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Identifiability of a mathematical model plays a crucial role in the parameterization of the model. In this study, we established the structural identifiability of a susceptible-exposed-infected-recovered (SEIR) model given different combinations of input data and investigated practical identifiability with respect to different observable data, data frequency, and noise distributions. The practical identifiability was explored by both Monte Carlo simulations and a correlation matrix approach. Our results showed that practical identifiability benefits from higher data frequency and data from the peak of an outbreak. The incidence data gave the best practical identifiability results compared to prevalence and cumulative data. In addition, we compared and distinguished the practical identifiability by Monte Carlo simulations and a correlation matrix approach, providing insights into when to use which method for other applications.

Chronic otitis media with effusion (COME) is a common cause of hearing loss in children and adults. Laryngopharyngeal reflux (LPR) is often overlooked in the clinical management of COME complicated by LPR. This study aimed to investigate the presence and concentration of trypsin and pepsin in the middle ear effusion (MEE), as well as the recurrence rate of otitis media with effusion (OME) in COME patients with trypsin-/pepsin-positive MEE after acid-suppressive treatment (AST). In this study, trypsin and pepsin were found in the MEE of COME patients. Follow-up results showed that the recurrence rate of OME within 1 year was significantly lower in the AST group than in the non-AST group. Taken together, patients with COME can be offered pepsin detection of MEE, and if the pepsin test is positive, acid-suppressing drugs such as proton pump inhibitors could be recommended to prevent the recurrence of OME.

Metasurfaces have shown unique application value in the field of holography due to its outstanding ability to manipulate electromagnetic waves. However, improving the design efficiency and imaging quality remains a challenging task. In this work, we propose a deep learning method that can design holographic metasurface structures on demand, with the Mean Absolute Error (MAE) of 0.04 for both amplitude and phase. We utilize this method to inverse design all-silicon-based metasurfaces operating in the terahertz range, achieving a MAE of 0.015 for two target images. This method not only significantly enhances the design efficiency of holographic metasurfaces but also enables continuous modulation of both phase and amplitude. Consequently, it greatly improves both the design efficiency and imaging quality of holographic metasurfaces, providing a new direction for their design.

Abstract The specific mechanisms underlying bacteria‐triggered cell death and osteogenic dysfunction in host bone marrow mesenchymal stem cells (BMSCs) remain unclear, posing a significant challenge to the repair of infected bone defects. This study identifies ferroptosis as the predominant cause of BMSCs death in the infected bone microenvironment. Mechanistically, the bacteria‐induced activation of the innate immune response in BMSCs leads to upregulation and phosphorylation of interferon regulatory factor 7 (IRF7), thus facilitating IRF7‐dependent ferroptosis of BMSCs through the transcriptional upregulation of acyl‐coenzyme A synthetase long‐chain family member 4 (ACSL4). Moreover, it is found that intervening in ferroptosis can partially rescue cell injuries and osteogenic dysfunction. Based on these findings, a hydrogel composite 3D‐printed scaffold is designed with reactive oxygen species (ROS)‐responsive release of antibacterial quaternized chitosan and sustained delivery of the ferroptosis inhibitor Ferrostatin‐1 (Fer‐1), capable of eradicating pathogens and promoting bone regeneration in a rat model of infected bone defects. Together, this study suggests that ferroptosis of BMSCs is a promising therapeutic target for infected bone defect repair.

In Parkinson's disease (PD), exogenous ghrelin protects dopaminergic neurons through its receptor, growth hormone secretagogue receptor (GHSR). However, in contrast to the strikingly low levels of ghrelin, GHSR is highly expressed in the substantia nigra (SN). What role does GHSR play in dopaminergic neurons is unknown. In this study, using GHSR knockout mice (Ghsr−/− mice) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model, we found that GHSR deletion aggravated dopaminergic neurons degeneration, and the expression and activity of GHSR were significantly reduced in PD. Furthermore, we explored the potential mechanism that GHSR deficiency aggregated PD-related neurodegeneration. We showed that DEPTOR, a subunit of mTORC1, was overexpressed in Ghsr−/− mice, positively regulating autophagy and enhancing autophagy initiation. The expression of lysosomal markers was abnormal, implying lysosomal dysfunction. As a result, the damaged mitochondria could not be effectively eliminated, which ultimately exacerbated the injury of nigral dopaminergic neurons. In particular, we demonstrated that DEPTOR could be transcriptionally regulated by KLF4. Specific knockdown of KLF4 in dopaminergic neurons effectively alleviated neurodegeneration in Ghsr−/− mice. In summary, our results suggested that endogenous GHSR deletion-compromised autophagy by impairing lysosomal function, is a key contributor to PD, which provided ideas for therapeutic approaches involving the manipulation of GHSR.

Abstract Background and aims Chemotherapy resistance in colorectal cancer have been faced with significant challenges in recent years. Particular interest is directed to tumor microenvironment function. Recent work has, identified a small molecule named Divertin that prevents myosin light chain kinase 1(MLCK1) recruitment to the perijunctional actomyosin ring(PAMR), restores barrier function after tumor necrosis factor(TNF)-induced barrier loss and prevents disease progression in experimental inflammatory bowel disease. Studies have shown that MLCK is a potential target for affecting intestinal barrier function, as well as for tumor therapy. However, the relative contributions of MLCK expression and chemotherapy resistance in colorectal cancers have not been defined. Methods Statistical analysis of MYLK gene expression differences in colorectal cancer patients and normal population and prognosis results from The Cancer Genome Atlas(TCGA) data. Cell activity was detected by Cell counting Kit-8. Cell proliferation was detected by monoclonal plate. The apoptosis was detected by flow cytometry and western blot. Determine the role of MLCK1 in inducing 5-Fluorouracil(5-Fu) resistance in colorectal cancer cells was detected by overexpression of MLCK1 and knock-down expression of MLCK1. Results MLCK1 is expressed at different levels in different colorectal cancer cells, high MLCK1 expressing cell lines are less sensitive to 5-Fu, and low MLCK1 expressing cell lines are more sensitive to 5-Fu. MLCK1 high expression enhances resistance to 5-Fu in colorectal cancer cells and the sensitivity to 5-Fu was increased after knocking down the expression of MLCK1, that might be closely correlated to TNFR2/NF-κB pathway. Conclusions MLCK1 high expression can enhance resistance to 5-Fu in colorectal cancer cells and the sensitivity to 5-Fu was increased after knocking down the expression of MLCK1, that might be closely correlated to TNFR2/NF-κB pathway, which will provide a new method for the treatment of colorectal cancer patients who are resistant to 5-Fu chemotherapy.

BackgroundDepression is a chronic psychiatric condition that places significant burdens on individuals, families, and societies. The rapid evolution of non-invasive brain stimulation techniques has facilitated the extensive clinical use of Transcranial Magnetic Stimulation (TMS) for depression treatment. In light of the substantial recent increase in related research, this study aims to employ bibliometric methods to systematically review the global research status and trends of TMS in depression, providing a reference and guiding future studies in this field.MethodsWe retrieved literature on TMS and depression published between 1999 and 2023 from the Science Citation Index Expanded (SCIE) and Social Science Citation Index (SSCI) databases within the Web of Science Core Collection (WoSCC). Bibliometric analysis was performed using VOSviewer and CiteSpace software to analyze data on countries, institutions, authors, journals, keywords, citations, and to generate visual maps.ResultsA total of 5,046 publications were extracted covering the period from 1999 to 2023 in the field of TMS and depression. The publication output exhibited an overall exponential growth trend. These articles were published across 804 different journals, BRAIN STIMULATION is the platform that receives the most articles in this area. The literature involved contributions from over 16,000 authors affiliated with 4,573 institutions across 77 countries. The United States contributed the largest number of publications, with the University of Toronto and Daskalakis ZJ leading as the most prolific institution and author, respectively. Keywords such as “Default Mode Network,” “Functional Connectivity,” and “Theta Burst” have recently garnered significant attention. Research in this field primarily focuses on TMS stimulation patterns, their therapeutic efficacy and safety, brain region and network mechanisms under combined brain imaging technologies, and the modulation effects of TMS on brain-derived neurotrophic factor (BDNF) and neurotransmitter levels.ConclusionIn recent years, TMS therapy has demonstrated extensive potential applications and significant implications for the treatment of depression. Research in the field of TMS for depression has achieved notable progress. Particularly, the development of novel TMS stimulation patterns and the integration of TMS therapy with multimodal techniques and machine learning algorithms for precision treatment and investigation of brain network mechanisms have emerged as current research hotspots.

This investigation's primary objective is to analyze the fluid dynamics and heat transfer enhancement in an irregular enclosure. Several physical phenomena such as Alumina-water nanofluids, magnetic field, non-uniform heating and amplitude of non-uniform heating are taken into account. A thorough investigation using machine learning algorithms (MLAs) and computational fluid dynamics (CFD) is carried out. Initially, for CFD phase the coupled non-linear dimensionless governing equations of the considered problem are solved numerically by adapting a Finite Element method (FEM) using appropriate boundary conditions. The analysis considers a range of physical parameters, such as the Hartmann number (0–20), nanoparticle volume friction (0–0.04), Ryleigh number (103-105), offset temperature (0.1–1), frequency (1-10) and non-uniform heating amplitude (0.1–1). The numerical results are explicated in the form of streamlines, isotherms, heatlines structures. The impact of these factors on entropy generation is also explored. In addition, three popular MLAs, Random Forest (RF), Artificial Neural Network (ANN) and Support Vector Machine (SVM) were used to save the computational costs. The finding explore Hartmann number and nanoparticle volume friction has decreasing trend on total entropy production and heat transfer rate. The entropy production decreases up to 42.02 % for Hartman number and for nanoparticles it decreases 12.61 %. However, the non-uniform heating amplitude has opposite effect on irreversibility factor. Also, compared to other MLAs, the ANN model demonstrates more accurate predictions. The objective is to propose novel concept for enhancing the performance of cooling systems and optimizing energy utilization across diverse technical domain.

Rapid industrialization and urbanization have caused severe soil contamination with cadmium (Cd) necessitating effective remediation strategies. Phytoremediation is a widely adopted technology for remediating Cd-contaminated soil. Previous studies have shown that Abelmoschus manihot has a high Cd accumulation capacity and tolerance indicating its potential for Cd soil remediation. However, the mechanisms underlying its response to Cd stress remain unclear. In this study, physiological, transcriptomic, and metabolomic analyses were conducted to explore the response of A. manihot roots to Cd stress at different time points. The results revealed that Cd stress significantly increased malondialdehyde (MDA) levels in A. manihot, which simultaneously activated its antioxidant defense system, enhancing the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) by 19.73%–50%, 22.87%–38.89%, and 32.31%–45.40% at 12 h, 36 h, 72 h, and 7 days, respectively, compared with those in the control (CK). Moreover, transcriptomic and metabolomic analyses revealed 245, 5,708, 9,834, and 2,323 differentially expressed genes (DEGs), along with 66, 62, 156, and 90 differentially expressed metabolites (DEMs) at 12 h, 36 h, 72 h, and 7 days, respectively. Through weighted gene coexpression network analysis (WGCNA) of physiological indicators and transcript expression, eight hub genes involved in phenylpropanoid biosynthesis, signal transduction, and metal transport were identified. In addition, integrative analyses of metabolomic and transcriptomic data highlighted the activation of lipid metabolism and phenylpropanoid biosynthesis pathways under Cd stress suggesting that these pathways play crucial roles in the detoxification process and in enhancing Cd tolerance in A. manihot. This comprehensive study provides detailed insights into the response mechanisms of A. manihot to Cd toxicity.

Abstract Background Metastasis is the leading cause of death among prostate cancer (PCa) patients. Obesity is associated with both PCa-specific and all-cause mortality. High-fat diet (HFD) is a risk factor contributing to obesity. However, the association of HFD with PCa metastasis and its underlying mechanisms are unclear. Methods Tumor xenografts were conducted by intrasplenic injections. The ability of migration or invasion was detected by transwell assay. The expression levels of RPS27 were detected by QRT-PCR and western blot. Results The present study verified the increase in PCa metastasis caused by HFD in mice. Bioinformatics analysis demonstrated increased RPS27 in the experimentally induced PCa in HFD mice, indicating that it is an unfavorable prognostic factor. Intrasplenic injections were used to demonstrate that RPS27 overexpression promotes, while RPS27 knockdown significantly reduces, PCa liver metastasis. Moreover, RPS27 inhibition suppresses the effects of HFD on PCa metastasis. Further mRNA sequencing analysis revealed that RPS27 promotes PCa metastasis by selectively enhancing the expression of various genes. Conclusion Our findings indicate that HFD increases the risk of PCa metastasis by elevating RPS27 expression and, subsequently, the expression of genes involved in PRAD progression. Therefore, RPS27 may serve as a novel target for the diagnosis and treatment of metastatic PCa.

Abstract Background Previous studies of singletons evaluating prenatal phthalate exposure and early neurodevelopment reported mixed results and the associations could be biased by parental, obstetrical, and genetic factors. Methods A co-twin control design was employed to test whether prenatal phthalate exposure was associated with children’s neurocognitive development. We collected information from 97 mother-twin pairs enrolled in the Wuhan Twin Birth Cohort between March 2016 and October 2018. Fourteen phthalate metabolites were measured in maternal urine collected at each trimester. Neurodevelopmental differences in twins at the age of two were examined as the outcome of interest. Multiple informant model was used to examine the covariate-adjusted associations of prenatal phthalate exposure with mental development index (MDI) and psychomotor development index (PDI) scores assessed at 2 years of age based on Bayley Scales of Infant Development (Second Edition). This model also helps to identify the exposure window of susceptibility. Results Maternal urinary levels of mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (β = 1.91, 95% CI: 0.43, 3.39), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (β = 1.56, 95% CI: 0.33, 2.79), and the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) (β = 1.85, 95% CI: 0.39, 3.31) during the first trimester showed the strongest and significant positive associations with intra-twin MDI difference. When stratified with twin chorionicity, the positive associations of monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), individual DEHP metabolites, and ∑DEHP exposure during pregnancy with intra-twin neurodevelopmental differences were more significant in monochorionic diamniotic (MCDA) twins than those in dichorionic diamniotic (DCDA) twins. Conclusions Neurodevelopmental differences in MCDA twins were strongly associated with prenatal phthalate exposure. Our findings warrant further confirmation in longitudinal studies with larger sample sizes.

Abstract Background Abdominal distension is a relatively common complication in postoperative lung cancer patients, which affects patients’ early postoperative recovery to varying degrees. However, the current status of the incidence of abdominal distension in postoperative lung cancer patients and the affecting factors are not well understood. This study aims at exploring the incidence of abdominal distension in postoperative lung cancer patients in ICU based on real-world data and analyzing its influencing factors. Methods A retrospective cohort study was conducted, encompassing patients who underwent lung cancer resections in the Lung Cancer Center of West China Hospital of Sichuan University from April 2020 to April 2021. Nevertheless, patients younger than 18 years and those whose information was limited in medical records were excluded. All data were obtained from the hospital HIS system. In this study, the influencing factors of abdominal distension were analyzed by univariate analysis and multiple logistic regression methods. Results A total of 1317 patients met eligibility criteria, and were divided into the abdominal distended group and the non-distended group according to whether abdominal distension occurred after surgery. Abdominal distension occurred in a total of 182 cases(13.8%). The results of the univariate analysis showed that, compared with the non-distended group, the abdominal distended group had these features as follows: more women (P = 0.021), older (P = 0.000), lower BMI (P = 0.000), longer operation duration (P = 0.031), more patients with open thoracotomy (P = 0.000), more patients with pneumonectomy (p = 0.002), more patients with neoadjuvant chemotherapy (P = 0.000), more days of hospitalization on average (P = 0.000), and higher costs of hospitalization on average (P = 0.032). Multifactor logistic regression analysis showed that sex (OR = 0.526; 95% CI = 0.378 ~0.731), age (OR = 1.154; 95%CI = 1.022 ~1.304) and surgical approach (OR = 4.010; 95%CI = 2.781 ~5.781) were independent influencing factors for the occurrence of abdominal distension in patients after lung cancer surgery in ICU. Conclusions The incidence of abdominal distension was high in postoperative lung cancer patients in ICU, and female, older and patients with open thoracotomy were more likely to experience abdominal distension. Trial registration The study was approved by the Chinese Clinical Trials Registry (registration number was ChiCTR2200061370).

Abstract Background This study was designed to perform a comparative analysis between endoscopic ultrasonography (EUS) and double contrast-enhanced ultrasonography (DCEUS) for the preoperative diagnosis of gastric stromal tumors (GSTs). Methods A retrospective study was conducted involving 139 patients with histologically confirmed GSTs. All patients preoperatively underwent DCEUS and EUS. The pathology reports were treated as the baseline and were retrospectively compared with the findings of EUS and DCEUS. Results Of the 139 lesions, 120 and 113 were correctly identified by DCEUS and EUS, respectively, with an accuracy of 86.3% and 81.3%. The results revealed an insignificant difference between these two methods (p = 0.189). Conclusions DCEUS can display not only the locations, sizes, shapes, borders, internal echoes, but also show the blood perfusion patterns of GSTs. It is a highly accurate, noninvasive, and convenient method to be used at the pre-treatment stage.

Scientific evaluation of cultivated land quality (CLQ) is necessary for promoting rational utilization of cultivated land and achieving one of the Sustainable Development Goals (SDGs): Zero Hunger. However, the CLQ evaluation system proposed in previous studies was diversified, and the methods were inefficient. In this study, based on China’s first national standard “Cultivated Land Quality Grade” (GB/T 33469-2016), we constructed a unified county-level CLQ evaluation system by selecting 15 indicators from five aspects—site condition, environmental condition, physicochemical property, nutrient status and field management—and used the Delphi method to calculate the membership degree of the indicators. Taking Jimo district of Shandong Province, China, as a case study, we compared the performance of three machine learning models, including random forest, AdaBoost, and support vector regression, to evaluate CLQ using multi-temporal remote sensing data. The comprehensive index method was used to reveal the spatial distribution of CLQ. The results showed that the CLQ evaluation based on multi-temporal remote sensing data and machine learning model was efficient and reliable, and the evaluation results had a significant positive correlation with crop yield (r was 0.44, p < 0.001). The proportions of cultivated land of high-, medium- and poor-quality were 27.43%, 59.37% and 13.20%, respectively. The CLQ in the western part of the study area was better, while it was worse in the eastern and central parts. The main limiting factors include irrigation capacity and texture configuration. Accordingly, a series of targeted measures and policies were suggested, such as strengthening the construction of farmland water conservancy facilities, deep tillage of soil and continuing to construct well-facilitated farmland. This study proposed a fast and reliable method for evaluating CLQ, and the results are helpful to promote the protection of cultivated land and ensure food security.

Using the co-seismic response data from the DSQ water-tube tiltmeter and the VS vertical pendulum tiltmeter at the Ganzhou seismic center station in Jiangxi, we analyze the maximum response amplitude, the delay time and the continuous response time of the two instruments. The results show that: ① There is a positive correlation between the continuous response time and magnitude; ② There is a positive correlation between the delay time and epicenter distance; ③ Because of the differences of instruments design and observation principle, the recorded co-seismic response signals are different.

Abstract Sexual reproduction in fungi promotes genetic diversity and helps the fungus to adapt to environmental stresses. Fusarium verticillioides is a heterothallic filamentous ascomycete that is a major cause of maize ear and stalk rot worldwide, while also posing a threat to human and animal health by producing various mycotoxins. Sexual reproduction in F. verticillioides is controlled by the MAT-1 and MAT-2 loci, which mandate that only strains of opposite mating types can mate to yield perithecia and ascospores. Nevertheless, there exists a phenomenon called ‘spore killing’, in which only four typical ascospores appear in the asci following a cross between a strain carrying the spore killer allele (Sk K ) and one with the spore killer sensitive allele (Sk S ). In this study, 31 isolates of F. verticillioides collected from eight provinces in China during the maize growing season from 2014 to 2020 were compared based on their mating type, spore killing genotype, and pathogenicity. To determine the mating types and spore killing genotypes of these isolates, partial sequences were amplified from the MAT loci and the SKC1 gene, respectively. The PCR results showed that out of the 31 isolates, 18 were MAT-1 and 13 were MAT-2, and that 25 had Sk K genotypes and 6 had Sk S genotypes. Genetic crosses between LNF15-11 (MAT-2) and 18 MAT-1 isolates produced normal perithecia with varying numbers. However, crosses between LNF15-11 and the 3 isolates (SDF18-36, HNF14-8, and GSF19-6) produced only four ascospores per ascus, while the remaining isolates except SDF18-28, yielded eight ascospores per ascus. These findings suggest that the SKC1 amplicon variation can be used to differentiate Sk K and Sk S genotypes in the field and that the 3 isolates are truly Sk S genotypes with the MAT-1 allele. Altogether, this study contributes to our knowledge of the mating type and spore killing genotype of F. verticillioides in China and offers valuable strain resources for investigating heterothallic sexual reproduction.

In this study, a zein-stabilized lemon essential oil Pickering emulsion (ZLPE) was incorporated into a carboxymethyl cellulose/gelatin (CMC/GL) composite film to develop a bio-based packaging material with bioactive properties. The average droplet size of the ZLPE was measured at 3.62 ± 0.08 μm, with a zeta potential of −31.33 ± 0.32 mV, highlighting its excellent stability. The image results of confocal laser microscopy and scanning electron microscopy validated the uniform distribution of ZLPE in the film. The incorporation of ZLPE reduced the water solubility of films by 45.90% and decreased its water vapor permeability by 22.61%, thereby enhancing its hydrophobicity. Additionally, the ZLPE-loaded film improved mechanical properties, enhanced UV-blocking capabilities, and increased thermal stability. The introduction of ZLPE led to the antioxidant activity of the CMC/GL film increasing by six times the original level and endowed it with outstanding antibacterial properties. As a result, cherries packaged with the ZLPE film demonstrated superior preservation performance and extended shelf life in the preservation experiment, exhibiting the film’s potential as a food packaging material.

Hyperproliferative keratinocytes and subcutaneous inflammation contribute to the characteristic symptoms of psoriasis, including erythema, scales, or scaly plaques on the skin. These symptoms significantly affect patients’ quality of life and cause severe physical and psychological distress. However, current treatment strategies have limited therapeutic effect and may lead to adverse side effects. In this study, we present the novel organic photosensitizer TBTDC [5-(((5-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)methylene)amino)-3-methylthiophene-2,4-dicarbonitrile] nanoparticles (NPs) with aggregation-induced emission (AIE) characteristics to mediate photodynamic therapy (TBTDC NP-PDT) for psoriasis treatment. We demonstrate that TBTDC NPs effectively generate reactive oxygen species upon light irradiation and lead to significant apoptosis of psoriatic keratinocytes. Furthermore, TBTDC NPs exhibit high cellular uptake in diseased keratinocytes and induce endoplasmic reticulum stress (ERS)-mediated autophagy, which can also enhance apoptosis. Importantly, TBTDC NPs show no cytotoxicity toward keratinocytes. These unique properties of TBTDC NPs enable remarkable therapeutic effects against psoriasis-like skin lesions and related inflammation in vivo. Overall, our AIE-active TBTDC NP-PDT represents a promising strategy for treating psoriasis in clinical settings.

Abstract Background Although biomedical implants have been widely used in orthopedic treatments, two major clinical challenges remain to be solved, one is the bacterial infection resulting in biofilm formation, and the other is aseptic loosening during implantation due to over-activated osteoclastogenesis. These factors can cause many clinical issues and even lead to implant failure. Thus, it is necessary to endow implants with antibiofilm and aseptic loosening-prevention properties, to facilitate the integration between implants and bone tissues for successful implantation. To achieve this goal, this study aimed to develop a biocompatible titanium alloy with antibiofilm and anti-aseptic loosening dual function by utilizing gallium (Ga) as a component. Methods A series of Ti-Ga alloys were prepared. We examined the Ga content, Ga distribution, hardness, tensile strength, biocompatibility, and anti-biofilm performance in vitro and in vivo. We also explored how Ga3+ ions inhibited the biofilm formation of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) and osteoclast differentiation. Results The alloy exhibited outstanding antibiofilm properties against both S. aureus and E. coli in vitro and decent antibiofilm performance against S. aureus in vivo. The proteomics results demonstrated that Ga3+ ions could disturb the bacterial Fe metabolism of both S. aureus and E. coli, inhibiting bacterial biofilm formation. In addition, Ti-Ga alloys could inhibit receptor activator of nuclear factor-κB ligand (RANKL)-dependent osteoclast differentiation and function by targeting iron metabolism, then suppressing the activation of the NF-κB signaling pathway, thus, showing their potential to prevent aseptic loosening. Conclusion This study provides an advanced Ti-Ga alloy that can be used as a promising orthopedic implant raw material for various clinical scenarios. This work also revealed that iron metabolism is the common target of Ga3+ ions to inhibit biofilm formation and osteoclast differentiation.

Abstract Background Both the crystalline and soluble forms of cholesterol increase macrophage secretion of interleukin 1β (IL-1β), aggravating the inflammatory response in atherosclerosis (AS). However, the link between cholesterol and regulatory T cells (Tregs) remains unclear. This study aimed to investigate the effect of cholesterol treatment on Tregs. Methods Differentiation of induced Tregs (iTregs) was analyzed using flow cytometry. The expression of hypoxia-inducible factor-1a (HIF-1a) and its target genes was measured by western blotting and/or RT-qPCR. Two reporter jurkat cell lines were constructed by lentiviral transfection. Mitochondrial function and the structure of natural Tregs (nTregs) were determined by tetramethylrhodamine (TMRM) and mitoSOX staining, Seahorse assay, and electron microscopy. The immunoregulatory function of nTregs was determined by nTreg-macrophage co-culture assay and ELISA. Results Cholesterol treatment suppressed iTreg differentiation and impaired nTreg function. Mechanistically, cholesterol induced the production of mitochondrial reactive oxygen species (mtROS) in naïve T cells, inhibiting the degradation of HIF-1α and unleashing its inhibitory effects on iTreg differentiation. Furthermore, cholesterol-induced mitochondrial oxidative damage impaired the immunosuppressive function of nTregs. Mixed lymphocyte reaction and nTreg-macrophage co-culture assays revealed that cholesterol treatment compromised the ability of nTregs to inhibit pro-inflammatory conventional T cell proliferation and promote the anti-inflammatory functions of macrophages. Finally, mitoTEMPO (MT), a specific mtROS scavenger, restored iTreg differentiation and protected nTreg from further deterioration. Conclusion Our findings suggest that cholesterol may aggravate inflammation within AS plaques by acting on both iTregs and nTregs, and that MT may be a promising anti-atherogenic drug.

Rice bran is an important byproduct of the rice polishing process, rich in nutrients, but it is underutilized and often used as feed or discarded, resulting in a huge amount of waste. In this study, rice bran was fermented by Lactobacillus fermentum MF423 to obtain a product with high antioxidant activity. First, a reliable and efficient method for assessing the antioxidant capacity of the fermentation products was established using high-performance liquid chromatography (HPLC), which ensured the consistency of the batch fermentation. The fermented rice bran product (FLRB) exhibited significant antioxidant activity in cells, C. elegans, and hyperlipidemic mice. Transcriptome analysis of mouse livers showed that the expression of plin5 was upregulated in diabetic mice administered FLRB, thereby preventing the excessive production of free fatty acids (FFAs) and the subsequent generation of large amounts of reactive oxygen species (ROS). These studies lay the foundation for the application of rice bran fermentation products.

Neuromedin U receptor 2 is an emerging attractive target for treating obesity. Here, a Cryo-EM structure of NmU-25–NMU2–Gi1 provides the structural basis for the designation of highly selective drugs.

Current in vitro models for osteosarcoma investigation and drug screening, including two-dimensional (2D) cell culture and tumour spheroids (i.e. cancer stem-like cells), lack extracellular matrix (ECM). Therefore, results from traditional models may not reflect real pathological processes in genuine osteosarcoma histological structures. Here, we report a three-dimensional (3D) bioprinted osteosarcoma model (3DBPO) that contains osteosarcoma cells and shrouding ECM analogue in a 3D frame. Photo-crosslinkable bioinks composed of gelatine methacrylamide and hyaluronic acid methacrylate mimicked tumour ECM. We performed multi-omics analysis, including transcriptomics and DNA methylomics, to determine differences between the 3DBPO model and traditional models. Compared with 2D models and tumour spheroids, our 3DBPO model showed significant changes in cell cycle, metabolism, adherens junctions, and other pathways associated with epigenetic regulation. The 3DBPO model was more sensitive to therapies targeted to the autophagy pathway. We showed that simulating ECM yielded different osteosarcoma cell metabolic characteristics and drug sensitivity in the 3DBPO model compared with classical models. We suggest 3D printed osteosarcoma models can be used in osteosarcoma fundamental and translational research, which may contribute to novel therapeutic strategy discovery.

Summary: Emerging evidence supports that intestinal microbial metabolite short-chain fatty acids (SCFAs) increase the pool of regulatory T cells (Tregs) in the colonic lamina propria (cLP) and protect against nonintestinal inflammatory diseases, such as atherosclerosis and post-infarction myocardial inflammation. However, whether and how SCFAs protect the inflamed aortas of subjects with abdominal aortic aneurysm (AAA) remains unclear. Here, the authors revealed the protective effect of SCFAs on AAA in mice and the expansion of Tregs in the cLP, and propionate exerted Treg-dependent protection against AAA by promoting the recirculation of cLP-Tregs through colonic draining lymph nodes (dLNs) to the inflamed aorta.

Objective: To evaluate the interbody fusion efficacy and biocompatibility of a graft-free cage made of polyetheretherketone/calcium silicate composite/porous tantalum (PEEK/CS/pTa cage) compared with a PEEK/CS cage with an autogenous bone graft in a goat model. Methods: PEEK/CS/pTa and PEEK/CS cages were prepared through an injection-moulding method. The PEEK/CS composites and porous tantalum were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive spectroscopy (EDS) mapping. Then, adult goats were chosen for C2/C3 and C3/C4 discectomy via the anterior cervical approach and randomly implanted with PEEK/CS/pTa and PEEK/CS/cages with autogenous bone grafts. The fusion performance and osseointegration of the cages were evaluated by X-ray imaging, magnetic resonance imaging (MRI) scanning, and bone histomorphometry analysis. Moreover, the concentrations of Ca and Si in urine, serum, tissue around the fusion segments and major organs of the goats were determined by inductively coupled plasma–optical emission spectrometry (ICP–OES). Histological observation of major organs of the goats was used to evaluate the biosafety of PEEK/CS/pTa and PEEK/CS cages. Results: X-ray and MRI imaging suggested that both PEEK/CS/pTa cages and PEEK/CS cages maintained similar average intervertebral space heights. The tissue volumes in the fusion area were comparable between the two groups of cages at 26 weeks after surgery. Histological morphometric data showed that PEEK/CS/pTa cages and PEEK/CS cages with autogenous bone grafts had similar bone contact and osseointegration at 12 and 26 weeks. Element determination of serum, urine, spinal cord, dura matter, bone and organs showed that the CS/PEEK cages did not cause abnormal systemic metabolism or accumulation of calcium and silicon in local tissues and major organs of goats after implantation. No obvious pathological changes were found in the heart, liver, spleen, liver or kidney tissues. Conclusion: Overall, these results suggested that the graft-free PEEK/CS/pTa cage showed similar bony fusion performance to the PEEK/CS cages with autogenous bone grafts. The cages releasing calcium and silicon had good biological safety in vivo.The translational potential of this article: This study provided a new graft-free interbody fusion solution to patients with degenerative disc diseases, which could avert potential donor-site complications. This study also provided a detailed assessment of element excretion and accumulation of Ca and Si in vivo, which validated the biosafety of this new type of bioactive interbody fusion cage.

Ni–Al–Ti nanocomposite coatings were synthesized by electrodeposition. The tailoring role of Al and Ti particles in the co-deposition behaviors of nanocomposite coatings was comprehensively investigated by analyzing the time-dependent current density and electric field near the co-deposited particles. The results showed that the Al and Ti particles caused different co-deposition behaviors of Ni deposits, consequently bringing in the gradual increase in the surface dendritic structure, the refinement of grain sizes, and the decrease in the [200] fiber texture of the nanocomposite coatings with the decrease in the Al/Ti weight ratio. COMSOL simulations verified the different co-deposition mechanisms of Ni grains near the two kinds of particles, which was vitally determined by the different conditions of current density and electric field near the particles. The micro-hardness results revealed that the decreased Al/Ti weight ratio led to enhanced micro-hardness of the nanocomposite coating; in addition, the maximum hardness of the nanocomposite coating was 604.3 HV0.2 for an Al/Ti weight ratio of 1:4. Thus, the time-dependent current density and electric field near co-deposited Al and Ti particles determined the microstructure and property of the Ni–Al–Ti nanocomposite coatings.

Rice productivity relies heavily on nitrogen fertilization, and improving nitrogen use efficiency (NUE) is important for hybrid rice breeding. Reducing nitrogen inputs is the key to achieving sustainable rice production and reducing environmental problems. Here, we analyzed the genome-wide transcriptomic changes in microRNAs (miRNAs) in the indica rice restorer cultivar Nanhui 511 (NH511) under high (HN) and low nitrogen (LN) conditions. The results showed that NH511 is sensitive to nitrogen supplies and HN conditions promoted the growth its lateral roots at the seedling stage. Furthermore, we identified 483 known miRNAs and 128 novel miRNAs by small RNA sequencing in response to nitrogen in NH511. We also detected 100 differentially expressed genes (DEGs), including 75 upregulated and 25 downregulated DEGs, under HN conditions. Among these DEGs, 43 miRNAs that exhibited a 2-fold change in their expression were identified in response to HN conditions, including 28 upregulated and 15 downregulated genes. Additionally, some differentially expressed miRNAs were further validated by qPCR analysis, which showed that miR443, miR1861b, and miR166k-3p were upregulated, whereas miR395v and miR444b.1 were downregulated under HN conditions. Moreover, the degradomes of possible target genes for miR166k-3p and miR444b.1 and expression variations were analyzed by qPCR at different time points under HN conditions. Our findings revealed comprehensive expression profiles of miRNAs responsive to HN treatments in an indica rice restorer cultivar, which advances our understanding of the regulation of nitrogen signaling mediated by miRNAs and provides novel data for high-NUE hybrid rice cultivation.

Background: We aimed to analyse the discrepancy in clinical features and prognosis between molecular subtypes in primary ductal carcinoma in situ (DCIS) patients with lumpectomy. Methods: Primary DCIS patients were identified from the Surveillance, Epidemiology, and End Results registries database from 2010 to 2017. Based on immunohistochemistry markers of hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2), enrolled DCIS cases were divided into four molecular subtypes, HR-HER2-, HR-HER2+, HR + HER2+, and HR + HER2-. Clinical features and prognosis were compared between molecular subtypes. Radiotherapy (RT) effects on prognosis were also analysed in each molecular subtype. Results: A total of 5,628 DCIS cases were retrospectively enrolled in this study. HR-HER2-, HR-HER2+, HR+HER2+, and HR+HER2- are 299 (5.3%), 498 (8.8%), 1,086 (19.3%), and 3,745 (66.5%), respectively. HR + HER2- cases have smaller tumor size (72.6%, P

Highlights The DC-targeting immune-regulating nanostrategy was firstly employed to treat RA. The complex immune regulating effects was realized through a portable, convenient and green nanomaterial. Highlighting the significance of zinc and oxygen homeostasis for the immunoregulation of RA by inducing tDCs with modified ZnO2 NPs. Expanding the notion of ion homeostasis regulation with a larger variety of distinct metal or nonmetal ions.

Abstract Diabetic osteoporosis (DOP) is the leading complication continuously threatening the bone health of patients with diabetes. A key pathogenic factor in DOP is loss of osteocyte viability. However, the mechanism of osteocyte death remains unclear. Here, we identified ferroptosis, which is iron-dependent programmed cell death, as a critical mechanism of osteocyte death in murine models of DOP. The diabetic microenvironment significantly enhanced osteocyte ferroptosis in vitro, as shown by the substantial lipid peroxidation, iron overload, and aberrant activation of the ferroptosis pathway. RNA sequencing showed that heme oxygenase-1 (HO-1) expression was notably upregulated in ferroptotic osteocytes. Further findings revealed that HO-1 was essential for osteocyte ferroptosis in DOP and that its promoter activity was controlled by the interaction between the upstream NRF2 and c-JUN transcription factors. Targeting ferroptosis or HO-1 efficiently rescued osteocyte death in DOP by disrupting the vicious cycle between lipid peroxidation and HO-1 activation, eventually ameliorating trabecular deterioration. Our study provides insight into DOP pathogenesis, and our results provide a mechanism-based strategy for clinical DOP treatment.

Abstract Background To investigate the analgesic effect of perioperative use of duloxetine in patients received total knee arthroplasty (TKA). Method This prospective randomized, double-blind, placebo-controlled trial study was registered in the Chinese Clinical Trial Registry (ChiCTR2000033910). 100 patients were finally enrolled. The hospital pharmacy prepared small capsules containing either duloxetine or starch (placebo) which were all identical in appearance and weight (50:50). The 100 enrolled patients were given a capsule (containing either 60 mg duloxetine or 60 mg placebo) every night before sleep since preoperative day 2 till postoperative day 14 (17 days in all) by a nurse who were not involved in this trial. Other perioperative managements were the same in the two groups. The primary outcome was the VAS score, including rVAS (visual analogue scale at rest) and aVAS (visual analogue scale upon ambulation) throughout the perioperative period. The secondary outcomes included opioid consumption, range of motion, including both active range of motion (aROM) and passive range of motion (pROM) and adverse events. The patients were followed up everyday until 7 days after TKA, afterwards, they were followed up at the time of 3 weeks and 3 months after TKA. Result rVAS in duloxetine group were significantly less than placebo group throughout the postoperative period: 4.7 ± 2.3 vs 5.9 ± 2.6 (P = 0.016) at 24 h postoperative; 2.1 ± 1.6 vs 2.8 ± 1.7 (P = 0.037) at 7 days postoperative. In terms of aVAS, similarly, duloxetine group had less aVAS than placebo group throughout the postoperative period: 6.2 ± 2.1 vs 7.1 ± 2.2 (P = 0.039) at 24 h postoperative; 3.3 ± 1.7 vs 4.1 ± 2.0 (P = 0.034) at 7 days postoperative. Patients in duloxetine group consumed significantly less opioids per day than the placebo group: 24.2 ± 10.1 g vs 28.5 ± 8.3 g (P = 0.022) at 24 h postoperative; 2.7 ± 2.5 g vs 4.1 ± 2.6 g (P = 0.007) at 7 days postoperative. aROM in duloxetine group were significantly better than placebo group until postoperative day 6, the aROM became comparable between the two groups: 110.2 ± 9.9° in duloxetine group vs 107.5 ± 11.5° in control group (P = 0.211). In terms of pROM, duloxetine group had significantly better pROM until postoperative day 5, the pROM became comparable between the two groups: 103.8 ± 12.1° in duloxetine group vs 99.5 ± 10.8° in control group (P = 0.064). No significant difference was found between the two groups in the rates of dizziness, bleeding, sweating, fatigue and dryness of mouth. In the placebo group, more patients got nausea/vomiting and constipation (P

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease with complex disease mechanisms. Here the authors report that the E3 ubiquitin-protein ligase Trim31 mitigates development of NASH via inhibition of rhomboid 5 homolog 2 (Rhbdf2) in mice.

Pre-spill and post-spill passive acoustic data collected by multiple fixed acoustic sensors monitoring about 2400 km2 area to the west of the Deepwater Horizon oil spill in the northern Gulf of Mexico (GoM) were analyzed to understand long term local density trends and habitat use by different species of beaked whales. The data were collected in the Mississippi Valley/Canyon area between 2007 and 2017. A multistage algorithm based on unsupervised machine learning was developed to detect and classify different species of beaked whales and to derive species- and site-specific densities in different years before and after the oil spill. The results suggest that beaked whales continued to occupy and feed in these areas following the Deepwater Horizon oil spill thus raising concerns about (1) potential long-term effects of the spill on these species and (2) the habitat conditions after the spill. The average estimated local density of Cuvier’s beaked whales at the closest site, about 16 km away from the spill location showed statistically significant increase from July 2007 to September 2010, and then from September 2010 to 2015. This is the first acoustic study showing that Gervais’ beaked whales are predominantly present at the shallow site and that Cuvier’s species dominate at two deeper sites, supporting the habitat division (ecological niche) hypothesis. The findings call for continuing high-spatial-resolution long-term observations to fully characterize baseline beaked whale population and habitat use, to understand the causes of regional migrations, and to monitor the long-term impact of the spill.

Background: Hepatocellular carcinoma (HCC) is one of the most malignant type of cancers. Leuci carboxyl methyltransferase 1 (LCMT1) is a protein methyltransferase that plays an improtant regulatory role in both normal and cancer cells. The aim of this study is to evaluate the expression pattern and clinical significance of LCMT1 in HCC. Methods: The expression pattern and clinical relevance of LCMT1 were determined using the Gene Expression Omnibus (GEO) database, the Cancer Genome Atlas (TCGA) program, and our datasets. Gain-of-function and loss-of-function studies were employed to investigate the cellular functions of LCMT1 in vitro and in vivo. Quantitative real-time polymerase chain reaction (RT-PCR) analysis, western blotting, enzymatic assay, and high-performance liquid chromatography were applied to reveal the underlying molecular functions of LCMT1. Results: LCMT1 was upregulated in human HCC tissues, which correlated with a “poor” prognosis. The siRNA-mediated knockdown of LCMT1 inhibited glycolysis, promoted mitochondrial dysfunction, and increased intracellular pyruvate levels by upregulating the expression of alani-neglyoxylate and serine-pyruvate aminotransferase (AGXT). The overexpression of LCMT1 showed the opposite results. Silencing LCMT1 inhibited the proliferation of HCC cells in vitro and reduced the growth of tumor xenografts in mice. Mechanistically, the effect of LCMT1 on the proliferation of HCC cells was partially dependent on PP2A. Conclusions: Our data revealed a novel role of LCMT1 in the proliferation of HCC cells. In addition, we provided novel insights into the effects of glycolysis-related pathways on the LCMT1regulated progression of HCC, suggesting LCMT1 as a novel therapeutic target for HCC therapy.

Abstract. Objective:. Observational studies indicate that insomnia may increase the risk of developing and/or dying from cardiovascular diseases, especially coronary artery disease (CAD). Our purpose is to explore the underlying causal relationship between genetic variants susceptible to insomnia and the risk of CAD by Mendelian randomization analysis. Methods:. The study was conducted using publicly available statistical data on genetic variants identified from a genome-wide association meta-analysis of insomnia (n = 113,006 individuals) and a genome-wide association meta-analysis of CAD (n = 184,305 individuals), which consisted of both cases and non-cases. The genetic association between variants and CAD was assessed by the variants’ association with insomnia, and estimations were integrated by an inverse-variance weighted meta-analysis. Results:. Among the Mendelian randomized analytical sample, 8 variants were associated with insomnia complaints and CAD. And there was no pleiotropic association with the latent confounders. In addition, in the inverse-variance weighted meta-analysis (the estimations combined from the 8 variants), the odds ratio was 1.15 (95% CI: 1.05–1.25; P = 0.002) for CAD, and in the weighted method analysis, the odds ratio was 1.14 (95% CI: 1.03–1.27; P = 0.015) for CAD. Conclusions:. All of the data indicated that some valuable variants might involve in the development of CAD by leading the insomnia. Therefore, insomnia might be a causal factor for CAD, and improving the quality of sleep might be a new way for populations with insomnia to prevent CAD.

Background: Lincang City in Yunnan Province on the China-Myanmar border, has reached the World Health Organization recommended coverage (95%) for measles-containing vaccine (MCV), but measles outbreaks still occur. We conducted a survey in Lincang City to determine the measles vaccination status of children on the China–Myanmar border. Methods: We used multistage sampling among children aged 8–83 months. Information on measles vaccination status was obtained from the child’s vaccination certificate, and serum samples were tested using commercially available ELISA kits. Results: A total of 938 children were surveyed. The vaccination coverage rate was 98.9% (95% CI: 98.2–99.6%) for measles–containing vaccine dose 1 (MCV1), and 95.8% (95% CI:94.9–96.7%) for measles–containing vaccine dose 2 (MCV2). The timely vaccination coverage rate was 52.0% (95% CI:48.8–55.2%) for MCV1, and 74.1% (95% CI: 82.9–89.0%) for MCV2. The timely-and–complete vaccination coverage rate was 41.0% (95% CI: 36.7–45.3%). The median delay period was 33 (95% CI: 27–39) days for MCV1, and 196 (95% CI: 146–246) days for MCV2. The seropositivity rate in children aged less than 7 years was 94.0% (95% CI: 92.5–95.5%) with a geometric mean titer of 1210.1 mIU/mL. Conclusions: The MCV coverage was high, but timely and timely-and-complete vaccination coverage were low and insufficient to prevent measles outbreaks. It is necessary to add the timely and timely-and-complete vaccination coverage as indicators of vaccination to provide a more complete picture of measles immunization status.

In recent year, the identification of characteristics of earthquake and explosion is one of the key technologies for earthquake event classification and recognition, and has made to a considerable development and progress. The overall review of existing identification and characteristic extraction method is carried out, in order to establish a platform for identification of characteristics of earthquake and explosion future researches.

Abstract Background Although middle-aged and elderly users are the main group targeted by health maintenance-oriented WeChat official accounts (HM-WOAs), few studies have explored the relationship of these accounts and their users. Exploring the factors that influence the continuous adoption of WOAs is helpful to strengthen the health education of middle-aged and elderly individuals. Objective We developed a new theoretical model and explored the factors that influence middle-aged and elderly individuals' continuous usage intention for HM-WOA. Performance expectancy mediated the effects of the model in explaining continuous usage intention and introduced health literacy into the model. Methods We established a hybrid theoretical model on the basis of the unified theory of acceptance and use of technology 2 model (UTAUT2), the health belief model (BHM), protection motivation theory (PMT), and health literacy. We collected valid responses from 396 middle-aged and elderly users aged ≥ 45 years in China. To verify our hypotheses, we analyzed the data using structural equation modeling. Results Performance expectancy (β = 0.383, P

Background: Clinic treatment of diabetic foot ulcers (DFUs) is considerably challenging. Impaired wound healing may be caused by poor vascularization and dysfunction of the extracellular matrix, which leads to poor re-epithelialization and increased risk of infection. In this study, we evaluated the treatment potential of a functional dressing comprising quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan) and magnesium (Mg) on DFUs. Methods: Dressings were prepared by vacuum freeze-drying. The cellular proliferation, migration, and angiogenesis potential of the functional dressings were determined in vitro. Methicillin-resistant Staphylococcus aureus (MRSA, ATCC43300) and methicillin-resistant Staphylococcus epidermidis 287 (MRSE287) were used to evaluate the antibacterial efficiency of the dressings. Finally, a diabetic rat model with infected wounds was used to further evaluate the effects of functional dressings on the healing of DFUs. Results: Functional dressings facilitated the migration of human dermal fibroblasts and human umbilical vein endothelial cells (HUVECs), while also stimulating angiogenesis in HUVECs. Additionally, the functional dressing could effectively eradicate MRSA and MRSE, exhibiting excellent antibacterial ability against drug-resistant bacteria. The results of in vivo microbiological and histological tests demonstrated effective anti-infection ability and wound-healing potential of this functional dressing. Conclusions: The dual-functional dressing exhibited wound-healing ability and anti-infection efficiency, demonstrating potential application prospects in DFU treatment. Translational potential of this article: As one of the common and serious complications of diabetes, DFUs do not heal easily, causing great suffering to patients. Therefore, improvement in the prognosis of DFUs is a crucial clinical need. The dual-functional dressing prepared in this study was proven to improve the treatment of DFUs, both in vitro and in vivo. Considering its urgent clinical necessity and good biocompatibility of its raw materials, such as alginate, Mg, and chitosan derivatives, this dual-functional dressing presents good prospects for clinical translation.

Ischemia/reperfusion caused by cardiac arrest (CA) disturbs endoplasmic reticulum (ER) homeostasis and redox balance in neurons. AA147, originally developed as a pharmacologic activator of the activating transcription factor 6 (ATF6), can protect multiple tissues from ischemia/reperfusion injury (IRI) by decreasing reactive oxygen species (ROS) and restoring ER function. However, it is unclear whether pharmacologic treatment of AA147 could ameliorate post-CA cerebral IRI and whether it is associated with proteostasis regulation and anti-oxidative stress mechanism. In the present study, mice were subjected to 9 min-CA surgery followed by cardiopulmonary resuscitation (CPR). AA147 or vehicle was administered 1 day before the operation and 15 min after the return of spontaneous circulation. We found that AA147 restored neurological function and reduced dead neurons in mice suffering from CA. Moreover, AA147 inhibited CA/CPR-caused neuronal apoptosis and ER stress, indicated by reduced TUNEL-positive neurons, surged expression of Bcl-2/Bax, and down expression of cleaved caspase-3, caspase-12, C/EBP homologous protein (CHOP). The expression of ATF6 and its regulated gene glucose-regulated protein 78 (GRP78) increased significantly after the administration of AA147, suggesting the activation of the ATF6 pathway. In addition, AA147 also alleviated the upsurge of the ROS generation and MDA levels as well as increased SOD activity, accompanied by enhancement of the nuclear factor E2-related factor 2 (Nrf2) and its modulated heme-oxygenase-1 (HO-1) expressions. Cotreatment of AA147 with inhibitors of the ATF6 or Nrf2 significantly suppressed AA147-dependent reductions in ROS scavenging and neuronal death after CA/CPR. The results suggested that AA147 could confer neuroprotection against post-CA cerebral IRI through inhibition of oxidative stress along with ER stress-associated apoptosis, which is attributed to the coregulation of both ATF6 and Nrf2 signaling pathways activity. Our findings support the potential for AA147 as a therapeutic approach to improve post-CA brain injury.

Improving plant nitrogen-use efficiency (NUE) has great significance for various crops, particularly in hybrid breeding. Reducing nitrogen inputs is key to achieving sustainable rice production and mitigating environmental problems. In this study, we analyzed the transcriptomic and physiological changes in two indica restorer lines (Nanhui511 [NH511] and Minghui23 [MH23]) under high nitrogen (HN) and low nitrogen (LN) conditions. Compared to MH23, NH511 was more sensitive to different nitrogen supplies and exhibited higher nitrogen uptake and NUE under HN conditions by increasing lateral root and tiller numbers in the seedling and maturation stages, respectively. NH511 also exhibited a lower survival rate than MH23 when planted in a chlorate-containing hydroponic solution, indicating its HN uptake ability under different nitrogen-supply conditions. Transcriptomic analysis showed that NH511 has 2456 differentially expressed genes, whereas MH23 had only 266. Furthermore, these genes related to nitrogen utilization showed differential expression in NH511 under HN conditions, while the opposite was observed in MH23. Our findings revealed that NH511 could be regarded as elite rice and used for breeding high-NUE restorer lines by regulating and integrating nitrogen-utilization genes, which provides novel insights for the cultivation of high-NUE hybrid rice.

Abstract Background Pancreatic cancer (PC) is one of the most lethal cancer types with high degree of malignancy and poor prognosis. Recent studies have shown that long non-coding RNAs (lncRNAs) were associated with the initiation and progression of pancreatic cancer. In the current study, we have investigated the expression, biological function and mechanism of a lncRNA CTD-3252C9.4 in pancreatic cancer. Methods The expression of CTD-3252C9.4 in pancreatic cancer cells and tissues was measured by qRT-PCR. In vitro and in vivo functional experiments assays were implemented for identifying CTD-3252C9.4 function in pancreatic cancer. Molecular relationships among CTD-3252C9.4, IRF1 and IFI6 were investigated via luciferase reporter assay, pulldown assay and ChIP assays. Results CTD-3252C9.4 was found remarkably decreased in pancreatic cancer cells and tissues. Overexpression of CTD-3252C9.4 suppressed migration, invasion and proliferation, yet facilitated apoptosis of pancreatic cancer cells both in vitro and in vivo. Then, IFI6 was identified as a downstream target that could be down-regulated by CTD-3252C9.4 and IFI6 overexpression could counteract the effects of CTD-3252C9.4 upregulation on the survival and apoptosis of pancreatic cancer cells. Furthermore, mechanism experiments revealed that IRF1 was a transcriptional factor of IFI6 that can be blocked by CTD-3252C9.4 to inhibit IFI6 transcription. Conclusion Our data indicated that CTD-3252C9.4 could promote pancreatic cancer cell apoptosis and restrain cell growth via binding IRF1 and preventing the transcription of IFI6, which may become a potential therapeutic target for pancreatic cancer.

Background: The intention of Chinese people older than age 5 to accept the pertussis vaccination is unknown, which is important for the future design of an effective pertussis vaccination program in China. Method: We conducted a cross-sectional survey among people older than age 5 in China. A 24-item questionnaire was used to explore the determinants of intention to accept a pertussis vaccination, and for children and adolescents (≦15 years old), their guardian was required to help answer the questionnaire on their behalf. Univariate and multivariate logistic regression was used to analyze the influencing factors of intention. Results: A total of 3,041 individuals participated in our survey and 3025 completed the questionnaire, among which 1938 (64.07%) reported a positive intention to be vaccinated. A multiple logistic regression analysis revealed that the main positive factors for the intention to accept pertussis vaccination were younger age (Odd ratio [OR] 0.838, P

The earthquake early warning system is formed by seismic stations and the urgent information systems. Many seismic stations are added to the original seismic monitoring network and old operation systems are upgraded. Early warning and emergency earthquake information to the public and government departments can be published rapidly. This article introduces the earthquake early warning network of Jiangxi Province and evaluates the seismic monitoring capability.

Large bone defects face a high risk of pathogen exposure due to open wounds, which leads to high infection rates and delayed bone union. To promote successful repair of infectious bone defects, fabrication of a scaffold with dual functions of osteo-induction and bacterial inhibition is required. This study describes creation of an engineered progenitor cell line (C3H10T1/2) capable of doxycycline (DOX)-mediated release of bone morphogenetic protein-2 (BMP2). Three-dimensional bioprinting technology enabled creation of scaffolds, comprising polycaprolactone/mesoporous bioactive glass/DOX and bioink, containing these engineered cells. In vivo and in vitro experiments confirmed that the scaffold could actively secrete BMP2 to significantly promote osteoblast differentiation and induce ectopic bone formation. Additionally, the scaffold exhibited broad-spectrum antibacterial capacity, thereby ensuring the survival of embedded engineered cells when facing high risk of infection. These findings demonstrated the efficacy of this bioprinted scaffold to release BMP2 in a controlled manner and prevent the occurrence of infection; thus, showing its potential for repairing infectious bone defects.

We relocated 545 earthquakes that occurred in northern Jiangxi Province，from January 2008 to July 2019，using the double-difference location algorithm to improve relative location accuracy. Compared with the initial locations，the results of precise relocation in Jiujiang，Yichun and Xinyu areas are more concentrated. According to the precise relocation results，composite fault plane solution was calculated with the grid point test method. The result shows that the direction of maximum principal stress of Jiujiang and adjacent areas is nearly EW and that of the minimum principal stress is nearly NS，which is basically consistent with the previous research results. It is considered that the more research is needed to further refine and analyze characteristics of tectonic stress field in Jiujiang area. In Yichun and adjacent areas，the direction of maximum principal stress is nearly EW and that of the minimum principal stress is NNE and the area is in a thrust stress regime.