‡è‚¥èƒ–å„¿ç«¥éžé ’ç²¾æ€§è„‚è‚ªè‚ç— çš„å ³è”.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder in overweight and obese children, and its etiology and pathogenesis remain unclear, lacking effective preventive and therapeutic measures. This study aims to explore the association between whole blood copper, zinc, calcium, magnesium and iron levels and NAFLD in overweight and obese children aged 6 to 17 years, providing a scientific basis for the prevention and intervention of early NAFLD in overweight and obese children. METHODS: A cross-sectional study design was used to collect relevant data from overweight and obese children who visited the Hunan Children's Hospital from January 2019 to December 2021 through questionnaire surveys. Fasting blood samples were collected from the subjects, and various indicators such as blood glucose, blood lipid, and mineral elements were detected. All children were divided into an overweight group (n=400) and a NAFLD group (n=202). The NAFLD group was divided into 2 subgroups according to the ALT level: A non-alcoholic fatty liver (NAFL) group and a non-alcoholic steatohepatitis (NASH) group. Logistic regression analysis was used to analyze the association between minerals (copper, zinc, calcium, magnesium, and iron) and NAFLD, NAFL and NASH. RESULTS: A total of 602 subjects were included, of whom 73.6% were male, with a median age of 10 (9, 11) years, and a body mass index (BMI) of 24.9 (22.7, 27.4) kg/m2. The intergroup comparison results showed that compared with the overweight group, the NAFLD group had higher levels of age, BMI, diastolic blood pressure (DBP), systolic blood pressure (SBP), triglyceride (TG), low density lipoprotein (LDL), alanine transaminase (ALT) and aspartate aminotransferase (AST), and lower level of high density lipoprotein (HDL). The NAFL group had higher levels of age, BMI, DBP, SBP, ALT, and AST, and lower levels of HDL compared with the overweight group. The levels of age, BMI, DBP, SBP, TG, LDL, ALT, and AST of NASH were higher than those in the overweight group, while the level of HDL was lower than that in overweight group (all P<0.017). After adjusting for a variety of confounders, the OR of NAFLD for the highest quantile of iron was 1.79 (95% CI 1.07 to 3.00) compared to the lowest quantile, and no significant association was observed between copper, zinc, calcium, and magnesium, and NAFLD. The subgroup analysis of NAFLD showed that the OR for the highest quantile of iron in children with NAFL was 2.21 (95% CI 1.26 to 3.88), while no significant association was observed between iron level and NASH. In addition, no significant associations were observed between copper, zinc, calcium, and magnesium levels and NAFL or NASH. CONCLUSIONS: High iron level increases the risk of NAFLD (more likely NAFL) in overweight and obese children, while copper, zinc, calcium, magnesium, and other elements are not associated with the risk of NAFLD in overweight and obese children.

Fine-Tuning Electron Transfer for Nanozyme Design.

Nanozymes, with their versatile composition and structural adaptability, present distinct advantages over natural enzymes including heightened stability, customizable catalytic activity, cost-effectiveness, and simplified synthesis process, making them as promising alternatives in various applications. Recent advancements in nanozyme research have shifted focus from serendipitous discovery toward a more systematic approach, leveraging machine learning, theoretical calculations, and mechanistic explorations to engineer nanomaterial structures with tailored catalytic functions. Despite its pivotal role, electron transfer, a fundamental process in catalysis, has often been overlooked in previous reviews. This review comprehensively summarizes recent strategies for modulating electron transfer processes to fine-tune the catalytic activity and specificity of nanozymes, including electron-hole separation and carrier transfer. Furthermore, the bioapplications of these engineered nanozymes, including antimicrobial treatments, cancer therapy, and biosensing are also introduced. Ultimately, this review aims to offer invaluable insights for the design and synthesis of nanozymes with enhanced performance, thereby advancing the field of nanozyme research.

Sitting Time and Its Interaction With Physical Activity in Relation to All-Cause and Heart Disease Mortality in U.S. Adults With Diabetes.

OBJECTIVE: To evaluate whether associations between sitting time and all-cause and heart disease mortality are modified by physical activity in adults with diabetes. RESEARCH DESIGN AND METHODS: Data came from 6,335 U.S. adults with diabetes from National Health and Nutrition Examination Survey 2007-2018 (baseline), with mortality follow-up through 2019. Sitting time and moderate to vigorous physical activity (MVPA) were self-reported. Cox models were adjusted for sociodemographics, lifestyle factors, and medical conditions. RESULTS: Over a median follow-up of 5.9 years, 1,278 all-cause and 354 heart disease deaths were documented (mean age, 59.6 years; 48.3% female). Longer sitting time was associated with greater all-cause and heart disease mortality risk in inactive (MVPA <10 min/week) or insufficiently active (MVPA 10 to <150 min/week) adults with diabetes, but not in active adults (MVPA ≥150 min/week) (all-cause mortality: P = 0.003 for interaction; heart disease mortality: P = 0.008 for interaction). CONCLUSIONS: In adults with diabetes, meeting guideline-recommended physical activity may offset the elevated all-cause and heart disease mortality risk associated with excessive sitting time.

Inhalable Polymeric Microparticles for Phage and Photothermal Synergistic Therapy of Methicillin-Resistant Staphylococcus aureus Pneumonia.

Acute methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is a common and serious lung infection with high morbidity and mortality rates. Due to the increasing antibiotic resistance, toxicity, and pathogenicity of MRSA, there is an urgent need to explore effective antibacterial strategies. In this study, we developed a dry powder inhalable formulation which is composed of porous microspheres prepared from poly(lactic-co-glycolic acid) (PLGA), internally loaded with indocyanine green (ICG)-modified, heat-resistant phages that we screened for their high efficacy against MRSA. This formulation can deliver therapeutic doses of ICG-modified active phages to the deep lung tissue infection sites, avoiding rapid clearance by alveolar macrophages. Combined with the synergistic treatment of phage therapy and photothermal therapy, the formulation demonstrates potent bactericidal effects in acute MRSA pneumonia. With its long-term stability at room temperature and inhalable characteristics, this formulation has the potential to be a promising drug for the clinical treatment of MRSA pneumonia.

Dispel some mist on circulating biopterins: measurement, physiological interval and pathophysiological implication.

BACKGROUND AND AIMS: Biopterins, including tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), and biopterin (B), were crucial enzyme cofactors in vivo. Despite their recognized clinical significance, there remain notable research gaps and controversies surrounding experimental outcomes. This study aims to clarify the biopterins-related issues, including analytical art, physiological intervals, and pathophysiological implications. MATERIALS AND METHODS: A novel LC-MS/MS method was developed to comprehensively profile biopterins in plasma, utilizing chemical derivatization and cold-induced phase separation. Subsequently, apparently healthy individuals were enrolled to investigate the physiological ranges. And the relationships between biopterins and biochemical indicators were analyzed to explore the pathophysiological implications. RESULTS: The developed method was validated as reliable for detecting biopterins across the entire physiological range. Timely anti-oxidation was found to be essential for accurate assessment of biopterins. The observed overall mean ± SDs levels were 3.51 ± 0.94, 1.54 ± 0.48, 2.45 ± 0.84 and 5.05 ± 1.14 ng/mL for BH4, BH2, BH4/BH2 and total biopterins. The status of biopterins showed interesting correlations with age, gender, hyperuricemia and overweight. CONCLUSION: In conjunction with proper anti-oxidation, the newly developed method enables accurate determination of biopterins status in plasma. The observed physiological intervals and pathophysiological implications provide fundamental yet inspiring support for further clinical researches.

Natural Protein Photon Upconversion Supramolecular Assemblies for Background-Free Biosensing.

The diagnosis of disease biomarkers is crucial for the identification, monitoring, and prognostic assessment of malignant disease. However, biological samples with autofluorescence, complex components, and heterogeneity pose major challenges to reliable biosensing. Here, we report the self-assembly of natural proteins and the triplet-triplet annihilation upconversion (TTA-UC) pair to form upconverted protein clusters (∼8.2 ± 1.1 nm), which were further assembled into photon upconversion supramolecular assemblies (PUSA). This PUSA exhibited unique features, including a small size (∼44.1 ± 4.1 nm), oxygen tolerance, superior biocompatibility, and easy storage via lyophilization, all of which are long sought after for photon upconversion materials. Further, we have revealed that the steric hindrance of the annihilator suppresses the stacking of the annihilator in PUSA, which is vital for maintaining the water dispersibility and enhancing the upconversion performance of PUSA. In conjunction with sarcosine oxidase, this near infrared (NIR)-excitable PUSA nanoprobe could perform background-free biosensing of urinary sarcosine, which is a common biomarker for prostatic carcinoma (PCa). More importantly, this nanoprobe not only allows for qualitative identification of urinary samples from PCa patients by the unaided eye under NIR-light-emitting diode (LED) illumination but also quantifies the concentration of urinary sarcosine. These remarkable findings have propelled photon upconversion materials to a new evolutionary stage and expedited the progress of upconversion biosensing in clinical diagnostics.

[Effects of Four Amendments on Cadmium Bioavailability and Enzyme Activity in Purple Soil].

In this study, the effects of four types of amendments on effective Cd and Cd content in different parts of prickly ash soil and soil enzyme activity were studied, which provided scientific basis for acidification improvement of purple soil and heavy metal pollution control. A field experiment was conducted. Six treatments were set up:no fertilizer (CK), only chemical fertilizer (F), lime + chemical fertilizer (SF), organic fertilizer + chemical fertilizer (OM), biochar + chemical fertilizer (BF), and vinasse biomass ash + chemical fertilizer (JZ). Soil pH; available Cd (DTPA-Cd); Cd content in branches, leaves, shells, and seeds of Zanthoxylum; as well as the activities of catalase (S-CAT), acid phosphatase (S-ACP), and urease (S-UE) in different treatments were studied, and their relationships were clarified. The results showed following:① The two treatments of vinasse biomass ash + chemical fertilizer and lime + chemical fertilizer significantly increased soil pH (P < 0.05) to 3.39 and 2.25 units higher than that in the control, respectively. Compared with that in the control treatment, the content of available Cd in soil under vinasse biomass ash + chemical fertilizer and lime + chemical fertilizer treatment decreased by 28.91 % and 20.90 %, respectively. ② The contents of Cd in leaves, shells, and seeds of Zanthoxylum were decreased by 31.33 %, 30.24 %, and 34.01 %, respectively. The Cd enrichment ability of different parts of Zanthoxylum was different, with the specific performances being leaves > branches > seeds > shells. Compared with that of the control, the enrichment coefficient of each part of Zanthoxylum treated with vinasse biomass ash + chemical fertilizer decreased significantly(P < 0.05)by 27.54 %-40.0 %. ③ The changes in catalase and urease activities in soil treated with amendments were similar. Compared with those in the control group, the above two enzyme activities were significantly increased by 191.26 % and 199.50 %, respectively, whereas the acid phosphatase activities were decreased by 16.45 %. Correlation analysis showed that soil available Cd content was significantly negatively correlated with soil pH value(P < 0.01), S-CAT and S-UE enzyme activities were significantly positively correlated with soil pH(P < 0.01), and the soil available Cd content was significantly negatively correlated (P < 0.01); the S-ACP enzyme showed the complete opposite trends. The application of lime and vinasse biomass ash to acidic purple soil had the most significant effect on neutralizing soil acidity. It was an effective measure to improve acidic purple soil and prevent heavy metal pollution by reducing the effective Cd content in soil and improving the soil environment while inhibiting the absorption and transfer of Cd in various parts of Zanthoxylum.

2D Materials-Based Thermal Interface Materials: Structure, Properties, and Applications.

The challenges associated with heat dissipation in high-power electronic devices used in communication, new energy, and aerospace equipment have spurred an urgent need for high-performance thermal interface materials (TIMs) to establish efficient heat transfer pathways from the heater (chip) to heat sinks. Recently, emerging 2D materials, such as graphene and boron nitride, renowned for their ultrahigh basal-plane thermal conductivity and the capacity to facilitate cross-scale, multi-morphic structural design, have found widespread use as thermal fillers in the production of high-performance TIMs. To deepen the understanding of 2D material-based TIMs, this review focuses primarily on graphene and boron nitride-based TIMs, exploring their structures, properties, and applications. Building on this foundation, the developmental history of these TIMs is emphasized and a detailed analysis of critical challenges and potential solutions is provided. Additionally, the preparation and application of some other novel 2D materials-based TIMs are briefly introduced, aiming to offer constructive guidance for the future development of high-performance TIMs.