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Abstract Objective The purpose of this study is to observe whether there is a difference in the anesthetic effect of remimazolam tosilate and remimazolam besylate in daytime hysteroscopic surgery, so as to provide reference for clinical application. Methods Fifty patients, aged 18–65 years, ASA I-II, scheduled for hysteroscopy under total intravenous anesthesia were selected. The patients were randomly divided into two groups (n = 25): remimazolam tosilate group (group T) and remimazolam besylate group ( group R). The main observation index was the induction dose of remimazolam; secondary observation indicators were sleep time, anesthesia maintenance time, recovery time, induction maintenance dose of alfentanil, maintenance dose of remimazolam, and incidence of adverse events during anesthesia ( hypertension, hypotension, bradycardia, tachycardia). Results There was no significant difference in anesthesia induction dose, recovery time, sleep time, anesthesia maintenance time, and incidence of adverse events during anesthesia ( body movement, cough, hypertension, hypotension, bradycardia, tachycardia) between the two groups (P > 0.05). Conclusion There was no significant difference in the anesthetic effect of remimazolam tosilate and remimazolam besylate in daytime hysteroscopic surgery. Clinical trial Registration Chinese Clinical Trial Registry, ChiCTR2400081688.

Abstract Liquid biopsy is a minimally invasive method that uses biofluid samples instead of tissue samples for cancer diagnosis. Exosomes are small extracellular vesicles secreted by donor cells and act as mediators of intercellular communication in human health and disease. Due to their important roles, exosomes have been considered as promising biomarkers for liquid biopsy. However, traditional methods for exosome isolation and cargo detection methods are time-consuming and inefficient, limiting their practical application. In the past decades, many new strategies, such as microfluidic chips, nanowire arrays and electrochemical biosensors, have been proposed to achieve rapid, accurate and high-throughput detection and analysis of exosomes. In this review, we discussed about the new advance in exosome-based liquid biopsy technology, including isolation, enrichment, cargo detection and analysis approaches. The comparison of currently available methods is also included. Finally, we summarized the advantages and limitations of the present strategies and further gave a perspective to their future translational use. Graphical Abstract

ObjectiveTo analyze the effects of aryl organophosphate esters (aryl-OPEs) on female reproductive health. MethodsUrine samples from 571 women with infertility who sought in vitro fertilization-embryo transfer treatment at the Reproductive Center of Peking University People's Hospital from January 2018 to January 2021 were tested for concentrations of four aryl-OPE metabolites: diphenyl phosphate (DPHP), 4-hydroxyphenyl diphenyl phosphate (4-OH-TPHP), 2-ethyl-5-hydroxyhexyl diphenyl phosphate (5-OH-EHDPP), and 4-(hydroxymethyl)phenyl di-p-tolyl phosphate (4-OH-MDTP). Continuous independent variable data were converted into categorical variables, divided into four levels (Q1, Q2, Q3, Q4) using the 25th, 50th, and 75th percentiles as cut-off points. After reassigning values to the independent variables in each group, they were incorporated into the regression model as continuous variables for trend testing. Using multivariable linear mixed models, the correlations between aryl-OPE metabolite concentrations and reproductive hormones [estradiol (E2), progesterone (P), testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL)] and infertility causes were assessed by adjusting for relevant covariates (age, BMI, smoking status, education level, infertility reason, and primary infertility diagnosis). ResultsThe detection rates of the four aryl-OPE metabolites were all > 80%. The results of the multivariable linear regression model showed that the concentrations of 4-OH-MDTP and 5-OH-EHDPP in urine were associated with decreased E2 levels (P < 0.05). The E2 level in the 4-OH-MDTP Q3 group was significantly lower by 20.59% compared to the Q1 group, and in the 5-OH-EHDPP Q4 group, it decreased by 34.52% compared to the Q1 group. The exposure concentrations of 4-OH-TPHP and DPHP showed a significant positive correlation with progesterone levels (P < 0.05). The progesterone level in the 4-OH-TPHP Q3 group was significantly increased by 42.42% compared to the Q1 group, and in the DPHP Q4 group, it was significantly increased by 32.85% compared to the Q1 group. In the analysis of infertility causes, the concentrations of 4-OH-TPHP and 4-OH-MDTP in patients with polycystic ovary syndrome (PCOS) and endometriosis were significantly higher than those in women undergoing in vitro fertilization due to male factors. Moreover, the risk of PCOS and endometriosis increased in the 4-OH-TPHP and 4-OH-MDTP Q2-Q4 groups compared to the Q1 group. ConclusionAryl-OPEs can interfere with estrogen and progesterone levels in women. The parent compounds and metabolites may be associated with the occurrence of PCOS and endometriosis and could be one of the causes of infertility.

Abstract Tumor cells remodel the phenotype and function of tumor microenvironment (TME) cells to favor tumor progression. Previous studies have shown that neutrophils in TME are polarized to N2 tumor-associated neutrophils (TANs) by tumor derived factors, thus promoting tumor growth and metastasis, angiogenesis, therapy resistance, and immunosuppression. Exosomes act as critical intercellular messengers in human health and diseases including cancer. So far, the biological roles of exosomes from N2 TANs in gastric cancer have not been well characterized. Herein, we represented the first report that exosomes from N2 TANs promoted gastric cancer metastasis in vitro and in vivo. We found that exosomes from N2 TANs transferred miR-4745-5p/3911 to gastric cancer cells to downregulate SLIT2 (slit guidance ligand 2) gene expression. Adenovirus-mediated overexpression of SLIT2 reversed the promotion of gastric cancer metastasis by N2 TANs derived exosomes. We further revealed that gastric cancer cells induced glucose metabolic reprogramming in neutrophils through exosomal HMGB1 (high mobility group protein B1)/NF-κB pathway, which mediated neutrophil N2 polarization and miR-4745-5p/3911 upregulation. We further employed ddPCR (droplet digital PCR) to detect the expression of miR-4745-5p/3911 in N2 TANs exosomes from human serum samples and found their increased levels in gastric cancer patients compared to healthy controls and benign gastric disease patients. Conclusively, our results indicate that N2 TANs facilitate cancer metastasis via regulation of SLIT2 in gastric cancer cells by exosomal miR-4745-5p/3911, which provides a new insight into the roles of TME cells derived exosomes in gastric cancer metastasis and offers a potential biomarker for gastric cancer diagnosis.

Objectives: This study aimed to characterize a tigecycline-resistant hypervirulent Klebsiella pneumoniae (HvKP) strain, identified as KLZT, which carries the tigecycline resistance gene cluster tmexC2-tmexD2-toprJ2 belonging to ST29 and serotype K212. Methods: Antimicrobial susceptibility and virulence phenotypes were assessed, followed by whole-genome sequencing (WGS) using PacBio II and MiSeq sequencers. Genome annotation was carried out using the RAST server and bioinformatics analysis revealed the genetic characteristics of this strain. Results: Antimicrobial and virulence phenotype testing indicated that K. pneumoniae strain KLZT could be considered as a multidrug-resistant HvKP. WGS analysis showed that KLZT has a single 5,536,506-bp chromosome containing three plasmids 290,963 bp (pKLZT-1), 199,302 bp (pKLZT-2), and 4820 bp (pKLZT-3) in size, and also includes the ST29 and K212 serotypes. Four (blaSHV-187, oqxA, oqxB, and fosA6) and six resistance genes (tmexC2-tmxeD2-toprJ2, blaOXA-1, aac(6′)-Ib-cr, catB3, arr-3, and blaLEN27) were identified from chromosomal and plasmid pKLZT-1, respectively. Gene-based analysis of the resistance genes of plasmid pKLZT-1 showed that the tigecycline resistance gene cluster-carrying region was flanked by umuC and umuD (umuD-hps-IS5-tmexC2-tmexD2-toprJ2-umuC), as well as other resistance genes and virulence factors (ureB, ureC, and ureG), which were carried by IS5075-Tn3-intI1 -aac(6′)-Ib-cr-blaOXA-1-catB3-arr-3-blaLEN27-Tn3-ISkpn26-ureBCG-IS5075. Conclusions: WGS has revealed that a multidrug-resistant strain, HvKP KLZT, belonging to ST29 with capsular serotype K212, contains a multidrug-resistance plasmid.

Objective: To explore the neuroprotective effects of the Shaoyao Gancao decoction (SGD) against excitatory damage in PC12 cells and the role of the Src-NR2-nNOS pathway mediation by SGD in regulating γ-aminobutyric acid (GABA)-glutamate (Glu) homeostasis. Methods: N-Methyl-d-aspartic acid (NMDA) was used to establish a PC12 cell excitability injury model. To investigate the neuroprotective effect of SGD, a cell counting kit-8 (CCK-8) assay was used to determine PC12 cell viability, Annexin V/Propidium Iodide (Annexin V/PI) double staining was used to determine PC12 cell apoptosis, and Ca2+ concentration was observed using laser confocal microscopy. GABA receptor agonists and antagonists were used to analyze the neuroprotective interactions between γ-aminobutyric acid (GABA) and NMDA receptors. Additionally, molecular biology techniques were used to determine mRNA and protein expression in the Src-NR2-nNOS pathway. We analyzed the correlations between the regulatory sites of GABA and NMDA interactions, excitatory neurotoxicity, and brain damage at the molecular level. Results: NMDA excitotoxic injury manifested as a significant decrease in cell activity, increased apoptosis and caspase-3 protein expression, and a significant increase in intracellular Ca2+ concentration. Administration of SGD, a GABAA receptor agonist (muscimol), or a GABAB receptor agonist (baclofen) decreased intracellular Ca2+ concentrations, attenuated apoptosis, and reversed NMDA-induced upregulation of caspase-3, Src, NMDAR2A, NMDAR2B, and nNOS. Unexpectedly, a GABAA receptor antagonist (bicuculline) and a GABAB receptor antagonist (saclofen) failed to significantly increase excitatory neurotoxicity. Conclusions: Taken together, these results not only provide an experimental basis for SGD administration in the clinical treatment of central nervous system injury diseases, but also suggest that the Src-NR2A-nNOS pathway may be a valuable target in excitotoxicity treatment.

Abstract Simulating and predicting Arctic sea ice accurately remains an academic focus due to the complex and unclear mechanisms of Arctic sea ice variability and model biases. Meanwhile, the relevant forecasting and monitoring authorities are searching for models to meet practical needs. Given the previous ideal performance of cGENIE model in other fields and notable features, we evaluated the model’s skill in simulating Arctic sea ice using multiple methods and it demonstrates great potential and combined advantages. On this basis, we examined the direct drivers of sea-ice variability and predicted the future spatio-temporal changes of Arctic sea ice using the model under different Representative Concentration Pathways (RCP) scenarios. Further studies also found that Arctic sea ice concentration shows large regional differences under RCP 8.5, while the magnitude of the reduction in Arctic sea ice thickness is generally greater compared to concentration, showing a more uniform consistency of change.

Abstract Introduction Previous studies have explored the connections between various ocular biological parameters with myopia. Our previous study also found that pupil data can predict the myopic progression during the interventions for myopia. However, studies exploring the association between pupil diameter and myopia in preschoolers with myopia were lacking. Hence this study was aimed to investigate the association between pupil diameter and myopia in preschoolers with myopia based on a real-world, large-scale dataset. Methods Data containing 650,671 preschoolers were collected from a total of 1943 kindergartens in Shenzhen, China. Refraction and pupil parameters were collected. After data filtering, the occurrence of myopia and its association with age, gender, pupil diameter, and other variables, were analyzed. Random forest (RF) and eXtreme gradient boosting (XGBoost) were selected from seven machine learning algorithms to build the model. The mean decrease accuracy (MDA), mean decrease Gini (MDG), and gain feature importance (GFI) techniques were employed to quantify the importance of pupil diameter and other features. Results After the assessments, 51,325 valid records with complete pupil data were included, and 3468 (6.76%) were identified as myopia based on the calculated cycloplegic refraction. Preschoolers with myopia presented reduced pupil diameter and greater variation (5.00 ± 0.99 mm) compared to non-myopic preschoolers (6.22 ± 0.67 mm). A nonlinear relationship was found according to the scatterplots between pupil diameter and refraction (R 2 = 0.14). Especially preschoolers with myopia had reduced pupil diameter compared to emmetropic preschoolers, but hyperope did not experience additional pupil enlargement. After adjusting for other covariates, this relationship is still consistent (P

Abstract Background The optimal timing of performing ICSI on immature oocytes for POSEIDON patients is still unknown to get better early embryonic development outcomes. The purpose of this study was to implore the most appropriate time to carry out ICSI on in vitro maturation GV and MI oocytes for POSEIDON patients. Methods Two hundred thirty-nine immature oocytes from 163 POSEIDON patients were prospectively performed ICSI at different timings: P-ICSI (ICSI was performed on in vitro matured oocytes 4–6 h after the first polar body extrusion, N = 81), R-ICSI (ICSI was performed on in vitro matured oocytes less than 4 h after the first polar body extrusion, N = 80), and E-ICSI (ICSI was performed on in vitro matured oocytes the next day after oocytes retrieval, N = 78). Fertilization and embryonic development outcomes were collected and statistically analyzed. Mitochondria distribution of cytoplasm of in vitro matured oocytes with different time cultures after the first polar body (PB1) extrusion was stained. Results Compared to the E-ICSI group, more day 3 embryos from P-ICSI became blastocysts after sequential culture though without statistical significance (OR = 3.71, 95% CI: 0.94—14.63, P = 0.061). Compared to the E-ICSI group, more embryos from both P-ICSI and R-ICSI groups were clinically used with statistical significance (OR = 5.67, 95% CI: 2.24—14.35, P = 0.000 for P-ICSI embryos; OR = 3.23, 95% CI: 1.23—8.45, P = 0.017 for R-ICSI embryos). Compared to the E-ICSI group, transferred embryos from P-ICSI and R-ICSI had a higher implantation rate though without statistical significance (35.3% for P-ICSI embryos; 9.1% or R-ICSI embryos and 0% for E-ICSI embryos, P = 0.050). Among the three group, there were most healthy babies delivered from the P-ICSI group (5, 1 and 0 for P-ICSI, R-ICSI and E-ICSI respectively). The mitochondria in the cytoplasm of in vitro matured oocytes with a less than 4 h and 4–6 h culture after PB1 extrusion presented semiperipheral and diffused distribution patterns, respectively. Conclusions Our results revealed P-ICSI (ICSI was performed on in vitro matured oocytes 4–6 h after the first polar body extrusion) provided the most efficient method to utilize the immaturation oocytes basing on embryos utilization and live birth outcome for low prognosis patients under the POSEIDON classification. The mitochondria distribution of the in vitro matured oocytes’ cytoplasm from P-ICSI varied that from R-ICSI.

Abstract The extracytoplasmic function (ECF) sigma factor AlgU is involved in the regulation of various virulence-related pathways in Pseudomonas syringae, especially alginate biosynthesis and motility, and the role of AlgU differs among P. syringae pathovars. However, to date, the mechanism of its regulation in virulence of P. syringae pv. actinidiae (Psa) is still unclear. ECF sigma factors are a class of alternative sigma factors that typically function with anti-sigma factors as part of cell-surface signaling systems. Under non-inducing conditions, AlgU remains inhibited by anti-sigma factors such as MucA and MucB. To investigate the function of AlgU in Psa, mutant strains lacking algU or lacking algU with mucA and mucB genes, as well as complementary and overexpression strains of algU were generated, respectively. The results showed that AlgU was highly conserved among P. syringae pathovars and positively regulated growth rate, pathogenicity, and resistance to osmotic and oxidative stress of Psa QSY6. While AlgU did not affect the motility and exopolysaccharide production of Psa, its abundant expression enhanced the swimming ability of QSY6 and reduced its production of extracellular polysaccharides. Furthermore, AlgU regulates a number of virulence-related factors, including the Hrp system, the type VI secretion system, and flagellar synthesis. Specifically, AlgU induced the expression of hrpL and hrpRS in vivo, and repressed the transcription of hrpL and tssC in vitro, while promoting the expression of hrpS, fliC, and tssJ. This study contributes to a better understanding of the mechanisms of virulence regulation of AlgU in Psa.

Abstract Background Pseudomonas syringae pv. actinidiae (Psa) is an important bacterial plant pathogen that causes severe damage to the kiwifruit industry worldwide. Three Psa strains were recently obtained from different kiwifruit orchards in Anhui Province, China. The present study mainly focused on the variations in virulence and genome characteristics of these strains based on the pathogenicity assays and comparative genomic analyses. Results Three strains were identified as biovar 3 (Psa3), along with strain QSY6 showing higher virulence than JZY2 and YXH1 in pathogenicity assays. The whole genome assembly revealed that each of the three strains had a circular chromosome and a complete plasmid. The chromosome sizes ranged from 6.5 to 6.6 Mb with a GC content of approximately 58.39 to 58.46%, and a predicted number of protein-coding sequences ranging from 5,884 to 6,019. The three strains clustered tightly with 8 Psa3 reference strains in terms of average nucleotide identity (ANI), whole-genome-based phylogenetic analysis, and pangenome analysis, while they were evolutionarily distinct from other biovars (Psa1 and Psa5). Variations were observed in the repertoire of effectors of the type III secretion system among all 15 strains. Moreover, synteny analysis of the three sequenced strains revealed eight genomic regions containing 308 genes exclusively present in the highly virulent strain QSY6. Further investigation of these genes showed that 16 virulence-related genes highlight several key factors, such as effector delivery systems (type III secretion systems) and adherence (type IV pilus), which might be crucial for the virulence of QSY6. Conclusion Three Psa strains were identified and showed variant virulence in kiwifruit plant. Complete genome sequences and comparative genomic analyses further provided a theoretical basis for the potential pathogenic factors responsible for kiwifruit bacterial canker.

ObjectiveAcute aneurysmal rupture can be treated with endovascular therapy or surgical clipping. For patients with concurrent acute hydrocephalus, the placement of an external ventricular drainage (EVD) is required. This study aims to investigate the impact of pre-treatment EVD placement on rebleeding in ruptured aneurysms and to examine the influence of dual antiplatelet therapy and the sequencing of dual antiplatelet therapy with EVD placement on EVD-related hematomas.MethodsWe reviewed the clinical data of 83 patients with ruptured aneurysms who underwent EVD placement from a total of 606 aneurysm patients consecutively admitted between January 2018 and January 2023. The analysis focused on the impact of pre-treatment EVD placement on aneurysmal rebleeding and the effect of dual antiplatelet therapy and its sequencing with EVD placement on EVD-related hematomas.ResultsAmong the 503 patients with ruptured aneurysms, 83 required EVD placement. EVD was placed before aneurysm treatment in 63 patients and after treatment in 20 patients. The number of aneurysmal rebleeding cases in the pre-treatment EVD group and non-EVD group was 1 (1.6%) and 20 (4.8%), respectively (p = 0.406). 31 patients (37.3%) underwent stent-assisted embolization or flow diversion requiring dual antiplatelet therapy, while 52 patients (62.7%) underwent simple embolization or surgical clipping without antiplatelet therapy. EVD-related hematomas occurred in 14 patients (16.9%), with 10 cases (32.3%) in those receiving dual antiplatelet therapy and 4 cases (7.7%) in those not receiving antiplatelet therapy (p = 0.01). Among 16 patients who had EVD placed before dual antiplatelet therapy, 4 (25%) developed EVD-related hematomas. Of the 15 patients who had EVD placed after dual antiplatelet therapy, 6 (40%) developed EVD-related hematomas (p = 0.458).ConclusionIn patients with aneurysmal subarachnoid hemorrhage (aSAH) and acute hydrocephalus, the placement of EVD before aneurysm treatment does not increase the risk of rebleeding. However, dual antiplatelet therapy increases the risk of EVD-related hematoma, and the sequence of EVD placement relative to dual antiplatelet therapy does not appear to significantly affect the outcome of EVD-related hematoma.

Diabetic retinopathy (DR) is a chronic complication of diabetes. Given that adiponectin plays a key role in DR progression, this study aims to elucidate the molecular mechanisms of sDR progression related to adiponectin. First, we extracted the microarray dataset GSE60436 from the Gene Expression Omnibus (GEO) database to identify hub genes associated with DR. Pathway enrichment analysis revealed a focus on inflammation, oxidative stress, and metabolic disease pathways. Gene Set Enrichment Analysis (GSEA) identified nine significant pathways related to DR. Immune infiltration analysis indicated increased infiltration of fibroblasts and endothelial cells in DR patients. Second, at the gene level, single-cell RNA sequencing (scRNA-seq) results showed a decrease in ADIPOQ gene expression as the disease progressed in our mouse models. At the protein level, ELISA results from sera of 31 patients and 11 control subjects demonstrated significantly lower adiponectin expression in the proliferative diabetic retinopathy (PDR) group compared to controls. Our findings reveal that adiponectin is involved in the advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE) axis, as evidenced by hub gene analysis, scRNA-seq, and ELISA. In conclusion, adiponectin acts as a central molecule in the AGEs-RAGE axis, regulated by ADIPOQ, to influence DR progression.

The development of a Digital Intelligence Quotient (DQ) scale for primary school students is the basis for research on the DQ of primary school students, which helps to scientifically diagnose the level and the current average DQ among Chinese primary school students. This study developed and validated a scale applicable to the assessment of DQ in Chinese primary school students where, the initial scale was first constructed; Then 1109 valid datasets were collected through purposive sampling and divided into Sample A and Sample B; Sample A was subjected to exploratory factor analysis and Sample B was tested by confirmatory factor analysis; The final validated scale consists of 22 items in 7 dimensions: digital identity, digital use, digital safety, digital security, digital emotional intelligence, digital literacy and digital rights. The scale has high reliability and validity and thus can be used as a reliable instrument for assessing DQ in Chinese primary school students.

Abstract Purpose To evaluate the association of body stature with ocular biometrics and refraction in preschool children. Methods A cross-sectional, school-based study was conducted in Shenzhen, China. Preschool children aged 3 to 6 from 10 randomly-selected kindergartens were recruited. Ocular biometric parameters, including axial length (AL), anterior chamber depth (ACD), vitreous chamber depth (VCD), corneal radius curvature (CR), axial length to corneal radius ratio (AL-to-CR ratio) and lens thickness (LT) were measured using non-contact partial-coherence laser interferometry. Cycloplegic refractions were obtained by a desktop autorefractor. Body height and weight were measured using standard procedures. The association between body stature and ocular biometrics were analyzed with univariable and multivariable regression model. Results A total of 373 preschoolers were included. AL, ACD, VCD, CR, and AL-to-CR ratio, were positively associated with height and weight (p

Abstract Background The pathophysiological mechanisms of diabetic retinopathy (DR), a blinding disease, are intricate. DR was thought to be a microvascular disease previously. However, growing studies have indicated that the retinal microglia-induced inflammation precedes microangiopathy. The binary concept of microglial M1/M2 polarization paradigms during inflammatory activation has been debated. In this study, we confirmed microglia had the most significant changes in early DR using single-cell RNA sequencing. Methods A total of five retinal specimens were collected from donor SD rats. Changes in various cells of the retina at the early stage of DR were analyzed using single-cell sequencing technology. Results We defined three new microglial subtypes at cellular level, including two M1 types (Egr2 + M1 and Egr2 − M1) and one M2 type. We also revealed the anatomical location between these subtypes, the dynamic changes of polarization phenotypes, and the possible activation sequence and mutual activation regulatory mechanism of different cells. Furthermore, we constructed an inflammatory network involving microglia, blood-derived macrophages and other retinal nonneuronal cells. The targeted study of new disease-specific microglial subtypes can shorten the time for drug screening and clinical application, which provided insight for the early control and reversal of DR. Conclusions We found that microglia show the most obvious differential expression changes in early DR and reveal the changes in microglia in a high-glucose microenvironment at the single-cell level. Our comprehensive analysis will help achieve early reversal and control the occurrence and progression of DR.

More and more evidence has showed that low glycaemic index (GI) diet was a benefit to the Type 2 Diabetes Mellitus (T2DM). However, the detailed mechanism was not clear. Here, we detected the effects of low-GI diet on the HFD/STZ-induced T2DM rats model. Our results showed that low-GI diet significantly decreased triglyceride and glucose level in the serum of T2DM rats, and increased the level of insulin and C-peptide in T2DM rats. Besides, low-GI diet also increased Bacteroidota at the phylum level. And at the genus level, low-GI diet promoted the proliferation of the abundance of Turicibacter, Lactobacillus, Desulfovibrio, Prevotellaceae, Lachnospiraceae, Monoglobus, Xylanophilum and Roseburia. Moreover, we also found that low-GI diet significantly improved the contents of valeric acid, acetic acid, propionic acid, isobutyric acid, butyric acid, 2-methylbutyrate, isovaleric acid, 4-methylvaleric acid and hexanoic acid; upregulated the levels of peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and G protein-coupled receptor 41 (GPR41); and increased the numbers of L-cells (P

Abstract M2‐polarized tumor‐associated macrophages (M2 TAMs) promote cancer progression. Exosomes mediate cellular communication in the tumor microenvironment (TME). However, the roles of exosomes from M2 TAMs in gastric cancer progression are unclear. Herein, it is reported that M2 TAMs‐derived exosomes induced aerobic glycolysis in gastric cancer cells and enhanced their proliferation, metastasis, and chemoresistance in a glycolysis‐dependent manner. It is identified that MALAT1 (metastasis‐associated lung adenocarcinoma transcript 1) is enriched in M2 TAM exosomes and confirmed that MALAT1 transfer from M2 TAMs to gastric cancer cells via exosomes mediates this effect. Mechanistically, MALAT1 interacted with the δ‐catenin protein and suppressed its ubiquitination and degradation by β‐TRCP. In addition, MALAT1 upregulated HIF‐1α expression by acting as a sponge for miR‐217‐5p. The activation of β‐catenin and HIF‐1α signaling pathways by M2 TAM exosomes collectively led to enhanced aerobic glycolysis in gastric cancer cells. Finally, a dual‐targeted inhibition of MALAT1 in both gastric cancer cells and macrophages by exosome‐mediated delivery of siRNA remarkably suppressed gastric cancer growth and improved chemosensitivity in mouse tumor models. Taken together, these results suggest that M2 TAMs‐derived exosomes promote gastric cancer progression via MALAT1‐mediated regulation of glycolysis. The findings offer a potential target for gastric cancer therapy.

Introduction: Epidemiological evidence over the last few decades has consistently shown that exposure to endocrine-disrupting chemicals (EDCs) is associated with adverse reproductive health outcomes, including male and female infertility, poor-pregnancy outcomes, and increased risk of diseases in childhood and beyond. To investigate the effects of EDCs and lifestyle on all aspects of reproduction (including early oocyte development, fertilization, embryo development, embryo implantation, abortion, and preterm birth).Methods: We performed this cohort study on patients receiving in vitro fertilization (IVF) treatment. Biological samples including urine, serum, follicular fluid, semen, fetal tissue, decidua, and placenta, were obtained.Results: By studying the correlations between reproductive outcomes and environmental pollutant exposure and lifestyle, we determined the toxicological mechanisms and health effects of EDCs on female reproductive health. We found that higher concentrations of per- and polyfluoroalkyl substances were correlated with polycystic ovary syndrome (PCOS). Using specific biomarkers, we also detected the concentrations of organophosphorus flame retardants (OPFRs) in urine and found that OPFRs may disrupt hormone homeostasis.Discussion: All of these results reveal EDCs may disrupt female reproduction.

This paper introduces a new green decomposition model of carbon productivity that aims to further analyze the regional differences in carbon productivity and its interaction with regional industrial performance. We combine desired outputs and undesired outputs orientation, and multiple factor inputs to derive a new green decomposition theorem, establish a new green decomposition model of carbon productivity, and obtain nine effects of regional carbon productivity differences. Empirical analysis is conducted using input-output data from 29 provinces and 15 industries in China, comparing the differences in carbon productivity from both the provincial and industry perspectives and exploring the mechanism of action. This paper provides theoretical basis and empirical evidence for regional carbon productivity enhancement and economic and industrial optimization from the perspective of multi-factor inputs, as well as policy insights for regional low-carbon transition development.

One potential solution to the problems of energy storage and conversion is the use of reversible protonic ceramic electrochemical cells (R-PCEC), which are based on the solid oxide fuel cell (SOFC) technology and offer a flexible route to the generation of renewable fuels. However, the R-PCEC development faces a range of significant challenges, including slow oxygen reaction kinetics, inadequate durability, and poor round-trip efficiency resulting from the inadequacy of an air electrode. To address these issues, we report novel B-sites doped Pr0.5Ba0.5Co0.7Fe0.3O3−δ (PBCF) with varying amounts of Sn as the air electrode for R-PCEC to further enhance electrochemical performance at lower temperatures. At 600 ℃, R-PCEC with an air electrode consisting of Pr0.5Ba0.5Co0.7Fe0.25Sn0.05O3+δ has achieved peak power density of 1.12 W∙cm−2 in the fuel cell mode and current density of 1.79 A∙cm−2 in the electrolysis mode at a voltage of 1.3 V. Moreover, R-PCECs have shown good stability in the electrolysis mode of 100 h. This study presents a practical method for developing durable high-performance air electrodes for R-PCECs.

Although the underwater optical communication system (UWOC) plays an important role in many marine applications, the acquisition, pointing and tracking (APT) problems are still great challenges in a long or turbid water channel. The Orthogonal Frequency Division Multiplexing (OFDM) and the space-time block coding (STBC) technologies have been introduced in UWOC systems to improve spectral efficiency and data transmission reliability. On these foundations, a multi-input multi-output (MIMO) mode is proposed and verified in this article to reduce the alignment requirement. In experiments, two sets of 450 nm blue laser diodes (LDs) and PIN photodiodes are selected as light sources and receivers, and then parallel light beams are generated and modulated using an Alamouti coding for its anti-interference ability. The receiving plane is rotated to simulate the various alignment situations, and the system performance of MIMO-OFDM and single-input single-output OFDM (SISO-OFDM) are compared in tap water and turbid water. The results show that the spatial diversity in MIMO can extend the communication range and its single-sided maximum detection angle range is 92% and 112% higher than the SISO system, respectively.

Objective: To explore and validate the potential targets of Paeoniae Radix Alba (P. Radix, Bai Shao) in protecting against chemical liver injury through network pharmacology, molecular docking technology, and in vitro cell experiments. Methods: Network pharmacology was used to identify the common potential targets of P. Radix and chemical liver injury. Molecular docking was used to fit the components, which were subsequently verified in vitro. A cell model of hepatic fibrosis was established by activating hepatic stellate cell (HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1. The cells were exposed to different concentrations of total glucosides of paeony (TGP), the active substance of P. Radix, and then evaluated using the cell counting kit-8 assay, enzyme-linked immunosorbent assay, and western blot. Results: Analysis through network pharmacology revealed 13 key compounds of P. Radix, and the potential targets for preventing chemical liver injury were IL-6, AKT serine/threonine kinase 1, jun proto-oncogene, heat shock protein 90 alpha family class A member 1 (HSP90AA1), peroxisome proliferator activated receptor gamma (PPARG), PTGS2, and CASP3. Gene Ontology (GO) enrichment analysis indicated the involvement of response to drugs, membrane rafts, and peptide binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation. Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1, PTGS2, PPARG, and CASP3. Different concentrations of TGP can inhibit the expression of COL-Ⅰ, COL-Ⅲ, IL-6, TNF-α, IL-1β, HSP-90α, and PTGS2 while increasing the expression of PPAR-γ and CASP3 in activated HSC-LX2 cells. Conclusion: P. Radix primarily can regulate targets such as HSP90AA1, PTGS2, PPARG, CASP3. TGP, the main active compound of P. Radix, protects against chemical liver injury by reducing the inflammatory response, activating apoptotic proteins, and promoting the apoptosis of activated HSCs.

In complex data environments, rational handling of unbalanced datasets is key to improving the reliability of early disease prediction. Early warning of disease risk in both temporal and spatial terms, contributes to disease prevention and treatment. To this end, a bi-dimensional substratum information mining model based on Association Rule Digging with Dynamic Thresholding and Weight Optimization (ARDdtwo) was proposed for the early diagnosis of thyroid cancer. It is an integrated assessment framework consisting of association rule digging by constructing a dynamic threshold model (ADRcdt) for qualitative analysis, and a self-optimizing component importance measurement model (SoCIM) for quantitative analysis. ARDcdt incorporates temporal and spatial features of sparse data to address the distributional bias problem. Moreover, new importance diagnostic calculations were designed to further identify high-risk low-frequency (HRLF). The SoCIM can determine the relative weight of each component by assessing its level of risk in the overall system based on the Risk Enhancement Level (REL) and Risk Reduction Level (RRL), realizing the self-adjustment and optimization of the weight setting. Finally, the model was validated through an empirical analysis. The evaluation of the research work shows that improved results were achieved, such as accuracy, f1-score, and precision, with optimized values of 36.04%,56.57%, and 53.89%, respectively. The overall area under the curve for the model was 0.882. This proves the validity of the proposed model for practical applications. For patients, it can simplify the pathological process and reduce the examination costs.

Abstract Background The decline in the quantity and quality of mitochondria are closely associated with infertility, particularly in advanced maternal age. Transferring autologous mitochondria into the oocytes of infertile females represents an innovative and viable strategy for treating infertility, with no concerns regarding ethical considerations. As the donor cells of mitochondria, stem cells have biological advantages but research and evidence in this area are quite scarce. Methods To screen out suitable human autologous ooplasmic mitochondrial donor cells, we performed comprehensive assessment of mitochondrial physiology, function and metabolic capacity on a varity of autologous adipose, marrow, and urine-derived mesenchymal stromal cells (ADSC, BMSC and USC) and ovarian germline granulosa cells (GC). Further, to explore the biosafety, effect and mechanism of stem cell-derived mitochondria transfer on human early embryo development, randomized in-vitro basic studies were performed in both of the young and aged oocytes from infertile females. Results Compared with other types of mesenchymal stromal cells, USC demonstrated a non-fused spherical mitochondrial morphology and low oxidative stress status which resembled the oocyte stage. Moreover, USC mitochondrial content, activity and function were all higher than other cell types and less affected by age, and it also exhibited a biphasic metabolic pattern similar to the pre-implantation stage of embryonic development. After the biosafety identification of the USC mitochondrial genome, early embryos after USC mitochondrial transfer showed improvements in mitochondrial content, activity, and cytoplasmic Ca2+ levels. Further, aging embryos also showed improvements in embryonic morphological indicators, euploidy rates, and oxidative stress status. Conclusion Autologous non-invasively derived USC mitochondria transfer may be an effective strategy to improve embryonic development and metabolism, especially in infertile females with advanced age or repeated pregnancy failure. It provides evidence and possibility for the autologous treatment of infertile females without invasive and ethical concerns.

Abstract Background Retinoblastoma (RB) is the most common prevalent intraocular malignancy among infants and children, particularly in underdeveloped countries. With advancements in genomics and transcriptomics, noncoding RNAs have been increasingly utilized to investigate the molecular pathology of diverse diseases. Aims This study aims to establish the competing endogenous RNAs network associated with RB, analyse the function of mRNAs and lncRNAs, and finds the relevant regulatory network. Methods and Results This study establishes a network of competing endogenous RNAs by Spearman correlation analysis and prediction based on RB patients and healthy children. Enrichment analyzes based on Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes are conducted to analyze the potential biological functions of lncRNA and mRNA networks. Weighted gene co‐expression network analysis (WGCNA) is employed to identify gene cluster modules exhibiting the strongest correlation with RB. The results indicate a significant correlation between the lncRNA MIR17HG (R = .73, p = .02) and the RB phenotype. ceRNA networks reveal downstream miRNAs (hsa‐mir‐425‐5p and hsa‐mir455‐5p) and mRNAs (MDM2, IPO11, and ITGA1) associated with MIR17Hg. As an inhibitor of the p53 signaling pathway, MDM2 can suppress the development of RB. Conclusion In conclusion, lncRNAs play a role in RB, and the MIR17HG/hsa‐mir‐425‐5p/MDM2 pathway may contribute to RB development by inhibiting the p53 signaling pathway.

Currently kiwifruit picking process mainly leverages manual labor, which has low productivity and high labor intensity, meanwhile, the existing kiwifruit picking machinery also has low picking efficiency and easily damages fruits. In this regard, a kiwifruit picking robot suitable for orchard operations was developed in this paper for kiwifruit grown in orchard trellis style. First, based on the analysis of kiwifruit growth pattern and cultivation parameters, the expected design requirements and objectives of a kiwifruit picking robot were proposed, and the expected workflow of the robot in the kiwifruit orchard environment was given, which in turn led to a multi-fruit envelope-cutting kiwifruit picking robot was designed. Then, the D-H method was used to establish the kinematic Equations of the kiwifruit-picking robot, the forward and inverse kinematic calculations were carried out, and the Monte Carlo method was used to analyze the workspace of the robot. By planning the trajectory of the robotic arm and calculating critical nodes in the picking path, the scheme of trajectory planning of the robot was given, and MATLAB software was applied to simulate the motion trajectory as well as to verify the feasibility of the trajectory planning scheme and the picking strategy. Finally, a kiwifruit picking test bed was set up to conduct picking tests in the form of fruit clusters. The results show that the average time to pick each cluster of fruit was 9.7s, the picking success rate was 88.0%, and the picking damage rate was 7.3%. All the indicators met the requirements of the expected design of the kiwifruit-picking robot.

Abstract The interaction between tumor cells and stromal cells within the tumor microenvironment plays a critical role in cancer progression. Mesenchymal stem cells (MSCs) are important tumor stromal cells that exhibit pro-oncogenic activities when reprogrammed by the tumor. However, the precise mechanisms underlying MSC reprogramming in gastric cancer remain not well understood. QRT-PCR, western blot, and immunohistochemistry were used to examine gene and protein expression levels. In vitro and in vivo experiments were conducted to assess the biological functions of gastric cancer cells. RNA-sequencing, RNA immunoprecipitation (RIP), and meRIP assays were performed to investigate underlying molecular mechanisms. We found a significant increase in the expression and N6-methyladenosine (m6A) modification levels of colony-stimulating factor 2 (CSF2) in gastric cancer MSCs. CSF2 gene overexpression induced the reprogramming of normal MSCs into cancer-promoting MSCs, thereby enhancing the proliferation, migration, and drug resistance of gastric cancer cells through the secretion of various pro-inflammatory factors. Additionally, we demonstrated that the m6A reader IGF2BP2 bound to and stabilized CSF2 mRNA in gastric cancer MSCs. Notably, overexpression of IGF2BP2 mimicked the effect of CSF2 on MSCs, promoting gastric cancer progression. Finally, we unveiled that CSF2 induced the ubiquitination of Notch1 to reprogram MSCs. Our study highlights a critical role of IGF2BP2-mediated m6A modification of CSF2 in reprogramming MSCs, which presents a promising therapeutic target for gastric cancer.

Abstract Background We aimed to develop an accurate model to predict live birth for patients receiving in vitro fertilization and embryo transfer (IVF-ET) treatment. Methods This is a prospective nested case–control study. Women aged between 18 and 38 years, whose body mass index (BMI) were between the range of 18.5–24 kg/m2, who had an endometrium of ≥ 8 mm at the thickest were enrolled from 2018/9 to 2020/8. All patients received IVF-ET treatment and were followed up until Jan. 2022 when they had reproductive outcomes. Endometrial samples during the window of implantation (LH + 6 to 9 days) were subjected to analyze specific endometrial receptivity genes’ expression using real-time PCR (RT-PCR). Patients were divided into live birth group and non-live birth group based on IVF-ET outcomes. Clinical signatures relevant to live birth were collected, analyzed, and used to establish a predictive model for live birth by univariate analysis (clinical model). Specific endometrial receptivity genes’ expression was analyzed, selected, and used to construct a predictive model for live birth by The Least Absolute Shrinkage and Selection Operator (LASSO) analysis (gene model). Finally, significant clinical factors and genes were used to construct a combined model for predicting live birth using multivariate logistical regression (combined model). Different models’ Area Under Curve (AUC) were compared to identify the most predictive model. Results Thirty-nine patients were enrolled in the study, twenty-four patients had live births, fifteen did not. In univariate analysis, the odds of live birth for women with ovulation dysfunction was 4 times higher than that for women with other IVF-ET indications (OR = 4.0, 95% CI: 1.125 − 8.910, P = 0.018). Age, body mass index, duration of infertility, primary infertility, repeated implantation failure, antral follicle counting, ovarian sensitivity index, anti-Mullerian hormone, controlled ovarian hyperstimulation protocol and duration, total dose of FSH/hMG, number of oocytes retrieved, regiment of endometrial preparation, endometrium thickness before embryo transfer, type of embryo transferred were not associated with live birth (P > 0.05). Only ovulation dysfunction was used to construct the clinical model and its AUC was 0.688. In lasso analysis, GAST, GPX3, THBS2 were found to promote the risk of live birth. AUCs for GAST, GPX3, THBS2 reached to 0.736, 0.672, and 0.678, respectively. The gene model was established based on these three genes and its AUC was 0.772. Ovulation dysfunction, GAST, GPX3, and THBS2 were finally used to construct the combined model, reaching the highest AUC (AUC = 0.842). Conclusions Compared to the single model, the combined model of clinical (Ovulation dysfunction) and specific genes (GAST, GPX3, THBS2) was more accurate to predict live birth for IVF-ET patients.

The rotor cage is a key component of the classifying device, and its structural parameters directly affect classification performance. To improve the classification performance of the straw micro-crusher classifying device, this paper proposes a CFD-ML-GA (Computational Fluid Dynamics-Machine Learning-Genetic Algorithm) method to quantitatively analyze the coupled effects of rotor cage structural parameters on classification performance. Firstly, CFD and orthogonal experimental methods are used to qualitatively investigate the effects of the number of blades, length of rotor blades, and blade installation angle on the classification performance. The conclusion obtained is that the blade installation angle exerts the greatest effect on classification performance, while the number of blades has the least effect. Subsequently, four machine learning algorithms are used to build a cut size prediction model, and, after comparison, the Random Forest Regression (RFR) model is selected. Finally, RFR is integrated with a Genetic Algorithm (GA) for quantitative parameter optimization. The quantitative analysis results of GA indicate that with 29 blades, a blade length of 232.8 mm, and a blade installation angle of 36.8°, the cut size decreases to 47.6 μm and the classifying sharpness index improves to 0.62. Compared with the optimal solution from the orthogonal experiment, the GA solution reduces the cut size by 9.33% and improves the classifying sharpness index by 9.68%. This validates the feasibility of the proposed method.

Modeling and simulating the underwater optical imaging process can assist in optimizing the configuration of underwater optical imaging technology. Based on the Monte Carlo (MC) method, we propose an optical imaging model which is tailored for deep-sea luminescent objects. Employing GPU parallel acceleration expedites the speed of MC simulation and ray-tracing, achieving a three-order-of-magnitude speedup over a CPU-based program. A deep-sea single-lens imaging system is constructed in the model, composed of a luminescent object, water medium, double-convex lens, aperture diaphragm, and sensor. The image of the luminescent object passing through the imaging system is generated using the forward ray-tracing method. This model enables an intuitive analysis of the inherent optical properties of water and imaging device parameters, such as sensor size, lens focal length, field of view (FOV), and camera position on imaging outcomes in the deep-sea environment.

This paper investigates the influence of the concentration and particle size of h-BN nanoparticles in a nanofluid on the surface integrity of 304 austenitic stainless steel during turning, focusing on the cutting force, friction coefficient, cutting temperature, surface roughness, surface residual stress, work hardening capacity, and 3D surface topography. The results show that, compared to dry cutting, the addition of 3 wt.% h-BN nanofluid can reduce the friction coefficient on the rake face by 38.9%, lower the cutting temperature by 43.5%, decrease the surface roughness by 53.8%, decrease the surface residual stress by 61.6%, and reduce the work hardening degree by 27.5%. Two-dimensional profiles and the 3D surface topography display a more balanced peak–valley distribution. Furthermore, by studying the effect of different h-BN particle sizes in nanofluids on the surface integrity of the machined workpiece, it was found that nanoscale particles have a greater tendency to penetrate the tool–chip interface than submicron particles. Moreover, the h-BN particles in the nanofluid play a “rolling effect” and “microsphere” effect, and the sesame oil will also form a lubricating oil film in the knife-chip contact area, thereby reducing the friction coefficient, reducing the cutting force, and improving the machining surface quality.

Abstract Esophageal stricture is a debilitating condition that negatively impacts patients' quality of life after undergoing endoscopic mucosal resection (EMR). Despite its significance, this disease remains underexplored due to the lack of a stable animal model. Under direct visualization with choledochoscopy, we retrogradely damaged the esophageal mucosal layer through the gastrostomy to create a rat model of esophageal stricture. The development of histological defects in the mucosal layer was assessed over a 2-week period after model induction. Then the models were evaluated using X-ray barium radiography, Hematoxylin–Eosin, Masson’s trichrome, Sirius red, and Victoria blue staining, multiphoton microscopic imaging. Additionally, the molecular mechanisms of esophageal stricture were explored by conducting RNA transcriptome sequencing, PCR, immunohistochemistry, and immunofluorescence staining. We successfully established fifteen rat models of esophageal stricture by injuring the mucosal layer. In the model group, the mucosal defect initially occurs and subsequently repaired. The epithelium was absent and was plastically remodeled by collagen during the acute inflammatory phase (Day 1), proliferation phase (Day 7), anaphase of proliferation (Day 10), and plastic remodeling phase (Day 14). We observed increased expression of COL1A1, acta2, FGF, IL-1, and TGF-β1 pathway in the model group. We established a highly repeatable rat model of esophageal stricture, and our results suggest that the mucosal defect of the esophagus is a critical factor in esophageal stricture development, rather than damage to the muscularis layer. We identified Atp4b, cyp1a2, and gstk1 as potential targets for treating esophageal stricture, while the TGF-β pathway was found to play an important role in its development.

Abstract Background Metabolites in spent embryo culture medium correlate with the embryo’s viability. However, there is no widely accepted method using metabolite dada to predict successful implantation. We sought to combine metabolomic profiling of spent embryo culture medium and clinical variables to create an implantation prediction model as an adjunct to morphological screening of day 3 embryos. Methods This investigation was a prospective, nested case-control study. Forty-two day 3 embryos from 34 patients were transferred, and the spent embryo culture medium was collected. Twenty-two embryos implanted successfully, and the others failed. Metabolites in the medium relevant to implantation were detected and measured by Liquid Chromatography-Mass Spectrometry. Clinical signatures relevant to embryo implantation were subjected to univariate analysis to select candidates for a prediction model. Multivariate logistical regression of the clinical and metabolomic candidates was used to construct a prediction model for embryo implantation potential. Results The levels of 13 metabolites were significantly different between the successful and failed groups, among which five were most relevant and interpretable selected by Least Absolute Shrinkage and Selection Operator regression analysis. None of the clinical variables significantly affected day 3 embryo implantation. The most relevant and interpretable set of metabolites was used to construct a prediction model for day 3 embryo implantation potential with an accuracy of 0.88. Conclusions Day 3 embryos’implantation potential could be noninvasively predicted by the spent embryo culture medium’s metabolites measured by LC-MS. This approach may become a useful adjunct to morphological evaluation of day 3 embryos.

Abstract Diabetic retinopathy (DR) is one of the most prevalent retinal disorders worldwide, and it is a major cause of vision impairment in individuals of productive age. Research has demonstrated the significance of autophagy in DR, which is a critical intracellular homeostasis mechanism required for the destruction and recovery of cytoplasmic components. Autophagy maintains the physiological function of senescent and impaired organelles under stress situations, thereby regulating cell fate via various signals. As the retina's functional and fundamental unit, the retinal neurovascular unit (NVU) is critical in keeping the retinal environment's stability and supporting the needs of retinal metabolism. However, autophagy is essential for the normal NVU structure and function. We discuss the strong association between DR and autophagy in this review, as well as the many kinds of autophagy and its crucial physiological activities in the retina. By evaluating the pathological changes of retinal NVU in DR and the latest advancements in the molecular mechanisms of autophagy that may be involved in the pathophysiology of DR in NVU, we seek to propose new ideas and methods for the prevention and treatment of DR.

Abstract Background Cataract is commonly observed in patients with primary angle-closure glaucoma; however, its underlying pathological mechanisms remain unclear. This study aimed to improve our knowledge on the pathological processes involved in primary angle-closure glaucoma (PACG) by identifying potential prognostic genes associated with cataract progression. Methods Thirty anterior capsular membrane samples were collected from PACG patients with cataracts and age-related cataracts. Differentially expressed genes (DEGs) between these two cohorts were analyzed using high-throughput sequencing. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to screen the DEGs, and potential prognostic markers and their coexpression network were then predicted by bioinformatic analyses. The DEGs were further validated by reverse transcription-quantitative polymerase chain reaction. Results A total of 399 DEGs were found to be specifically associated with cataracts development in PACG patients, among which 177 and 221 DEGs were upregulated and downregulated, respectively. STRING and Cytoscape network analyses revealed seven genes—CTGF, FOS, CAV1, CYR61, ICAM1, EGR1, and NR4A1—that were remarkably enriched and mainly involved in the MAPK, PI3K/Akt, Toll-like receptor, and TNF signaling pathways. RT-qPCR-based validation further confirmed that the sequencing results were accurate and reliable. Conclusions Herein, we identified seven genes and their signaling pathways that may contribute to cataract progression in patients with high intraocular pressure. Taken together, our findings highlight new molecular mechanisms that may explain the high incidence of cataracts in PACG patients. In addition, the genes identified herein may represent new foundations for the development of therapeutic strategies for PACG with cataract.

It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression. This study included all eligible 156 cervical cancers diagnosed during 2003-2008 and followed up through 2014, 102 cervical intraepithelial neoplasia (CIN) patients, and 16 participants with normal cervix identified at the same period. Correlation of expression of TPP1 and hTERT in these lesions was assessed using Kappa statistics. TPP1 was knocked down by siRNA in three cervical cancer cell lines. We assessed mRNA expression using quantitative real-time polymerase chain reaction and protein expression using tissue microarray-based immunohistochemical staining. We further analyzed the impact of TPP1 expression on the overall survival of cervical cancer patients by calculating the hazard ratio (HR) with 95% confidence intervals (CIs) using the multivariable-adjusted Cox regression model. Compared to the normal cervix, high TPP1expression was significantly associated with CIN 3 and cervical cancers (P

Abstract Proton‐conducting solid oxide fuel cells (H‐SOFCs) have the potential to be a promising technology for energy conversion and storage. To achieve high chemical compatibility and catalytic activity, nickel‐doped barium ferrate with triple conducting ability is developed as cathodes for H‐SOFCs, presenting an impressive electrochemical performance at intermediate temperatures. The cell performance with the optimized BaCe0.26Ni0.1Fe0.64O3–δ (BCNF10) composite cathode reaches an outstanding performance of 1.04 W cm−2 at 600 °C. The high electrocatalytic capacity of the nickel‐doped barium ferrate cathode can be attributed to its significant proton conductivity which is confirmed through hydrogen permeation experiments. Density functional theory (DFT) calculations are further conducted to reveal that the presence of nickel can enhance processes of hydration formation and proton migration, leading to improve proton conductivity and electro‐catalytic activity.

Abstract Adiponectin, one of the most ubiquitous adipokines found in the blood, plays a major role in glucolipid metabolism and energy metabolism and regulation. In recent years, a growing body of research indicates that adiponectin also plays a significant role in diabetic retinopathy. In the present review, we specifically address the protective effects of adiponectin on the development and progression of diabetic retinopathy through improvement in insulin resistance, alleviation of oxidative stress, limiting of inflammation, and prevention of vascular remodeling, with the aim to explore new potential approaches and targets for the prevention and treatment of diabetic retinopathy.

Abstract tRNA-derived fragments (tRFs) are an emerging category of small non-coding RNAs that are generated from cleavage of mature tRNAs or tRNA precursors. The advance in high-throughput sequencing has contributed to the identification of increasing number of tRFs with critical functions in distinct physiological and pathophysiological processes. tRFs can regulate cell viability, differentiation, and homeostasis through multiple mechanisms and are thus considered as critical regulators of human diseases including cancer. In addition, increasing evidence suggest the extracellular tRFs may be utilized as promising diagnostic and prognostic biomarkers for cancer liquid biopsy. In this review, we focus on the biogenesis, classification and modification of tRFs, and summarize the multifaceted functions of tRFs with an emphasis on the current research status and perspectives of tRFs in cancer.

Disulfidptosis is a newly discovered form of programmed cell death that is induced by disulfide stress. It is closely associated with various cancers, including head and neck squamous cell carcinoma (HNSCC). However, the factors involved in the modulation of disulfidptosis-related genes (DRGs) still remain unknown. In this study, we established and validated a novel risk score model composed of 11 disulfidptosis-related lncRNAs (DRLs) based on 24 DRGs in HNSCC. The results revealed strong correlations between the 11-DRL prognostic signature and clinicopathological features, immune cell infiltration, immune-related functions, and disulfidptosis-associated pathways, including NADPH and disulfide oxidoreductase activities. Furthermore, we studied and verified the involvement of ALMS1-IT1, one of the 11 model DRLs, in the disulfidptosis of HNSCC cell lines. A series of assays demonstrated that ALMS1-IT1 modulated cell death under starvation conditions in a pentose phosphate pathway (PPP)-dependent manner. Knockdown of ALMS1-IT1 inhibited the PPP, contributing to a decline in NADPH levels, which resulted in the formation of multiple intermolecular disulfide bonds between actin cytoskeleton proteins and the collapse of F-actin in the cytoplasm. Therefore, ALMS1-IT1, which is highly expressed in SLC7A11high cells, can be considered a promising therapeutic target for disulfidptosis-focused treatment strategies for cancer and other diseases.

To better serve the public, urban attractions must understand the public's likes and dislikes and continually adapt and optimize their service in response. However, traditional methods for gauging public opinion, such as questionnaires and individual interviews, cannot meet the need for large-scale, time-efficient, and high-precision public preference surveys: only large volumes of online tourist review data will suffice. This study takes Beijing and Shenzhen, the two top-tier cities in North and South China, as subjects to conduct an online review of visitor data for urban attractions in the two cities. Specifically, the influence of attraction features on public perception is quantitatively analyzed from three dimensions—spatial, temporal and resource type—which are combined with Natural Language Processing (NLP), Textual Data Mining, and Econometric analysis. The results show that the influence of four types of features—First impression, Economical, Service and Environmental features—on public perception remains largely consistent under different model conditions. However, different landscape types and attributes affect preferences in different ways. To be precise, water has radically different effects on public preferences in the north and south, with water features in urban attractions in the south contributing less to positive public perceptions. Meanwhile, water features significantly increase preferences for natural landscapes. Furthermore, public perceptions were found to be heavily influenced by public health emergencies (COVID-19). In the two cities studied, the proportion of positive reviews was higher after 2020 than before, as were the regression model indices. Drawing on these results, several suggestions are put forward for the optimization and adaptation of urban attractions.

Solid oxide fuel cells (SOFCs) are widely recognized as efficient energy sources that have the potential to shape the future of energy development. Among various types of SOFCs, the low-temperature operation of proton-conducting SOFCs (H–SOFCs) offers distinct advantages for wide commercialization compared to oxygen-ion conducting SOFCs (O–SOFCs). However, the commercialization of H–SOFCs is hindered by several challenges, including slow oxygen reduction kinetics and long-term instability of cathode materials. The electrochemical performance of the cathode system in H–SOFCs is limited by the poor proton conductivity of the cathode material and the scarcity of surface reaction sites. Additionally, the presence of undesirable phases induced by elements such as Cr and CO2 adversely affects the chemical stability and catalytic activity of the cathode. Thermal stress arising from the mismatch in coefficient of thermal expansion between the cathode and electrolyte further adds to the challenges. Therefore, this comprehensive review presents underlying mechanisms and potential solutions to overcome the challenges in H–SOFCs, leading to higher efficiency and wider commercialization of H–SOFCs.

Blockchain technology has been applied to the government’s supervision mechanism of the platform ecosystem, considering the inaccurate timing of the Chinese government’s supervision of the platform ecosystem. This study establishes a game model to study the government’s decision-making behavior, total social welfare, and participants in the platform ecosystem. Research suggests that although government regulation can improve overall social welfare, excessive regulation inhibits the development of platform enterprises. Hence, this study further analyzes the government’s regulatory interval facing the platform ecosystem, constructs an application scenario of blockchain that enables timely government regulation, and establishes the regulatory interval as the trigger mechanism of smart contracts in the blockchain. The smart contract can send an alarm, and the government can intervene in the platform ecosystem for supervision if the evaluation result is within the regulatory interval. The government will not intervene in the platform ecosystem for regulation (if the government is inside the platform ecosystem at this time, the government will withdraw; if it is not inside the platform ecosystem, it will remain unchanged) if the assessment result exceeds the regulatory range.

Abstract Background Castration is one of the most common surgical procedures performed in dogs. However, based on increasing evidence, male animals experience significant pain after castration. Astragalus polysaccharide (APS), one of the main bioactive components in A. membranaceus bunge, has been widely used as part of Fu‐Zheng therapy to enhance natural defense mechanisms. Introduction This study was carried out to determine the effects of supplementing different doses of Astragalus polysaccharide (APS; control, 0 mg/kg; APSL, 400 mg/kg; and APSH, 800 mg/kg) for 8 weeks on the haematology and serum chemistry profiles, immune response, and oxidative stress status in weanling beagle dogs. Methods After adapting to the experimental environment for 1 week, 18 male beagle dogs (Sichuan Institute of Musk Deer Breeding, China; average initial weight, 3.80 ± 0.43 g; age, 3‐month‐old) were randomly allotted to diets supplemented with three doses of APS (Control, 0 mg/kg; low, 400 mg/kg; and high, 800 mg/kg), referred to as control, APSL, and APSH, respectively; six dogs were assigned to each treatment. The dogs were fed the respective diets twice daily at 08:30 and 16:30 h in sufficient quantity to supply the metabolizable energy requirements for 8 weeks. On day 43 (19 weeks old), the dogs were castrated. On days 42 (prior to castration, 19 weeks old), 50 (day 7 after castration, 20 weeks old), and 57 (day 14 after castration, 21 weeks old) to measure the haematology, blood chemistry, immune response, and oxidative stress status parameters. Results Based on our findings, the APSH diet decreased weight gain and increased the feed to gain ratio in dogs (P < 0.05). At 14 days after castration, the wound was almost closed, slightly swollen, dry, and clean in the groups supplemented with APS. In addition, optimal APS supplementation was found to decrease erythrocyte count (RBC), haematocrit (HCT), alkaline phosphatase (ALP), alanine aminotransferase (ALT), C‐reactive protein (CRP), interleukin 1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α) levels, and cortisol and protein carbonyl (PC) concentrations (P < 0.05). Moreover, the mean corpuscular haemoglobin (MCH) and platelet (PLT) levels, interleukin 10 (IL‐10) and glutathione (GSH) content, and Cu/Zn superoxide dismutase (SOD1), catalase (CAT), and glutathione peroxidase (Se‐GPx) activities were increased in the APS supplemented groups (P < 0.05) Conclusion This study demonstrated that supplementing weanling beagle dogs with optimum APS could positively affect wound healing by improving their haematological profile (decreased RBC and HCT content, increased MCH and PLT levels), serum biochemical parameters (decreased ALP and ALT content), immune status (decreased CRP, IL‐1β, and TNF‐α levels; increased IL‐10 content), and antioxidant defense (decreased cortisol and PC content; increased GSH content, and SOD1, CAT, and Se‐GPx activities). However, the detailed mechanism whereby APS regulates these changes requires further investigation. In addition, the results of this study suggest that 400 mg/kg diet is the optimum APS dose for beagle dogs.

In order to study the interaction between betanin and whey protein isolate (WPI) and the effect of whey protein isolate on the thermal stability of betanin, WPI-Betanin complex was constructed by self-assembly method. UV-vis spectroscopy was used to verify the formation of complex. The mechanism of complex formation and the changes of protein structure were investigated by fluorescence spectroscopy and circular dichroism, and the complex was visualized by molecular simulation technology. The results showed that betanin and whey protein isolate formed a complex mainly through van der Waals force and hydrogen bond, and the number of binding sites was about 1. The formation of the complex resulted in increased turbidity and decreased surface hydrophobicity of the protein, and the quenching mechanism was static, with a quenching constant of 1.78×103 L/mol at room temperature. The interaction changed secondary structure contents and the microenvironment of tryptophan and tyrosine in whey protein isolate. Moreover, the thermal stability of betanin was improved by WPI. The retention rate of betanin increased from 6.17% to 27.26% after heating at 80 ℃ for 1 h. This study provides a theoretical basis for the application and development of functional protein pigment complex and the color protection of betanin.

Purpose To explore the effect of image-guided systems in phacoemulsification with intraocular lens (IOL) implantation.Methods We searched Pubmed, Embase and China National Knowledge Infrastructure (inception to January 20, 2021). Two researchers extracted data and assessed paper quality independently. Uncorrected distance visual acuity (UDVA) before and after surgery, best corrected visual acuity (BCVA) before and after surgery, preoperative cylinder, postoperative residual refractive cylinder, postoperative corneal cylinder, IOL misalignment, and intraocular pressure (IOP) were compared.Results We included 14 studies with 885 cataract eyes. All data were performed using Review Manager 5.3 (RevMan 5.3) (https://revman.cochrane.org/). Cases of all preoperative outcomes showed no significant difference between image-guided group and manual group. There was no significant difference in postoperative UDVA (Standard mean difference (SMD: −0.11, 95% CI: −0.32 to 0.11, I2 = 59%, p = 0.33)), BCVA (SMD: 0.03, 95% CI: −0.12 to 0.18, I2 = 36%, p = 0.72), corneal cylinder (Weighted mean difference WMD: 0.13, 95% CI: −0.06 to −0.32, I2 = 0%, p = 0.17), IOP (WMD: −0.37, 95% CI: −1.36 to −0.62, I2 = 9%, p = 0.46) between two groups. There was less residual refractive cylinder in image-guided group than in manual group (WMD: −0.20, 95% CI: −0.26 to −0.14, I2 = 59%, p＜0.00001). It is more accurate in IOL alignment when combined with image-guided systems (WMD: −1.20, 95% CI: −1.43 to −0.96, I2 = 14%, p

ABSTRACT Introduction: The totally thoracoscopic approach for mitral valve (MV) disease is a minimally invasive method. We investigated the procedure’s feasibility, safety and effectiveness when it was performed by an experienced operator. Methods: We retrospectively analysed 96 consecutive patients with MV disease treated between March 2016 and November 2019 by minimally invasive procedures. The procedures were performed on a femoral artery-vein bypass through two ports, including a main operation port and a thoracoscopic port. The clinical data of patients were collected, including preoperative cardiac function, operative data, postoperative complications, and follow-up. Results: A total of 96 patients (57 male patients; average age, 49.7±14.5 years; left ventricular ejection fraction, 65.6±7.7%) were enrolled in this study. No intraoperative conversion incision or death occurred. The cardiopulmonary bypass and aortic cross-clamp times were 163.8±50.6 minutes and 119.7±38.9 minutes, respectively. Postoperative chest tube drainage in the first 24 hours was 232.8±108.1 ml. The ventilation time and length of intensive care unit stay were 13.2±6.2 hours and 2.9±2.2 days, respectively. One patient died of disseminated intravascular coagulation and prosthesis thrombosis 3 days after the operation, fearing anticoagulant-related hemorrhage. The overall success rate of valve repair during 1-year follow-up was 97.9%. Conclusion: The totally thoracoscopic procedure on mitral valves by an experienced surgeon is technically feasible, safe, effective and worthy of widespread adoption in clinical practice.