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Abstract Background Chronic infection by Helicobacter pylori strains expressing cytotoxin-associated gene A (CagA) are the strongest risk factor for gastric cancer. CagA can be classified into East Asian-type and Western-type (CagAE and CagAW), with CagAE being more closely associated with gastric cancer. This study aimed to investigate the impact of CagAE on intracellular signaling pathways to explain its high oncogenicity. Results Mutant H. pylori strains expressing either CagAE or CagAW were generated by transforming CagAE/W-expression plasmid into CagA-deleted G27 strain (G27ΔCagA). In human gastric epithelial cells (GES-1) infection, CagAE induced more severe cytopathic changes, including higher interleukin-8 (IL-8) secretion, reduced cell viability, more pronounced “hummingbird phenotype” alterations, and increased cell migration and invasion compared to CagAW. Transcriptome analysis revealed that CagAE had a stronger effect on the up-regulation of key intracellular processes, including tumor necrosis factor-ɑ (TNF-ɑ) signal pathway via nuclear factor kappa-B (NF-κB), inflammatory response, interferon-γ (IFN-γ) response, hypoxia, ultraviolet (UV) response, and Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) signaling. A significant upregulation of hypoxia-related genes was a notable feature of CagAE. GES-1 cells infected with CagAE exhibited more severe intracellular hypoxia and higher levels of reactive oxygen species (ROS) than those infected with CagAW. Inhibition of hypoxia-inducible factor-1α (HIF-1α), which blocks hypoxia signaling, mitigated CagAE-induced cell migration, emphasizing the role of hypoxia in mediating CagAE effects. Conclusions The study provides transcriptome evidence of CagA-associated intracellular regulation during H. pylori infection, demonstrating that CagAE exerts stronger effects on intracellular signaling than CagAW. These findings offer insights into the heightened carcinogenic potential of CagAE in H. pylori-induced gastric cancer.

Abstract Angiogenesis following cerebral ischemia is crucial for restoring blood supply to the ischemic region. Extracellular vesicles (EVs) derived from endothelial progenitor cells (EPCs) offer potential therapeutic benefits in the treatment of cerebral ischemia. Houshiheisan (HSHS) has been shown to improve clinical outcomes in ischemic stroke patients, reduce cerebral ischemic damage in rats, and protect endothelial cells. However, the potential effects of HSHS-modified EPC-derived EVs (EVsHSHS) for cerebral ischemia remain unexplored. This study investigated the impact of EVsHSHS on angiogenesis using rats with permanent middle cerebral artery occlusion (pMCAO) and brain microvascular endothelial cells (BMECs) subjected to oxygen-glucose deprivation (OGD). Results demonstrated that EVsHSHS promoted the proliferation, migration, and tube formation of BMECs in vitro. In vivo, high doses of EVsHSHS exhibited better performance than equivalent doses of unmodified EPC-derived EVs in reducing cerebral infarction volume, improving cortical blood perfusion, decreasing neurological deficit scores, and increasing cortical microvessel density at day 7 post-modeling. The pro-angiogenic effects of EVsHSHS following cerebral ischemia were associated with the regulation of miR-126 and the PIK3R2/PI3K/AKT pathway.

Abstract Background Ages of 0–3 years are critical stages for children’s neurodevelopment. However, the impact of the home nurturing environment on early childhood neurodevelopment remains unclear. Objective To explore the role of the home nurturing environment on early childhood neurodevelopment and to provide evidence of an association between fostering quality home nurturing and achieving optimal neurodevelopment. Participants and setting An online cross-sectional survey using the stratified sampling method was conducted from 16 June, 2021 to 18, February, 2022 in all 13 communities of Minhang District, Shanghai. A total of 2,402 children aged 0–3 years with balanced sex distribution were included. Methods The quality of home nurturing environments was measured using validated Child Home Nurture Environment Scales. Neurodevelopment was measured using the Ages and Stages Questionnaire - Third edition (ASQ-3). Generalized Linear Mixed Modeling was used to analyze the association between the quality of home nurturing environments and neurodevelopment. Results Among children aged 0–1, neglect or restriction was reported as the most prevalent problem (8.02%) among home nurturing environment dimensions, and was associated with an increased risk of suspected fine motor development delay (OR = 2.82, 95% CI: 1.18–6.69, P = 0.019). Among children aged 1–3, inadequate parental warmth, as the foremost (16.10%) problem, was associated with an increased risk of suspected gross motor development delay (OR = 4.12, 95% CI: 1.35–12.53, P = 0.013) and suspected personal-social development delay (OR = 12.50, 95%CI: 1.48-105.36, P = 0.020). Conclusions Poor home nurturing environments were associated with an increased risk of suspected early childhood neurodevelopment delay. There exists a need for services to guide for establishing a quality home nurturing environment.

H10 subtype avian influenza viruses (AIV) have been circulating in China for 40 years. H10 AIVs in China have expanded their host range from wild birds to domestic poultry and mammals, even human. Most of the H10 subtype AIVs reported in China were isolate from the southeast part. We isolated an H10N3 AIV, A/Chicken/Liaoning/SY1080/2021 (SY1080), from live poultry market (LPM) in Liaoning Province of the Northeast China. SY1080 replicated efficiently in mice lungs and nasal turbinates without prior adaptation. We systematically compared SY1080 with other H10 subtype isolates in China. Phylogenetic analysis showed that SY1080 and most of the H10 strains belonged to the Eurasian lineage. H10 AIVs in China have formed 63 genotypes. SY1080 as well as the H10N3 strains from human infections belonged to G60 genotype. H10Nx AIV acquired multiple mammalian adaptive and virulence related mutations during circulation and the recent reassortants derived internal genes from chicken H9N2 AIVs. The H10Nx subtypes AIVs posed potential threat to public health. These results suggested we should strengthen the surveillance and evaluation of H10 subtype strains.

Abstract A nomogram to estimate the risk of linezolid-induced thrombocytopenia in patients with renal impairment is not available. The aim of the study is to develop a nomogram for predicting linezolid-induced thrombocytopenia in patients with renal impairment and to investigate the incremental value of PNU-142300 concentration beyond clinical factors and linezolid trough concentration (Cmin) for risk prediction. Logistic regression was used to identify independent risk factors for linezolid-induced thrombocytopenia in patients with renal impairment and nomograms were established. The performance of the nomograms was assessed in terms of area under the receiver operating characteristic curve (AUROC), net reclassification improvement (NRI), integrated discrimination improvement (IDI) , decision curve analysis (DCA) and calibration. Internal validation and external validation of the nomograms were also performed. Four nomograms were created: nomogram A including total bilirubin, creatinine clearance and concomitant mannitol use; nomogram B containing linezolid Cmin additionally; nomogram C containing total bilirubin, concomitant mannitol use, linezolid Cmin, and PNU142300 concentration; nomogram D including total bilirubin, concomitant mannitol use, and PNU142300 concentration. Nomogram C improved the prediction performance than nomogram A (AUROC 0.881 vs. 0.749; NRI 0.290; IDI 0.226) and nomogram B (AUROC 0.881 vs. 0.812; NRI 0.152; IDI 0.130) in the training cohort. DCA analysis showed that nomogram C yielded a greater net benefit. Compared with nomogram A and nomogram B, nomogram C also showed superior discriminatory efficacy, good calibration and clinical usefulness in the external validation cohort. The nomogram containing PNU-142300 concentration and linezolid Cmin had better predictive capability than that containing linezolid Cmin for predicting linezolid-induced thrombocytopenia in patients with renal impairment.

Abstract To investigate the role and molecular mechanism of miR-126 in unilateral ureteral occlusion (UUO). We used bioinformatics to analyse miRNAs specifically expressed in UUO. The mouse model of UUO was established using RAW264.7 cells cultured in vitro and in vivo. The mice were divided into control group, miR-126-NC (negative control) group and miR-126-KD (knockdown) group. Then the relative expression of miR-126 was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), the renal fibrosis was detected by Masson staining, and the protein expression of CD68, collagen I and collagen III in the kidney was detected by immunofluorescence assay. Immunohistochemistry detects α-SMA expression. Moreover, Western blotting was performed to measure the expressions of p-PI3K, CD163, CD206, CD86, iNOS, IL-1β, p-FAK, p-Rac-1, p-IRS-1 and MMP9. The relative fluorescence intensity of F-actin and p-FAK was detected by immunofluorescence assay, and the phagocytosis ability of macrophages was determined by phagocytosis assay with fluorescent microspheres. Bioinformatics analysis reveals miR-126-specific overexpression in UUO. Successful transfection of miR-126-NC and miR-126-KD was confirmed by RT-PCR. The selective reduction of miR-126 was validated by Masson, immunohistochemistry and immunofluorescence staining to decrease the area of UUO-induced renal fibrosis and to lower the expression of CD68, α-SMA, collagen I, and collagen III. The reduction of iNOS expression may also be achieved with selective knockdown of miR-126, as verified by cell tests. enhances the phagocytic ability of macrophages and the expression of p-PI3K, CD206, p-FAK, F-actin, p-Rac-1, p-IRS-1 and MMP9. MiR-126 can inhibit the PI3K signaling pathway, promote M1 macrophage polarization, and suppress the activation of FAK and Rac-1, thus accelerating the progression of UUO.

Abstract Retinal neovascularisation is a major cause of blindness in patients with proliferative diabetic retinopathy (PDR). It is mediated by the complex interaction between dysfunctional ganglion cells, microglia, and vascular endothelial cells. Notably, retinal microglia, the intrinsic immune cells of the retina, play a crucial role in the pathogenesis of retinopathy. In this study, we found that lysophosphatidylserines (LysoPS) released from injured ganglion cells induced microglial extracellular trap formation and retinal neovascularisation. Mechanistically, LysoPS activated the GPR34-PI3K-AKT-NINJ1 signalling axis by interacting with the GPR34 receptor on the microglia. This activation upregulated the expression of inflammatory cytokines, such as IL-6, IL-8, VEGFA, and FGF2, and facilitated retinal vascular endothelial cell angiogenesis. As a result, inhibition of the GPR34-PI3K-AKT-NINJ1 axis significantly decreased microglial extracellular trap formation and neovascularisation by suppressing LysoPS-induced microglial inflammatory responses, both in vitro and in vivo. This study reveals the crucial role of apoptotic ganglion cells in activating microglial inflammation in PDR, thereby enhancing our understanding of the pathogenesis of retinal neovascularisation.

Abstract Owing to the widespread integration of renewable distributed energy resources (DERs), the system frequency stability has been jeopardized by the non‐inertial and stochastic units caused by power electronic devices. The integrated energy system (IES) that combines multi‐vector energy resources can provide energy compensation among sub‐systems in a coordinated fashion to further alleviate the volatility on the electric grid. Under the framework of IES, a virtual power plant (VPP) can aggregate multi‐entities and multi‐vector energy resources to participate in the frequency regulation service while pursuing profit maximization. A three‐stage optimal scheduling model of IES‐VPP that fully considers the cycle life of energy storage systems (ESSs), bidding strategies and revenue settlement has been proposed in this paper under the modified PJM frequency regulation market framework to motivate the aggregated resources to respond to the frequency regulation market actively. The simulation results under various scenarios have verified the feasibility and effectiveness of the proposed model through techno‐economic analysis, the advantages of IES‐VPP have been demonstrated compared with a single vector energy system.

Abstract The placenta, a temporary but essential organ for gestational support, undergoes intricate morphological and functional transformations throughout gestation. However, the spatiotemporal patterns of gene expression underlying placentation remain poorly understood. Utilizing Stereo-seq, we constructed a Mouse Placentation Spatiotemporal Transcriptomic Atlas (MPSTA) spanning from embryonic day (E) 7.5 to E14.5, which includes the transcriptomes of large trophoblast cells that were not captured in previous single-cell atlases. We defined four distinct strata of the ectoplacental cone, an early heterogeneous trophectoderm structure, and elucidated the spatial trajectory of trophoblast differentiation during early postimplantation stages before E9.5. Focusing on the labyrinth region, the interface of nutrient exchange in the mouse placenta, our spatiotemporal ligand–receptor interaction analysis unveiled pivotal modulators essential for trophoblast development and placental angiogenesis. We also found that paternally expressed genes are exclusively enriched in the placenta rather than in the decidual regions, including a cluster of genes enriched in endothelial cells that may function in placental angiogenesis. At the invasion front, we identified interface-specific transcription factor regulons, such as Atf3, Jun, Junb, Stat6, Mxd1, Maff, Fos, and Irf7, involved in gestational maintenance. Additionally, we revealed that maternal high-fat diet exposure preferentially affects this interface, exacerbating inflammatory responses and disrupting angiogenic homeostasis. Collectively, our findings furnish a comprehensive, spatially resolved atlas that offers valuable insights and benchmarks for future explorations into placental morphogenesis and pathology.

Abstract Background With the rapid development of animal husbandry, the demand for protein feed resources is increasing. Cottonseed meal (CSM) and soybean meal (SBM) are rich sources of protein. However, their application is limited due to the existence of anti-nutrients, which can be harmful to the digestion and absorption. A strain of Bacillus subtilis (Mafic-Y7) was isolated from digesta of intestines of Tibetan pigs. The strain showed high protease activity, which helps in degrading proteinic anti-nutritional factors in grain meal and in vitro degradation of free gossypol. In order to better understand this isolated strain, whole genome of Mafic-Y7 strain was sequenced and analyzed. Different effects on various grain meals were identified. Result The GC-depth Poisson distributions showed no bias suggesting high-quality genome assembly of Mafic-Y7. The whole genome sequencing showed that one chromosome with 4,248,845 base pairs(bp)and the genes total length with 3,736,524 bp was predicted in Mafic-Y7. Additionally, Mafic-Y7 possessed 4,254 protein-coding genes, and several protease genes were annotated by aligning them with databases. There are 55 protease genes, one phytase gene and one laccase gene were annotated in the gene sequence of Mafic-Y7. The average nucleotide identity between Mafic-Y7 and the GCA-000009045.1 homologous genome was 0.9938, suggesting a close genetic relationship between them at the species level. Compared with the closest four whole genomes, Mafic-Y7 was annotated the most abundant of protease genes (55 genes). The fermentation supernatant of Mafic-Y7 could increase the content of small peptides, water-soluble proteins, and acid-soluble proteins in vitro by 411%, 281% and 317% in SBM and 420%, 257% and 338% in CSM. After fermentation in grain meal by Mafic-Y7, the degradation rate of anti-nutritional factors in SBM, such as trypsin inhibitor, glycinin, and β-conglycinin was greater than 70%, and lectin was greater than 30%. The degradation rates of anti-nutritional factors in CSM, such as gossypol and phytic acid, were 82% and 26%, respectively.

Abstract Marine heatwaves have attracted great attention for their devastating impacts on marine organisms. However, the influence of marine heatwaves on phytoplankton community structure, a key aspect of pelagic ecosystems, remains elusive, especially in the biologically productive eastern boundary upwelling systems. Here, using a combination of multi-satellite observations and model outputs, we discover that phytoplankton in these upwelling systems exhibit not only a marked reduction in biomass (~50%), but also a significant shift toward smaller species in community structures during marine heatwaves, featuring a substantially increased/decreased dominance in picophytoplankton/microphytoplankton. This change in community structure is positively related to the intensity and duration of marine heatwaves, and is likely a result of community competition under reduced nutrient supply due to weakened coastal upwelling associated with poleward wind anomalies. These findings invite us to rethink the dominance of phytoplankton in the eastern boundary upwelling systems under extreme conditions, and may have important implications for local fisheries and carbon cycle under the ongoing warming.

Abstract Asymptomatic intracranial atherosclerotic stenosis (aICAS) is a major risk factor for cerebrovascular events. The study aims to construct and validate a nomogram for predicting the risk of aICAS. Participants who underwent health examinations at our center from September 2019 to August 2023 were retrospectively enrolled. The participants were randomly divided into a training set and a testing set in a 7:3 ratio. Firstly, in the training set, least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were performed to select variables that were used to establish a nomogram. Then, the receiver operating curves (ROC) and calibration curves were plotted to assess the model’s discriminative ability and performance. A total of 2563 neurologically healthy participants were enrolled. According to LASSO-Logistic regression analysis, age, fasting blood glucose (FBG), systolic blood pressure (SBP), hypertension, and carotid atherosclerosis (CAS) were significantly associated with aICAS in the multivariable model (adjusted P

Abstract Against the backdrop of digitization and global warming, fintech plays a crucial role in accelerating the growth of green finance, driving innovation in the financial industry, and catalyzing the low-carbon transformation of economic activities. This paper utilizes city panel data from 2007 to 2019 to examine the direct impact of fintech on carbon emission efficiency (CEE), the transmission channels of green technological innovation and green finance, and the spatial spillover effects, using dynamic panel models, mediation effect models, and dynamic spatial Durbin models (SDM). The study finds that: (i) Fintech significantly improves CEE, and this conclusion remains robust after accounting for potential endogeneity issues and conducting robustness tests. (ii) Mechanism analysis reveals that green finance and green technological innovation are the primary channels through which fintech influences CEE. (iii) Results from the dynamic SDM model indicate that fintech has a significant positive spatial spillover effect on CEE, with the long-term spillover effect being smaller than the short-term spillover effect. (iv) Heterogeneity analysis reveals that fintech’s improvement effect on CEE is mainly evident in eastern regions, emerging first-tier and first-tier cities, and non-resource-based cities. Our research provides new insights for policymakers on achieving China’s dual-carbon goals through the promotion of fintech development, green finance, and green technological innovation. It also aids in the coordinated development of fintech among cities and the formulation of differentiated policies, providing a theoretical foundation and empirical support for future research.

Abstract Background As a potential model organism for studies of environmental and cell biology, Paramecium duboscqui is a special euryhaline species of Paramecium that can be found in fresh, brackish, or marine water in natural salinity ranges between 0‰ and 33‰. However, the genome information as well as molecular mechanisms that account for its remarkable halotolerant traits remain extremely unknown. To characterize its genome feature, we combined PacBio and Illumina sequencing to assemble the first high-quality and near-complete macronuclear genome of P. duboscqui. Meanwhile, comparative transcriptomic profiles under different salinities gave underlying insight into the molecular mechanism of its adaptations to environmental salinity. Results The results showed that the MAC genome of P. duboscqui comprises 160 contigs, with 113 of them possessing telomere (~ 28.82 Mb haploid genome size). Through comparative genomic analyses with the other ciliate, we found that gene families encoding transmembrane transporter proteins have been expanded in P. duboscqui, showing enormous potential in salinity adaptation. Like other Paramecium, P. duboscqui utilizes TGA as its only termination codon and has reassigned TAA and TAG to encode glutamine. P. duboscqui showed different growth rates under different salinities, with an optimum growth rate in 5‰ salinity. A comparison of the transcriptomic profiles among P. duboscqui grown under different concentrations showed that genes involved in protein folding, oxygen respiration, and glutathione-dependent detoxification were upregulated in the high-salt group, whereas genes encoding DNA-binding proteins and transcription factors were upregulated in the low-salt group, suggesting distinct mechanisms for responding to low and high salinity. Weighted gene coexpression network analysis (WGCNA) linked the hub genes expressed at 30‰ salinity to cysteine-type peptidase activity, lipid transfer, sodium hydrogen exchange, and cell division, with the hub genes expressed at 0‰ salinity involved in transmembrane transport and protein localization. Conclusions This study characterizes a new euryhaline model Paramecium, provides novel insights into Paramecium evolution, and describes the molecular mechanisms that have allow P. duboscqui to adapt to different osmotic environments.

Abstract Background The post COVID-19 health condition of Chinese residents infected with Omicron is not clear after the change of epidemic prevention policies. This study aimed to clarify the epidemiology and associated factors about health status of rehabilitation patients. Methods A quick questionnaire study based on C19-YRSm was conducted in mainland China through internet from May 1, 2023, to May 7, 2023. Chinese native speakers infected with Omicron variant agreed to participate were included. Persisting symptom and living habits were simultaneously inquired. Logistic regression analysis was used to identify the associated factors. Results In this study 753 individuals were included. Of whom 57.90% were males, 89.38% did not seek medical service, 99.47% recovered within less than 120 days. Breathlessness (47.68%), cognitive impairment (44.89%), Anxiety/mood changes (33.20%), pain/discomfort (32.94%), fatigue or tiredness not improved by rest (32.27%) and post-exertional malaise (30.01%) were the top reported key symptoms. Less than 10% respondents reported functional limitations. The prevalence of fever was reported greater than that of other symptoms, with dry eyes at 14.87%, appetite change at 14.34%, and hair loss at 12.22%. Middle age (OR: 2.353, 95%CI: 1.171 ~ 4.729), underlying diseases (OR: 2.293, 95%CI: 1.216 ~ 4.324), severe key symptom (OR: 6.168, 95%CI: 1.376 ~ 27.642) and at least one other symptom (OR: 1.847, 95%CI: 1.225 ~ 2.718)during the recovery were the risk factors of poor overall health after infection (current overall health score

Abstract The irradiated tumor itself represents an opportunity to establish endogenous in situ vaccines. However, such in situ cancer vaccination (ISCV) triggered by radiation therapy (RT) alone is very weak and hardly elicits systemic anticancer immunity. In this study, we develop two-dimensional risedronate-manganese nanobelts (RMn-NBs) as an adjuvant for RT to address this issue. RMn-NBs exhibit good T2 magnetic resonance imaging performance and enhanced Fenton-like catalytic activity, which induces immunogenic cell death. RMn-NBs can inhibit the HIF-1α/VEGF axis to empower RT and synchronously activate the cGAS/STING pathway for promoting the secretion of type I interferon, thereby boosting RT-triggered ISCV and immune checkpoint blockade therapy against primary and metastatic tumors. RMn-NBs as a nano-adjuvant for RT show good biocompatibility and therapeutic efficacy, presenting a promising prospect for cancer radiotherapy and immunotherapy.

Abstract Background Quality caregiver-infant interaction is crucial for infant growth, health, and development. Traditional methods for evaluating the quality of caregiver-infant interaction have predominantly relied on rating scales or observational techniques. However, rating scales are prone to inaccuracies, while observational techniques are resource-intensive. The utilization of easily collected medical records in conjunction with machine learning techniques offers a promising and viable strategy for accurate and efficient assessment of caregiver-infant interaction quality. Methods This study was conducted at a follow-up outpatient clinic at two tertiary maternal and infant health centers located in Shanghai, China. 68 caregivers and their 3-15-month-old infants were videotaped for 3–5 min during playing interactions in non-threatening environment. Two trained experts utilized the Infant CARE-Index (ICI) procedure to assess whether the caregivers were sensitive or not in a dyadic context. This served as the gold standard. Predictors were collected through Health Information Systems (HIS) and questionnaires, which included accessible features such as demographic information, parental coping ability, infant neuropsychological development, maternal depression, parent-infant interaction, and infant temperament. Four classification models with fivefold cross-validation and grid search hyperparameter tuning techniques were employed to yield prediction metrics. Interpretable analyses were conducted to explain the results. Results The score of sensitive caregiver-infant interaction was 6.34 ± 2.62. The Random Forest model gave the best accuracy (83.85%±6.93%). Convergent findings identified infant age, care skills of infants, mother age, infant temperament-regulatory capacity, birth weight, positive coping, health-care-knowledge-of-infants, type of caregiver, MABIS-bonding issues, ASQ-Fine Motor as the strongest predictors of interaction sensitivity between infants and their caregiver. Conclusions The proposed method presents a promising and efficient approach that synergistically combines rating scales and artificial technology to detect important features of caregiver-infant interactions. This novel approach holds several implications for the development of automatic computational assessment tools in the field of nursing studies.

To study the quality discrepancy of jujube vinegar brewed from different jujube varieties, six types of jujube vinegar made from different varieties of jujube were evaluated by the analysis of basic physicochemical components (such as pH, total acid, total phenol and total flavone), color, in vitro functional activity (antioxidant capacity and lipid-lowering ability), organic acids, amino acids, and volatile aroma components, combined with electronic nose and sensory evaluation. The results showed that there were significant differences in the quality of jujube vinegar brewed from different jujubes. In terms of physical and chemical analysis, the total acid and total flavonoids of Xinjiang jujube vinegar were the highest, which were 54.87 g/L and 1168.84 mg RE/L, respectively. By contrast, the total phenolic content of Xinjiang Jun-jujube jujube vinegar was the highest, which was 1815.63 mg GAE/L. Henan Lingbao jujube vinegar and Fuping jujube vinegar had better color values. Xinjiang Jujube vinegar showed the best antioxidant and lipid lowering activities. Fuping jujube vinegar had the lowest total organic acid content of 47.07 g/L. Xinjiang gray jujube vinegar and Xinjiang Jun-jujube vinegar had higher essential amino acid and total amino acid content, while Hebei Fuping jujube vinegar had lower amino acid content. A total of 41 volatile aromas were detected in 6 kinds of jujube vinegar, and there were certain differences in the types and contents of volatile aromas contained in different kinds of jujube vinegar. The sensory evaluation showed that all jujubes were suitable for brewing jujube vinegar, among which Xinjiang Hui-jujube vinegar had the best sensory acceptance. In summary, there were certain differences in the quality of 6 kinds of jujube vinegar. The high functional activity of Xinjiang Jun-jujube vinegar made it more suitable as a functional fruit vinegar. Based on the high sensory acceptance of Xinjiang Hui-jujube vinegar, the Xinjiang Hui-jujube would be suitable for the vinegar processing too.

Abstract Background Arecae Semen is a traditional herbal medicine widely used in the medical service and food industry, but in recent years, the carcinogenesis of edible Arecae Semen chewing has aroused comprehensive attention, therefore it is necessary to evaluate its medicinal properties. Increasing evidence has shown that Arecae Semen Compounds (ASC) possess antidepressant ability. This study aimed to evaluate the effectiveness and safety of ASC in the treatment of depression. Methods We retrieved articles in eight databases from their inception to May 2024. Randomized controlled trials (RCTs) comparing the effects of ASC alone or combined with routine treatment in patients with depression were identified. The Cochrane risk of bias (ROB) tool (ROB 2) was used for assessing the ROB in the included trials. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of the evidence for the review outcomes. The outcomes included Hamilton depression rating scale (HAMD) scores, depression-related symptoms, serum dopamine levels, and adverse events. Stata 14.0 was used for data analysis calculating standardized mean difference (SMD) for continuous outcomes and relative risk (RR) for binary outcomes, both with 95% confidence intervals (CI). Results Nine RCTs involving 787 patients were included in this review. ASC lowered HAMD scores (SMD − 3.43, 95% CI − 5.24 to − 1.61; I 2 = 95.2%, P

Abstract Viral encephalitis is characterized by inflammation of the brain parenchyma caused by a variety of viruses, among which the Japanese encephalitis (JE) virus (JEV) is a typical representative arbovirus. Neuronal death, neuroinflammation, and breakdown of the blood brain barrier (BBB) constitute vicious circles of JE progression. Currently, there is no effective therapy to prevent this damage. Growth arrest specific gene 6 (GAS6) is a secreted growth factor that binds to the TYRO3, AXL, and MERTK (TAM) family of receptor tyrosine kinases and has been demonstrated to participate in neuroprotection and suppression of inflammation in many central nervous system (CNS) diseases which has great potential for JE intervention. In this study, we found that GAS6 expression in the brain was decreased and was reversely correlated with viral load and neuronal loss. Mice with GAS6/TAM signalling deficiency showed higher mortality and accelerated neuroinflammation during peripheral JEV infection, accompanied by BBB breakdown. GAS6 directly promoted the expression of tight junction proteins in bEnd.3 cells and strengthened BBB integrity, partly via AXL. Mice administered GAS6 were more resistant to JEV infection due to increased BBB integrity, as well as decreased viral load and neuroinflammation. Thus, targeted GAS6 delivery may represent a strategy for the prevention and treatment of JE especially in patients with impaired BBB.

Abstract Objective Clinical studies have demonstrated the effectiveness of arthrocentesis in managing temporomandibular joint disorders (TMDs). However, there is a lack of consensus among these studies regarding the selection of injectables. Furthermore, an increasing number of drugs have been tested for TMDs in recent years, complicating the decision-making process for clinicians. This study conducted a network meta-analysis of randomized controlled trials (RCTs) to compare the clinical efficacy of different arthrocentesis treatment regimens. Methods We conducted a comprehensive search of Embase, PubMed, Cochrane Library, and Web of Science to gather articles on RCTs pertaining to the management of TMDs using arthrocentesis. This search spanned from inception of these databases up to July 29, 2024. We then performed a network meta-analysis using Stata 17.0 software. The outcome indicators used were VAS scores and changes in unassisted maximum opening. To determine the efficacy of each regimen, we employed surface-under the cumulative ranking curve (SUCRA) ranking. Result Forty RCTs were included, encompassing 1904 temporomandibular joints (TMJs) cases. Treatment options encompass platelet-rich plasma (PRP), hyaluronic acid (HA), corticosteroids (CS), bone marrow concentrate (BMAC), injectable platelet-rich fibrin (i-PRF), concentrated growth factor (CGF), Tenoxicam (TX), microfragmented adipose tissue (FAT), and their combination regimens. The SUCRA ranking revealed that the most effective treatment options at 1-, 3-, and 6-months post-arthrocentesis were HA + PRP, i-PRF, and BMAC, respectively. Conclusion HA + PRP, i-PRF and BMAC may represent the optimal arthrocentesis agents for the management of TMDs symptoms and restoration of TMJ function in the short, medium, and long term, respectively. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42024563975.

Abstract Ancient Platycladus orientalis holds significant ecological, landscape, historical, and cultural value. In northern China, leaf blight has significantly impacted the growth and ornamental value of ancient P. orientalis. In this study, 26 blight leaf samples of ancient P. orientalis were collected in Beijing, China. Phylogenetic analysis based on the concatenated internal transcribed spacer (ITS), β-tubulin (tub2), and RNA polymerase second largest subunit (rpb2) DNA sequence data combined with fungal morphological characteristics revealed three taxa of Nothophoma, i.e. N. platycladus, N. spiraeae, and N. juglandis. Of which, N. platycladus is a species new to science. Koch’s postulates indicated that all these three species of Nothophoma could cause leaf blight of P. orientalis.

Abstract Medullary thyroid carcinoma (MTC) is a rare type of thyroid malignancy that accounts for approximately 1–2% of all thyroid cancers (TCs). MTC include hereditary and sporadic cases, the former derived from a germline mutation of rearrangement during transfection (RET) proto-oncogene, whereas somatic RET mutations are frequently present in the latter. Surgery is the standard treatment for early stage MTC, and the 10-year survival rate of early MTC is over 80%. While for metastatic MTC, chemotherapy showing low response rate, and there was a lack of effective systemic therapies in the past. Due to the high risk (ca. 15–20%) of distant metastasis and limited systemic therapies, the 10-year survival rate of patients with advanced MTC was only 10–40% from the time of first metastasis. Over the past decade, targeted therapy for RET has developed rapidly, bringing hopes to patients with advanced and progressive MTC. Two multi-kinase inhibitors (MKIs) including Cabozantinib and Vandetanib have been shown to increase progression-free survival (PFS) for patients with metastatic MTC and have been approved as choices of first-line treatment. However, these MKIs have not prolonged overall survival (OS) and their utility is limited due to high rates of off-target toxicities. Recently, new generation TKIs, including Selpercatinib and Pralsetinib, have demonstrated highly selective efficacy against RET and more favorable side effect profiles, and gained approval as second-line treatment options. Despite the ongoing development of RET inhibitors, the management of advanced and progressive MTC remains challenging, drug resistance remains the main reason for treatment failure, and the mechanisms are still unclear. Besides, new promising therapeutic approaches, such as novel drug combinations and next generation RET inhibitors are under development. Herein, we overview the pathogenesis, molecular genetics and current management approaches of MTC, and focus on the recent advances of RET inhibitors, summarize the current situation and unmet needs of these RET inhibitors in MTC, and provide an overview of novel strategies for optimizing therapeutic effects.

Groundwater is an important water supply source in Xining City. Previous works have found that iron-rich groundwater limits water development and utilization. However, few studies focus on the distribution characteristics and mechanism of iron-rich groundwater in different types of aquifers in Xining City. Based on the hydrochemical data of 144 groundwater samples, combined with the geological and hydrogeological conditions, the distribution characteristics and influencing factors of iron content in groundwater in different aquifers were analyzed by methods of statistics and geostatistics. The results show that the exceeding standard ratio of iron in groundwater of unconsolidated sediments aquifer (Area Ⅰ) is 27. 85%, which is 1. 6 times and 2. 7 times higher than that of clastic rocks fissure-pore aquifer (Area Ⅱ) and bedrock aquifer (Area Ⅲ), respectively. The proportion of iron-rich groundwater (concentration greater than 0. 3 mg/L) in construction land area is significantly higher than in areas with other land use types. The redox environment and human activities (such as industrial wastewater, domestic sewage, and infiltration of iron-rich river water) may be the main factors affecting the increase of iron content in groundwater in Area I. In addition to the redox environment, Agricultural nitrogen fertilizer use and domestic sewage discharge are also important factors affecting iron-rich groundwater in Area Ⅱ. The iron-rich groundwater in Area Ⅲ is mainly controlled by redox conditions. On the regional scale, the distribution of iron-rich groundwater presents in bands or spots along the river. The iron deposits releasing in the primary strata and human activities (industrial wastewater) are the main source of iron ions in the shallow groundwater in the study area. The migration and enrichment of iron in groundwater are mainly controlled by redox conditions, and affected by the runoff condition, without relation to pH and salt effect. This study can provide scientific basis for urban water environment management in Xining City and similar arid and semi-arid areas.

Abstract Background Pulmonary fibrosis (PF) is an aging-related progressive lung disorder. The aged lung undergoes functional and structural changes termed immunosenescence and inflammaging, which facilitate the occurrence of fibrosis. Interleukin-10 (IL-10) is a potent anti-inflammatory and immunoregulatory cytokine, yet it remains unclear how IL-10 deficiency-induced immunosenescence participates in the development of PF. Methods Firstly we evaluated the susceptibility to fibrosis and IL-10 expression in aged mice. Then 13-month-old wild-type (WT) and IL-10 knockout (KO) mice were subjected to bleomycin(BLM) and analyzed senescence-related markers by PCR, western blot and immunohistochemistry staining of p16, p21, p53, as well as DHE and SA-β-gal staining. We further compared 18-month-old WT mice with 13-month-old IL-10KO mice to assess aging-associated cell senescence and inflamation infiltration in both lung and BALF. Moreover, proliferation and apoptosis of alveolar type 2 cells(AT2) were evaluated by FCM, immunofluorescence, TUNEL staining, and TEM analysis. Recombinant IL-10 (rIL-10) was also administered intratracheally to evaluate its therapeutic potential and related mechanism. For the in vitro experiments, 10-week-old naïve pramily lung fibroblasts(PLFs) were treated with the culture medium of 13-month PLFs derived from WT, IL-10KO, or IL-10KO + rIL-10 respectively, and examined the secretion of senescence-associated secretory phenotype (SASP) factors and related pathways. Results The aged mice displayed increased susceptibility to fibrosis and decreased IL-10 expression. The 13-month-old IL-10KO mice exhibited significant exacerbation of cell senescence compared to their contemporary WT mice, and even more severe epithelial-mesenchymal transition (EMT) than that of 18 month WT mice. These IL-10 deficient mice showed heightened inflammatory responses and accelerated PF progression. Intratracheal administration of rIL-10 reduced lung CD45 + cell infiltration by 15%, including a 6% reduction in granulocytes and a 10% reduction in macrophages, and increased the proportion of AT2 cells by approximately 8%. Additionally, rIL-10 significantly decreased α-SMA and collagen deposition, and reduced the expression of senescence proteins p16 and p21 by 50% in these mice. In vitro analysis revealed that conditioned media from IL-10 deficient mice promoted SASP secretion and upregulated senescence genes in naïve lung fibroblasts, which was mitigated by rIL-10 treatment. Mechanistically, rIL-10 inhibited TGF-β-Smad2/3 and PTEN/PI3K/AKT/ERK pathways, thereby suppressing senescence and fibrosis-related proteins. Conclusions IL-10 deficiency in aged mice leads to accelerated cell senescence and exacerbated fibrosis, with IL-10KO-PLFs displaying increased SASP secretion. Recombinant IL-10 treatment effectively mitigates these effects, suggesting its potential as a therapeutic target for PF. Graphical Abstract

Abstract Cutaneous T-cell lymphoma (CTCL) is a group of primary and secondary cutaneous malignancies characterized by aberrant T-cells in the skin. Diagnosing CTCL in its early stage can be difficult because of CTCL’s ability to mimic benign cutaneous inflammatory skin diseases. CTCL has multiple subtypes with different disease progression and diagnostic parameters despite similar clinical manifestations. The accurate diagnosis and prognosis of a varied range of diseases require the detection of molecular entities to capture the complete footprint of disease physiology. Non-coding RNAs (ncRNAs) have recently been discovered as major regulators of CTCL gene expression. They can affect tumor cell growth, migration, programmed cell death (PCD), and immunoregulation through interactions with the tumor microenvironment (TME), which in turn affect CTCL progression. This review summarizes recent advances in how ncRNAs regulate CTCL cell activity, especially their role in PCD. It also discusses the potential use of ncRNAs as diagnostic and prognostic biomarkers for different subtypes of CTCL. Furthermore, prospective targets and therapeutic approaches influenced by ncRNAs are presented. A better appreciation of the intricate epigenetic landscape of CTCL is expected to facilitate the creation of innovative targeted therapies for the condition.

Abstract Positron emission tomography/computed tomography (PET/CT) is a molecular imaging method commonly used to diagnose and differentiate Parkinson’s disease (PD). This study aimed to evaluate the performance of PET/CT with 11C-2β-Carbomethoxy-3β-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) tracers in the differential diagnosis between PD, multiple system atrophy parkinsonian type (MSA-P), progressive supranuclear palsy (PSP) and vascular parkinsonism (VP) using the data of 220 patients with clinical PD-like symptoms. Of the 220 enrolled patients, 166 (PD, n = 80; MSA-P, n = 54; PSP, n = 15; VP, n = 17) completed the motor, cognitive and PET/CT assessment and were included in this study. 11C-CFT and 18F-FDG PET/CT images were analyzed using the SNBPI toolbox and CortexID Suite software. The uptake values of 11C-CFT and 18F-FDG PET/CT were compared among the groups after controlling for covariates using generalized linear models. Receiver operating characteristic (ROC) curves were generated to estimate the diagnostic values. Patients with PSP showed the most significant reduction on 11C-CFT PET/CT, while patients with PD and MSA-P showed similar reductions, and patients with VP did not show any significant reduction in 11C-CFT uptake. The areas under the curve (AUCs) for 11C-CFT PET/CT for distinguishing PD from VP, PSP, and MSA-P were 0.902, 0.830, and 0.580, respectively, and 0.728 for distinguishing advanced-stage PD from PSP. On 18F-FDG PET/CT, the AUCs for distinguishing PD from PSP and MSA-P were 0.968 and 0.963, respectively. These results suggest that 11C-CFT and 18F-FDG PET/CT complement each other in improving the accuracy in differential diagnosis of PD.

Abstract Bottom cold water mass provides abundant nutrients and cool water in summer, playing a pivotal role in the productivity of marine ecosystem and sustainable aquaculture development. Located in the most densely populated region, the Yellow Sea cold water mass (YSCWM) is a unique one influencing hundreds of millions of people living in the rim of the Yellow Sea. As anthropogenic carbon emissions continue, how the YSCWM will be altered by climate change becomes a pressing issue, but remains elusive. Using an unprecedented set of climate models with high resolution and biogeochemical components, we find that the volume of the YSCWM will shrink by 48% to 2040–2050, along with the bottom temperature warming of 0.4 ± 0.1 °C dec−1 and the dissolved oxygen concentration declining of 0.09 ± 0.04 mg (L dec)−1. The significant destruction of the YSCWM is driven by the strengthened Yellow Sea Warm Current (YSWC). The reduced land-sea thermal contrast is the cause of the circulation change, by weakening the East Asian winter monsoon. Due to the resultant profound habitat reduction for marine life, predicting the change of the YSCWM will have far-reaching influences on the future policy-making for sustainable development of offshore aquaculture.

Abstract Horticultural crops yield considerable economic benefits, vital for supply stability and income enhancement. Plant breeders' rights (PBR) form a foundation, offering breeders essential safeguards to secure benefits and sustain breeding efforts. Therefore, comprehending the status and challenges in horticultural crop variety protection is vital for advancing horticulture. These crops encompass five primary categories: ornamental plants, fruit trees, vegetables, tea, and edible fungi. This article reviews the distinctness, uniformity, and stability (DUS) testing guidelines and progress in molecular identification research for Chinese horticultural crops from 1999 to 2022. Additionally, it statistically analyzes data from the Chinese Ministry of Agriculture and Rural Affairs and the Forestry Knowledge Service System on PBR applications and grants for all horticultural crop breeders. This review aims to provide a comprehensive understanding of the current state of horticultural crop variety protection in China. By thoroughly analyzing the existing status and challenges, the article seeks to enhance the international standing of plant variety protection in Chinese horticulture.

Abstract Realizing an efficient turnover frequency in the acidic oxygen evolution reaction by modifying the reaction configuration is crucial in designing high-performance single-atom catalysts. Here, we report a “single atom–double site” concept, which involves an activatable inert manganese atom redox chemistry in a single-atom Ru-Mn dual-site platform with tunnel Ni ions as the trigger. In contrast to conventional single-atom catalysts, the proposed configuration allows direct intramolecular oxygen coupling driven by the Ni ions intercalation effect, bypassing the secondary deprotonation step instead of the kinetically sluggish adsorbate evolution mechanism. The strong bonding of Ni ions activates the inert manganese terminal groups and inhibits the cross-site disproportionation process inherent in the Mn scaffolding, which is crucial to ensure the dual-site platform. As a result, the single-atom Ru-Ni-Mn octahedral molecular sieves catalyst delivers a low overpotential, adequate mass activity and good stability.

Abstract Objective To investigate the current state of oral frailty in oldely patients with require dental implants, analyze influencing factors in the characteristics of oral frailty across different patient categories, and provide a reference for clinical staff to identify high-risk groups and develop proactive management strategies. Methods Between January 2024 and March 2024, 654 patients with dental implants were selected using convenience sampling from six secondary and tertiary stomatological hospitals in Jiangsu and Zhejiang provinces. Data were collected via a general information questionnaire and the Oral Frailty Index-8. The latent profiles of oral frailty were examined, and univariate and Logistic regression analyses were conducted to determine the impact of various factors on these profiles. Results In this cross-sectional study, 605 valid questionnaires were returned, yielding an effective rate of 92.58%. The mean oral frailty score was 6.64 ± 1.21, with the sample comprising 223 males and 382 females, averaging 72.54 ± 6.33 years old. Oral frailty was categorized into three latent profiles: high (20.50%), moderate (53.72%), and low (25.78%) frailty groups. Factor analysis indicated that age, gender, education level, family income, number of implants, and dyslipidemia significantly predicted the classification of these profiles (P

Abstract Background Coral reefs experience frequent and severe disturbances that can overwhelm their natural resilience. In such cases, ecological restoration is essential for coral reef recovery. Sexual reproduction has been reported to present the simplest and most cost-effective means for coral reef restoration. However, larval settlement and post-settlement survival represent bottlenecks for coral recruitment in sexual reproduction. While bacteria play a significant role in triggering coral metamorphosis and settlement in many coral species, the underlying molecular mechanisms remain largely unknown. In this study, we employed a transcriptome-level analysis to elucidate the intricate interactions between bacteria and coral larvae that are crucial for the settlement process. Results High Metabacillus indicus strain cB07 inoculation densities resulted in the successful induction of metamorphosis and settlement of coral Pocillopora damicoris larvae. Compared with controls, inoculated coral larvae exhibited a pronounced increase in the abundance of strain cB07 during metamorphosis and settlement, followed by a significant decrease in total lipid contents during the settled stage. The differentially expressed genes (DEGs) during metamorphosis were significantly enriched in amino acid, protein, fatty acid, and glucose related metabolic pathways. In settled coral larvae induced by strain cB07, there was a significant enrichment of DEGs with essential roles in the establishment of a symbiotic relationship between coral larvae and their symbiotic partners. The photosynthetic efficiency of strain cB07 induced primary polyp holobionts was improved compared to those of the negative controls. In addition, coral primary polyps induced by strain cB07 showed significant improvements in energy storage and survival. Conclusions Our findings revealed that strain cB07 can promote coral larval settlement and enhance post-settlement survival and fitness. Manipulating coral sexual reproduction with strain cB07 can overcome the current recruitment bottleneck. This innovative approach holds promise for future coral reef restoration efforts.

Abstract Deep vein thrombosis (DVT) is a leading cause of morbidity and mortality after trauma. Here, we integrate plasma metabolomics and proteomics to evaluate the metabolic alterations and their function in up to 680 individuals with and without DVT after trauma (pt-DVT). We identify 28 metabolites and 2 clinical parameter clusters associated with pt-DVT. Then, we develop a panel of 9 metabolites (hexadecanedioic acid, pyruvic acid, L-Carnitine, serotonin, PE(P-18:1(11Z)/18:2(9Z,12Z)), 3-Hydroxycapric acid, 5,6-DHET, 3-Methoxybenzenepropanoic acid and pentanenitrile) that can predict pt-DVT with high performance, which can be verified in an independent cohort. Furthermore, the integration analysis of metabolomics and proteomics data indicates that the upregulation of glycolysis/gluconeogenesis-TCA cycle may promote thrombosis by regulating ROS levels in red blood cells, suggesting that interfering with this process might be potential therapeutic strategies for pt-DVT. Together, our study comprehensively delineates the metabolic and hematological dysregulations for pt-DVT, and provides potential biomarkers for early detection.

The sulfate process for bamboo pulp production encounters silicon interference during the pulping stage, necessitating desilication before the alkali recovery section. This study investigated the desilication of bamboo pulping black liquor (BPBL), demonstrating that silicon was removed effectively by adding Mg/Al compound desilication agent to the BPBL via burning at high temperature. The desilication extent can reach 84% when the desilication agent is added in the proportion of Mg/Al (magnesium sulfate and sodium metaluminate) in the ratio 1.25:0.75. Subsequently, less-silicon white mud (LSWM) can be prepared after black liquor (BL) combustion desilication. LSWM was compared with normal WM as a blank sample, and the morphology and physicochemical properties of two kinds of WM were characterized. X-ray diffractometry revealed that both types of WM are primarily composed of calcite crystalline CaCO3 and hydrated CaSiO3. Scanning electron microscopy, X-ray photoelectron spectroscopy, and particle size analysis demonstrated the reduced content of CaSiO3 generated in the LSWM. This result indicated that the Mg/Al compound desilication agent removed the silicon from the green liquor (GL), thereby reducing the residual silicon in WM. This reduction is beneficial to the calcination recovery and comprehensive utilization of WM.

Abstract Background Intravitreal injections of angiogenesis inhibitors have proved efficacious in the majority of patients with ocular angiogenesis. However, one-fourth of all treated patients fail to derive benefits from intravitreal injections. tRNA-derived small RNA (tsRNA) emerges as a crucial class of non-coding RNA molecules, orchestrating key roles in the progression of human diseases by modulating multiple targets. Through our prior sequencing analyses and bioinformatics predictions, tRNA-Cys-5-0007 has shown as a potential regulator of ocular angiogenesis. This study endeavors to elucidate the precise role of tRNA-Cys-5-0007 in the context of ocular angiogenesis. Methods Quantitative reverse transcription PCR (qRT-PCR) assays were employed to detect tRNA-Cys-5-0007expression. EdU assays, sprouting assays, transwell assays, and Matrigel assays were conducted to elucidate the involvement of tRNA-Cys-5-0007 in endothelial angiogenic effects. STZ-induced diabetic model, OIR model, and laser-induced CNV model were utilized to replicate the pivotal features of ocular vascular diseases and evaluate the influence of tRNA-Cys-5-0007 on ocular angiogenesis and inflammatory responses. Bioinformatics analysis, luciferase activity assays, RNA pull-down assays, and in vitro studies were employed to elucidate the anti-angiogenic mechanism of tRNA-Cys-5-0007. Exosomal formulation was employed to enhance the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007. Results tRNA-Cys-5-0007 expression was down-regulated under angiogenic conditions. Conversely, tRNA-Cys-5-0007 overexpression exhibited anti-angiogenic effects in retinal endothelial cells, as evidenced by reduced proliferation, sprouting, migration, and tube formation abilities. In diabetic, laser-induced CNV, and OIR models, tRNA-Cys-5-0007 overexpression led to decreased ocular vessel leakage, inhibited angiogenesis, and reduced ocular inflammation. Mechanistically, these effects were attributed to the targeting of vascular endothelial growth factor A (VEGFA) and TGF-β1 by tRNA-Cys-5-0007. The utilization of an exosomal formulation further potentiated the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007. Conclusions Concurrent targeting of tRNA-Cys-5-0007 for anti-angiogenic and anti-inflammatory therapy holds promise for enhancing the effectiveness of current anti-angiogenic therapy.

Pressure ulcers (PUs) are common skin injuries known for their high morbidity, rapid onset, susceptibility to infection, and challenging healing process. One potential therapy for PUs is cell-based therapy using mesenchymal stem cells (MSCs). However, poor survival and low cell retention of MSCs on skin lesions limit their therapeutic effects and applications. In this study, we prepared an extracellular matrix (dECM) hydrogel decellularized from the human umbilical cord (UC). A patch composed of UC-dECM and UC-MSCs was employed in the treatment of PUs in C57BL/6 mice. Our results indicate that the UC-dECM hydrogel effectively sustains cell viability, enhances the stemness-related gene expression in UC-MSCs, and promotes human umbilical vein endothelial cells (HUVECs) migration and angiogenesis. Compared to the groups treated with the patch containing only UC-dECM, injection of UC-MSCs or gauze dressing, the patch combining UC-dECM hydrogel with UC-MSCs significantly accelerated PU healing. This positive outcome can be attributed to the promotion of tissue re-epithelialization, collagen deposition, angiogenesis, and inflammation inhibition. Our results suggest that the composite patch, comprised of UC-dECM hydrogel and UC-MSCs, may be a promising therapeutic approach for PU treatment.

The objective of this research was to investigate and compare the effects of various protein or protein-based powders (WPC, SPI, BSA and hemoglobin) addition on transform of texture properties in egg white (EW)/egg yolk (EY) gels. Results showed that the highest hardness value (38.5 N) was detected in BSA-treated EW gels, while the lowest values (46.6 N) were obtained in hemoglobin-treated EY gels. Additionally, significantly increased value of free –SH groups was obtained in SPI/BSA/hemoglobin-treated EW/EY solutions, and increased value of protein solubility was obtained in EY solutions treated by WPC/SPI/BSA/hemoglobin relative to those of the control. The EW solutions treated by BSA/hemoglobin reached significantly higher H0 values than those of other groups. SDS-PAGE analysis showed that the hemoglobin-treated EW solution had slightly intense bands of ovoinhibitor, ovotransferrin and ovalbumin, and the EY solutions treated by WPC/SPI/BSA had higher level of covalent crosslinking. The EW gels treated by WPC/hemoglobin exhibited relatively more ordered protein secondary structures (α-helix and β-sheet) than those of the SPI group. SEM results suggested that WPC/BSA-treated EW gels developed uniform, porous and fiber-like structure, while SPI/BSA-treated EY gels developed rougher structure.

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 Background Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic, while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs. Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection (HAR) that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure, in which process the MHC II molecule plays critical roles. Methods Thus, we generate a 4‐gene (GGTA1, CMAH, β4GalNT2, and CIITA) knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously. Results We successfully obtained 4KO piglets with deficiency in all alleles of genes, and at cellular and tissue levels. Additionally, the safety of our animals after gene editing was verified by using whole‐genome sequencing and karyotyping. Piglets have survived for more than one year in the barrier, and also survived for more than 3 months in the conventional environment, suggesting that the piglets without MHC II can be raised in the barrier and then gradually mated in the conventional environment. Conclusions 4KO piglets have lower immunogenicity, are safe in genomic level, and are easier to breed than the model with both MHC I and II deletion.

Colletotrichum species can function as plant pathogens, saprobes or endophytes on a wide variety of plant hosts and are considered amongst the ten most significant genera of plant pathogens globally. China contributes almost half the walnut production in the world. However, Colletotrichum species occurring on walnut remain largely unresolved in China. To explore the Colletotrichum species found on walnut in China, 470 walnut fruit or leaf samples with anthracnose were collected from 14 main walnut-producing regions across seven provinces. A total of 165 Colletotrichum strains were isolated from these samples. The Colletotrichum isolates were identified, based on morphological characteristics and sequence analyses of ACT, CHS-1, GAPDH, ITS and TUB2. Twelve species, including 11 known Colletotrichum species (C. boninense, C. citrulli, C. fioriniae, C. fructicola, C. godetiae, C. juglandicola, C. karsti, C. mengyinense, C. pandanicola, C. peakense and C. siamense) and a novel species (C. chinensis sp. nov.) were identified. The species distribution revealed regional prevalence as follows: C. mengyinense was the most dominant species in Gansu, C. mengyinense and C. siamense in Shandong, C. chinensis in Beijing, C. pandanicola in Shaanxi and C. godetiae in Yunnan. Colletotrichum siamense was the sole species isolated in Sichuan and Xinjiang Provinces. Koch’s postulates were fulfilled, demonstrating that all 12 species cause anthracnose on walnut. This is the first report of C. boninense, C. citrulli and C. karsti as pathogens of walnut anthracnose worldwide.

Abstract Background Haemaphysalis qinghaiensis is a tick species distributed only in China. Due to its ability to transmit a variety of pathogens, including species of the genera Anaplasma, Rickettsia, Babesia, and Theileria, it seriously endangers livestock husbandry. However, the microbial community of the midgut of H. qinghaiensis females collected from yaks and Tibetan sheep has not yet been characterized using metagenomic sequencing technology. Methods Haemaphysalis qinghaiensis were collected from the skins of yaks and Tibetan sheep in Gansu Province, China. Genomic DNA was extracted from the midguts and midgut contents of fully engorged H. qinghaiensis females collected from the two hosts. Metagenomic sequencing technology was used to analyze the microbial community of the two groups. Results Fifty-seven phyla, 483 genera, and 755 species were identified in the two groups of samples. The ticks from the two hosts harbored common and unique microorganisms. At the phylum level, the dominant common phyla were Proteobacteria, Firmicutes, and Mucoromycota. At the genus level, the dominant common genera were Anaplasma, Ehrlichia, and Pseudomonas. At the species level, bacteria including Anaplasma phagocytophilum, Ehrlichia minasensis, and Pseudomonas aeruginosa along with eukaryotes such as Synchytrium endobioticum and Rhizophagus irregularis, and viruses such as the orf virus, Alphadintovirus mayetiola, and Parasteatoda house spider adintovirus were detected in both groups. In addition, the midgut of H. qinghaiensis collected from yaks had unique microbial taxa including two phyla, eight genera, and 23 species. Unique microorganisms in the midgut of H. qinghaiensis collected from Tibetan sheep included two phyla, 14 genera, and 32 species. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the functional genes of the microbiome of H. qinghaiensis were annotated to six pathways, and the metabolic pathways included 11 metabolic processes, in which the genes involved in carbohydrate metabolism were the most abundant, followed by the genes involved in lipid metabolism. Conclusions These findings indicate that most of the microbial species in the collected H. qinghaiensis ticks were the same in both hosts, but there were also slight differences. The analytical data from this study have enhanced our understanding of the midgut microbial composition of H. qinghaiensis collected from different hosts. The database of H. qinghaiensis microbe constructed from this study will lay the foundation for predicting tick-borne diseases. Furthermore, a comprehensive understanding of tick microbiomes will be useful for understanding vector competency and interactions with ticks and midgut microorganisms. Graphical abstract

Abstract Background The transposons of the hAT superfamily are the most widespread transposons ever known. SLEEPER genes encode domesticated transposases from the hAT superfamily, which may have lost their transposable functions during long-term evolution and transformed into host proteins that regulate plant growth and development. Results This study identified 162 members of the SLEEPER gene family from Brassica napus. These members are widely distributed on 19 chromosomes, mainly in the Cn subgenome, and have promoters with various cis-acting elements related to hormone regulation, abiotic stress, and growth and development regulation. Most of the genes in this family contain similar conserved domains and motifs, and the closer the genes are distributed on evolutionary branches, the more similar their structures are. Transcriptome sequencing performed on tissues at different growth stages from B. napus line 3529 indicated that these genes had different expression patterns, and nearly half of the genes were not detectably expressed in all samples. Conclusions This study investigated the gene structure, expression patterns, evolutionary features, and gene localization of the SLEEPER family members to confirm the significance of these genes in the growth of B. napus, providing a reference for the study of transposon domestication and outstanding genetic resources for the genetic improvement of B. napus.

Abstract Infertility is not a fatal disease but it really produces infertility-related stress and affects individuals’ quality of life to a great extent. This study aims to investigate the relations among infertility-related stress, negative emotions and quality of life in infertile outpatients, and suppose gender difference as well as Dark Triad, which contained three dark personality traits: Machiavellianism, narcissism, and psychopathy, would moderate the relations. 105 infertile outpatients age range 20–49 completed a cross-sectional questionnaire on the Fertility Quality of Life scale, the Fertility Problem Inventory, the Hospital Anxiety and Depression Scale a the Chinese version of Dirty Dozen. Results showed that negative emotions mediated the relations between infertility-related stress and quality of life. Dark Triad could not moderate the relations between infertility-related stress, negative emotions, and quality of life, but gender can moderate the associations between infertility-related stress and negative emotions. Specifically, the association between infertility-related stress and negative emotions was stronger in men than in women. Infertility-related stress has direct and indirect effects on infertile outpatients’ quality of life. It is important to consider the important roles of emotions and gender difference between patients, and delivering targeted intervention programs.

This is an article in the field of mineral processing engineering. Molybdenum has many good physical and chemical properties and is widely used in many fields. Molybdenum is mainly derived from molybdenite, but the resources of the easily beneficiated molybdenum ore have been gradually reduced after long-term development. Nowadays, talc-type and other refractory molybdenum ores have gradually become the focus of research. The separation of talc and molybdenite is a difficult point in the separation of talc-type molybdenum ores. The two has similar surface structures and natural floatability, and the separation is very difficult. This article summarizes the current research progress of talc-type molybdenum ore beneficiation technology and reagents, and proposes to strengthen the research and development of selective grinding of talc-type molybdenum ores and organic macromolecular reagents, and deepen the mechanism and effect of reagents and mineral surfaces. The study of the raw ore technological mineralogy is an important direction for sorting the talc-type molybdenum ore in the future.

Inborn errors of the signal transducer and activator of transcription 1 (STAT1) result in four types of immunodeficiency disease with varying degrees of impaired STAT1 function: autosomal recessive (AR) complete STAT1 deficiency, AR partial STAT1 deficiency, autosomal dominant (AD) STAT1 deficiency, and AD STAT1 gain-of-function (STAT1-GOF). Of which, the STAT1-GOF mutations promote a clinical syndrome of immune dysregulation characterized by recurrent infections, especially chronic mucocutaneous candidiasis (CMC) and Talaromyces marneffei infection and predisposition to humoral autoimmunity. STAT1-GOF mutations lead to enhanced phosphorylation of STAT1 (pSTAT1), delayed dephosphorylation, and impaired nuclear dephosphorylation. As a result, the development of T helper (Th) 17 cells is impaired, limiting the production of interleukin (IL)-17, which plays an important role in antifungal immunity. Additionally, mutations can also cause a decrease in the proportion of CD4+, CD8+, and natural killer (NK) cells. Recent research demonstrated that in the absence of overt infection, STAT-GOF mice can disrupt naïve CD4+ T cell homeostasis and promote expansion and differentiation of abnormal T-follicular helper/T-helper 1-like (Tfh/Th1-like) T cells and germinal center-like (GC-like) B cells, and thus reminds us of the complex molecular mechanism of autoimmune disease with/without fungal infection, which may further involve specific clinical treatment including antifungal and anti-autoimmunity therapies. In addition, sex and location of mutation were also associated with the clinical phenotype. Individuals with DNA binding domain (DBD) mutations had a higher prevalence of autoimmunity and aberrant B cell activation. Disrupted CD4+ T cell homeostasis occurred sooner and more robustly in females, highlighting the importance of specific treatment to normalize STAT1 expression and restore immune tolerance in patients with STAT1-GOF syndrome. Herein, we provide a comprehensive review of STAT1-GOF aiming to further clarify the regulatory mechanism of cellular and humoral immune deficiency in patients with fungal infection with or without autoimmunity.

Abstract Infections caused by pathogenic Escherichia coli are a serious threat to human health, while conventional antibiotic susceptibility tests (AST) have a long turn-around time, and rapid antibiotic susceptibility methods are urgently needed to save lives in the clinic, reduce antibiotic misuse and prevent emergence of antibiotic-resistant bacteria. We optimized and validated the feasibility of a novel rapid AST based on SYBR Green I and Propidium Iodide (SGPI-AST) for E. coli drug susceptibility test. A total of 112 clinical isolates of E. coli were collected and four antibiotics (ceftriaxone, cefoxitin, imipenem, meropenem) were selected for testing. Bacterial survival rate of E. coli was remarkably linearly correlated with S value at different OD600 values. After optimizing the antibiotic concentrations, the sensitivity and specificity of SGPI-AST reached 100%/100%, 97.8%/100%, 100%/100% and 98.4%/99% for ceftriaxone, cefoxitin, imipenem and meropenem, respectively, and the corresponding concordances of the SGPI-AST with conventional AST were 1.000, 0.980, 1.000 and 0.979, respectively. The SGPI-AST can rapidly and accurately determine the susceptibility of E. coli clinical isolates to multiple antibiotics in 60 min, and has the potential to be applied to guide the precise selection of antibiotics for clinical management of infections caused by pathogenic E. coli.

Abstract To achieve high power conversion efficiency in perovskite/silicon tandem solar cells, it is necessary to develop a promising wide-bandgap perovskite absorber and processing techniques in relevance. To date, the performance of devices based on wide-bandgap perovskite is still limited mainly by carrier recombination at their electron extraction interface. Here, we demonstrate assembling a binary two-dimensional perovskite by both alternating-cation-interlayer phase and Ruddlesden−Popper phase to passivate perovskite/C60 interface. The binary two-dimensional strategy takes effects not only at the interface but also in the bulk, which enables efficient charge transport in a wide-bandgap perovskite solar cell with a stabilized efficiency of 20.79% (1 cm2). Based on this absorber, a monolithic perovskite/silicon tandem solar cell is fabricated with a steady-state efficiency of 30.65% assessed by a third party. Moreover, the tandem devices retain 96% of their initial efficiency after 527 h of operation under full spectral continuous illumination, and 98% after 1000 h of damp-heat testing (85 °C with 85% relative humidity).

Abstract Background Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disorder characterized by recurrent edema, facial palsies, and nerve dysfunctions often associated with the plicata tongue. Although the etiology of MRS is not well understood, there is growing evidence suggesting an autoimmune involvement. Case presentation This paper presents a case report of a 25-year-old male with MRS as the initial symptom, followed by temporomandibular joint osteoarthritis (TMJ-OA). A comprehensive diagnosis and multidisciplinary treatment approach including surgery, local injections, and oral medication were implemented, resulting in a favorable prognosis. Conclusions These findings support the hypothesis that MRS is a systemic granulomatous disease caused by autoimmunity, which may also influence the occurrence and development of TMJ-OA through immune-related mechanisms. This study emphasizes the significance of systemic immune regulation in the treatment of patients with MRS and TMJ-OA comorbid conditions.

Abstract Objective Early childhood caries has become a globally crucial oral health problem over the decades. Most studies have discussed the association between low birth weight and early childhood caries; however, studies focusing on high birth weight have been relatively limited. This study aimed to assess the impact of high birth weight on the incidence and severity of dental caries in 4–5-year-old children. Subjects and methods Study subjects included 491 children from a birth cohort study at 4–5 years of age. Data on dental caries, prenatal and perinatal factors, and socio-demographic determinants were recorded. Logistic regression models adjusted for potential confounders were performed to analyze the data. Two-sided P-value