The function role of HIGD1A in nonalcoholic steatohepatitis from chronic hepatitis B.

BACKGROUND: Accompanied by the growing prevalence of nonalcoholic fatty liver disease (NAFLD), the coexistence of chronic hepatitis B (CHB) and NAFLD has increased. In the context of CHB, there is limited understanding of the factors that influence the development of NASH. METHODS: We enrolled CHB combined NAFLD patients who had liver biopsy and divided them to NASH vs. non-NASH groups. A whole transcriptome chip was used to examine the expression profiles of long noncoding RNAs (lncRNAs) and mRNA in biopsied liver tissues. The function analysis of HIGD1A were performed. We knocked down or overexpressed HIGD1A in HepG2.2.15 cells by transient transfection of siRNA-HIGD1A or pcDNA-HIGD1A. In vivo investigations were conducted using hepatitis B virus (HBV) transgenic mice. RESULTS: In 65 patients with CHB and NAFLD, 28 were patients with NASH, and 37 were those without NASH. After screening 582 differentially expressed mRNAs, GO analysis revealed differentially expressed mRNAs acting on nicotinamide adenine dinucleotide phosphate (NADPH), which influenced redox enzyme activity. KEGG analysis also shown that they were involved in the NAFLD signaling pathway. The function analysis revealed that HIGD1A was associated with the mitochondrion. Then, both in vivo and in vitro CHB model, HIGD1A was significantly higher in the NASH group than in the non-NASH group. HIGD1A knockdown impaired mitochondrial transmembrane potential and induced cell apoptosis in HepG2.2.15 cells added oleic acid and palmitate. On the contrary, hepatic HIGD1A overexpression ameliorated free fatty acids-induced apoptosis and oxidative stress. Furthermore, HIGD1A reduced reactive oxygen species (ROS) level by increasing glutathione (GSH) expression, but Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/Acetyl-CoA carboxylase (ACC) pathway was not involved. CONCLUSION: Both in vivo and in vitro CHB model, an upward trend of HIGD1A was observed in the NASH-related inflammatory response. HIGDIA played a protective role in cells against oxidative stress. Our data suggested that HIGD1A may be a positive regulator of NASH within the CHB context.

Effectiveness and safety of augmentative plating technique in managing nonunion following intramedullary nailing of long bones in the lower extremity: A systematic review and meta-analysis.

PURPOSE: To methodically assess the effectiveness of augmentative plating (AP) and exchange nailing (EN) in managing nonunion following intramedullary nailing for long bone fractures of the lower extremity. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to gather clinical studies regarding the use of AP and EN techniques in the treatment of nonunion following intramedullary nailing of lower extremity long bones. The search was conducted up until May 2023. The original studies underwent an independent assessment of their quality, a process conducted utilizing the Newcastle-Ottawa scale. Data were retrieved from these studies, and meta-analysis was executed utilizing Review Manager 5.3. RESULTS: This meta-analysis included 8 studies involving 661 participants, with 305 in the AP group and 356 in the EN group. The results of the meta-analysis demonstrated that the AP group exhibited a higher rate of union (odds ratio: 8.61, 95% confidence intervals (CI): 4.12 - 17.99, p < 0.001), shorter union time (standardized mean difference (SMD): -1.08, 95 % CI: -1.79 - -0.37, p = 0.003), reduced duration of the surgical procedure (SMD: -0.56, 95 % CI: -0.93 - -0.19, p = 0.003), less bleeding (SMD: -1.5, 95 % CI: -2.81 - -0.18), p = 0.03), and a lower incidence of complications (relative risk: -0.17, 95 % CI: -0.27 - -0.06, p = 0.001). In the subgroup analysis, the time for union in the AP group in nonisthmal and isthmal nonunion of lower extremity long bones was shorter compared to the EN group (nonisthmal SMD: -1.94, 95 % CI: -3.28 - -0.61, p < 0.001; isthmal SMD: -1.08, 95 % CI: -1.64 - -0.52, p = 0.002). CONCLUSION: In the treatment of nonunion in diaphyseal fractures of the long bones in the lower extremity, the AP approach is superior to EN, both intraoperatively (with reduced duration of the surgical procedure and diminished blood loss) and postoperatively (with an elevated union rate, shorter union time, and lower incidence of complications). Specifically, in the management of nonunion of lower extremity long bones with non-isthmal and isthmal intramedullary nails, AP demonstrated shorter union time in comparison to EN.

Tandem mass tag (TMT) quantitative protein analysis-based proteomics and parallel reaction monitoring (PRM) validation revealed that MST4 accelerates osteosarcoma proliferation by increasing MRC2 activity.

Osteosarcoma is one of the most common orthopedic malignancies and is characterized by rapid disease progression and a poor prognosis. Currently, research on methods to inhibit osteosarcoma proliferation is still limited. In this study, we found that MST4 levels were significantly increased in osteosarcoma cell lines and tumor tissues compared to normal controls and demonstrated that MST4 is an influential factor in promoting osteosarcoma proliferation both in vivo and in vitro. Proteomic analysis was performed on osteosarcoma cells in the MST4 overexpression and vector expression groups, and 545 significantly differentially expressed proteins were identified and quantified. The candidate differentially expressed protein MRC2 was then identified using parallel reaction monitoring validation. Subsequently, MRC2 expression was silenced with small interfering RNA (siRNA), and we were surprised to find that this alteration affected the cell cycle of MST4-overexpressing osteosarcoma cells, promoted apoptosis and impaired the positive regulation of osteosarcoma growth by MST4. In conclusion, this study identified a novel approach for suppressing osteosarcoma proliferation. Reduction of MRC2 activity inhibits osteosarcoma proliferation in patients with high MST4 expression by altering the cell cycle, which may be valuable for treating osteosarcoma and improving patient prognosis.

Efficacy comparison of antibiotic bone cement-coated implants and external fixations for treating infected bone defects.

PURPOSE: This study aimed to investigate the clinical efficacy of antibiotic bone cement-coated implants compared with external fixations for treating infected bone defects. METHODS: We retrospectively enrolled 119 patients with infected bone defects in our hospital from January 2010 to June 2021, of which 56 were treated with antibiotic bone cement-coated implants and 63 were with external fixation. RESULTS: The pre-operative and post-operative haematological indexes were tested to assess the infection control; the post-operative CRP level in the internal fixation group was lower than that in the external fixation group. No statistical significance was found in the rate of infection recurrence, loosening and rupture of the fixation, and amputation between the two groups. Twelve patients in the external fixation group had pin tract infection. In the evaluation of the Paley score scale, bone healing aspect revealed no significant difference between the two groups, while in the limb function aspect, antibiotic cement-coated implant group showed a much better score than the external fixation group (P = 0.002). The anxiety evaluation scale result also showed lower score in the antibiotic cement implant group (P < 0.001). CONCLUSIONS: Compared with external fixation, antibiotic bone cement-coated implant had the same effect on controlling infection and was more effective in recovering limb function and mental health in the first-stage treatment of infected bone defects after debridement.

Genome-Wide Identification of HSF Gene Family in Kiwifruit and the Function of AeHSFA2b in Salt Tolerance.

Heat shock transcription factors (HSFs) play a crucial role in regulating plant growth and response to various abiotic stresses. In this study, we conducted a comprehensive analysis of the AeHSF gene family at genome-wide level in kiwifruit (Actinidia eriantha), focusing on their functions in the response to abiotic stresses. A total of 41 AeHSF genes were identified and categorized into three primary groups, namely, HSFA, HSFB, and HSFC. Further transcriptome analysis revealed that the expression of AeHSFA2b/2c and AeHSFB1c/1d/2c/3b was strongly induced by salt, which was confirmed by qRT-PCR assays. The overexpression of AeHSFA2b in Arabidopsis significantly improved the tolerance to salt stress by increasing AtRS5, AtGolS1 and AtGolS2 expression. Furthermore, yeast one-hybrid, dual-luciferase, and electrophoretic mobility shift assays demonstrated that AeHSFA2b could bind to the AeRFS4 promoter directly. Therefore, we speculated that AeHSFA2b may activate AeRFS4 expression by directly binding its promoter to enhance the kiwifruit's tolerance to salt stress. These results will provide a new insight into the evolutionary and functional mechanisms of AeHSF genes in kiwifruit.

Comparative Transcriptomic Analysis Revealed the Suppression and Alternative Splicing of Kiwifruit (Actinidia latifolia) NAP1 Gene Mediating Trichome Development.

Kiwifruit (Actinidia chinensis) is commonly covered by fruit hairs (trichomes) that affect kiwifruit popularity in the commercial market. However, it remains largely unknown which gene mediates trichome development in kiwifruit. In this study, we analyzed two kiwifruit species, A. eriantha (Ae) with long, straight, and bushy trichomes and A. latifolia (Al) with short, distorted, and spare trichomes, by second- and third-generation RNA sequencing. Transcriptomic analysis indicated that the expression of the NAP1 gene, a positive regulator of trichome development, was suppressed in Al compared with that in Ae. Additionally, the alternative splicing of AlNAP1 produced two short transcripts (AlNAP1-AS1 and AlNAP1-AS2) lacking multiple exons, in addition to a full-length transcript of AlNAP1-FL. The defects of trichome development (short and distorted trichome) in Arabidopsis nap1 mutant were rescued by AlNAP1-FL but not by AlNAP1-AS1. AlNAP1-FL gene does not affect trichome density in nap1 mutant. The qRT-PCR analysis indicated that the alternative splicing further reduces the level of functional transcripts. These results indicated that the short and distorted trichomes in Al might be caused by the suppression and alternative splicing of AlNAP1. Together, we revealed that AlNAP1 mediates trichome development and is a good candidate target for genetic modification of trichome length in kiwifruit.

Application of vancomycin-impregnated calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan injectable hydrogels combined with BMSC sheets for the treatment of infected bone defects in a rabbit model.

BACKGROUND: The choice of bone substitutes for the treatment of infected bone defects (IBDs) has attracted the attention of surgeons for years. However, single-stage bioabsorbable materials that are used as carriers for antibiotic release, as well as scaffolds for BMSC sheets, need further exploration. Our study was designed to investigate the effect of vancomycin-loaded calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan (CSH/n-HA/CMCS) hydrogels combined with BMSC sheets as bone substitutes for the treatment of IBDs. METHODS: BMSCs were harvested and cultured into cell sheets. After the successful establishment of an animal model with chronic osteomyelitis, 48 New Zealand white rabbits were randomly divided into 4 groups. Animals in Group A were treated with thorough debridement as a control. Group B was treated with BMSC sheets. CSH/n-HA/CMCS hydrogels were implanted in the treatment of Group C, and Group D was treated with CSH/n-HA/CMCS+BMSC sheets. Gross observation and micro-CT 3D reconstruction were performed to assess the osteogenic and infection elimination abilities of the treatment materials. Histological staining (haematoxylin and eosin and Van Gieson) was used to observe inflammatory cell infiltration and the formation of collagen fibres at 4, 8, and 12 weeks after implantation. RESULTS: The bone defects of the control group were not repaired at 12 weeks, as chronic osteomyelitis was still observed. HE staining showed a large amount of inflammatory cell infiltration around the tissue, and VG staining showed no new collagen fibres formation. In the BMSC sheet group, although new bone formation was observed by gross observation and micro-CT scanning, infection was not effectively controlled due to unfilled cavities. Some neutrophils and only a small amount of collagen fibres could be observed. Both the hydrogel and hydrogel/BMSCs groups achieved satisfactory repair effects and infection control. Micro-CT 3D reconstruction at 4 weeks showed that the hydrogel/BMSC sheet group had higher reconstruction efficiency and better bone modelling with normal morphology. HE staining showed little aggregation of inflammatory cells, and VG staining showed a large number of new collagen fibres. CONCLUSIONS: Our preliminary results suggested that compared to a single material, the novel antibiotic-impregnated hydrogels acted as superior scaffolds for BMSC sheets and excellent antibiotic vectors against infection, which provided a basis for applying tissue engineering technology to the treatment of chronic osteomyelitis.

Genome-Wide Expression Profiling Analysis of Kiwifruit GolS and RFS Genes and Identification of AcRFS4 Function in Raffinose Accumulation.

The raffinose synthetase (RFS) and galactinol synthase (GolS) are two critical enzymes for raffinose biosynthesis, which play an important role in modulating plant growth and in response to a variety of biotic or abiotic stresses. Here, we comprehensively analyzed the RFS and GolS gene families and their involvement in abiotic and biotic stresses responses at the genome-wide scale in kiwifruit. A total of 22 GolS and 24 RFS genes were identified in Actinidia chinensis and Actinidia eriantha genomes. Phylogenetic analysis showed that the GolS and RFS genes were clustered into four and six groups, respectively. Transcriptomic analysis revealed that abiotic stresses strongly induced some crucial genes members including AcGolS1/2/4/8 and AcRFS2/4/8/11 and their expression levels were further confirmed by qRT-PCR. The GUS staining of AcRFS4Pro::GUS transgenic plants revealed that the transcriptionlevel of AcRFS4 was significantly increased by salt stress. Overexpression of AcRFS4 in Arabidopsis demonstrated that this gene enhanced the raffinose accumulation and the tolerance to salt stress. The co-expression networks analysis of hub transcription factors targeting key AcRFS4 genes indicated that there was a strong correlation between AcNAC30 and AcRFS4 expression under salt stress. Furthermore, the yeast one-hybrid assays showed that AcNAC30 could bind the AcRFS4 promoter directly. These results may provide insights into the evolutionary and functional mechanisms of GolS and RFS genes in kiwifruit.

Clinical features of hepatitis B patients at immune-tolerance phase with basal core promoter and/or precore mutations.

Little data exist on basal core promoter/precore (BCP/PC) mutations in chronic hepatitis B (CHB) patients at the immune-tolerance (IT) phase. We studied consecutive treatment-naïve, CHBe-antigen (HBeAg)-positive patients who had undergone liver biopsy and genotyping. Those in the IT phase or immune-clearance (IC) phase were enrolled for comparison of the frequency of BCP/PC mutations and their clinical presentations. Subgroup analyses for the IT group were also performed between patients with and without mutations, and IC patients between fibrosis stages ≤2 vs fibrosis >2. Among 301 patients enrolled, 88/301 (29.24%) and 213/301 (70.76%) were at the IT and IC phase, respectively. The frequency of BCP/PC mutations in IT phase was significantly lower than those in IC phase (15.91% vs 64.79%, P < .001). The BCP mutation only was significantly more frequent than the PC mutation in both groups and also in all IC subgroups. IT patients with BCP/PC mutations had significantly higher quantitative anti-HBc levels compared with those of patients with wild-type virus (P < .05). They also had significantly lower mean levels of alanine transaminase, aspartate transaminase, total bilirubin and qAnti-HBc compared with those of IC patients (all P < .05). Additionally, they were significantly younger in mean age, had higher platelet count, higher levels of HBV DNA and surface antigen, as well as higher frequency of genotype B than those of IC patients with fibrosis >2 (all P < .05). BCP/PC mutations were found in IT patients with CHB. They had distinct clinical characteristics when compared with patients with wild-type or at IC phase. Further studies are needed to understand their natural history and treatment outcomes.

Quantitative toxicological study of dose-dependent arsenic-induced cells via synchrotron-based STXM and FTIR measurement.

Inorganic arsenic (iAs) is a well-known naturally occurring metalloid with abundant hazards to our environment, especially being a human carcinogen through arsenic-contaminated drinking water. The iAs-related contamination is usually examined by a chemical assay system or fluorescence staining technique to investigate iAs accumulation and its deleterious effects. In this work, we present a dual-modality measurement and quantitative analysis methods for the overall evaluation of various dose-dependent iAs-related cytotoxicological manifestations by the combination of the synchrotron-radiation-based scanning transmission soft X-ray microscopy (SR-STXM) and Fourier transform infrared micro-spectroscopy (SR-FTIR) techniques. The gray level co-occurrence matrix (GLCM) based machine learning was employed on SR-STXM data to quantify the cytomorphological feature changes and the dose-dependent iAs-induced feature classifications with increasing doses. The infrared spectral absorption peaks and changes of dose-dependent iAs-induced cells were obtained by the SR-FTIR technique and classified by the multi-spectral-variate principle component analysis (PCA-LDA) method, showing the separated spatial distribution of dose-dependent groups. In addition, the quantitative comparisons of trivalent and pentavalent iAs under high dose conditions (iAsIII_H & iAsV_H) demonstrated that iAsIII_H and its compounds were more toxic than iAsV_H. This method has a potential in providing the morphological and spectral characteristics evolution of the iAs-related cells or particles, revealing the actual risk of arsenic contamination and metabolism.

MiR-296 Promotes Osteoblast Differentiation by Upregulating Cbfal.

We aim to identify the potential role of miR-296, which is a class of endogenous non-coding RNAs in regulating osteoblast differentiation. Human osteoblast cell line, hFOB 1.19 cells, were transfected with miR-296 overexpression or inhibition plasmid to upregulate or downregulate miR-296 expression, and then co-transfected with anti-Cbfal antibody to knockdown Cbfal. Alizarin red staining, alkaline phosphatase (ALP) activity, and enzyme-linked immunosorbent assay assays were performed to evaluate the extent of osteoblast differentiation. MTT assays were applied to measure cell proliferation. Wound healing and transwell assays were used to determine the ability of osteoblast migration and invasion. Flow cytometry assay was used to measure cell apoptosis and cell cycle change. The mRNA and protein expression of Cbfal, OSX, and Col-1 were confirmed by RT-qPCR and western blot respectively. We found that miR-296 overexpression contributed to a significant enhancement of matrix mineralization, ALP activity, and osteocalcin expression comparing with the negative control, whereas knockdown of miR-296 caused an opposite result. Meanwhile, the treatment of miR-296 promotes osteoblast migration, invasion, and proliferation, while it inhibits cell apoptosis. Compared with the negative control groups, the cells transfected with miR-296 also presented a much higher expression of Cbfal, OSX, and Col-1. Further experiments confirmed that the positive regulatory role of miR-296 in osteoblast differentiation is achieved by upregulating Cbfal expression. In conclusion, miR-296 promotes osteoblast differentiation by upregulating Cbfal expression in hFOB 1.19 cells, which may be used as a potential therapeutic target for the treatment of bone diseases in future.

Restenosis Prevention With Drug Eluting or Covered Stents in Femoropopliteal Arterial Occlusive Disease: Evidence From a Comprehensive Network Meta-analysis.

BACKGROUND/OBJECTIVE: Endovascular interventions for femoropopliteal (FP) arterial diseases are limited by the development of restenosis. Current drug coated devices are capable of preventing restenosis by releasing antiproliferative agents to the vessel wall. However, default strategies for the treatment of FP diseases remain controversial. The aim of this study was to investigate the efficacy differences between drug eluting stents (DES), covered stents (CS), and other commonly used endovascular treatments in FP lesions, including drug coated balloons (DCBs), bare metal stents (BMS), and percutaneous transluminal angioplasty (PTA). METHODS: A comprehensive network meta-analysis was conducted using data from relevant randomised control trials published up to 16 December 2018. Primary patency and target lesion revascularisation (TLR) at 12 months were set as the primary and secondary end points, respectively. RESULTS: Twenty-eight eligible trials including 4728 patients were selected. DES was ranked as the most effective treatment in the multidimensional analysis of primary patency; however, there was no significant difference in the efficacy of DES and that of CS, DCB, and BMS. However, in short lesions (<10 cm), DES was significantly more effective than DCB (odds ratio 0.35; 95% confidence interval 0.15-0.83). Primary patency at 12 months was significantly lower with PTA. In terms of preventing TLR, DCB was ranked first, followed by DES, CS, BMS, and PTA. TLR was significantly higher with PTA than with other treatment strategies. CONCLUSION: The findings of this network meta-analysis suggest that this is not the appropriate time to identify the best endovascular treatment strategy for the FP segment. DES is effective in maintaining mid-term patency, especially in short lesions, whereas DCB seems more suitable for clinical use.

Rapid qualitative and quantitative analysis of elemental composition of Cu(In, Ga)Se2 thin films using laser-induced breakdown spectroscopy.

The composition of Cu, In, Ga, and Se constituting the Cu(In,Ga)Se2 (CIGS) layer is important for the performance of the thin film. Laser-induced breakdown spectroscopy (LIBS) is very useful in quantitative analysis of elemental composition. In this paper, detection parameters of LIBS were optimized, and the CIGS thin films deposited at different sputtering powers were detected. LIBS results showed that the intensity ratio (Ga/(ln+Ga)) of the analytical spectral line of CIGS film increased initially then reduced with an increase of the sputtering power, and the evolution was consistent with optical bandgaps calculated from the transmission spectra. The intensity ratios of Ga/(ln+Ga) and Cu/(ln+Ga) detected were very highly correlated corresponding to the value obtained from energy dispersive x-ray spectroscopy. All results indicate that it is available and feasible of LIBS to fabricate high-performance CIGS thin film using the one-step radio frequency magnetron sputtering method.

Genistein promotes cartilage repair and inhibits synovial inflammatory response after anterior cruciate ligament transection in rats by regulating the Wnt/ß-catenin axis.

To confirm the protective mechanism of genistein on osteoarthritis (OA). Firstly, we constructed an anterior cruciate ligament transection (ACLT) rat model and administered two doses of genistein via gavage. The effects of the drug on cartilage damage repair and synovitis in OA rats were evaluated through pain-related behavioral assessments, pathological staining, detection of inflammatory factors, and western blot analysis. Secondly, we constructed IL-1-induced chondrocytes and synovial fibroblast models, co-incubated them with genistein, and evaluated the protective effects of genistein on both types of cells through cell apoptosis and cytoskeleton staining. To verify the role of this pathway, we applied the GSK3ß inhibitor TWS119 and the Wnt/ß-catenin inhibitor XAV939 to ACLT rats and two types of cells to analyze the potential mechanism of genistein's action on OA. Our results confirmed the protective effect of genistein on joint cartilage injury in ACLT rats and its alleviating effect on synovitis. The results of cell experiments showed that genistein can protect IL-1ß-induced chondrocytes and synovial fibroblasts, inhibit IL-1ß-induced cell apoptosis, increase the fluorescence intensity of F-actin, and inhibit inflammatory response. The results of in vivo and in vitro mechanism studies indicated that TWS119 and XAV939 can attenuate the protective effects of genistein on OA rats and IL-1-induced cell damage. Our research confirmed that genistein may be an effective drug for treating osteoarthritis. Furthermore, we discussed and confirmed that the GSK3ß/Wnt/ß-catenin axis serves as a downstream signaling pathway of genistein, providing theoretical support for its application.

Visual Gustation via Regulable Elastic Photonic Crystals.

The unique structural sensitivity of photonic crystals (PCs) endows them with stretchable or elastic tunability for light propagation and spontaneous emission modulation. Hydrogel PCs have been demonstrated to have biocompatibility and flexibility for potential human health detection and environmental security monitoring. However, current elastic PCs still possess a fixed elastic modulus and uncontrollable structural colors based on a tunable elastic modulus, posing considerable challenges for in situ detection, particularly in wearable or portable sensing devices. In this work, we introduced a novel chemo-mechanical transduction mechanism embedded within a photonic crystal nanomatrix, leading to the creation of structural colors and giving rise to a visual gustation sensing experience. By utilizing the captivating structural colors generated by the hydrogel PC, we employ abundant optical information to identify various analytes. The finite element analysis proved the electric field distribution in the PC matrix during stretch operations. The elastic-optical behaviors with various chemical cosolvents, including cations, anions, saccharides, or organic acids, were investigated. The mechanism of the Hofmeister effect regulating the elasticity of hydrogels was demonstrated with the network nanostructure of the hydrogels. The hydrogel PC matrix demonstrates remarkable capability in efficiently distinguishing a wide range of cations, anions, saccharides, and organic acids across various concentrations, mixtures, and even real food samples, such as tastes and soups. Through comprehensive research, a precise relationship between the structural colors and the elastic modulus of hydrogel PCs has been established, contributing to the biomatching elastic-optics platform for wearable devices, a dynamic environment, and clinical or health monitoring auxiliary.

LncRNA H19/miR-107 regulates endothelial progenitor cell pyroptosis and promotes flow recovery of lower extremity ischemia through targeting FADD.

BACKGROUND: Peripheral artery disease (PAD) is an ischemic disease with a rising incidence worldwide. The lncRNA H19 (H19) is enriched in endothelial progenitor cells (EPCs), and transplantation of pyroptosis-resistant H19-overexpressed EPCs (oe-H19-EPCs) may promote vasculogenesis and blood flow recovery in PAD, especially with critical limb ischemia (CLI). METHODS: EPCs isolated from human peripheral blood was characterized using immunofluorescence and flow cytometry. Cell proliferation was determined with CCK8 and EdU assays. Cell migration was assessed by Transwell and wound healing assays. The angiogenic potential was evaluated using tube formation assay. The pyroptosis pathway-related protein in EPCs was detected by western blot. The binding sites of H19 and FADD on miR-107 were analyzed using Luciferase assays. In vivo, oe-H19-EPCs were transplanted into a mouse ischemic limb model, and blood flow was detected by laser Doppler imaging. The transcriptional landscape behind the therapeutic effects of oe-H19-EPCs on ischemic limbs were examined with whole transcriptome sequencing. RESULTS: Overexpression of H19 in EPCs led to an increase in proliferation, migration, and tube formation abilities. These effects were mediated through pyroptosis pathway, which is regulated by the H19/miR-107/FADD axis. Transplantation of oe-H19-EPCs in a mouse ischemic limb model promoted vasculogenesis and blood flow recovery. Whole transcriptome sequencing indicated significant activation of vasculogenesis pathway in the ischemic limbs following treatment with oe-H19-EPCs. CONCLUSIONS: Overexpression of H19 increases FADD level by competitively binding to miR-107, leading to enhanced proliferation, migration, vasculogenesis, and inhibition of pyroptosis in EPCs. These effects ultimately promote the recovery of blood flow in CLI.

The influence of the selection of non-geological disasters sample spatial range on the evaluation of environmental geological disasters susceptibility: a case study of Liulin County.

The reasonable selection of non-geological disaster samples is of great significance to improve the accuracy of geological disaster assessment, reduce the cost of disaster management, and maintain the sustainable development of ecological environment. Liulin County was selected as the study area. This paper creatively divided non-geological disaster sampling areas by macro-geomorphology, and carried out susceptibility mapping based on random forest (RF) and frequency ratio-random forest (FR-RF) models. The accuracy of each model was evaluated by receiver operating characteristic curve (ROC) combined with the distribution characteristics of geological disasters and the actual urban construction in the study area. The results show that the FR-RF model constructed by selecting non-geological disaster samples in hilly area is most suitable for the susceptibility mapping of this study area. The different results in different sampling areas are mainly due to the great changes in the representativeness of non-geological disaster samples. The distance from the roads is the most important factor affecting the occurrence of disasters in the study area. The statistical results of disaster management cost estimation and gross domestic product (GDP) value show that the disaster management cost of HFR-RF model decreases by 13.45% on average compared with other models, and the ratio of GDP to disaster management cost is relatively high. These research results promote the progress of geological disaster prevention technology, maintain the stability of geological environment, and are of great significance to the stable and sustainable development of local economy.

Susceptibility assessment of environmental geological disasters in Liulin County based on RF: from the perspective of positive and negative sample proportion.

The rational selection of the proportion between geological disasters (positive samples) and non-geological disasters (negative samples) holds significant importance in enhancing the precision of geological disaster susceptibility assessment and maintaining the sustainable development of the ecological environment. This paper, using Liulin County as an example, employs correlation analysis to select appropriate evaluation factors. A Random Forest (RF) model, based on GIS technology, is used for susceptibility mapping. Sample ratios of 1:1, 1:1.5, 1:3, 1:5, and 1:10 are applied. The results indicate that, through a confusion matrix test, the model's predictive performance reaches a "tipping point" at a sample ratio of 1:5. The receiver operating characteristic (ROC) curve test shows that the 1:5 model performs best. Combining the proportion of susceptibility zones and disaster points, 1:5 is identified as the most suitable ratio for assessing geological disaster susceptibility in the study area. High and very high susceptibility zones are primarily concentrated in the central and northern regions alongside roads and rivers, making these areas key focuses for disaster prevention and reduction in Liulin County. The accuracy of the model's predictions increases with a greater number of samples, but it does not continue to rise indefinitely; accuracy declines after a critical threshold is crossed. These research findings complement prior studies, promote advances in geological disaster prevention technology, and maintain geological environmental stability, all of which are crucial for the local economy's stability and sustainable development.

Clinical Features of Non-Alcoholic Fatty Liver Disease in the Non-Lean Population.

INTRODUCTION: The prevalence of non-alcoholic fatty liver disease (NAFLD) in non-lean patients is significantly increased, and obesity significantly increases the risk of cirrhosis and HCC in NAFLD patients. However, whether there is a difference in clinical manifestations of NAFLD between overweight and obesity remains unclear. The objective of this study was to assess the clinical and histological features of NAFLD among a non-lean population. METHODS: Current study enrolled consecutive non-lean (body mass index [BMI] >23 kg/m2) patients with NAFLD and available liver biopsy results. Patients were stratified by BMI into two groups for the comparison of their clinical and histological variables, which included the overweight (BMI 23∼<28 kg/m2) and the obese (BMI ≥28 kg/m2). Risk factors for moderate to severe fibrosis (stage >1) were also analyzed through the logistic regression model. RESULTS: Among 184 non-lean patients with metabolic-associated fatty liver disease enrolled, 65 and 119 were overweight and obese, respectively. Patients in the obesity group had a significantly lower level of gamma-glutamyl transpeptidase, higher levels of platelet, glucose, prothrombin time, and more common of moderate to severe inflammatory activity when compared to those in the overweight group. However, a significant low frequency of moderate to severe fibrosis was found in the obesity group versus the overweight group (19.33% vs. 40.00%, p = 0.002). Binary logistics regression analysis of fibrosis found that aspartate transaminase (AST), BMI, alanine transaminase (ALT), and cholesterol (CHOL) were independent predictors for moderate to severe fibrosis in non-lean patients with NAFLD. Compared with the traditional fibrosis-4 (AUC = 0.77) and aminotransferase to platelet ratio index (AUC = 0.79) indexes, the combined index based on AST, BMI, ALT, and CHOL was more accurate in predicting moderate to severe fibrosis in non-lean patients with NAFLD (AUC = 0.87). CONCLUSIONS: Clinical and histological features differed between obesity and overweight patients with NAFLD. When compared to the traditional serum markers, the combination index including AST, BMI, ALT, and CHOL provided a better model to predict moderate to severe fibrosis in non-lean patients with NAFLD.