Search

Abstract Aims To investigate the efficacy of the integrated data platform of cloud hospital combined with dietary management for adults with type 2 diabetes. Materials and Methods We conducted a randomized controlled clinical trial. One hundred eighty patients with type 2 diabetes were randomly allocated into a control group (Group A) and an experimental group (Group B). Routine standard diabetes care was applied to the patients in Group A. The integrated data platform with dietary management was applied to Group B. Individualized diabetes education videos were sent to the patients through the platform. The primary endpoint was the change in HbA1c and change in body weight from baseline to Week 12 during the follow‐up. Results At Week 12, HbA1c was 7.4 ± 0.7%, 6.9 ± 0.9% in Groups A and B, P

Texture inheritance, texture weakening, and a complete texture transition within different solidified molten pool (MP) have been achieved by manipulating various processing parameters of conduction mode in laser remelted magnesium-aluminum (Mg–Al)-based AZ31 alloy. At a low laser power (P = 100 W), restricted number of temperature gradient directions on moving solid/liquid (S/L) interfaces within small MP leads to strong texture inheritance. Tilting angles 20°–45° away from building direction (B.D.) in {0001} plane is a preferential growth direction of texture inheritance. In contrast, spontaneous texture weakening has occurred due to frequently varied temperature gradient directions within increasing MP size in higher P cases. Meanwhile, increasing scanning speed V has a significant effect on weakening the texture as well as refining grains in the solidified MP. Furthermore, fine grains formation with random orientations in MP bottom at both high P (400 W) and high V (20, 30, and 50 mm/s) leads to the occurrence of a bimodal structure, which is affected by solidification characteristics as well as thermal convection. For the case of the highest P and the highest V, a texture transition has occurred as tilting angles of 45°–90° away from B.D. in {0001} plane within MP, compared to 0°–45° texture of base material for the Mg–Al-based alloy in the study.

Abstract Metabolic disorder significantly contributes to diabetic vascular complications, including diabetic retinopathy, the leading cause of blindness in the working-age population. However, the molecular mechanisms by which disturbed metabolic homeostasis causes vascular dysfunction in diabetic retinopathy remain unclear. O-GlcNAcylation modification acts as a nutrient sensor particularly sensitive to ambient glucose. Here, we observe pronounced O-GlcNAc elevation in retina endothelial cells of diabetic retinopathy patients and mouse models. Endothelial-specific depletion or pharmacological inhibition of O-GlcNAc transferase effectively mitigates vascular dysfunction. Mechanistically, we find that Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-binding motif (TAZ), key effectors of the Hippo pathway, are O-GlcNAcylated in diabetic retinopathy. We identify threonine 383 as an O-GlcNAc site on YAP, which inhibits its phosphorylation at serine 397, leading to its stabilization and activation, thereby promoting vascular dysfunction by inducing a pro-angiogenic and glucose metabolic transcriptional program. This work emphasizes the critical role of the O-GlcNAc-Hippo axis in the pathogenesis of diabetic retinopathy and suggests its potential as a therapeutic target.

Abstract Thyroid cancer (TC) represents one of the most prevalent endocrine malignancies, with a rising incidence worldwide. Epigenetic alterations, which modify gene expression without altering the underlying DNA sequence, have garnered significant attention in recent years. Increasing evidence underscores the pivotal role of epigenetic modifications, including DNA methylation, RNA methylation, and histone methylation, in the pathogenesis of TC. This review provides a comprehensive overview of these reversible and environmentally influenced epigenetic modifications, highlighting their molecular mechanisms and functional roles in TC. Additionally, the clinical implications, challenges associated with studying these epigenetic modifications, and potential future research directions are explored. Graphical Abstract

Abstract Obesity has become a global public health problem, and its relationship with gastrointestinal diseases has become a major concern. The visceral adiposity index (VAI) is a novel index to assess the distribution and content of visceral fat, and this study aimed to investigate the association between VAI and bowel habits (chronic diarrhea, chronic constipation) and inflammatory bowel disease (IBD). The 2005–2010 National Health and Nutrition Examination Survey (NHANES) dataset was used for the cross-sectional survey. Bowel habits and IBD were defined by self-report. Multiple logistic regression models were used to test the linear association of VAI with bowel habits and IBD. Fitted smoothed curves and threshold effects analyses were used to characterize nonlinear relationships. This cross-sectional study included 10,391 adults (≥ 20 years). After adjusting for covariates, there was a significant negative association between VAI and chronic constipation (OR [95% CI]: 0.97 [0.95, 1.00]) but no significant association with IBD (OR [95% CI]: 0.97 [0.87, 1.07]). Additionally, there was a nonlinear association between VAI and chronic diarrhea with a breakpoint of 3.08, with a positive correlation between the two on the left side of the breakpoint and no statistical significance on the right side. Subgroup analyses and interaction tests showed that maintaining sleep health was associated with a low risk of chronic constipation. Elevated VAI levels were negatively associated with chronic constipation, and elevated levels were positively associated with chronic diarrhea at VAI

Abstract Background Malaria is a mosquito-transmitted disease that kills more than half a million people annually. The lack of effective malaria vaccines and recently increasing malaria cases urge innovative approaches to prevent malaria. Previously, we reported that the extract from the soil-dwelling fungus Purpureocillium lilacinum, a common fungus from the soil, reduced Plasmodium falciparum oocysts in Anopheles gambiae midguts after mosquitoes contacted the treated surface before feeding. Methods We used liquid chromatography to fraction fungal crude extract and tract the active fraction using a contact-wise approach and standard membrane feeding assays. The purified small molecules were analyzed using precise mass spectrometry and tandem mass spectrometry. Results We isolated four active small molecules from P. lilacinum and determined them as leucinostatin A, B, A2, and B2. Pre-exposure of mosquitoes via contact with very low-concentration leucinostatin A significantly reduced the number of oocysts. The half-maximal response or inhibition concentration (EC50) via pre-exposure was 0.7 mg/m2, similar to atovaquone but lower than other known antimalarials. The inhibitory effect of leucinostatin A against P. falciparum during intraerythrocytic development, gametogenesis, sporogonic development, and ookinete formation, with the exception of oocyst development, suggests that leucinostatins play a part during parasite invasion of new cells. Conclusions Leucinostatins, secondary metabolites from P. lilacinum disrupt malaria development, particular transmission to mosquitoes by contact. The contact-wise malaria control as a nonconventional approach is highly needed in malaria-endemic areas. Graphical Abstract

Abstract Lactoferrin is a natural multifunctional glycoprotein with potential antidepressant-like effects. However, the mechanism of its antidepressant effect has not been explored from the perspective of gut flora metabolism. Therefore, we employed both 16S rDNA gene sequencing and LC–MS metabolomics analysis to investigate the regulatory effects and mechanisms of lactoferrin in a rat model of depression. After one week of acclimatization, twenty-four 7-week-old male Sprague–Dawley rats were randomly and equally assigned into three groups: the control group, the model group, and the lactoferrin intervention group. The control group rats were housed under standard conditions, while the rats in the model and lactoferrin intervention groups were individually housed and exposed to chronic unpredictable mild stress for 44 days simultaneously. The lactoferrin intervention group was provided with water containing 2% lactoferrin (2 g/100 ml). Behavioural tests were conducted at week 7. Upon completion of the behavioral tests, the rats were anesthetized with isoflurane, humanely euthanized using a rat guillotine, and tissue samples were collected for further experiments. The results indicated that lactoferrin intervention led to an increase in sucrose solution consumption, horizontal movement distance, number of cross platforms, and residence time in the target quadrant. Additionally, it resulted in an increase in jejunal tight junction protein ZO-1 expression and a suppression of serum expression of inflammatory factors, Lipopolysaccharide and Diamine oxidase. In summary, lactoferrin can regulate the metabolic disorder of intestinal flora, reduce intestinal permeability, and further regulate the metabolic balance of hippocampal tissues through the microbiota-gut-brain axis. This process ultimately alleviates the depression-like behavior in rats.

Abstract During the progression of proliferative vitreoretinopathy (PVR) following ocular trauma, previously quiescent retinal pigment epithelial (RPE) cells transition into a state of rapid proliferation, migration, and secretion. The elusive molecular mechanisms behind these changes have hindered the development of effective pharmacological treatments, presenting a pressing clinical challenge. In this study, by monitoring the dynamic changes in chromatin accessibility and various histone modifications, we chart the comprehensive epigenetic landscape of RPE cells in male mice subjected to traumatic PVR. Coupled with transcriptomic analysis, we reveal a robust correlation between enhancer activation and the upregulation of the PVR-associated gene programs. Furthermore, by constructing transcription factor regulatory networks, we identify the aberrant activation of enhancer-driven RANK-NFATc1 pathway as PVR advanced. Importantly, we demonstrate that intraocular interventions, including nanomedicines inhibiting enhancer activity, gene therapies targeting NFATc1 and antibody therapeutics against RANK pathway, effectively mitigate PVR progression. Together, our findings elucidate the epigenetic basis underlying the activation of PVR-associated genes during RPE cell fate transitions and offer promising therapeutic avenues targeting epigenetic modulation and the RANK-NFATc1 axis for PVR management.

TiAl composite with core-shell structure was in-situ synthesized incorporating BN nanosheets and graphene oxide into TiAl alloy using SPS, and the hot deformation behaviors were subsequently investigated on a Gleeble-1500D thermal simulation machine. The microstructural evolution and the influence of ceramic particles on hot deformation were revealed using OM, SEM, TEM, and EBSD. The results demonstrated a refined microstructure of TiAl composite induced by ceramic particles providing extra nucleation sites for DRX, contributing to lower flow stress, with peak stresses of 387 and 360 MPa for TiAl alloy and TiAl composite deformed at 1200 °C/1s−1, respectively. Moreover, dislocation slip was inhibited by ceramic particles leading to dislocation pile-up, facilitating the nucleation and growth of DRX at lamellar colony boundaries and α2/γ interfaces. Notably, the “shell” composed of TiB2 and Ti2AlN nanoparticles coordinated the deformation of lamellar colonies with different orientations, improving the hot workability of TiAl composite.

Background/purpose: The dental adhesive market is constantly evolving to meet the demands of dentists and patients, but new products and upgrades should be rigorously evaluated before being used in clinical practice. This study investigated the physicomechanical properties and dentin bonding efficacy of a newly upgraded universal adhesive compared to its predecessor. Materials and methods: Twenty-four molars were divided into four groups (n = 6/group) based on adhesive (new vs. predecessor) and application mode [self-etch (SE) vs. etch-and-rinse (ER)] for evaluating their dentin microtensile bond strength (μTBS), failure pattern, and bonding interface. Additional thirty-six molars’ crowns were perpendicularly sectioned to obtain flat mid-coronal dentin discs. The opposing dentin surfaces of each disc received contrasting treatments (new/predecessor adhesive applied in SE/ER mode), resulting in six interventions. The bonded discs (n = 6/intervention) were used to assess the adhesives’ survival probability employing a double-sided μTBS test. The other physicomechanical properties examined were adhesives’ oxygen inhibition layer (OIL), viscosity, hardness, elastic modulus, degree of conversion (DC), and in-situ DC. Results: Both adhesive versions showed similar μTBS (P > 0.05), failure pattern (P > 0.05), and survival probability (P > 0.008). ER mode promoted resin tag formation and exhibited a slender adhesive layer for both adhesives. The newer adhesive version showed a thinner adhesive layer in general with narrower OIL (P

Introduction: Guilingji, a famous traditional Chinese medicine (TCM) formula, has been used to combat aging and male sexual dysfunction in China for centuries. To date, there has been little evidence-based clinical research on the use of Guilingji to treat idiopathic oligo-asthenoteratozoospermia (OAT), and the therapeutic mechanism from a metabolic perspective needs to be investigated further. Methods: This was a multicenter, double-blind, randomized controlled clinical study of 240 patients with idiopathic OAT recruited from four hospitals between January 2020 and January 2022. Patients were randomly assigned in a 1꞉1 ratio to receive oral Guilingji capsules or placebo for 12 weeks. The total progressive motile sperm count (TPMSC) was considered the primary outcome, and the other sperm parameters, seminal plasma parameters and serum hormones were considered the secondary outcome. A nontargeted metabolomics analysis of serum from OAT patients before and after Guilingji administration was performed by HPLC–MS to identify key metabolites. Furthermore, we used a rat model to show spermatogenesis phenotypes to validate the effect of the key metabolites screened from the patients. Results: At weeks 4, 8 and 12, TPMSC and other sperm parameters were significantly improved in the Guilingji group compared with the placebo group (P

Abstract The potato cyst nematode Globodera rostochiensis originates from the Andean Mountain region in South America and has unintentionally been introduced to all inhabited continents. Several studies have examined the population genetic structure of this pest in various countries by using microsatellite markers. However, merging microsatellite data produced from different laboratories is challenging and can introduce uncertainty when interpreting the results. To overcome this challenge and to explore invasion routes of this pest, we have genotyped 22 G. rostochiensis populations from all continents. Within populations, the highest genetic diversity was observed in the South American populations, the European populations showed an intermediate level of genetic diversity and the remaining populations were the less diverse. This confirmed pre-existing knowledge such as a first introduction event from South America to Europe, but the less diverse populations could originate either from South America or from Europe. At the continental scale, STRUCTURE genetic clustering output indicated that North America and Asia have experienced at least two introduction events. Comparing different evolutionary scenarios, the Approximate Bayesian Computation analysis showed that Europe served as a secondary distribution centre for the invasion of G. rostochiensis into all other continents (North America, Africa, Asia and Oceania).

Abstract Critical illness can significantly alter the composition and function of the human microbiome, but few studies have examined these changes over time. Here, we conduct a comprehensive analysis of the oral, lung, and gut microbiota in 479 mechanically ventilated patients (223 females, 256 males) with acute respiratory failure. We use advanced DNA sequencing technologies, including Illumina amplicon sequencing (utilizing 16S and ITS rRNA genes for bacteria and fungi, respectively, in all sample types) and Nanopore metagenomics for lung microbiota. Our results reveal a progressive dysbiosis in all three body compartments, characterized by a reduction in microbial diversity, a decrease in beneficial anaerobes, and an increase in pathogens. We find that clinical factors, such as chronic obstructive pulmonary disease, immunosuppression, and antibiotic exposure, are associated with specific patterns of dysbiosis. Interestingly, unsupervised clustering of lung microbiota diversity and composition by 16S independently predicted survival and performed better than traditional clinical and host-response predictors. These observations are validated in two separate cohorts of COVID-19 patients, highlighting the potential of lung microbiota as valuable prognostic biomarkers in critical care. Understanding these microbiome changes during critical illness points to new opportunities for microbiota-targeted precision medicine interventions.

An innovative two-step approach of self-propagating high-temperature synthesis (SHS) and spark plasma sintering (SPS) was developed to rapidly fabricate MoSi2 and Mo(Al,Si)2 ceramics for high-temperature anti-oxidation applications. The SHS process predominantly promoted the synthesis of high-purity and high-yield MoSi2 and Mo(Si,Al)2 phases in the alloyed powders. Subsequently, dense and crack-free MoSi2 and Mo(Al,Si)2 ceramics were produced using SPS. 1500 °C oxidation tests of the ceramics (100 h) revealed the formation of a protective SiO2 oxide layer on the surface of MoSi2 ceramics, while an Al-Si-O composite glassy oxide layer formed on Mo(Si,Al)2 ceramics, which exhibited better thermal stability and lower oxygen permeability compared to the single SiO2 oxide layer. However, an excessive Al content (>0.05 at.%) compromised the oxidation resistance due to the emergence of a Si-depleted Mo5(Si,Al)3 layer with inferior oxidation resistance, which was caused by the high-temperature diffusion of Si. Therefore, via this novel two-step SHS-SPS technique compact and crack-free Mo(Si,Al)2 ceramics can be rapidly synthesized at high temperatures. When trace amount of Al was added (0.05 at.%), Mo(Si0.95Al0.05)2 showed optimum high-temperature oxidation resistance.

ObjectiveTo develop a guideline for selecting biomarkers in the diagnosis and assessment in patients with axial spondyloarthritis (axSpA).MethodA joint effort was carried out by the core team, the literature review team and the multidisciplinary voting panel to formulate recommendations regarding biomarkers in axSpA, using an evidence-based and consensus-based strategy. Certainty of evidence and strength of recommendation were determined, and levels of agreement within the voting panel were calculated.ResultsA total of 20 recommendations were formulated in this guideline, with levels of agreement ranging from 6.48 to 9.71. The two strong recommendations, HLA-B27 testing in patients suspected of axSpA and regular-interval monitoring of CRP/ESR represent the status quo of axSpA evaluation, while the 13 conditional recommendations represent the promising biomarkers with clinical utility in diagnosis, disease activity assessment, prediction of radiographic progression and therapeutic responses. This guideline does not dictate clinical choices of tests on axSpA, and decisions should be made based on comprehensive consideration of costs, accessibility, patients’ values and willingness as well as the objective of testing in the local context.ConclusionThis guideline addresses the interpretation of the clinical significance of biomarkers in axSpA, and the biomarkers endorsed in this guideline composed a clinical toolkit for healthcare professionals to choose from.

This study investigates the effectiveness of Shenlin Baizhu powder in managing non-alcoholic fatty liver disease (NAFLD) during pregnancy and its mechanism through the PI3K/AKT/mTOR signaling pathway. Eight healthy male and 24 female Sprague-Dawley rats were used. After acclimatization, 6 female rats were fed normal chow, and 18 female rats were fed high-fat chow to induce NAFLD. After 8 weeks, female rats were mated with males to create a pregnant NAFLD model. The rats were divided into four groups: normal feeding, high-fat diet with saline, high-fat diet with 1.6 g/kg Shenlin Baizhu powder, and high-fat diet with 4.8 g/kg Shenlin Baizhu powder. Maternal body weight, serum and liver levels of aspartate aminotransferase (AST), alanine transaminase (ALT), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), related inflammatory indexes interleukin-1 β (IL-1 β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured. Liver tissue was examined using hematoxylin and oil red O staining, and protein expression related to the PI3K/AKT/mTOR pathway was assessed via Western blotting, immunohistochemistry and RT-PCR. Results showed significant weight gain and increases in ALT, AST, TG, TC, LDL-C, IL-1β, TNF-α, and IL-6, along with decreased HDL-C in NAFLD rats compared to controls. The high and low-dose Shenlin Baizhu powder groups exhibited improvements in body weight, liver histopathology, and reductions in serum TG, TC, LDL-C, ALT, AST, IL-1β, TNF-α, and IL-6, with increased HDL-C levels. Notably, the high-dose group showed greater efficacy in reducing hepatic fat accumulation, liver function markers, blood lipids, and inflammatory indexes, and decreased expression of hepatic PPARγ mRNA, SREBP1 mRNA, AKT mRNA, and related proteins. Shenlin Baizhu powder demonstrates potential in ameliorating high-fat diet-induced NAFLD in pregnant rats, likely through modulation of the PI3K/AKT/mTOR pathway, suggesting its therapeutic potential for gestational NAFLD.

PurposeParotid gland metastases originating from breast origin are extremely rare, with their clinical presentation, therapeutic approaches, and prognostic indicators remaining to be elucidate.MethodsA comprehensive retrospective review was conducted, analyzing the clinical characteristics and prognostic factors of 57 patients diagnosed with parotid metastasis of breast cancer in the existing literature. Notably, our study included two unique cases of patients who developed contralateral and ipsilateral parotid metastases, occurring 5 years and 32 years respectively after primary surgery. This analysis aimed to provide a deeper understanding of the disease presentation and identify potential prognostic indicators.ResultsThe primary clinical manifestation presented in breast cancer patients with parotid metastases was painless masses in the parotid glands, synchronously or metachronously occurred with primary breast tumors. The predominant pathological subtype among these patients was invasive ductal carcinoma. Out of the 57 patients studied, 24 (42.1%) exhibited metastases solely in the ipsilateral parotid gland, while 18 cases (31.6%) involved either the contralateral or bilateral parotid gland. Patients may solely exhibit metastasis in the parotid gland, or they may present with concurrent multiple metastases in other organs. Patients who suffered from parotid metastases, either merely or accompanied with bone-only metastasis, exhibited significantly longer overall survival (OS) rates compared to those who had concomitant metastases in other organs (1.23 ± 0.26 years vs 4.46 ± 0.77 years, P=0.046). While no statistically significant differences in OS were observed among patients presenting with metastases in the ipsilateral, contralateral, or bilateral parotid glands, a notable variance could be discerned from the Kaplan-Meier curve analysis. Additionally, no significant difference in survival was exhibited between patients with different interval of progression from primary breast sites to initial diagnosis of parotid metastases (uDF), nor for patients who were treated with surgery or palliative therapy.ConclusionParotid metastasis, a rare and distinctive form of breast cancer metastasis, demands particular scrutiny in patients exhibiting metastasis to multiple organs or contralateral or bilateral parotid glands.

Objectives: This study aimed to evaluate the therapeutic effects of forsythoside A (FA) on brain injury induced by severe acute pancreatitis (SAP) using a murine model. Methods: Mice were induced with 3.5 % sodium taurocholate to model SAP-induced brain injury (SAP-IBI) and were randomly assigned to four distinct treatment regimens: the SAP-IBI model group (SAP-IBI), low-dose FA treatment group (FA L+SI), middle-dose FA treatment group (FA M+SI), and high-dose FA treatment group (FA H+SI). A sham-operation group (SO) served as a negative control. Serum levels of interleukin-1β (IL-1β) and IL-18 were quantified via ELISA, and serum amylase levels were assessed using optical turbidimetry. mRNA expression levels of AIM2, ASC, Caspase-1, and GAPDH in hippocampal brain tissue were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Protein levels of NLRP3, GSDMD, IL-1β, and IL-18 in hippocampal brain tissue were evaluated using Western blotting. Neurological function in surviving mice was assessed through modified neurological severity scores (mNSS). Transmission electron microscopy (TEM) provided ultrastructural analysis of the hippocampus. Additionally, water content and pathological changes in hippocampal brain tissue were examined 24 hours post-operation, along with other relevant indicators. Results: At 24 hours post-operation, the FA H+SI group exhibited significantly reduced levels of serum amylase, IL-1β, and IL-18, along with decreased expression of AIM2, ASC, and Caspase-1 mRNA. Furthermore, NLRP3 protein levels, water content, pancreas and hippocampal brain pathological scores, and mNSS were significantly lower compared to the SAP-IBI group (P

Abstract Background Colorectal signet-ring cell carcinoma (SRCC) is a rare cancer with a bleak prognosis. The relationship between its clinicopathological features and survival remains incompletely elucidated. Tumor deposits (TD) have been utilized to guide the N staging in the 8th edition of American Joint Committee on Cancer (AJCC) staging manual, but their prognostic significance remains to be established in colorectal SRCC. Patients and methods The subjects of this study were patients with stage III/IV colorectal SRCC who underwent surgical treatment. The research comprised two cohorts: a training cohort and a validation cohort. The training cohort consisted of 631 qualified patients from the SEER database, while the validation cohort included 135 eligible patients from four independent hospitals in China. The study assessed the impact of TD on Cancer-Specific Survival (CSS) and Overall Survival (OS) using Kaplan-Meier survival curves and Cox regression models. Additionally, a prognostic nomogram model was constructed for further evaluation. Results In both cohorts, TD-positive patients were typically in the stage IV and exhibited the presence of perineural invasion (PNI) (P

Abstract Objective Recurrent pregnancy loss (RPL) patients have higher absolute numbers of decidual natural killer (dNK) cells with elevated intracellular IFN-γ levels leading to a pro-inflammatory cytokine milieu, which contributes to RPL pathogenesis. The main objective of this study was twofold: first to explore the regulatory effects and mechanisms of villus-derived exosomes (vEXOs) from induced abortion patients or RPL patients at the level of intracellular IFN-γ in dNK cells; second to determine the validity of application of vEXOs in the treatment of unexplained RPL (uRPL) through in vitro experiments and mouse models. Methods Exosomes were isolated from villus explants by ultracentrifugation, co-cultured with dNK cells, and purified by enzymatic digestion and magnetically activated cell sorting. Flow cytometry, enzyme-linked immunosorbent assays, and RT-qPCR were used to determine IFN-γ levels. Comparative miRNA analysis of vEXOs from induced abortion (IA) and uRPL patients was used to screen potential candidates involved in dNK regulation, which was further confirmed by luciferase reporter assays. IA-vEXOs were electroporated with therapeutic miRNAs and encapsulated in a China Food and Drug Administration (CFDA)-approved hyaluronate gel (HA-Gel), which has been used as a clinical biomaterial in cell therapy for > 30 years. In vivo tracking was performed using 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyaine iodide (DiR) labelling. Tail-vein and uterine horn injections were used to evaluate therapeutic effects of the engineered exosomes in an abortion-prone mouse model (CBA/J × DBA/2 J). Placental growth was evaluated based on placental weight. IFN-γ mRNA levels in mouse placentas were measured by RT-qPCR. Results IFN-γ levels were significantly higher in dNK cells of uRPL patients than in IA patients. Both uRPL-vEXOs and IA-vEXOs could be efficiently internalized by dNK cells, whereas uRPL-vEXOs could not reduce the expression of IFN-γ by dNK cells as much as IA-vEXOs. Mechanistically, miR-29a-3p was delivered by vEXOs to inhibit IFN-γ production by binding to the 3′ UTR of IFN-γ mRNA in dNK cells. For in vivo treatment, application of the HA-Gel effectively prolonged the residence time of vEXOs in the uterine cavity via sustained release. Engineered vEXOs loaded with miR-29a-3p reduced the embryo resorption rate in RPL mice with no signs of systemic toxicity. Conclusion Our study provides the first evidence that villi can regulate dNK cell production of IFN-γ via exosome-mediated transfer of miR-29a-3p, which deepens our understanding of maternal–fetal immune tolerance for pregnancy maintenance. Based on this, we developed a new strategy to mix engineered vEXOs with HA-Gel, which exhibited good therapeutic effects in mice with uRPL and could be used for potential clinical applications in uRPL treatment. Graphical Abstract

Abstract Immunotherapy had shown good antitumor activity in a variety of solid tumors, but low benefit in CRC, so there was an urgent need to explore new biomarkers. We evaluated the role of KMT2C using publicly available data from the Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC). In addition, further analysis was performed in an internal cohort. Moreover, the mutant profiles of KMT2C was analyzed in a large CRC cohort. The relationship between clinical pathologic features and KMT2C were analyzed with using the two-sided chi-squared test or the Fisher exact test. Clinicopathologic characteristics associated with overall survival using Cox regression and the Kaplan–Meier method. We found that KMT2C-mutated CRC patients in the immunotherapy cohort had significantly improved OS compared with KMT2C WT patients (P = 0.013). However, this phenomenon did not exist in non-immunotherapy cohort. Our cohort validated the value of KMT2C mutations in predicting better clinical outcomes, including ORR (P

Bioabsorbable zinc (Zn)-based materials for bone defect repair have received increasing attention. Based on 3D printing technology, this study innovatively designed and manufactured pure Zn and Ti6Al4V porous scaffolds. The pore size of the scaffold was 700 μm and the porosity was 70%. Compared with the traditional Ti6Al4V scaffolds, it was found that the Zn scaffolds had a larger deformation, the ultimate compressive stress was 18 MPa, but the ultimate strain could exceed 20%, while Ti6Al4V was only 6%. The elastic modulus of the Zn scaffolds was also lower than that of Ti6Al4V, which was 0.25 GPa, which can meet bone repair requirements in the non-weight-bearing area. However, Zn scaffolds had better strain capacity and lower elastic modulus, so they had less stress-shielding effect on bone. Degradation experiments also proved that the Zn scaffold had good degradation performance. Further in vivo and in vitro experiments showed that the Zn scaffolds had better osteogenic ability than the Ti6Al4V scaffolds. The findings of our study underscore the potential of integrating pure Zn into 3D printed scaffolds for their application in orthopedic scenarios.

Point cloud completion aims to utilize algorithms to repair missing parts in 3D data for high-quality point clouds. This technology is crucial for applications such as autonomous driving and urban planning. With deep learning’s progress, the robustness and accuracy of point cloud completion have improved significantly. However, the quality of completed point clouds requires further enhancement to satisfy practical requirements. In this study, we conducted an extensive survey of point cloud completion methods, with the following main objectives: (i) We classified point cloud completion methods into categories based on their principles, such as point-based, convolution-based, GAN-based, and geometry-based methods, and thoroughly investigated the advantages and limitations of each category. (ii) We collected publicly available datasets for point cloud completion algorithms and conducted experimental comparisons using various typical deep-learning networks to draw conclusions. (iii) With our research in this paper, we discuss future research trends in this rapidly evolving field.

Objective This scoping review and meta-analysis aimed to map the evidence regarding prognostic factors in Chinese patients with immunoglobulin light chain (AL) amyloidosis and to identify current research gaps.Methods We searched EMBASE, PubMed, and CNKI databases from their inception to 15 September 2021. All studies investigated the association between any prognostic factor and target outcomes, including overall survival (OS), progression-free survival (PFS), and end-stage renal disease (ESRD) in Chinese patients with AL amyloidosis.Results This scoping review included 52 studies, of which 44 with 6,432 patients contributed to the multivariate prognostic analysis. Multivariate analysis identified a total of 106 factors that correlated with OS, 16 factors with PFS, and 18 factors with ESRD. Five prognostic factors were significantly associated with PFS, and 11 prognostic factors were significantly associated with ESRD. Meta-analysis was only available for prognostic factors without heterogeneous cutoff values, for which hazard ratios (HRs) and their 95% confidence intervals (CIs) were reported. Meta-analysis showed that bone marrow plasma cells (BMCs) (HR: 1.96, 95% CI: 1.21–3.19, p

Combined exposure to phthalate esters (PAEs) has garnered increasing attention due to potential synergistic effects on human health. This study aimed to develop an in vitro model using human macrophages to evaluate the combined toxicity of PAEs and explore the underlying mechanisms. A high-throughput screening system was engineered by expressing a PPRE-eGFP reporter in THP-1 monocytes to monitor macrophage polarization upon PAEs exposure. Individual PAEs exhibited varied inhibitory effects on M2 macrophage polarization, with mono(2-ethylhexyl) phthalate (MEHP) being the most potent. Isobologram analysis revealed additive interactions when MEHP was combined with other PAEs, resulting in more pronounced suppression of M2 markers compared to individual compounds. Mechanistic studies suggested PAEs may exert effects by modulating PPARγ activity to inhibit M2 polarization. Notably, an equimolar mixture of six PAEs showed additive inhibition of M2 markers. In vivo experiments corroborated the combined hepatotoxic effects, with mice exposed to a PAEs mixture exhibiting reduced liver weight, dyslipidemia, and decreased hepatic M2 macrophages compared to DEHP alone. Transcriptome analysis highlighted disruptions in PPAR signaling, and distinct pathway alterations on cholesterol metabolism in the mixture group. Collectively, these findings underscore the importance of evaluating mixture effects and provide a novel approach for hazard assessment of combined PAEs exposure with implications for environmental health risk assessment.

Introduction Postoperative radiotherapy in patients with breast cancer with one to three lymph node metastases, particularly within the pT1–2N1M0 cohort with a low clinical risk of local–regional recurrence (LRR), has incited a discourse surrounding personalised treatment strategies. Multigene testing for Recurrence Index (RecurIndex) model capably differentiates patients based on their level of LRR risk. This research aims to validate whether a more aggressive treatment approach can enhance clinical outcomes in N1 patients who possess a clinically low risk of LRR, yet a high RecurIndex-determined risk of LRR. Specifically, this entails postoperative whole breast irradiation combined with regional lymph node irradiation (RNI) following breast-conserving surgery or chest wall irradiation with RNI after mastectomy.Methods and analysis The RIGAIN (RecurIndex-Guided postoperative radiotherapy with or without Avoidance of Irradiation of regional Nodes in 1–3 node-positive breast cancer) Study is a multicentre, prospective, randomised, open-label, phase III clinical trial that is being conducted in China. In this study, patients with low clinical LRR risk but high RecurIndex-LRR risk are randomly assigned in a 1:1 ratio to the experimental group or the control group. In the experimental group, RNI is performed and the control group omits RNI. Efficacy and safety analyses will be conducted, enrolling a total of 540 patients (270 per group). The primary endpoint is invasive disease-free survival, and secondary endpoints include any first recurrence, LRR-free survival, distant metastasis-free survival, recurrence-free survival, overall survival, disease-free survival, breast cancer-specific mortality and assessment of patient quality of life. The study began in April 2023 and with a follow-up period of 60 months after the last participant completes radiation therapy.Ethics and dissemination The study was approved by the Ethics Committee of Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University (SYSKY-2022-097-02, V.3.1). It adheres to the Helsinki Declaration and Good Clinical Practice. Research findings will be submitted for publication in peer-reviewed journals.Trial registration number NCT04069884.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, with relapse being a major obstacle to successful treatment. Our understanding of the mechanisms driving chemotherapy resistance and ultimately relapse in leukemia remains incomplete. Herein, we investigate the impact of the tumor microenvironment on leukemia cell drug responses using human plasma-like media (HPLM), designed to mimic physiological conditions more accurately ex vivo. We demonstrate that while most chemotherapeutics maintain an efficacy in HPLM comparable to standard tissue culture media, the thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) exhibit significantly reduced potency and efficacy against both B- and T- leukemia cells in HPLM. By merging our understanding of thiopurines’ mechanism of action with the metabolites supplemented in HPLM compared to standard media, we proposed and subsequently validated the hypothesis that hypoxanthine, a purine derivative, is responsible for conferring resistance to the thiopurines. Importantly, the concentration of hypoxanthine required for resistance is comparable to physiological levels found in vivo, supporting clinical relevance. Our findings demonstrate the utility of a more physiologic media in identifying and characterizing mechanisms by which the microenvironment can enable resistance. Understanding such interactions may inform strategies to overcome drug resistance and improve therapeutic outcomes in pediatric leukemia.

Abstract The photoreceptor cilium is vital for maintaining the structure and function of the retina. However, the molecular mechanisms underlying the photoreceptor cilium integrity and retinal homeostasis are largely unknown. Herein, it is shown that kinesin family member 11 (KIF11) localizes at the transition zone (connecting cilium) of the photoreceptor and plays a crucial role in orchestrating the cilium integrity. KIF11 depletion causes malformations of both the photoreceptor ciliary axoneme and membranous discs, resulting in photoreceptor degeneration and the accumulation of drusen‐like deposits throughout the retina. Mechanistic studies show that the stability of KIF11 is regulated by an interplay between its UFMylation and ubiquitination; UFMylation of KIF11 at lysine 953 inhibits its ubiquitination by synoviolin 1 and thereby prevents its proteasomal degradation. The lysine 953‐to‐arginine mutant of KIF11 is more stable than wild‐type KIF11 and also more effective in reversing the ciliary and retinal defects induced by KIF11 depletion. These findings identify a critical role for KIF11 UFMylation in the maintenance of photoreceptor cilium integrity and retinal homeostasis.

Abstract Purpose Radical surgery, the first‐line treatment for patients with hepatocellular cancer (HCC), faces the dilemma of high early recurrence rates and the inability to predict effectively. We aim to develop and validate a multimodal model combining clinical, radiomics, and pathomics features to predict the risk of early recurrence. Materials and Methods We recruited HCC patients who underwent radical surgery and collected their preoperative clinical information, enhanced computed tomography (CT) images, and whole slide images (WSI) of hematoxylin and eosin (H & E) stained biopsy sections. After feature screening analysis, independent clinical, radiomics, and pathomics features closely associated with early recurrence were identified. Next, we built 16 models using four combination data composed of three type features, four machine learning algorithms, and 5‐fold cross‐validation to assess the performance and predictive power of the comparative models. Results Between January 2016 and December 2020, we recruited 107 HCC patients, of whom 45.8% (49/107) experienced early recurrence. After analysis, we identified two clinical features, two radiomics features, and three pathomics features associated with early recurrence. Multimodal machine learning models showed better predictive performance than bimodal models. Moreover, the SVM algorithm showed the best prediction results among the multimodal models. The average area under the curve (AUC), accuracy (ACC), sensitivity, and specificity were 0.863, 0.784, 0.731, and 0.826, respectively. Finally, we constructed a comprehensive nomogram using clinical features, a radiomics score and a pathomics score to provide a reference for predicting the risk of early recurrence. Conclusions The multimodal models can be used as a primary tool for oncologists to predict the risk of early recurrence after radical HCC surgery, which will help optimize and personalize treatment strategies.

High energy density, long cyclability, and enhanced stability in a small footprint achieved through microfabrication are crucial for micro lithium‐ion batteries. Herein, a 3D Si‐clad NiSn anode characterized by a dendritic NiSn network and silicon nanoparticles is proposed. The dendritic network facilitates fast ion/electron transfer and provides expansion space for the silicon, while the uniformly distributed silicon enhances capacity and stability. The anode, scalable to the hundred‐micron scale, is fabricated via one‐step electrodeposition incorporating the dynamic template technique. This technique generates interconnected pores extending from the inner to the outer surface of the anode, facilitating electrolyte penetration and ion transport. As a result, the anodes in the Swagelok cells exhibit an ultrahigh areal capacity of up to 28.2 mAh cm−2 and an enhanced stability of 91% capacity retention after 300 cycles. The dendritic Si‐clad NiSn anode, based on microfabrication, presents an excellent opportunity to advance micro energy systems.

Abstract Background Ovarian stimulation (OS) during assisted reproductive technology (ART) appears to be an independent factor influencing the risk of low birth weight (LBW). Previous studies identified the association between LBW and placenta deterioration, potentially resulting from disturbed genomic DNA methylation in oocytes caused by OS. However, the mechanisms by which OS leads to aberrant DNA methylation patterns in oocytes remains unclear. Methods Mouse oocytes and mouse parthenogenetic embryonic stem cells (pESCs) were used to investigate the roles of OS in oocyte DNA methylation. Global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels were evaluated using immunofluorescence or colorimetry. Genome-wide DNA methylation was quantified using an Agilent SureSelectXT mouse Methyl-Seq. The DNA methylation status of mesoderm-specific transcript homologue (Mest) promoter region was analyzed using bisulfite sequencing polymerase chain reaction (BSP). The regulatory network between estrogen receptor alpha (ERα, ESR1) and DNA methylation status of Mest promoter region was further detected following the knockdown of ERα or ten-eleven translocation 2 (Tet2). Results OS resulted in a significant decrease in global 5mC levels and an increase in global 5hmC levels in oocytes. Further investigation revealed that supraphysiological β-estradiol (E2) during OS induced a notable decrease in DNA 5mC and an increase in 5hmC in both oocytes and pESCs of mice, whereas inhibition of estrogen signaling abolished such induction. Moreover, Tet2 may be a direct transcriptional target gene of ERα, and through the ERα-TET2 axis, supraphysiological E2 resulted in the reduced global levels of DNA 5mC. Furthermore, we identified that MEST, a maternal imprinted gene essential for placental development, lost its imprinted methylation in parthenogenetic placentas originating from OS, and ERα and TET2 combined together to form a protein complex that may promote Mest demethylation. Conclusions In this study, a possible mechanism of loss of DNA methylation in oocyte caused by OS was revealed, which may help increase safety and reduce epigenetic abnormalities in ART procedures.

Metal component defect detection plays an important role in industrial manufacturing. However, it is a challenging task to detect defects from the metal component surface due to these problems: 1) Some defects are small and appear randomly on the metal component; 2) There is low-intensity contrast between defect areas and surrounding ones. To solve these issues, a Scale Adaptive Attention Network (SAA-Net) is proposed for defect detection from metal parts, where the Interactive Spatial Position Attention (ISPA) module is devised to detect small defects from the metal part surface by modeling the interdependence between pixels; then, the Dual Local-Global Transformer (DLGT) module is designed to distinguish the defect regions from the surrounding normal ones by fusing the overall attributes and key features. Experiments on the MPDD dataset demonstrate the effectiveness of the proposed SAA-Net, achieving the performance of 97.5%, 90.7%, and 96.1% on the pixel AUC, AP, and sPRO, respectively, further assisting in metal part detection in manufacturing.

Abstract To combat infections, silver was used extensively in biomedical field but there was a need for a capping agent to eliminate its cytotoxic effects. In this study, polymeric calcium polyphosphate was doped by silver with three concentrations 1, 3 or 5 mol.% and were characterized by TEM, XRD, FTIR, TGA. Moreover, cytotoxicity, antibacterial, cell migration and DNA fragmentation assays were done to assure its safety. The results showed that the increase in silver percentage caused an increase in particle size. XRD showed the silver peaks, which indicated that it is present in its metallic form. The TGA showed that thermal stability was increased by increasing silver content. The antibacterial tests showed that the prepared nanoparticles have an antibacterial activity against tested pathogens. In addition, the cytotoxicity results showed that the samples exhibited non-cytotoxic behavior even with the highest doping concentration (5% Ag-CaPp). The cell migration assay showed that the increase in the silver concentration enhances cell migration up to 3% Ag-CaPp. The DNA fragmentation test revealed that all the prepared nanoparticles caused no fragmentation. From the results we can deduce that 3% Ag-CaPp was the optimum silver doped calcium polyphosphate concentration that could be used safely for medical applications.

The potato cyst nematode (Globodera rostochiensis) is an obligate root pathogen of potatoes. G. rostochiensis encodes several highly expanded effector gene families, including the Gr4D06 family; however, little is known about the function of this effector family. We cloned four 29D09 genes from G. rostochiensis (named Gr29D09v1/v2/v3/v4) that share high sequence similarity and are homologous to the Hg29D09 and Hg4D06 effector genes from the soybean cyst nematode (Heterodera glycines). Phylogenetic analysis revealed that Gr29D09 genes belong to a subgroup of the Gr4D06 family. We showed that Gr29D09 genes are expressed exclusively within the nematode's dorsal gland cell and are dramatically upregulated in parasitic stages, indicating involvement of Gr29D09 effectors in nematode parasitism. Transgenic potato lines overexpressing Gr29D09 variants showed increased susceptibility to G. rostochiensis. Transient expression assays in Nicotiana benthamiana demonstrated that Gr29D09v3 could suppress reactive oxygen species (ROS) production and defense gene expression induced by flg22 and cell death mediated by immune receptors. These results suggest a critical role of Gr29D09 effectors in defense suppression. The use of affinity purification coupled with nanoliquid chromatography–tandem mass spectrometry identified potato hexokinase 1 (StHXK1) as a candidate target of Gr29D09. The Gr29D09–StHXK1 interaction was further confirmed using in planta protein–protein interaction assays. Plant HXKs have been implicated in defense regulation against pathogen infection. Interestingly, we found that StHXK1 could enhance flg22-induced ROS production, consistent with a positive role of plant HXKs in defense. Altogether, our results suggest that targeting StHXK1 by Gr29D09 effectors may impair the positive function of StHXK1 in plant immunity, thereby aiding nematode parasitism. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Based on a line-of-sight (LOS) guidance law for a curve parametrized path, a finite-time backstepping control is proposed for the kinematic path-following of an underactuated autonomous surface vehicle (ASV). Finite-time observer is utilized to estimate the unknown external disturbances accurately. The first-order Levant differentiator is introduced into the finite-time filter technique, such that the output of filter can not only approximate the derivative of the virtual control, but also avoid the singularity problem of real heading control. The integral terminal sliding mode is employed to improve the tracking performance and converging rate in the surging velocity control. By virtue of Lyapunov function, all the signals in the closed-loop system can be guaranteed uniformly ultimate boundedness, and accurate path-following task can be fulfilled in finite time. The simulation results and comparative analysis validate the effectiveness and robustness of the proposed control approach.

Pressure is a critical component of preparation processes regardless of its magnitude, whether it is a few megapascals, such as in metal squeeze casting, or thousands of megapascals, such as in the experimental preparation of amorphous materials, quasicrystals and nanocrystals. Spinodal decomposition and ordering are two common forms of unstable phase transformation in solid solutions. Reasonable regulation of these two transformations can effectively control microstructures and improve properties. Therefore, the study of solid solution instability under the effect of ultrahigh pressure is of great significance for regulating the properties of high-entropy alloys (HEAs). From this perspective, CoCrFeNiAl HEAs were prepared under pressures of ambient pressure, 4 GPa and 7 GPa. Both solid spinodal decomposition and ordering of the BCC structure were detected when CoCrFeNiAl HEAs are solidified at ambient pressure. Nevertheless, after high-pressure solidification, liquid‒liquid phase spinodal decomposition occurred. One phase was rich in (Fe, Cr), and the other phase was rich in (Ni, Al). Both phases experienced solid spinodal decomposition during cooling. Discontinuous precipitates were generated in the (Ni, Al)-rich solid phase, each with a size of approximately 1.4 μm. Furthermore, a graphic thermodynamic model was established to reveal the solidification behavior. After solidification at 7 GPa, the corrosion rate of the alloy decreased by 98.3 %; that is, the high pressure greatly improved the corrosion resistance of the alloy. This improvement was attributed to the influences of high pressures on the dynamics of spinodal decomposition processes.

Abstract Under natural conditions, most Hibiscus syriacus L. individuals form very few mature seeds or the mature seeds that do form are of poor quality. As a result, seed yield is poor and seeds have low natural germinability. These phenomena strongly hinder utilization of the excellent germplasm resources of H. syriacus. The study has shown that pollen activity and stigma receptivity were high on the day of anthesis, and the pistils and stamens were fertile. Pollen release and stigma receptivity were synchronous. But in styles following self and cross-pollination, pollen tube abnormalities (distortion and twisting of the pollen tubes) and callose deposition were observed. Cross-pollinated pollen tubes elongated faster and fewer pollen tube abnormalities were observed compared with self-pollinated pollen tubes. And during embryo development, abnormalities during the heart-shaped embryo stage led to embryo abortion. Imbalance in antioxidant enzyme activities and low contents of auxin and cytokinin during early stages of embryo development may affect embryo development. Therefore, a low frequency of outcrossing and mid-development embryo abortion may be important developmental causes of H. syriacus seed abortion. Nutrient deficiencies, imbalance in antioxidant enzyme activities, and a high content of abscisic acid at advanced stages of seed development may be physiological causes of seed abortion.

AbstractBackground Amyloid light chain (AL) amyloidosis is the most common systemic amyloidosis. The objective of this scoping review was to map the available literature on the diagnosis of AL amyloidosis in China.Materials and Methods The published academic papers related to the diagnosis of AL amyloidosis were screened from 1 January 2000 to 15 September 2021. Chinese patients who have suspected AL amyloidosis were included. The included studies were categorized into accuracy studies and descriptive studies based on if the studies supplied the diagnostic accuracy data or not. The information on the diagnostic methods reported by included studies was synthesized.Results Forty-three articles were included for the final scoping review, with 31 belonging to descriptive studies and 12 having information on diagnostic accuracy. Although cardiac involvement was second top in Chinese patients with AL amyloidosis, a cardiac biopsy was rare. Next, we found light chain classification and monoclonal (M-) protein identification were essential methods for the diagnosis of AL amyloidosis in China. In addition, some combined tests (e.g. immunohistochemistry and serum free light chain, immunohistochemistry and immunofixation electrophoresis, and serum free light chain and immunofixation electrophoresis) can increase the sensitivity of the diagnosis. Finally, several adjuvant methods (e.g. Imaging, N-terminal-pro hormone BNP, and brain natriuretic peptide test) were important for AL amyloidosis diagnosis.Conclusion This scoping review details the characteristics and results of the recently published studies on diagnosing AL Amyloidosis in China. Biopsy is the most important method for AL Amyloidosis diagnosis in China. In addition, combined tests and some adjuvant methods played essential roles in the diagnosis. Further research is required to determine an acceptable and feasible diagnostic algorithm after symptom onset. REGISTRATION: INPLASY2022100096KEY MESSAGESThis scoping review details the characteristics and results of the recently published studies on diagnosing Amyloid light chain (AL) Amyloidosis in China.Biopsy is the most important method for AL Amyloidosis diagnosis in China.Combined tests and some adjuvant methods played essential roles in the diagnosis.

Macroporous H5PMo10V2O40(n)/biochar (abbreviated as HPMoV(n)/biochar, where n is the loading amount of HPMo: 12 wt.%, 28 wt.%, 44 wt.%, 53 wt.%, and 63 wt.%) were fabricated from popcorn biocarbon and H5PMo10V2O40. The materials exhibited a pore size of 8–50 μm and high specific surface areas, allowing them to efficiently catalyze the degradation of phthalic acid esters (PAEs) in water. HPMoV(n)/biochar contained double-functional sites with strong Brønsted acidity and redox properties; additionally, biochar promoted electron transfer between the polyanions and PAEs and confined the generation of reactive oxygen species inside the pores. At the same time, macropores and high porosity endowed the materials with high adsorption capacities toward PAEs, even long carbon-chain esters such as diallyl phthalate and diethylhexyl phthalate. These characteristics allowed HPMoV(44)/biochar to degrade 80%–88% of PAEs within 90 min through tandem hydrolysis–oxidation. The mineralization of diethyl phthalate was confirmed by the 72.5% and 64.4% reductions in chemical oxygen demand and total organic carbon, respectively, at atmospheric pressure. HPMoV(44)/biochar exhibited heterogeneity and high stability in the degradation of diethyl phthalate. Furthermore, the material could be reused at least eight times with only 1.9% and 3.0% loss of mass and activity, respectively.

Inorganic nanoparticles have been widely used as fillers to modify dielectric elastomers to simultaneously improve mechanical and dielectric performances. Elegant interface design is crucial for achieving synergy between fillers and elastomers. Herein, we show that diborate ester polymers can both improve the interfacial compatibility between inorganic nanoparticles and elastomers and enhance the dielectric performances. The diborate ester polymers are derived from the condensation reaction between tetrakis(dimethylamino)diborane (or tetrahydroxydiborane) and a three‐armed catechol monomer. Choosing TiO2 nanoparticles as the inner core, a series of TiO2@diborate ester polymer core‐shell nanoparticles are synthesized. Density functional theory (DFT) calculations indicate that the diborate ester polymer shell tightly bonds to the surface of TiO2 through two dissociative bidentate bridging modes of the catechol monomer (absorption energy: −11.049 eV). These core‐shell nanoparticles can soften and tough polydimethylsiloxane (PDMS) and show enhanced interfacial binding affinity to PDMS than naked TiO2 nanoparticles. The fabricated composites have high dielectric constants (up to 6.8) and low dielectric losses (

Objective To characterise subphenotypes of self-reported symptoms and outcomes (SRSOs) in postacute sequelae of COVID-19 (PASC).Design Prospective, observational cohort study of subjects with PASC.Setting Academic tertiary centre from five clinical referral sources.Participants Adults with COVID-19 ≥20 days before enrolment and presence of any new self-reported symptoms following COVID-19.Exposures We collected data on clinical variables and SRSOs via structured telephone interviews and performed standardised assessments with validated clinical numerical scales to capture psychological symptoms, neurocognitive functioning and cardiopulmonary function. We collected saliva and stool samples for quantification of SARS-CoV-2 RNA via quantitative PCR.Outcomes measures Description of PASC SRSOs burden and duration, derivation of distinct PASC subphenotypes via latent class analysis (LCA) and relationship with viral load.Results We analysed baseline data for 214 individuals with a study visit at a median of 197.5 days after COVID-19 diagnosis. Participants reported ever having a median of 9/16 symptoms (IQR 6–11) after acute COVID-19, with muscle-aches, dyspnoea and headache being the most common. Fatigue, cognitive impairment and dyspnoea were experienced for a longer time. Participants had a lower burden of active symptoms (median 3 (1–6)) than those ever experienced (p

Background: Parathyroid carcinoma is a rare endocrine malignancy. Considering that clinicians develop appropriate treatment strategies based on patients' survival expectations. Therefore, the present study aimed to develop a survival prediction model to guide clinical decision-making. Methods: We retrospectively analyzed 362 parathyroid carcinoma patients diaagnosed in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Correlations between outcome events and variables were analyzed using univariate and multifactorial Cox regression, and variables screened by the multifactorial Cox risk proportional model were used to construct a survival prediction model. The model was evaluated using Receiver Operating Characteristic (ROC) curves, decision curve analysis (DCA), and C-index and calibration curves. Results: Univariate and multifactorial COX analyses revealed five independent prognostic factors for parathyroid carcinoma patients, which were subsequently used to develop the nomogram prediction model. In the training cohort, the C-index of the nomogram in predicting the overall survival (OS) was 0.747 (0.686–0.808), the area under the receiver operator characteristics curve(AUC)values of the nomogram in prediction of the 3, 5, and 10-year OS were 0.718 (0617-0.819), 0.711 (0.614–0.808) and 0.706 (0.610–0.803), respectively. In the validation cohort, the C-index was 0.740 (0.645–0.835), The AUC for 3, 5, and 10-years OS were 0.736 (0.584–0888), 0.698 (0.551–0.845) and 0.767 (0.647–0.887), respectively. The C-index, time-dependent ROC curve, calibration curve, and DCA showed that the Nomogram had a clear advantage. Conclusion: The developed nomogram can be applied in clinical practice to help clinicians to assess patient prognosis.

Abstract Background Lymph node metastasis (LNM) significantly impacts the prognosis of individuals diagnosed with cervical cancer, as it is closely linked to disease recurrence and mortality, thereby impacting therapeutic schedule choices for patients. However, accurately predicting LNM prior to treatment remains challenging. Consequently, this study seeks to utilize digital pathological features extracted from histopathological slides of primary cervical cancer patients to preoperatively predict the presence of LNM. Methods A deep learning (DL) model was trained using the Vision transformer (ViT) and recurrent neural network (RNN) frameworks to predict LNM. This prediction was based on the analysis of 554 histopathological whole‐slide images (WSIs) obtained from Qilu Hospital of Shandong University. To validate the model's performance, an external test was conducted using 336 WSIs from four other hospitals. Additionally, the efficiency of the DL model was evaluated using 190 cervical biopsies WSIs in a prospective set. Results In the internal test set, our DL model achieved an area under the curve (AUC) of 0.919, with sensitivity and specificity values of 0.923 and 0.905, respectively, and an accuracy (ACC) of 0.909. The performance of the DL model remained strong in the external test set. In the prospective cohort, the AUC was 0.91, and the ACC was 0.895. Additionally, the DL model exhibited higher accuracy compared to imaging examination in the evaluation of LNM. By utilizing the transformer visualization method, we generated a heatmap that illustrates the local pathological features in primary lesions relevant to LNM. Conclusion DL‐based image analysis has demonstrated efficiency in predicting LNM in early operable cervical cancer through the utilization of biopsies WSI. This approach has the potential to enhance therapeutic decision‐making for patients diagnosed with cervical cancer.

Abstract Background Biological research is generating high volumes of data distributed across various sources. The inconsistent naming of proteins and their encoding genes brings great challenges to protein data integration: proteins and their coding genes usually have multiple related names and notations, which are difficult to match absolutely; the nomenclature of genes and proteins is complex and varies from species to species; some less studied species have no nomenclature of genes and proteins; The annotation of the same protein/gene varies greatly in different databases. In summary, a comprehensive set of protein/gene synonyms is necessary for relevant studies. Results In this study, we propose an approach for protein and its encoding gene synonym integration based on protein ontology. The workflow of protein and gene synonym integration is composed of three modules: data acquisition, entity and attribute alignment, attribute integration and deduplication. Finally, the integrated synonym set of proteins and their coding genes contains over 128.59 million terminologies covering 560,275 proteins/genes and 13,781 species. As the semantic basis, the comprehensive synonym set was used to develop a data platform to provide one-stop data retrieval without considering the diversity of protein nomenclature and species. Conclusion The synonym set constructed here can serve as an important resource for biological named entity identification, text mining and information retrieval without name ambiguity, especially synonyms associated with well-defined species categories can help to study the evolutionary relationships between species at the molecular level. More importantly, the comprehensive synonyms set is the semantic basis for our subsequent studies on Protein–protein Interaction (PPI) knowledge graph.

This study aims to comprehensively determine the influence of high pressure on the microstructure and corrosion properties of a designed high-entropy alloy (Al3Cr2Mo2SiTi2). By characterizing the microstructure and morphology of the alloy, we have confirmed that the intermetallic compound volume fraction decreases and the peritectic reaction occurs during the solidification process of the alloy under 4 GPa. Moreover, the intermetallic compound phase A1 changes from (Ti, Mo)5Si3 (K1 phase) at ambient pressure to (Ti, Mo) Si2 at 4 GPa, and the volume fraction of the Cr-rich (C1 phase) phase increases from 20% to 64%. This special transformation, induced by high pressure, significantly optimizes the corrosion resistance of the alloy.

The incidence of liver diseases is high worldwide. Many factors can cause liver fibrosis, which in turn can lead to liver cirrhosis and even liver cancer. Due to the shortage of donor organs, immunosuppression, and other factors, only a few patients are able to undergo liver transplantation. Therefore, how to construct a bioartificial liver that can be transplanted has become a global research hotspot. With the rapid development of three-dimensional (3D) bioprinting in the field of tissue engineering and regenerative medicine, researchers have tried to use various 3D bioprinting technologies to construct bioartificial livers in vitro. In terms of the choice of bioinks, liver decellularized extracellular matrix (dECM) has many advantages over other materials for cell-laden hydrogel in 3D bioprinting. This review mainly summarizes the acquisition of liver dECM and its application in liver 3D bioprinting as a bioink with respect to availability, printability, and biocompatibility in many aspects and puts forward the current challenges and prospects.

To refine the grain size and improve the mechanical properties of ultrahigh-strength aluminum alloy (Al-10Zn-1.9Mg-1.6Cu-0.12Zr), the Al-Ti-B-Er grain refiner was prepared by the melt reaction method using the aluminum melt and Al + Ti + B precursor. The results exhibit that the Al-Ti-B-Er grain refiner is mainly composed of a block TiAl3 phase, and loose agglomerated nano-sized TiB2 and Al3Er phases. The microstructure of ultrahigh-strength aluminum is significantly affected by the Al-Ti-B-Er refiner, which changes from dendrite to equiaxial grain with increasing Al-Ti-B-Er content, and the size of the eutectic phase is significantly refined. The high-efficiency refinement of Al-Ti-B-Er is due to Er promoting the uniform distribution of TiAl3 particles and the formation of loose agglomerated nano-sized TiB2 particles. The optimal addition content of Al-Ti-B-Er into ultrahigh-strength aluminum alloys is 1 wt%, whose grain size is approximately 40 µm. Additionally, the strength and ductility of ultrahigh-strength aluminum alloys are simultaneously improved by adding 1wt% Al-Ti-B-Er after the T6 treatment, reaching 756 MPa and 20%, respectively. This enhancement in strength and ductility is mainly attributed to grain refinement and the eutectic phase refinement.