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Abstract Background Ulcerative colitis (UC) is a chronic intestinal inflammation, resulting in a global healthcare challenge with no real specific medicine. Natural medicines are recognized as a potential clinical alternative therapy, but their applications are limited by poor solubility and low bioavailability. Results In this work, inspired by the natural medicines of ancient China, novel functional carbon dots derived from Magnetite and Medicated Leaven (MML-CDs) were synthesized by hydrothermal method, and confirmed their ultrasmall nano-size (3.2 ± 0.6 nm) and Fe doped surface structure, thereby with excellent gastrointestinal stability, remarkable capabilities in eliminating ROS, and highly biocompatibility. With no external stimuli, the oral administration of MML-CDs demonstrated obvious alleviation to UC. Further experiments pointed that MML-CDs could improve hemostasis capability, suppress inflammation reactions and oxidative stress, and up-regulate the expression of tight junction proteins. Furthermore, MML-CDs also showed well regulation in the dysbiosis of intestinal flora. Conclusion Overall, above evidence reveals that green-synthesized MML-CDs can significantly alleviate intestinal bleeding, inhibit colon inflammation, and repair colonic barrier damage, further regulating intestinal flora and intestinal inflammation microenvironment. Our findings provide an efficient oral administration of MML-CDs as a novel therapy strategy for ulcerative colitis. Graphical Abstract

Abstract Smartphone addiction, emerging from excessive use of smartphones, poses a challenge to inhibitory control functions within society. This research employed transcranial direct current stimulation (tDCS) as an intervention alongside the stop signal task (SST) to explore behavioral distinctions between individuals with smartphone addiction and a non-addicted control group, focusing on the efficacy of tDCS intervention. The participant cohort comprised 80 individuals, divided into an addiction group (39 participants, with 19 receiving active tDCS and 20 receiving sham tDCS) and a control group (41 participants, with 20 receiving active tDCS and 21 receiving sham tDCS), with anodal stimulation applied over the right dorsolateral prefrontal cortex (dlPFC) and cathodal placement over the left arm. The findings indicate that university students struggling with smartphone addiction exhibit reduced inhibitory control compared to their non-addicted peers, while maintaining similar levels of general cognitive control. Remarkably, tDCS interventions were observed to enhance inhibitory control in both groups. Although the improvement in the addiction group appeared more pronounced numerically than in the control group, no significant interaction with group was noted. However, a higher percentage of participants in the smartphone addiction (SA) group exhibited enhanced response inhibition under active tDCS. This study demonstrates the inhibitory control deficits in individuals addicted to smartphones and underscores the potential of tDCS in enhancing response inhibition. It provides a valuable reference for future tDCS research targeting smartphone addiction and highlights the importance of developing healthier smartphone usage habits.

Abstract Porcine epidemic diarrhea virus (PEDV) is a serious disease that poses a significant threat to the pig industry. This study focused on analyzing the Spike protein of PEDV, which harbors crucial antigenic determinants, in identifying dominant epitopes. Immunoinformatics tools were used to screen for B-cell, CD4+ and CD8+ predominance epitopes. These epitopes were then connected to the N-terminal of ferritin to form a self-assembled nanoparticle vaccine. Various physical and chemical properties of the candidate vaccine were analyzed, including secondary structure prediction, tertiary structure modeling, molecular docking, immune response simulation and computer cloning. The results demonstrated that the candidate vaccine was antigenic, soluble, stable, non-allergic, and formed a stable complex with the target receptor TLR-3. Immune simulation analysis showed that the candidate vaccine effectively stimulated both cellular and humoral reactions, leading to increased related cytokines production. Furthermore, efficient and stable expression of the candidate vaccine was achieved through reverse translation in the Escherichia coli K12 expression system following codon optimization and in silico cloning. The developed nanoparticle candidate vaccine in this study holds promise as an effective PEDV vaccine candidate, offering a new approach for the research, development and improvement of vaccines targeting porcine enteric diarrhea coronavirus.

Abstract Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. Osteocalcin plays an important role in energy metabolism. In this study, we investigated the mechanism of action of chemically synthesized osteocalcin (csOCN) in ameliorating NAFLD. We demonstrated for the first time that csOCN attenuates lipid accumulation in the liver and hepatocytes by modulating CD36 protein expression. In addition, we found that the expression of p-AMPK, FOXO1 and BCL6 decreased and the expression of CD36 increased after OA/PA induction compared to the control group, and these effects were reversed by the addition of csOCN. In contrast, the therapeutic effect of csOCN was inhibited by the addition of AMPK inhibitors and BCL6 inhibitors. This finding suggested that csOCN regulates CD36 expression via the AMPK-FOXO1/BCL6 axis. In NAFLD mice, oral administration of csOCN also activated the AMPK pathway and reduced CD36 expression. Molecular docking revealed that osteocalcin has a docking site with CD36. Compared to oleic acid and palmitic acid, osteocalcin bound more strongly to CD36. Laser confocal microscopy results showed that osteocalcin colocalized with CD36 at the cell membrane. In conclusion, we demonstrated the regulatory role of csOCN in fatty acid uptake pathways for the first time; it regulates CD36 expression via the AMPK-FOXO1/BCL6 axis to reduce fatty acid uptake, and it affects fatty acid transport by may directly binding to CD36. There are indications that csOCN has potential as a CD36-targeted drug for the treatment of NAFLD.

Abstract This study aims to elucidate the detailed metabolic implications of varying monacolin K levels and sterilization methods on Monascus‐fermented rice products (MFRPs), acclaimed for their health benefits and monacolin K content. Advanced metabolite profiling of various MFRP variants was conducted using ultrahigh‐performance liquid chromatography coupled with tandem time‐of‐flight mass spectrometry (UHPLC‐Q‐TOF MS). Statistical analysis encompassed t‐tests, ANOVA, and multivariate techniques including PCA, PLS‐DA, and OPLS‐DA. Notable variations in metabolites were observed across MFRPs with differing monacolin K levels, particularly in variants such as MR1‐S, MR1.5‐S, MR2‐S, and MR3‐S. Among the 524 identified metabolites, significant shifts were noted in organic acids, derivatives, lipids, nucleosides, and organic oxygen compounds. The study also uncovered distinct metabolic changes resulting from different sterilization methods and the use of highland barley as a fermentation substitute for rice. Pathway analysis shed light on affected metabolic pathways, including those involved in longevity regulation, cGMP‐PKG signaling, and the biosynthesis of unsaturated fatty acids. The research provides critical insights into the complex metabolic networks of MFRPs, underscoring the impact of fermentation substrates and conditions on monacolin K levels and their health implications. This study not only guides the nutritional optimization of MFRPs but also emphasizes the strategic importance of substrate choice and sterilization techniques in enhancing the nutritional and medicinal value of these functional foods.

Abstract Background Triple negative breast cancer (TNBC) is a type of breast cancer that is negative for oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, is highly malignant and aggressive, lacks of corresponding targeted therapy, and has a relatively poor prognosis. Therefore, understanding the mechanism of TNBC development and formulating effective treatment strategies for inducing cell death are still urgent tasks in the treatment of TNBC. Research has shown that uncarboxylated osteocalcin can promote the proliferation of prostate cancer, lung adenocarcinoma and TNBC cells, but the mechanism by which GluOC affects TNBC growth and metastasis needs further study. Methods MDA-MB-231 breast cancer cells were used for in vitro cell analysis. Key target molecules or pathways were identified by RNA sequencing, and migration ability was detected by scratch assays, Transwell assays, cell adhesion assays and western blot analysis. Fluorescence staining, colony detection, qRT‒PCR and flow cytometry were used to detect apoptosis, oxidative stress, the cell cycle and the stemness of cancer cells, and a xenotransplantation model in BALB/C nude mice was used for in vivo analysis. Results This study demonstrated that GluOC facilitates the migration of MDA-MB-231 breast cancer cells through the ROCK1/MYPT1/MLC2 signalling pathway and promotes the proliferation of TNBC cells via the ROCK1/JAK2/PIK3CA/AKT signalling pathway. Experiments in nude mice demonstrated that GluOC promoted tumour cell proliferation and metastasis in tumour-bearing mice, which further clarified the molecular mechanism of TNBC growth and invasion. Conclusion Our findings highlight the importance of GluOC in driving TNBC progression and its association with poor patient outcomes. This study clarifies the functional effects of GluOC on TNBC growth, providing insight into the molecular basis of TNBC and potentially providing new ideas for developing targeted therapies to improve patient outcomes.

Foodborne pathogens are one of the important factors affecting food safety. Efficient and rapid detection technology of foodborne pathogens is particularly important to ensure food safety. Among the rapid detection methods of foodborne pathogens, molecular biology technology has been widely used because of its advantages of strong specificity, high accuracy, and fast detection speed. This paper introduces the application of various molecular biological techniques in the rapid detection of foodborne pathogens, including polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), nuclear acid sequence-based amplification (NAS-BA), recombinase polymerase amplification (PRA), recombinase-aided isothermal amplification (RAA), and gene chip (GC). The application status, application scope and existing problems of these technologies are also analyzed and summarized to provide theoretical reference for the rapid detection of foodborne pathogens in the future.

AbstractChinese herbs contain substances that regulate female hormones. Our study confirmed that Zingiberis rhizoma carbonisata contains Zingiberis rhizoma-based carbon dots (ZR-CDs), which exert regulatory effects on serum oestradiol and FSH in mice and show impacts on endometrial growth and follicular development that potentially affect the ability of female fertility. ZR-CDs were characterized to clarify the microstructure, optical features, and functional group characteristics. It shows that ZR-CDs are spherical carbon nanostructures ranging from 0.97 to 2.3 nm in diameter, with fluorescent properties and a surface rich in functional groups. We further investigated the impact of ZR-CDs on oestradiol and FSH in serum, growth, and the development of ovarian and uterine using normal female mice and exogenous oestradiol intervention model. It was observed that ZR-CDs accelerated oestrogen metabolism and attenuated oestradiol-induced endometrial hyperplasia. Simultaneously, ZR-CDs triggered an increase in FSH, even in the presence of high-serum oestradiol that inhibits FSH secretion. Our findings suggest that ZR-CDs could be a potential therapeutic treatment for anovulatory menstruation.

Abstract Landscape stability is a paramount concern within the field of landscape ecology. Indices of landscape patterns not only facilitate an effective analysis of land use transformations but also delve into the mechanisms of landscape disturbances across various spatial and temporal dimensions. Utilizing land use data spanning from 2014 to 2022 for the Shibing and Libo-Huanjiang South China Karst (SCK) World Heritage Sites (WHSs), this study delves into the landscape dynamics of these areas over the past 8 years. This investigation employs landscape pattern indices and a moving window technique to construct a landscape stability evaluation model, incorporating indices such as the Contagion Index, Patch Density, and Total Edge Contrast. Moreover, the study employs Moran's I, a spatial autocorrelation index, to scrutinize the shifts in geographical heterogeneity of landscape stability within the said period. The findings reveal: (1) Between 2014 and 2022, the landscape patterns of the Shibing and Libo-Huanjiang WHSs have undergone significant transformations, with Woodland emerging as the predominant landscape type and its area exhibiting an upward trend in recent years. (2) The level of fragmentation within the research area has decreased, landscape diversity has diminished, and the aggregation index has risen, according to the landscape pattern indices from 2014 to 2022, indicating that conservation measures have significantly influenced the evolution of landscape patterns. (3) Throughout most of the study period, landscape stability predominantly remained at a relatively stable level, albeit with noticeable fluctuations in years heavily impacted by human activities. (4) The areas of high-high agglomeration and the hotspots of the heritage sites were primarily concentrated within the core zones of these sites, suggesting focused areas of conservation and landscape integrity.

Abstract Background Childhood adversities may lead to decreased activity participation in later life, impacting memory health in ageing adults. Childhood adversities related to deprivation and threat, as conceptualized by the Dimensional Model of Adversity, can exhibit distinct impacts on cognitive and emotional outcomes in children and younger adults. This study examined the potential influence of childhood deprivation and threat on memory function in later life and the mediating role of activity participation in these relationships. Methods This study used data from the first wave of Panel Study of Active Ageing and Society (PAAS), a representative survey of Hong Kong residents aged 50 or above (N = 1,005). Key variables included late-life memory function measured by delayed recall test, deprivation- and threat-related childhood adversities, and the frequency of participation in informal and formal types of activities. Mediation tests were used for analysis. Results Childhood deprivation was associated with a lower late-life memory function, whereas threat was not. The negative effects of childhood deprivation and its subdomain, economic hardship, on memory function were mediated by activity participation. Total participation scores presented the strongest mediating effect (17.3–20.6%), with formal activities playing a more substantial mediating role than informal activities in mitigating the effect of childhood deprivation. Conclusions These findings expand the applicability of the Dimensional Model of Adversity to ageing populations, highlighting the influence of deprivation on life-long cognitive development. Furthermore, this study revealed an indirect mechanism by which childhood deprivation affects memory health in old age through diverse activity participation.

Abstract. Background:. The ability to generate functional hepatocytes without relying on donor liver organs holds significant therapeutic promise in the fields of regenerative medicine and potential liver disease treatments. Clustered regularly interspaced short palindromic repeats (CRISPR) activator (CRISPRa) is a powerful tool that can conveniently and efficiently activate the expression of multiple endogenous genes simultaneously, providing a new strategy for cell fate determination. The main purpose of this study is to explore the feasibility of applying CRISPRa for hepatocyte reprogramming and its application in the treatment of mouse liver fibrosis. Method:. The differentiation of mouse embryonic fibroblasts (MEFs) into functional induced hepatocyte-like cells (iHeps) was achieved by utilizing the CRISPRa synergistic activation mediator (SAM) system, which drove the combined expression of three endogenous transcription factors—Gata4, Foxa3, and Hnf1a—or alternatively, the expression of two transcription factors, Gata4 and Foxa3. In vivo, we injected adeno-associated virus serotype 6 (AAV6) carrying the CRISPRa SAM system into liver fibrotic Col1a1-CreER; Cas9fl/fl mice, effectively activating the expression of endogenous Gata4 and Foxa3 in fibroblasts. The endogenous transcriptional activation of genes was confirmed using real-time quantitative polymerase chain reaction (RT-qPCR) and RNA-seq, and the morphology and characteristics of the induced hepatocytes were observed through microscopy. The level of hepatocyte reprogramming in vivo is detected by immunofluorescence staining, while the improvement of liver fibrosis is evaluated through Sirius red staining, alpha-smooth muscle actin (α-SMA) immunofluorescence staining, and blood alanine aminotransferase (ALT) examination. Results:. Activation of only two factors, Gata4 and Foxa3, via CRISPRa was sufficient to successfully induce the transformation of MEFs into iHeps. These iHeps could be expanded in vitro and displayed functional characteristics similar to those of mature hepatocytes, such as drug metabolism and glycogen storage. Additionally, AAV6-based delivery of the CRISPRa SAM system effectively induced the hepatic reprogramming from fibroblasts in mice with live fibrosis. After 8 weeks of induction, the reprogrammed hepatocytes comprised 0.87% of the total hepatocyte population in the mice, significantly reducing liver fibrosis. Conclusion:. CRISPRa-induced hepatocyte reprogramming may be a promising strategy for generating functional hepatocytes and treating liver fibrosis caused by hepatic diseases.

Abstract Background The incidence of mental health problems among medical graduate students is much higher than among students of other disciplines. This can have adverse consequences for the medical students themselves as well as their future patients. This study aims to understand the pressures faced by Chinese medical students and the current status of mental health education. It also propose recommendations for the current situation and prospects for the future. Method The authors conducted in-depth semi-structured interviews with 22 master’s students from five medical schools during November 2023. All interview sessions were recorded and transcribed verbatim. The transcriptions were analyzed using the Colaizzi’s seven-step method. Result Three main themes were extracted from the students’ statements: sources of psychological stress, ways to cope with stress, and perspectives on mental health education. The study showed that current mental health education in China is mostly in the form of printed mental health education manuals and mental health lectures, and there is no active tiered intervention for students at different levels. It is suggested that reforms should be made to shift to a model where the school proactively identifies problems and intervenes based on feedback. Conclusion This study reveals the widespread psychological stress and shortcomings in current education methods. To address these challenges, institutions should develop tailored interventions, including tiered support systems, open dialogue promotion, and resilience training. Future research should focus on evaluating innovative interventions’ effectiveness, ultimately fostering a supportive environment that enhances students’ success and contributes to a healthier healthcare workforce.

Abstract Pure organic phosphorescence resonance energy transfer is a research hotspot. Herein, a single-molecule phosphorescence resonance energy transfer system with a large Stokes shift of 367 nm and near-infrared emission is constructed by guest molecule alkyl-bridged methoxy-tetraphenylethylene-phenylpyridines derivative, cucurbit[n]uril (n = 7, 8) and β-cyclodextrin modified hyaluronic acid. The high binding affinity of cucurbituril to guest molecules in various stoichiometric ratios not only regulates the topological morphology of supramolecular assembly but also induces different phosphorescence emissions. Varying from the spherical nanoparticles and nanorods for binary assemblies, three-dimensional nanoplate is obtained by the ternary co-assembly of guest with cucurbit[7]uril/cucurbit[8]uril, accompanying enhanced phosphorescence at 540 nm. Uncommonly, the secondary assembly of β-cyclodextrin modified hyaluronic acid and ternary assembly activates a single intramolecular phosphorescence resonance energy transfer process derived from phenyl pyridines unit to methoxy-tetraphenylethylene function group, enabling a near-infrared delayed fluorescence at 700 nm, which ultimately applied to mitochondrial targeted imaging for cancer cells.

Background: Anti-Program-Death-1 (PD-1) is a standard adjuvant therapy for patients with resected melanoma. We hypothesized that there are discrepancies in survival, recurrence pattern and toxicity to adjuvant PD-1 between different ethnicities and melanoma subtypes. Objective: We performed a multicenter cohort study incorporating 6 independent institutions in Australia, China, Japan, and the United States. The primary outcomes were recurrence free survival (RFS) and overall survival (OS). Secondary outcomes were disease recurrence patterns and toxicities. Results: In total 534 patients were included. East-Asian/Hispanic/African reported significantly poorer RFS/OS. Nonacral cutaneous or melanoma of unknown primary reported the best RFS/OS, followed by acral, and mucosal was the poorest. Within the nonacral cutaneous or melanoma of unknown primary subtypes, East-Asian/Hispanic/African reported significantly poorer RFS/OS than Caucasian. In the multivariate analysis incorporating ethnicity/melanoma-subtype/age/sex/stage/lactate dehydrogenase/BRAF (v-Raf murine sarcoma viral oncogene homolog B)-mutation/adjuvant radiotherapy, East-Asian/Hispanic/African had independently significantly poorer outcomes (RFS: HR, 1.71; 95% CI, 1.19-2.44 and OS: HR, 2.34; 95% CI, 1.39-3.95), as was mucosal subtype (RFS: HR, 3.25; 95% CI, 2.04-5.17 and OS: HR, 3.20; 95% CI, 1.68-6.08). Mucosal melanoma was an independent risk factor for distant metastasis, especially liver metastasis. East-Asian/Hispanic/African had significantly lower incidence of gastrointestinal/musculoskeletal/respiratory/other-rare-type-toxicities; but higher incidences of liver toxicities. Limitations: A retrospective study. Conclusions: Ethnicity and melanoma subtype are associated with survival and recurrence pattern in melanoma patients treated with adjuvant anti-PD-1. Toxicity profile differs by ethnicity and may require a precision toxicity surveillance strategy.

Gd2Zr2O7 is one of the most promising new generation of ceramic materials for high temperature thermal barrier coatings. However, it still has great potential of improving thermal and mechanical properties and contributing tobetter thermal cycling performance of the coating. Doping rare earth elements in Gd2Zr2O7 is an effective method to enhance its thermal and mechanical properties. In this paper, the first principles is used to calculate the thermophysical properties of doped Gd2Zr2O7 with 16 rare earth elements, including modulus of elasticity, Debye temperature, minimum high-temperature thermal conductivity, high temperature thermal expansion coefficient, and fracture toughness, by which all doped Gd2Zr2O7 ceramics were ranked using the entropy method. The results show that doping with Pr, Sm, Yb, and Nd showed superior comprehensive performance. Specially, (Gd0.875Pr0.125)2Zr2O7 has the lowest Young's modulus of 244 MPa, Pugh ratio of 0.53, Debye temperature of 523.4 K, thermal conductivity of 1.27 W/(m·K), and the largest coefficient of thermal expansion of 9.19 × 10−6 K−1, and (Gd0.875Ho0.125)2Zr2O7 has the highest fracture toughness of 2.21 MPa·m1/2.

Abstract Background The World Health Organization (WHO) published the Integrated Care for Older People (ICOPE) framework to help healthcare providers cope with the population aging crisis. However, the relevant evidence on the demands of older people and the compensatory capacity of the environment is limited. This study reports for the first time the level of the ICOPE demand in Western China that includes the impact of geographic accessibility of medical resources (GAMR) on ICOPE demand and the potential mechanism of health status. Methods A cross-sectional questionnaire survey was conducted among 1200 adults aged 60 years and older selected through multi-stage stratified cluster sampling to obtain relevant data, including ICOPE demand, health status, and GAMR. Propensity score matching (PSM) was used to analyze the impact of GAMR on ICOPE demand among older people and those with different health statuses. Results Among the prospective research participants, 1043 were eligible for the study. The mean score of ICOPE demand among all participants was 3.68 (standard deviation [SD] = 0.78). After adjusting for covariates between high and low GAMR groups (1:1 match), ICOPE demand was significantly higher in the low GAMR group than in the high GAMR group (average treatment effect on the treated [ATT] = 0.270, p

Abstract Lysine lactylation (Kla) links metabolism and gene regulation and plays a key role in multiple biological processes. However, the regulatory mechanism and functional consequence of Kla remain to be explored. Here, we report that HBO1 functions as a lysine lactyltransferase to regulate transcription. We show that HBO1 catalyzes the addition of Kla in vitro and intracellularly, and E508 is a key site for the lactyltransferase activity of HBO1. Quantitative proteomic analysis further reveals 95 endogenous Kla sites targeted by HBO1, with the majority located on histones. Using site-specific antibodies, we find that HBO1 may preferentially catalyze histone H3K9la and scaffold proteins including JADE1 and BRPF2 can promote the enzymatic activity for histone Kla. Notably, CUT&Tag assays demonstrate that HBO1 is required for histone H3K9la on transcription start sites (TSSs). Besides, the regulated Kla can promote key signaling pathways and tumorigenesis, which is further supported by evaluating the malignant behaviors of HBO1- knockout (KO) tumor cells, as well as the level of histone H3K9la in clinical tissues. Our study reveals HBO1 serves as a lactyltransferase to mediate a histone Kla-dependent gene transcription.

Abstract This research aimed to investigate effects of different yeast culture (YC) levels on in vitro fermentation characteristics and bacterial and fungal community under high concentrate diet. A total of 5 groups were included in the experiment: control group without YC (CON), YC1 (0.5% YC proportion of substrate dry matter), YC2 (1%), YC3 (1.5%) and YC4 (2%). After 48 h of fermentation, the incubation fluids and residues were collected to analyze the ruminal fermentation parameters and bacterial and fungal community. Results showed that the ruminal fluid pH of YC2 and YC4 groups was higher (P

This study aimed to investigate the dose-effect of iron on growth performance, antioxidant function, intestinal morphology, and mRNA expression of jejunal tight junction protein in 1- to 21-d-old yellow-feathered broilers. A total of 720 1-d-old yellow-feathered male broilers were allocated to 9 treatments with 8 replicate cages of 10 birds per cage. The dietary treatments were consisted of a basal diet (contained 79.6 mg Fe kg–1) supplemented with 0, 20, 40, 60, 80, 160, 320, 640, and 1,280 mg Fe kg–1 in the form of FeSO4·7H2O. Compared with the birds in the control group, birds supplemented with 20 mg Fe kg–1 had higher average daily gain (ADG) (P

Studying contaminant transport in the capillary fringe (CF), a crucial part of the vadose zone, offers insights into the mechanisms controlling pollution in soils and groundwater aquifers. This paper investigated contaminant transport in the CF by continuously injecting a conservative tracer (NaCl) and graphene oxide nanoparticle (GONP), an adsorptive contaminant, into a sandbox. After entering the CF from the unsaturated zone, both NaCl and GONP underwent lateral transport. The breakthrough curves (BTCs) for NaCl and GONP were derived from water samples collected at predetermined sampling holes. Subsequently, contaminant transport in the CF was modeled using a one-dimensional–two-dimensional (1D-2D) coupled hydrodynamic model. This model incorporated lateral dispersivity (αL = 1.198 cm) and longitudinal dispersivity (αT = 0.286 cm), calculated using a point-by-point method. The hydrodynamic dispersion coefficients obtained were then applied to the Brooks and Corey (BC) and the van Genuchten (VG) parametric models. The BC model more accurately simulated the NaCl migration compared to the VG model, leading to its application in simulating GONP transport in the CF. However, the simulated BTCs for GONP showed a lag behind the measured data, especially at high ionic strengths. This discrepancy was attributed to the variable adsorption partition coefficient of GONP under different ionic conditions. During the experiment, GONP adsorption onto the porous media's surface altered the capillary dynamics, notably increasing capillary rise height, decreasing seepage velocity, and reducing GONP dispersion. Therefore, it is necessary to consider the adsorption capacity of the contaminants in order to accurately assess their transport within the vadose zone.

As a broad-spectrum anticancer drug, cisplatin is widely used in the treatment of tumors in various systems. Unfortunately, several serious side effects of cisplatin limit its clinical application, the most common of which are nephrotoxicity and ototoxicity. Studies have shown that cochlear hair cell degeneration is the main cause of cisplatin-induced hearing loss. However, the mechanism of cisplatin-induced hair cell death remains unclear. The present study aimed to explore the potential role of activating transcription factor 6 (ATF6), an endoplasmic reticulum (ER)-localized protein, on cisplatin-induced ototoxicity in vivo and in vitro. In this study, we observed that cisplatin exposure induced apoptosis of mouse auditory OC-1 cells, accompanied by a significant increase in the expression of ATF6 and C/EBP homologous protein (CHOP). In cell or cochlear culture models, treatment with an ATF6 agonist, an ER homeostasis regulator, significantly ameliorated cisplatin-induced cytotoxicity. Further, our in vivo experiments showed that subcutaneous injection of an ATF6 agonist almost completely prevented outer hair cell loss and significantly alleviated cisplatin-induced auditory brainstem response (ABR) threshold elevation in mice. Collectively, our results revealed the underlying mechanism by which activation of ATF6 significantly improved cisplatin-induced hair cell apoptosis, at least in part by inhibiting apoptosis signal-regulating kinase 1 expression, and demonstrated that pharmacological activation of ATF6-mediated unfolded protein response is a potential treatment for cisplatin-induced ototoxicity.

Summary: Hypoxia promotes tumorigenesis and lactate accumulation in esophageal squamous cell carcinoma (ESCC). Lactate can induce histone lysine lactylation (Kla, a recently identified histone marks) to regulate transcription. However, the functional consequence of histone Kla under hypoxia in ESCC remains to be explored. Here, we reveal that hypoxia facilitates histone H3K9la to enhance LAMC2 transcription for proliferation of ESCC. We found that global level of Kla was elevated under hypoxia, and thus identified the landscape of histone Kla in ESCC by quantitative proteomics. Furthermore, we show a significant increase of H3K9la level induced by hypoxia. Next, MNase ChIP-seq and RNA-seq analysis suggest that H3K9la is enriched at the promoter of cell junction genes. Finally, we demonstrate that the histone H3K9la facilitates the expression of LAMC2 for ESCC invasion by in vivo and in vitro experiments. Briefly, our study reveals a vital role of histone Kla triggered by hypoxia in cancer.

Abstract We report the development of a head-mounted photoacoustic fiberscope for cerebral imaging in a freely behaving mouse. The 4.5-gram imaging probe has a 9-µm lateral resolution and 0.2-Hz frame rate over a 1.2-mm wide area. The probe can continuously monitor cerebral oxygenation and hemodynamic responses at single-vessel resolution, showing significantly different cerebrovascular responses to external stimuli under anesthesia and in the freely moving state. For example, when subjected to high-concentration CO2 respiration, enhanced oxygenation to compensate for hypercapnia can be visualized due to cerebral regulation in the freely moving state. Comparative studies exhibit significantly weakened compensation capabilities in obese rodents. This new imaging modality can be used for investigating both normal and pathological cerebrovascular functions and shows great promise for studying cerebral activity, disorders and their treatments.

To meet the practical needs of classified collection, graded treatment, and quality recycling of coal chemical wastewater, and in accordance with the standardization requirements of wastewater resource utilization, the Standardization Administration of China released the national standard GB/T 42,866-2023 ″Guidelines for Coal Chemical Wastewater Treatment and Recycling Technology” on August 6, 2023, for the first time. Based on the standard, this paper comprehensively and systematically sorts out and analyzes the characteristics, processes, water circulation systems, and standardization paths of units such as coal chemical wastewater collection and treatment, recycling, and the treatment of concentrated brine water, through extensive industry research. Furthermore, by integrating typical engineering case practices, this paper explains the feasibility of the paths, which provides technical guidance and experience for relevant cases of coal chemical wastewater treatment and recycling. It is also of great importance for promoting the standardized management and development of coal chemical wastewater treatment and recycling worldwide.

Abstract With the rapid development of intelligent and connected vehicles, the experimental road test for the advanced driving assistance system (ADAS) is dramatically increasing around the world. Considering its high cost and hazardous situations, simulation test based on a dummy model is becoming a promising way for ADAS road test practice to reduce the experiment expanses. This study proposed a methodology for the evaluation of the performance of human and dummies with distinct designed materials based on the data extracted from the Doppler effect of millimeter-wave radar. Echo data of 8 different angles from 0 to 360 degrees, with the an interval of 45 degrees, at the same distance between the test object and the signal source is collected. Meanwhile, the echo energy is collected for correlation modeling and analysis among groups. By evaluating the performance of humans and dummies via statistical analysis, a close correlation was found which results verified the substitutability of the dummy for the ADAS experiment test. The correlation coefficient between human and dummies ranges from 0.75 to 0.93. The support vector machine (SVM) model was developed and fitted to predict the echo energy in diverse environments. The mean average error (MAE) is 5.42–11.42 in the training and testing datasets while root mean square error (RMSE) is 0.43–0.90. The methods developed in the study can simulate the real ADAS road test environment and support future experimental research.

Abstract Background Hepcidin is the master regulator of iron homeostasis. Hepcidin downregulation has been demonstrated in the brains of Alzheimer’s disease (AD) patients. However, the mechanism underlying the role of hepcidin downregulation in cognitive impairment has not been elucidated. Methods In the present study, we generated GFAP-Cre-mediated hepcidin conditional knockout mice (Hamp GFAP cKO) to explore the effect of hepcidin deficiency on hippocampal structure and neurocognition. Results We found that the Hamp GFAP cKO mice developed AD-like brain atrophy and memory deficits. In particular, the weight of the hippocampus and the number of granule neurons in the dentate gyrus were significantly reduced. Further investigation demonstrated that the morphological change in the hippocampus of Hamp GFAP cKO mice was attributed to impaired neurogenesis caused by decreased proliferation of neural stem cells. Regarding the molecular mechanism, increased iron content after depletion of hepcidin followed by an elevated level of the inflammatory factor tumor necrosis factor-α accounted for the impairment of hippocampal neurogenesis in Hamp GFAP cKO mice. These observations were further verified in GFAP promoter-driven hepcidin knockdown mice and in Nestin-Cre-mediated hepcidin conditional knockout mice. Conclusions The present findings demonstrated a critical role for hepcidin in hippocampal neurogenesis and validated the importance of iron and associated inflammatory cytokines as key modulators of neurodevelopment, providing insights into the potential pathogenesis of cognitive dysfunction and related treatments. Graphical Abstract

Objectives: Intrinsic capacity impairment results in poor outcomes among older adults. Here we tested handgrip strength as a screening tool for IC impairment in community-dwelling older adults in Xinjiang, China. We assessed the diagnostic accuracy and established optimal cut-off points for handgrip strength in the detection of intrinsic capacity impairment. Methods: In total, 1072 participants were included using a multilevel random sampling method. Intrinsic capacity was constructed according to the definition of the Integrated Care for Older People screening tool proposed by the WHO. Results: Altogether, 73.4 % (787/1072) participants had intrinsic capacity impairment. The prevalence of intrinsic capacity impairment for hearing, vision, mobility, cognition, psychological, and vitality domains was 8.6 %, 4.8 %, 39.6 %, 47.3 %, 12.0 %, and 18.8 %, respectively. The adjusted odds ratios [95 % confidence interval) for handgrip strength was 0.935 [0.914–0.956]. The area under the curve of the receiver operating characteristic curve for handgrip strength of older men, and handgrip strength of older women with intrinsic capacity impairment were 0.7278, and 0.7534, respectively. The handgrip strength cut-off points were 28.47 kg (60–69 years), 25.76 kg (70–79 years), and 24.45 kg (≥80 years) for men, and 20.75 kg (60–69 years), 19.90 kg (70–79 years), and 16.17 kg (≥80 years) for women. Conclusions: Handgrip strength can be used as a convenient tool for evaluating intrinsic capacity. Weak handgrip strength and low education level were associated with intrinsic capacity impairment in community-dwelling older adults in Xinjiang. Using the cut-off points of handgrip strength for different age groups and genders, older adults with impaired intrinsic capacity can be identified, which may reduce the occurrence of adverse outcomes.

Metallurgical defects in metal laser additive manufacturing (LAM) are inevitable due to complex non-equilibrium thermodynamics. A laser ultrasonic system was designed for detecting surface/near-surface defects in the layer-by-layer LAM process. An approach was proposed for ultrasonic imaging of defects based on variable time window intensity mapping with adaptive 2σ threshold denoising. The Gaussian mixture model hypothesis and expectation-maximization algorithm can automatically differentiate between components dominated by defects and background noises, thereby providing an adaptive threshold that accommodates detection environments and surface roughness levels. Results show that the ultrasonic wave reflection at defect boundaries diminishes far-field ultrasonic intensity upon pulsed laser irradiation on surface defects, enabling defect size and location characterization. This method is applicable to LAM samples with a significant surface roughness of up to 37.5 μm. It can detect superficial and near-surface defects down to 0.5 mm in diameter and depth, making it significant for online defect detection in additive manufacturing.

Background The sustained effectiveness of anti-programmed cell death protein-1/programmed death-ligand 1 treatment is limited to a subgroup of patients with advanced nasopharyngeal carcinoma (NPC), and the specific biomarker determining the response to immunotherapy in NPC remains uncertain.Methods We assessed the associations between pre-immunotherapy and post-immunotherapy serum lipoproteins and survival in a training cohort (N=160) and corroborated these findings in a validation cohort (N=100). Animal studies were performed to explore the underlying mechanisms. Additionally, the relationship between high-density lipoprotein-cholesterol (HDL-C) levels and M1/M2-like macrophages, as well as activated CD8+T cells in tumor tissues from patients with NPC who received immunotherapy, was investigated.Results The lipoproteins cholesterol, HDL-C, low-density lipoprotein-cholesterol, triglycerides, apolipoprotein A-1 (ApoA1), and apolipoprotein B, were significantly altered after immunotherapy. Patients with higher baseline HDL-C or ApoA1, or those with increased HDL-C or ApoA1 after immunotherapy had longer progression-free survival, a finding verified in the validation cohort (p

Agricultural soils contaminated with heavy metals poison crops and disturb the normal functioning of rhizosphere microbial communities. Different crops and rhizosphere microbial communities exhibit different heavy metal resistance mechanisms. Here, indoor pot studies were used to assess the mechanisms of grain and soil rhizosphere microbial communities on chromium (Cr) stress. Millet grain variety ‘Jingu 21’ (Setaria italica) and soil samples were collected prior to control (CK), 6 hours after (Cr_6h), and 6 days following (Cr_6d) Cr stress. Transcriptomic analysis, high-throughput sequencing and quantitative polymerase chain reaction (qPCR) were used for sample determination and data analysis. Cr stress inhibited the expression of genes related to cell division, and photosynthesis in grain plants while stimulating the expression of genes related to DNA replication and repair, in addition to plant defense systems resist Cr stress. In response to chromium stress, rhizosphere soil bacterial and fungal community compositions and diversity changed significantly (p

Objective(s)This study aimed to identify the key elements and develop a formation mechanism model of quality geriatric care behavior for nursing assistants.MethodsThis qualitative research employed the strategy of grounded theory proposed by Strauss and Corbin. Furthermore, the data was collected by participatory observation and semi-structured interviews. A total of 12 nursing managers, 63 nursing assistants, and 36 older people from 9 nursing homes in 6 cities were interviewed, whereas for the observatory survey, participants were recruited from 2 nursing homes.ResultsThe comparative and analysis process revealed 5 key elements of quality geriatric care behavior, including holistic care, personalized care, respect, positive interaction, and empowerment. Based on the Capability-Opportunity-Motivation-Behavior (COM-B) model, key elements and the 3 stages of quality geriatric care behavior (negative behavior cognition stage, practice exchange run-in stage, and positive behavior reinforcement stage), the theoretical framework of the formation mechanism was established.ConclusionThe results indicated that nursing assistants’ capabilities, motivation, and organizational and environmental support are vital for quality care behaviors. The theoretical framework established in this study provides theoretical support and practical reference to policymakers, institutional administrators, and healthcare professionals for improving nursing assistant’s care behaviors.

Abstract The vaginal microbiome plays an essential role in the reproductive health of human females. As infertility increases worldwide, understanding the roles that the vaginal microbiome may have in infertility and in vitro fertilization (IVF) treatment outcomes is critical. To determine the vaginal microbiome composition of 1411 individuals (1255 undergoing embryo transplantation) and their associations with reproductive outcomes, clinical and biochemical features are measured, and vaginal samples are 16S rRNA sequenced. Our results suggest that both too high and too low abundance of Lactobacillus is not beneficial for pregnancy; a moderate abundance is more beneficial. A moderate abundance of Lactobacillus crispatus and Lactobacillus iners (~80%) (with a pregnancy rate of I‐B: 54.35% and III‐B: 57.73%) is found beneficial for pregnancy outcomes compared with a higher abundance (>90%) of Lactobacillus (I‐A: 44.81% and III‐A: 51.06%, respectively). The community state type (CST) IV‐B (contains a high to moderate relative abundance of Gardnerella vaginalis) shows a similar pregnant ratio (48.09%) with I‐A and III‐A, and the pregnant women in this CST have a higher abundance of Lactobacillus species. Metagenome analysis of 71 samples shows that nonpregnant women are detected with more antibiotic‐resistance genes, and Proteobacteria and Firmicutes are the main hosts. The inherent differences within and between women in different infertility groups suggest that vaginal microbes might be used to detect infertility and potentially improve IVF outcomes.

Different from the direct delivery of chemodynamic agents into tumor tissue for chemodynamic therapy (CDT), this work reports the fabrication of heterojunction sonosensitizers (CD/TiSe2) for the in situ generation of chemodynamic agents by responding to tumor microenvironment (TME), realizing the in situ CDT‐enhanced sono‐immunotherapy. The in situ redox of TiSe2 in acidic TME leads to the formation of TiOxSe2−x containing Se (0), selenate, and Ti3+/Ti4+ redox couple, which can facilitate in situ CDT through a Ti3+‐mediated Fenton‐like reaction and consume overexpressed glutathione (GSH) via a Ti4+‐mediated GSH depletion. Moreover, Se ions generated through the in situ redox process promote the maturation of dendritic cells, consequently activating the adaptive immune responses. In another aspect, the construction of heterojunctions within carbon dots and TiSe2 improves the reactive oxygen species (ROS) generation efficiency of TiSe2 in a cascaded manner, which enhances the sonodynamic activity and amplifies the chemodynamic performance. More importantly, the ROS produced by in situ CDT and sonodynamic therapy efficiently triggers immunogenic cell death through a synergistic therapy based on the elicitation of antitumor immunity with the aid of an immune checkpoint blockade. This work thus provides a distinct paradigm of transition metal selenide‐originated in situ Fenton‐like agent generation for in situ CDT‐enhanced sono‐immunotherapy.

BackgroundNurse turnover has become a salient issue in healthcare system worldwide and seriously compromises patient outcomes. Social support is considered an effective contributor to alleviate nurse turnover intention (TI). However, the degree of correlation between social support and nurse TI remains elusive.AimsThis study aims to evaluate the strength of the effectiveness of social support on TI among nurses as well as its potential moderators.DesignThis systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.MethodsTo obtained qualified studies, two researchers searched Embase, PubMed, Web of science, CINAHL, CNKI, WanFang, and Chinese Medical Journal Full Text Database from inception to January 6, 2024. Meta-analysis, publication bias, and sensitivity analysis were carried out on the included studies using CMA 3.0 software, and the moderating effect was verified through meta-analysis of variance (ANOVA).ResultsA total of 38 studies were obtained, involving 63,989 clinical nurses. The comprehensive effect size of the random effect model showed a significant medium negative correlation between social support and TI among nurses (p

Desertification poses a serious threat to ecosystem health, and with global changes, the variability and uncertainty of ecological functions in semi-arid alpine regions are increasing. A pressing issue is quantifying how desertification affects the soil system functions in these areas. However, empirical evidence is still lacking in exploring the interaction between desertification degradation gradients and soil functions under natural conditions by coupling soil physicochemical properties, soil microbiota, and vegetation. For this purpose, we conducted a survey sampling of soil and vegetation at five sites with no, light, moderate, severe and extremely severe desertification in Qinghai Area of Qilian Mountains National Park, China. We introduced a new concept soil health stability (SHS) to represent the actual health status of soil systems in semi-arid alpine regions and assessed the impact of desertification on this stability. We observed that the intensification of desertification has led to a significant decrease in soil organic matter, relative abundance of soil microorganisms, and plant factors. The contributions of plant factors and soil microbiota to SHS showed a negative correlation with the degradation gradient. SHS varied across different degradation gradients, rather than following a single linear relationship, with a relatively rapid decline in the transition from non-desertification to moderate desertification. Our work emphasizes that the coupled contributions of soil physicochemical properties, soil microbiota, and vegetation to SHS. It calls for intensified prevention and treatment of mild and moderate desertification, while providing new methods and deeper scientific understanding for accurately evaluating soil system functions in semi-arid alpine regions.

Abstract Background Apatinib is an oral small‐molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor‐2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC. Methods This retrospective study included 100 human epidermal growth factor receptor‐2 (HER2)‐negative mBC patients who received low‐dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression‐free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS. Results The median follow‐up time for this study was 38.1 months. Among 100 patients with HER2‐negative mBC, 66 were hormone receptor (HR)‐positive/HER2‐negative and 34 were triple‐negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2–6.8 months) and 23.0 months (95% CI, 19.9–26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR‐positive /HER2‐negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety‐five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3–4. The most common Grades 3–4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%). Conclusion Low‐dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2‐negative mBC.

The pervasive use of smartphones, while enhancing accessibility to information and communication, has raised concerns about its potential negative effects on physical and mental health, including the impairment of decision-making abilities. This study investigates the influence of smartphone addiction on decision-making in college students. A sample of 80 individuals aged 17 to 26 was selected and divided into two groups based on their Smartphone Addiction Scale-Short Version (SAS-SV) scores. Participants underwent the Iowa Gambling Task (IGT) to evaluate their decision-making in risky and uncertain conditions, while fNIRS recorded their prefrontal cortex activity. The study found that individuals prone to smartphone addiction tend to make riskier choices in risky situations. However, when faced with decisions based on ambiguity, the smartphone addiction group showed increased brain activity in the dlPFC (specifically in channels 4, 9, and 11) compared to when making risky decisions. Despite this increased brain activation, there was no observable difference in behavior between the addiction-prone and control groups in ambiguous scenarios. Notably, the left dlPFC (e.g., channel 4) exhibited significantly higher activation in the addiction group compared to the control group. Findings suggest that smartphone addiction can detrimentally influence decision-making, behaviorally and neurologically, particularly in uncertain contexts. This study supports the classification of smartphone addiction as a genuine addiction and underscores its significance in psychiatric research. In essence, our research underscores the adverse effects of excessive smartphone use on decision-making processes, reinforcing the necessity to treat smartphone addiction as a pressing public health issue.

Abstract Under physical conditions such as TC = 68 °C, Vanadium dioxide (VO2) undergoes a reversible transformation from a monoclinic phase to a tetragonal rutile phase. This transformation is accompanied by a series of changes in physical properties, including transmittance, conductivity, and refractive index, which make it an excellent functional material. Based on this, VO2 has been extensively researched and applied in the fields of electronics and optics, yielding remarkable results and making it a hot research material. This paper reviews the phase transition mechanisms and optical/electrical properties of VO2, as well as its phase transition hysteresis. From the application perspective, this paper summarizes the modulation content under various external excitations and the element doping effects. Finally, this paper summarizes the classic VO2‐based devices, and points out the development direction and potential of VO2 in optics and electronics. This review provides a systematic summary of VO2, which is useful for its practical applications.

Cancer-associated fibroblasts (CAFs) provide suitable conditions for growth of tumor cell and facilitate tumor progression. Hence, we aimed to identify a CAFs-related gene signature associated with the prognosis of patients with breast cancer (BRCA). We downloaded datasets from Gene Expression Omnibus (GEO) and confirmed the correlation between CAFs infiltration scores and prognosis. By performing weighted gene co-expression network analysis (WGCNA) and Lasso Cox regression analysis, we constructed a four-gene (COL5A3, FN1, POSTN, and RARRES2) prognostic CAFs signature model. Based on the median risk score of CAFs, patients with BRCA were divided into high- and low-risk groups. Compared with low-risk group, patients in high-risk group exhibited a poor prognosis and limited response to immunotherapy. Furthermore, patients with high CAFs risk scores were found to have a detrimental prognosis due to the induction of immunosuppressive cell infiltration, resulting in an immunosuppressive tumor microenvironment. Importantly, we found that CAFs overexpressing FN1 and POSTN significantly promoted the wound healing and invasion ability of tumor cells in vitro validation. Taking together, we identified a four-gene prognostic CAFs signature, which was proven to be a reliable indicator for prognosis and therapeutic efficacy in patients with BRCA. This study provided evidence for novel CAFs-based stromal therapy.

Background: Sarcopenia is a harmful condition common among older adults for which no treatment is available. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (FN14) are known to play important roles in the pathogenesis of sarcopenia. This study investigated alterations in methylation in TWEAK and Fn14 to identify potential targets for the managing sarcopenia. Materials and methods: Through an epidemiological investigation, we detected methylation of CpG islands (CpGs) in TWEAK and Fn14 in community-dwelling older adult of Xinjiang by bisulfite sequencing. Significant CpGs associated with sarcopenia were selected for detection in 152 older individuals by pyrosequencing. Associations between CpG methylation, plasma inflammatory marker levels, and sarcopenia were analyzed. Results: Of 38 CpGs in TWEAK and 30 CpGs in Fn14 detected in 60 individuals, 6 CpGs showed lower methylation in sarcopenia patients compared with control individuals. In 152 older adults, covariance analysis with adjustment for age, gender, triglyceride level, obesity, diabetes, and hypertension showed that the methylation levels of 6 CpGs (CpG8, CpG12, CpG13, CpG20 and CpG21of TWEAK, and CpG24 of Fn14) were significantly lower in sarcopenia patients than in control individuals. With adjustment for additional confounding factors, covariate variance analysis showed that plasma TWEAK, TNF-α and IL-10 levels in the sarcopenia group were significant higher than those in the control group (P = 0.007, P

Abstract N‐glycosylation has important implications for the physicochemical properties and biochemical activity of breast milk proteins. However, an in‐depth characterization of site‐specific N‐glycans in breast milk serum proteins is lacking. In this study, 875 site‐specific N‐glycans attached to 114 serum glycoproteins from breast colostrum (BC) and 427 site‐specific N‐glycans attached to 60 serum glycoproteins from breast mature milk (BM) were identified and quantified using label‐free site‐specific glycoproteomics. Among them, 24 site‐specific N‐glycans mapping to 11 N‐glycosites on 9 glycoproteins were significantly increased, and 76 site‐specific N‐glycans mapping to 19 N‐glycosites on 13 glycoproteins were significantly decreased. Gene ontology annotation analysis showed that BC and BM serum N‐glycoproteins were mainly enriched in complement activation, classical pathway, extracellular exosome part, and immunoglobulin receptor binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that BC and BM serum N‐glycoproteins were mainly involved in the PI3K‐Akt signaling pathway. Additionally, breast milk serum N‐glycoproteins carried fucosylated core structures as well as Lewis and sialylated branch structures that may contribute to neonatal retinal homeostasis. These results provide a molecular basis for understanding the unique biological activities of breast milk serum N‐glycoproteins.

Abstract The serine/threonine kinase, PINK1, and the E3 ubiquitin ligase, Parkin, are known to facilitate LC3-dependent autophagosomal encasement and lysosomal clearance of dysfunctional mitochondria, and defects in this process contribute to a variety of cardiometabolic and neurological diseases. Although recent evidence indicates that dynamic actin remodeling plays an important role in PINK1/Parkin-mediated mitochondrial autophagy (mitophagy), the underlying signaling mechanisms remain unknown. Here, we identify the RhoGAP GRAF1 (Arhgap26) as a PINK1 substrate that regulates mitophagy. GRAF1 promotes the release of damaged mitochondria from F-actin anchors, regulates mitochondrial-associated Arp2/3-mediated actin remodeling and facilitates Parkin-LC3 interactions to enhance mitochondria capture by autophagosomes. Graf1 phosphorylation on PINK1-dependent sites is dysregulated in human heart failure, and cardiomyocyte-restricted Graf1 depletion in mice blunts mitochondrial clearance and attenuates compensatory metabolic adaptations to stress. Overall, we identify GRAF1 as an enzyme that coordinates cytoskeletal and metabolic remodeling to promote cardioprotection.

Abstract Background Avian bornavirus (ABV) is a neurotropic virus, it has been established as the primary causative agent of proventricular dilatation disease (PDD). However, substantial international trade and transnational trafficking of wild birds occur, potentially enabling these birds to harbor and transmit pathogens to domestic poultry, adversely affecting their well-being. Real-time RT-PCR was employed to detect the presence of PaBV-4 in parrots imported to China in 2022. Results In 2022, a total of 47 cloacal swabs from 9 distinct species of parrots were collected at the Wildlife Rescue Monitoring Center in Guangdong, China. The purpose of this collection was to detect the presence of PaBV-4. Using real-time PCR techniques, it was determined that the positive rate of PaBV-4 was 2.12% (1 out of 47) in parrots. The PaBV-4 virus was detected in a Amazona aestiva that had been adopted for one month. Conversely, all other species tested negative for the virus. Subsequently, the whole genome of the PaBV-4 GD2207 strains was sequenced, and the homology and genetic evolution between these strains and previously published PaBV-4 strains on GenBank were analyzed using DNAStar and MEGA7.0 software. The findings revealed that the full-length genome of PaBV-4 consisted of 8915 nucleotides and encoded six proteins. Additionally, it exhibited the highest nucleotide similarity (99.9%) to the GZ2019 strain, which causes death and severe clinical symptoms in Aratinga solstitialis. Furthermore, when compared to other strains of PaBV-4, the GD2207 strain demonstrated the highest amino acid homology with GZ2019. The phylogenetic analysis demonstrated that the GD2207 strain clustered with various strains found in Japanese, American, and German parrots, indicating a close genetic relationship with PaBV-4, but it revealed a distant relationship with PaBV-5 Cockg5 from America. Notably, the GD2207 was closely associated with the GZ2019 strain from Aratinga solstitialis in China. Conclusion This study presents the preliminary identification of PaBV-4 in Amazona aestiva parrots, emphasizing its importance as the predominant viral genotype linked to parrot infections resulting from trade into China. Through genetic evolution analysis, it was determined that the GD2207 strain of PaBV-4 exhibits the closest genetic relationship with GZ 2019 (Aratinga solstitialis, China), M14 (Ara macao, USA), AG5 (Psittacus erithacus, USA) and 6758 (Ara ararauna, Germany) suggesting a shared ancestry.

AbstractAs an autoimmune disease of the colon, the incidence of ulcerative colitis (UC) remains high. Carbon dots (CDs), a new type of nanomaterials, display excellent biological activity and are expected to inspire a new treatment for UC. A green method was used to carbonise rhei radix rhizoma (RRR) and extract CDs to study their anti-ulcer activity. The RRR-based carbon dots (RRR-CDs) were characterised by electron microscopy, optical techniques, and other techniques. The results indicated RRR-CDs have abundant chemical groups, excellent solubility and tiny size (1.374 nm–4.533 nm), which may be conducive to the exertion of inherent activity. Using a classic dextran sodium sulphate (DSS)-induced UC mouse model, for the first time, it was demonstrated RRR-CDs have significant anti-ulcerative activity in improving DAI score (from 2.8 to 1.6), colon length (4.15 to 6.08), and histopathology in mice. The underlying mechanisms of anti-ulcerative activity may be related to haemostatic, antioxidant, and anti-inflammatory activities to protect the mucosal barrier. RRR-CDs have symptomatic and potential mechanisms of treatment and are expected to become a candidate drug for the treatment of UC. This not only further expands the basis for the biological activity of CDs, but provides a potential treatment plan for solving thorny diseases in clinical practice.

Abstract The HIV-1 Tat protein hijacks the Super Elongation Complex (SEC) to stimulate viral transcription and replication. However, the mechanisms underlying Tat activation and inactivation, which mediate HIV-1 productive and latent infection, respectively, remain incompletely understood. Here, through a targeted complementary DNA (cDNA) expression screening, we identify PRMT2 as a key suppressor of Tat activation, thus contributing to proviral latency in multiple cell line latency models and in HIV-1-infected patient CD4+ T cells. Our data reveal that the transcriptional activity of Tat is oppositely regulated by NPM1-mediated nucleolar retention and AFF4-induced phase separation in the nucleoplasm. PRMT2 preferentially methylates Tat arginine 52 (R52) to reinforce its nucleolar sequestration while simultaneously counteracting its incorporation into the SEC droplets, thereby leading to its functional inactivation to promote proviral latency. Thus, our studies unveil a central and unappreciated role for Tat methylation by PRMT2 in connecting its subnuclear distribution, liquid droplet formation, and transactivating function, which could be therapeutically targeted to eradicate latent viral reservoirs.

Carotenoids are involved in the formation of plant leaf color as well as photosystem photoprotection. This study showed that blue light significantly induced up-regulation of the total carotenoid content in the inner leaves of orange-head Chinese cabbage (OHCC). Furthermore, the transcriptomic analysis revealed that blue light treatment induced up-regulation of genes in photosynthesis (BrHY5-2, BrCOP1 and BrDET1) and the methylerythritol 4-phosphate pathways (BrGGPS, BrDXS and BrHDR) upstream of the carotenoid metabolic pathway. Carotenoid metabolomic analysis revealed that the accumulation of several orange and red carotenoids (lycopene, zeaxanthin, β-carotene, lutein, and β-cryptoxanthin) after blue light treatment contributed to the deepening of the leaf coloration, suggesting that short-term blue light treatment could be used to boost nutritional quality. The light signal gene BrHY5-2 participated in the blue light-induced transcriptional regulation of carotenoid biosynthesis in OHCC. Overexpression of BrHY5-2 in Arabidopsis significantly increased the total carotenoid content and the sensitivity to blue light. The above findings revealed new insights about blue-light-induced carotenoid synthesis and accumulation in OHCC lines. They suggested a new engineering approach to increase the nutritional value of vegetables.

Background:Cervical cancer (CC) is a prevalent gynecological carcinoma, and patients infected with human papillomavirus (HPV) have a higher morbidity rate.Aims:To explore the effects of ETS-like transcription factor 4 (ELK4) in patients with HPV+ CC.Study design:In vitro cell lines and human-sample study.Methods:The ELK4 levels in human tissue (65 HPV+ CC tissue and 25 HPV− normal cervical tissue) and cell lines (human cervical epithelial immortalized cell line H8 and CC cell lines HeLa [HPV18], CaSki [HPV16], and SiHa [HPV−]) were quantified using qRT-PCR and western blot assay. ELK4 knockdown transfection was effective and confirmed by western blotting. The MTT and EDU assays were used to evaluate cell viability and proliferation, respectively. Flow cytometry was used to detect the CC cell cycle stage. Stem cell markers, such as cluster of differentiation 133 (CD133), CD44, and aldehyde dehydrogenase 1, and the cervicospheres formed were measured. ChIP-qPCR and luciferase activity experiments were used to assess the bond between ELK4 and F-box protein 22 (FBXO22).Results:ELK4 was highly expressed in the HPV+ CC tissue. CC cells with ELK4 knockdown had lower viability and proliferation than the control cells. ELK4 knockdown blocked the progression of the cell cycle from G1 to S phase. ELK4 knockdown suppressed the stem cell-like characteristics of the HPV+ CC cells. ELK4 bonded with the FBXO22 promoter, inhibiting the levels of phosphatase and tensin homolog (PTEN).Conclusion:ELK4 facilitated cell cycle progression and stem cell-like characteristics by regulating the FBXO22/PTEN axis. Thus, ELK4 could be a potential therapeutic target to arrest the progress of HPV-associated CC.

Sugar–sugar glycosyltransferases play important roles in constructing complex and bioactive saponins. Here, we characterized a series of UDP-glycosyltransferases responsible for biosynthesizing the branched sugar chain of bioactive steroidal saponins from a widely known medicinal plant Paris polyphylla var. yunnanensis. Among them, a 2′-O-rhamnosyltransferase and three 6′-O-glucosyltrasferases catalyzed a cascade of glycosylation to produce steroidal diglycosides and triglycosides, respectively. These UDP-glycosyltransferases showed astonishing substrate promiscuity, resulting in the generation of a panel of 24 terpenoid glycosides including 15 previously undescribed compounds. A mutant library containing 44 variants was constructed based on the identification of critical residues by molecular docking simulations and protein model alignments, and a mutant UGT91AH1Y187A with increased catalytic efficiency was obtained. The steroidal saponins exhibited remarkable antifungal activity against four widespread strains of human pathogenic fungi attributed to ergosterol-dependent damage of fungal cell membranes, and 2′-O-rhamnosylation appeared to correlate with strong antifungal effects. The findings elucidated the biosynthetic machinery for their production of steroidal saponins and revealed their potential as new antifungal agents.

The Resource for Coronavirus 2019 (RCoV19) is an open-access information resource dedicated to providing valuable data on the genomes, mutations, and variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this updated implementation of RCoV19, we have made significant improvements and advancements over the previous version. Firstly, we have implemented a highly refined genome data curation model. This model now features an automated integration pipeline and optimized curation rules, enabling efficient daily updates of data in RCoV19. Secondly, we have developed a global and regional lineage evolution monitoring platform, alongside an outbreak risk pre-warning system. These additions provide a comprehensive understanding of SARS-CoV-2 evolution and transmission patterns, enabling better preparedness and response strategies. Thirdly, we have developed a powerful interactive mutation spectrum comparison module. This module allows users to compare and analyze mutation patterns, assisting in the detection of potential new lineages. Furthermore, we have incorporated a comprehensive knowledgebase on mutation effects. This knowledgebase serves as a valuable resource for retrieving information on the functional implications of specific mutations. In summary, RCoV19 serves as a vital scientific resource, providing access to valuable data, relevant information, and technical support in the global fight against COVID-19. The complete contents of RCoV19 are available to the public at https://ngdc.cncb.ac.cn/ncov/.