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Abstract Background The incidence of androgenetic alopecia in males is on the rise annually, with hair transplantation using follicular unit extraction (FUE) gaining increasing acceptance as an appropriate treatment for these individuals. Methods A retrospective study was undertaken, involving 158 male patients diagnosed with androgenetic alopecia, who underwent treatment between January 2016 and December 2020 at the Medical Cosmetology Department of the First Affiliated Hospital of Xi’an Medical University. Demographic data and treatment characteristics were documented and analyzed. Clinical efficacy, operation-related complications, patient satisfaction rates, and quality of life scores were assessed and analyzed. Results Following FUE hair transplantation, over 90% of the hair follicles survived in 158 patients, with more than 85% of patients achieving a hair follicle survival rate exceeding 95% at 12 months post-operation. Patient satisfaction rates exceeded 98%, while the complication rate was below 6%. Conclusion Our findings demonstrate that FUE is a minimally invasive hair transplant technique associated with a high hair follicle survival rate and optimal hair density. This approach proves effective in treating male androgenetic alopecia and merits further clinical application.

Abstract This study aimed to identify potential markers that can predict Parkinson’s disease with mild cognitive impairment (PDMCI). We retrospectively collected general demographic data, clinically relevant scales, plasma samples, and neuroimaging data (T1-weighted magnetic resonance imaging (MRI) data as well as resting-state functional MRI [Rs-fMRI] data) from 173 individuals. Subsequently, based on the aforementioned multimodal indices, a support vector machine was employed to investigate the machine learning (ML) classification of PD patients with normal cognition (PDNC) and PDMCI. The performance of 29 classifiers was assessed based on various combinations of indicators. Results demonstrated that the optimal classifier in the validation set was composed by clinical + Rs-fMRI+ neurofilament light chain, exhibiting a mean Accuracy of 0.762, a mean area under curve of 0.840, a mean sensitivity of 0.745, along with a mean specificity of 0.783. The ML algorithm based on multimodal data demonstrated enhanced discriminative ability between PDNC and PDMCI patients.

Abstract Aim This study aimed to investigate the impact of bedside case-based learning on critical thinking and capacity for self-directed learning in a group of midwifery students in China. Background Bedside teaching is a well-established educational tool to improve the clinical practice of medical, nursing, and midwifery students. A new pedagogical approach; bedside case-based learning (BCBL) is an interactive teaching approach involving small-group, student-educator discussion to describe the etiology and management of a patient case. This new approach has been gradually integrated into Chinese midwifery education programs to promote clinical problem-solving skills, knowledge application, teamwork, and collaboration. Design A quasi-experimental pre-test-post-test group design. Methods This study used a quasi-experimental pre-test-post-test group design. A convenience sample of 67 third-year students majoring in midwifery at the university were prospectively enrolled in this study. Pre- and post-BCBL class surveys were conducted using the Self-Rating Scale of Self-Directed Learning (SRSSDL) and the Critical Thinking Disposition Inventory-Chinese Version (CTDI-CV) to assess changes in self-learning and critical thinking abilities before and after the intervention. Results Following bedside case-based learning, the total scores for self-directed learning capacity and critical thinking increased, although there were no statistically significant differences (P > 0.05). Conclusions Although there were no statistically significant differences between pre- and post-test results, students’ self-assessed scores in self-directed learning and critical thinking improved between pre- and post-test.

Abstract Background Coxsackievirus (CV) A6 has emerged as an important causative agent in global outbreaks of hand, foot, and mouth disease (HFMD), which typically presents as a mild illness with a large generalized rash, herpes. However, some patients can develop encephalitis, pneumonia, myocarditis and liver injury. Our previous study took the view that CVA6 could replicate in mouse liver, leading to acute liver injury; however, the precise underlying mechanism remains elusive. Methods 10-day-old wild-type (WT, C57BL/6J) and NLRP3 knock-out (KO) mice were intraperitoneal (i.p.) inoculated with a lethal dose of the CVA6 strain. The muscle homogenate supernatant from normal mice was used to inoculate mock-infected mice. At 5 days post infection (dpi), the mouse liver was taken out for histopathological analyses and molecular biology experiments. Results Our in vivo experiments demonstrated that CVA6 caused severe liver injury in mice, as evidenced by pathological changes in liver slices, elevated liver injury markers (e.g., AST, ALT, LDH) and pro-inflammatory cytokines (e.g., IL-6, MCP-1, TNF-α, IL-1β). Further results revealed the activation of NLRP3 inflammasome characterized by the increase in the expression of NLRP3, Cleaved-Casp-1 (p20), mature IL-1β and IL-18. Importantly, upon CVA6 infection, NLRP3 KO mice exhibited attenuated pathological damage and reduced levels of pro-inflammatory cytokines production (e.g., TNF-α and IL-1β) compared with WT mice. Finally, increased levels of blood ALT, AST, LDH were strongly correlated with the severity of CVA6 patients. Conclusion Collectively, our findings suggest that the activation of NLRP3 inflammasome is involved in CVA6 infection-induced acute liver injury, providing novel insights into CVA6 infection associated adverse clinical outcomes.

Abstract This study explored the pathogenesis of human immunodeficiency virus (HIV) and monkeypox co-infection, identifying candidate hub genes and potential drugs using bioinformatics and machine learning. Datasets for HIV (GSE 37250) and monkeypox (GSE 24125) were obtained from the GEO database. Common differentially expressed genes (DEGs) in co-infection were identified by intersecting DEGs from monkeypox datasets with genes from key HIV modules screened using Weighted Gene Co-Expression Network Analysis (WGCNA). After gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and construction of protein-protein interaction (PPI) network, candidate hub genes were further screened based on machine learning algorithms. Transcriptional factors (TFs) and miRNA-candidate hub gene networks were constructed to understand regulatory mechanisms and protein-drug interactions to identify potential therapeutic drugs. Seven candidate hub genes—MX2, ADAR, POLR2H, RPL5, IFI16, IFIT2, and RPS5—were identified. TFs and miRNAs associated with these hub genes, playing a key role in regulating viral infection and inflammation due to the activation of antiviral innate immunity, were also identified through network analysis. Potential therapeutic drugs were screened based on these hub genes: AZT, a nucleotide reverse transcriptase inhibitor, suppressed viral replication in HIV and monkeypox co-infection, while mefloquine inhibited inflammation due to the activation of antiviral innate immunity. In conclusion, the study identified candidate hub genes, their transcriptional regulation, signaling pathways, and small-molecule drugs in HIV and monkeypox co-infection, contributing to understanding the pathogenesis of HIV and monkeypox co-infection and informing precise therapeutic strategies.

Abstract Alpha oscillations are associated with various psychiatric disorders, with many studies focusing on the prefrontal cortex, where transcranial alternating current stimulation (TACS) is applied in the alpha frequency band. This approach often involves selecting individualized alpha frequencies to resonate with their endogenous alpha oscillations. While strong alpha oscillations (8–13 Hz) are typically induced when the eyes are closed, they can also occur during the resting state with eyes open. However, it remains unclear whether these alpha oscillations share a common neural generation mechanism. Exploring which of these alpha oscillations is more suitable as a stable alpha peak frequency is a question of significant interest. Therefore, to systematically study this issue, we specifically collected resting-state electroencephalographic (EEG) data from the prefrontal region of 40 individuals, under both eyes-open and closed- eye conditions, with multiple follow-ups extending up to nine months. Through spectral analysis on each person’s entire dataset and averaging the results, we observed a significant positive correlation between the alpha-band power in the eyes-open and the eyes-closed states, in terms of both absolute power and relative power. Further analysis revealed that this correlation was primarily contributed by the periodic activity within the alpha band. Upon modelling the oscillatory components, we discovered distinct differences in the oscillatory characteristics-such as number of the alpha sub-oscillations between the eyes-open state and the eyes-closed state. Our study is the first to systematically explored the relationship between alpha oscillations in the prefrontal cortex in the eyes-open and eyes-closed states, identifying both shared part of the neural generation mechanism and some distinct neural mechanisms that are unique to each state.

Abstract Acute lung injury (ALI) is a common critical respiratory disease in clinical practice, especially in the ICU, with a high mortality rate. The pathogenesis of ALI is relatively complex, mainly involving inflammatory response imbalance, oxidative stress, cell apoptosis, and other aspects. However, currently, the treatment measures taken based on the above mechanisms have not had significant effects. Recent research shows that mitochondrial dysfunction and pyroptosis play an important role in ALI, but there is not much analysis on the relationship between mitochondrial dysfunction and pyroptosis at present. This article reviews the situation of mitochondrial dysfunction in ALI, pyroptosis in ALI, whether mitochondrial dysfunction is related to pyroptosis in ALI, and how to do so, and further analyzes the relationship between them in ALI. This review describes how to alleviate mitochondrial dysfunction, and then suppress the associated immunological pyroptosis, providing new ideas for the clinical treatment of ALI.

Abstract Background This current study aimed to investigate the relationship between the triglyceride-glucose (TyG) index and in-hospital all-cause mortality of coronary artery disease (CAD) in patients with different glucose metabolic statuses. Methods Participants were divided into three groups according to tertiles of the TyG index. Glucose metabolic status was classified as normal glucose regulation, pre-diabetes mellitus, and diabetes mellitus (DM). The primary outcome was in hospital all-cause mortality. Results We observed a significant relationship between the TyG index and in-hospital deaths of patients with CAD in this study. After adjusting for multiple factors in the logistic regression model, the TyG index was still an independent risk factor, and the T3 group (OR, 2.311; 95% CI = 1.237–4.317; P = 0.009) was correlated with a 2.311-fold risk compared with the T1 group. In the subgroup analysis of different glucose metabolic status, the T3 group (OR, 1.541; 95% CI: 1.013–2.344; P = 0.043) were associated with a significantly higher risk of in-hospital deaths in CAD patients with DM. Conclusions An increased TyG index was correlated with a higher risk of in-hospital all-cause mortality. Our study indicated that TyG index could be a valuable predictor of in-hospital death of CAD patients, especially for individuals with DM.

Tea's popularity and flavor are influenced by factors like cultivation and processing methods and shaping techniques also have an impact on tea flavor. This study employed targeted metabolomics and chemometrics to investigate how shaping techniques affect the flavor of milk-flavored white tea (MFWT). The results showed that the tea cake sample with the shortest pressing time (Y90) has the highest amino acid content and milky aroma intensity. There were variations in amino acids, catechins, and soluble sugars among MFWT samples with different shaping techniques. The total contents of amino acids and catechins in tea cake sample (Y90) were significantly lower than those in the loose tea sample (SC) and bundle-like tea sample (SG), while the total sugar content was significantly higher than that in SC (P1) in Y90 remained lower relative to SC and SG (P

Abstract NLRP3 inflammasomes- pyroptosis axis is activated by microcirculation dysfunction and touched off severe acute pancreatitis (SAP). Activation of PGC-1α can improve microcirculation dysfunction by promoting mitochondrial biogenesis. Resveratrol (RSV), one typical SIRT1 agonist, possesses the ability of alleviating SAP and activing PGC-1α. Therefore, the study was designated to explore whether the protective effect of RSV in SAP was though suppressing NLRP3 inflammasomes- pyroptosis axis via advancing SIRT1/PGC-1α-dependent mitochondrial biogenesis. The models of SAP were induced by treating with sodium taurodeoxycholate in rats and AR42J cells. The pathological injury, water content (dry/wet ratio) and microcirculation function of pancreas, activity of lipase and amylase were used to evaluate pancreatic damage. The expression of inflammatory cytokine was measured by ELISA and RT-PCR. The damage of mitochondrial was evaluated by measuring the changes in Mitochondrial Membrane Potential (ΔΨm), mitochondrial ROS, ATP content and MDA as well as relocation of mtDNA and the activity of SOD and GSH. The expressions of NLRP3 inflammasomes- pyroptosis axis proteins were detected by Western blotting as well as SIRT1/PGC-1α/NRF1/TFAM pathway protein. Moreover, the modification of PGC-1α was measured by co-immunoprecipitation. The results displayed that RSV can significantly improve the damage of pancreas and mitochondrial, decrease the expression of pro-inflammatory factor and the activation of NLRP3 inflammasomes- pyroptosis axis, promote the expression of an-inflammatory factor and the deacetylation of PGC-1α together with facilitating SIRT1/PGC-1α-mediating mitochondrial biogenesis. Therefore, the protective effect of RSV in SAP is though inactivation of NLRP3 inflammasomes- pyroptosis axis via promoting mitochondrial biogenesis in a SIRT1/PGC-1α-dependent manner.

Abstract In response to the safety and stability issues of current electric vehicle charging connection devices, this study proposes a charging system planning for electric vehicles with different capacity charging piles based on the user behavior characteristics of electric vehicles and Monte Carlo methods. It is found that the predicted results under the set management strategy are most consistent with the trend of actual load changes. Moreover, in the prediction of weekly load, the research strategy has better performance than traditional unmanaged strategies. Under the research scheme, the average charging speed of charging piles with capacity of A and B in the peak period was 41.4 min/ and 18.8 min/, respectively, which increased by 29.3% and 11.7% respectively compared with 58.6 min/ and 21.3 min/ in the normal period. The total economic cost of the research plan was 4.871 million yuan, which was 67.0 million yuan and 3.833 million yuan lower than the control methods 1 and 2, respectively. The total number of charging stations of types a and b that need to be purchased for the research method decreased by 18.47% and 63.24% compared to the comparative method 3. The results indicate that the research method significantly improves the utilization rate of charging stations in the electric vehicle charging system. This study has important application value in the intelligent management of electric vehicle charging systems.

Abstract Excessive DNA damage triggers various types of programmed cell death (PCD), yet the regulatory mechanism of DNA damage-induced cell death is not fully understood. Here, we report that PANoptosis, a coordinated PCD pathway, including pyroptosis, apoptosis and necroptosis, is activated by DNA damage. The Z-DNA binding protein 1 (ZBP1) is the apical sensor of PANoptosis and essential for PANoptosome assembly in response to DNA damage. We find endogenous retroviruses (ERVs) are activated by DNA damage and act as ligands for ZBP1 to trigger PANoptosis. By using ZBP1 knock-out and knock-in mice disrupting ZBP1 nucleic acid-binding activity, we demonstrate that ZBP1-mediated PANoptosis contributes to the toxic effects of chemotherapeutic drugs, which is dependent on ZBP1 nucleic acid-binding activity. We found that ZBP1 expression is downregulated in tumor tissue. Furthermore, in colorectal cancer patients, dsRNA is induced by chemotherapy and sensed by ZBP1 in normal colonic tissues, suggesting ZBP1-mediated PANoptosis is activated by chemotherapy in normal tissues. Our findings indicate that ZBP1-mediated PANoptosis is activated by DNA damage and contributes to the toxic side effects of DNA-damage-based chemotherapy. These data suggest that ZBP1 could be a promising therapeutic target to alleviate chemotherapy-related side effects.

Abstract Background Hepatocellular carcinoma (HCC) is a malignant tumor characterized by a high mortality rate. The occurrence and progression of HCC are linked to oxidative stress. Glyoxalase-1 (GLO1) plays an important role in regulating oxidative stress, yet the underlying mechanism remains unclear. GLO1 may serve as a prognostic biomarker and therapeutic target for HCC. Methods Based on TCGA database hepatocellular carcinoma samples, we conducted a bioinformatics analysis to explore the correlation between GLO1 expression and HCC cell proliferation and viability. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that differentially expressed genes (DEGs) were mainly enriched in the cell cycle pathway. We analyzed the relationships between GLO1 and 24 genes enriched in the cell cycle pathway using a protein-protein interaction (PPI) network. Finally, experimental validation was performed to assess GLO1’s impact on the distribution of cells at different cell cycle stages and on the proliferation and migration of HCC cells. Results Our study demonstrated that GLO1 was overexpressed in HCC tissues and was associated with a poor prognosis. Data analysis indicated that overexpression of GLO1 activated the cell cycle pathway and positively correlated with expression of the majority of key cell cycle genes. Experimental validation showed that GLO1 expression affects the number of HCC cells in G2 and S phases and regulates HCC cell proliferation and migration. Conclusions GLO1 represents a promising therapeutic target for HCC, providing valuable insights into its role in the viability and proliferation of HCC cells.

Abstract Background SARC-F questionnaire is a simple and convenient tool for sarcopenia screening, and SARC-CalF is a modified version of it. The developments of their Chinese versions are warranted for the clinical use for Chinese population. This study aimed to culturally adapt the SARC-F questionnaire into Chinese using standardized methods, validate the reliability and diagnostic accuracy of the Chinese version SARC-F and SARC-CalF against five sarcopenia diagnosis criteria, and determine optimal cut-off values for clinical practice in Chinese population. Methods The translation and cross-cultural adaptation of SARC-F into Chinese were conducted following the methodological report from European Union Geriatric Medicine Society Sarcopenia Special Interest Group. The Chinese version of SARC-F was validated through a diagnostic test, using diagnostic criteria of sarcopenia recommended by the revised 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) consensus, Asian Working Group for Sarcopenia (AWGS2019) consensus, the International Working Group on Sarcopenia (IWGS), the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium and the Sarcopenia Definition and Outcomes Consortium (SDOC). Additional analysis was done against the criteria of severe sarcopenia according to the revised EWGSOP2 and AWGS2019. Results The Chinese version of SARC-F was well translated and demonstrated good reliability and acceptability. The diagnostic test included 1859 community-dwelling older individuals from two medical centers. Against five different definitions of sarcopenia, the Chinese version of SARC-F showed reasonable diagnostic accuracy for sarcopenia screening (AUC 0.614–0.821), and was demonstrated low sensitivity (13.7–37.9%) but high specificity (94.8–97.7%) with a cut-off value of ≥ 4. SARC-CalF significantly enhanced the diagnostic accuracy of SARC-F when using definitions of EWGSOP2, AWGS2019 and IWGS (all P ≤ 0.001). A score of ≥ 2 for SARC-F and ≥ 7 for SARC-CalF were established as optimal cut-off points for identifying older individuals as at risk of sarcopenia in Chinese population. Conclusions The Chinese version SARC-F is of reasonable reliability and validity for sarcopenia screening. Despite its low sensitivity, it proves to be a useful tool to identify severe cases in community taking advantage of its simplicity. SARC-CalF appears to be a more suitable screening tool for clinical use in detecting sarcopenia.

Abstract Background Previous research has examined the associations of preschoolers’ 24-h movement behaviours, including light and moderate-to-vigorous physical activity (LPA and MVPA), sedentary behaviour (SB), sleep, with physical fitness in isolation, ignoring intrinsically compositional nature of movement data while increasing the risk of collinearity. Thus, this study investigated the associations of preschoolers’ 24-h Movement behaviours composition with physical fitness, estimated changes in physical fitness when time was reallocated between movement behaviours composition, and determined whether associations differ between different genders, using compositional data analysis. Methods In the cross-sectional study, a total of 275 preschoolers (3 ~ 6 y) from China were included. SB, LPA and MVPA times were objectively monitored with an ActiGraph GT9X accelerometer for 7 consecutive days. Sleep duration was obtained using parental reports. Physical fitness parameters, including upper and lower limb strength, static balance, speed-agility, and cardiorespiratory fitness (CRF), were determined with the PREFIT battery. The associations of 24-h movement behaviours composition with each physical fitness parameter were examined employing compositional multivariable linear regression models. The changes following time reallocation among behaviours were estimated employing compositional isotemporal substitution analyses. Results Greater MVPA, but not LPA, was significantly related to better upper and lower limb strength, speed-agility, and CRF. Reallocating time from LPA or SB to MVPA was related to better physical fitness. The associations were non-symmetrical: the estimated detriments to physical fitness from replacing MVPA with LPA or SB were larger than the estimated benefits associated with adding MVPA of the same magnitude. The aforementioned associations with lower limb strength, CRF, and speed-agility were observed in boys, while associations with upper and lower limb strength were noted in girls. Conclusion Our findings reinforce the importance of physical activity (PA) intensity for the development of physical fitness in preschoolers. Replacing LPA or SB time with MVPA may be an appropriate strategy for enhancing preschoolers’ physical fitness.

Abstract There is an urgent need to identify predictive biomarkers of Parkinson’s disease (PD) with cognitive impairment (PDCI) in order to individualize patient management, ensure timely intervention, and improve prognosis. The aim of this study was to screen for these biomarkers by comparing the plasma proteome and metabolome of PD patients with or without cognitive impairment. Proteomics and metabolomics analyses were performed on a discover cohort. A machine learning model was used to identify candidate protein and metabolite biomarkers of PDCI, which were validated in an independent cohort. The predictive ability of these biomarkers for PDCI was evaluated by plotting receiver operating characteristic curves and calculating the area under the curve (AUC). Moreover, we assessed the predictive ability of these proteins in combination with neuroimaging. In the discover cohort (n = 100), we identified 25 protein features with best results in the machine learning model, including top-ranked PSAP and H3C15. The two-proteins were used for model construction, achieving an Area under the curve (AUC) of 0.951 in the train set and AUC of 0.981 in the test set. Similarly, the model gives a rank list of endogenous metabolite features, Glycocholic Acid and 6-Methylnicotinamide were two top features. Combining these two markers further got the AUC of 0.969 in train set and 0.867 in the test set. To validate the performance of the protein biomarkers, we performed targeted analysis of selected proteins (H3C15 and PSAP) and proteins likely associated with PDCI (NCAM2 and LAMB2) using parallel reaction monitoring in validation cohort (n = 116). The AUC of the classifier built with H3C15 and PSAP is 0.813. Moreover, when combining H3C15, PSAP, NCAM2, and LAMB2, the model achieved AUC of 0.983 in the train set, AUC of 0.981 in the test set, and AUC of 0.839 in the validation set. Furthermore, we verified that these protein markers we discovered can improve the predictive effect of neuroimaging on PDCI: the classifier built with neuroimaging features had AUC of 0.833, which improved to 0.905 when combined with H3C15. Taken together, our integrated proteomics and metabolomics analysis successfully identified potential biomarkers for PDCI. Additionally, H3C15 showed promise in enhancing the predictive performance of neuroimaging for cognitive impairment.

Abstract The application of biochar to soil is widely recognized as a promising strategy for enhancing the accumulation and stability of soil organic carbon (SOC), which is crucial in mitigating climate change. However, the influence of interactions between plants and biochar on soil microbial communities and their involvement in SOC mineralization and stability remains unclear. This understanding is essential for optimizing carbon (C) sequestration in systems involving plants, soil, and biochar. In this study, employing a 13C natural abundance approach, we investigated the effect of biochar on the maize rhizosphere priming effect (RPE) in paddy soil. We also examined alterations in microbial communities and functional genes related to C degradation and fixation. Over the 99 days of maize growth, biochar application increased RPE and total SOC while decreasing dissolved organic C. It also elevated soil pH, resulting in shifts in fungal and bacterial community structure, favoring oligotrophic species. Fungal and bacterial assemblies were dominated by deterministic and stochastic processes, respectively. While the abundance of fungal guilds varied irregularly, bacterial guilds were uniformly enriched under biochar-plant interactions. Functional traits such as ecoenzymatic activities, bacterial guilds, and functional genes predominantly affected RPE under biochar application. Bacterial functional genes associated with C degradation and fixation were concurrently enhanced with biochar application. Our results indicate that interactions between plants and biochar can enhance native SOC mineralization and accumulation in a short timeframe by modulating functional traits of soil microorganisms, particularly the bacterial community involved in C degradation and fixation. Graphical Abstract

Abstract Focused ultrasound ablation surgery (FUAS) is a minimally invasive treatment option that has been utilized in various tumors. However, its clinical advancement has been hindered by issues such as low safety and efficiency, single image guidance mode, and postoperative tumor residue. To address these limitations, this study aimed to develop a novel multi-functional gas-producing engineering bacteria biological targeting cooperative system. Pulse-focused ultrasound (PFUS) could adjust the ratio of thermal effect to non-thermal effect by adjusting the duty cycle, and improve the safety and effectiveness of treatment.The genetic modification of Escherichia coli (E.coli) involved the insertion of an acoustic reporter gene to encode gas vesicles (GVs), resulting in gas-producing E.coli (GVs-E.coli) capable of targeting tumor anoxia. GVs-E.coli colonized and proliferated within the tumor while the GVs facilitated ultrasound imaging and cooperative PFUS. Additionally, multifunctional cationic polyethyleneimine (PEI)-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PEI-PLGA/EPI/PFH@Fe3O4) containing superparamagnetic iron oxide (SPIO, Fe3O4), perfluorohexane (PFH), and epirubicin (EPI) were developed. These nanoparticles offered synergistic PFUS, supplementary chemotherapy, and multimodal imaging capabilities.GVs-E.coli effectively directed the PEI-PLGA/EPI/PFH@Fe3O4 to accumulate within the tumor target area by means of electrostatic adsorption, resulting in a synergistic therapeutic impact on tumor eradication.In conclusion, GVs-E.coli-mediated multi-functional nanoparticles can synergize with PFUS and chemotherapy to effectively treat tumors, overcoming the limitations of current FUAS therapy and improving safety and efficacy. This approach presents a promising new strategy for tumor therapy. Graphical Abstract

Abstract Homozygous familial hypercholesterolemia (HoFH), is a rare genetic disorder characterized by dual mutations in the low-density lipoprotein receptor (LDLR) gene, leading to dysfunctional or absent LDLRs, often accompanied by severe premature Atherosclerotic Cardiovascular Disease (ASCVD) and exhibiting refractoriness to aggressive pharmacological interventions. Double filtration plasmapheresis (DFPP), a form of lipoprotein apheresis (LA), has been effectively utilized as an adjunctive treatment modality to reduce serum LDL-C levels in refractory cases of HoFH. Here, we report a case of a 36-year-old female with HoFH who developed xanthomas on her limbs and waist at age 7. Despite maximum-tolerated doses of statins from age 32, combined with ezetimibe and evolocumab, her LDL-C levels remained critically elevated at 12–14 mmol/L. Her genetic testing confirmed a homozygous LDLR mutation. At 35 years old, she experienced exertional chest pain, and percutaneous coronary intervention revealed severe calcific left main stenosis, necessitating stent implantation. Subsequently, she initiated once every 1–2 months DFPP. Pre-DFPP, her LDL-C and total cholesterol (TC) levels were 13.82 ± 3.28 and 15.45 ± 0.78 mmol/L, respectively. Post-DFPP, her LDL-C and TC levels significantly decreased to 2.43 ± 0.33 mmol/L (81.76 ± 4.11% reduction) and 3.59 ± 0.41 mmol/L (76.76 ± 2.75% reduction), respectively. Lipoprotein (a) and triglycerides also decreased by 89.10 ± 1.39% and 42.29 ± 15.68%,respectively. Two years later, there was no progression of coronary artery disease, and her symptoms and xanthomas regressed significantly. Collectively, DFPP effectively reduces LDL-C levels in refractory cases of HoFH and contributes to delaying ASCVD progression, representing an efficacious adjunctive therapeutic modality.

In China, the Innovation Demonstration Zone for the National Sustainable Development Agenda is a key initiative for executing the United Nations (UN) 2030 Agenda for Sustainable Development. The Zone also plays critical roles in addressing the developmental bottlenecks that China faces and sharing Chinese insights into global sustainable development efforts. On July 15, 2022, the State Council endorsed the Zone’s establishment in Zaozhuang City, Shandong Province, where it focuses on innovation-led sustainable development in rural areas. Research into the levels, impediments, interdependencies, and evolutionary trends of rural sustainable development is crucial. Therefore, this research aimed to assist in comprehensively assessing developmental challenges and facilitating the harmonious advancement of social, economic, and environmental aspects in rural areas. In pursuit of the three fundamental dimensions of the UN’s Sustainable Development Goals (SDGs), namely development’s drivers, quality, and equity, this study was grounded in China’s national Rural Revitalization Strategy and the demands of sustainable development strategies. It also aligns with the UN 2030 Agenda for Sustainable Development and the associated SDG indicators. Focusing on four key areas, namely production elements, natural elements, social elements, and rural governance, this study developed an evaluation index system for assessing the level of rural sustainable development. It employed a range of analytical models, including the game theory-based combination empowerment method, barrier degree model, coupling degree model, coupling coordination degree model, and gray prediction GM(1,1) model, to analyze the status and evolving trends of rural sustainable development in Zaozhuang City from 2015 to 2022. The key findings were as follows: ① Relative to the baseline year 2015, the sustainable development level in Zaozhuang’s rural areas has shifted toward an improved state overall. ② The primary barrier to achieving rural sustainable development in Zaozhuang is the city’s rural governance system. ③ While the components of rural sustainable development in Zaozhuang are in the early stages of both basic and moderate coordination, an overall enhancement has occurred in their integrative coordination. ④ Between 2023 and 2025, the level of integrative coordination in Zaozhuang is expected to rise steadily. However, reaching a state of advanced coordination will require additional time for development.

Due to the common characteristics of major communicable and non-communicable chronic diseases targeted by major disease prevention and control measures – such as variability and ambiguity – both face common challenges in the implementation of group strategy. Additionally, these strategies must be conducted within the units/institutions/communities where people work, study, and live, focusing on groups rather than individuals, thus inherently involving organizational behavior. This paper proposes addressing the common issues of group prevention and control of major diseases from the perspective of organizational behavior, leveraging collective power through organizational roles. Moreover, based on relevant studies, it preliminarily introduces four organizational behavior elements aimed at addressing these common issues and analyzes the interrelationships among these four elements.

Abstract Mesenchymal stem cells (MSCs) in tumor microenvironment (TME) are crucial for the initiation, development, and metastasis of cancer. The impact and mechanism of MSCs on bladder cancer are uncertain. Here we analyzed 205 patient samples to explore the relationships between tumor-stroma ratio and clinicopathological features. A co-culture model and nude mouse transplantation were used to explore the biological roles and molecular mechanisms of MSCs on bladder cancer cells. We found that a high tumor-stroma ratio was significantly associated with a larger tumor size and higher T stage, pathological grade, number of vascular invasions, and poor overall survival. MSCs in TME promoted the ability of bladder cancer cells to proliferate, migrate, and invade in vitro and in vivo. Next, we demonstrated that MSCs enhance mitochondrial autophagy and mitochondrial biogenesis of bladder cancer cells, and increase energy production, thereby promoting bladder cancer cell progression. Kynurenine (Kyn) produced by MSCs could enhance mitochondrial function by activating the AMPK pathway. IDO1 inhibitor could reverse the tumor‑promoting effects of MSCs in vitro and in vivo. Our results demonstrated that tryptophan metabolites Kyn of MSCs in TME could enhance mitochondrial function by activating the AMPK pathway, thereby promoting bladder cancer cell progression.

Abstract The prognosis of extensive-stage small cell lung cancer is usually poor. In this study, a combined model based on pre-treatment CT radiomics and clinical features was constructed to predict the OS of extensive-stage small cell lung cancer after chemotherapy with immunotherapy.Clinical data of 111 patients with extensive stage small-cell lung cancer who received first-line immunotherapy combined with chemotherapy in our hospital from December 2019 to December 2021 were retrospectively collected. Finally, 93 patients were selected for inclusion in the study, and CT images were obtained through PACS system before treatment. All patients were randomly divided into a training set (n = 66) and a validation set (n = 27). Images were imported into ITK-SNAP to outline areas of interest, and Python software was used to extract radiomics features. A total of 1781 radiomics features were extracted from each patient’s images. The feature dimensions were reduced by MRMR and LASSO methods, and the radiomics features with the greatest predictive value were screened. The weight coefficient of radiomics features was calculated, and the linear combination of the feature parameters and the weight coefficient was used to calculate Radscore. Univariate cox regression analysis was used to screen out the factors significantly associated with prognosis from the radiomics and clinical features, and multivariate cox regression analysis was performed to establish the prognosis prediction model of extensive stage small cell lung cancer. The degree of metastases was selected as a significant clinical prognostic factor by univariate cox regression analysis. Seven radiomics features with significance were selected by LASSO-COX regression analysis, and the Radscore was calculated according to the coefficient of the radiomics features. An alignment diagram survival prediction model was constructed by combining Radscore with the number of metastatic lesions. The study population was stratified into those who survived less than 11 months, and those with a greater than 11 month survival. The C-index was 0.722 (se = 0.044) and 0.68(se = 0.074) in the training and the validation sets, respectively. The Log_rank test results of the combination model were as follows: training set: p

Abstract Background BCR-ABL is a constitutively active tyrosine kinase that stimulates multiple downstream signaling pathways to promote the survival and proliferation of chronic myeloid leukemia (CML) cells. The clinical application of specific BCR-ABL tyrosine kinase inhibitors (TKIs) has led to significantly improved prognosis and overall survival in CML patients compared to previous treatment regimens. However, direct targeting of BCR-ABL does not eradicate CML cells expressing T315I-mutated BCR-ABL. Our previous study revealed that inhibiting CREB binding protein (CBP) is efficacious in activating β-catenin/p300 signaling, promoting cell differentiation and inducing p53/p21-dependent senescence regardless of BCR-ABL mutation status. We hypothesize that the specific inhibition of CBP may represent a novel strategy to promote β-catenin/p300-mediated differentiation and suppress cancer cell proliferation for treating CML patients. Methods The anticancer efficacy of PBA2, a novel CBP inhibitor, in CML cells expressing wild-type or T315I-mutated BCR-ABL was investigated in vitro and in vivo. Cell differentiation was determined by the nitroblue tetrazolium (NBT) reduction assay. The extent of cellular senescence was assessed by senescence-associated β-galactosidase (SA-β-Gal) activity. Cytotoxicity was measured by MTS assay. RNA interference was performed to evaluate the cell proliferation effects of CBP knockdown. The interaction of β-catenin and CBP/p300 was examined by co-immunoprecipitation assay. Results PBA2 exhibited significantly higher anticancer effects than imatinib in CML cells harboring either wild-type or T315I-mutated BCR-ABL both in vitro and in vivo. Mechanistically, PBA2 reduced CBP expression and promoted β-catenin-p300 interaction to induce cell differentiation and senescence. Conclusion Our data supported the rational treatment of CML by inhibiting the β-catenin/CBP pathway regardless of BCR-ABL mutation status.

Abstract Given the surpassing of the Shockley-Quiesser efficiency limit in conventional p-n junction photovoltaic effect, bulk photovoltaic effect (BPVE) has garnered significant research interest. However, the BPVE primarily focuses on a narrow wavelength range, limiting its potential applications. Here we report a giant infrared bulk photovoltaic effect in tellurene (Te) for broad-spectrum neuromodulation. The generated photocurrent in uniformly illuminated Te excludes other photoelectric effects and is attributed to the BPVE. The bulk photovoltaic wavelength in Te spans a wide range from the ultraviolet (390 nm) to the mid-infrared (3.8 µm). Moreover, the photocurrent density of 70.4 A cm−2 under infrared light simulation outperforms that in previous ultraviolet and visible semiconductors as well as infrared semimetals. Te attached to the dendrites or somata of the cortical neurons successfully elicit action potentials under broad-spectrum light irradiation. This work lays the foundation for the further development of infrared BPVE in narrow bandgap materials.

Abstract Background X-linked agammaglobulinemia (XLA), also referred to as Bruton’s tyrosine kinase deficiency, is a rare genetic disorder that affects the immune system. We conducted genetic analysis on patients suffering from immunodeficiency by utilizing Next-Generation Sequencing techniques, as well as their closest relatives, to facilitate accurate diagnosis, offer genetic counseling services, and enhance our comprehension of XLA.

Objective: To establish a method for simultaneous determination of nine active components in the fermented tea of Trametes versicolor, and analyze the changes of nine active components and antioxidant activities fermentation before and after. Methods: Using gradient elution at a flow rate of 1.0 mL/min, an Agilent C18 column (4.6 mm×250 mm, 5 μm) was used with a mobile of 0.05% phosphoric acid solution (A) and acetonitrile (B) as the mobile phase. The detection wavelength was 280 nm and the column temperature was 30 ℃. Results: Compared with the control group unfermented green tea, there was no significant change in the caffeine content of fermented tea. The increasing rates of gallic acid, theobromine and gallatechin gallate content in fermented tea were 0.4613%, 0.3118% and 0.5770%, respectively. The decreasing rates of egallatechin, theophylline, epigallocatechin, epicatechin and epigallocatechin gallate content in fermented tea were 0.0156%, 0.0178%, 1.2938%, 1.1062% and 4.0241%, respectively. In vitro antioxidant activity studies revealed that DPPH· scavenging capacity and ·OH scavenging capacity were significantly (P

Abstract Background Follicular cysts contribute significantly to reproductive loss in high-yield dairy cows. This results from the death of follicular granulosa cells (GCs) caused by oxidative stress. Quercetin is known to have significant antioxidant and anti-apoptotic effects. However, the effect of quercetin on follicular cysts has yet been elucidated. Therefore, this study aimed to explore the anti-oxidant and anti-apoptosis effects and potential molecular mechanisms of quercetin in H2O2-induced primary cow GCs and 3-nitropropionic acid (3-NPA)-induced mouse model of oxidative stress and thus treat ovarian cysts in dairy cows. Results In this study, compared with estrus cows, cows with follicular cysts showed heightened levels of oxidative stress and increased follicular cell apoptosis, while autophagy levels were reduced. A model of oxidative stress was induced in vitro by H2O2 and showed significant increases in apoptosis together with reduced autophagy. These effects were significantly ameliorated by quercetin. Effects similar to those of quercetin were observed after treatment of cells with the reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC). Further investigations using chloroquine (autophagy inhibitor), rapamycin (autophagy activator), selisistat (SIRT1 inhibitor), and compound C (AMPK inhibitor) showed that chloroquine counteracted the effects of quercetin on oxidative stress-induced apoptosis, while rapamycin had the same effect as quercetin. In addition, the SIRT1/AMPK pathway inhibitors antagonized quercetin-mediated mitigation of the effects of oxidative stress on increased apoptosis and reduced autophagy. Consistent with the results in vitro, in mouse ovarian oxidative stress model induced by 3-NPA, quercetin activated autophagy through the SIRT1/AMPK signaling pathway, while alleviating oxidative stress damage and inhibiting apoptosis in mouse ovaries. Conclusions These findings indicate that quercetin can inhibit apoptosis in GCs and restore ovarian function by activating autophagy through the SIRT1/ROS/AMPK signaling pathway, suggesting a new direction for the treatment of ovarian follicular cysts in high-yield dairy cows.

Abstract Background Off-label intranasal administration of injectable dexmedetomidine has been widely applied in the pediatric sedation setting. However, the development of an improved drug delivery system that is easy to use is needed. We developed a novel dexmedetomidine nasal spray that can be administered directly without dilution or configuration for pediatric pre-anesthetic sedation. This nasal spray has a fixed dose and is stable during storage. To the best of our knowledge, this is the first licensed nasal spray preparation of dexmedetomidine worldwide. Objective To evaluate the pre-anesthetic sedation efficacy and safety of the novel dexmedetomidine nasal spray in children. Methods The study was conducted at 11 sites in China between 24 November 2021 and 20 May 2022 and was registered in ClinicalTrials.gov (NCT05111431, first registration date: 20/10/2021). Subjects (n = 159) between 2 and 6 years old who were to undergo elective surgery were randomized to the dexmedetomidine group (n = 107) or the placebo group (n = 52) in a 2:1 ratio. The dosage was 30 µg or 50 µg based on the stratified body weight. The primary outcome measure was the proportion of subjects who achieved the desired child-parent separation and Ramsay scale ≥ 3 within 45 min of administration. Safety was monitored via the assessments of adverse events, blood pressure, heart rate, respiratory rate and blood oxygen saturation. Results The proportion of subjects achieving desired parental separation and Ramsay scale ≥ 3 within 45 min was significantly higher in the dexmedetomidine group (94.4%) vs the placebo group (32.0%) (P

Transcutaneous implants that penetrate through skin or mucosa are susceptible to bacteria invasion and lack proper soft tissue sealing. Traditional antibacterial strategies primarily focus on bacterial eradication, but excessive exposure to bactericidal agents can induce noticeable tissue damage. Herein, a rechargeable model (HPI-Ti) was constructed using perylene polyimide, an aqueous battery material, achieving temporal-sequence regulation of bacterial killing and soft tissue sealing. Charge storage within HPI-Ti is achieved after galvanostatic charge, and chemical discharge is initiated when immersed in physiological environments. During the early discharge stage, post-charging HPI-Ti demonstrates an antibacterial rate of 99.96 ± 0.01 % for 24 h, preventing biofilm formation. Contact-dependent violent electron transfer between bacteria and the material causes bacteria death. In the later discharge stage, the attenuated discharging status creates a gentler electron-transfer micro-environment for fibroblast proliferation. After discharge, the antibacterial activity can be reinstated by recharge against potential reinfection. The antibacterial efficacy and soft tissue compatibility were verified in vivo. These results demonstrate the potential of the charge-transfer-based model in reconciling antibacterial efficacy with tissue compatibility.

Dynamic cross-linked networks (DCNs) endow thermoset rubber with self-healability and recyclability to extend its lifetime and alleviate environmental pollution. However, the contradiction between high self-healing and mechanical properties in DCNs rubber is always difficult to be resolved. Herein, we used boronic ester (BO) and Diels-Alder dynamic covalent bonds (DA) to synthesize polybutadiene-based dual networks rubber (PB-BO-DA) via thiol-ene reaction. This approach achieved a tensile strength of 16.46 MPa and 99% self-healing efficiency, facilitated by extensive intermolecular interactions (π-π packing and N-B coordination) and fully dynamic cross-linking. In addition, multiple dynamic cross-linked networks (MDCNs) polybutadiene-based rubber also show excellent shape memory ability and recyclability. This strategy might open a helpful pathway to fabricate intelligent multifunctional polymers with high strength and high self-healing efficiency.

Artificial intelligence (AI) holds significant promise in transforming medical imaging, enhancing diagnostics, and refining treatment strategies. However, the reliance on extensive multicenter datasets for training AI models poses challenges due to privacy concerns. Federated learning provides a solution by facilitating collaborative model training across multiple centers without sharing raw data. This study introduces a federated attention-consistent learning (FACL) framework to address challenges associated with large-scale pathological images and data heterogeneity. FACL enhances model generalization by maximizing attention consistency between local clients and the server model. To ensure privacy and validate robustness, we incorporated differential privacy by introducing noise during parameter transfer. We assessed the effectiveness of FACL in cancer diagnosis and Gleason grading tasks using 19,461 whole-slide images of prostate cancer from multiple centers. In the diagnosis task, FACL achieved an area under the curve (AUC) of 0.9718, outperforming seven centers with an average AUC of 0.9499 when categories are relatively balanced. For the Gleason grading task, FACL attained a Kappa score of 0.8463, surpassing the average Kappa score of 0.7379 from six centers. In conclusion, FACL offers a robust, accurate, and cost-effective AI training model for prostate cancer pathology while maintaining effective data safeguards.

Objective To conduct Rh blood group serological testing and third-generation sequencing(TGS) on 22 RhD variant voluntary blood donors in Chongqing and explore the phenotypic distribution and genotyping of RhD variants in Chongqing. Methods From January to August 2023, individuals who participated in blood donation in our blood center were selected as the study objects. RhD variant phenotype identification was performed using routine serological methods. Once the RhD variants were identified, tests on different antigenic epitopes of RhD were conducted using a D-screen assay kit. Furthermore, after the genomic DNA from 22 RhD variant blood samples was extracted, imbraided primers design and multi-segment amplification and splicing were used to sequence the full-length RHD gene for TGS. The RHD gene sequence was analyzed using SnapGene software. Results Among the 22 RhD variants, 8 were DVI type 3 (36.36%), with the main mutation of RHD-CE (3-6)-D hybrid allele. Six cases (27.27%) showed partial weak D15 type, with the main mutation of c.845G>A. There were 6 cases of Asia type Del (27.27%), with the main mutation of c.1227G>A. One case was weak D17 type with a mutation of c.340C>T and 1 case speculated to be partial D (c.491A>T, p. Asp164Val, missense mutation). Conclusion The most common RhD variant phenotype among blood donors in Chongqing is DVI type 3, and the full-length haplotype sequence of RHD variant alleles can be obtained by Pacific Bioscience single-molecule real-time sequencing(SMRT).

Objective To explore the causes and nursing strategies of red blood cell spillage in apheresis platelet donors, so as to avoid adverse reactions to blood donation and platelet discarding and improve blood donation services. Methods A nursing flowchart for red blood cell spillage was developed based on literature. One case of red blood cell spillage in a apheresis platelet donor as attached, and corresponding literature review was conducted. Results After the nursing intervention through the nursing flowchart of red cell spillage, platelet apheresis was successfully conducted. The donor felt good and did not experience any adverse reaction to blood donation, and with no more red blood cell spillage. By reviewing relevant literature, the incidence, principles, causes, treatments, prevention of adverse reactions to blood donation and psychological care methods of red blood cell spillage were systematically summarized. Conclusion Red blood cell spillage in apheresis platelet donors occurs occasionally, and a flowchart of care for red blood cell spillage can help blood station staff quickly identify the cause and handle it correctly to avoid mishandling whicn can result in adverse reactions or discarding of platelets.

Abstract Although thrombocytopenia on admission to the ICU is associated with increased in-hospital mortality in septic patients, the role of longitudinally measured platelet counts, which are dynamically changing, is unclear. We aimed to identify patterns of dynamic platelet count trajectories and evaluate their association with outcomes and thrombocytopenia in septic patients. We tested the longitudinal platelet trajectory patterns of sepsis patients within the first four days of ICU admission in the MIMIC-IV database and their association with 28-day mortality, and independently validated our findings in the eICU-CRD database. Statistical methods used included multivariate regression, propensity score analysis, doubly robust estimation, gradient boosting model, and inverse probability weighting to ensure the robustness of our findings. A total of 22,866 septic patients were included in our study. The trajectory analysis categorizes patients into ascending (AS), stable (ST), or descending (DS) patterns. The risk of 28-day mortality was increased in the DS patients (OR = 2.464, 95%CI 1.895–3.203, p

Abstract Background Hepatitis B virus (HBV) infection is a major concern regarding blood safety in countries with a high HBV prevalence, such as China. We aimed to understand the prevalence of HBV infection among blood donors in Chongqing and provide an important basis for developing appropriate blood screening strategies. Methods Dual enzyme-linked immunosorbent assays (ELISAs) for hepatitis B surface antigen (HBsAg) were conducted in parallel with nucleic acid testing (NAT) of donors. All HBsAg-reactive and/or HBV DNA-positive blood samples were tested for HBsAg and hepatitis B DNA levels. Results A total of 117,927 blood donor samples were collected from the Chongqing Blood Center between April 2020 and November 2020. In total, 473 HBV-ineligible samples were retained for HBsAg and DNA confirmation. A total of 272 samples were confirmed to be HBsAg+, including 2 HBV DNA − and 270 HBV DNA + samples. A total of 201 donations were HBsAg−, including 72 HBV DNA − samples. The rate of HBV infection was 65.33% (309/473) in men, which was significantly higher than that in women (p

Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is a severe disease with substantial economic consequences for the swine industry. The DEAD-box helicase 3 (DDX3X) is an RNA helicase that plays a crucial role in regulating RNA metabolism, immunological response, and even RNA virus infection. However, it is unclear whether it contributes to PRRSV infection. Recent studies have found that the expression of DDX3X considerably increases in Marc-145 cells when infected with live PRRSV strains Ch-1R and SD16; however, it was observed that inactivated viruses did not lead to any changes. By using the RK-33 inhibitor or DDX3X-specific siRNAs to reduce DDX3X expression, there was a significant decrease in the production of PRRSV progenies. In contrast, the overexpression of DDX3X in host cells substantially increased the proliferation of PRRSV. A combination of transcriptomics and metabolomics investigations revealed that in PRRSV-infected cells, DDX3X gene silencing severely affected biological processes such as ferroptosis, the FoxO signalling pathway, and glutathione metabolism. The subsequent transmission electron microscopy (TEM) imaging displayed the typical ferroptosis features in PRRSV-infected cells, such as mitochondrial shrinkage, reduction or disappearance of mitochondrial cristae, and cytoplasmic membrane rupture. Conversely, the mitochondrial morphology was unchanged in DDX3X-inhibited cells. Furthermore, silencing of the DDX3X gene changed the expression of ferroptosis-related genes and inhibited the virus proliferation, while the drug-induced ferroptosis inversely promoted PRRSV replication. In summary, these results present an updated perspective of how PRRSV infection uses DDX3X for self-replication, potentially leading to ferroptosis via various mechanisms that promote PRRSV replication.

Abstract Background Accumulating studies have highlighted the significant role of circulating metabolomics in the etiology of reproductive system disorders. However, the causal effects between genetically determined metabolites (GDMs) and reproductive diseases, including primary ovarian insufficiency (POI), polycystic ovary syndrome (PCOS), and abnormal spermatozoa (AS), still await thorough clarification. Methods With the currently most comprehensive genome-wide association studies (GWAS) data of metabolomics, systematic two-sample Mendelian randomization (MR) analyses were conducted to disclose causal associations between 1,091 blood metabolites and 309 metabolite ratios with reproductive disorders. The inverse-variance weighted (IVW) method served as the primary analysis approach, and multiple effective MR methods were employed as complementary analyses including MR-Egger, weighted median, constrained maximum likelihood (cML-MA), contamination mixture method, robust adjusted profile score (MR-RAPS), and debiased inverse-variance weighted method. Heterogeneity and pleiotropy were assessed via MR-Egger intercept and Cochran’s Q statistical analysis. Outliers were detected by Radial MR and MR-PRESSO methods. External replication and metabolic pathway analysis were also conducted. Results Potential causal associations of 63 GDMs with POI were unearthed, and five metabolites with strong causal links to POI were emphasized. Two metabolic pathways related to the pathogenesis of POI were pinpointed. Suggestive causal effects of 70 GDMs on PCOS were detected, among which 7 metabolites stood out for strong causality with elevated PCOS risk. Four metabolic pathways associated with PCOS mechanisms were recognized. For AS, 64 GDMs as potential predictive biomarkers were identified, particularly highlighting two metabolites for their strong causal connections with AS. Three pathways underneath the AS mechanism were identified. Multiple assessments were conducted to further confirm the reliability and robustness of our causal inferences. Conclusion By extensively assessing the causal implications of circulating GDMs on reproductive system disorders, our study underscores the intricate and pivotal role of metabolomics in reproductive ill-health, laying a theoretical foundation for clinical strategies from metabolic insights.

Abstract Circular RNA (circRNA) is thought to mediate the occurrence and development of human cancer and usually acts as a tiny RNA (miRNA) sponge to regulate downstream gene expression. However, it is not clear whether and how circACVR2A (hsa_circ_0001073) is involved in the progression of HCC. The purpose of this study is to clarify the potential role and molecular mechanism of circACVR2A in regulating the progression of hepatocellular carcinoma cells (HCC). The abundance of related proteins in circACVR2A, microRNA (miR511-5p) and PI3K-Akt signaling pathway was determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) or Western blotting. Cell viability, invasion and apoptosis were analyzed by CCK-8, Transwell analysis and Tunel staining, respectively. The interaction between circACVR2A and microRNA was evaluated by double luciferase reporter gene assay. The results showed that circACVR2A was highly expressed in hepatocellular carcinoma cell lines. Our in vivo and in vitro data showed that circACVR2A promoted the proliferation, migration and invasion of HCC. In terms of mechanism, we found that circACVR2A can directly interact with miR511-5p and act as a miRNA sponge to regulate the expression of related proteins in PI3K-Akt signaling pathway. In HCC, circACVR2A can mediate miR-511-5p/mRNA network to activate PI3K signal pathway. This shows that the molecular regulatory network with circACVR2A as the core is a new potential target for diagnosis and treatment of hepatocellular carcinoma.

Abstract The separation and purification of chemical raw materials, particularly neutral compounds with similar physical and chemical properties, represents an ongoing challenge. In this study, we introduce a class of water-soluble macrocycle compound, calix[2]azolium[2]benzimidazolone (H), comprising two azolium and two benzimidazolone subunits. The heterocycle subunits form a hydrophobic binding pocket that enables H1 to encapsulate a series of neutral guests in water with 1:1 or 2:1 stoichiometry, including aldehydes, ketones, and nitrile compounds. The host-guest complexation in the solid state was further confirmed through X-ray crystallography. Remarkably, H1 was shown to be a nonporous adaptive crystal material to separate valeraldehyde from the mixture of valeraldehyde/2-methylbutanal/pentanol with high selectivity and recyclability in the solid states. This work not only demonstrates that azolium-based macrocycles are promising candidates for the encapsulation of organic molecules but also shows the potential application in separation science.

Abstract The deep ultraviolet (DUV) micro-light emitting diode (μLED) has serious electron leakage and low hole injection efficiency. Meanwhile, with the decrease in the size of the LED chip, the plasma-assisted dry etching process will cause damage to the side wall of the mesa, which will form a carrier leakage channel and produce non-radiative recombination. All of these will reduce the photoelectric performance of μLED. To this end, this study introduces polarized bulk charges into the hole supply layer (p-HSL) and the electron supply layer (n-ESL) respectively (dual-polarized structure) of the DUV μLED at an emission wavelength of 279 nm to enhance the binding of carriers and increase the injection efficiency of carriers. This is because the polarization-induced bulk charge can shield the polarized sheet charge on the interface and reduce the polarization electric field. The reduced polarization electric field in p-HSL can increase the effective barrier height of the conduction band in the p-type region and reduce the effective barrier height of the valence band. The decrease in the polarized electric field of n-HSL can reduce the thermal velocity of electrons, thereby enhancing the electron injection efficiency, reducing the Shockley–Read–Hall (SRH) recombination, and increasing the effective barrier height of the valence band. The study results indicate that the electron concentration and hole concentration of a μLED with dual polarization were increased by 77.93% and 93.6%, respectively. The optical power and maximum external quantum efficiency of μLED reached 31.04 W/cm2 and 2.91% respectively, and the efficiency droop is only 2.06% at 120 A/cm2. These results provide a new approach to solving the problem of insufficient carrier injection and SRH recombination in high-performance DUV μLEDs.

Abstract Background There is evidence suggesting that Notch1 signaling pathway contributes to the development of hand, foot, and mouth disease (HFMD); however, the role of Notch1 gene polymorphisms in the severity of coxsackievirus A6 (CVA6)-related HFMD remains unclear. This study aimed to investigate the correlation between Notch1 gene polymorphisms and the severity of CVA6-related HFMD. Methods A total of 196 patients (Chinese Han population) diagnosed with CVA6-related HFMD through nucleic acid testing were included in this study. Among them, 97 patients were classified as severe cases, while 99 cases were categorized as mild. The mRNA levels of Notch1 in the peripheral blood leukocytes of HFMD patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was utilized for genotyping of rs3124599, rs3124603, and rs3124591. Results The frequencies of rs3124599 alleles were G (39.0%) and A (61.0%), while the frequencies of rs3124599 genotypes were GG (12.2%), GA (53.6%), and AA (34.2%), respectively. In the recessive model, the frequency of rs3124599 AA genotypes significantly increased in severe patients, compared to mild patients (P 0.05), no additional statistical analysis was performed. After adjusting for age and sex, patients with rs3124599 AA genotype had a significantly higher risk of severe HFMD in comparison to G allele carriers (GA/GG), with an odds ratio (95% confidence interval) of 2.010 (1.094, 3.691). Meanwhile, the mRNA levels of Notch1 were found to be significantly higher in severe patients compared to mild patients (P

Abstract Background Ferroptosis is associated with the pathological progression of hemorrhagic injury and ischemia–reperfusion injury. According to our previous study, exosomes formed through bone marrow mesenchymal stem cells modified with miR-340-3p (MB-exos) can restore damaged endometrium. However, the involvement of ferroptosis in endometrial injury and the effect of MB-exos on ferroptosis remain elusive. Methods The endometrial injury rat model was developed. Exosomes were obtained from the supernatants of bone marrow mesenchymal stromal cells (BMSCs) and miR-340/BMSCs through differential centrifugation. We conducted RNA-seq analysis on endometrial tissues obtained from the PBS and MB-exos groups. Ferroptosis was induced in endometrial stromal cells (ESCs) by treating them with erastin or RSL3, followed by treatment with B-exos or MB-exos. We assessed the endometrial total m6A modification level after injury and subsequent treatment with B-exos or MB-exos by methylation quantification assay. We performed meRIP-qPCR to analyze m6A modification-regulated endogenous mRNAs. Results We reveal that MB-exos facilitate the injured endometrium to recover by suppressing ferroptosis in endometrial stromal cells. The injured endometrium showed significantly upregulated N 6-methyladenosine (m6A) modification levels; these levels were attenuated by MB-exos through downregulation of the methylase METTL3. Intriguingly, METTL3 downregulation appears to repress ferroptosis by stabilizing HMOX1 mRNA, thereby potentially elucidating the mechanism through which MB-exos inhibit ferroptosis in ESCs. We identified YTHDF2 as a critical m6A reader protein that contributes to HMOX1 mRNA degradation. YTHDF2 facilitates HMOX1 mRNA degradation by identifying the m6A binding site in the 3′-untranslated regions of HMOX1. In a rat model, treatment with MB-exos ameliorated endometrial injury-induced fibrosis by inhibiting ferroptosis in ESCs. Moreover, METTL3 short hairpin RNA-mediated inhibition of m6A modification enhanced the inhibitory effect of MB-exos on ferroptosis in endometrial injury. Conclusions Thus, these observations provide new insights regarding the molecular mechanisms responsible for endometrial recovery promotion by MB-exos and highlight m6A modification-dependent ferroptosis inhibition as a prospective therapeutic target to attenuate endometrial injury.

Abstract Background This study aims to analyze the efficacy of metformin on carotid intima media thickness (CIMT) and flow-mediated dilation (FMD) for patients with polycystic ovary syndrome (PCOS). Methods A literature search of PubMed, Embase, and the Cochrane Library from inception to December 2023 was conducted. Then, after studies selection and data extraction, the mean difference (MD) with a 95% confidence interval (CI) was used to evaluate metformin efficacy in CIMT and FMD for PCOS patients. Heterogeneity was investigated through subgroup and sensitivity analysis. The protocol of our study has been registered in PROSPERO (CRD42024497239). Results A total of 12 studies with 248 patients were included. CIMT was lower in the endpoint group (after metformin) compared with the baseline group (before metformin) (MD = -0.11, 95% CI = -0.21 to -0.01, p = 0.04). FMD was higher in the endpoint group compared with the baseline group (MD = 3.25, 95% CI = 1.85 to 4.66, p

Abstract Background kangaroo care (KC), endorsed by the World Health Organization, is an evidence-based intervention that plays a pivotal role in mitigating preterm infant mortality and morbidity. However, this intervention has not been fully integrated into healthcare systems in China. This study aimed to gain insight into parents’ perceptions and experiences of KC for preterm infants to contribute to the KC implementation on a larger scale. Methods This study employed a descriptive qualitative design, using face-to-face, semi-structured, in-depth interviews. Fifteen parents participating in KC for preterm infants in the neonatal intensive care units (NICUs) were purposively sampled from four hospitals across four cities in Zhejiang Province, China. Thematic analysis was employed to analyze the data. Results Four themes and twelve subthemes regarding the parents’ perceptions and experiences about KC were identified. The four themes included: (1) Low motivation upon initial engagement with KC, (2) Dynamic fluctuations of emotional states during KC, (3) Unexpected gains, and (4) Barriers to participation. Conclusions Parents’ perceptions and experiences of KC was a staged process, with parents exhibiting distinct cognitive patterns and unique experiences at each stage. Overall, as KC progresses, parents’ experiences tended to become increasingly positive, despite potential obstacles encountered along the way. To enhance the implementation of KC, healthcare providers could utilize prenatal and postnatal education programs. These programs aim to enhance the understanding of KC among parents of preterm infants, fostering sustained engagement in KC practices.

Abstract Establishing prediction models of pregnancy outcomes for recurrent pregnancy loss women at specific gestational weeks will provide patients and physicians with more precise information, ultimately leading to time and cost savings associated with unnecessary revisits. Therefore, our aim was to develop a prediction model for first trimester pregnancy loss in RPL patients. We used ultrasound indices during the first trimester of pregnancy in combination with demographic characteristics and commonly used serum markers. The independent risk factors for each week were as follows: age and P in the fifth week; age, mGSD and CRL in the sixth week; age, hCG and CRL in the seventh week; CRL in the eighth week; mGSD and CRL in ninth week. The corresponding AUC was 0.671, 0.796, 0.872, 0.871, 0.813, respectively. There is a linear relationship between age and first trimester pregnancy loss. hCG 48.3 mm in ninth gestational week was associated with a higher risk of pregnancy loss. These models and thresholds may help physicians and patients make more informed decisions together. Further studies are needed to confirm the results.

Abstract Background Many long noncoding RNAs (lncRNAs) with altered expression significantly influence colorectal cancer (CRC) progression and behavior. The functions of many lncRNAs in CRC are not clear yet. This study aimed to discover novel lncRNA entities and comprehensively examine and validate their roles and underlying molecular mechanisms in CRC. Methods Tissue samples, both tumourous and non-tumourous, from three CRC patients were submitted for sequencing. Following expression validation in samples from ten patients and four CRC cell lines. The lncRNA KCNMA1-AS2 was synthesized by In-vitro transcription RNA synthesis and the lncRNA was directly transfected into CRC cell lines to overexpress. Functional assays including MTT proliferation assay, Annexin-V/propidium iodide apoptosis assay, wound healing migration assay and cell cycle assays were performed to evaluate the effect of overexpression of KCNMA1-AS2. Furthermore, the binding of KCNMA1-AS2 to miR-1227-5p was confirmed using dual luciferase reporter assays and qPCR analyses. Subsequent bioinformatics analyses identified 58 potential downstream targets of miR-1227-5p across three databases. Results In this study, we identified the lncRNA KCNMA1-AS2, the expression of which was down-regulated consistently in cancer tissues and CRC cell lines compared to non-cancerous tissues. The overexpression of lncRNA KCNMA1-AS2 led to significant reduction in CRC cell proliferation and migration, increase in cell apoptosis, and more cells arrested in S phase. Additionally, the interaction between KCNMA1-AS2 and miR-1227-5p was confirmed through dual luciferase reporter assay and qPCR analysis. It is also putatively predicted that MTHFR and ST8SIA2 may be linked to CRC based on bioinformatics analyses. Conclusions LncRNA KCNMA1-AS2 exhibited distinct gene expression patterns in both CRC tissue and cell lines, impacting various cellular functions while also acting as a sponge for miR-1227-5p.The findings spotlight lncRNA KCNMA1-AS2 as a potential marker for diagnosis and treatment of CRC.

Abstract This study aimed to investigate the effects of tea green leafhopper damage on the sensory quality and metabolite composition of Oriental Beauty by using tea leaves from different varieties of tea plants and processing factories. The results indicated that tea green leafhopper damage could reduce bitterness and increase the level of fruity aroma, which was related to the content changes of catechin components and alcohol substances. Furthermore, the tea green leafhopper salivary treatment experiment revealed that the decrease of catechin content and increase of theaflavin content were mainly influenced by the action of saliva and mechanical injury, and changes in volatile components such as linalool oxidation were responsible for the alteration in aroma. These findings provide a theoretical reference for the aroma formation and quality improvement of Oriental Beauty.