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The microstructure, phase transformation behavior, heat treatment effects, and their impacts on the mechanical properties and high-temperature oxidation resistance of IN718 nickel-based superalloy processed by selective laser melting (SLM) both before and after heat treatment was systematically investigated. The heat treatment process involved a two-step aging at 720 °C for 8 h plus 620 °C for 10 h with a controlled slow cooling rate of 10 °C/min. Through the comprehensive use of scanning electron microscopy (SEM), X-ray diffraction (XRD), electron backscattering diffraction (EBSD), and transmission electron microscopy (TEM), the evolution of the microstructure and its mechanism of influence on material properties were revealed. The study identified the formation of γ phase, γ′ phase, γ'' phase, δ phase, and Laves phase during the SLM forming process. Heat treatment played a key role in improving the microstructure and properties of the SLM-processed alloy, with experimental results showing that the mechanical performance and high-temperature oxidation resistance were significantly enhanced after heat treatment. Specifically, the material after heat treatment exhibited a yield strength of 1472 MPa, a tensile strength of 1608 MPa, and an elongation of 9.2%, which represented increases of 76.5%, 38.4%, and 16.5% respectively, compared to the as-printed alloy. Moreover, the oxidation resistance at 1000 °C of the heat-treated samples improved significantly, with weight loss reduced from −0.17 mg/cm2 before heat treatment to −0.15 mg/cm2. Microstructural analysis further indicated that heat treatment optimized the crystal orientation, promoted the formation of more precipitated phases and reduced defects, thereby enhancing the overall performance of the material. This work provides significant scientific insights into understanding and optimizing the IN718 nickel-based superalloy processed by SLM, demonstrating the crucial role of heat treatment in improving its microstructure and properties.

This study explores the plastic deformation mechanism and microstructural evolution of as-homogenized and as-forging Inconel 718 alloy through low temperature and slow strain rate hot compression deformation. The stress-strain curves of Inconel 718 alloy were analyzed by modulating the deformation temperature, strain rate, and strain, and the extreme grain refinement process from cast billets (with abnormally coarse grains) to the final compression sample was revealed. The results show that the true stress levels are lower during both low temperature and slow strain rate hot compression, relative to high temperature and fast strain rate deformation. For the as-homogenized Inconel 718 sample, the same grain refinement as the high temperature and fast strain rate (i.e. forging deformation) was achieved by the low temperature and slow strain rate compression deformation. For Inconel 718 samples after forging, uniform, equiaxed, fine grains with an average size of 2.9 μm are obtained at lower deformation temperatures and slower strain rates. Based on these results this low temperature and slow strain rate metallic forming process demonstrates the potential for the application of plastic deformation in controlling grain size, morphology, and distribution, providing a direct, economical, and efficient approach to achieving fine equiaxed grain structures in as-forging metallic materials.

Summary: Background: The ubiquitin regulatory X (UBX) domain-containing proteins (UBXNs) are putative adaptors for ubiquitin ligases and valosin-containing protein; however, their in vivo physiological functions remain poorly characterised. We recently showed that UBXN3B is essential for activating innate immunity to DNA viruses and controlling DNA/RNA virus infection. Herein, we investigate its role in adaptive immunity. Methods: We evaluated the antibody responses to multiple viruses and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza in tamoxifen-inducible global and constitutive B cell-specific Ubxn3b knockout mice; quantified various immune populations, B lineage progenitors/precursors, B cell receptor (BCR) signalling and apoptosis by flow cytometry, immunoblotting and immunofluorescence microscopy. We also performed bone marrow transfer, single-cell and bulk RNA sequencing. Findings: Both global and B cell-specific Ubxn3b knockout mice present a marked reduction in small precursor B-II (>60%), immature (>70%) and mature B (>95%) cell numbers. Transfer of wildtype bone marrow to irradiated global Ubxn3b knockouts restores normal B lymphopoiesis, while reverse transplantation does not. The mature B population shrinks rapidly with apoptosis and higher pro and activated caspase-3 protein levels were observed following induction of Ubxn3b knockout. Mechanistically, Ubxn3b deficiency leads to impaired pre-BCR signalling and cell cycle arrest. Ubxn3b knockout mice are highly vulnerable to respiratory viruses, with increased viral loads and prolonged immunopathology in the lung, and reduced production of virus-specific IgM/IgG. Interpretation: UBXN3B is essential for B lymphopoiesis by maintaining constitutive pre-BCR signalling and cell survival in a cell-intrinsic manner. Funding: United States National Institutes of Health grants, R01AI132526 and R21AI155820.

BackgroundThe correlation between oxidative stress and female infertility pathogenesis was established, and the oxidative balance score (OBS) can serve as a measure of overall oxidative stress burden within an individual. Prior reports have not addressed the relationship between OBS and female infertility. This study endeavors to investigate the association between infertility risk in female and OBS.MethodsThe analysis focused on data from the National Health and Nutrition Examination Survey 2013-2018. OBS was determined from 16 dietary components and 4 lifestyle components. Multivariate logistic regression was employed to investigate the relationship between OBS and female infertility. Further stratified analysis was conducted to examine the associations across various subgroups. To elucidate the dose-response relationship between infertility risk in female and OBS, a restricted cubic spline function was employed.ResultsThe study included a total of 1410 participants. Through weighted multivariable logistic regression analysis, we observed a consistent inverse correlation between OBS and the risk of female infertility [OR (95% CI) = 0.97 (0.95, 0.99), p = 0.047]. When participants were segregated into quartiles based on OBS, those in the highest quartile had a 61% [OR (95% CI) = 0.39 (0.2, 0.79), p = 0.01] reduced risk of infertility compared to those in the lowest quartile of OBS. A trend test assessing OBS by quartile also revealed the relationship between OBS and female infertility. This correlation remained constant across both dietary and lifestyle OBS. Additionally, lifestyle OBS and female infertility exhibited a nonlinear association. A sensitivity analysis verified the consistency of our findings.ConclusionThe study found that a higher OBS is associated with a lower prevalence of female infertility. These results emphasized the potential role of oxidative homeostasis in the pathogenesis of infertility and highlighted the importance of follow-up studies and prevention strategies.

Abstract Background β-Propeller protein-associated neurodegeneration (BPAN) is a genetic neurodegenerative disease caused by mutations in WDR45. The impairment of autophagy caused by WDR45 deficiency contributes to the pathogenesis of BPAN; however, the pathomechanism of this disease is largely unknown. Lipid dyshomeostasis is involved in neurogenerative diseases, but whether lipid metabolism is affected by Wdr45 deficiency and whether lipid dyshomeostasis contributes to the progression of BPAN are unclear. Methods We generated Wdr45 knockout SN4741 cell lines using CRISPR‒Cas9-mediated genome editing, then lipid droplets (LDs) were stained using BODIPY 493/503. Chaperone-mediated autophagy was determined by RT-qPCR and western blotting. The expression of fatty acid synthase (Fasn) was detected by western blot in the presence or absence of the lysosomal inhibitor NH4Cl and the CMA activator AR7. The interaction between Fasn and HSC70 was analyzed using coimmunoprecipitation (Co-IP) assay. Cell viability was measured by a CCK-8 kit after treatment with the Fasn inhibitor C75 or the CMA activator AR7. Results Deletion of Wdr45 impaired chaperone-mediated autophagy (CMA), thus leading to lipid droplet (LD) accumulation. Moreover, Fasn can be degraded via CMA, and that defective CMA leads to elevated Fasn, which promotes LD formation. LD accumulation is toxic to cells; however, cell viability was not rescued by Fasn inhibition or CMA activation. Inhibition of Fasn with a low concentration of C75 did not affect cell viability but decreases LD density. Conclusions These results suggested that Fasn is essential for cell survival but that excessive Fasn leads to LD accumulation in Wdr45 knockout cells.

Abstract Objectives This study aimed to explore the bidirectional association between frailty and social relationships in older adults while distinguishing between interpersonal and intrapersonal effects. Methods A prospective cohort study of community-dwelling older adults was conducted in Japan in three waves spanning six years with follow-ups in every three years. Random intercept cross-lagged panel model was used to explore temporal associations between frailty and social relationships. Results Data for 520 participants (mean age 73.02 [SD 6.38] years, 56.7% women) were analyzed. Across individuals, frailty was associated with social relationships (β = -0.514, p

Abstract Background Several studies have indicated that skin holds promise as a potential sample for detecting pathological α-Syn and serving as a diagnostic biomarker for α-synucleinopathies. Despite reports in Chinese PD patients, comprehensive research on skin α-Syn detection using RT-QuIC is lacking. Objective This study aimed to evaluate the diagnostic performance of skin samples using RT-QuIC from PD patients in the Chinese population. Methods Patients with sporadic PD and controls were included according to the British PD Association Brain Bank diagnostic criteria. The seeding activity of misfolded α-Syn in these skin samples was detected using the RT-QuIC assay after protein extraction. Biochemical and morphological analyses of RT-QuIC products were conducted by atomic force microscopy, transmission electron microscopy, Congo red staining, and dot blot analysis. Result 30 patients clinically diagnosed with PD and 28 controls with non-α-synucleinopathies were included in this study. 28 of 30 PD patients demonstrated positive α-Syn seeding activity by RT-QuIC assay. In contrast, no α-Syn seeding activity was detected in the 28 control samples, with an overall sensitivity and specificity of 93.3% and 100%, respectively (P

Abstract Background Intractable postpartum hemorrhage (PPH) during cesarean section has been a significant concern for obstetricians. We aimed to explore the effectiveness and safety of a new type of uterine compression suture, the step-wise surgical technique of knapsack-like sutures for treating intractable PPH caused by uterine atony and placenta factors in cesarean section. Methods The step-wise surgical technique of knapsack-like sutures was established on the basis of the artful combination of vertical strap-like sutures and an annular suture-ligation technique. This novel surgical technique was applied to 34 patients diagnosed with PPH during cesarean section due to severe uterine atony and placental factors in our department. The hemostatic effects, clinical outcomes and follow-up visit results were all reviewed and analyzed. Results This new uterine compression suture successfully stopped bleeding in 33 patients, and the effective rate was 97.06%. Only 1 patient failed and was changed to use bilateral uterine arterial embolization and internal iliac artery embolization. The follow-up visits indicated that 33 patients restored menstruation except for 1 who was diagnosed with amenorrhea. The gynecological ultrasound tests of all the patients suggested good uterine involutions, and they had no obvious complaints such as hypogastralgia. Conclusions This step-wise surgical technique of knapsack-like uterine compression sutures can compress the uterus completely. It is a technique that can conserve the uterus and fertility function without special equipment in caesarean section for PPH, with the characteristics of being safe, simple and stable (3 S) with rapid surgery, reliable hemostasis and resident doctor to operation (3R).

Abstract The Retinoic acid-Inducible Gene I (RIG-I) like receptors (RLRs) are the major viral RNA sensors essential for the initiation of antiviral immune responses. RLRs are subjected to stringent transcriptional and posttranslational regulations, of which ubiquitination is one of the most important. However, the role of ubiquitination in RLR transcription is unknown. Here, we screen 375 definite ubiquitin ligase knockout cell lines and identify Ubiquitin Protein Ligase E3 Component N-Recognin 5 (UBR5) as a positive regulator of RLR transcription. UBR5 deficiency reduces antiviral immune responses to RNA viruses, while increases viral replication in primary cells and mice. Ubr5 knockout mice are more susceptible to lethal RNA virus infection than wild type littermates. Mechanistically, UBR5 mediates the Lysine 63-linked ubiquitination of Tripartite Motif Protein 28 (TRIM28), an epigenetic repressor of RLRs. This modification prevents intramolecular SUMOylation of TRIM28, thus disengages the TRIM28-imposed brake on RLR transcription. In sum, UBR5 enables rapid upregulation of RLR expression to boost antiviral immune responses by ubiquitinating and de-SUMOylating TRIM28.

The growth and quality of medicinal plants depend heavily on environmental variables. The quality of Rubia cordifolia, an important medicinal plant, is determined by the two main secondary metabolites of the root, purpurin and mollugin. However, their relationship with environmental factors has not been studied. In this study, the purpurin and mollugin contents of R. cordifolia roots from different sampling sites in China were measured using ultra-high-performance liquid chromatography, and the correlations between the two secondary metabolites and environmental variables were analyzed. The results showed that there were significant differences in the contents of purpurin and mollugin in the roots of R. cordifolia at different sampling points. The content of purpurin ranged from 0.00 to 3.03 mg g-1, while the content of mollugin ranged from 0.03 to 10.09 mg g-1. The quality of R. cordifolia in Shanxi, Shaanxi and Henan border areas and southeastern Liaoning was higher. Liaoning is expected to become a R. cordifolia planting area in Northeast China. Correlation and regression analysis revealed that the two secondary metabolites were affected by different environmental factors, the two secondary metabolites contents were positively correlated with longitude and latitude, and negatively correlated with soil nutrients. In addition, higher temperature and shorter sunshine duration facilitated the synthesis of purpurin. Annual precipitation might be the main factor limiting the quality of R. cordifolia because it had opposite effects on the synthesis of two major secondary metabolites. Therefore, this study is of great significance for the selection of R. cordifolia planting areas and the improvement of field planting quality.

BackgroundKaposiform hemangioendothelioma (KHE) is a rare vascular tumor with a high risk of mortality. Few studies with large samples of KHE have been reported. KHE may develop into the Kasabach–Merritt phenomenon (KMP), which is characterized by thrombocytopenia and consumptive coagulopathy. The features of severe symptomatic anemia and life-threatening low platelets make the management of KHE associated with KMP challenging.ObjectiveThe aim of this study was to examine the clinical characteristics of patients with KHE and discuss the treatment experience for different risk groups of KHE.MethodsThrough a retrospective review of 70 patients diagnosed with KHE between 2017 and 2022 in our center, we classify lesions into three clinicopathological stages based on the tumor involving depth, and divided the severity of KHE into three levels by estimating clinicopathological stages and severity of thrombocytopenia. Treatments of different severity groups were estimated with sufficient data.ResultsIn our cohort, 27% were neonates, and KHE lesion occurred at birth in 84% of patients. There was a slight male predominance (32 girls and 38 boys). Common clinical characteristics included associated coagulation disorder (100%), locally aggressive cutaneous blue–purple mass (89%), thrombocytopenia (78%), and local pain or joint dysfunction (20%). The lower extremities were the dominant location (35%), followed by the trunk (29%), the maxillofacial region and neck (24%), and the upper extremities (10%). Of the total cohort, 78% developed KMP; the median age at which thrombocytopenia occurred was 27.8 days. The median platelet count of patients who were associated with KMP was 24,000/µL in our cohort. Ninety-two percent of patients were given surgery treatment and 89% of these patients were given high-dose methylprednisolone (5-6 mg/kg daily) before surgery. In 55 patients with KMP, 36% were sensitive to high-dose corticosteroid therapy. Patients from the low-risk group (eight cases) underwent operation, all of whom recovered without recurrence after a maximum follow-up of 5 years. Out of 26 patients from the high-risk group, 25 underwent surgery treatment, with 1 case undergoing secondary surgery after recurrence and 1 case taking sirolimus. Out of 36 cases from the extremely high-risk group, 32 underwent surgery (including 2 cases who underwent external carotid artery ligation and catheterization), 3 of whom underwent secondary operation after recurrence, and the remaining 4 cases took medicine. The mean length of having sirolimus was 21 months; two cases stopped taking sirolimus due to severe pneumonia. Two cases died at 1 and 3 months after discharge.ConclusionsOur study describes the largest assessment of high-risk patients with KHE who have undergone an operation to date, with 5 years of follow-up to track recovery, which provides invaluable knowledge for the future treatment of patients with KHE and KMP from different risk groups: Early surgical intervention may be the most definitive treatment option for most patients with KHE; multimodality treatment is the best choice for the extremely high-risk group.

Janus monolayers of transition metal dichalcogenides (TMDCs) are promising building blocks for moiré superlattices because of their built‐in electric field and clean fabrication process. In particular, Janus TMDC monolayers can be chemically converted from conventional TMDC monolayers by atomic substitution, enabling the direct formation of lattice‐mismatched heterobilayers from TMDC bilayers. However, the moiré superlattices of Janus heterobilayers have not been studied experimentally. Herein, this work reports the fabrication and characterization of semiconductor moiré superlattices in chemically tailored Janus heterobilayers. The MoSSe/MoSe2 (or WSSe/WSe2) Janus heterobilayers are prepared by replacing the top layer Se atoms with S atoms in MoSe2 (or WSe2) bilayer using H2 plasma treatment. Scanning transmission electron microscopy reveals that an average moiré period of about 14 nm formed due to lattice mismatch resulting from the chalcogen substitutions. The cryogenic photoluminescence spectra show sharp, near‐infrared emissions, which are attributed to excitons trapped by moiré potentials based on comparison with theoretical calculations. The Janus‐based heterostructures provide a long‐period moiré system with built‐in potential even for nontwisted heterobilayers, allowing the functionalization of confined and correlated electron systems.

Abstract Asterias amurensis has attracted widespread concern because of its population outbreaks, which has impacted fisheries and aquaculture, as well as disrupting local ecosystems. A high-quality reference genome is necessary to better investigate mechanisms of outbreak and adaptive changes. Combining PacBio HiFi and Hi-C sequencing data, we generated a chromosome-level A. amurensis genome with a size of 491.53 Mb. The contig N50 and scaffold N50 were 8.05 and 23.75 Mb, respectively. The result of BUSCO analysis revealed a completeness score of 98.85%. A total of 16,531 protein-coding genes were predicted in the genome, of which 94.63% were functionally annotated. The high-quality genome assembly resulting from this study will provide a valuable genetic resource for future research on the mechanism of population outbreaks and invasion ecology.

Abstract Background The immune system played a multifaceted role in ovarian cancer (OC) and was a significant mediator of ovarian carcinogenesis. Various immune cells and immune gene products played an integrated role in ovarian cancer (OC) progression, proved the significance of the immune microenvironment in prognosis. Therefore, we aimed to establish and validate an immune gene prognostic signature for OC patients’ prognosis prediction. Methods Differently expressed Immune-related genes (DEIRGs) were identified in 428 OC and 77 normal ovary tissue specimens from 9 independent GEO datasets. The Cancer Genome Atlas (TCGA) cohort was used as a training cohort, Univariate Cox analysis was used to identify prognostic DEIRGs in TCGA cohort. Then, an immune gene-based risk model for prognosis prediction was constructed using the LASSO regression analysis, and validated the accuracy and stability of the model in 374 and 93 OC patients in TCGA training cohort and International Cancer Genome Consortium (ICGC) validation cohort respectively. Finally, the correlation among risk score model, clinicopathological parameters, and immune cell infiltration were analyzed. Results Five DEIRGs were identified to establish the immune gene signature and divided OC patients into the low- and high-risk groups. In TCGA and ICGC datasets, patients in the low-risk group showed a substantially higher survival rate than high-risk group. Receiver operating characteristic (ROC) curves, t-distributed stochastic neighbor embedding (t-SNE) analysis and principal component analysis (PCA) showed the good performance of the risk model. Clinicopathological correlation analysis proved the risk score model could serve as an independent prognostic factor in 2 independent datasets. Conclusions The prognostic model based on immune-related genes can function as a superior prognostic indicator for OC patients, which could provide evidence for individualized treatment and clinical decision making.

Abstract A comprehensive atlas of cis-regulatory elements and their dynamic activity is necessary to understand the transcriptional basis of cellular structure maintenance, metabolism, and responses to the environment. Here we show, using matched single-nucleus chromatin accessibility and RNA-sequencing from juvenile male C57BL6 mice, an atlas of accessible chromatin regions in both normal and denervated skeletal muscles. We identified cell-type-specific cis-regulatory networks, highlighting the dynamic regulatory circuits mediating transitions between myonuclear types. Through comparison of normal and perturbed muscle, we delineated the reprogramming of cis-regulatory networks in response to denervation, described the interplay of promoters/enhancers and target genes. We further unveil a hierarchical structure of transcription factors that delineate a regulatory network in atrophic muscle, identifying ELK4 as a key atrophy-related transcription factor that instigates muscle atrophy through TGF-β1 regulation. This study furnishes a rich genomic resource, essential for decoding the regulatory dynamics of skeletal muscle in both physiological and pathological states.

Web3, the next generation of the Internet, represents a decentralized and democratized web. Although it has garnered significant public interest and found numerous real-world applications, there is a limited understanding of people's perceptions and experiences with Web3. In this study, we conducted an empirical study to investigate the categories of Web3 applications and their popularity, as well as the potential challenges and opportunities within this emerging landscape. Our research was carried out in two phases. In the first phase, we analyzed 200 popular Web3 projects associated with 10 leading Web3 venture capital firms. In the second phase, we collected and examined code-related data from GitHub and market-related data from blockchain browsers (e.g., Etherscan) for these projects. Our analysis revealed that the Web3 ecosystem can be categorized into two groups, i.e., Web3 infrastructure and Web3 applications, with each consisting of several subcategories or subdomains. We also gained insights into the popularity of these Web3 projects at both the code and market levels and pointed out the challenges in the Web3 ecosystem at the system, developer, and user levels, as well as the opportunities it presents. Our findings contribute to a better understanding of Web3 for researchers and developers, which in turn promotes further exploration and advancement in this innovative field.

Grain number per spike (GNS) is a crucial component of grain yield and plays a significant role in improving wheat yield. To identify quantitative trait loci (QTL) associated with GNS, a recombinant inbred line (RIL) population derived from the cross of Zhongkemai 13F10 and Chuanmai 42 was employed to conduct QTL mapping across eight environments. Based on the bulked segregant exome sequencing (BSE-Seq), genomic regions associated with GNS were detected on chromosomes 5A and 6A. According to the constructed genetic maps, two major QTL QGns.cib-5A (LOD = 4.35–8.16, PVE = 8.46–14.43%) and QGns.cib-6A (LOD = 3.82–30.80, PVE = 5.44–12.38%) were detected in five and four environments, respectively. QGns.cib-6A is a QTL cluster for other seven yield-related traits. QGns.cib-5A and QGns.cib-6A were further validated using linked Kompetitive Allele Specific PCR (KASP) markers in different genetic backgrounds. QGns.cib-5A exhibited pleiotropic effects on productive tiller number (PTN), spike length (SL), fertile spikelet number per spike (FSN), and ratio of grain length to grain width (GL/GW) but did not significantly affect thousand grain weight (TGW). Haplotype analysis revealed that QGns.cib-5A and QGns.cib-6A were the targets of artificial selection during wheat improvement. Candidate genes for QGns.cib-5A and QGns.cib-6A were predicted by analyzing gene annotation, spatiotemporal expression patterns, and orthologous and sequence differences. These findings will be valuable for fine mapping and map-based cloning of genes underlying QGns.cib-5A and QGns.cib-6A.

The diameter distribution function (DDF) is a crucial tool for accurately predicting stand carbon storage (CS). The current key issue, however, is how to construct a high-precision DDF based on stand factors, site quality, and aridity index to predict stand CS in multi-species mixed forests with complex structures. This study used data from 70 survey plots for mixed broadleaf Populus davidiana and Betula platyphylla forests in the Mulan Rangeland State Forest, Hebei Province, China, to construct the DDF based on maximum likelihood estimation and finite mixture model (FMM). Ordinary least squares (OLS), linear seemingly unrelated regression (LSUR), and back propagation neural network (BPNN) were used to investigate the influences of stand factors, site quality, and aridity index on the shape and scale parameters of DDF and predicted stand CS of mixed broadleaf forests. The results showed that FMM accurately described the stand-level diameter distribution of the mixed P. davidiana and B. platyphylla forests; whereas the Weibull function constructed by MLE was more accurate in describing species-level diameter distribution. The combined variable of quadratic mean diameter (Dq), stand basal area (BA), and site quality improved the accuracy of the shape parameter models of FMM; the combined variable of Dq, BA, and De Martonne aridity index improved the accuracy of the scale parameter models. Compared to OLS and LSUR, the BPNN had higher accuracy in the re-parameterization process of FMM. OLS, LSUR, and BPNN overestimated the CS of P. davidiana but underestimated the CS of B. platyphylla in the large diameter classes (DBH ≥18 ​cm). BPNN accurately estimated stand- and species-level CS, but it was more suitable for estimating stand-level CS compared to species-level CS, thereby providing a scientific basis for the optimization of stand structure and assessment of carbon sequestration capacity in mixed broadleaf forests.

BackgroundOverwhelming evidence points to that genetic factors contributing to the development of Alzheimer’s disease (AD) and Parkinson’s disease (PD). Genome-Wide Association Study (GWAS) has come a long way in the last decade. So far, a large number of GWAS studies have been published on neurological diseases and many other diseases, providing us with a wealth of genetic information and unique biological insights.MethodsGenomic DNA was extracted from both patients’ and controls’ peripheral blood samples utilizing the Blood Genome Extraction Kit. Single nucleotide polymorphisms (SNPs) were genotyped employing the enhanced multiple ligase detection reaction (iMLDR) technology.ResultsA case-control study was conducted, involving 211 AD patients, 508 PD patients (including 117 with dementia), and 412 healthy individuals. Age and sex stratification analysis revealed that rs871269/TNIP1 was associated with LOAD (p = 0.035), and rs5011436/TMEM106B was associated with AD in males (p = 0.044) in the genotype model. In the allele model, rs871269/TNIP1 was found to be associated with PD in the Chinese Han population (p = 0.0035, OR 0.741, 95% CI 0.559-0.983), and rs708382/GRN was identified as a risk factor for Parkinson’s disease dementia (PDD) in the Chinese Han population (p = 0.004, odds ratio (OR) 0.354, 95% confidence interval (CI) 0.171-0.733). However, no significant associations with AD or PD were observed for the remaining four loci (rs113020870/AGRN, rs6891966/HAVCR2, rs2452170/NTN5, rs1761461/LILRB2) in terms of allele or genotype frequencies.ConclusionThis study identifies rs871269/TNIP1 as a potential risk factor for both LOAD and PD, rs708382/GRN as a risk factor for PDD, and rs5011436/TMEM106B as associated with AD in males when stratified by age.

The treatment of the large amount of coal slime and municipal sewage sludge in Shanxi Province and even the country is facing unprecedented challenges. Clean combustion technology is the preferred method for sewage sludge-coal slime co-processing. In order to explore the interaction of sludge - coal mud combustion, provide a basis for cleaning and efficient combustion utilization. This paper uses thermal heavy mass spectral (TG-MS) to study the precipitation characteristics of combustion characteristics and pollutant gas products (CH4, CO, CO2, NH3, HCN, NO, NO2, H2S, CH3SH, COS, SO2, CS2, SO3), in the combustion and coal burning process in sludge and coal mud. At the same time, the Coats-Redfern Integral Law is used to dynamically explore the mid-combustion process of sludge and coal mud alone. The results show that there is a significant interaction in the process of coal burning in sludge and coal mud. Sludge and coal mud promote each other, improve the overall reaction performance, in which the combustion characteristics are optimal when the coal slime is blended 20%. It indicates that the increase in sludge ratio does not affect the combustion performance of the fuel overall. The Em of sludge and coal slime were 51.170 kJ/mol and 78.538 kJ/mol, sludge can reduce the average activation energy of the mixed sample, and the actual Em of the mixed sample is lower than the calculation. The kinetic model is (D3→D4) when the sludge is alone; the combustion kinetic model (F1) when the coal slime is separate, and the interval kinetic model of the mixed sample is (D3→D1→D3/F1), indicating interaction the reaction mechanism during the combustion can be changed. When the coal slime is blended 20%, the inhibition of the greenhouse body (319.742%) is preferably inhibited; when the coal slime is blended 80%, the difference (636.492%) and the inhibitory inhibition containing traditional (534.811%); indicating interaction is a great inhibitory effect on the traditional form of integrated varieties, in which the inhibitory effect of the contaminant contaminated body content is most (319.740%) when the coal slime is blended 20%.

Luffa (Luffa aegyptiaca, synonym Luffa cylindrica) is a tropical and subtropical climbing plant belonging to the cucumber family (Cucurbitaceae), natively cultivated in South and Southeast Asia. There are two main species of luffa grown in Florida: smooth luffa (Luffa aegyptiaca Mill.), primarily grown in small gardens and angled luffa (Luffa acutangula (L.) Roxb.), basically grown for commercial production (https://edis.ifas.ufl.edu/publication/HS1285). It is commonly called sponge gourd, Egyptian cucumber, or Vietnamese luffa. Young fruits are edible and rich with nutritional and medicinal value (Partap et al. 2012; Azeez, Bello, and Adedeji et al. 2013). The mature fruit has strong fibrous insides, which can be used as natural porous fiber (Siqueira, Bras, and Dufresne 2010; Sivakandhan et al. 2020) for dishwashing or shower scrubbing. This publication is written for growers, state and county Extension faculty, and students interested in crop production.

Background/objectiveSocial physique anxiety (SPA) is a prevalent psychological issue among emerging adults, regardless of gender. Many studies have shown that high levels of SPA are associated with various negative consequences on both physical and mental well-being. Considering the potential severity of SPA’s consequences and its high prevalence among emerging adults, it is imperative to investigate the factors and mechanisms that contribute to SPA in this population. Although prior studies have identified associations between emerging adulthood, digital media use, and SPA in young individuals, the underlying mechanisms remain unclear. The objective of this study is to examine the associations between SPA, emerging adulthood characteristics, digital media dependency, and exercise empowerment.MethodsIn this cross-sectional study, Chinese college students were recruited using snowball sampling. The study utilized an online survey to assess SPA, emerging adulthood characteristics, digital media dependency, and exercise empowerment. The collected data was analyzed using path analysis.ResultsA total of 1,661 Chinese college students (mean age = 19.63 ± 0.32 years, 44.97% male) were included in this study. The results showed that SPA exhibited positive correlations with responsibility and instability in emerging adulthood characteristics, digital media dependency, and exercise empowerment. Additionally, digital media dependency showed positive correlations with responsibility and instability, as well as with exercise empowerment. Furthermore, exercise empowerment demonstrated positive correlations with self-exploration, responsibility, instability, and possibilities in emerging adulthood characteristics. SPA can be directly influenced by digital media dependency, self-exploration, and instability. Furthermore, digital media dependency has a positive indirect impact on SPA through exercise empowerment. Similarly, self-exploration also has a positive indirect impact on SPA through exercise empowerment. On the other hand, instability has a negative indirect impact on SPA through exercise empowerment.ConclusionThis study provides new insights into the complex correlations with emerging adulthood characteristics, digital media dependency, exercise empowerment, and SPA. Instability, self-exploration in emerging adulthood characteristics, as well as digital media dependency, have the potential to influence SPA among college students through exercise empowerment Interventions and strategies aimed at addressing these psychological factors may prove beneficial in reducing SPA among emerging adults, especially college students.

Calponin 2 (CNN2) is a prominent actin stabilizer. It regulates fatty acid oxidation (FAO) by interacting with estrogen receptor 2 (ESR2) to determine kidney fibrosis. However, whether CNN2 is actively involved in acute kidney injury (AKI) remains unclear. Here, we report that CNN2 was induced in human and animal kidneys after AKI. Knockdown of CNN2 preserved kidney function, mitigated tubular cell death and inflammation, and promoted cell proliferation. Distinct from kidney fibrosis, proteomics showed that the key elements in the FAO pathway had few changes during AKI, but we identified that 3-hydroxymethylglutaryl-CoA synthase 2 (Hmgcs2), a rate-limiting enzyme of endogenous ketogenesis that promotes cell self-renewal, was markedly increased in CNN2-knockdown kidneys. The production of ketone body β-hydroxybutyrate and ATP was increased in CNN2-knockdown mice. Mechanistically, CNN2 interacted with ESR2 to negatively regulate the activities of mitochondrial sirtuin 5. Activated sirtuin 5 subsequently desuccinylated Hmgcs2 to produce energy for mitigating AKI. Understanding CNN2-mediated discrete fine-tuning of protein posttranslational modification is critical to optimize organ performance after AKI.

Abstract Purpose This study aimed to determine the effect and mechanism of action of adenosine 2 receptor (A2R) activation on myocardial ischemia reperfusion injury (MIRI) under diabetic conditions. Methods MIRI type 2 diabetic rats and H9C2 cardiomyocytes were treated with A2R agonist and then subjected to hypoxia for 6 h and reoxygenation for 18 h. Myocardial damage, and infarct size were determined by cardiac ultrasound. Indicators of cardiomyocyte injury, creatine kinase-MB and cardiac troponin I were detected by Enzyme Linked Immunosorbent Assay. Endoplasmic reticulum stress (ERS) was determined through measuring the expression levels of ERS related genes GRP78, p-IRE1/IRE1, and p-JNKJNK. The mechanism of A2R cardio protection in MIRI through regulating ERS induced autophagy was determined by investigating the ER resident protein IRE-1. The ER-stress inducer Tunicamycin, and the IRE-1 inhibitor STF in combination with the A2R agonist NECA were used, and the cellular responses were assessed through autophagy proteins expression Beclin-1, p62, LC3 and apoptosis. Results NECA improved left ventricular function post MIRI, limited myocardial infarct size, reduced myocardial damage, decreased cardiomyocytes apoptosis, and attenuated ERS induced autophagy through regulating the IRE-XBP1s-CHOP pathway. These actions resulted into overall protection of the myocardium against MIRI. Conclusion In summary, A2R activation by NECA prior to ischemia attenuates apoptosis, reduces ERS induced autophagy and restores left ventricular function. This protective effect occurs through regulating the IRE1-XBPs-CHOP related mechanisms. NECA is thus a potential target for the treatment of MIRI in patient with type 2 diabetes.

Abstract With the rapid increment of the demand for data sharing among parties, data is considered a cornerstone component to provide value in the big data environment. Concerns regarding sharing data security have impeded the development of cross‐domain data interaction. Therefore, an access control model for data security sharing cross‐domain is proposed, Fabric‐ABAC, that is based on Hyperledger Fabric and Attribute‐based Access Control (ABAC). In order to solve the data security challenges caused by a trusted central organization implementation, a distributed environment is constructed that consists of stakeholders among parties. The unified attribute model is designed for multi‐environment combined with smart contracts. Fabric‐ABAC realizes multi‐level, fine‐grained, and auditable access control, enabling data security through automatic permission verification. Considering the ledger is visible to all participants in consortium blockchain, it is necessary to protect the confidentiality of sensitive data. Thus, Proxy Re‐Encryption (PRE), which is implemented by smart contracts, is adopted in the scheme to realize the ciphertext interaction without the third party. The security of PRE and the access control model used in Fabric‐ABAC is discussed to show that a secure environment for data sharing is provided. Moreover, the completeness of the implementation and effectiveness of the system performance in the multi‐domain environment is demonstrated in the experimental results.

The early Parkinson’s disease (PD) with mild cognitive impairment (ePD-MCI) is a typical non-motor symptom reflected by the brain dysfunction of PD, which can be well depicted by the dynamic characteristics of brain functional connectivity networks. The aim of this study is to determine the unclear dynamic changes in functional connectivity networks induced by MCI in early PD patients. In this paper, the electroencephalogram (EEG) of each subject was reconstructed into the dynamic functional connectivity networks with five frequency bands based on adaptive sliding window method. By evaluating the fluctuations of dynamic functional connectivity and the transition stability of functional network state in ePD-MCI patients compared with early PD without mild cognitive impairment patients, it was found that in the alpha band, the functional network stability of central region, right frontal, parietal, occipital, and left temporal lobes was abnormally increased, and the dynamic connectivity fluctuations in these regions were significantly decreased in ePD-MCI group. In the gamma band, ePD-MCI patients showed decreased functional network stability in the central, left frontal, and right temporal lobes, and active dynamic connectivity fluctuations in the left frontal, temporal, and parietal lobes. The aberrant duration of network state in ePD-MCI patients was significantly negatively correlated with cognitive function in the alpha band, which might pave the way to identify and predict cognitive impairment in early PD patients.

Abstract Polycystic ovary syndrome (PCOS), a common reproductive endocrine disease, has clinically heterogeneous characteristics. Recently, cuproptosis causes several diseases by killing cells. Hence, we aimed to explore cuproptosis-related molecular clusters in PCOS and construct a prediction model. Based on the GSE5090, GSE43264, GSE98421, and GSE124226 datasets, an analysis of cuproptosis regulators and immune features in PCOS was conducted. In 25 cases of PCOS, the molecular clusters of cuproptosis-related genes and the immune cell infiltration associated with PCOS were investigated. Weighted gene co-expression network analysis was used to identify differentially expressed genes within clusters. Next, we compared the performance of the random forest model, support vector machine model, generalized linear model, and eXtreme Gradient Boosting for deciding the optimum machine model. Validation of the predictive effectiveness was accomplished through nomogram, calibration curve, decision curve analysis, and using other two datasets. PCOS and non-PCOS controls differed in the dysregulation of cuproptosis-related genes and the activation of immunoreaction. Two cuproptosis-related molecular clusters associated with PCOS were identified. Significant heterogeneity was noted in immunity between the two clusters based on the analysis of immune infiltration. The immune-related pathways related to cluster-specific differentially expressed genes in Cluster1 were revealed by functional analysis. With a relatively low residual error and root mean square error and a higher area under the curve (1.000), the support vector machine model demonstrated optimal discriminative performance. An ultimate 5-gene-based support vector machine model was noted to perform satisfactorily in the other two validation datasets (area under the curve = 1.000 for both). Moreover, the nomogram, calibration curve, and decision curve analysis showed that PCOS subtypes can be accurately predicted. Our study results helped demonstrate a comprehensive understanding of the complex relationship between cuproptosis and PCOS and establish a promising prediction model for assessing the risk of cuproptosis in patients with PCOS.

Abstract Current non-invasive prenatal screening (NIPS) analyzes circulating fetal cell-free DNA (cfDNA) in maternal peripheral blood for selected aneuploidies or microdeletion/duplication syndromes. Many genetic disorders are refractory to NIPS largely because the maternal genetic material constitutes most of the total cfDNA present in the maternal plasma, which hinders the detection of fetus-specific genetic variants. Here, we developed an innovative sequencing method, termed coordinative allele-aware target enrichment sequencing (COATE-seq), followed by multidimensional genomic analyses of sequencing read depth, allelic fraction, and linked single nucleotide polymorphisms, to accurately separate the fetal genome from the maternal background. Analytical confounders including multiple gestations, maternal copy number variations, and absence of heterozygosity were successfully recognized and precluded for fetal variant analyses. In addition, fetus-specific genomic characteristics, including the cfDNA fragment length, meiotic error origins, meiotic recombination, and recombination breakpoints were identified which reinforced the fetal variant assessment. In 1129 qualified pregnancies tested, 54 fetal aneuploidies, 8 microdeletions/microduplications, and 8 monogenic variants were detected with 100% sensitivity and 99.3% specificity. Using the comprehensive cfDNA genomic analysis tools developed, we found that 60.3% of aneuploidy samples had aberrant meiotic recombination providing important insights into the mechanism underlying meiotic nondisjunctions. Altogether, we show that the genetic deconvolution of the fetal and maternal cfDNA enables thorough and accurate delineation of fetal genome which paves the way for the next-generation prenatal screening of essentially all types of human genetic disorders.

Abstract Background Microglia pyroptosis-mediated neuroinflammation is thought to be the crucial pathogenesis of sepsis-associated encephalopathy (SAE). Erbin has been reported to be associated with various inflammatory diseases. However, the role of Erbin in SAE and the relationship between Erbin and microglia pyroptosis are unknown. In this study, we investigated the promising role and underlying molecular mechanism of Erbin in the regulation of microglia pyroptosis. Methods WT and Erbin knockout mice underwent cecum ligation perforation (CLP) to induce SAE. Primary mouse microglia and BV2 cells were treated with LPS/nigericin in vitro. Behavioral tests were performed to evaluate cognitive function. Nissl staining and transmission electron microscopy were used to assess histological and structural lesions. ELISA and qPCR were carried out to detect neuroinflammation. Western blot and immunofluorescence were used to analyze protein expression. Flow cytometry and confocal microscopy were utilized to observe the Ca2+ changes in the cytoplasm and endoplasmic reticulum (ER). To further explore the underlying mechanism, STF083010 was administered to block the IRE1α/Xbp1s pathway. Results Erbin deletion resulted in more pronounced neuronal damage and cognitive impairment in mice that underwent CLP. Erbin knockout promoted microglial pyroptosis and inflammatory cytokines secretion in vivo and in vitro, which was mediated by activation of the IRE1α/Xbp1s. Treatment with the selective inhibitor STF083010 significantly inhibited IRE1α/Xbp1s pathway activity, decreased intracytoplasmic Ca2+, attenuated microglial pyroptosis, reduced pro-inflammatory cytokine secretion, lessened neuronal damage, and improved cognitive function. Conclusions In SAE, Erbin inhibits IRE1/Xbp1s pathway activity and reduces the ER Ca2+ influx to the cytoplasm, reducing microglial pyroptosis.

Abstract Background Skeletal muscle exhibits remarkable plasticity under both physiological and pathological conditions. One major manifestation of this plasticity is muscle atrophy that is an adaptive response to catabolic stimuli. Because the heterogeneous transcriptome responses to catabolism in different types of muscle cells are not fully characterized, we applied single‐nucleus RNA sequencing (snRNA‐seq) to unveil muscle atrophy related transcriptional changes at single nucleus resolution. Methods Using a sciatic denervation mouse model of muscle atrophy, snRNA‐seq was performed to generate single‐nucleus transcriptional profiles of the gastrocnemius muscle from normal and denervated mice. Various bioinformatics analyses, including unsupervised clustering, functional enrichment analysis, trajectory analysis, regulon inference, metabolic signature characterization and cell–cell communication prediction, were applied to illustrate the transcriptome changes of the individual cell types. Results A total of 29 539 muscle nuclei (normal vs. denervation: 15 739 vs. 13 800) were classified into 13 nuclear types according to the known cell markers. Among these, the type IIb myonuclei were further divided into two subgroups, which we designated as type IIb1 and type IIb2 myonuclei. In response to denervation, the proportion of type IIb2 myonuclei increased sharply (78.12% vs. 38.45%, P

PurposeTo evaluate the significance of magnetic resonance (MR) intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) quantitative parameters in predicting early efficacy of high-intensity focused ultrasound (HIFU) ablation of uterine fibroids before treatment.Method64 patients with 89 uterine fibroids undergoing HIFU ablation (51 sufficient ablations and 38 insufficient ablations) were enrolled in the study and completed MR imaging and IVIM-DWI before treatment. The IVIM-DWI parameters, including D (diffusion coefficient), D* (pseudo-diffusion coefficient), f (perfusion fraction) and relative blood flow (rBF) were calculated. The logistic regression (LR) model was constructed to analyze the predictors of efficacy. The receiver operating characteristic (ROC) curve was drawn to assess the model’s performance. A nomograph was constructed to visualize the model.ResultsThe D value of the sufficient ablation group (931.0(851.5-987.4) × 10−6 mm2/s) was significantly lower than that of the insufficient ablation group (1052.7(1019.6-1158.7) × 10−6 mm2/s) (p0.05). The LR model was constructed with D value, fibroid position, ventral skin distance, T2WI signal intensity, and contrast enhanced degree. The area under the ROC curve, specificity, and sensitivity of the model were 0.858 (95% confidence interval: 0.781, 0.935), 0.686, and 0.947. The nomogram and calibration curves confirmed that the model had excellent performance.ConclusionThe IVIM-DWI quantitative parameters can be used to predict early effects of HIFU ablation on uterine fibroids. A high D value before treatment may indicate that the treatment will be less effective in the early stages.

Abstract Adonis amurensis Regel et Radde is an early spring plant in northeastern China that has great ornamental value because it blooms before other plants have sprouted. It has not been used to its full potential due to environmental restrictions on its growth. It will be extremely important for its application to comprehend the possible habitat of A. amurensis and the critical environmental factors controlling its distribution under current and future climatic scenarios. In this work, two climate change scenarios of 2041–2060 and 2081–2100 were utilized to predict the suitable habitat of A. amurensis. The results showed that the suitable habitat was mainly distributed along the Changbai Mountains, with a total area of 303,090 km2, and the potential and high‐potential habitat area were 141,218 and 161,872 km2, respectively. In the future climate scenarios, the suitable habitat of A. amurensis was still distributed along the Changbai Mountains, but the area was reduced. In ssp126 and ssp585 scenarios of 2041–2060 and 2081–2100, the area was reduced by 7.13% and 22.34% and 18.66% and 8.09%, respectively. The reduced suitable habitat was mainly located in central Heilongjiang (southeastern Xiao Xing'an Ling), central Jilin, and northeastern Liaoning. The suitable habitat was significantly influenced by precipitation, mainly affected by annual precipitation, followed by precipitation seasonality, soil surface pH, and slope. The results of this study can serve as empirical support for the artificial cultivation, ecological restoration, and long‐term use of A. amurensis.

Objective: In the fibrotic kidneys, the extent of a formed deleterious microenvironment is determined by cellular mechanical forces. This process requires metabolism for energy. However, how cellular mechanics and metabolism are connected remains unclear. Methods: A multi-disciplinary approach was employed: the fibrotic kidney disease models were induced by renal ischemia-reperfusion injury and unilateral ureteral obstruction in Calponin 2 (CNN2) knockdown mice. Proteomics, bioinformatics, and in vivo and in vitro molecular experimental pathology studies were performed. Result: Our proteomics revealed that actin filament binding and cell metabolism are the two most dysregulated events in the fibrotic kidneys. As a prominent actin stabilizer, CNN2 was predominantly expressed in fibroblasts and pericytes. In CKD patients, CNN2 levels was markedly induced in blood. In mice, CNN2 knockdown preserves kidney function and alleviates fibrosis. Global proteomics profiled that CNN2 knockdown enhanced the activities of the key rate-limiting enzymes and regulators of fatty acid oxidation (FAO) in the diseased kidneys. Inhibiting carnitine palmitoyltransferase 1α in the FAO pathway resulted in lipid accumulation and extracellular matrix deposition in the fibrotic kidneys, which were restored after CNN2 knockdown. Bioinformatics and chromatin immunoprecipitation showed that CNN2 interactor, estrogen receptor 2 (ESR2), binds peroxisome proliferator-activated receptor-α (PPARα) to transcriptionally regulate FAO downstream target genes expression amid kidney fibrosis. In vitro, ESR2 knockdown repressed the mRNA levels of PPARα and the key genes in the FAO pathway. Conversely, activation of PPARα reduced CNN2-induced matrix inductions. Conclusions: Our results suggest that balancing cell mechanics and metabolism is crucial to develop therapeutic strategies to halt kidney fibrosis.

BackgroundIn the past few decades, heat waves and seasonal variation linked with global warming are causing frequent fluctuations of water temperature in aquatic environments, resulting in further challenges for marine organisms. As a poikilothermic marine animal and a temperate species, sea cucumber A. japonicus is also very sensitive to temperature variation and shows a limited ability to adapt to environmental temperature changes. However, the molecular mechanisms by which A. japonicus perceives signals from such a diverse environment including the trigger of aestivation still remain unclear. TRP (transient receptor potential) superfamily, as the great potential “sentinel” of the organism in response to the changes of the external environment signals, perceived little attention and will be the future great candidates for sensory function research in echinoderm.MethodsBLAST program was applied to identify the AjTRPs based on A. japonicus transcriptome database. Gene structure analysis of AjTRPs and phylogenetic analysis of TRPs were performed. The expression profiles of AjTRPs in different tissues and in response to different heat stress treatments (chronic/ acute) were measured using qRT-PCR.ResultsA total of 54 TRPs were identified in A. japonicus. Gene structure analysis showed that the exon numbers and the domains of AjTRPs varied greatly. Phylogenetic analysis indicated that AjTPRs were mainly grouped into six subfamilies: TRPA, TRPM, TRPC, TRPV, TRPML, and TRPP. Copy numbers of each TRP member in marine invertebrates including A. japonicus were more than those in vertebrates, however some TRP channel members were lost in invertebrates. Expression profile detection suggested that the representative 15 AjTRP genes belonging to 6 subfamilies were expressed in all tissues examined.ConclusionOur findings indicate that the plastic evolutionary history of TRP channel genes and suggest that TRPM2-1, TRPM2-2, TRPM3, and TRPC3-1 are potential thermo-TRP proteins involved in thermal regulation in A. japonicus. This work facilitates the knowledge of TRP-mediated sensory systems in echinoderms, provides new insights into the mechanisms of aestivation and global warming adaptation in marine invertebrates.

Systematic studies on the mechanism underlying Fe2O3-catalyzed NO reduction in a reducing atmosphere during sludge combustion remain limited. In this study, density functional theory was employed to investigate the adsorption properties of NH3, CO, and NO on the α-Fe2O3(001) surface, and the mechanisms underlying the NH3 and CO reduction of NO during the adsorption process. The results demonstrated that NH3, CO, and NO chemically adsorbed on the surface Fe top site, thereby generating distinctly high adsorption energies. NO exhibited the highest adsorption energy. With regard to the catalytic mechanisms of NH3 and CO during NO reduction, the α-Fe2O3(001) surface exhibited different characteristics. NH3 reduction of NO tended to follow the Eley–Rideal (E-R) mechanism. The dissociation of -NH2NO is the rate-determining step for the NH3 reduction of NO. The presence of α-Fe2O3(001) reduced the dissociation energy barriers of NH3 and NH2NO, thereby catalyzing the reduction reaction. In contrast, NO dissociation was more challenging during the CO reduction of NO. The α-Fe2O3(001) surface reduced the dissociation barrier of the NO-NO dimer from 2.04 to 1.53 eV. Two adsorbed NO molecules first formed NO-NO dimers; these then dissociated into N2O and atomic oxygen, thereby catalyzing the reduction reaction.

Abstract Background Overmedicalization in labor management and delivery, including labor induction, is an increasing global concern. But detailed epidemiological data on labor induction in China remains unclear. Methods This was a cross-sectional study of data (2015–2016) from 96 hospitals in 24 (of 34) Chinese administrative divisions. Multivariable logistic regression analysis was used to assess the association between medical conditions and cesarean delivery among women undergoing induction. Linear regression analysis was performed to assess the association between the prelabor cesarean delivery and labor-induction rates in each hospital. The impacts of labor induction and prelabor cesarean delivery on maternal and neonatal outcomes were compared in low-risk women. Results Among 73 901 eligible participants, 48.1% were nulliparous. The overall weighted rate of labor induction in China was 14.2% (95% CI, 11.1–17.2%), with 18.4% (95% CI, 14.5–22.3%) in nulliparas and 10.2% (95% CI, 7.7–12.8%) in multiparas. Regardless of the induction method, the overall vaginal delivery rate was 72.9% (95% CI, 68.6–77.3%) in nulliparas and 86.6% (95% CI, 79.7–93.5%) in multiparas. Hospitals with a higher rate of nonmedically indicated cesarean delivery had a lower labor-induction rate in nulliparas (β = − 0.57%; 95% CI, − 0.92 to − 0.22%; P = 0.002). Compared with prelabor cesarean delivery, labor induction in low-risk women was not associated with adverse maternal and neonatal outcomes. Conclusion The 2015–2016 labor-induction rate in China was 18.4% in nulliparas and 10.2% in multiparas. The proportion of prelabor cesarean delivery may contribute to regional differences in the labor-induction rate. Compared with prelabor cesarean delivery, labor induction in low-risk women may not increase severe maternal and neonatal morbidity.

Abstract Background This study aimed to search for blood biomarkers among the profiles of patients with RA-ILD by using machine learning classifiers and probe correlations between the markers and the characteristics of RA-ILD. Methods A total of 153 RA patients were enrolled, including 75 RA-ILD and 78 RA-non-ILD. Routine laboratory data, the levels of tumor markers and autoantibodies, and clinical manifestations were recorded. Univariate analysis, least absolute shrinkage and selection operator (LASSO), random forest (RF), and partial least square (PLS) were performed, and the receiver operating characteristic (ROC) curves were plotted. Results Univariate analysis showed that, compared to RA-non-ILD, patients with RA-ILD were older (p

Abstract Background One-lung ventilation (OLV) is widely used in thoracic surgery. However, OLV may also increase CERO2 and aggravate delayed cognitive recovery. Here, we aimed to investigate the effect of dexmedetomidine (DEX) on cognitive function in rats undergoing OLV. Methods Sprague-Dawley rats were randomly divided into two-lung ventilation (TLV) group, OLV group and OLV treated with DEX group. Group DEX received 25 μg/kg DEX i.p. 30 min before induction. After mechanical ventilation (MV), Morris water maze (MWM) test was carried out to examine spatial memory function. Western blotting was used to detect pERK1/2, pCREB, Bcl-2 and BAX in hippocampal tissues. Transmission electron microscopy (TEM) was used to observe the hippocampal CA1 region. Results Post-MV, compared with group OLV, group DEX showed increases in percentage of target quadrant time (P

Adenomyosis is a diffuse or localized organic disease caused by benign invasion of endometrial glands and stroma into the myometrium. It is a common disease that seriously affects reproductive health of women in childbearing age. Due to the unknown etiology and pathophysiological mechanism, and the lack of unified diagnostic criteria and effective treatment methods, total or subtotal hysterectomy has become a radical treatment for adenomyosis, which will lead to the complete loss of fertility. With the continuous exploration of the treatment to adenomyotic patients who have infertility or fertility intentions, new drugs, surgical methods and treating concepts appears. Adopt individualized conservative therapeutic strategies for patients with different conditions, preserve the uterus as much as possible and protect the patient’s fertility, which will play an important role on the follow-up assisted reproductive treatment and long-term management of adenomyosis.

Purpose. Tumor immunity serves an essential role in the occurrence and development of thyroid cancer (THCA). The aim of this study is to establish an immune-related prognostic model for THCA patients by using immune-related genes (IRGs). Methods. Wilcox test was used to screen the differentially expressed immune-related genes (DEIRGs) in THCA and normal tissues, then the DEIRGs related to prognosis were identified using univariate Cox regression analysis. According to The Cancer Genome Atlas (TCGA) cohort, we developed a least absolute shrinkage and selection operator (LASSO) regression prognostic model and performed validation analyses regard to the predictive value of the model in internal (TCGA) and external (International Cancer Genome Consortium) cohorts respectively. Finally, we analyzed the correlation among the prognostic model, clinical variables, and immune cell infiltration. Results. Eighty-two of 2,498 IRGs were differentially expressed between THCA and normal tissues, and 18 of them were related to prognosis. LASSO Cox regression analysis identified seven DEIRGs with the greatest prognostic value to construct the prognostic model. The risk model showed high predictive value for the survival of THCA in two independent cohorts. The risk score according to the risk model was positively associated with poor survival and the infiltration levels of immune cells, it can evaluate the prognosis of THCA patients independent of any other clinicopathologic feature. The prognostic value and genetic alternations of seven risk genes were evaluated separately. Conclusion. Our study established and verified a dependable prognostic model associated with immune for THCA, both the identified IRGs and immune-related risk model were clinically significant, which is conducive to promoting individualized immunotherapy against THCA.

Background and objectiveA considerable number of pregnant women who were supplemented with folate and vitamin B12 were selected as major participants in studying the one-carbon metabolic (OCM) pathway. Our study aimed to explore the effects of OCM-related indicators on pregnancy-induced hypertension (PIH) and preeclampsia (PE) in pregnant women with folate and vitamin B12 supplementation.Subjects and methodsA total of 1,178 pregnant women who took multivitamin tablets containing 800 μg folate and 4 μg vitamin B12 daily from 3 months before pregnancy to 3 months after pregnancy were enrolled in this study. These pregnant women were classified into three groups: the normotensive group (n = 1,006), the PIH group (n = 131), and the PE group (n = 41). The information on age, weight, body mass index (BMI), number of embryos, gravidity, parity, and OCM-related indicators (serum level of homocysteine, folate, and vitamin B12; MTHFR C677T genotype) was collected.ResultsThe accuracy of the prediction model based on the screened independent risk factors (hyperhomocysteine, OR = 1.170, 95% CI = 1.061–1.291; high folate status, OR = 1.018, 95% CI = 0.999–1.038; and high BMI, OR = 1.216, 95% CI = 1.140–1.297) for PIH in subjects with MTHFR CC genotype (AUC = 0.802) was obviously higher than that in subjects with MTHFR CT, TT genotype (AUC = 0.684,0.685, respectively) by receiver operating characteristic curve analysis. The homocysteine level of the PIH group was significantly higher than that of the normotensive group only in subjects with the MTHFR CC genotype (p = 0.005). A negative correlation between homocysteine and folate appeared in subjects with MTHFR CT + TT genotype (p = 0.005). A model including multiple embryos, nulliparas, and lower folate could predict the process from PIH to PE (AUC = 0.781, p < 0.0001).ConclusionThe prediction model composed of homocysteine, folate, and BMI for PIH was suitable for subjects with MTHFR CC genotype in pregnant women with supplementation of folate and vitamin B12. Lower folate levels could be an independent risk factor in developing the process from PIH to PE.

The etiology of neuropsychiatric disorders involves complex biological processes at different omics layers, such as genomics, transcriptomics, epigenetics, proteomics, and metabolomics. The advent of high-throughput technology, as well as the availability of large open-source datasets, has ushered in a new era in system biology, necessitating the integration of various types of omics data. The complexity of biological mechanisms, the limitations of integrative strategies, and the heterogeneity of multi-omics data have all presented significant challenges to computational scientists. In comparison to early and late integration, intermediate integration may transform each data type into appropriate intermediate representations using various data transformation techniques, allowing it to capture more complementary information contained in each omics and highlight new interactions across omics layers. Here, we reviewed multi-modal intermediate integrative techniques based on component analysis, matrix factorization, similarity network, multiple kernel learning, Bayesian network, artificial neural networks, and graph transformation, as well as their applications in neuropsychiatric domains. We depicted advancements in these approaches and compared the strengths and weaknesses of each method examined. We believe that our findings will aid researchers in their understanding of the transformation and integration of multi-omics data in neuropsychiatric disorders.

Abstract Background Obesity among women of childbearing age has becoming an important public health concern. We aimed to describe the trends of central obesity among Chinese women of childbearing age from 2004 to 2011 and to examine its associations with nutrients intake and daily behaviors. Methods Longitudinal data were derived from the China Health and Nutrition Survey. Participants consisted of 2481 women aged 15–44 years old. WC (Waist circumference) and WHtR (Waist to height ratio) were adopted as indicators of central obesity. Generalized linear mixed model was performed to analyze the associations of nutrients intake and daily behaviors with central obesity. Results From 2004 to 2011, the prevalence of central obesity among Chinese women of childbearing age increased from 21.6 to 30.7% (WC as indice) or from 22.8 to 32.6% (WHtR as indice) (both p

Abstract Background Accumulating evidence suggests sleep duration may be involved in metabolic regulation. However, studies regarding the association with the early stage of the metabolic disease are limited, and the findings were inconsistent. Methods A study among 4922 asymptomatic adults was conducted based on a Chinese national survey in 2009. The early stage of metabolic diseases was evaluated using three proxies: triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), the product of triglyceride and fasting glucose (TyG), and lipid accumulation product (LAP). Multivariable linear and logistic regression models were used to explore the associations of sleep duration with the three indicators. Results The linear regression models revealed that, among females, sleep duration

The early diagnosis of Parkinson’s disease (PD) has always been a difficult problem to be solved clinically. At present, there is no clinical auxiliary diagnostic index for reference. We attempted to extract potential biomarkers for early PD from the currently used scalp EEG detection methods in clinical practice. We calculated the phase synchronization index to quantify the synchrony of EEG channels in various frequency bands (delta, theta, alpha and beta bands) of early PD. The results showed that the synchronization of early PD in the delta band was significantly lower than the healthy level, and the brain region reflecting the lower synchronization was located in the temporal lobe, the posterior temporal lobe, the parietal lobe (the posterior center) and the occipital lobe. Moreover, this lower synchronicity is consistent with weaker brain functional connections. Besides, by constructing functional brain network, the graph theoretic topological features of each frequency band of early PD are presented. We have found that early PD has characteristics of small world network in the delta and beta bands, and functional integration and separation characteristics of brain network in early PD are significantly abnormal in the delta, theta, alpha and beta bands. These results indicate that early PD has significant pathological changes from the perspective of brain function network analysis, and its characteristics can be described by multiple features, which may provide auxiliary guidance for the clinical diagnosis of early PD, and also provide theoretical support for the brain function changes of early PD.

Background: To evaluate the safety profiles and role of antepartum transabdominal amnioinfusion (TA) in detecting fetal anomalies in pregnant women with oligohydramnios during the second trimester. Methods: Pregnant women with a diagnosis of oligohydramnios at 16 0/7 to 27 0/7 weeks of gestation were evaluated at our center between June 2014 and April 2020. Data collected included maternal and fetal clinical characteristics, ultrasonographic or magnetic resonance imaging findings, chromosomal results, and perinatal mortality. Pregnancy outcomes and procedure-related complications were then analyzed. Results: The study analyzed 106 pregnant women with severe oligohydramnios, at a mean gestational age of 22+3 weeks. Out of these, 71 women received TA while the remaining 35 did not. Only two patients (2.82%) suffered adverse events of chorioamnionitis post-TA. Nineteen additional cases of fetal anomalies were detected following TA, leading to a significantly increased detection rate (24/71 vs 43/71, p = 0.001). Among the TA group, eight pregnancies without obvious fetal pathologies were delivered alive, and all newborns were discharged in good condition. Conclusions: TA is a safe and valuable procedure for pregnant women with severe oligohydramnios in the second trimester that improved the detection rate of fetal structural anomalies. TA may lead to favorable outcomes in pregnancies without obvious fetal pathologies.

BackgroundSepsis remains the leading cause of postoperative death in elderly patients and is defined as organ dysfunction with proven or suspected infection according to Sepsis-3 criteria. To better avoid potential non-linear associations between the risk factors, we firstly used a tree-based analytic methods to explore the putative risk factors of geriatric sepsis based on the criteria in the study.MethodsData of 7,302 surgical patients aged ≥ 65 years at the Third Affiliated Hospital of Sun Yat-sen University from January 2015 to September 2020 were collected. An analytic method that combined tree-based analysis with the method of Mantel-Haenszel and logistic regression was adopted to assess the association between 17 putative risk factors and postoperative sepsis defined by the Sepsis-3 guideline by controlling 16 potential confounding factors.ResultsAmong the 16 potential covariates, six major confounders were statistically identified by the tree-based model, including cerebrovascular diseases, preoperative infusion of red blood cells, pneumonia, age ≥ 75, malignant tumor and diabetes. Our analysis indicated that emergency surgery increases the risk of postoperative sepsis in elderly patients by more than six times. The type of surgery is also a crucial risk factor for sepsis, particularly transplantation and neurosurgery. Other risk factors were duration of surgery > 120 min, administration of steroids, hypoalbuminemia, elevated creatinine, blood urea nitrogen, hematocrit, platelets, glucose, white blood cell count, abnormal neutrophil-to-lymphocyte ratio and elevated hsCRP-to-albumin ratio.ConclusionsOur study uses an effective method to explore some risk factors for postoperative sepsis in elderly by adjusting many potential confounders and it can provide information for intervention design.

Airborne dust deposition on the solar photovoltaic panels can significantly decrease the photovoltaic efficiency performance. Dust deposition characteristics and influences on building-integrated photovoltaic panels were studied by shear stress transfer k-ω turbulence model with inlet profiles and discrete particle model. The influences of dust size, wind velocity, and building roof inclination on the dust deposition behaviors were studied carefully. The air flow fields, the dust particle trajectories, the deposition rate on solar photovoltaic panels and the photovoltaic efficiency decrease by dust deposition were obtained and analyzed in the study. The three-dimensional simulation has great difference on the wind flow structures compared with two-dimensional simulation. The size of the separation vortex in the three-dimensional simulation is significantly smaller than that in two-dimensional simulation. The secondary flow structures become more significant in the rear of the building. The dust deposition rate is firstly increased and then decreased with the increasing of dust diameter. The maximum deposition rate is 2.54% for 150 μm particles. The minimum deposition rate is just 0.03% for 500 μm particles. The maximum deposition rate is 1.39%, 2.54% or 3.74% for the roof inclination angle of 16.7°, 22.6°or 36.9°, respectively. When particle size is 150 μm, the dust motions are determined by the air flow fields, mass inertia and gravitational settling. The photovoltaic efficiency reduction is significantly higher with increasing of dust size. The present model can conveniently estimate the photovoltaic efficiency decrease by dust deposition in realistic engineering application.

Anti-citrullinated protein antibodies (ACPAs) are highly specific for the diagnosis of rheumatoid arthritis (RA). However, about one-third of RA patients are negative for ACPAs, which presents a challenge to the early diagnosis of RA. The purpose of this study was to analyze differences in lymphocyte subsets and CD4+ T cell subsets between ACPA+ and ACPA- RA patients, and to evaluate the value of matrix metalloproteinase-3 (MMP-3) as a diagnostic and monitoring marker in ACA- RA patients. A total of 145 ACPA+ RA patients, 145 ACPA- RA patients, and 38 healthy controls (HCs) were included in this study. Peripheral lymphocyte subsets were detected using flow cytometry, and serum MMP-3 was detected using chemiluminescence. Information about joint symptoms, other organ involvement, and related inflammatory markers was also collected. The results showed that, compared to ACPA- RA patients, ACPA+ cases had greater imbalances between peripheral CD4+ T cell subsets, mainly manifested as an increase in T-helper 1 (Th1) cells (p < 0.001) and decrease in regulatory T (Treg) cells (p = 0.029). This makes these patients more prone to inflammatory reactions and joint erosion. MMP-3 levels in ACPA+ and ACPA- RA patients were significantly higher than in HCs (p < 0.001), and MMP-3 could effectively distinguish between ACPA- RA patients and HCs (area under the curve [AUC] = 0.930, sensitivity 84.14%, specificity 92.11%). MMP-3 was also a serum marker for distinguishing between RA patients with low and high disease activities. Further analysis showed that MMP-3 was positively correlated with the levels of inflammatory markers and disease activity, and negatively correlated with the levels of lymphocyte subsets. In addition, with improvements in the disease, MMP-3 levels decreased, and further increased as the patients started to deteriorate. In summary, our research showed that there was a mild imbalance between peripheral CD4+ T cell subsets in ACPA- RA patients. MMP-3 may be used as a potential marker for early diagnosis of ACPA- RA. MMP-3 was an important index for RA disease evaluation, disease activity stratification, and prognosis.

ObjectiveThe aim of this study was to investigate the correlations of plasma neurodegenerative proteins and electroencephalography (EEG) dynamic functional network (DFN) parameters with disease progression in early Parkinson’s disease (PD) with different motor subtypes, including tremor-dominant (TD) and postural instability and gait disorder (PIGD).MethodsIn our study, 33 patients with PD (21 TD and 12 PIGD) and 33 healthy controls (HCs) were enrolled. Plasma neurofilament light chain (NfL), α-synuclein (α-syn), total-tau (t-tau), β-amyloid 42 (Aβ42), and β-amyloid 40 (Aβ40) levels were measured using an ultrasensitive single-molecule array (Simoa) immunoassay. All the patients with PD underwent EEG quantified by DFN analysis. The motor and non-motor performances were evaluated by a series of clinical assessments. Subsequently, a correlation analysis of plasma biomarkers and EEG measures with clinical scales was conducted.ResultsIn the TD group, plasma NfL exhibited a significant association with MDS-UPDRS III and Montreal Cognitive Assessment (MoCA). A higher Aβ42/40 level was significantly related to a decrease in Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) in the PIGD group. In terms of the correlation between EEG characteristic parameters and clinical outcomes, trapping time (TT) delta was positively correlated with MDS-UPDRS III and MoCA scores in the TD group, especially in the prefrontal and frontal regions. For other non-motor symptoms, there were significant direct associations of kPLI theta with HAMD and HAMA, especially in the prefrontal region, and kPLI gamma was particularly correlated with Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores in the prefrontal, frontal, and parietal regions in the TD group. Furthermore, there was a significant positive correlation between plasma t-tau and kPLI, and pairwise correlations were found among plasma NfL, theta TT, and MoCA scores in the TD group.ConclusionThese results provide evidence that plasma neurodegenerative proteins and EEG measures have great potential in predicting the disease progression of PD subtypes, especially for the TD subtype. A combination of these two kinds of markers may have a superposition effect on monitoring and estimating the prognosis of PD subtypes and deserves further research in larger, follow-up PD cohorts.