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Abstract Background In clinical practice, psoriasis is a prevalent chronic inflammatory cutaneous disease featured with the development of red plaque with silvery scales, which considerably affects cutaneous health and quality of life of those afflicted. Objective This research aimed to examine the association between the body roundness index (BRI) and psoriasis, using data sourced from the National Health and Nutrition Examination Survey (NHANES). Methods Our study used a cross-sectional design, including 8,479 adults, of whom 234 were diagnosed with psoriasis. Multivariable logistic regression was used to analyze the relationship between BRI and psoriasis, with stepwise adjustments for covariables. Results Results from multivariable logistic regression analyses indicated a significant positive relationship between BRI and the risk of developing psoriasis; specifically, after comprehensive adjustment for covariables, per 1 unit increase in BRI was linked to an 11% rise in psoriasis risk (OR = 1.11, 95% CI = 1.05–1.17). Furthermore, psoriasis patients exhibited higher average BRI compared to non-psoriasis patients and a greater prevalence of comorbidities such as hypertension and smoking. Conclusion These findings suggest that higher BRI is positively correlated with the risk of psoriasis in the adult population in the US. BRI could potentially act as a practical anthropometric index for more accurately predicting the risk of developing psoriasis.

Abstract Choroidal neovascularization (CNV) is a leading cause of visual impairment in wet age-related macular degeneration (wAMD). Recent investigations have validated the potential of reducing glutamine synthetase (GS) to inhibit neovascularization formation, offering prospects for treating various neovascularization-related diseases. In this study, we devised a CRISPR/Cas9 delivery system employing the nucleic acid aptamer AS1411 as a targeting moiety and exosome-liposome hybrid nanoparticles as carriers (CAELN). Exploiting the binding affinity between AS1411 and nucleolin on endothelial cell surfaces, the delivery system was engineered to specifically target the glutamine synthetase gene (GLUL), thereby attenuating GS levels and continuously suppressing CNV. CAELN exhibited spherical and uniform dispersion. In vitro cellular investigations demonstrated gene editing efficiencies of CAELN ranging from 42.05 to 55.02% and its capacity to inhibit neovascularization in HUVEC cells. Moreover, in vivo pharmacodynamic studies conducted in CNV rabbits revealed efficacy of CAELN in restoring the thickness of intra- and extranuclear tissues. The findings suggest that GS is a novel target for the inhibition of pathological CNV, while the development of AS1411-modified exosome-liposome hybrid nanoparticles represents a novel delivery method for the treatment of neovascular-related diseases.

Abstract Climate warming threatens global food security by exacerbating pressures on degraded soils under intensive crop production. Conservation agriculture is promoted as a sustainable solution that improves soil health and sustains crop yields in a changing climate, but these benefits may be affected by long-term warming. Here, we investigate the effects of conservation agriculture compared to conventional agriculture on 17 soil properties, microbial diversity and crop yields, during eight-years’ experimental warming. An overall positive effect of warming on soil health over time under conservation agriculture is characterized by linear increases in soil organic carbon and microbial biomass carbon. Warming-triggered shifts in microbial biomass carbon and fungal diversity (saprogen richness) are directly linked to a 9.3% increase in wheat yields over eight years, but only under conservation agriculture. Overall, conservation agriculture results in an average 21% increase in soil health and supports similar levels of crop production after long-term warming compared to conventional agriculture. Our work provides insights into the potential benefits of conservation agriculture for long-term sustainable food production because improved soil health improves resilience to the effects of climate warming.

ABSTRACT Importance Nutrition is associated with neurodevelopment. Infants at high risk of cerebral palsy (CP) usually suffer from undernutrition, yet the relationship between nutritional status and neurodevelopmental levels is unclear. Objective To describe the nutritional status characteristics of infants at high risk of CP, and to explore the relationship between neurodevelopmental levels and nutritional status. Methods This single‐center cross‐sectional study enrolled infants at high risk of CP, with corrected age from 0 days to 12 months. Weight and height were measured and calculated into z‐scores, which were used to classify the nutritional status based on the World Health Organization growth charts and American Society for Parenteral and Enteral Nutrition standards. The Bayley Scales of Infant and Toddler Development were used to evaluate the developmental levels of gross motor, fine motor, cognition, receptive communication, and expressive communication. Results A total of 479 infants at high risk of CP were recruited, with 43.4% classified as undernutrition. Compared to those with normal neurodevelopment, the odds of moderate and severe undernutrition were about 1.8 and 3.9 times higher in gross motor delay, 2.2 and 3.1 times higher in fine motor delay, 2.5 and 9.4 times higher in cognition delay, 2.2 and 3.9 times higher in receptive communication delay, and 3.0 and 5.6 times higher in expressive communication delay. There were significant positive correlations between nutritional status and neurodevelopmental levels (P < 0.001). Interpretation Undernutrition and neurodevelopmental delays are prevalent among infants at high risk of CP. Worse nutritional status was correlated with lower neurodevelopmental levels.

Titanium hydride (TiH2), a promising high-energy additive, is doped into PTFE/Al to optimize the energy output structure of the reactive jet and strive for better aftereffect damage ability to the target. Six types of PTFE/Al/TiH2 reactive liners with different TiH2 content are prepared by the molding and sintering method. The energy release characteristics of PTFE/Al/TiH2 reactive jet are tested by the transient explosion energy test, and are characterized from pressure and temperature. The reaction delay time, pressure history, and temperature history of the energy release process are obtained, then the actual value of released energy and reaction efficiency of the reactive jet are calculated. The results show that the peak pressure and temperature of the PTFE/Al/TiH2 jet initially increase and then decrease with increasing TiH2 content. When the TiH2 content is 10%, the actual value of released energy and reaction efficiency increased by 24% and 6.4%, respectively, compared to the PTFE/Al jet. The reaction duration of the reactive material is significantly prolonged as the TiH2 content increased from 0% to 30%. Finally, combined with the energy release behaviors of PAT material and the dynamic deformation process of liner, the enhancement mechanism of TiH2 on energy release of the reactive jet is expounded.

Social media offers extensive reach and inclusive engagement potential for projects and stakeholders. Current studies document its use for project information dissemination, building project awareness and project stakeholder assessment. However, studies into the use of social media in project stakeholder engagement remains scant. To date, there is lack of theoretically based guidance for project stakeholder engagement via social media in a pragmatic sense. In this paper, we advocate social media as a useful platform for online naturalistic inquiry of stakeholder engagement and propose a methodology for the analysis of stakeholder issues via social media to enhance engagement. We combine netnography, thematic, emotion work, and sentiment analyses to demonstrate operationalisation of the methodology for stakeholder issue analysis in the context of infrastructure projects. In doing so, we outline steps to identify, analyse and prioritise stakeholder issues for infrastructure projects via social media and discuss its implications for research and practice.

Flammulina velutipes (F. velutipes) residues polysaccharide (FVRP) is a high molecular weight polysaccharide with diverse bioactivities extracted from F. velutipes residues (FVR). However, high molecular weight polysaccharides have been shown to face significant challenges in crossing the cell membrane barrier, thereby limiting their absorption and application in the body. Therefore, an ultrasonic-assisted H2O2-Fe3+ method was employed for the first time to degrade FVRP, resulting in the production of a new polysaccharide, FVRPF. Compared with FVRP, there was no significant difference in the main chemical structure of FVRPF, but the monosaccharide composition ratio varied. and FVRPF had lower molecular weight and stronger antioxidant capacity. Moreover, FVRPF could be degraded by human microbiota, modulate gut microbiota composition, and increase the production of total short-chain fatty acids (SCFAs). These findings suggest that FVRPF holds potential as a promising prebiotic for applications in the food and pharmaceutical industries.

Objective We aim to investigate the joint effect of triglyceride-glucose (TyG) index and polygenic risk scores (PRS) of urate transporter genes ABCG2 and SLC2A9 on hyperuricemia.Methods Baseline data from two prospective population-based cohort studies, including 30,453 individuals aged 50 years or older, were used to analyze the association between TyG index and hyperuricemia. A case-control study was then designed from the cohorts to investigate the interaction between genetic predisposition and TyG index on hyperuricemia among 595 matched pairs. PRS was constructed using 14 single nucleotide polymorphisms located in the ABCG2 and SLCA29 genes.Results In both sexes, higher TyG index levels were correlated with elevated serum urate (SUA) levels (p values in both sexes < 0.001). In men, per unit increase of TyG was associated with a 1.44-fold (95% confidence interval [CI]: 1.35–1.55) higher risk of hyperuricemia after adjusted for covariates. In women, this estimate was 1.69 (1.51–1.89). Demonstrated by the restrict cubic spline model, TyG index was both linearly and non-linearly associated with elevated SUA (both p values < 0.001). Association between TyG index and hyperuricemia was stronger among people with higher genetic risk, and vice versa. Compared to people with TyG < 9 and PRS < 2, the odds ratios (ORs) (95% CIs) for hyperuricemia in the TyG

Adhere to the concept of low-carbon environmental protection and turning waste into treasure, polysaccharides from Flammulina velutipes residue polysaccharide (FVRP) has been developed and possesses diverse bioactivities, comprising antioxidant, hypoglycemic, and relieving heavy metal damage, which still has the disadvantages of high molecular weight and low bioavailability. The current work is the first to prepare a degraded polysaccharide (FVRPV) from FVRP by ultrasonic assisted H2O2-Vc technique in order to reduce its molecular weight, thereby improving its activity and bioavailability. Our results found that the molecular weight and average particle size were declined, but the monosaccharide composition and characteristic functional group types of FVRPV had no impact. The structural changes of polysaccharides analyzed by XRD, Congo Red test, I2-KI, SEM, and methylation analysis indicated that the surface morphology and glycosidic bond composition of FVRPV possessed longer side chains and a greater number of branches with an amorphous crystal structure devoid of a triple helix configuration, and had experienced notable alterations after ultrasonic assisted H2O2-Vc treatment. Meanwhile, the in vitro antioxidant capacity of FVRPV had significantly increased compared to FVRP, implying ultrasonic assisted H2O2-Vc technique maybe a effective method to enhance the bioactivity of polysaccharides. In addition, the content of polysaccharide, reducing sugar, and uronic acid in FVRPV was significantly decreased, but antioxidant capacity of fermentation broth was stronger by in vitro human fecal fermentation. The 16S rDNA sequencing data displayed that FVRPV can enrich probiotics and reduce the abundance of pathogenic bacteria through different metabolic pathways mediated by gut microbiota, thereby exerting its potential probiotic effects. The interesting work provides a novel degraded polysaccharide by ultrasonic assisted H2O2-Vc technique, laying a foundation for developing FVRPV as a new antioxidant and prebiotic.

Cinnamyl alcohol dehydrogenase (CAD) is a crucial enzyme in the final stage of lignin monomer biosynthesis. This study focuses on the CAD gene family within Gossypium hirsutum. Through comprehensive genomic analysis, we identified 29 GhiCAD genes within the Gossypium hirsutum genome using a bioinformatics approach. Phylogenetic analysis revealed that the GhiCAD family can be categorized into four subgroups, which are closest to the evolutionary relationship with Arabidopsis thaliana. There are multiple cis-acting elements on the promoters of GhiCAD genes associated with abiotic stress responses. Some GhiCAD genes demonstrated high expression in various tissues like root, leaf, and sepal, as well as in fiber and ovule at different developmental stages (10 days post anthesis (DPA), 15 DPA, 20 DPA, 25 DPA). The transcript levels of GhiCAD23 were notably elevated when exposed to PEG treatment and drought stress (DS). GhiCAD23 is also co-expressed with many known drought response genes, suggesting its involvement in the plant’s reaction to DS. Employing virus-induced gene silencing (VIGS) technology to silence the GhiCAD23 gene, it was found that silencing GhiCAD23 reduced the tolerance of cotton to DS. Under DS, the relative leaf water content, superoxide dismutase (SOD), and catalase (CAT) enzyme activities of the GhiCAD23-silenced cotton plants were decreased by 31.84%, 30.22% and 14.19%, respectively, while malondialdehyde (MDA) was increased by 72.16% compared with the control cohort. Drought promotes the accumulation of lignin, and it was found that silencing the GhiCAD23 reduces lignin accumulation in cotton under DS. The analysis of phenotypic and physiological indicators indicates that GhiCAD23 is vital in cotton’s resistance to DS. This investigation provides an important reference for future comprehensive exploration of the GhiCAD23 gene’s function in cotton’s DS response mechanism.

Exosomes, key components of the tumour microenvironment, can mediate intercellular communication through the delivery of various signalling molecules, including microribonucleic acids (miRNAs), and ultimately participate in regulating the process of tumour development. In this study, we aimed to investigate the reason and mechanism by which exosomal miRNAs derived from gastric cancer cells affect carcinogenesis and metastasis. Among these miRNAs, microRNA-128-3p (miR-128-3p) was highly expressed in serum exosomes isolated from gastric cancer patients, as confirmed by high-throughput sequencing and subsequent experiments. Coculture of gastric cancer-derived exosomes overexpressing miR-128-3p with human umbilical vein endothelial cells (HUVECs) significantly enhanced HUVEC proliferation, migratio n and angiogenesis. Bioinformatics analysis suggested SASH1 as the target gene of miR-128-3p. The dual luciferase assay and Western blot analysis results confirmed that miR-128-3p directly targeted SASH1 to inhibit its expression in HUVECs. Therefore, this study provides preliminary evidence that gastric cancer-derived exosomal miR-128-3p promotes tumour angiogenesis by targeting SASH1, reveals the potential diagnostic and therapeutic value of cancer-derived exosomal miR-128-3p, and provides new insights into the novel molecular mechanisms regulating metastasis. This study provides further information for understanding the role of gastric cancer-derived exosomal miR-128-3p in cancer progression and to discover new therapeutic targets.

ABSTRACT Background The increasing incidence of endometrial cancer (EC) has highlighted the need for improved early detection methods. This study aimed to develop and validate a novel DNA methylation classifier, EMPap, for EC detection using cervical scrapings. Methods EMPap incorporated the methylation status of BHLHE22 and CDO1, along with age and body mass index (BMI), into a logistic regression model to calculate the endometrial cancer methylation (EM) score for identifying EC in cervical scrapings. We enrolled 1297 patients with highly suspected EC, including 196 confirmed EC cases, and assessed the EMPap performance in detecting EC. Results EMPap demonstrated robust diagnostic accuracy, with an area under the curve of 0.93, sensitivity of 90.3%, and specificity of 89.3%. It effectively detected EC across various disease stages, grades, and histological subtypes, and consistently performed well across patient demographics and symptoms. EMPap correctly identified 87.5% of the type II ECs and 53.8% of premalignant lesions. Notably, compared with transvaginal ultrasonography (TVS) in patients with postmenopausal bleeding, EMPap exhibited superior sensitivity (100% vs. 82.0%) and specificity (85.2% vs. 38.5%). In asymptomatic postmenopausal women, EMPap maintained high sensitivity (89.5%) and negative predictive value (NPV) (98.3%). Conclusions This study demonstrated the potential of EMPap as an effective tool for EC detection. Despite the limited sample size, EMPap showed promise for identifying type II EC and detecting over 50% of premalignant lesions. As a DNA methylation classifier, EMPap can reduce unnecessary uterine interventions and improve diagnosis and outcomes.

Abstract Invasion and migration are the key hallmarks of cancer, and aggressive growth is a major factor contributing to treatment failure and poor prognosis in glioblastoma. Protein arginine methyltransferase 6 (PRMT6), as an epigenetic regulator, has been confirmed to promote the malignant proliferation of glioblastoma cells in previous studies. However, the effects of PRMT6 on glioblastoma cell invasion and migration and its underlying mechanisms remain elusive. Here, we report that PRMT6 functions as a driver element for tumor cell invasion and migration in glioblastoma. Bioinformatics analysis and glioma sample detection results demonstrated that PRMT6 is highly expressed in mesenchymal subtype or invasive gliomas, and is significantly negatively correlated with their prognosis. Inhibition of PRMT6 (using PRMT6 shRNA or inhibitor EPZ020411) reduces glioblastoma cell invasion and migration in vitro, whereas overexpression of PRMT6 produces opposite effects. Then, we identified that PRMT6 maintains the protein stability of EZH2 by inhibiting the degradation of EZH2 protein, thereby mediating the invasion and migration of glioblastoma cells. Further mechanistic investigations found that PRMT6 inhibits the transcription of TRAF6 by activating the histone methylation mark (H3R2me2a), and reducing the interaction between TRAF6 and EZH2 to enhance the protein stability of EZH2 in glioblastoma cells. Xenograft tumor assay and HE staining results showed that the expression of PRMT6 could promote the invasion of glioblastoma cells in vivo, the immunohistochemical staining results of mouse brain tissue tumor sections also confirmed the regulatory relationship between PRMT6, TRAF6, and EZH2. Our findings illustrate that PRMT6 suppresses TRAF6 transcription via H3R2me2a to enhance the protein stability of EZH2 to facilitate glioblastoma cell invasion and migration. Blocking the PRMT6-TRAF6-EZH2 axis is a promising strategy for inhibiting glioblastoma cell invasion and migration.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used in therapy of ischemic heart disease. However, there are still remaining issues that limit the therapeutic efficacy, such as immune rejection and low retention of hiPSC-CMs. Human adipose mesenchymal stromal cells (hADSCs) have been reported to be able to regulate the immune response, promote angiogenesis and promote the maturation of hiPSC-CMs. In this study, we co-cultured these two types of cells on fiber scaffold made of biodegradable poly (D,L-lactic-co-glycolic acid) (PLGA) polymer for several days to develop a composited 3D cardiac tissue sheet. As expected, the cells formed 231.00 ± 15.14 μm thickness tissue, with improved organization, alignment, ECM condition, contractile ability, and paracrine function compared to culture hiPSC-CMs only on PLGA fiber. Furthermore, the composited 3D cardiac tissue sheet significantly promoted the engraftment and survival after transplantation. The composited 3D cardiac tissue sheet also increased cardiac function, attenuated ventricular remodeling, decreased fibrosis, and enhanced angiogenesis in rat myocardial infarction model, indicating that this strategy wound be a promising therapeutic option in the clinical scenario.

A ternary system of PTFE/Al/Bi2O3 is constructed by incorporating PTFE-based reactive material and thermite for enhancing the energy release of the PTFE-based reactive material. The effects of Bi2O3 in the PTFE/Al/Bi2O3 on both mechanical properties and the energy release were investigated through various tests such as thermogravimetry-differential scanning calorimetry, adiabatic oxygen bomb test and split Hopkinson pressure bar test. The microstructure observed through scanning electron microscope and X-ray diffraction results are used to analyze the ignition and reaction mechanism of PTFE/Al/Bi2O3. The results indicate that the PTFE/Al/Bi2O3 are capable of triggering the exothermic reaction of molten PTFE/Bi2O3 and Al/Bi2O3 over the PTFE/Al reactive materials, thereby promoting reactions. The excessive aluminum in the ternary system is beneficial for increasing energy release. The ignition of shock-induced chemical reactions in PTFE/Al/Bi2O3 is closely related to the material fracture. The dominant mechanism for hot-spot generation under Split Hopkinson Pressure Bar test is the frictional temperature rise at the microcrack after failure.

Alkaline metal oxides have received significant attention recently due to their abundance, inherent conductivity, optical absorption, and thermal stability. Here, a straightforward co-precipitation method was employed to obtain both undoped BaO and Mo-doped BaO nanoparticles. Various techniques were used to characterize the synthesized nanoparticles’ structural, Raman spectral, optical, thermal, and electrical properties. X-ray diffraction (XRD) results revealed that Mo was successfully doped into tetragonal nanocrystalline BaO. The W-H plot showed that as Mo doping increases from 2 % to 6 %, the crystallite size grows while the lattice structure remains well-ordered with even strain distribution. Scanning electron microscopy (SEM) was used to examine its surface features. The purity and crystalline character of the samples were further confirmed via Raman spectroscopy, which shows that the peak intensity of the spectra increases with the increase of particle size owing to the rise in the force constant. UV spectroscopy was used to observe the energy band gap, which is found to decrease from 4.2 eV to 3.8 eV, and then it drops to 3.4 eV as the Mo content increases. This is reasonable because of the size-dependent attraction between metallic ions and conduction electrons. PL spectra concluded that Mo doping leads to the enhancement of the optical characteristics of BaO. Adding Mo to BaO also modifies the material’s thermal properties, potentially affecting its suitability for applications that require thermal durability. This finding exhibits that even slight doping of Mo4+ into BaO can significantly impact their structural, thermal, optical, and electrical characteristics. It enriches the existing body of knowledge of BaO nanoparticles and lays the foundation for its future research.

To explore whether the intestinal damage of yak colibacillosis resulted from the regulation of Zonulin expression by its pathogenic bacteria, the overexpression and interference plasmids of Zonulin were designed and cultured in Tranwell after cell transfection. Then qRT-PCR and Western blot were used to detect the results of cell transfection, 200 mL 1×105 CFU/mL E.coli O78 was added for 4 hours, transmembrane resistance was measured by transmembrane resistance meter, FD4 fluorescence concentration in the lower chamber was detected by enzyme labeling instrument, bacterial translocation was measured by CFU counting method, and epithelial mucin (MUC1, MUC2) and tight junction protein (FABP2, Occludin, ZO-1) were detected by qRT-PCR.ResultsThe Zonulin gene overexpression and knockout cell lines were successfully constructed, the TEER value of the barrier of Zonulin overexpression cell lines began to decrease at 1 h after the addition of E.coli O78 and reached the lowest value at 4 h, and the TEER value of Zonulin interference cell lines decreased within 1-4 h after the addition of E.coli O78. At 4 h, the FD4 passing capacity of Zonulin overexpression cell lines was significantly higher than that of interfering cell lines, reaching twice as much as siRNA-1. The amount of bacterial translocation in overexpressed cell lines increased rapidly within 1-4 h, and the concentration of E.coli in the lower chamber was significantly higher than that in the siRNA-1 group at 4 h, but there was no significant change in the siRNA-1 group in the 1-4 h. There was no significant change in the mRNA level of MUC1 in Zonulin overexpression and interference cell lines after the addition of E.coli O78. In the overexpression group, the mRNA levels of MUC2, Occludin, and ZO-1 were significantly decreased, and the mRNA level of FABP2 was increased considerably. These results suggest stimulate epithelial cells to secrete Zonulin protein. Many Zonulin proteins regulate the opening of tight junction structures, reduce the transmembrane resistance of the cell barrier, and improve the permeability of the cell barrier and the amount of bacterial translocation.

Abstract The utilization of diverse energy storage devices is imperative in the contemporary society. Taking advantage of solar power, a significant environmentally friendly and sustainable energy resource, holds great appeal for future storage of energy because it can solve the dilemma of fossil energy depletion and the resulting environmental problems once and for all. Recently, photo‐assisted energy storage devices, especially photo‐assisted rechargeable metal batteries, are rapidly developed owing to the ability to efficiently convert and store solar energy and the simple configuration, as well as the fact that conventional Li/Zn‐ion batteries are widely commercialized. Considering many puzzles arising from the rapid development of photo‐assisted rechargeable metal batteries, this review commences by introducing the fundamental concepts of batteries and photo‐electrochemistry, followed by an exploration of the current advancements in photo‐assisted rechargeable metal batteries. Specifically, it delves into the elucidation of device components, operating principles, types, and practical applications. Furthermore, this paper categorizes, specifies, and summarizes several detailed examples of photo‐assisted energy storage devices. Lastly, it addresses the challenges and bottlenecks faced by these energy storage systems while providing future perspectives to facilitate their transition from laboratory research to industrial implementation.

Abstract Background Aberrant DNA methylation is a vital molecular alteration commonly detected in type I endometrial cancers (EC), and tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine (5hmC) play significant roles in DNA demethylation. However, little is known about the function and correlation of TET2 and 5hmC co-expressed in EC. This study intended to investigate the clinical significance of TET2 and 5hmC in EC. Methods The levels of TET2 and 5hmC were detected in 326 endometrial tissues by immumohistochemistry, and the correlation of their level was detected by Pearson analysis. The association between the levels of TET2 and 5hmC and clinicopathologic characteristics was analyzed. Prognostic value of TET2 and 5hmC was explored by Kaplan–Meier analysis. The Cox proportional hazard regression model was used for univariate and multivariate analyses. Results Based on the analysis results, TET2 protein level was positively correlated with 5hmC level in EC tissues (r = 0.801, P

Membrane proteins are crucial for various cellular processes and are key targets in pharmacological research. Their interactions with ligands are essential for elucidating cellular mechanisms and advancing drug development. To study these interactions without altering their functional properties in native environments, several advanced optical imaging methods have been developed for in situ and label-free quantification. This review focuses on recent optical imaging techniques such as surface plasmon resonance imaging (SPRi), surface plasmon resonance microscopy (SPRM), edge tracking approaches, and surface light scattering microscopy (SLSM). We explore the operational principles, recent advancements, and the scope of application of these methods. Additionally, we address the current challenges and explore the future potential of these innovative optical imaging strategies in deepening our understanding of biomolecular interactions and facilitating the discovery of new therapeutic agents.

PurposeDifficulties remain in dose optimization and evaluation of cervical cancer radiotherapy that combines external beam radiotherapy (EBRT) and brachytherapy (BT). This study estimates and improves the accumulated dose distribution of EBRT and BT with deep learning–based dose prediction.Materials and methodsA total of 30 patients treated with combined cervical cancer radiotherapy were enrolled in this study. The dose distributions of EBRT and BT plans were accumulated using commercial deformable image registration. A ResNet-101–based deep learning model was trained to predict pixel-wise dose distributions. To test the role of the predicted accumulated dose in clinic, each EBRT plan was designed using conventional method and then redesigned referencing the predicted accumulated dose distribution. Bladder and rectum dosimetric parameters and normal tissue complication probability (NTCP) values were calculated and compared between the conventional and redesigned accumulated doses.ResultsThe redesigned accumulated doses showed a decrease in mean values of V50, V60, and D2cc for the bladder (−3.02%, −1.71%, and −1.19 Gy, respectively) and rectum (−4.82%, −1.97%, and −4.13 Gy, respectively). The mean NTCP values for the bladder and rectum were also decreased by 0.02‰ and 0.98%, respectively. All values had statistically significant differences (p < 0.01), except for the bladder D2cc (p = 0.112).ConclusionThis study realized accumulated dose prediction for combined cervical cancer radiotherapy without knowing the BT dose. The predicted dose served as a reference for EBRT treatment planning, leading to a superior accumulated dose distribution and lower NTCP values.

Abstract Retinoid-related orphan receptor gamma t (RORγt) is the lineage-specific transcription factor for T helper 17 (Th17) cells. Our previous study demonstrated that STAT3 likely participates in the activation of RORCE2 (a novel enhancer of the RORγt gene) in Th17 cells. However, the detailed mechanism is still unclear. Here, we demonstrate that both STAT3 and SOX-5 mediate the enhancer activity of RORCE2 in vitro. Deletion of the STAT3 binding site (STAT3-BS) in RORCE2 impaired RORγt expression and Th17 differentiation, resulting in reduced severity of experimental autoimmune encephalomyelitis (EAE). Mechanistically, STAT3 and SOX-5 bind the RORCE2 region and recruit the chromatin remodeling factor BRG1 to remodel the nucleosomes positioned at this region. Collectively, our data suggest that STAT3 and SOX-5 mediate the differentiation of Th17 cells through the induction of BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells.

Abstract Background Heart failure (HF) is a major cause of death worldwide. The most effective treatment for HF is heart transplantation, but its use is limited by the scarcity of donor hearts. Recently, stem cell-based therapy has emerged as a promising approach for treating myocardial infarction. Our research group has been investigating the use of human induced pluripotent stem cell-derived cardiomyocyte patches as a potential therapeutic candidate. We have successfully conducted eight cases of clinical trials and demonstrated the safety and effectiveness of this approach. However, further advancements are necessary to overcome immune rejection and enhance therapeutic efficacy. In this study, we propose a novel and efficient technique for constructing mesenchymal stem cell (MSC) tissue sheets, which can be transplanted effectively for treating myocardial infarction repair. Methods We applied a one-step method to construct the human adipose-derived mesenchymal stem cell (hADSC) tissue sheet on a poly(lactic-co-glycolic acid) fiber scaffold. Histology, immunofluorescence, and paracrine profile assessment were used to determine the organization and function of the hADSC tissue sheet. Echocardiography and pathological analyses of heart sections were performed to evaluate cardiac function, fibrosis area, angiogenesis, and left ventricular remodeling. Results In vitro, the hADSC tissue sheet showed great organization, abundant ECM expression, and increased paracrine secretion than single cells. In vivo, the hADSC tissue sheet group demonstrated improved cardiac functional recovery, less ventricular remodeling, decreased fibrosis, and enhanced angiogenesis than the MI group. Conclusions We developed thick and functional hADSC tissue sheets via the one-step strategy. The hADSC tissue sheet showed excellent performance in treating myocardial infarction in the rat model. Graphical Abstract

The shrub/dwarf tree Haloxylon ammodendron is a prevalent woody plant used to combat desertification in the arid and semi-arid regions of northwestern China. Despite its drought resistance, artificial stands of this species experience significant degradation approximately ten years post-afforestation. Stumping, which involves cutting a portion of the above-ground part of shrubs/trees, is a common practice aimed at reducing water consumption and enhancing the growth of these stands. However, the impact of stumping on the sap flow of H. ammodendron remain inadequately understood, posing challenges to the sustainable management of these artificial stands. In this study, we monitored the sap flow of H. ammodendron subjected to various stumping treatments in the Ulan Buh Desert using the PS-TDP8 tree sap flow monitoring system. Concurrently, we measured several meteorological factors with an automatic weather station. We examined the changes in sap flow velocity following stumping and its response to meteorological factors to elucidate water use during growth. Our findings indicate that both the change in sap flow velocity and characteristics were closely associated with the degree of stumping. The initiation time of sap flow for H. ammodendron under different stumping treatments was earlier than that of the control group. The daily mean value and daily accumulation of sap flow followed the order: 50% stumping > control (no stumping) > 75% stumping > 100% stumping. Sap flow velocity and daily sap flow accumulation increased at 50% stumping but decreased at 75% and 100% stumping. Stumping altered the relationships between sap flow velocity and meteorological factors, with the correlation coefficient between these variables decreasing as the degree of stumping increased. The sap flow following stumping was primarily influenced by both the degree of stumping and meteorological factors. These results may contribute to a better understanding of water transport during the growth of H. ammodendron following stumping.

Surface plasmon resonance (SPR) biosensors are extensively utilized for analyzing molecular interactions due to their high sensitivity and label-free detection capabilities. Recent innovations in surface-sensitive biosensors with dielectric surfaces address the inherent limitations associated with traditional gold surfaces, such as thermal effects and biocompatibility issues, which can impede broader applications. This review examines state-of-the-art biosensor configurations, including total internal reflection, optical waveguide, photonic crystal resonators, Bloch surface wave biosensors, and surface electrochemical biosensors, which can enhance analyte signals and augment the molecular detection efficiency at the sensor interface. These technological advancements not only improve the resolution of binding kinetics analysis and single-molecule detection but also extend the analytical capabilities of these systems. Additionally, this review explores prospective advancements in augmenting field enhancement and incorporating multimodal sensing functionalities, emphasizing the significant potential of these sophisticated biosensing technologies to profoundly enhance our understanding of molecular interactions.

Abstract Background There is limited longitudinal evidence on the hypertensive effects of long-term exposure to ambient O3. We investigated the association between long-term O3 exposure at workplace and incident hypertension, diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), and mean arterial pressure (MAP) in general working adults. Methods We conducted a cohort study by recruiting over 30,000 medical examination attendees through multistage stratified cluster sampling. Participants completed a standard questionnaire and comprehensive medical examination. Three-year ambient O3 concentrations at each employed participant’s workplace were estimated using a two-stage machine learning model. Mixed-effects Cox proportional hazards models and linear mixed-effects models were used to examine the effect of O3 concentrations on incident hypertension and blood pressure parameters, respectively. Generalized additive mixed models were used to explore non-linear concentration-response relationships. Results A total of 16,630 hypertension-free working participants at baseline finished the follow-up. The mean (SD) O3 exposure was 45.26 (2.70) ppb. The cumulative incidence of hypertension was 7.11 (95% CI: 6.76, 7.47) per 100 person-years. Long-term O3 exposure was independently, positively and non-linearly associated with incident hypertension (Hazard ratios (95% CI) for Q2, Q3, and Q4 were 1.77 (1.34, 2.36), 2.06 (1.42, 3.00) and 3.43 (2.46, 4.79), respectively, as compared with the first quartile (Q1)), DBP (β (95% CI) was 0.65 (0.01, 1.30) for Q2, as compared to Q1), SBP (β (95% CI) was 2.88 (2.00, 3.77), 2.49 (1.36, 3.61) and 2.61 (1.64, 3.58) for Q2, Q3, and Q4, respectively), PP (β (95% CI) was 2.12 (1.36, 2.87), 2.03 (1.18, 2.87) and 2.14 (1.38, 2.90) for Q2, Q3, and Q4, respectively), and MAP (β (95% CI) was 1.39 (0.76, 2.02), 1.04 (0.24, 1.84) and 1.12 (0.43, 1.82) for Q2, Q3, and Q4, respectively). The associations were robust across sex, age, BMI, and when considering PM2.5 and NO2. Conclusions To our knowledge, this is the first cohort study in the general population that demonstrates the non-linear hypertensive effects of long-term O3 exposure. The findings are particularly relevant for policymakers and researchers involved in ambient pollution and public health, supporting the integration of reduction of ambient O3 into public health interventions.

Abstract Background The aim of study was to observe the effect of increased lactate levels during high-intensity interval training (HIIT) on protein lactylation, identify the target protein, and investigate the regulatory effect of lactylation on the function of the protein. Methods C57B/L6 mice were divided into 3 groups: the control group, HIIT group, and dichloroacetate injection + HIIT group (DCA + HIIT). The HIIT and DCA + HIIT groups underwent 8 weeks of HIIT treatment, and the DCA + HIIT group was injected DCA before HIIT treatment. The expression of lipid metabolism-related genes was determined. Protein lactylation in subcutaneous adipose tissue was identified and analyzed using 4D label-free lactylation quantitative proteomics and bioinformatics analyses. The fatty acid synthase (FASN) lactylation and activity was determined. Results HIIT had a significant effect on fat loss; this effect was weakened when lactate production was inhibited. HIIT significantly upregulated the protein lactylation while lactate inhibition downregulated in iWAT. FASN had the most modification sites. Lactate treatment increased FASN lactylation levels, inhibited FASN activity, and reduced palmitate and triglyceride synthesis in 3T3-L1 cells. Conclusions This investigation revealed that lactate produced by HIIT increased protein pan-lactylation levels in iWAT. FASN lactylation inhibited de novo lipogenesis, which may be an important mechanism in HIIT-induced fat loss.

With the increasing need for public health and drug development, combination therapy has become widely used in clinical settings. However, the risk of unanticipated adverse effects and unknown toxicity caused by drug-drug interactions (DDIs) is a serious public health issue for polypharmacy safety. Traditional experimental methods for detecting DDIs are expensive and time-consuming. Therefore, many computational methods have been developed in recent years to predict DDIs with the growing availability of data and advancements in artificial intelligence. In silico methods have proven to be effective in predicting DDIs, but detecting potential interactions, especially for newly discovered drugs without an existing DDI network, remains a challenge. In this study, we propose a predicting method of DDIs named HAG-DDI based on graph attention networks. We consider the differences in mechanisms between DDIs and add learning of semantic-level attention, which can focus on advanced representations of DDIs. By treating interactions as nodes and the presence of the same drug as edges, and constructing small subnetworks during training, we effectively mitigate potential bias issues arising from limited data availability. Our experimental results show that our method achieves an F1-score of 0.952, proving that our model is a viable alternative for DDIs prediction. The codes are available at: https://github.com/xtnenu/DDIFramework.

IntroductionThe etiology of Escherichia coli in yaks, along with its drug resistance, results in economic losses within the yak breeding industry. The utilization of lactic acid bacteria treatment has emerged as a viable alternative to antibiotics in managing colibacillosis.MethodsTo elucidate the therapeutic mechanisms of Lactobacillus against Escherichia coli-induced intestinal barrier damage in yaks, we employed yak epithelial cells as the experimental model and established a monolayer epithelial barrier using Transwell. The study encompassed four groups: a control group, a model group (exposed to E. coli O78), a low-dose Lactobacillus group (E. coli O78 + 1 × 105CFU LAB), and a high-dose Lactobacillus group (E. coli O78 + 1 × 107CFU LAB). Various techniques, including transmembrane resistance measurement, CFU counting, RT-qPCR, and Western Blot, were employed to assess indicators related to cell barrier permeability and tight junction integrity.ResultsIn the Model group, Escherichia coli O78 significantly compromised the permeability and tight junction integrity of the yak epithelial barrier. It resulted in decreased transmembrane resistance, elevated FD4 flux, and bacterial translocation. Furthermore, it downregulated the mRNA and protein expression of MUC2, Occludin, and ZO-1, while upregulating the mRNA expression and protein expression of FABP2 and Zonulin, thereby impairing intestinal barrier function. Contrastingly, Lactobacillus exhibited a remarkable protective effect. It substantially increased transmembrane resistance, mitigated FD4 flux, and reduced bacterial translocation. Moreover, it significantly upregulated the mRNA and protein expression of MUC2, Occludin, and ZO-1, while downregulating the mRNA and protein expression of FABP2 and Zonulin. Notably, high-dose LAB demonstrated superior regulatory effects compared to the low-dose LAB group.DiscussionIn conclusion, our findings suggest that Lactobacillus holds promise in treating yak colibacillosis by enhancing mucin and tight junction protein expression. Furthermore, we propose that Lactobacillus achieves these effects through the regulation of Zonulin.

Summary: Human iPSC-derived cardiomyocytes (hiPSC-CMs) exhibit functional immaturity, potentially impacting their suitability for assessing drug proarrhythmic potential. We previously devised a traveling wave (TW) system to promote maturation in 3D cardiac tissue. To align with current drug assessment paradigms (CiPA and JiCSA), necessitating a 2D monolayer cardiac tissue, we integrated the TW system with a multi-electrode array. This gave rise to a hiPSC-derived closed-loop cardiac tissue (iCT), enabling spontaneous TW initiation and swift pacing of cardiomyocytes from various cell lines. The TW-paced cardiomyocytes demonstrated heightened sarcomeric and functional maturation, exhibiting enhanced response to isoproterenol. Moreover, these cells showcased diminished sensitivity to verapamil and maintained low arrhythmia rates with ranolazine—two drugs associated with a low risk of torsades de pointes (TdP). Notably, the TW group displayed increased arrhythmia rates with high and intermediate risk TdP drugs (quinidine and pimozide), underscoring the potential utility of this system in drug assessment applications.

Abstract This paper presents a comprehensive study on the numerical and parametric study of geocell-reinforced cohesive soil beds, focusing on different infill materials. The numerical calculations were validated against model test results using FLAC3D software. Subsequently, the verified model was expanded to the geocell-reinforced cohesive soil beds. Six cases were simulated to investigate the reinforced performance, including pressure-settlement responses, bearing capacity improvement factor, settlement reduction percentage, and surface deformation. The numerical findings emphasize that the significance of superior geocell reinforcement should not overshadow the consideration of soil infill’s mechanical properties. In the case of cohesive soil as the infill material, the poor improvement in geocell-reinforced performance may be attributed to its low modulus and cohesion. Parametric studies suggest that geocells significantly impact reinforced performance when the infill material consists of foundation soil with a higher modulus and lower cohesion. Further, according to this numerical study, cohesionless soil with a modulus of 20 MPa and friction of 40° is the optimum infill soil in pockets to reinforce cohesive soil beds.

Abstract. Background:. Microsatellite instability (MSI) is a key biomarker for cancer immunotherapy and prognosis. Integration of MSI testing into a next-generation-sequencing (NGS) panel could save tissue sample, reduce turn-around time and cost, and provide MSI status and comprehensive genomic profiling in single test. We aimed to develop an MSI calling model to detect MSI status along with the NGS panel-based profiling test using tumor-only samples. Methods:. From January 2019 to December 2020, a total of 174 colorectal cancer (CRC) patients were enrolled, including 31 MSI-high (MSI-H) and 143 microsatellite stability (MSS) cases. Among them, 56 paired tumor and normal samples (10 MSI-H and 46 MSS) were used for modeling, and another 118 tumor-only samples were used for validation. MSI polymerase chain reaction (MSI-PCR) was performed as the gold standard. A baseline was built for the selected microsatellite loci using the NGS data of 56 normal blood samples. An MSI detection model was constructed by analyzing the NGS data of tissue samples. The performance of the model was compared with the results of MSI-PCR. Results:. We first intersected the target genomic regions of the NGS panels used in this study to select common microsatellite loci. A total of 42 loci including 23 mononucleotide repeat sites and 19 longer repeat sites were candidates for modeling. As mononucleotide repeat sites are more sensitive and specific for detecting MSI status than sites with longer length motif and the mononucleotide repeat sites performed even better than the total sites, a model containing 23 mononucleotide repeat sites was constructed and named Colorectal Cancer Microsatellite Instability test (CRC-MSI). The model achieved 100% sensitivity and 100% specificity when compared with MSI-PCR in both training and validation sets. Furthermore, the CRC-MSI model was robust with the tumor content as low as 6%. In addition, 8 out of 10 MSI-H samples showed alternations in the four mismatch repair genes (MLH1, MSH2, MSH6, and PMS2). Conclusion:. MSI status can be accurately determined along the targeted NGS panels using only tumor samples. The performance of mononucleotide repeat sites surpasses loci with longer repeat motif in MSI calling.

PurposeThe objective of this study was to investigate the risk of cardiovascular toxicities related to PD-1/PD-L1 inhibitors in solid tumors.MethodsA literature search was performed following the participants, interventions, comparisons, outcomes, and study design (PICOS) principles, and the study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data analysis was conducted using Review Manager version 5.4.ResultsThis meta-analysis included 69 randomized controlled trials (RCTs) divided into five groups based on the treatment regimens: PD-1/PD-L1 + chemotherapy versus chemotherapy, PD-1/PD-L1 versus chemotherapy, PD-1/PD-L1 versus placebo, PD-1/PD-L1 + CTLA-4 versus PD-1/PD-L1 and PD-1/PD-L1 + CTLA-4 versus chemotherapy. Compared to chemotherapy treatment alone, PD-1/PD-L1 +chemotherapy significantly increased the risk of hypertension [all-grade (OR = 1.27, 95% CI [1.05, 1.53], p = 0.01); grade 3–5 (OR = 1.36, 95% CI [1.04, 1.79], p = 0.03)], hypotension [all-grade (OR = 2.03, 95% CI [1.19, 3.45], p = 0.009); grade 3–5 (OR = 3.60, 95% CI [1.22, 10.60], p = 0.02)], arrhythmia [all-grade (OR = 1.53, 95% CI [1.02, 2.30], p = 0.04); grade 3–5 (OR = 2.91, 95% CI [1.33, 6.39], p = 0.008)] and myocarditis [all-grade (OR = 2.42, 95% CI [1.06, 5.54], p = 0.04)]. The risk of all-grade hypotension (OR = 2.87, 95% CI [1.26, 6.55], p = 0.01) and all-grade arrhythmia (OR = 2.03, 95% CI [1.13, 3.64], p = 0.02) significantly increased when treated with PD-1/PD-L1 inhibitors compared to the placebo. The risks of cardiovascular toxicities are significantly higher with PD-1+CTLA-4 compared to PD-1 alone (OR = 2.02, 95% CI [1.12, 3.66], p = 0.02).ConclusionPD-1/PD-L1 inhibitor leads to an increased risk of cardiovascular toxicities, especially hypertension, hypotension, arrhythmia, and myocarditis.

Background: The association of specific PM2.5 chemical constituents with childhood overweight or obesity (OWOB) remain unclear. Furthermore, the long-term impacts of PM2.5 exposure on the trajectory of children's body mass index (BMI) have not been explored. Methods: We conducted a longitudinal study among 1,450,830 Chinese children aged 6–19 years from Beijing and Zhongshan in China during 2005–2018 to examine the associations of PM2.5 and its chemical constituents with incident OWOB risk. We extracted PM2.5 mass and five main component exposure from Tracking Air Pollution in China (TAP) dataset. Cox proportional hazards models were applied to quantify exposure–response associations. We further performed principal component analysis (PCA) to handle the multi-collinearity and used quantile g-computation (QGC) approach to analyze the impacts of exposure mixtures. Additionally, we selected 125,863 children with at least 8 physical examination measurements and combined group-based trajectory models (GBTM) with multinomial logistic regression models to explore the impacts of exposure to PM2.5 mass and five constituents on BMI and BMI Z-score trajectories during 6–19 years. Results: We observed each interquartile range increment in PM2.5 exposure was significantly associated with a 5.1 % increase in the risk of incident OWOB (95 % confidence Interval [CI]: 1.036–1.066). We also found black carbon, sulfate, organic matter, often linked to fossil combustion, had comparable or larger estimates of the effect (HR = 1.139–1.153) than PM2.5. Furthermore, Exposure to PM2.5 mass, sulfate, nitrate, ammonium, organic matter and black carbon was significantly associated with an increased odds of being in a larger BMI trajectory and being assigned to persistent OWOB trajectory. Conclusions: Our findings provide evidence that the constituents mainly from fossil fuel combustion may have a perceptible influence on increased OWOB risk associated with PM2.5 exposure in China. Moreover, long-term exposure to PM2.5 contributes to an increased odds of being in a lager BMI and a persistent OWOB trajectories.

A novel therapeutic regimen showed that the oncolytic type II herpes simplex virus (oHSV2) was able to prevent colorectal cancer growth, recurrence, and metastasis. However, no study has yet explored whether oHSV2 has an impact on the development of diffuse large B-cell lymphoma (DLBCL). We chose the clinical chemotherapeutic drug doxorubicin (DOX) as a positive control to evaluate the effect of oHSV2 infection on the apoptotic, invasive, and proliferative capacity of DLBCL cells. We next further explored the therapeutic efficacy of oncolytic virus oHSV2 or DOX in DLBCL tumor bearing BALB/c mice, and evaluated the infiltration of CD8 + T cells and CD4 + T cells in tumor tissues. A pathological approach was used to explore the effects of oHSV2 on various organs of tumor bearing mice, including the heart, liver, and kidney. Next, SU-DHL-4 cells were co-cultured with cytotoxic T lymphocytes (CTLs) to mimic the tumor immune microenvironment (TME), to explore the impact of oHSV2 on the immune environment at the cellular level, and then analyzed the relationship between oHSV2 and the PD-1/PD-L1 immune-checkpoint. Subsequently, we further validated the efficacy of combined oHSV2 and PD-L1 treatment on transplanted tumor growth in mice at the in vivo level. DLBCL cells were sensitive to the action of the oncolytic virus oHSV2, and the decline in their proliferative activity showed a time-and dose-dependent manner. oHSV2 and DOX intervention preeminently increased the cell apoptosis, restrained cell proliferation and invasion, with the greatest changes occurring in response to oHSV2 infection. oHSV2 application effectively improved the immune status of the tumor microenvironment, favoring the invasion of CD8 + T and CD4 + T cells, thereby enhancing their antitumor effects. Besides, oHSV2 treatment has a safety profile in the organs of tumor bearing mice and indeed inhibits the PD-1/PD-L1 immune checkpoint in DLBCL. Interestingly, the combination of oHSV2 and PD-L1 antibodies results in more profound killing of DLBCL cells than oHSV2 infection alone, with a significant increase in the proportion of CD4 + T cells and CD8 + T cells. The antitumor effect was the best after combining oHSV2 and PD-L1 antibodies, suggesting that the combination therapy of oHSV2 and PD-L1 would have a better prospect for clinical application.

Diffuse large B-cell lymphoma (DLBCL) is a B-cell lymphoma with a high degree of aggressiveness. Recently, evidence has shown that miR-525-5p is decreased in DLBCL, suggesting its possible involvement in tumor progression. In this study, miR-525-5p suppressed proliferation, invasion and clonogenicity, and increased apoptosis of U2932 cells, whereas miR-525-5p silencing enhanced tumor cell growth. Next, miR-525-5p targets the 3′-UTR of Myd88, and Myd88 protein was increased in lymphoma tissues. Similar to the miR-525-5p mimic, Myd88 siRNA suppressed proliferation, invasion, and clonogenicity, and enhanced apoptosis of U2932 cells. We observed that Myd88 reversed the inhibitory effect of miR-525-5p on tumor cell growth by transfecting cells with miR-525-5p mimics alone or together with Myd88 overexpression vector. In addition, in vivo studies have shown that compared to the control group, U2932 cells with upregulated miR-525-5p expression have a reduced ability to induce tumor formation. In conclusion, our results demonstrate that miR-525-5p inhibits the progression of DLBCL through the Myd88/NF-κB pathway, which largely fills the gap of previous studies, and our results may provide a new reference for the targeted treatment of DLBCL.

PurposeThis study aims to explore and compare Chinese university students’ preferences for various physical activity motivation programs.Patients and methodsA cross-sectional study was conducted in China from February 25 to March 25, 2022. Participants anonymously completed an online questionnaire based on a DCE. A total of 1,358 university students participated in the survey. The conditional logit model (CLM), willingness to accept (WTA), and propensity score matching (PSM) were used to assess college students’ preferences for different attributes and levels of physical activity incentive programs.ResultsRespondents identified the number of bonus, exercise time, and academic rewards as the three most significant attributes of the athletic incentive program. The importance of each attribute varied based on individual characteristics such as gender and BMI. In CLM, college students displayed a preference for a “¥4” bonus amount (OR: 2.04, 95% CI 1.95–2.13), “20 min” of exercise time (OR: 1.85, 95% CI 1.79–1.92), and “bonus points for comprehensive test scores” as academic rewards (OR: 1.33, 95% CI 1.28–1.37). According to the WTA results, college students were willing to accept the highest cost to obtain academic rewards tied to composite test scores.ConclusionThe number of bonus, exercise time, and academic rewards emerge as the three most crucial attributes of physical activity incentive programs. Furthermore, college students with different characteristics exhibit heterogeneity in their preferences for such programs. These findings can guide the development of programs and policies aimed at motivating college students to engage in physical activities.

Abstract Background The desert shrub Nitraria tangutorum Bobr. is important for its resistance to salt and alkali in Northwest China. It is an ecologically important species in this region and provides edible and medicinal berries. This study showed a mutant of N. tangutorum (named Jincan, JC) that has a strong yellow pericarp vs red in a wild type (represented by NT). Results In this study, the secondary metabolic and molecular mechanisms responsible for Nitraria fruit coloration were investigated using LC–MS-based widely targeted metabolomics and transcriptomics data. As a result of our study, 122 and 104 flavonoid metabolites were differentially expressed throughout the mature and transition stages between JC and NT, respectively. Furthermore, two cyanidin derivatives (cyanidin 3-O-glucoside and cyanidin-3-O-(2''-O-glucosyl) glucoside) and one pelargonidin derivative (pelargonidin-3-O-glucoside) were identified only in the NT phenotype. The functional genes F3H (flavanone 3-hydroxylase), F3'H (flavonoid 3′-hydroxylase) and UFGT (flavonoid 3-O-glucosyltransferase) and the transcription factors MYB, bHLH, NAC and bZIP were significantly downregulated in JC. Meanwhile, the activity of UFGT was extremely low in both periods of JC, with a five-fold higher enzymatic activity of UFGT in RT than in YT. In summary, due to the lack of catalysis of UGFT, yellow fruit of JC could not accumulate sufficient cyanidin and pelargonidin derivatives during fruit ripening. Conclusion Taken together, our data provide insights into the mechanism for the regulation of anthocyanin synthesis and N. tangutorum fruit coloration and provide a theoretical basis to develop new strategies for developing bioactive compounds from N. tangutorum fruits.

Calcineurin B-like (CBL) proteins are a class of important Ca2+ receptors that play key roles in plant stress response. CBLs have been shown to participate in responses to abiotic stresses such as drought, salt, and cold in many plant species, including Arabidopsis and rice. However, little is known about their potential functions in the desert halophyte Nitraria tangutorum. Here, we have identified 11 CBL genes distributed across six chromosomes of N. tangutorum and categorized them into four groups through phylogenetic analysis. Synteny analysis showed that they have strong collinear relationships and have undergone purifying selection during their evolution. NtCBL promoter regions contain a variety of cis-acting elements related to hormone and environmental stress responses. Real-time quantitative PCR showed that the expression of NtCBLs differed significantly among various tissues and was upregulated by salt and drought stress. We chose NtCBL1-1 for an in-depth functional characterization and observed that transgenic Arabidopsis plants expressing NtCBL1-1 exhibited increased tolerance to both drought and salt stress. Compared to wild-type Arabidopsis, transgenic lines showed higher germination rates, slower chlorophyll degradation, more soluble proteins, and reduced accumulation of the oxidative stress marker malondialdehyde. These findings indicate that NtCBL1-1 plays a significant role in responding to drought and salt stress, laying the foundation for further investigations into the functional mechanisms of NtCBL genes in N. tangutorum.

Abstract. Background:. Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. Methods:. In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan–Meier analysis, receiver operating characteristic curve (ROC). Results:. A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes (CKMT1B, SMR3B, and OR11M1P) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. Conclusions:. A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.

Abstract Main goal of the JUNO experiment is to determine the neutrino mass ordering using a 20 kt liquid-scintillator detector. Its key feature is an excellent energy resolution of at least 3% at 1 MeV, for which its instruments need to meet a certain quality and thus have to be fully characterized. More than 20,000 20-inch PMTs have been received and assessed by JUNO after a detailed testing program which began in 2017 and elapsed for about four years. Based on this mass characterization and a set of specific requirements, a good quality of all accepted PMTs could be ascertained. This paper presents the performed testing procedure with the designed testing systems as well as the statistical characteristics of all 20-inch PMTs intended to be used in the JUNO experiment, covering more than fifteen performance parameters including the photocathode uniformity. This constitutes the largest sample of 20-inch PMTs ever produced and studied in detail to date, i.e. 15,000 of the newly developed 20-inch MCP-PMTs from Northern Night Vision Technology Co. (NNVT) and 5000 of dynode PMTs from Hamamatsu Photonics K. K.(HPK).

Abstract Background Health interventions can delay or prevent the occurrence and development of diabetes. Dynamic nomogram and risk score (RS) models were developed to predict the probability of developing type 2 diabetes mellitus (T2DM) and identify high-risk groups. Methods Participants (n = 44,852) from the Beijing Physical Examination Center were followed up for 11 years (2006–2017); the mean follow-up time was 4.06 ± 2.09 years. Multivariable Cox regression was conducted in the training cohort to identify risk factors associated with T2DM and develop dynamic nomogram and RS models using weighted estimators corresponding to each covariate derived from the fitted Cox regression coefficients and variance estimates, and then undergone internal validation and sensitivity analysis. The concordance index (C-index) was used to assess the accuracy and reliability of the model. Results Of the 44,852 individuals at baseline, 2,912 were diagnosed with T2DM during the follow-up period, and the incidence density rate per 1,000 person-years was 16.00. Multivariate analysis indicated that male sex (P

Abstract Background Arterial stiffness, glycemic control and blood pressure are risk factors of macrovascular complications in type 2 diabetes. This study aimed to investigate the combined association of arterial stiffness, glycemic control and hypertension status with the occurrence of diabetic macrovascular complication. Methods A total of 1870 patients of diabetes were enrolled from Beijing Health Management Cohort between 2008 and 2018 as baseline, and then followed for macrovascular complication onset. We proposed a composite risk score (0–4) by arterial stiffness severity, pool glycemic control and hypertension status. Cox model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). Results The mean age (SD) of this population was 59.90 (12.29) years. During a median follow-up of 4.0 years, 359 (19.2%) patients developed macrovascular complication. Compared to the normal arterial stiffness and good glycemic control group, patients with severe arterial stiffness and pool glycemic control had the highest risk of macrovascular complications (HR: 2.73; 95% CI: 1.42–5.25). Similarly, those of severe arterial stiffness and hypertension had the highest risk (HR: 2.69; 95% CI: 1.61–4.50). Patients of the composite score > 2 had a significantly increased risk of macrovascular complication. Conclusion This study suggested the clinical importance of combined evaluation of arterial stiffness, glycemic control and hypertension status for the risk stratification and management of macrovascular complication of type 2 diabetes.

SET-domain group histone methyltransferases (SDGs) are known to play crucial roles in plant responses to abiotic stress. However, their specific function in cotton’s response to drought stress has not been well understood. This study conducted a comprehensive analysis of the SDG gene family in Gossypium hirsutum, identifying a total of 82 SDG genes. An evolutionary analysis revealed that the SDG gene family can be divided into eight subgroups. The expression analysis shows that some GhSDG genes are preferentially expressed in specific tissues, indicating their involvement in cotton growth and development. The transcription level of some GhSDG genes is induced by PEG, with GhSDG59 showing significant upregulation upon polyethylene glycol (PEG) treatment. Quantitative polymerase chain reaction (qPCR) analysis showed that the accumulation of transcripts of the GhSDG59 gene was significantly upregulated under drought stress. Further functional studies using virus-induced gene silencing (VIGS) revealed that silencing GhSDG59 reduced cotton tolerance to drought stress. Under drought conditions, the proline content, superoxide dismutase (SOD) and peroxidase (POD) enzyme activities in the GhSDG59-silenced plants were significantly lower than in the control plants, while the malondialdehyde (MDA) content was significantly higher. Transcriptome sequencing showed that silencing the GhSDG59 gene led to significant changes in the expression levels of 1156 genes. The KEGG enrichment analysis revealed that these differentially expressed genes (DEGs) were mainly enriched in the carbon metabolism and the starch and sucrose metabolism pathways. The functional annotation analysis identified known drought-responsive genes, such as ERF, CIPK, and WRKY, among these DEGs. This indicates that GhSDG59 is involved in the drought-stress response in cotton by affecting the expression of genes related to the carbon metabolism and the starch and sucrose metabolism pathways, as well as known drought-responsive genes. This analysis provides valuable information for the functional genomic study of SDGs and highlights potential beneficial genes for genetic improvement and breeding in cotton.

Molybdenum disulfide (MoS2) is a promising anode material for lithium-ion batteries (LIBs) due to its distinctive graphene-like structure and high specific capacity. However, its commercial application is hindered by the severe volume expansion during lithiation/delithiation and poor conductivity. In this paper, we report a facile one-pot enhanced hydrothermal synthesis strategy to prepare high-performance MoS2/C composite materials. The results indicate that the as-prepared MoS2/C composite is a subspheroidal core–shell structure material, with uniform coating, good particle dispersion, and an average grain size of approximately 80 nm. The morphology of the composite remained unchanged even after annealing at 500 °C for 2 h. The addition of glucose can accelerate the nucleation and growth of MoS2, and higher hydrothermal temperatures can improve the product yield. The addition of PVP has little effect on the yield, but significantly reduces the particle size. The XPS analysis reveals that the MoO3 may be generated as an intermediate product during the hydrothermal process. The electrochemical test results show that the unannealed MoS2/C samples exhibit discharge-specific capacities of 705.2 mAh·g−1 and 625.7 mAh·g−1 after the first cycle and the 100th cycle, respectively, at a current density of 500 mA·g−1, with a capacity retention rate of 88.7%. In contrast, the specific capacity of the MoS2/C specimens after annealing at 500 °C for 2 h shows a tendency to decrease and then slowly increase during the cycles, and the discharge specific capacity is 582.3 mAh·g−1 after the 100th cycle, which is lower than that of the unheated sample. The impedance analysis reveals that the lithium-ion diffusion coefficient of the MoS2/C material without calcination is 2.11 × 10−18 cm·s−2, which is superior to that of the annealed MoS2/C and pristine MoS2 samples. This characteristic is favorable for lithiation/delithiation during the charge/discharge process.

Major depressive disorder (MDD) and bipolar disorder (BD) share clinical features, which complicates their differentiation in clinical settings. This study proposes an innovative approach that integrates structural connectome analysis with machine learning models to discern individuals with MDD from individuals with BD. High-resolution MRI images were obtained from individuals diagnosed with MDD or BD and from HCs. Structural connectomes were constructed to represent the complex interplay of brain regions using advanced graph theory techniques. Machine learning models were employed to discern unique connectivity patterns associated with MDD and BD. At the global level, both BD and MDD patients exhibited increased small-worldness compared to the HC group. At the nodal level, patients with BD and MDD showed common differences in nodal parameters primarily in the right amygdala and the right parahippocampal gyrus when compared with HCs. Distinctive differences were found mainly in prefrontal regions for BD, whereas MDD was characterized by abnormalities in the left thalamus and default mode network. Additionally, the BD group demonstrated altered nodal parameters predominantly in the fronto-limbic network when compared with the MDD group. Moreover, the application of machine learning models utilizing structural brain parameters demonstrated an impressive 90.3% accuracy in distinguishing individuals with BD from individuals with MDD. These findings demonstrate that combined structural connectome and machine learning enhance diagnostic accuracy and may contribute valuable insights to the understanding of the distinctive neurobiological signatures of these psychiatric disorders.

IntroductionWe aimed to investigate the association between greenness around schools, long-term gaseous air pollution exposure (SO2 and CO), and blood pressure in children and adolescents.MethodsFrom 2006 to 2018, a total of 219,956 Chinese children and adolescents aged 7–17 years in Beijing and Zhongshan were included in this longitudinal study. Annual average concentrations of SO2 and CO and the mean values of normalized difference vegetation index around schools were calculated. We used the generalized estimation equation model, restricted cubic spline model, and Cox model to analyze the health effects.ResultsAmong all the subjects, 52,515 had the first onset of HBP. During the follow-up, HBP's cumulative incidence and incidence density were 23.88% and 7.72 per 100 person-year respectively. Exposures to SO2 and CO were significantly associated with SBP [β = 1.30, 95% CI: (1.26, 1.34) and 0.78 (0.75, 0.81)], DBP [β = 0.81 (0.79, 0.84) and 0.46 (0.44, 0.48)] and HBP [HR = 1.58 (1.57, 1.60) and 1.42 (1.41, 1.43)]. The risks of HBP attributed to SO2 and CO pollution would be higher in school-aged children in the low greenness group: the attributable fractions (AFs) were 26.31% and 20.04%, but only 13.90% and 17.81% in the higher greenness group. The AFs were also higher for normal-BMI children and adolescents in the low greenness group (AFs = 30.90% and 22.64%, but 14.41% and 18.65% in the high greenness group), while the AFs were not as high as expected for obese children in the low greenness group (AFs = 10.64% and 8.61%), nor was it significantly lower in the high greenness group (AFs = 9.60% and 10.72%).DiscussionGreenness could alleviate the damage effects of SO2/CO exposure on the risks of HBP among children and adolescents, and the benefit is BMI sensitivity. It might offer insights for policymakers in making effective official interventions to prevent and control the prevalence of childhood HBP and the future disease burden caused by air pollution.

Proteolysis targeting chimeria (PROTAC) degrades target proteins by utilizing the ubiquitin-proteasome pathway, subverting the concept of traditional small molecule inhibitors. Among the common mutation targets of non-small cell lung cancer (NSCLC), PROTAC technology has successfully achieved the effective degradation of kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK ) and other proteins in preclinical studies. PROTAC drugs with their unique event-driven advantages, are expected to overcome acquired drug resistance caused by small molecule inhibitors and show good therapeutic potential for undruggable targets, thereby providing a new strategy for the treatment of NSCLC.