RNAi targeting LMAN1-MCFD2 complex promotes anticoagulation in mice.

Combined deficiency of coagulation factor V (FV) and factor VIII (FVIII) is a rare bleeding disease caused by variants in either lectin mannose binding 1 (LMAN1) or multiple coagulation factor deficiency 2 (MCFD2) gene. Reducing the level of FVIII by inhibiting the LMAN1-MCFD2 complex may become a new anticoagulant approach. We aimed to find a new therapeutic option for anticoagulation by RNA interference (RNAi) targeting LMAN1 and MCFD2. siRNA sequences with cross-homology between mice and humans were designed based on LMAN1 or MCFD2 transcripts in NCBI and were screened with the Dual-Luciferase reporter assay. The optimal siRNAs were chemically modified and conjugated with three N-acetylgalactosamine molecules (GalNAc-siRNA), promoting their targeted delivery to the liver. The expression of LMAN1 and MCFD2 in cell lines or mice was examined by RT-qPCR and western blotting. For the mice administered with siRNA, we assessed their coagulation function by measuring APTT and the activity of FVIII factor. After administration, siRNAs GalNAc-LMAN1 and GalNAc-MCFD2 demonstrated effective and persistent LMAN1 and MCFD2 inhibition. 7 days after injection of 3mg/kg GalNAc-LMAN1, the LMAN1 mRNA levels reduced to 19.97% ± 3.78%. MCFD2 mRNA levels reduced to 32.22% ± 13.14% with injection of 3mg/kg GalNAc-MCFD2. After repeated administration, APTT was prolonged and the FVIII activity was remarkably decreased. The tail bleeding test of mice showed that the amount of bleeding in the treated group did not significantly increase compared with the control group. Our study confirms that therapy with RNAi targeting LMAN1-MCFD2 complex is effective and can be considered a viable option for anticoagulation drugs. However, the benefits and potential risk of bleeding in thrombophilic mice model needs to be evaluated.

Chinese Herbal Compound Xiaoliu Pingyi Recipe Inhibits the Growth of Lung Adenocarcinoma by Regulating the Tumor Vascular Microenvironment.

BACKGROUND: The traditional Chinese medicine (TCM) Xiaoliu Pingyi recipe (XLPYR) has been clinically used for several decades, demonstrating favorable therapeutic effects. However, the underlying regulatory mechanisms remain unclear. The aim of this study was to explore the anti-tumor effects of XLPYR and its regulatory role in the vascular microenvironment through in vivo and in vitro experiment. MATERIALS AND METHODS: In the in vivo study, a C57BL/6J mouse model of lung adenocarcinoma (LUAD) allografts was established, and various interventions were administered for 14 days (Model group: administered normal saline via oral gavage; Pemetrexed (PEM) group: intraperitoneally injected with a solution of pemetrexed, once every 3d; XLPYR group: administered XLPYR via oral gavage; Combination (COMBI) group: received XLPYR via oral gavage simultaneously with intraperitoneal injection of pemetrexed solution). Tumor volume and weight were then compared among the groups. The impact of XLPYR on the tumor vascular microenvironment was assessed using immunohistochemistry staining. In the in vitro study, XLPYR-containing serum was prepared by oral administration to SD rats. The CCK-8 assay evaluated the effect of the serum on the proliferation of normal lung epithelial BEAS-2B cells and LUAD A549 cells, determining the optimal intervention concentrations. The cell migration and invasion abilities were evaluated using the wound-healing assay and Transwell assay, respectively. Finally, ELISA assay measured VEGF secretion levels in the LUAD cell supernatant, and RT-qPCR and Western Blot were employed to detect differences in HIF-1α, VEGFA, Ang-2, and PI3K/Akt mRNA and protein expression levels in both in vivo and in vitro experiments. RESULTS: In the in vivo study, XLPYR significantly inhibited the growth of mice LUAD allografts, with enhanced anti-tumor effects observed with prolonged drug intervention. Immunohistochemistry staining revealed reduced MVD and increased pericyte coverage in all intervention groups. Regarding vascular function, FITC-Dextran extravasation in the tumor tissues of the Model group was significantly higher than in the intervention groups, particularly with lower extravasation in the COMBI group compared to the PEM group. In the in vitro study, XLPYR demonstrated a time- and concentration-dependent inhibitory effect on LUAD cells, and with greater sensitivity in inhibiting LUAD cells compared to BEAS-2B cells. The wound-healing assay and Transwell assay confirmed that XLPYR significantly suppressed the migration and invasion abilities of LUAD cells. ELISA experiments further revealed a significant decrease in VEGF expression in the supernatant of each intervention group. RT-qPCR and Western Blot results showed consistent findings between the in vivo and in vitro experiments. HIF-1α, VEGFA, and Ang-2 mRNA and protein expression levels were significantly downregulated in the PEM group, XLPYR group, and COMBI group. There were no significant differences in the expression of PI3K and Akt mRNA and total protein, but the expression levels of phosphorylated p-PI3K and p-Akt were notably downregulated. CONCLUSION: XLPYR significantly inhibited C57BL/6J mouse LUAD allograft growth and improved the vascular microenvironment, thereby intervening in tumor angiogenesis and inducing vascular normalization. It suppressed LUAD cell proliferation, migration, and invasion, while reducing VEGF concentration in the cell supernatant. The regulatory mechanism may involve inhibiting PI3K/Akt protein phosphorylation and downregulating angiogenesis-related factors, such as HIF-1α, VEGF, and Ang-2.

IL-16 Mediates the Effect of Circulating Metabolites on Postmenopausal Osteoporosis: A Two-Step, Multivariable Mendelian Randomization Study.

Objectives: This study aimed to explore the relationship between circulating metabolites and postmenopausal osteoporosis (PMOP) and to assess the mediating role of inflammatory factors. Methods: Utilizing summary-level data from genome-wide association studies (GWAS) and employing a Mendelian Randomization approach, a two-sample MR analysis was conducted to assess the relationship between circulating metabolites and PMOP. Additionally, a two-step MR was used to quantify the mediating impact of inflammatory factors on the effect of circulating metabolites on PMOP. Results: The results revealed a significant association between certain metabolites and the risk of PMOP, notably the ratio of free cholesterol to total lipids in very large VLDL particles (OR: 1.399, 95% CI: 1.002-1.954, p = 0.048) and IL-16 (OR: 0.773, 95% CI: 0.608-0.983, p = 0.036). IL-16 was found to partially mediate the impact of circulating metabolites on PMOP, with a mediation effect of 10.4%. Conclusion: This study underscores the crucial role of circulating metabolites and inflammatory factors in PMOP pathogenesis. A causal relationship between circulating metabolites and PMOP was established, with IL-16 mediating some effects. These findings hold promise for clinical applications in early detection, personalized medicine, and the identification of therapeutic targets for PMOP.

The Role of MiR-375 in Migration and Invasion of H.pylori-induced Gastric Cancer Cell Model.

This article aimed to investigate the mechanism of miR-375 in Hp-induced gastric cancer cells (GCCs) model. Human normal gastric mucosal epithelial cell (GMEC) line GES-1 and human GCCs strain MKN45 were used as research objects. The expression of miR-375 was detected after H.pylori (Hp) infection of GCCs. The cell activity was detected by, 53-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, and the cell multiplication was determined by cell counting kit-8 (CCK-8) method. Transwell assay was used to detect the effect of cell invasion and migration ability. The expression levels of JAK1 and STAT3 proteins were determined by Western blot (WB). MiR-375 was increased in GCCs after Hp infection, and JAK1, STAT3, p-JAK1, and p-STAT3 in GCCs after Hp infection were visibly increased. In addition, the overexpressed miR-375 promoted the multiplication activity, migration, and invasion ability of GCCs. MiR-375 promotes Hp-induced migration and invasion of GCCs by targeting JAK1/STAT3. This article reveals the important role of miR-375 in Hp-induced GC, which provides new clues for further study of its mechanism and therapeutic targets.

Insights into the interaction mechanisms between Microcystin-degrading bacteria and Microcystis aeruginosa.

Interactions between bacteria and cyanobacteria influence the occurrence and development of harmful cyanobacterial blooms (HCBs). Bloom-forming cyanobacteria and cyanotoxin-degrading bacteria are essential in HCBs, nonetheless, their interactions and the underlying mechanisms remain unclear. To address this gap, a typical microcystin-LR (MC-LR)-degrading bacterium and a toxic Microcystis aeruginosa strain were co-cultivated to investigate their interactions. The cyanobacterial growth was enhanced by 24.8 %-44.3 % in the presence of the bacterium in the first 7 days, and the cyanobacterium enhanced the bacterial growth by 59.2 %-117.5 % throughout the growth phases, suggesting a mutualistic relationship between them. The presence of the bacterium increased cyanobacterial intracellular MC-LR content on days 4, 8, and 10 while reducing the extracellular MC-LR concentration, revealing the dual roles of the bacterium in enhancing cyanotoxin production and degrading cyanotoxins. The bacterium alleviated the oxidative stress, which may be crucial in promoting cyanobacterial growth. Critical functional genes related to cyanobacterial photosynthesis and MC-LR synthesis, and bacterial MC-LR degradation were up-regulated in the presence of the bacterium and cyanobacterium, respectively. Moreover, extracellular polymeric substances (EPS) were produced at the cell interface, implying EPS play a role in cyanobacterial-bacterial interactions. This study is the first to unveil the interaction mechanisms between cyanotoxin-degrading bacteria and bloom-forming cyanobacteria, shedding light on the dynamics of HCBs.

Hydrogen-bond organic-framework-based electrochemical sensor for highly sensitive determination of trace cadmium ions in environmental and e-cigarette samples.

BACKGROUND: The heavy metal ion Cd2+ is acutely toxic, and excessive concentrations can have adverse effects on human production and life, and even lead to significant public health risks and environmental impacts. There are several mature non-electrochemical methods for heavy metal detection, but these methods are characterized by high cost, which makes it difficult to be applied to the field for timely detection. Therefore, it is necessary to prepare a new electrochemical sensor that is environmentally friendly and capable of detecting Cd2+ in the environment quickly, easily and sensitively. RESULTS: In this study, hydrogen-bonded organic frameworks (HOFs) were synthesized by a simple hydrothermal reaction. The prepared materials consisted of only C, N and O and had a thin lamellar structure. The HOFs were integrated into a novel electrochemical sensor to achieve accurate detection of Cd2+ ions in real aqueous environments by square wave anodic dissolution voltammetry. The sensor has a wide linear range and a detection limit as low as 0.13 µg/L. Several real water samples, such as tap water, lake water, and e-cigarette digest, were analyzed to simulate the working environment of the sensor, and the results showed that the recoveries of Cd2+ ranged from 95.75 % to 101.2 %. SIGNIFICANCE: We pioneered the detection of heavy metal ions Cd2+ in e-cigarette digestate samples with the innovative use of HOFs as the sensor material, which demonstrated the potential application in electrochemical sensing with extremely low background current value and high sensitivity, providing new ideas for environmental monitoring and public health control.

Dynamic changes in and correlations between microbial communities and physicochemical properties during the composting of cattle manure with Penicillium oxalicum.

BACKGROUND: Penicillium oxalicum is an important fungal agent in the composting of cattle manure, but the changes that occur in the microbial community, physicochemical factors, and potential functions of microorganisms at different time points are still unclear. To this end, the dynamic changes occurring in the microbial community and physicochemical factors and their correlations during the composting of cattle manure with Penicillium oxalicum were analysed. RESULTS: The results showed that the main phyla observed throughout the study period were Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, Halanaerobiaeota, Apicomplexa and Ascomycota. Linear discriminant analysis effect size (LEfSe) illustrated that Chitinophagales and Eurotiomycetes were biomarker species of bacteria and eukaryote in samples from Days 40 and 35, respectively. Bacterial community composition was significantly correlated with temperature and pH, and eukaryotic microorganism community composition was significantly correlated with moisture content and NH4+-N according to redundancy analysis (RDA). The diversity of the microbial communities changed significantly, especially that of the main pathogenic microorganisms, which showed a decreasing trend or even disappeared after composting. CONCLUSIONS: In conclusion, a combination of high-throughput sequencing and physicochemical analysis was used to identify the drivers of microbial community succession and the composition of functional microbiota during cattle manure composting with Penicillium oxalicum. The results offer a theoretical framework for explaining microecological assembly during cattle manure composting with Penicillium oxalicum.

Five-Year Outcomes of Bioresorbable Stent Therapy for Coronary Heart Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The efficacy of bioresorbable vascular scaffolds (BVS) compared to metallic stents for the treatment of coronary heart disease remains controversial. The analysis of clinical outcomes at five years following the initial treatment has yet to be reviewed. This study sought to assess the five-year outcomes in randomized controlled trials of BVS in the treatment of coronary heart disease using a systematic review and meta-analysis. Methods: A systematic database search was conducted from their inception to June 30th, 2023 using various Medical Subject Headings (MeSH) terms including: "Coronary Disease", "Bioresorbable stent", "Randomized controlled trials". Results: After a rigorous selection process, a total of five high-quality articles were finally included in this study. Each trial demonstrated a low risk of bias. After 5 years, bioresorbable stents showed outcomes similar to conventional metal stents in terms of cardiac mortality. However, they were inferior in terms of lesion revascularization rates, in-stent thrombosis rates, target lesion failure, target vessel failure, and myocardial infarction. Conclusions: While bioresorbable stents are comparable to metallic stents in terms of cardiac mortality rates, they exhibit significant drawbacks that warrant clinical consideration.

PRECISE: Preoperative Radiotherapy to Elicit Critical Immune Stimulating Effects - A Phase II Clinical Trial.

PURPOSE: Radiotherapy is an under-investigated tool for priming the immune system in intact human breast cancers. We sought here to investigate if a preoperative radiotherapy boost delivered was associated with a significant change in tumor infiltrating lymphocytes in the tumor in estrogen receptor positive, HER2Neu non-amplified breast cancers. METHODS AND MATERIALS: 20 patients were enrolled in a phase II clinical trial and received either 7.5Gy x 1 fraction or 2Gy x 5 fractions, completed 6-8 days prior to surgery. Percent stromal tumor infiltrating lymphocytes (TIL) were evaluated on hematoxylin and eosin-stained samples. Short-term safety was assessed based on time to surgery, toxicities, and cosmesis up to 6 months following boost. RESULTS: Stromal TIL increased 6-8 days following completion of boost radiotherapy (median 3.0 (IQR 1.0-6.5) prior to radiotherapy vs. median 5.0 (IQR 1.5-8.0) post radiotherapy, p=0.0037. Zero grade ≥ 3 toxicities up to 6 months following boost were experienced. 94% (16/17) patients with 6 month follow-up cosmetic assessment following breast conservation had good-excellent cosmesis by physician assessment. CONCLUSION: In this phase II trial, preoperative radiotherapy boost resulted in a short-term increase in stromal TIL with minimal toxicities. Preoperative breast radiotherapy appears to be safe and may be a feasible means for priming the tumor microenvironment.

Home-based advanced care is a solution to quality health care in rural Taiwan: Lessons learned during the COVID-19 pandemic.

BACKGROUND/PURPOSE: The integrated home-based medical care (iHBMC) program has been implemented by the Taiwanese government since 2016. The pandemic of coronavirus disease 2019 (COVID-19) accelerated the shift from hospital-based to community-based healthcare, with a special focus on advanced home care for frail older adults. This study focuses on home-based advanced care, such as hospital at home (HaH), aiming to explore the feasibility and resilience of HaH within a home-based medical care model in a rural community in Taiwan. METHODS: We conducted a retrospective review of medical records from February 2020 to August 2022. Two clinical professionals reviewed and abstracted data from the electronic medical records of 189 patients receiving home healthcare during the COVID-19 pandemic. The HaH event was calculated if patients had any acute infection and received treatment at home. RESULTS: A total of 62 HaH events occurred during 2020-2022 and the average HaH events per person was 1.4. In these events, the top reason for patients receiving HaH was pneumonia, followed by urinary tract infection, soft tissue infection, and sepsis. 77.4% of patients completed the HaH treatment and did not experience any recurrent acute infections in the 30-day follow-up. CONCLUSION: Different forms of home healthcare enhance the resilience of medical care provision in rural areas. As Taiwan approaches a hyper-aged society by 2025, it is crucial that National Health Insurance policies support various home-based care models that address transportation issues and maintain high care standards in underserved rural areas.

Associations of Perchlorate, Nitrate, and Thiocyanate with Bone Mineral Density in the US General Population: A Multi-Cycle Study of NHANES 2011-2018.

BACKGROUND: Perchlorate, nitrate, and thiocyanate are widely recognized as endocrine disrupting chemicals, which are closely related to thyroid function. Animal and human studies show a correlation between thyroid hormone and bone mineral density (BMD). However, it remains unknown whether perchlorate, nitrate, and thiocyanate were associated with BMD. This study aimed to explore the association between perchlorate, nitrate, and thiocyanate exposure with BMD. METHOD: A cross-sectional analysis among 5607 participants from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) was conducted in the present study. Perchlorate, nitrate, and thiocyanate were detected in urine by ion chromatography. Survey-weighted generalized linear regression, restricted cubic splines, and qgcomp models were used to assess the association of BMDs with single and mixed perchlorate, nitrate, and thiocyanate exposures. In addition, age, gender, and BMI stratified these associations. RESULTS: Negative associations were found between perchlorate and nitrate with BMDs. Furthermore, based on the qgcomp model results, the combined association of perchlorate, nitrate, and thiocyanate exposure was negatively associated with BMDs (ß = -0.017, 95% CI: -0.041, -0.024 for total BMD; ß = -0.017, 95% CI: -0.029, -0.005 for lumbar BMD). Additionally, there was a significant effect after gender, age, and BMI stratification between perchlorate, nitrate, and thiocyanate with BMDs in the normal weight group (ß = -0.015, 95% CI: -0.020, -0.011 for total BMD; ß = -0.022, 95% CI: -0.028, -0.016 for lumbar BMD) and children and adolescents group (ß = -0.025, 95% CI: -0.031, -0.019 for total BMD; ß -0.017, 95% CI: -0.029, -0.005 for lumbar BMD). CONCLUSIONS: The present study indicated a negative correlation between BMDs and urinary perchlorate, nitrate, and thiocyanate levels, with nitrate being the main contributor to the mixture effect. People with normal weight and children and adolescents were more likely to be affected.

Discovery of Novel Imidazo[1,2-a]pyridine-Based HDAC6 Inhibitors as an Anticarcinogen with a Cardioprotective Effect.

Cardiotoxicity associated with chemotherapy has gradually become the major cause of death in cancer patients. The development of bifunctional drugs with both cardioprotective and antitumor effects has become the future direction. HDAC6 plays important roles in the progression, treatment, and prognosis of cancer and cardiovascular diseases, but bifunctional inhibitors have not been reported. Herein, structure-activity relationship studies driven by pharmacophore-based remodification and fragment-based design were performed to yield highly potent HDAC6 inhibitor I-c4 containing imidazo[1,2-a]pyridine. Importantly, I-c4 effectively suppressed the growth of MGC-803 xenografts in vitro and in vivo by inhibiting the deacetylation pathway without causing myocardial damage after long-term administration. Meanwhile, I-c4 could mitigate severe myocardial damage against H2O2 or myocardial ischemia/reperfusion in vitro and in vivo. Further studies revealed that the cardioprotective effect of I-c4 was associated with reduction of inflammatory cytokines. Taken together, I-c4 may represent a novel lead compound for further development of an anticarcinogen with a cardioprotective effect.

Targeted discovery of clerodane diterpenoids from Tinospora sinensis as immunomodulatory agents.

Under the guidance of MS/MS-based molecular networking, five new clerodane diterpenoid glucosides, tinosinesides R-V (1-5), along with 15 known diterpenoids (6-20), were isolated from the stems of Tinospora sinensis. Compound 1 represents the first example of diterpenoid bearing a thio sugar and compound 5 is the first 18,19-dinor-clerodane with cis-fused A/B ring. The structures of the new compounds were elucidated by spectroscopic means, and their absolute configurations were established on the basis of time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculation and chemical methods. Selected compounds were evaluated for their immunomodulatory effect and several compounds could enhance the proliferation of B lymphocytes. Preliminary mechanistic studies disclosed that 3 could promote B cell generation and inhibit B cell differentiation.

Evaluating the efficiency of online course resource allocation in universities of China.

Curriculum is the core element of talent cultivation in universities, and its quality directly determines that of the talent cultivation. However, the efficiency of online course resource allocation in universities of China is unacceptable, and the corresponding driving mechanisms are unclear. Based on the data of iCourses platform for a top university (H University) of China, this paper develops the DEA-Malmquist index and Tobit regression model to evaluate the efficiency of university online course resource allocation and explore its main influencing factors. The empirical results indicate that, first of all, humanities and social sciences outperform natural sciences in the resource allocation efficiency of online courses. Compared with non-national premium online courses, the resource investment redundancy of national premium online courses appears relatively lower. Secondly, from the perspective of temporal changes, the total factor productivity of online course resource allocation generally has a downward trend. The innovation effect of technological progress is more significant, while the catch-up effect of technical efficiency is clearly insufficient. Scale efficiency is the main factor hindering its improvement. Finally, in terms of the factors affecting the efficiency of online course resource allocation, teachers' research guidance capability, teaching research skills, and the number of courses offered have significantly positive impact.

Diterpenoid DGT alleviates atopic dermatitis-like responses in vitro and in vivo via targeting IL-4Rα.

BACKGROUND: Atopic dermatitis is a common chronic inflammatory skin disease characterized by relapsing eczema and intense itch. DGT is a novel synthetic heterocyclic diterpenoid derived from plants. Its therapeutic potential and mechanism(s) of action are poorly understood. OBJECTIVES: We investigated the potent therapeutic effect of DGT on atopic dermatitis, exploring the underlying mechanisms and determining whether DGT is a safe and well-tolerated topical treatment. METHODS: We observed anti-inflammatory effects of DGT on tumor necrosis factor-α/interferon-γ-treated human keratinocytes, and anti-allergic effects on immunoglobulin E-sensitized bone marrow-derived mast cells. In vivo, DGT was topically applied to two experimental mouse models of atopic dermatitis: oxazolone-induced sensitization and topically applied calcipotriol. Then the therapeutic effects of DGT were evaluated physiologically and morphologically. Moreover, we performed nonclinical toxicology and safety pharmacology research, including general toxicity, pharmacokinetics, and safety pharmacology on the cardiovascular, respiratory, and central nervous systems. RESULTS: In keratinocytes, DGT reduced the expression of inflammatory factors, promoting the expression of barrier functional proteins and tight junctions and maintaining the steady state of barrier function. DGT also inhibited the activation and degranulation of mast cells induced by immunoglobulin E. Moreover, we found that interleukin-4 receptor-α was the possible target of DGT. Meanwhile, DGT had therapeutic effects on oxazolone/calcipotriol-treated mice. Notably, our pharmacology results demonstrated that DGT was safe and nontoxic in our studies. CONCLUSION: DGT's potent anti-inflammatory effects and good safety profile suggest that it is a potential candidate for the treatment of atopic dermatitis.

Detecting Pb2+ in aqueous environment and live cells by amphiphilic pillar[5]arene-assembled supramolecular sensor based on host-guest charge transfer mechanism.

Water-soluble fluorescent chemosensors for lead ion are highly desirable in environmental detection and bioimagery. Based on a water-soluble pillar[5]arene WP5 and imidazolium terminal functionalized 2,2'-bibenzimidazole derivative BIHB, we report a host-guest charge transfer assembly BIHB-2WP5 for sensitive and selective detection of Pb2+ in pure aqueous media. As a result of its high electron-rich cavity, WP5 can bind electron-deficiency guest BIHB with various host/guest stoichiometry to easily tune the microtopography of assembly from nanoparticle to nanocube. In view of the good biocompatibility and sensitivity, the supramolecular assembly BIHB-2WP5 was used as a fluorescent probe for the detection of Pb2+ in living cells and a smartphone Pb2+ detection device was constructed for the in situ test.

NH2-MIL-88B@TP-TA@CuS for photothermal catalytic synergistic antibacterial activity.

Reactive oxygen species (ROS) provide a promising way to fight bacterial infection and meet the persistent challenge of antibiotic resistance. Nanoenzyme mimics natural enzyme and becomes an effective regulator of ROS level. In this study, NH2-MIL-88B with high specific surface area was selected as the core, and the covalent organic skeleton material TP-TA COF was wrapped by "sequential growth" technology. Subsequently, through the second hydrothermal treatment, the inorganic material CuS with excellent photothermal performance was integrated into the outer layer, and the NH2-MIL-88B@TP-TA@CuSX composite nanoenzyme was synthesized. Different from the traditional nano-enzyme, NH2-MIL-88B@TP-TA@CuSX nano-enzyme still has good catalytic effect under neutral conditions (pH=7). In addition, NH2-MIL-88B@TP-TA@CuSX has good near infrared (NIR) absorption rate and high photothermal conversion efficiency (PTCE is 48.7 %), which can be used for photothermal treatment (PTT) of bacteria. Mild photothermal effect can further enhance the enzyme-like catalytic activity of NH2-MIL-88B@TP-TA@CuSX, so that H2O2 can be more efficiently catalyzed to produce a large number of ROS. The experimental results in vitro show that NH2-MIL-88B@TP-TA@CuSX can effectively kill Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in the presence of laser irradiation and H2O2.

Nut consumption, gut microbiota, and body fat distribution: results of a large, community-based population study.

OBJECTIVE: We aimed to investigate the relationships among nut consumption, gut microbiota, and body fat distribution. METHODS: We studied 2255 Chinese adults in the Lanxi Cohort living in urban areas in Lanxi City, China. Fat distribution was assessed by dual-energy x-ray absorptiometry, and nut consumption was assessed using food frequency questionnaires. 16S ribosomal RNA (rRNA) sequencing was performed on stool samples from 1724 participants. Linear regression and Spearman correlation were used in all analyses. A validation study was performed using 1274 participants in the Lanxi Cohort living in rural areas. RESULTS: Nut consumption was beneficially associated with regional fat accumulation. Gut microbial analysis suggested that a high intake of nuts was associated with greater microbial α diversity. Six genera were found to be associated with nut consumption, and the abundance of genera Anaerobutyricum, Anaerotaenia, and Fusobacterium was significantly associated with fat distribution. Favorable relationships between α diversity and fat distribution were also observed. Similar relationships between gut microbiota and fat distribution were obtained in the validation analysis. CONCLUSIONS: We have shown that nut consumption is beneficially associated with body fat distribution and gut microbiota diversity and taxonomy. Furthermore, the microbial features related to high nut intake are associated with a favorable pattern of fat distribution.

Disorganisation of basement membrane zone architecture impairs melanocyte residence in vitiligo.

The basement membrane zone is the interface between the epidermis and dermis, and it is disrupted in several skin conditions. Here, we report the results of a comprehensive investigation into the structural and molecular factors of the basement membrane zone in vitiligo, a dermatological disorder characterised by depigmented patches on the skin. Using electron microscopy and immunofluorescence staining, we confirmed abnormal basement membrane zone morphology and disrupted basement membrane zone architecture in human vitiliginous skin. Furthermore, we identified elevated expression of matrix metalloproteinase 2 (MMP2) in human dermal fibroblasts as a key factor responsible for basement membrane zone matrix degradation. In our in vitro and ex vivo models, overexpression of MMP2 in fibroblasts led to basement membrane zone disruption and melanocyte disappearance. Importantly, we reveal that the loss of melanocytes in vitiligo is primarily linked to their weakened adhesion to the basement membrane, mediated by binding between integrin ß1 and laminin and discoidin domain receptor 1 and collagen IV. Finally, inhibition of matrix metalloproteinase 2 expression reversed depigmentation in a mouse model of vitiligo. In conclusion, our research shows the importance of basement membrane zone integrity in melanocyte residence and offers new avenues for therapeutic interventions to address this challenging skin condition. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

EQ-5D-5L Population Scores in Mainland China: Results From a Nationally Representative Survey 2021.

OBJECTIVES: There is a lack of monitoring changes in the population scores of the most recent version, EQ-5D-5L, in mainland China. This study aimed to address this knowledge gap by assessing the EQ-5D-5L scores in mainland China using a nationally representative sample. METHODS: Data were extracted from the 2021 Survey of Health Index of Chinese Families, which covered 31 provinces/autonomous regions/municipalities in mainland China. The survey used a multistage quota sampling strategy encompassing 120 prefecture-level cities. Quotas were allocated to each prefecture-level city in accordance with the 2020 China Population Census. This approach resulted in a final sample of 11 030 eligible questionnaires. The utility index (UI) and EuroQol Visual Analog Scale (EQ VAS) scores were reported for the entire sample (age-gender-urban/rural weighted) and by the characteristics of the study participants. RESULTS: The study participants had a weighted mean UI of 0.939 (SD 0.135) and EQ VAS score of 80.19 (SD 18.39). The most commonly reported problem was anxiety/depression (26.37%), whereas self-care was the least reported problem (6.18%). Those who were male, were younger, lived without chronic conditions and disabilities, had higher levels of education, earned higher monthly household income, and were covered by basic medical insurance for urban employees had higher scores in both the UI and EQ VAS. CONCLUSION: This study revealed slightly lower UI scores despite a much higher drop in EQ VAS scores whereas China maintained minimum cases of COVID-19 in 2021 compared with the population norms recorded in 2019. Further studies are warranted to unveil the full impacts of COVID-19 outbreaks.