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Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The 5-methylcytosine (m5C) RNA methyltransferase NSUN2 is involved in cell proliferation and metastasis and is upregulated in a variety of cancers. However, the biological function and regulatory mechanism of NSUN2-mediated m5C modification have not been well studied in HCC. Our results showed that NSUN2 is upregulated and associated with poor prognosis in HCC patients after hepatectomy. NSUN2 overexpression significantly promoted HCC growth and metastasis, whereas NSUN2 knockdown had the opposite effect. m5C RNA immunoprecipitation sequencing (m5C-RIP-Seq) revealed that m5C hypermethylation correlates with mRNA overexpression and that NSUN2-mediated m5C hypermethylation promotes metabolism in HCC patients. Mechanistically, our data revealed that PKM2, a terminal enzyme in the glycolytic pathway, is a downstream target of NSUN2-mediated m5C modification. Specifically, NSUN2 could stabilize PKM2 mRNA by increasing the m5C level of the m5C site C773 in the 3′-UTR of PKM2 mRNA. In addition, rescue assays revealed that NSUN2 promotes HCC glycolysis and progression by upregulating PKM2. In conclusion, this study revealed that NSUN2-mediated m5C modification promotes glycolysis and the progression of hepatocellular carcinoma by stabilizing PKM2 mRNA, and provides a potential prognostic factor and therapeutic target for HCC patients.

Abstract Background Family income to poverty ratio (PIR) may have independent effects on diet and lifestyle factors and the development of prediabetes and diabetes, as well as on mortality. It is unclear how the protective effect of a healthy lifestyle against death differs between individuals with different glucose metabolic profiles and whether PIR mediates this effect. This study aimed to explore whether healthy lifestyle and family PIR reduced the risk of all-cause mortality in participants with different metabolic status and the mediating role of PIR. Subjects and methods In total, 21,411 participants from the 2001–2018 National Health and Nutrition Examination Survey (NHANES) and follow-up until 2019 were included. The weighted healthy lifestyle score was constructed based on smoking, alcohol consumption, physical activity, diet (HEI-2015), and body mass index. Generalized linear regression models were used to analyze the association between healthy lifestyle, PIR, and all-cause mortality. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals, Kaplan-Meier survival curve was used to analyze the all-cause mortality associated with PIR and lifestyle. Furthermore, the mediation proportion of PIR in all-cause mortality attributed to healthy lifestyle was analyzed among participants with normal glucose regulation, prediabetes, or diabetes after multivariable adjustment. Results There were significant differences in healthy lifestyle and PIR among people with normal glucose regulation, prediabetes and diabetes. During a mean follow-up of 92 months, participants with prediabetes or diabetes were also likely to have a higher mortality rate, respectively 583 (8.3%) and 263 (12.7%). More than 2 healthy lifestyles were associated with 42% (HR, 0.58; 95% CI, 0.35–0.95) to 76% (HR, 0.24; 95% CI, 0.12–0.44) reduced risk of all-cause mortality among participants with prediabetes, but among those with diabetes, who had ≥ 4 healthy lifestyles were associated with 72% reduced risk of all-cause mortality (HR, 0.28; 95% CI, 0.09–0.90). The middle and high PIR were associated with at least a 37% (HR, 0.63; 95% CI, 0.47–0.83) to 65% (HR, 0.35; 95% CI, 0.18–0.68) lower risk of all-cause mortality in participants with prediabetes and diabetes. Furthermore, PIR mediated 5.81-14.93% and 7.72-10.10% of the association between healthy lifestyle and all-cause mortality among normal glucose regulation and prediabetic participants, respectively. However, the mediating effect of PIR was not significant among diabetic participants. Conclusions Our findings highlight the importance of promoting adherence to a healthy lifestyle and improving PIR in prediabetic patients to reduce the risk of all-cause mortality, and the protective effect is more significant with more healthy lifestyles and higher PIR. This study can help clinicians and health systems develop more targeted treatments for people with different metabolic levels.

Highlights The succinonitrile-based deep eutectic electrolyte, characterized by strong ion–dipole interactions, can establish an anion-rich Li+ solvation structure while exhibiting high ionic conductivity and Li+ transference number. Precisely regulating multiple ion–ion, ion–dipole, and dipole–dipole interactions facilitates the transition of the Li+ solvation structure from solvent dominance to anion dominance. Optical microscopy and Micro-CT analysis can demonstrate that the anion-derived solid electrolyte interphase effectively mitigates the irreversible volume expansion of silicon oxide.

Nonalcoholic fatty liver disease (NAFLD) is an escalating global health issue, leading to liver fat accumulation, inflammation, fibrosis, and potential liver failure. In our preliminary network pharmacological study, it was hypothesized that Pedalitin (PED), a flavonoid found in black sesame plants, might exhibit protective effects against NAFLD. However, the effects and mechanisms of PED underlying its action on NAFLD are not yet fully understood. This study aimed to explore the potential effects and mechanisms of PED on NAFLD using a combination of network pharmacology, molecular docking, and the LO2 cell model. Potential targets for PED and NAFLD were predicted through public databases. Protein-protein interaction (PPI) networks were constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Molecular docking was used to predict the target genes that could bind to PED. In vitro experiments using the LO2 cell model indicated that PED significantly reduced TG level (p ​

Abstract The prevalence of digestive system tumours (DST) poses a significant challenge in the global crusade against cancer. These neoplasms constitute 20% of all documented cancer diagnoses and contribute to 22.5% of cancer‐related fatalities. The accurate diagnosis of DST is paramount for vigilant patient monitoring and the judicious selection of optimal treatments. Addressing this challenge, the authors introduce a novel methodology, denominated as the Multi‐omics Graph Transformer Convolutional Network (MGTCN). This innovative approach aims to discern various DST tumour types and proficiently discern between early‐late stage tumours, ensuring a high degree of accuracy. The MGTCN model incorporates the Graph Transformer Layer framework to meticulously transform the multi‐omics adjacency matrix, thereby illuminating potential associations among diverse samples. A rigorous experimental evaluation was undertaken on the DST dataset from The Cancer Genome Atlas to scrutinise the efficacy of the MGTCN model. The outcomes unequivocally underscore the efficiency and precision of MGTCN in diagnosing diverse DST tumour types and successfully discriminating between early‐late stage DST cases. The source code for this groundbreaking study is readily accessible for download at https://github.com/bigone1/MGTCN.

Background In this study, effective antigens of mRNA vaccine were excavated from the perspective of ICD, and ICD subtypes of PRAD were further distinguished to establish an ICD landscape, thereby determining suitable vaccine recipients.Research design and methods TCGA and MSKCC databases were applied to acquire RNA-seq data and corresponding clinical data of 554 and 131 patients, respectively. GEPIA was employed to measure prognostic indices. Then, a comparison of genetic alterations was performed utilizing cBioPortal, and correlation of identified ICD antigens with immune infiltrating cells was analyzed employing TIMER. Moreover, ICD subtypes were identified by means of consensus cluster, and ICD landscape of PRAD was depicted utilizing graph learning-based dimensional reduction.Results In total, 4 PRAD antigens were identified in PRAD, including FUS, LMNB2, RNPC3, and ZNF700, which had association with adverse prognosis and infiltration of APCs. PRAD patients were classified as two ICD subtypes based on their differences in molecular, cellular, and clinical features. Furthermore, ICD modulators and immune checkpoints were also differentially expressed between two ICD subtype tumors. Finally, the ICD landscape of PRAD showed substantial heterogeneity among individual patients.Conclusions In summary, the research may provide a theoretical foundation for developing mRNA vaccine against PRAD as well as determining appropriate vaccine recipients.

Abstract Laboratory testing with adjustable loading amplitudes and durations remains the primary method for assessment of the safety of explosives under either launch or penetration environment. In this study, a novel impact testing laboratory equipment with loading amplitudes ranging from 0.1 to 1.0 GPa and pulse durations ranging from 1 to 8 ms is established. It was used to investigate the safety of a 2,4-dinitroanisole (DNAN)-based melt-cast explosive subjected to impact loading in either launch or penetration scenarios. The explosive’s response to the impact loading depends not only on the loading characteristics (peak pressure and maximum rate of pressure rise) but also on the confinements of the explosives. The ignition events of the explosives exhibited some randomness. A logistic regression analysis method was utilized to analyze such ignition events. This method can predict the ignition events of the DNAN-based melt-cast explosive with a high accuracy, which demonstrates the effectiveness of the method. The effect of the confinements of the explosives on the accuracy of this method was also investigated.

Abstract In recent research on building materials, researchers have increasingly focused on replacing cement with agricultural waste. This approach offers significant advantages in terms of reducing global CO2 emissions and promoting the sustainability of building materials. In this paper, the use of the agricultural waste walnut shell ash (WSA) to partially replace cement in sustainable green mortars is explored. Specifically, equal amounts of WSA (5%, 10% and 15%) were used to replace cement. To offset the reduction in strength caused by the partial replacement of cement with WSA, basalt fibers were added to the mortar mixture. The effect of these fibers on the mechanical properties of the WSA-reinforced mortar was examined in compression tests, split tensile tests, and flexural fatigue cycle tests. In the flexural fatigue tests, the parameter and length of basalt fibers were varied and different stress levels (0.85, 0.8 and 0.75) were applied. The fatigue equations were developed using the Weibull model and p–s–n curves with a survival probability of 0.5 were derived. The results showed that the compressive strength and split tensile strength of the specimens increased with the addition of basalt fibers, with maximum values of 34.7 MPa and 3.8 MPa, respectively, and maximum increases of 8.78% and 21.95%, respectively. In addition, the average fatigue life of WSA mortar was 247,541 cycles, which increased by 139.26% when the stress level was 0.75, fiber length was 9 mm, and dosage was 0.3%. The linear regression fitting showed good correlation and provided valuable insights for practical engineering applications.

Abstract The study investigates the global impact of land property rights on land use efficiency (LUE), as measured by the key indicator for United Nations Sustainable Development Goal 11.3.1, namely Land Consumption Rate to Population Growth Rate. By utilizing human-land change data from 165 countries spanning the period between 1990 and 2020, we have developed a fixed effects model and employed legal origins as an instrumental variable to examine the influence of land property rights security on LUE. Our findings demonstrate that the security of land property rights significantly influences LUE, with common law countries exhibiting higher levels of LUE compared to civil law countries while controlling for other variables. Stability in property rights encourages long-term investments in infrastructure and sustainable land management practices, thereby enhancing land productivity and mitigating urban sprawl. Furthermore, safeguarding property rights limits governments’ power to expropriate lands, facilitating rational and efficient land transactions that contribute towards achieving Sustainable Development Goals.

Abstract Integrated photon-pair sources are crucial for scalable photonic quantum systems. Thin-film lithium niobate is a promising platform for on-chip photon-pair generation through spontaneous parametric down-conversion (SPDC). However, the device implementation faces practical challenges. Periodically poled lithium niobate (PPLN), despite enabling flexible quasi-phase matching, suffers from poor fabrication reliability and device repeatability, while conventional modal phase matching (MPM) methods yield limited efficiencies due to inadequate mode overlaps. Here, we introduce a layer-poled lithium niobate (LPLN) nanophotonic waveguide for efficient photon-pair generation. It leverages layer-wise polarity inversion through electrical poling to break spatial symmetry and significantly enhance nonlinear interactions for MPM, achieving a notable normalized second-harmonic generation (SHG) conversion efficiency of 4615% W−1cm−2. Through a cascaded SHG and SPDC process, we demonstrate photon-pair generation with a normalized brightness of 3.1 × 106 Hz nm−1 mW−2 in a 3.3 mm long LPLN waveguide, surpassing existing on-chip sources under similar operating configurations. Crucially, our LPLN waveguides offer enhanced fabrication reliability and reduced sensitivity to geometric variations and temperature fluctuations compared to PPLN devices. We expect LPLN to become a promising solution for on-chip nonlinear wavelength conversion and non-classical light generation, with immediate applications in quantum communication, networking, and on-chip photonic quantum information processing.

Abstract Background Abdominal obesity, a significant risk factor for the progression of diabetic retinopathy (DR), may lead to improved visual outcomes through early assessment. This study aims to evaluate any potential associations between DR and novel lipid metabolism markers, including the Atherogenic Index of Plasma (AIP), Visceral Adiposity Index (VAI), and Lipid Accumulation Product (LAP). Methods This study aimed to elucidate the association between various lipid markers and DR by screening the National Health and Nutrition Examination Survey (NHANES) database in the United States from 2005 to 2008. To examine the correlation, multifactor logistic regression analysis, subgroup analysis, threshold effect analysis, interaction test, and smooth curve fitting were used. Results Among the 2591 participants included, the incidence of DR was 13.6% and the mean age was 59.55 ± 12.26 years. After adjusting for important confounding covariates, logistic regression studies suggested a possible positive association between LAP, VAI, AIP, and DR occurrence (odds ratio [OR] = 1.004; 95% confidence interval [CI]: 1.002, 1.006; P 0.05 for all interactions). Conclusion Studies have shown that elevated levels of LAP, VAI, and AIP increase the likelihood of DR, suggesting that they have the potential to be predictive markers of DR, emphasizing their potential utility in risk assessment and prevention strategies, and advocating for early intervention to mitigate the likelihood of DR.

Abstract Bitter gourd wilt, a severe vascular disease triggered by the soilborne pathogen Fusarium oxysporum f. sp. momordicae (FOM), markedly constrains bitter gourd yield. In this study, a novel strain BF19 of Brevibacillus brevis was isolated and identified, exhibiting strong antimicrobial activity against FOM through in vivo and in vitro experiments. To comprehensively assess the biocontrol potential of strain BF19, we conducted phenotypic, phylogenetic, and comparative genomics analyses. Phenotypic analysis revealed that BF19 exhibited 53.33% biocontrol efficacy and significantly increased the average plant height, root fresh weight, and dry weight. Whole-genome sequencing and comparative genomic analysis revealed numerous potential genes associated with biocontrol mechanisms in BF19. Importantly, the integration of metabolic cluster prediction with liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) revealed the presence of a macrobrevin antibiotic, a product of polyketide synthases (PKSs), predominantly in BF19 fermentation products. The effectiveness of the Br. brevis strain BF19 and its crude extract against bitter gourd wilt has also been confirmed. This study provides a genetic framework for future investigations on PKSs and establishes a scientific basis for optimizing field applications of microbial biopesticides derived from Br. brevis BF19.

Abstract Background X-linked recessive chondrodysplasia punctata 1 (CDPX1) is a rare congenital skeletal dysplasia characterized by stippled epiphyses, nasal hypoplasia, and brachytelephalangy. ARSL (formerly known as ARSE), a member of the sulfatase gene family located on Xp22.3, has been identified as the causative gene for CDPX1. The high clinical and genetic heterogeneity of CDPX1 presents a challenge to prenatal diagnosis. Case presentation A G1P0 woman in her 30s with an unremarkable prenatal course presented in the second trimester. Maternal diseases, tobacco, alcohol, and drug history during pregnancy were denied. Obstetrical ultrasound examination revealed a flattened nose and a flattened midface with echogenic alterations of lumbar spinous process in the fetus. Amniocentesis was performed for genetic testing. A normal karyotype and a negative result of CNV-seq were obtained. However, Whole exome sequencing (WES) in trios revealed a hemizygous ARSL variant [NM_000047.3:c.1108del p.(Trp370Glyfs*35)] in the fetus, which was maternally inherited as confirmed by Sanger sequencing. This variant was absent from the genomAD and HGMD databases. According to the ACMG guidelines, this variant was interpreted as likely pathogenic (PVS1 + PM2_Supporting). The couple decided to terminate the pregnancy. After induction of labour, a severe nasal hypoplasia was noted; and brachytelephalangy was not remarkable. Postmortem digital X-ray imaging revealed symmetrical stippled epiphyses of the vertebrae in all spine regions and enlargement of spinous process of L1-L4 vertebrae. Conclusion A novel frameshift deletion variant of ARSL and the associated fetal phenotype have been identified. This study provides useful information for prenatal diagnosis and genetic counseling of CDPX1.

Summary: Purpose: To evaluate the impacts of tele-exercise intervention with cancer patients’ quality of life, taking into account the influence of the duration of tele-exercise intervention, type of intervention, and gender of cancer patients on quality of life. Methods: The PubMed (MEDLINE), Embase, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and PsycINFO databases were searched from inception to August 21, 2023. The Cochrane Collaboration's risk of bias tool 2 was utilized to estimate the risk of bias, and the Grading of Recommendations, Assessment. For statistical analyses, R Studio was employed. Results: This meta-analysis contained eight trials. When compared to controls, tele-exercise interventions (SMD = 0.41, 95% CI: 0.12 to 0.70, p

Abstract Background Neoadjuvant chemotherapy may be considered for patients with ovarian cancer (OC) whose tumors are deemed unlikely to be completely cytoreduced to no gross residual disease (R0) or who are poor surgical candidates. This Ib/II study was designed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin as neoadjuvant chemotherapy for stages III–IV, unresectable OC. Methods Eligible patients with stage III–IV, unresectable OC were enrolled in this phase Ib/II study. All patients received neoadjuvant nab-paclitaxel (260 mg/m2, day 1, every 3 weeks) plus carboplatin (AUC 5, day 1, every 3 weeks) for 3 cycles before surgery, followed by 3–6 cycles of adjuvant chemotherapy. The phase Ib primary endpoint was safety; the phase II primary endpoint was the R0 resection rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety (for all populations). Results Sixty-two patients were enrolled and were given neoadjuvant therapy treated between October 2019 and December 2020, of whom 9 were in the phase Ib portion and 53 in the phase II portion. A total of 53 patients underwent surgery with an R0 resection rate of 73.6% (95% CI, 59.7–84.7%). With a median follow-up of 17.5 (range 0.7–36.7) months, for all patients, the best ORR was 83.9% (95% CI, 71.7–92.4%) with 47 partial responses, the median PFS was 18.6 (95% CI, 13.8–23.3%) months, and median OS was not reached. During the neoadjuvant chemotherapy, treatment-related adverse events (TRAEs) of any grade occurred in 91.9% (57/62) of all patients. The most common hematologic TRAEs were neutropenia (55/62, 88.7%), and non-hematologic toxicity was alopecia (36/62, 58.1%). Forty-nine patients (79.0%) experienced at least one grade 3–4 TRAEs, with the most common was neutropenia (44/62, 71.0%). Besides, delays in neoadjuvant chemotherapy and surgery due to AEs were observed in 9 (1 in phase Ib; 8 in phase II) and 7 (phase II) patients, respectively. Conclusions The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant chemotherapy nab-paclitaxel plus carboplatin in stage III-IV, unresectable OC. In addition, AEs resulting in chemotherapy and surgery delays should be cautiously considered in this clinical setting. Trial registration ClinicalTrials.gov, ChiCTR1900026893. Registered at 25 October 2019.

Abstract Currently, the global prevalence of myopia is high and on the rise, seriously affecting the health of students. Studies have suggested that dietary factors may be associated with the occurrence and development of myopia, but the results are inconsistent. This survey aims to analyze the correlation between dietary factors and myopia while controlling for more confounding factors. A multi-stage stratified cluster sampling method was performed to select 10,619 primary and secondary school students in Shenyang for visual examination, and questionnaires were administered to 6974 of them. Logistic regression was performed with myopia as the dependent variable and the variables with p

Abstract Purpose This study utilizes a meta-analytic approach to investigate the effects of cryoablation and robot-assisted partial nephrectomy on perioperative outcomes, postoperative renal function, and oncological results in patients. Methods This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Four electronic databases (PubMed, Embase, Web of Science, and the Cochrane Library database) were systematically searched to identify relevant studies published in English up to November 2023. The primary outcomes were perioperative results, complications, postoperative renal function and oncologic outcomes. Review Manager 5.4 was used for this analysis. Results This study included a total of 10 studies comprising 2,011 patients. Compared to RAPN (Robot-Assisted Partial Nephrectomy), the CA (Cryoablation) group had a shorter hospital stay [MD -1.76 days; 95% CI -3.12 to -0.41; p = 0.01], less blood loss [MD -104.60 ml; 95% CI -152.58 to -56.62; p

Abstract Background Bisphosphonates (BPs) are widely used to inhibit excessive osteoclast activity. However, the potential to compromise bone defect healing has limited their broader application. To better understand the influence of BPs on bone regeneration, we established a bone grafting model with Zoledronate administration, aiming to deepen the understanding of bone remodeling and mineralization processes. Methods A bone grafting model was established in the distal femurs of male Sprague–Dawley rats. The experimental group received systemic administration of Zoledronate (ZOL, 0.2 mg/kg, administered twice). Histological analysis and immunohistochemistry (IHC) were employed to assess osteoblastic and macrophage activity, tartrate-resistant acid phosphatase (TRAP) staining was used to evaluate osteoclastogenesis. Mineralization was assessed through Micro-CT analysis, Raman spectroscopy, and back-scatter scanning electron microscopy (BSE-SEM). Additionally, the in vitro effects of ZOL on osteoblast and osteoclast activity were investigated to further elucidate its impact on bone regeneration. Results In vivo, the ZOL group showed increased bone mass, as observed in histological and radiological assessments. However, Micro-CT, Raman spectroscopy, and BSE-SEM detection revealed lower mineralization levels in ZOL group's regenerated bone. Acid-etched SEM analysis showed abnormal osteocyte characteristics in ZOL-group’s regenerated bone. Simultaneously, elevated osteopontin (OPN), F4/80 expression along with reduced TRAP expressing was found in the grafting region of ZOL group. In vitro, ZOL did not negatively impact osteogenetic activity (ALP, BMP4, OCN expression) at the tested concentrations (0.02–0.5 g/ml) but significantly impaired mineralization and inhibited osteoclast formation, even at the lowest concentration. Conclusions This study highlights a less recognized negative effect of ZOL on bone mineralization during bone regeneration. More research is needed to elucidate the underlying mechanism.

Summary: Background: To date, comprehensive data on the distribution of chronic kidney disease (CKD), the most prevalent comorbidity in diabetes, among Chinese adults with diabetes is lacking. Additionally, research gaps exist in understanding the association between CKD and cardiovascular health (CVH), an integrated indicator of lifestyle and metabolic control, within a nationwide sample of Chinese adults with diabetes. Methods: A nationally community-based cross-sectional survey was conducted in 2018–2020. 58,560 residents diagnosed with diabetes aged 18–74 years nationwide were invited to participate, and 52,000 participants with complete CKD data were included in this study. CKD was identified by the presence of albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g) and/or decreased estimated glomerular filtration rate (eGFR,

A database of 115 bio-actives from seven subclasses, including information on retention time, parent ion m/z, fragment m/z, and isotopic fit, was established, and an instrumental method for simultaneous analysis of these targets was optimised. An ultrasound-assisted preparation method at 50 °C for 50 min with a 1:60 solid-liquid ratio, water as the solvent was proposed for the screening of unknown components and the antioxidant analysis in saffron. The self-built database and untargeted analysis identified 32 and 103 bio-actives in saffron, respectively. The comparative analysis revealed that the antioxidant capacity of saffron petals was superior to that of stigmas. Correlation and multivariate statistical analyses indicated that terpenoids may be the main active substances in stigmas, while flavonoids and carboxylic acid derivatives play a pivotal role in conferring antioxidant activity to de-stigmatised saffron. The method serves as an ideal tool for mining the functional components of saffron and other agricultural products.

ABSTRACT The relationship between hemodynamic parameters and body mass index (BMI) in the context of blood pressure regulation in hypertension is unclear. Here, we analyzed data from 1368 uncontrolled hypertensive patients, including key hemodynamic indicators such as heart rate (HR), cardiac index (CI), arterial stiffness (AS), systemic vascular resistance index (SVRI), and thoracic blood ratio (TBR). In this cohort, the average BMI across all hypertension patients was 26.859 ± 3.897 (kg/m2), with obese patients (BMI ≥ 28 kg/m2) averaging 31.01 ± 2.87 kg/m2 and non‐obese (BMI

Myasthenia gravis (MG) is an autoimmune disorder within the spectrum of neuromuscular rare diseases, characterized by fluctuating muscle weakness. This report presents a case of a middle-aged woman with a chronic onset of asymmetric upper limb weakness accompanied by difficulty in finger extension, without ptosis or fluctuation for 4 years. The patient was finally diagnosed with MG by a significant decrement of Compound Muscle Action Potential in repetitive nerve stimuli, positive anti-acetylcholine receptor antibodies as well as the presence of a mass located in the anterior mediastinum. With subsequent immunotherapies for one month, the patient exhibited marked enhancement in muscle strength, followed by an uneventful thymectomy. After two months, the patient’s symptoms were fully alleviated, as evidenced by the reduction in Quantitative MG Score from 9 to 4 points, Myasthenia Gravis Composite Score from 6 to 1 points, Myasthenia Gravis Activities of Daily Living Score from 4 to 1 points, and Myasthenia Gravis Quality of Life-15 score from 14 to 8 points respectively. This case highlights the importance of differentiating autoimmune disorders from hereditary neuromuscular diseases and initiating timely treatment.

IntroductionCataracts are associated with a decline in both cognitive and visual functions. This study examines postoperative changes in cognitive and visual functions in patients with age-related cataracts, focusing on the differential effects of unilateral and bilateral cataract surgeries on these functions. Additionally, the study evaluates changes in cognitive function following cataract surgery in individuals with mild cognitive impairment (MCI).MethodsA cohort of patients (n = 35, 59 eyes) aged 60 years and older (69.9 ± 7.0 years) with age-related cataracts who underwent unilateral or bilateral cataract surgery between May and June 2024 was selected. Cognitive and visual functions were evaluated preoperatively and at 1 week, 1 month, and 3 months postoperatively. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA). Visual function was assessed using a binocular visual function testing system based on virtual reality (VR) technology, which evaluated low spatial frequency suppression, simultaneous vision, stereopsis, and perceptual eye position under 3D viewing conditions without glasses. Based on preoperative MoCA scores, patients were classified into cognitively normal and mild cognitive impairment (MCI) groups.ResultsPatients with age-related cataracts demonstrated significant improvements in both cognitive and visual functions at 1 week, 1 month, and 3 months postoperatively, compared to preoperative assessments (p

Summary: Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with impaired regenerative capacity and poor postoperative prognosis following hepatectomy. Previous research has highlighted the importance of the gut–liver axis in the physiological and pathological processes of the liver. However, the contribution of gut bacteria to the regeneration of livers with MAFLD and its metabolic regulatory mechanisms remain elusive. Methods: Partial hepatectomy (PHx) was performed on C57Bl/6J mice fed with high-fat diet (HFD) for 12 weeks. Pathological examination, immunohistochemistry, and qRT-PCR analysis were performed to assess the severity of steatosis and proliferative potential. The gut microbiome was examined by 16S rRNA gene sequencing and shotgun metagenomics, whereas liver metabolomics was analysed via untargeted and targeted metabolomics using liquid chromatography-tandem mass spectrometry (LC-MS). Findings: HFD-induced hepatic steatosis in mice led to impaired liver regeneration following PHx. The gut microbiota and liver metabolites were altered along with the liver regeneration process. Longitudinal time-series analysis revealed dynamic alterations in these data, whereas correlation analysis screened out bacterial candidates that potentially influence liver regeneration in MAFLD by modulating metabolic pathways. Among these bacteria, the dominant bacterium Akkermansia was selected for subsequent investigation. MAFLD mice gavaged with Akkermansia muciniphila (A. muciniphila) exhibited reduced liver lipid accumulation and accelerated liver regeneration, possibly through the regulation of the tricarboxylic acid (TCA) cycle. Interpretation: These data demonstrated the interplay between the gut microbiome, liver metabolomics, and liver regeneration in mice with MAFLD. A. muciniphila has the potential to serve as a clinical intervention agent to accelerate postoperative recovery in MAFLD. Funding: This work was supported by the Research Project of Jinan Microecological Biomedicine Shandong Laboratory [JNL-2022008B]; the Zhejiang Provincial Natural Science Foundation of China [LZ21H180001]; the Fundamental Research Funds for the Central Universities [No. 2022ZFJH003].

The current case report presents a rare occurrence of cerebral infarction with bilateral sudden deafness as the primary symptom. The patient was a 59-year-old man with hypertension who tested positive for new coronary antibodies and had a long history of smoking and alcohol consumption. Despite receiving treatment for sudden deafness, the patient’s condition rapidly deteriorated and he was diagnosed with basilar artery occlusion and stenosis. The patient died 5 days after mechanical recanalization of the artery. Sudden binaural deafness is a rare clinical condition that may be a prodromal symptom of brainstem infarction. Early diagnosis and prompt treatment are essential for reducing mortality and disability.

BackgroundSqualene epoxidase (SQLE) is a key enzyme in cholesterol biosynthesis and has been shown to negatively affect tumor immunity and is associated with poor outcomes of immunotherapy in various cancers. While most research in this area has focused on the impact of cholesterol on immune functions, the influence of SQLE-mediated squalene metabolism within the tumor immune microenvironment (TIME) remains unexplored.MethodsWe established an immune-competent mouse model (C57BL/6) bearing mouse pancreatic cancer xenografts (KPC cells) with or without stable SQLE-knockdown (SQLE-KD) to evaluate the impact of SQLE-mediated metabolism on pancreatic cancer growth and immune functions. The effect of squalene on tumor growth and immune cells was tested by direct administration of squalene to C57BL/6 mice bearing KPC tumors. Flow cytometry analysis and immunohistochemical (IHC) staining of immune cells from the tumor tissues were performed to evaluate changes in immune function. We also employed RNA-sequencing to analyze the gene expression profiles in pancreatic cancer cells (PANC-1) treated with or without squalene. RT-PCR and Western blot analyses were used to investigate the relevant molecular mechanisms.ResultsWe show that SQLE is significantly overexpressed in pancreatic cancer, and abrogation of SQLE results in a significant increase in squalene accumulation within tumor cells. The elevated squalene inhibits CXCL1 transcription through its impact on the NF-κB pathway via p65, and thus reduces the recruitment of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) into the tumor microenvironment. Silencing of SQLE also leads to an increased proportion of CD8+ T cells in the tumor tissues and suppresses tumor growth in vivo. Importantly, direct administration of squalene, the metabolic substrate of SQLE, to immune-competent mice bearing KPC pancreatic cancer tumors causes a substantial decrease in CD206+ TAMs and MDSCs, thus releasing immune suppression and inhibiting tumor growth.ConclusionOur study shows that squalene is an important immune-modulating metabolite that inhibits the infiltration of immune-suppressive cells in TIME, and that SQLE exerts its tumor immune evasion effect by metabolic removal of squalene. Thus, SQLE-mediated squalene metabolic pathway could be a potential target to enhance antitumor immunity in pancreatic cancer.

BackgroundCoronary Artery Disease (CAD) is a leading cause of mortality, with an increasing number of patients affected by coronary artery stenosis each year. Coronary angiography (CAG) is commonly employed as the definitive diagnostic tool for identifying coronary artery stenosis. Physician Visual Assessment (PVA) is often used as the primary method to determine the need for further intervention, but its subjective nature poses challenges. This study sought to evaluate the differences of severity of diffuse and focal coronary stenosis between PVA and Quantitative Coronary Angiography (QCA).Methods293 patients with coronary artery disease (334 coronary lesions) underwent CAG and fractional flow reserve (FFR). PVA and QCA was used to quantify diameter stenosis (DS). DS ≥50% was defined as obstructive. FFR ≤0.8 was defined as myocardial ischemia.ResultsThe mean ± SD age of all patients was 66 ± 9 years. ΔDS between PVA and QCA was higher in diffuse lesions (16.45 ± 7.37%) than in focal lesions (14.39 ± 7.83%) (P = 0.04). DSPVA and DSQCA had linear negative correlation (rPVA = −0.3182, rQCA = −0.4054) with FFR in diffuse, while in focal, DSPVA and DSQCA had an even stronger linear negative correlation (rPVA = −0.4090, rQCA = −0.4861) with FFR. ROC analysis demonstrated that DSQCA had better discrimination capability for myocardial ischemia (FFR ≤ 0.80) than DSPVA in different of length stenosis.ConclusionsPVA was more likely to overestimate diameter stenosis in coronary arteries than QCA, and the severity of diffuse stenosis was more likely to be overestimated than that of focal stenosis.

IntroductionHyperuricemia (HUA) is a metabolic syndrome caused by purine metabolism disorders. Zanthoxyli Pericarpium (ZP) is a medicinal and food homologous plant, and its ripe peel is used to treat diseases and as a spice for cooking. Some studies have shown that ZP can inhibit the formation of xanthine oxidase and reduce the production of uric acid.MethodsThrough network pharmacology, ZP’s potential targets and mechanisms for HUA treatment were identified. Databases like TCMSP, UniProt, and Swiss Target Prediction were utilized for ZP’s active ingredients and targets. HUA-related targets were filtered using GeneCards, Drugbank, and Open Targets. Core targets for ZP’s HUA treatment were mapped in a PPI network and analyzed with Cytoscape. GO and KEGG pathway enrichments were conducted on intersected targets via DAVID. Molecular docking and virtual screening were performed to find optimal binding pockets, and ADMET screening assessed compound safety. Molecular dynamics simulations confirmed compound stability in binding sites.ResultsWe identified 81 ZP active ingredient targets, 140 HUA-related targets, and 6 drug targets, with xanthine dehydrogenase (XDH) as the top core target. Molecular docking revealed ZP’s active ingredients had strong binding to XDH. Virtual screening via Protein plus identified 48 compounds near the optimal binding pocket, with 2’-methylacetophenone, ledol, beta-sitosterol, and ethyl geranate as the most promising. Molecular dynamics simulations confirmed binding stability, suggesting ZP’s potential in HUA prevention and the need for further experimental validation.ConclusionOur study provides foundations for exploring the mechanism of the lowering of uric acid by ZP and developing new products of ZP. The role of ZP in the diet may provide a new dietary strategy for the prevention of HUA, and more experimental studies are needed to confirm our results in the future.

Coronavirus disease 2019 (COVID-19) is caused by the highly contagious virus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has caused hundreds of thousands of deaths worldwide. Finding more effective treatments has always been the focus of everyone’s attention. The study found that compared with western drugs, natural products have higher bioavailability and fewer side effects, which provides a good prospect for the development of natural product-based antiviral drugs against SARS-CoV-2. The role of nutritional interventions in disease management is receiving increasing attention. Therefore, we conducted a thorough analysis of the latest literature on the effects of natural products and nutrients on COVID-19, based on reports from both domestic and international sources, to elucidate their positive role in maintaining human health. In conclusion, this paper emphasizes the potential role of natural products and nutritional interventions in the treatment of SARS-CoV-2, and explores more efficient and safer SARS-CoV-2 response strategies.

Studies on the relationship between serum sex hormone-binding globulin (SHBG) levels and chronic kidney disease (CKD) remain limited and inconclusive. Therefore, this study aims to evaluate the effects of SHBG on CKD in a nationally representative population. We included a total of 7713 adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Multivariate logistic regression models were utilized to evaluate the association between SHBG levels and CKD, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Additionally, we employed a restricted cubic-spline regression model to explore potential dose-response associations. Among the participants, 4030 (52.2%) were women, and CKD was observed in 13.50% (1043/7713). After adjusting for various variables, SHBG levels were found to be associated with the risk of CKD (OR: 1.24; 95% CI: 1.11–1.38), indicating a 24% higher risk of CKD for SHBG levels (log2-transformed). A comparison between the highest quartile (Q4) and the lowest quartile (Q1) of SHBG levels revealed an OR of 1.51 (95% CI: 1.17–1.95) for CKD prevalence. Notably, while the association between SHBG and the risk of CKD disappeared when SHBG levels were

Road detection in remote sensing (RS) images plays a critical role in applications ranging from urban planning to autonomous navigation systems. However, accurate road extraction remains a challenging task due to the presence of textual-similar objects that can be visually confused with roads, and shadows that can obscure road features. For this regard, we present a novel end-to-end network that leverages multi-feature fusion and multi-attention. Multi-level dual residual blocks are introduced to capture multi-scale and multi-level road features. A channel attention feature fusion module fuses road features from the decoder while suppressing coarse-grain noises. Moreover, a difference channel feature fusion module filters out the interfering texture-similar features and irrelevant background features. Subsequently, a spatial channel feature enhancement module is designed to identify the mis-segmented regions and reclassify these pixels. We conducted extensive experiments on diverse datasets, demonstrating the effectiveness of our approach in improving road detection accuracy, especially in areas with shadows and textual-similar objects. The results indicate that our approach outperforms state-of-the-art methods in handling textual-similar objects and shadow-occluded roads, making it a valuable contribution to the field of road extraction in remote sensing images.

Abstract There is a relative scarcity of large-scale population studies investigating the relationship between the insulin resistance index of homeostasis model assessment (HOMA-IR) and vascular damage. Therefore, we assessed the association between HOMA-IR and vascular damage in adults aged 18 years and older in China. A total of 17,985 research subjects were included. Vascular damage markers and relevant laboratory tests were measured. HOMA-IR was calculated as (fasting insulin * fasting blood glucose)/22.5. Vascular damage included arteriosclerosis (ba-PWV > 1800 cm/s), peripheral artery disease (ABI 30 mg/g). The relationship between HOMA-IR and vascular damage was analyzed using the RCS. The restricted cubic spline (RCS) analysis suggested that HOMA-IR was nonlinearly associated with arteriosclerosis (P for no-liner

Abstract Nanocrystalline metallic materials have the merit of high strength but usually suffer from poor ductility and rapid grain coarsening, limiting their practical application. Here, we introduce a core-shell nanostructure in a multicomponent alloy to address these challenges simultaneously, achieving a high tensile strength of 2.65 GPa, a large uniform elongation of 17%, and a high thermal stability of 1173 K. Our strategy relies on an ordered superlattice structure that excels in dislocation accumulation, encased by a ≈3 nm disordered face-centered-cubic nanolayer acting as dislocation sources. The ordered superlattice with high anti-phase boundary energy retards dislocation motions, promoting their interaction and storage within the nanograins. The disordered interfacial nanolayer promotes dislocation emission and effectively accommodates the plastic strain at grain boundaries, preventing intergranular cracking. Consequently, the order-disorder core-shell nanostructure exhibits enhanced work-hardening capability and large ductility. Moreover, such core-shell nanostructure exhibits high coarsening resistance at elevated temperatures, enabling it high thermal stability. Such a design strategy holds promise for developing high-performance materials.

Abstract Background Although recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI. Results Here, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequently activating fibroblasts and macrophages to promote RILI development. In response to IR, elevated TNKS1BP1 interacted with and decreased CNOT4 to suppress EEF2 degradation. Ectopic expression of EEF2 accelerated AECII senescence. Using a model system of TNKS1BP1 knockout (KO) mice, we demonstrated that TNKS1BP1 KO prevents IR-induced lung tissue senescence and RILI. Conclusions Notably, this study suggested that a regulatory mechanism of the TNKS1BP1/CNOT4/EEF2 axis in AECII senescence may be a potential strategy for RILI.

Abstract Superconducting quantum bits (qubits) rely on ultra-thin, amorphous oxide tunneling barriers that can have significant inhomogeneities and defects as grown. This can result in relatively large uncertainties and deleterious effects in the circuits, limiting the scalability. Finding a robust solution to the junction reproducibility problem has been a long-standing goal in the field. Here, we demonstrate a transformational technique for controllably tuning the electrical properties of aluminum-oxide tunnel junctions. This is accomplished using a low-voltage, alternating-bias applied individually to the tunnel junctions, with which resistance tuning by more than 70% can be achieved. The data indicates an improvement of coherence and reduction of two-level system defects. Transmission electron microscopy shows that the treated junctions are predominantly amorphous, albeit with a more uniform distribution of alumina coordination across the barrier. This technique is expected to be useful for other devices based on ionic amorphous materials.

Purpose: To evaluate the effect of anterior-segment structure on vault and position after implantable collamer lens (ICL) implantation using ultrasound biomicroscopy. Methods: The retrospective case-control study included insufficient vault eyes (750 µm). The preoperative biometric parameters of the anterior-segment structure and basic data between the three groups were analyzed using one-way analysis of variance. Results: There were significant differences (P < 0.05) between the three groups in maximum ciliary body thickness (CBTmax), iris-zonule distance (IZD), and trabecular-ciliary angle (TCA). The vault gradually decreased as CBTmax decreased and TCA increased. In the pairwise comparison, the CBTmax comparison between the insufficient vault (750 µm) group was statistically significant (P = 0.024, 95% CI: −0.17–0.017 µm); the TCA comparison between the insufficient vault (750 µm) group was statistically significant (P = 0.005, 95% CI: 1.78°–12.15°); The IZD comparison between the insufficient vault (750 µm) group was statistically significant (P = 0.037, 95% CI: 0.0027–0.1119 µm). The analysis of 284 ICL haptics locations showed that there were 16.67%, 32.69%, and 70.83% haptics located in the ciliary sulcus in three groups, respectively. Conclusion: The vault and ICL haptics position are related to anterior-segment structure. A thinner and posteriorly positioned ciliary body would increase the risk of low vault and fewer ICL haptics located in the ciliary sulcus after ICL implantation. This provides guidance for the selection of the ICL size and placement position before surgery.

Achalinus sheni Ma, Xu, Qi, Wang, Tang, Huang & Jiang, 2023 was originally described based on only male specimens from Lianyuan City and Nanyue District, Hunan, China. So far, no information on the females of this species is available. After molecular systematics and morphological characters of recently collected specimens from Xinshao County, Hunan, several specimens (3 males and 1 female) were identified as this species. Therefore, we provided supplementary descriptions of the female characteristics of this species in this study. Meanwhile, we extended the description of this species.

Abstract Develop a radiomics nomogram that integrates deep learning, radiomics, and clinical variables to predict epidermal growth factor receptor (EGFR) mutation status in patients with stage I non-small cell lung cancer (NSCLC). We retrospectively included 438 patients who underwent curative surgery and completed driver-gene mutation tests for stage I NSCLC from four academic medical centers. Predictive models were established by extracting and analyzing radiomic features in intratumoral, peritumoral, and habitat regions of CT images to identify EGFR mutation status in stage I NSCLC. Additionally, three deep learning models based on the intratumoral region were constructed. A nomogram was developed by integrating representative radiomic signatures, deep learning, and clinical features. Model performance was assessed by calculating the area under the receiver operating characteristic (ROC) curve. The established habitat radiomics features demonstrated encouraging performance in discriminating between EGFR mutant and wild-type, with predictive ability superior to other single models (AUC 0.886, 0.812, and 0.790 for the training, validation, and external test sets, respectively). The radiomics-based nomogram exhibited excellent performance, achieving the highest AUC values of 0.917, 0.837, and 0.809 in the training, validation, and external test sets, respectively. Decision curve analysis (DCA) indicated that the nomogram provided a higher net benefit than other radiomics models, offering valuable information for treatment.

Abstract As an important pest on winter wheat, Rhopalosiphum padi (L.) causes damage to the wheat yield by sucking plant nutrients, transmitting plant viruses and producing mildew. R. padi has been reported to develop resistance to pyrethroids and neonicotinoids. To explore potential alternative approaches for R. padi control, the activity of 10 botanical insecticides was evaluated. Results suggested that the toxicity of rotenone and pyrethrins to R. padi were the highest and near to the commonly used chemical insecticides. When exposed to the low-lethal concentrations (LC10, LC30) of rotenone or pyrethrins for 24 h, the lifespan and fecundity of adults in F0 generation decreased significantly compared to control. The negative effect could also be observed in the F1 generation, including the decreased average offspring, longevity of adult, and prolonged nymph period. The population parameters in F1 generation of R. padi were also inhibited by exposing to the low-lethal concentrations of rotenone or pyrethrins, including the decreased net reproductive rate, intrinsic rate of natural increase, finite rate of population increase, and gross reproduction rate. Co-toxocity factor results showed that mixtures of rotenone and thiamethoxam, pyrethrins and thiamethoxam showed synergistic effect. Our work suggested that rotenone and pyrethrins showed negative effect on the population growth under low-lethal concentrations. They are suitable for R. padi control as foliar spraying without causing population resurgence.

Abstract Road defect detection is critical step for road maintenance periodic inspection. Current methodologies exhibit drawbacks such as low detection accuracy, slow detection speed, and the inability to support edge deployment and real-time detection. To solve this issue, we introduce an improved YOLOv8 road defect detection model. Firstly, we designed the EMA Faster Block structure using partial convolution to replace the Bottleneck structure in the YOLOv8 C2f module, and the enhanced C2f module was labeled as C2f-Faster-EMA. Secondly, we improved the model speed by introducing SimSPPF instead of SPPF. Finally, for the head, Detect-Dyhead, chosen to replace the original head, significantly improves the representation ability of heads without introducing any GFLOPs. Experimental results on the road defect detection dataset show that the improved model in this paper outperforms the original YOLOv8, with a 5.8% increase in average accuracy (mAP@0.5), and notable reductions of 22.33% in model size, 23.03% in parameter size, and 21.68% in computational complexity.

Abstract Computer-aided implant surgery has undergone continuous development in recent years. In this study, active and passive systems of dynamic navigation were divided into active dynamic navigation system group and passive dynamic navigation system group (ADG and PDG), respectively. Active, passive and semi-active implant robots were divided into active robot group, passive robot group and semi-active robot group (ARG, PRG and SRG), respectively. Each group placed two implants (FDI tooth positions 31 and 36) in a model 12 times. The accuracy of 216 implants in 108 models were analysed. The coronal deviations of ADG, PDG, ARG, PRG and SRG were 0.85 ± 0.17 mm, 1.05 ± 0.42 mm, 0.29 ± 0.15 mm, 0.40 ± 0.16 mm and 0.33 ± 0.14 mm, respectively. The apical deviations of the five groups were 1.11 ± 0.23 mm, 1.07 ± 0.38 mm, 0.29 ± 0.15 mm, 0.50 ± 0.19 mm and 0.36 ± 0.16 mm, respectively. The axial deviations of the five groups were 1.78 ± 0.73°, 1.99 ± 1.20°, 0.61 ± 0.25°, 1.04 ± 0.37° and 0.42 ± 0.18°, respectively. The coronal, apical and axial deviations of ADG were higher than those of ARG, PRG and SRG (all P

Abstract In recent studies, erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, has exhibited notable anticancer properties. Ferroptosis, a novel form of programmed cell death, holds potential as a strategy to overcome Temozolomide (TMZ) resistance in glioma by inducing ferroptosis in TMZ-resistant glioma cells. Here, utilizing various phenotyping experiments, including cell counting kit-8 (CCK-8) assays, EdU assays, transwell assays, neurosphere formation assays and extreme limiting dilution (ELDA) assays, we demonstrated that erianin exerts its anticancer activity on both TMZ sensitive and TMZ-resistant glioma stem cells (GSCs). Furthermore, we made an exciting discovery that erianin enhances TMZ sensitivity in TMZ-resistant GSCs. Subsequently, we demonstrated that erianin induced ferroptosis in TMZ-resistant GSCs and enhances TMZ sensitivity through inducing ferroptosis, which was confirmed by intracellular measurements of ROS, GSH, and MDA, as well as through the use of BODIPY (581/591) C11 and transmission electron microscopy. Conversely, the ferroptosis inhibitor ferrostatin-1 (Fer-1) blocked the effects of erianin. The underlying mechanism of ferroptosis induced by erianin was further explored through co-immunoprecipitation (Co-IP) assays, ubiquitination assays, protein stability assessments, chromatin immunoprecipitation (ChIP) assays and luciferase reporter gene assays. We found that erianin specifically targets REST, inhibiting its transcriptional repression function without altering its expression levels. Consequently, this suppression of REST’s role leads to an upregulation of LRSAM1 expression. In turn, LRSAM1 ubiquitinates and degrades SLC40A1, a protein that inhibits ferroptosis by exporting ferrous ions. By downregulating SLC40A1, erianin ultimately induces ferroptosis in TMZ-resistant GSCs. Taken together, our research demonstrates that the natural product erianin inhibits the malignant phenotype of GSCs and increases the sensitivity of TMZ in TMZ-resistant GSCs by inducing ferroptosis. These findings suggest erianin as a prospective compound for the treatment of TMZ-resistant glioma.

Abstract Aim Recent imaging studies have found significant abnormalities in the brain’s functional or structural connectivity among patients with high myopia (HM), indicating a heightened risk of cognitive impairment and other behavioral changes. However, there is a lack of research on the topological characteristics and connectivity changes of the functional networks in HM patients. In this study, we employed graph theoretical analysis to investigate the topological structure and regional connectivity of the brain function network in HM patients. Methods We conducted rs-fMRI scans on 82 individuals with HM and 59 healthy controls (HC), ensuring that the two groups were matched for age and education level. Through graph theoretical analysis, we studied the topological structure of whole-brain functional networks among participants, exploring the topological properties and differences between the two groups. Results In the range of 0.05 to 0.50 of sparsity, both groups demonstrated a small-world architecture of the brain network. Compared to the control group, HM patients showed significantly lower values of normalized clustering coefficient (γ) (P = 0.0101) and small-worldness (σ) (P = 0.0168). Additionally, the HM group showed lower nodal centrality in the right Amygdala (P

Objective To study the effect of Salidroside(Sal) on platelet activation and aggregation and the interaction between human platelets and MDA-MB-468 cells of breast cancer. Methods Human platelets were collected, platelet suspension was prepared, and platelets were treated with different concentrations of Sal. The effects of Sal on platelet activation and aggregation were detected by thromboelastogram(TEG) and flow cytometry. Breast cancer MDA-MB-468 cells were cultured in vitro, and human platelets were treated with different concentrations of Sal, and then activated by thrombin. The effects of Sal on the interaction between platelets and MDA-MB-468 cells were analyzed by adhesion test and scratch test. Results TEG detection: The ADP inhibition rate in the blank control group was (10.97±12.69)%, and the ADP inhibition rate in all Sal intervention groups was higher than that in the blank control group (P

Abstract Background Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria. Case presentation We report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone. Conclusions Monoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren’t enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome.

Abstract Background The coronavirus disease 2019 (COVID-19) has become a serious public health issue. In COVID-19 patients, the elevated levels of inflammatory cytokines lead to the manifestation of COVID-19 symptoms, such as lung tissue edema, lung diffusion dysfunction, acute respiratory distress syndrome (ARDS), secondary infection, and ultimately mortality. Mesenchymal stem cells (MSCs) exhibit anti-inflammatory and immunomodulatory properties, thus providing a potential treatment option for COVID-19. The number of clinical trials of MSCs for COVID-19 has been rising. However, the treatment protocols and therapeutic effects of MSCs for COVID-19 patients are inconsistent. This meta-analysis was performed to systematically determine the safety and efficacy of MSC infusion in COVID-19 patients. Methods We conducted a comprehensive literature search from PubMed/Medline, Web of Science, EMBASE, and Cochrane Library up to 22 November 2023 to screen for eligible randomized controlled trials. Inclusion and exclusion criteria for searched literature were formulated according to the PICOS principle, followed by the use of literature quality assessment tools to assess the risk of bias. Finally, outcome measurements including therapeutic efficacy, clinical symptoms, and adverse events of each study were extracted for statistical analysis. Results A total of 14 randomized controlled trials were collected. The results of enrolled studies demonstrated that patients with COVID-19 pneumonia who received MSC inoculation showed a decreased mortality compared with counterparts who received conventional treatment (RR: 0.76; 95% CI [0.60, 0.96]; p = 0.02). Reciprocally, MSC inoculation improved the clinical symptoms in patients (RR: 1.28; 95% CI [1.06, 1.55]; p = 0.009). In terms of immune biomarkers, MSC treatment inhibited inflammation responses in COVID-19 patients, as was indicated by the decreased levels of CRP and IL-6. Importantly, our results showed that no significant differences in the incidence of adverse reactions or serious adverse events were monitored in patients after MSC inoculation. Conclusion This meta-analysis demonstrated that MSC inoculation is effective and safe in the treatment of patients with COVID-19 pneumonia. Without increasing the incidence of adverse events or serious adverse events, MSC treatment decreased patient mortality and inflammatory levels and improved the clinical symptoms in COVID-19 patients. However, large-cohort randomized controlled trials with expanded numbers of patients are required to further confirm our results.

The gut has been a focal point in the research of digestive system disorders. The internal microbiota generates metabolites that function as signaling molecules and substrates, interacting with the intestinal wall and influencing host physiology and pathology. Besides, the gut microbiota and metabolites owe highly diverse types and quantities, posing challenges for quantitative analysis, and monitoring frequent interactions between digestive tract metabolites and the intestinal wall remains a challenge. However, research targeting gut microbiota metabolites has elucidated their relevance to digestive diseases. By modulating metabolites such as short-chain fatty acids, bile acids, and lipopolysaccharides, it is possible to intervene in the progression of diseases such as inflammatory bowel disease and non-alcoholic fatty liver disease. Currently, research on gut microbiota is advancing, and more work is required to explore the interactions between host, microbes and underlying mechanisms. In this review, we have revisited the generation of gut microbiota-related metabolites, their impact on diseases, and modes of interaction, emphasizing the significant role of metabolites in digestive system disorders. It is believed that the linkage between gut microbiota and diseases in current research can be established through metabolites, providing a framework and foundation for research in the field of metabolomics and fundamental mechanisms.

Abstract Background Objective and quantifiable markers are crucial for developing novel therapeutics for mental disorders by 1) stratifying clinically similar patients with different underlying neurobiological deficits and 2) objectively tracking disease trajectory and treatment response. Schizophrenia is often confounded with other psychiatric disorders, especially bipolar disorder, if based on cross-sectional symptoms. Awake and sleep EEG have shown promise in identifying neurophysiological differences as biomarkers for schizophrenia. However, most previous studies, while useful, were conducted in European and American populations, had small sample sizes, and utilized varying analytic methods, limiting comprehensive analyses or generalizability to diverse human populations. Furthermore, the extent to which wake and sleep neurophysiology metrics correlate with each other and with symptom severity or cognitive impairment remains unresolved. Moreover, how these neurophysiological markers compare across psychiatric conditions is not well characterized. The utility of biomarkers in clinical trials and practice would be significantly advanced by well-powered transdiagnostic studies. The Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project aims to address these questions through a large, multi-center cohort study involving East Asian populations. To promote transparency and reproducibility, we describe the protocol for the GRINS project. Methods The research procedure consists of an initial screening interview followed by three subsequent sessions: an introductory interview, an evaluation visit, and an overnight neurophysiological recording session. Data from multiple domains, including demographic and clinical characteristics, behavioral performance (cognitive tasks, motor sequence tasks), and neurophysiological metrics (both awake and sleep electroencephalography), are collected by research groups specialized in each domain. Conclusion Pilot results from the GRINS project demonstrate the feasibility of this study protocol and highlight the importance of such research, as well as its potential to study a broader range of patients with psychiatric conditions. Through GRINS, we are generating a valuable dataset across multiple domains to identify neurophysiological markers of schizophrenia individually and in combination. By applying this protocol to related mental disorders often confounded with each other, we can gather information that offers insight into the neurophysiological characteristics and underlying mechanisms of these severe conditions, informing objective diagnosis, stratification for clinical research, and ultimately, the development of better-targeted treatment matching in the clinic.

Abstract Background The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins are critical mediators in the gut-kidney axis that can cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role and underlying mechanism of the gut microbiota in HUA-induced renal injury remain unknown. Results A HUA rat model was first established by knocking out the uricase (UOX). HUA rats exhibited apparent renal dysfunction, renal tubular injury, fibrosis, NLRP3 inflammasome activation, and impaired intestinal barrier functions. Analysis of 16S rRNA sequencing and functional prediction data revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. A metabolomic analysis showed evident accumulation of gut-derived uremic toxins in the kidneys of HUA rats. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the effects of HUA-induced gut dysbiosis on renal injury. Mice recolonized with HUA microbiota exhibited severe renal injury and impaired intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3−/−) I/R mice, the deleterious effects of the HUA microbiota on renal injury and the intestinal barrier were eliminated. Conclusion Our results demonstrate that HUA-induced gut dysbiosis contributes to the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating the NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal diseases by targeting the gut microbiota and the NLRP3 inflammasome. Video Abstract Graphical Abstract