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Dazu vocal music, a unique and cherished intangible cultural heritage, serves as the focal point of this research conducted in Chongqing, China. The study's objective is to investigate the contribution of cultural transmission of Dazu vocal music in Chongqing through education and literacy. The research site, Dazu City, is the epicenter of this cultural treasure, encompassing various educational institutions from primary to tertiary levels that engage with this art form. Two key informants, comprising experienced instructors and cultural representatives, offer valuable insights into the educational initiatives and literacy practices supporting Dazu vocal music. Research tools, including observation and interview forms, are employed for data collection, culminating in a detailed analysis of the cultural transmission process. The study's results underscore education's pivotal role in preserving Dazu vocal music, fostering hand-son learning, and promoting cultural documentation, with literacy facilitating accessibility beyond oral traditions. These efforts positively impact the local community by enhancing cultural identity and pride. Despite challenges such as an aging practitioner population and shifting cultural dynamics, collaboration among stakeholders emerges as a promising strategy for ensuring the tradition's continuity. In conclusion, this research highlights the importance of education and literacy in preserving intangible cultural heritage, offering insights applicable to similar endeavors worldwide.

Objective To systematically evaluate the impact of chronic kidney disease (CKD) on pregnancy outcomes in pregnant patients. Methods Computer searching was conducted within the databases of MEDLINE, EMBASE, WANFANG DATA, China National Knowledge Infrastructure (CNKI) and China Biomedical Literature Database (CBM) from the establishment to July 2023 to identify the relevant literature items on the impact of CKD on pregnancy outcomes in pregnant patients. Two researchers independently screened the literature, extracted data and evaluated the quality of the included studies. Meta-analysis was performed with Review Manager 5.3 and STATA 17.0 software. ResultsA total of 15 case-control and cohort studies, including 2,785,115 subjects, were included for final analysis. The results of Meta-analysis demonstrated the following adverse pregnancy outcomes: CKD elevated the risk of adverse pregnancy outcomes, including preeclampsia (OR=2.68, 95%CI:1.47-4.89), gestational hypertension (OR=6.29, 95%CI:2.58-15.32), preterm birth (OR=4.62, 95%CI:2.78-7.67), small for gestational age (OR=1.54, 95%CI:1.24-1.91) and low birth weight (OR=2.44, 95%CI:1.78-3.35). CKD stage 3-5 patients were more prone to severe preeclampsia (OR=2.31, 95%CI:1.35-3.94), preterm birth (OR=5.06, 95%CI:3.28-7.79), small for gestational age (OR=3.85, 95%CI:1.91-7.76), low birth weight (OR=2.90, 95%CI:1.37-6.13) and fetal mortality (OR=3.41, 95%CI:1.33-8.73) as compared with CKD stage 1-2 counterparts. Pregnant patients with massive proteinuria were more prone to severe preeclampsia (OR=2.76, 95%CI:1.89-4.04), gestational hypertension (OR=2.38, 95%CI:1.62-3.50), preterm birth (OR=3.84, 95%CI:2.69-5.47), low birth weight (OR=2.38, 95%CI:1.62-3.50) and fetal mortality (OR=2.45, 95%CI:1.44-4.17) as compared with those with mild proteinuria. Conclusion CKD elevates the risk of adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm birth, small for gestational age and low birth weight. Pregnant patients with CKD stage 3-5 or massive proteinuria (≥1 g) are more prone to adverse pregnancy outcomes as compared with those with CKD stage 1-2 or mild proteinuria (

Abstract Background Hashimoto's thyroiditis (HT) is an autoimmune disorder with unclear molecular mechanisms. While current diagnosis is well-established, understanding of the gut-thyroid axis in HT remains limited. This study aimed to uncover novel molecular signatures in HT by integrating gut metagenome and host transcriptome data (miRNA/mRNA), potentially elucidating disease pathogenesis and identifying new therapeutic targets. Methods We recruited 31 early HT patients and 30 healthy controls in a two-stage study (discovery and validation). Blood and fecal samples underwent RNA and metagenomic sequencing, respectively. Integrative analysis included differential expression, weighted correlation network, correlation and random forest analyses. Regression models and ROC curve analysis were used to evaluate the significance of identified molecular signatures in HT. Results Integrative analysis revealed subtle changes in gut microbiota diversity and composition in early HT, increased abundance of Bacillota_A and Spirochaetota at the phylum level, and significant differences in 24 genera and 67 species. Ecological network analysis indicated an imbalance in the gut microbiota with reduced inhibitory interactions against pathogenic genera in HT. Functional analysis showed changes in infection- and immune-related pathways. Three characteristic species (Salaquimonas_sp002400845, Clostridium_AI_sp002297865, and Enterocloster_citroniae) were identified as most relevant to HT. Analysis of miRNA and mRNA expression profiles uncovered pathways related to immune response, inflammation, infection, metabolism, proliferation, and thyroid cancer in HT. Based on correlations with HT and interactions between them, six characteristic RNAs (hsa-miR-548aq-3p, hsa-miR-374a-5p, GADD45A, IRS2, SMAD6, WWTR1) were identified. Furthermore, our study uncovered significant gut microbiota-host transcriptome interactions in HT, revealing enrichment in metabolic, immune, and cancer-related pathways, particularly with strong associations among those 9 key molecular signatures. The validation stage confirmed improved HT classification accuracy by combining these signatures (AUC = 0.95, ACC = 0.85), suggesting their potential significance in understanding HT pathogenesis. Conclusion Our study reveals novel molecular signatures linking gut microbiome and host transcriptome in HT, providing new insights into the disease pathogenesis. These findings not only enhance our understanding of the gut-thyroid axis but also suggest potential new directions for therapeutic interventions in HT.

Abstract Background The coronavirus disease 2019 (COVID‐19) pandemic has markedly affected end‐of‐life care, notably increasing home deaths among cancer patients in Japan. This study investigated the characteristics of cancer patients who died at home during the pandemic and the associated factors before and during the pandemic. Methods Vital statistics from January 2015 to December 2022 were analyzed to evaluate trends in home deaths among cancer patients aged 0 to 113 years, pre‐pandemic (January 2015 to March 2020) and during the pandemic (April 2020 to December 2022). Home deaths were assessed by demographics, including age, sex, marital status, and residential location. Multivariable modified Poisson regression analyses were performed to identify factors associated with home deaths in both periods. Results Among 3,010,374 individuals, 11.6% (226,571/1,959,304) and 20.8% (218,429/1,051,070) died at home before and during the pandemic, respectively. In subgroup analysis depicting the trend of in‐home deaths by patient characteristics, only the age group showed a differential trend: the proportion of in‐home deaths was higher among older people before the pandemic, whereas it was higher among younger people during the pandemic. The multivariable analysis revealed the excess risk of in‐home deaths among people aged ≥65 years before the pandemic and among those aged

Abstract Metabolic-associated fatty liver disease (MAFLD) is a common chronic condition that poses a significant threat to human health. Mitochondrial dysfunction, particularly involving the mitochondrial Ca2+ uniporter (MCU), plays a key role in its pathogenesis. This study aimed to investigate the impact of the MCU gene on hepatic lipid metabolism in mice fed a high-fat diet. Using MCU knockout and wild-type mice, subjected to either a high-fat or normal diet for 14 weeks, we observed notable Steatosis and liver weight gain in MCU-deficient mice. Liver function markers, serum triglycerides, very low-density lipoprotein (VLDL) levels, and ApoB protein expression were all significantly elevated. Mechanistic studies revealed that MCU deletion led to mitochondrial dysfunction, increased oxidative stress. These findings highlight the critical role of the MCU gene in maintaining hepatic lipid balance and suggest its potential as a therapeutic target for managing nonalcoholic fatty liver disease.

Abstract Background This study investigated the factors influencing the prognosis of children with steroid-resistant nephrotic syndrome (SRNS) in patients from the Guangxi region. Methods We retrospectively analyzed clinical and pathological data of 279 patients with SRNS from six tertiary hospitals in Guangxi. Clinical data were compared between initial (I-SRNS) and secondary (S-SRNS) steroid resistance subgroups and Cox regression analysis was used to determine risk factors for chronic kidney disease (CKD) and CKD stage 5 (CKD5) in patients with SRNS. Results The median age of onset was 54 months. Thirty-three patients had extra-kidney manifestations. Fifty-two, 24, 57, 33, and 41 patients had hypertension, acute kidney injury, vitamin D deficiency, high intraocular pressure, and dwarfism, respectively. One hundred eighty-two and 92 patients had I-SRNS and S-SRNS, respectively. There were significant differences in sex, ethnicity, family history, incidence of hematuria, clinical classification, efficacy of immune agents, and prognosis between groups (P

Abstract Mammary epithelial cells, the only milk-producing cell type in the mammary gland, undergo dynamic proliferation and differentiation during pregnancy, culminating in lactation postpartum. The East FriEsian sheep ranks among the world’s most prolific dairy breeds, while the Sewa sheep, a unique dual-purpose breed autochthonous to the Qinghai-Tibet Plateau, exhibits significantly lower milk production. Employing tissue culture methods, we successfully established mammary epithelial cell lines from both breeds. Morphological assessment of mammary epithelial cells and immunofluorescence identification of Cytokeratin 7 and Cytokeratin 8 confirmed the epithelial identity of the isolated cells. Subsequent RNA-seq analysis of these in vitro epithelial cell lines revealed 1813 differentially expressed genes (DEGs). Among these, 1108 were significantly up-regulated and 705 were down-regulated in Sewa epithelial sheep cells compared to East FriEsian epithelial cells. KEGG enrichment analysis identified cellular processes, environmental information processing, human diseases, metabolism, and organismal systems as the primary functional categories associated with DEGs. Gene ontology (GO) terms annotation, categorized into molecular function, biological processes, and cellular component, yielded “binding and catalytic activity,” “molecular function regulator activity,” and “cellular process,” “biological regulation,” and “regulation of biological process” as the top three terms within each domain, respectively. Clusters of Orthologous Groups of proteins (KOG) classification further revealed that “signal transduction mechanisms” accounted for the largest proportion of DEGs among all KOG categories. Finally, based on these analyses, ATF3 and MPP7 were identified as promising candidate genes for regulating lactation.

To address the global climate crisis, achieving energy transitions is imperative. Establishing a new-type power system is a key measure to achieve CO2 emissions peaking and carbon neutrality. The core goal is to transform renewable energy resources into primary power sources. The large-scale integration of high proportions of renewable energy sources and power electronic devices will dramatically change the operational mechanisms and control strategies of power systems. Existing wind and solar converters mostly adopt the grid-following control mode, which leads to significant challenges in system security and stability as it is insufficient to support the frequency and voltage of the grid. On the other hand, grid- forming control technology (GFM) can provide voltage and frequency support for the system, and thus becomes an effective measure to improve the inertia and damping characteristics of power systems. This paper illustrates the principles, control strategies, equipment types, application scenarios, and project implementation of grid-forming technology. The simulation and analysis based on a renewable-dominated real new-type power system show that GFM can significantly enhance the frequency and voltage support capacity of the power system, improve renewable energy accommodation capacity and grid transmission capacity under weak grid conditions, and play an important role in enhancing the stability and power supply reliability of renewable-dominated new-type power systems.

Abstract Background Blastocyst morphology has been demonstrated to be associated with ploidy status. Existing artificial intelligence models use manual grading or 2D images as the input for euploidy prediction, which suffer from subjectivity from observers and information loss due to incomplete features from 2D images. Here we aim to predict euploidy in human blastocysts using quantitative morphological parameters obtained by 3D morphology measurement. Methods Multi-view images of 226 blastocysts on Day 6 were captured by manually rotating blastocysts during the preparation stage of trophectoderm biopsy. Quantitative morphological parameters were obtained by 3D morphology measurement. Six machine learning models were trained using 3D morphological parameters as the input and PGT-A results as the ground truth outcome. Model performance, including sensitivity, specificity, precision, accuracy and AUC, was evaluated on an additional test dataset. Model interpretation was conducted on the best-performing model. Results All the 3D morphological parameters were significantly different between euploid and non-euploid blastocysts. Multivariate analysis revealed that three of the five parameters including trophectoderm cell number, trophectoderm cell size variance and inner cell mass area maintained statistical significance (P

Abstract Symmetries and their anomalies are powerful tools for understanding quantum systems. However, realistic systems are often subject to disorders, dissipation and decoherence. In many circumstances, symmetries are not exact but only on average. This work investigates the constraints on mixed states resulting from non-commuting average symmetries. We will focus on the cases where the commutation relations of the average symmetry generators are violated by nontrivial phases, and call such average symmetry anomalous. We show that anomalous average symmetry implies degeneracy in the density matrix eigenvalues, and present several lattice examples with average symmetries, including XY chain, Heisenberg chain, and deformed toric code models. In certain cases, the results can be further extended to reduced density matrices, leading to a new lower bound on the entanglement entropy. We discuss several applications in the contexts of many body localization, quantum channels, entanglement phase transitions and also derive new constraints on the Lindbladian evolution of open quantum systems.

Background: Variations in the fusion (F) protein of respiratory syncytial virus (RSV) with main antigenic sites I–V and Ø may affect the development of RSV vaccines and therapies. Methods: In the study, 30 respiratory specimens positive for RSV were randomly selected from children with acute lower respiratory infections (ALRI) in Beijing every year from 2012 to 2021 for F gene sequencing. Then, 300 F gene sequences and 508 uploaded to GenBank from China were subjected to phylogenetic analysis. Results: The results indicated the nucleotide identities were 95.4–100% among 446 sequences of RSV A, and 96.3–100% among 362 of RSV B. The most common variant loci were N80K (100.00%) and R213S (97.76%) for site Ø, and V384I/T (98.43%) for site I among sequences of RSV A, and M152I (100.00%), I185V (100.00%), and L172Q/H (94.48%) for site V, and R202Q (99.45%) for site Ø among sequences of RSV B. N276S appears in 95.29% sequences of RSV A, while S276N and N262 I/S appear in 1.38% and 0.55% sequences of RSV B, respectively. No variation was found in all sequences at the binding sites of 14N4 and motavizumab. Conclusions: There were cumulative variations of the RSV F gene, especially at some binding sites of antigenic sites.

Abstract IL-1β represents an important inflammatory factor involved in the host response against GBS infection. Prior research has suggested a potential involvement of IL-1β in the process of ferroptosis. However, the relationship between IL-1β and ferroptosis in the context of anti-GBS infection remains uncertain. This research demonstrates that the occurrence of ferroptosis is essential for the host’s defense against GBS infection in a mouse model of abdominal infection, with peritoneal macrophages identified as the primary cells undergoing ferroptosis. Further research indicates that IL-1β induces lipid oxidation in macrophages through the upregulation of pathways related to lipid oxidation. Concurrently, IL-1β is not only involved in the initiation of ferroptosis in macrophages, but its production is intricately linked to the onset of ferroptosis. Ultimately, we posit that ferroptosis acts as a crucial initiating factor in the host response to GBS infection, with IL-1β playing a significant role in the resistance to infection by serving as a key inducer of ferroptosis.

This study examined the mediating effects of cognitive empathy and affective empathy in the relationship between dispositional awe and prosocial behaviour in medical students, and whether perceived stress moderated this association. A total of 631 medical students from two medical tertiary institutions in Liaoning Province, China, participated in this survey. The findings revealed that (1) dispositional awe was positively associated with prosocial behaviour; (2) the positive association between dispositional awe and prosocial behaviour was partially mediated by cognitive empathy and affective empathy; (3) perceived stress significantly attenuated the association between dispositional awe and cognitive empathy, and the association between cognitive empathy and prosocial behaviour. The findings yield practical implications for the improvement strategies of prosocial behaviour among medical students and provide suggestions for future educational interventions.

Abstract The rapid variation of influenza challenges vaccines and treatments, which makes an urgent task to develop the high-efficiency and low-toxicity new anti-influenza virus drugs. Selenium is one of the essential trace elements for the human body that possesses a good antiviral activity. In this study, we assessed anti-influenza A virus (H1N1) activity of polyethylene glycol (PEG)-modified gray selenium nanoparticles (PEG-SeNPs) on Madin-Darby Canine Kidney (MDCK) cells in vitro. CCK-8 assay showed that PEG-SeNPs had a protective effect on H1N1-infected MDCK cells. Moreover, PEG-SeNPs significantly reduced the mRNA level of H1N1. TUNEL-DAPI test showed that DNA damage reached a high level but effectively prevented after PEG-SeNPs treatment. Meanwhile, JC-1, Annexin V-FITC and cell cycle assay demonstrated the apoptosis induced by H1N1 was reduced greatly when treated with PEG-SeNPs. Furthermore, the downregulation of p-ATM, p-ATR and P53 protein, along with the upregualation of AKT protein indicated that PEG-SeNPs could inhibit H1N1-induced cell apoptosis through reactive oxygen species (ROS)-mediated related signaling pathways. Finally, Cytokine detection demonstrated PEG-SeNPs inhibited the production of pro-inflammatory factors after infection, including IL-1β, IL-5, IL-6, and TNF-α. To sum up, PEG-SeNPs might become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity.

Abstract This study aimed to investigate the therapeutic potential of human adipose‐derived mesenchymal stem cells (hADSCs) modified with recombinant adeno‐associated virus (rAAV) carrying the vascular endothelial growth factor 165 (VEGF165) gene in peripheral nerve injury (PNI). The hADSCs were categorized into blank, control (transduced with rAAV control vector), and VEGF165 (transduced with rAAV VEGF165 vector) groups. Subsequently, Schwann cell differentiation was induced, and Schwann cell markers were assessed. The sciatic nerve injury mouse model received injections of phosphate‐buffered saline (PBS group), PBS containing hADSCs (hADSCs group), rAAV control vector (control‐hADSCs group), or rAAV VEGF165 vector (VEGF165‐hADSCs group) into the nerve defect site. Motor function recovery, evaluated through the sciatic function index (SFI), and nerve regeneration, assessed via toluidine blue staining along with scrutiny of Schwann cell markers and neurotrophic factors, were conducted. Modified hADSCs exhibited enhanced Schwann cell differentiation and elevated expression of Schwann cell markers [S100 calcium‐binding protein B (S100B), NGF receptor (NGFR), and glial fibrillary acidic protein (GFAP)]. Mice in the VEGF165‐hADSCs group demonstrated improved motor function recovery compared to those in the other three groups, accompanied by increased fiber diameter, axon diameter, and myelin thickness, as well as elevated expression of Schwann cell markers (S100B, NGFR, and GFAP) and neurotrophic factors [mature brain‐derived neurotrophic factor (BDNF) and glial cell‐derived neurotrophic factor (GDNF)] in the distal nerve segment. rAAV‐VEGF165 modification enhances hADSC potential in PNI, promoting motor recovery and nerve regeneration. Elevated Schwann cell markers and neurotrophic factors underscore therapy benefits, providing insights for nerve injury strategies.

Abstract The current primary treatment approach for malignant pelvic tumors involves hemipelvic prosthesis reconstruction following tumor resection. In cases of Enneking type II + III pelvic tumors, the prosthesis necessitates fixation to the remaining iliac bone. Prevailing methods for prosthesis fixation include the saddle prosthesis, ice cream prosthesis, modular hemipelvic prosthesis, and personalized prosthetics using three-dimensional printing. To prevent failure of hemipelvic arthroplasty protheses, a novel fixation method was designed and finite element analysis was conducted. In clinical cases, the third and fourth sacral screws broke, a phenomenon also observed in the results of finite element analysis. Based on the original surgical model, designs were created for auxiliary dorsal iliac, auxiliary iliac bottom, auxiliary sacral screw, and auxiliary pubic ramus fixation. A nonlinear quasi-static finite element analysis was then performed under the maximum load of the gait cycle, and the results indicated that assisted sacral dorsal fixation significantly reduces stress on the sacral screws and relative micromotion exceeding 28 μm. The fixation of the pubic ramus further increased the initial stability of the prosthesis and its interface osseointegration ability. Therefore, for hemipelvic prostheses, incorporating pubic ramus support and iliac back fixation is advisable, as it provides new options for the application of hemipelvic tumor prostheses.

Abstract Background Central obesity was considered as a risk factor for falls among the older population. Waist circumference (WC), lipid accumulation product (LAP), visceral adiposity index (VAI), and the Chinese visceral adiposity index (CVAI) are considered as surrogate markers for abdominal fat deposition in increasing studies. Nevertheless, the longitudinal relationship between these indices and falls among the older population remains indistinct. This study aimed to explore the association between abdominal obesity indices and falls among older community-dwellers. Methods Our study included 3501 individuals aged ≥ 65 years from the Guangzhou Falls and Health Status Tracking Cohort at baseline in 2021 and then prospectively followed up in 2022. The outcome of interest was the occurrence of falls. The Kaplan-Meier curves and multivariable Cox regression analysis were used to explore the associations between abdominal obesity indices and falls. Moreover, the restricted cubic spline analysis (RCS) was conducted to test the non-linear relationships between abdominal obesity indices and hazards of falls incident. Results After a median follow-up period of 551 days, a total of 1022 participants experienced falls. The cumulative incidence rate of falls was observed to be higher among individuals with central obesity and those falling within the fourth quartile (Q4) of LAP, VAI, and CVAI. Participants with central obesity and those in Q4 of LAP, VAI, and CVAI were associated with higher risk of falls, with hazard ratios (HRs) of 1.422 (HR 95%CI: 1.255–1.611), 1.346 (1.176–1.541), 1.270 (1.108–1.457), 1.322 (1.154–1.514), respectively. Each 1-SD increment in WC, LAP, VAI, and CVAI was a significant increased risk of falls among participants. Subgroup analysis further revealed these results were basically stable and appeared to be significantly stronger among those females, aged 65–69 years, and with body mass index (BMI) ≥ 28 kg/m2. Additionally, RCS curves showed an overall upward trend in the risk of falls as the abdominal indices increased. Conclusions Abdominal obesity indices, as WC, LAP, VAI, and CVAI were significantly associated with falls among older community-dwellers. Reduction of abdominal obesity indices might be suggested as the strategy of falls prevention.

Avian Pasteurella multocida infection, can cause serious economic losses to the poultry industry every year. The inactivated vaccines of avian Pasteurella multocida are used to prevent infection. Increasing the cell density of avian Pasteurella multocida is the key to the application of these inactivated vaccines. This can be achieved by controlling the feeding strategy. This study aimed to achieve high-cell-density cultivation of avian Pasteurella multocida by applying an appropriate medium and a rational feeding strategy based on viable cell growth and dissolved oxygen level variation during a fermentation process. An optimized medium suited for the growth of avian P. multocida was used. Meanwhile, besides the online real-time determination of viable cell density, the concentration of glucose was maintained at 1.5 g/L using a glucose-stat feeding strategy after 2 h. The selected nutrient mixture, including yeast extract, tryptone, betaine, VB1, and VH, was fed using a dissolved oxygen feedback feeding strategy after 4 h. As a result, the viable cell density and cell count of avian P. multocida under optimized conditions were increased to OD600: 9.38 and 4.58×1010 CFU/mL, which were higher by 7.27 and 7.26 times than those under the original conditions, respectively.

Abstract Background Several studies have demonstrated that older adults with type 2 diabetes mellitus (T2DM) have a higher risk of falls compared to those without T2DM, which may lead to disability and a lower quality of life. While, limited prospective studies have quantified the associations in southern China. We conducted a longitudinal cohort study to quantify the associations between T2DM and falls and investigate the risk factors of falls among community-dwelling elderly people in Guangzhou, China. Methods The population-based study included 8800 residents aged 65 and over in 11 counties of Guangzhou at baseline in 2020 and then prospectively followed up through 2022. Of 6169 participants had complete follow-up and were included in the present study. A fall event was identified by self-reported. The Cox regression was applied to quantify the associations between T2DM and falls, and hazard ratios (HRs) were calculated to the factors associated with falls among participants. Results The median follow-up time for participants was 2.42 years. During the follow-up period, the incidence of falls among all participants was 21.96%. After adjusting for covariates in Cox regression models, T2DM remained a significant risk factor for falls, with HR of 1.781 (95% CI: 1.600-1.983) in the unadjusted covariates model and 1.757 (1.577–1.957) in the adjusted covariates model. Female (1.286, 1.136–1.457), older age (≥ 80: 1.448, 1.214–1.729), single marital status (1.239, 1.039–1.477), lower education level (primary school and below: 1.619, 1.004–1.361), hypertension (1.149, 1.026–1.286) and stroke (1.619, 1.176–2.228) were associated with a higher risk of falls, whereas everyday physical exercise (0.793, 0.686–0.918) was associated with a lower risk of falls. Conclusion Falls are common, with risks between T2DM and falls quantified and several factors investigated in the longitudinal cohort study among community-dwelling elderly people in Guangzhou, China. Targeted action on the risk factors may reduce the burden of falls in elderly people with T2DM in the future.

Abstract The sole use of single modality data often fails to capture the complex heterogeneity among patients, including the variability in resistance to anti-HER2 therapy and outcomes of combined treatment regimens, for the treatment of HER2-positive gastric cancer (GC). This modality deficit has not been fully considered in many studies. Furthermore, the application of artificial intelligence in predicting the treatment response, particularly in complex diseases such as GC, is still in its infancy. Therefore, this study aimed to use a comprehensive analytic approach to accurately predict treatment responses to anti-HER2 therapy or anti-HER2 combined immunotherapy in patients with HER2-positive GC. We collected multi-modal data, comprising radiology, pathology, and clinical information from a cohort of 429 patients: 310 treated with anti-HER2 therapy and 119 treated with a combination of anti-HER2 and anti-PD-1/PD-L1 inhibitors immunotherapy. We introduced a deep learning model, called the Multi-Modal model (MuMo), that integrates these data to make precise treatment response predictions. MuMo achieved an area under the curve score of 0.821 for anti-HER2 therapy and 0.914 for combined immunotherapy. Moreover, patients classified as low-risk by MuMo exhibited significantly prolonged progression-free survival and overall survival (log-rank test, P

Abstract Because nickel-titanium (NiTi) alloys have unique functions, such as superelasticity, shape memory, and hysteresis similar to bone in the loading-unloading cycles of their recoverable deformations. They likely offer good bone integration, a low loosening rate, individual customization, and ease of insertion. Due to the poor processability of NITI, traditional methods cannot manufacture NiTi products with complex shapes. Orthopedic NiTi implants need to show an adequate fracture elongation of at least 8%. Additive manufacturing can be used to prepare NiTi implants with complex structures and tunable porosity. However, as previously reported, additively manufactured NiTi alloys could only exhibit a maximum tensile fracture strain of 7%. In new reports, a selective laser melting (SLM)–NiTi alloy has shown greater tensile strain (15.6%). Nevertheless, due to the unique microstructure of additive manufacturing NiTi that differs from traditional NITI, the biocompatibility of SLM-NITI manufactured by this new process requires further evaluation In this study, the effects of the improved NiTi alloy on bone marrow mesenchymal stem cell (BMSC) proliferation, adhesion, and cell viability were investigated via in vitro studies. A commercial Ti-6Al-4V alloy was studied side-by-side for comparison. Like the Ti-6Al-4V alloy, the SLM-NiTi alloy exhibited low cytotoxicity toward BMSCs and similar effect on cell adhesion or cell viability. This study demonstrates that the new SLM-NiTi alloy, which has exhibited improved mechanical properties, also displays excellent biocompatibility. Therefore, this alloy may be a superior implant material in biomedical implantation. Graphical Abstract

Abstract In the KEYNOTE-811 study, anti-HER2 and immunotherapy treatments resulted in longer survival in HER2-positive gastric cancer patients with CPS ≥ 1, whereas CPS

Abstract A substantive body of evidence has demonstrated the significant roles of circular RNA (circRNA) in cancer. However, the contribution of dysregulated circRNAs to ovarian cancer (OC) remains elusive. We aim to elucidate the critical roles and mechanisms of hsa_circ_0020093, which was demonstrated to be downregulated in OC tissues in our previous study. In this study, we confirmed the decreased expression of hsa_circ_0020093 in OC tissues and cell lines and demonstrated the negative correlation between its expression and FIGO stage, abdominal implantation and CA125 level of OC patients. Through gain and loss of function studies, we confirmed the inhibitory role of hsa_circ_0020093 in ovarian tumor growth in vitro and in vivo. Mechanistically, based on the peri-nuclear accumulation of hsa_circ_0020093, we discovered the interaction between hsa_circ_0020093 and the mitochondrial protein LRPPRC by RNA pull-down, mass spectrometry, RNA Binding Protein Immunoprecipitation. As a result, qRT-PCR and transmission electron microscopy results showed that the mitochondria mRNA expression and mitochondria abundance were decreased upon hsa_circ_0020093-overexpression. Meanwhile, we also unearthed the hsa_circ_0020093/miR-107/LATS2 axis in OC according to RNA-sequencing, RIP and luciferase reporter assay data. Furthermore, LRPPRC and LATS2 are both reported as the upstream regulators of YAP, our study also studied the crosstalk between hsa_circ_0020093, LRPPRC and miR-107/LATS2, and unearthed the up-regulation of phosphorylated YAP in hsa_circ_0020093-overexpressing OC cells and xenograft tumors. Collectively, our study indicated the novel mechanism of hsa_circ_0020093 in suppressing OC progression through both hsa_circ_0020093/LRPPRC and hsa_circ_0020093/miR-107/LATS2 axes, providing a potential therapeutic target for OC patients.

Abstract Purpose The aim of this study was to identify factors that predict favorable functional outcomes in elderly patients with large-vessel occlusion acute ischemic stroke (LVO-AIS) who underwent mechanical thrombectomy (MT). Methods We conducted a retrospective observational study using the prospectively maintained Bigdata Observatory for Stroke of China (BOSC) to identify eligible patients who underwent MT for LVO-AIS at four comprehensive stroke centers between August 2019 and February 2022. Inclusion criteria included patients aged 80 years or older with a baseline modified Rankin Scale (mRS) 0–2, baseline National Institutes of Health Stroke Scale (NIHSS) > 6, baseline Alberta Stroke Program Early CT Score (ASPECTS) > 6 who received treatment within 24 h from symptom onset. Pertinent demographic, clinical, and procedural variables were collected. Multivariable regression analyses were performed to identify predictors of favorable long-term functional outcomes, defined as mRS 0–2 at 90 days. Results A total of 63 patients were included in the study with a mean age of 83 years. Patients with previous diagnosis of atrial fibrillation were more likely to have a favorable functional outcome (OR 2.09, 95% CI 2.09–407.33, p = 0.012), while a higher baseline NIHSS was associated with a less favorable functional outcome (OR 0.64, 95% CI 0.46–0.89, p = 0.007). In addition, there was an observed trend suggesting an association between higher baseline ASPECTS and favorable functional outcomes. This association did not reach statistical significance (OR 2.49, 95% CI 0.94–6.54, p = 0.065). Conclusion In this study, we identified factors that predicted a favorable functional outcome in elderly LVO-AIS patients undergoing MT. A higher baseline NIHSS decreased the odds of mRS 0–2 at 90 days, whereas a history of atrial fibrillation increased the odds of a favorable functional outcome. These results emphasize the complex relationship between clinical factors and functional recovery in this vulnerable population.

Abstract Objectives To evaluate the effects and benefits of training radiology residents on contrast-enhanced ultrasound (CEUS) according to the Liver Imaging Reporting and Data System (LI-RADS). Methods In total, 234 patients at high risk of hepatocellular carcinoma (HCC) who underwent CEUS were enrolled, including 27 lesions in the education set and 207 lesions in the test sets (a–d). Forty-five radiology residents and 4 radiology experts involved in CEUS LI-RADS training individually reviewed the test sets before, immediately after, and 3-months after training. The consistency with kappa values of the description of CEUS features, the classification of focal liver lesions (FLLs), and the diagnostic performance were evaluated. Results The level of agreement between the radiology experts and residents improved after training (all p 0.05). The sensitivity, specificity, positive predictive value, and area under the curve (AUC) based on the CEUS LI-RADS classification of the radiology experts in the diagnosis of HCC were 62.9%, 96.4%, 96.3%, and 0.796, respectively. The diagnostic performance of the radiology residents significantly improved after training (all p

Abstract Background Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation. The diagnosis of FCD is challenging. We generated a radiomics nomogram based on multiparametric magnetic resonance imaging (MRI) to diagnose FCD and identify laterality early. Methods Forty-three patients treated between July 2017 and May 2022 with histopathologically confirmed FCD were retrospectively enrolled. The contralateral unaffected hemispheres were included as the control group. Therefore, 86 ROIs were finally included. Using January 2021 as the time cutoff, those admitted after January 2021 were included in the hold-out set (n = 20). The remaining patients were separated randomly (8:2 ratio) into training (n = 55) and validation (n = 11) sets. All preoperative and postoperative MR images, including T1-weighted (T1w), T2-weighted (T2w), fluid-attenuated inversion recovery (FLAIR), and combined (T1w + T2w + FLAIR) images, were included. The least absolute shrinkage and selection operator (LASSO) was used to select features. Multivariable logistic regression analysis was used to develop the diagnosis model. The performance of the radiomic nomogram was evaluated with an area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration and clinical utility. Results The model-based radiomics features that were selected from combined sequences (T1w + T2w + FLAIR) had the highest performances in all models and showed better diagnostic performance than inexperienced radiologists in the training (AUCs: 0.847 VS. 0.664, p = 0.008), validation (AUC: 0.857 VS. 0.521, p = 0.155), and hold-out sets (AUCs: 0.828 VS. 0.571, p = 0.080). The positive values of NRI (0.402, 0.607, 0.424) and IDI (0.158, 0.264, 0.264) in the three sets indicated that the diagnostic performance of Model-Combined improved significantly. The radiomics nomogram fit well in calibration curves (p > 0.05), and decision curve analysis further confirmed the clinical usefulness of the nomogram. Additionally, the contrast (the radiomics feature) of the FCD lesions not only played a crucial role in the classifier but also had a significant correlation (r = -0.319, p

Abstract Objective To provide evidence for choosing surgical or nonsurgical treatment for epilepsy in patients with unilateral multilobar and hemispheric polymicrogyria (PMG). Methods We searched published studies until September 2022 related to unilateral multilobar and hemispheric PMG and included patients who were followed up at the Pediatric Epilepsy Centre of Peking University First Hospital in the past 10 years. We summarized the clinical characteristics and compared the long‐term outcomes after surgical or nonsurgical (anti‐seizure medications, ASMs) treatment. Results A total of 70 patients (49 surgical, 21 non‐surgical) with unilateral multilobar and hemispheric PMG were included. The median age at epilepsy onset was 2.5 years (1.0–4.1). The most common seizure types were focal and atypical absence seizures. In the whole cohort, 87.3% had hemiparesis and 67.1% had electrical status epilepticus during slow sleep (ESES). There were significant differences in age at epilepsy onset, extent of lesion, and EEG interictal discharges between the two groups. At the last follow‐up (median 14.1 years), the rates of seizure‐freedom (81.6% vs. 57.1%, p = 0.032) and ASM discontinuation (44.4% vs. 6.3%, p = 0.006) were higher in the surgical group than in the nonsurgical group. Patients in the surgical group had a higher rate of seizure‐freedom with complete resection/disconnection than with subtotal resection (87.5% vs. 55.6%, p = 0.078), but with no statistically significant difference. In the nonsurgical group, more extensive lesions were associated with worse seizure outcomes. Cognition improved postoperatively in 90% of surgical patients. Significance In patients with unilateral multilobar and hemispheric PMG, the age of seizure onset, the extent of the lesion and EEG features can help determine whether surgery should be performed early. Additionally, surgery could be more favorable for achieving seizure freedom and cognitive improvement sooner. Plain Language Summary We aim to summarize clinical characteristics and compare the long‐term outcomes after surgical and nonsurgical (ASM) treatment to provide a basis for treatment decisions for patients with unilateral multilobar and hemispheric polymicrogyria (PMG)‐related epilepsy. We found that patients with unilateral hemispheric and multilobar PMG had significantly higher rates of seizure freedom and ASM discontinuation with surgical treatment than with nonsurgical treatment. In the surgical group, seizure outcomes were better in patients treated with complete resection/disconnection than in those treated with subtotal resection, but the difference was not statistically significant.

The rapid development of messenger RNA (mRNA) vaccines formulated with lipid nanoparticles (LNPs) has contributed to control of the COVID-19 pandemic. However, mRNA vaccines have raised concerns about their potential toxicity and clinical safety, including side effects, such as myocarditis, anaphylaxis, and pericarditis. In this study, we investigated the potential of trehalose glycolipids-containing LNP (LNP S050L) to reduce the risks associated with ionizable lipids. Trehalose glycolipids can form hydrogen bonds with polar biomolecules, allowing the formation of a stable LNP structure by replacing half of the ionizable lipids. The efficacy and safety of LNP S050L were evaluated by encapsulating the mRNA encoding the luciferase reporter gene and measuring gene expression and organ toxicity, respectively. Furthermore, mice immunized with an LNP S050L-formulated mRNA vaccine expressing influenza hemagglutinin exhibited a significant reduction in organ toxicity, including in the heart, spleen, and liver, while sustaining gene expression and immune efficiency, compared to conventional LNPs (Con-LNPs). Our findings suggest that LNP S050L, a trehalose glycolipid-based LNP, could facilitate the development of safe mRNA vaccines with improved clinical safety.

Abstract Cancer is rarely the straightforward consequence of an abnormality in a single gene, but rather reflects a complex interplay of many genes, represented as gene modules. Here, we leverage the recent advances of model-agnostic interpretation approach and develop CGMega, an explainable and graph attention-based deep learning framework to perform cancer gene module dissection. CGMega outperforms current approaches in cancer gene prediction, and it provides a promising approach to integrate multi-omics information. We apply CGMega to breast cancer cell line and acute myeloid leukemia (AML) patients, and we uncover the high-order gene module formed by ErbB family and tumor factors NRG1, PPM1A and DLG2. We identify 396 candidate AML genes, and observe the enrichment of either known AML genes or candidate AML genes in a single gene module. We also identify patient-specific AML genes and associated gene modules. Together, these results indicate that CGMega can be used to dissect cancer gene modules, and provide high-order mechanistic insights into cancer development and heterogeneity.

Abstract Background To evaluate the efficiency of artificial intelligence (AI)-assisted diagnosis system in the pulmonary nodule detection and diagnosis training of junior radiology residents and medical imaging students. Methods The participants were divided into three groups. Medical imaging students of Grade 2020 in the Jinzhou Medical University were randomly divided into Groups 1 and 2; Group 3 comprised junior radiology residents. Group 1 used the traditional case-based teaching mode; Groups 2 and 3 used the ‘AI intelligent assisted diagnosis system’ teaching mode. All participants performed localisation, grading and qualitative diagnosed of 1,057 lung nodules in 420 cases for seven rounds of testing after training. The sensitivity and number of false positive nodules in different densities (solid, pure ground glass, mixed ground glass and calcification), sizes (less than 5 mm, 5–10 mm and over 10 mm) and positions (subpleural, peripheral and central) of the pulmonary nodules in the three groups were detected. The pathological results and diagnostic opinions of radiologists formed the criteria. The detection rate, diagnostic compliance rate, false positive number/case, and kappa scores of the three groups were compared. Results There was no statistical difference in baseline test scores between Groups 1 and 2, and there were statistical differences with Group 3 (P = 0.036 and 0.011). The detection rate of solid, pure ground glass and calcified nodules; small-, medium-, and large-diameter nodules; and peripheral nodules were significantly different among the three groups (P

Abstract The increasing severity and frequency of drought pose serious threats to plant species worldwide. Yet, we lack a general understanding of how various intensities of droughts affect plant traits, in particular root traits. Here, using a meta-analysis of drought experiments (997 effect sizes from 76 papers), we investigate the effects of various intensities of droughts on some of the key morphological root traits. Our results show that root length, root mean diameter, and root area decline when drought is of severe or extreme intensity, whereas severe drought increases root tissue density. These patterns are most pronounced in trees compared to other plant functional groups. Moreover, the long duration of severe drought decreases root length in grasses and root mean diameter in legumes. The decline in root length and root diameter due to severe drought in trees was independent of drought duration. Our results suggest that morphological root traits respond strongly to increasing intensity of drought, which further depends on drought duration and may vary among plant functional groups. Our meta-analysis highlights the need for future studies to consider the interactive effects of drought intensity and drought duration for a better understanding of variable plant responses to drought.

Abstract The objective of the path planning for a mobile robot is to generate a collision-free path from a starting position to a target position, aiming to realize a higher quality of path planning, an improved A* algorithm and a hybrid approach incorporating the dynamic window algorithm have been proposed for robot path planning in various environments in this paper. In global path planning, first, a bidirectional search strategy was introduced into to improve the searching efficiency, and an adaptive heuristic function was designed to reduce redundant search nodes. In the meantime, a filtering function for key path nodes and an enhanced jump point optimization method help to remove redundant nodes in the path, reduce turning angles, greatly shorten the path length, and smooth the path using cubic B-spline curves. Furthermore, in local path planning, the combination of key path nodes and the dynamic window approach (DWA) algorithm is utilized to achieve obstacle avoidance in dynamic environments and adjust the heading angle of the section enables seamless locomotion of the robot. Finally, the simulation experiments and physical experiments on the robot were conducted to validate that the proposed improved algorithm significantly improves the speed of path planning while also reducing the length of the planned path and improve the reliability of the algorithm when compared with other algorithms.

Rutelini is one of the largest tribes of Rutelinae, widely distributed but primarily in the New World. Recently, both larvae and adults of Parastasia ferrieri had been discovered in Liaoning Province of northeastern China from the Palearctic realm. The third-instar larvae of P. ferrieri were described using light and scanning electron microscopy in order to discover more morphological characters for larval taxonomy. The larvae of P. ferrieri exhibit remarkable features, including four protuberances on labrum, no helus on epipharynx, two scissorial teeth on each mandible, five stridulatory teeth plus a blunt protuberance on each maxilla, and the obtuse claws on the thoracic legs. The correlation between morphological features and feeding habits is briefly discussed.

We propose a method for enhancing the accuracy of bathymetry models based on a multilayer perceptron (MLP) neural network that integrates the differences in multisource marine geodetic data (MMGD) (longitude, latitude, reference bathymetry, slope, the meridional and prime components of vertical deflection, gravity anomaly, vertical gravity gradient, and mean dynamic topography). First, we use the MMGD differences between the shipborne sounding control points within 8′ × 8′ grid points and shipborne sounding control points as input data, as well as the differences between the topo_24.1 model and the measured bathymetric values at the control points as output data to train the MLP model. Second, we feed the input data from the central point of a 1′ × 1′ grid into the MLP model to obtain predictions, and then use the topo_24.1 model to recover the predicted bathymetry at the prediction point. We focus on the Caribbean Sea, and construct a Caribbean Bathymetric Chart of the Oceans (CBCO1) model using MLP neural network. The reliability of MMGD, a CBCO2 model using MMGD, and the reliability and effectiveness of the overall method are demonstrated through comparisons with the CBCO2, GEBCO_2022, topo_24.1, DTU18 models at the checkpoints.

Acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) are life-threatening syndromes that can develop at the end-stage of chronic hepatitis B virus (HBV) infection. Both ACLF and DC are complicated by hepatic and extrahepatic pathogeneses. To better understand the compartment-specific metabolic modulations related to their pathogenesis, HBV-DC, HBV-ACLF patients, and controls (30 each) were analyzed by metabolomics using portal (Port), hepatic vein (Hep), and peripheral (Peri) serum. Compartment ratios of metabolites (RatioHep/Port, RatioPeri/Hep, and RatioPort/Peri) were calculated. The liver tissues (10 per group) were analyzed using transcriptomics and metabolomics. An additional 75 patients with ACLF, 20 with DC, and 20 with liver cirrhosis (LC) were used to confirm oxlipid dysregulation. Both multi-omics datasets suggest suppressed energy, amino acid, and pyrimidine metabolism in the ACLF/DC liver. The serum metabolomic variations were contributed primarily by disease rather than sampling compartments, as both HBV-ACLF and HBV-DC patients demonstrated abnormal profiles of amino acids and peptides, indoles, purines, steroids, and benzimidazoles. In ACLF/DC patients, impaired hepatic metabolism resulted in a highly correlated hepatic and portal vein serum metabolome and release of inflammatory lipids and heme metabolites from the liver. HBV-ACLF showed higher RatioPeri/Hep of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher RatioPort/Peri of gut microbial metabolites. An inflammatory oxlipid outburst was confirmed in the early stages of HBV-ACLF. The inflammatory effects of the selected oxlipids were confirmed in monocytes. These findings support a synergy between liver-specific mechanisms and systemic inflammation in ACLF/DC development, and that pro-inflammatory oxlipids are metabolic signatures of early HBV-ACLF.

Prostate cancer (PCa) continues to rank among the most common malignancies in Europe and North America with significant mortality rates despite advancements in detection and treatment. Physical activity is often recommended to PCa patients due to its benefits in preventing disease recurrence and managing treatment-related side effects. However, physical activity may be challenging for elderly or bedridden patients. As such, vibration therapy has been proposed as a safe, effective, and easy to perform alternative treatment that may confer similar effects as physical exercise. Specifically, low-magnitude high frequency (LMHF) vibration has been shown to decrease breast cancer extravasation into the bone and reduce other types of cancer proliferation by impacting cell viability. Here, we investigated the effects of daily application of LMHF vibration (0.3 ​g, 60 ​Hz, 1 ​hour/day for 3 days) on prostate cancer growth and bone metastasis in vitro. Our findings suggest that LMHF vibration significantly reduces colony formation through a decrease in cell growth and proliferation. Moreover, using a 3D cell culture model, LMHF vibration significantly reduces PC3 spheroid size. Additionally, LMHF vibration reduces PCa cell extravasation into the bone microenvironment through the stimulation of osteocytes and subsequent osteocyte-endothelial cell cross talk. These findings highlight the potential of LMHF vibration for managing PCa growth and metastasis.

The process of urbanization generates substantial amounts of solid waste materials, including glass, red brick, concrete, and ceramic tile. Effective treatment methods for these waste materials are currently lacking, resulting in significant land wastage and environmental pollution. Utilizing these waste materials in the construction of asphalt pavements presents a viable solution for their high-quality and large-scale utilization. In this study, the properties of commonly produced urban solid waste materials, including glass, red brick, concrete, and ceramic tile, were investigated for their suitability as limestone porous asphalt mixtures. The physical and chemical properties of the coarse aggregate were examined using four groups of preliminary tests, including leakage analysis, scattering, rutting, and freeze-thaw splitting tests. The results revealed that the apparent relative density varied for different particle sizes within the range of 2.36–4.75 mm, 4.75–9.5 mm, 9.5–16 mm, and 13.2–16 mm. However, the dynamic stability of the glass specimen was only 740 times/mm, which falls significantly below the technical requirement of 1500 times/mm. Additionally, the high-temperature stability of the glass specimen was deemed unsatisfactory. The red brick test piece exhibited inadequate water stability due to its high-water absorption rate. Therefore, reducing the amount of waste glass and minimizing the incorporation of waste red brick are recommended. The findings of this study contribute to the expansion of application methods and techniques for urban solid waste, improving the utilization rate of solid waste resources. Furthermore, the study sheds light on the changes in the performance of solid waste aggregates mixed with porous asphalt mixtures, providing valuable insights for road engineering endeavors.

The diagnostic criteria for preeclampsia do not accurately reflect the pathophysiological characteristics of patients with preeclampsia. Conventional biomarkers and diagnostic approaches have proven insufficient to fully comprehend the intricacies of preeclampsia. This study aimed to screen differentially abundant metabolites as candidate biomarkers for preeclampsia. A propensity score matching method was used to perform a 1:1 match between preeclampsia patients (n = 70) and healthy control individuals (n = 70). Based on univariate and multivariate statistical analysis methods, the different characteristic metabolites were screened and identified. Least absolute shrinkage and selection operator (LASSO) regression analysis was subsequently used to further screen for differentially abundant metabolites. A receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic efficacy of the metabolites. A total of 1,630 metabolites were identified and quantified in maternal serum samples. Fifty-three metabolites were significantly increased, and two were significantly decreased in preeclampsia patients. The area under the curve (AUC) of the model composed of isobutyryl-L-carnitine and acetyl-leucine was 0.878, and the sensitivity and specificity in detecting preeclampsia were 81.4% and 87.1%, respectively. There are significant differences in metabolism between preeclampsia patients and healthy pregnant women, and a range of novel biomarkers have been identified. These findings lay the foundation for the use of metabolomic biomarkers for the diagnosis of preeclampsia.

ABSTRACTTo investigate the research levels, hotspots, and development trends regarding microRNAs in hypertension, this study conducted a visual analysis of studies on miRNA in hypertension based on the Web of Science core collection database using CiteSpace and VOSviewer analysis software along with literature from 2005–2023 as information data. Using citation frequency, centrality, and starting year as metrics, this study analyzed the research objects. It revealed the main research bodies and hotspots and evaluated the sources of literature and the distribution of knowledge from journals and authors. Finally, the potential research directions for miRNAs in hypertension are discussed. The results showed that the research field is in a period of vigorous development, and scholars worldwide have shown strong interest in this research field. A comprehensive summary and analysis of the current research status and application trends will prove beneficial for the advancement of this field.

AbstractBreast cancer is one of the most devastating cancers that have no cure. Many therapeutic and diagnostic strategies have been extensively studied in the past decade. Cancer nanotechnology has developed as a promising approach in preclinical examinations, allowing for the early exposure of primary tumors and metastases and the efficient destruction of cancer cells. The current study aims to fabricate and analyze polymeric nanoparticles for breast cancer therapy established on a copolymeric block of α-tocopheryl polyethylene glycol 1000-b-polycaprolactone (TPGS-b-PCL) incorporating paclitaxel (PTX) (termed as T-b-P@PTX). Characterization of the physical, chemical, and structural properties and the in vitro biological activity of TPGS-b-PCL (T-b-P@PTX) obtained by the nanoprecipitation method. The in vitro cytotoxicity of the nanoparticles was explored by MTT assay using MCF-7 breast cancer cells in a time-dependent manner. The IC50 values T-b-P@PTX for MCF-7 cells 543.7 ± 2.58, 130.2 ± 3.54, 66.99 ± 3.43 in 24, 48, 72-h. Biochemical experiments showed that T-b-P@PTX has a strong ability to induce cell death and to be internalized in the MCF-7 cells. Ethidium bromide (EB)-acridine orange (AO) and nuclear DAPI staining methods investigated the morphological changes of the cells. Considering all the advantages, Paclitaxel-loaded T-b-P@PTX polymeric nanoparticle is a promising approach for treating breast cancer.

The study of fine-grained sedimentation has consistently concentrated on investigating the mechanisms and principles governing the enrichment of organic matter. However, the lack of unified stratigraphic framework has always existed as fine-grained sedimentation covers two distinct grain-size grades, namely, mud and silt, which has impeded the progress of subsequent production research. This study exemplified this issue by analyzing the first member of the Qingshankou Formation in the southern Songliao Basin. We established reconstructed gamma and density curves that mitigated filter noise interference, integrated high-resolution sequence results with astronomical cycle divisions, and created a high-frequency isochronous stratigraphic framework for clastic fine-grained sedimentation by leveraging the weak sensitivity of sandstone density curves and the robust stability in eccentricity cycle extraction. This approach addresses the inconsistencies in stratigraphic division methodologies and mismatched outcomes stemming from the use varying techniques to delineate mud and silt components within clastic fine-grained sedimentary sequences. Furthermore, it elucidates how tectonic-scale variations in sediment supply coupled with potential accommodation changes dictate macroscopic stacking patterns within strata, whereas climate fluctuations on orbital time scales govern sand-mud progradation degrees within these layers, culminating in periodic rhythmic characteristics characterized by vertical sand-mud interbedding. A model for stratigraphic development pertaining to lake delta systems constrained by a “synchronous heterotopy” paradigm is proposed for the southern Songliao Basin. The organic matter enrichment pattern aligns with its filling dynamics, indicating an “overfilling” type developmental pattern at lower strata levels where organic material predominantly originates from terrestrial plant debris external to the basin; this material accumulates primarily within silty zones along layers—with areas exhibiting heightened enrichment values slightly lagging behind short-eccentric maxima positions. In contrast, under an upper “balanced filling” type developmental framework, sources of organic matter are derived both internally and externally relative to the basin—exhibiting substantial heterogeneity—and regions marked by elevated organic matter concentrations are directly associated with locations identified as short-eccentric maxima.

ABSTRACT: Zearalenone (ZEN), a mycotoxin produced by Fusarium species, is known for its reproductive toxicity as an estrogen analogue. However, there are limited knowledge about its hepatointestinal toxicity, as well as the role that gut microbiota and metabolites play in this process. In this study, a total of 24 thirty-week-old hens were fed to investigate the hepatointestinal toxicity subjected to long-term ZEN consumption at 2.0 mg/kg for 90 d. And we employed uncultured 16S rRNA sequencing for gut microbiota and untargeted metabolomics for fecal metabolites assessment. Notably, ZEN induced significant hepatic damage, as evidenced by hepatocyte necrosis, inflammatory cell infiltrate, increased liver lipopolysaccharide (LPS) and blood aspartate aminotransferase (AST) levels (P < 0.05). The decreased villus height, disruption of simple columnar epithelial cells, and exposure of the mucosal intrinsic layer were observed in the intestine. The gut microbial community composition and metabolites differed between ZEN group and control group. ZEN group exhibited higher gut microbial diversity (P < 0.05), lower Firmicutes/Bacteroidetes ratio and Lactobacillus abundance, and higher abundance in the genus such as Bacteroidetes, Parabacteroidetes and Desulfovibrio. Metabolomic analysis showed that ZEN treatment altered biosynthesis of siderophore group nonribosomal peptides and phenylpropanoids, metabolism of amino acid, digestion and absorption of vitamin and ABC transporters. Differential metabolites suggested that ZEN increase the risk of estrogen disorder, nucleic acid degradation, intestinal oxidative stress and inflammation. Neural network analysis showed that Ruminococcus was positively correlated with glyceric acid, and Prevotella was positively correlated with phenylacetylglycine. Both metabolites were positively correlated with blood AST level (P < 0.05), suggesting that intestinal microbe Ruminococcus and Prevotella might exacerbate liver damage by producing these harmful metabolites. Overall, we conclude that ZEN has damaged hepatointestinal system and the altered gut microbiota with resultant metabolite changes contribute to the adverse hepatointestinal effects of ZEN on laying hens. This study underscores the need for monitoring and mitigating ZEN exposure in poultry diets, highlighting its broader implications for animal health and food safety.