Search

Background Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease is associated with coronary artery lesion development. Purpose This study aimed to explore the factors associated with IVIG-resistance and construct and validate an interpretable machine learning (ML) prediction model in clinical practice. Methods Between December 2014 and November 2022, 602 patients were screened and risk factors for IVIG-resistance investigated. Five ML models are used to establish an optimal prediction model. The SHapley Additive exPlanations (SHAP) method was used to interpret the ML model. Results Na+, hemoglobin (Hb), C-reactive protein (CRP), and globulin were independent risk factors for IVIG-resistance. A nonlinear relationship was identified between globulin level and IVIG-resistance. The XGBoost model exhibited excellent performance, with an area under the receiver operating characteristic curve of 0.821, accuracy of 0.748, sensitivity of 0.889, and specificity of 0.683 in the testing set. The XGBoost model was interpreted globally and locally using the SHAP method. Conclusion Na+, Hb, CRP, and globulin levels were independently associated with IVIG-resistance. Our findings demonstrate that ML models can reliably predict IVIG-resistance. Moreover, use of the SHAP method to interpret the established XGBoost model's findings would provide evidence of IVIG-resistance and guide the individualized treatment of Kawasaki disease.

Abstract Background The RNA N 6-methyladenosine (m6A) modification has become an essential hotspot in epigenetic modulation. Serine–arginine protein kinase 1 (SRPK1) is associated with the pathogenesis of various cancers. However, the m6A modification of SRPK1 and its association with the mechanism of in lung adenocarcinoma (LUAD) remains unclear. Methods Western blotting and polymerase chain reaction (PCR) analyses were carried out to identify gene and protein expression. m6A epitranscriptomic microarray was utilized to the assess m6A profile. Loss and gain-of-function assays were carried out elucidate the impact of METTL3 and SRPK1 on LUAD glycolysis and tumorigenesis. RNA immunoprecipitation (RIP), m6A RNA immunoprecipitation (MeRIP), and RNA stability tests were employed to elucidate the SRPK1’s METTL3-mediated m6A modification mechanism in LUAD. Metabolic quantification and co-immunoprecipitation assays were applied to investigate the molecular mechanism by which SRPK1 mediates LUAD metabolism. Results The epitranscriptomic microarray assay revealed that SRPK1 could be hypermethylated and upregulated in LUAD. The main transmethylase METTL3 was upregulated and induced the aberrant high m6A levels of SRPK1. Mechanistically, SRPK1’s m6A sites were directly methylated by METTL3, which also stabilized SRPK1 in an IGF2BP2-dependent manner. Methylated SRPK1 subsequently promoted LUAD progression through enhancing glycolysis. Further metabolic quantification, co-immunoprecipitation and western blot assays revealed that SRPK1 interacts with hnRNPA1, an important modulator of PKM splicing, and thus facilitates glycolysis by upregulating PKM2 in LUAD. Nevertheless, METTL3 inhibitor STM2457 can reverse the above effects in vitro and in vivo by suppressing SRPK1 and glycolysis in LUAD. Conclusion It was revealed that in LUAD, aberrantly expressed METTL3 upregulated SRPK1 levels via an m6A-IGF2BP2-dependent mechanism. METTL3-induced SRPK1 fostered LUAD cell proliferation by enhancing glycolysis, and the small-molecule inhibitor STM2457 of METTL3 could be an alternative novel therapeutic strategy for individuals with LUAD.

Abstract Virus‒host protein‒lncRNA interaction (VHPLI) predictions are critical for decoding the molecular mechanisms of viral pathogens and host immune processes. Although VHPLI interactions have been predicted in both plants and animals, they have not been extensively studied in viruses. For the first time, we propose a new deep learning-based approach that consists mainly of a convolutional neural network and bidirectional long and short-term memory network modules in combination with transfer learning named CBIL‒VHPLI to predict viral–host protein‒lncRNA interactions. The models were first trained on large and diverse datasets (including plants, animals, etc.). Protein sequence features were extracted using a k-mer method combined with the one-hot encoding and composition–transition–distribution (CTD) methods, and lncRNA sequence features were extracted using a k-mer method combined with the one-hot encoding and Z curve methods. The results obtained on three independent external validation datasets showed that the pre-trained CBIL‒VHPLI model performed the best with an accuracy of approximately 0.9. Pretraining was followed by conducting transfer learning on a viral protein–human lncRNA dataset, and the fine-tuning results showed that the accuracy of CBIL‒VHPLI was 0.946, which was significantly greater than that of the previous models. The final case study results showed that CBIL‒VHPLI achieved a prediction reproducibility rate of 91.6% for the RIP-Seq experimental screening results. This model was then used to predict the interactions between human lncRNA PIK3CD-AS2 and the nonstructural protein 1 (NS1) of the H5N1 virus, and RNA pull-down experiments were used to prove the prediction readiness of the model in terms of prediction. The source code of CBIL‒VHPLI and the datasets used in this work are available at https://github.com/Liu-Lab-Lnu/CBIL-VHPLI for academic usage.

Abstract The lncRNA NEAT1 has been shown to promote the progression of several cancers, containing laryngeal squamous cell carcinoma (LSCC). However, the precise mechanism by which it promotes LSCC progression remains unclear. In this study, we verified the high expression of lncRNA NEAT1 in LSCC tissues and cells using RT-qPCR. Analysis of clinical data exhibited that high expression of lncRNA NEAT1 was associated with a history of smoking, worse T stage, lymph node metastasis, and later TNM stage in patients with LSCC. The promotion effect of lncRNA NEAT1 on LSCC cell proliferation, migration, invasion, and tumor growth in vivo was verified by CCK-8, plate clone formation, Transwell, and nude mouse tumorigenicity assays. Bioinformatics prediction and double luciferase reporter gene assay verified the binding of miR-411-3p to lncRNA NEAT1 and FZD3 mRNA, and inhibition of miR-411-3p reversed the inhibitory effect of lncRNA NEAT1 on FZD3 expression in LSCC cells. We also verified that lncRNA NEAT1-mediated FZD3 activation in the Wnt pathway affects LSCC development. In conclusion, we demonstrate that lncRNA NEAT1 promotes the progression of LSCC, and propose that the lncRNA NEAT1/miR-411-3p/FZD3 axis may be an effective target for LSCC therapy.

Abstract Nickel (Ni) and copper (Cu) contamination have become major threats to plant survival worldwide. 24-epibrassinolide (24-EBR) and melatonin (MT) have emerged as valuable treatments to alleviate heavy metal-induced phytotoxicity. However, plants have not fully demonstrated the potential mechanisms by which these two hormones act under Ni and Cu stress. Herein, this study investigated the impact of individual and combined application of 24-EBR and MT on the growth and physiological traits of Primula forbesii Franch. subjected to stress (200 μmol L–1 Ni and Cu). The experiments compared the effects of different mitigation treatments on heavy metal (HM) stress and the scientific basis and practical reference for using these exogenous substances to improve HM resistance of P. forbesii in polluted environments. Nickel and Cu stress significantly hindered leaf photosynthesis and nutrient uptake, reducing plant growth and gas exchange. However, 24-EBR, MT, and 24-EBR + MT treatments alleviated the growth inhibition caused by Ni and Cu stress, improved the growth indexes of P. forbesii, and increased the gas exchange parameters. Exogenous MT effectively alleviated Ni stress, and 24-EBR + MT significantly alleviated the toxic effects of Cu stress. Unlike HM stress, MT and 24-EBR + MT activated the antioxidant enzyme activity (by increasing superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)), significantly reduced reactive oxygen species (ROS) accumulation, and regulated ascorbate and glutathione cycle (AsA-GSH) efficiency. Besides, the treatments enhanced the ability of P. forbesii to accumulate HMs, shielding plants from harm. These findings conclusively illustrate the capability of 24-EBR and MT to significantly bolster the tolerance of P. forbesii to Ni and Cu stress.

Abstract Background To compare the repeatability and reproducibility of corneal and corneal epithelial thickness mapping using anterior segment optical coherence tomography (AS-OCT) according to tear film break-up time (TBUT). Methods The included eyes were divided into three subgroups according to TBUT (group 1: TBUT ≤ 5 s, group 2: 5 s 10 s). All eyes were imaged separately thrice by two operators to obtain the thickness maps (TMs) of the cornea and corneal epithelium based on spatial zones encompassing a 9-mm-diameter area. Each TM consisted of 25 areas. Intraoperator (repeatability) and interoperator (reproducibility) standard deviations (Sws), coefficients of variation (CoVs), and intraclass correlation coefficients (ICCs) among the tests were calculated and compared in all the areas. Results Altogether, 132 eyes of 67 subjects were included (50, 47, and 35 eyes in groups 1, 2, and 3; respectively). The ICCs of corneal epithelial thickness and corneal thickness were > 0.75 in most of the areas. Pairwise comparisons showed that AS-OCT exhibited lower repeatability in group 1 than in groups 2 and 3 (P

The first pandemic wave of coronavirus disease 2019 (COVID-19) induced a considerable increase in several antivirals and antibiotics in surface water. The common symptoms of COVID-19 are viral and bacterial infections, while comorbidities (e.g., hypertension and diabetes) and mental shock (e.g., insomnia and anxiety) are nonnegligible. Nevertheless, little is known about the long-term impacts of comorbidities and mental shock on organic micropollutants (OMPs) in surface waters. Herein, we monitored 114 OMPs in surface water and wastewater treatment plants (WWTPs) in Wuhan, China, between 2019 and 2021. The pandemic-induced OMP pollution in surface water was confirmed by significant increases in 26 OMP concentrations. Significant increases in four antihypertensives and one diabetic drug suggest that the treatment of comorbidities may induce OMP pollution. Notably, cotinine (a metabolite of nicotine) increased 155 times to 187 ng·L−1, which might be associated with increased smoking. Additionally, the increases in zolpidem and sulpiride might be the result of worsened insomnia and depression. Hence, it is reasonable to note that mental-health protecting drugs/behavior also contributed to OMP pollution. Among the observed OMPs, telmisartan, lopinavir, and ritonavir were associated with significantly higher ecological risks because of their limited WWTP-removal rate and high ecotoxicity. This study provides new insights into the effects of comorbidities and mental shock on OMPs in surface water during a pandemic and highlights the need to monitor the fate of related pharmaceuticals in the aquatic environment and to improve their removal efficiencies in WWTPs.

The forming, microstructure, mechanical properties and corrosion resistance of three kinds of vacuum electron beam welded joints with different shapes were studied. The results of X-ray inspection of the joints showed that the three shapes of welded joints could meet the requirements of the quality inspection. The results of microstructure characterization show that the worm or bone-like δ-ferrite appears in the upper and lower regions of the funnel-shaped and bell-shaped joints, while only a small amount of δ-ferrite appears in the local regions of the nail-shaped joints. The test results of mechanical properties show that the micro-hardness of the weld center in the three kinds of shaped joints is the lowest. All the specimens fracture in the weld, and the bell-shaped weld presents the highest impact energy and bending load. Funnel-shaped weld shows the worst corrosion resistance due to the element segregation of the weld. Thus, the bell-shaped joint exhibits the best comprehensive performance.

Abstract Background Case-based learning (CBL) methods have gained prominence in medical education, proving especially effective for preclinical training in undergraduate medical education. Tetralogy of Fallot (TOF) is a congenital heart disease characterized by four malformations, presenting a challenge in medical education due to the complexity of its anatomical pathology. Three-dimensional printing (3DP), generating physical replicas from data, offers a valuable tool for illustrating intricate anatomical structures and spatial relationships in the classroom. This study explores the integration of 3DP with CBL teaching for clinical medical undergraduates. Methods Sixty senior clinical medical undergraduates were randomly assigned to the CBL group and the CBL-3DP group. Computed tomography imaging data from a typical TOF case were exported, processed, and utilized to create four TOF models with a color 3D printer. The CBL group employed CBL teaching methods, while the CBL-3DP group combined CBL with 3D-printed models. Post-class exams and questionnaires assessed the teaching effectiveness of both groups. Results The CBL-3DP group exhibited improved performance in post-class examinations, particularly in pathological anatomy and TOF imaging data analysis (P

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. SFTS virus (SFTSV) is transmitted by tick bites and contact with the blood or body fluids of SFTS patients. Animal-to-human transmission of SFTS has been reported in Japan, but not in China. In this study, the possible transmission route of two patients who fed and cared for farm-raised fur animals in a mink farm was explored. Method An epidemiological investigation and a genetic analysis of patients, animals and working environment were carried out. Results It was found that two patients had not been bitten by ticks and had no contact with patients infected with SFTS virus, but both of them had skinned the dying animals. 54.55% (12/22) of the farm workers were positive for SFTS virus antibody. By analyzing the large, medium and small segments sequences, the viral sequences from the two patients, animals and environments showed 99.9% homology. Conclusion It is suspected that the two patients may be directly infected by farm-raised animals, and that the virus may have been transmitted by aerosols when skinning dying animals. Transmission by direct blood contacts or animal bites cannot be ignored.

Abstract Rab27A is a small GTPase-mediating exosome secretion, which participates in tumorigenesis of multiple cancer types. Understanding the biological role of Rab27A in non-small cell lung cancer (NSCLC) is of great importance for oncological research and clinical treatment. In this study, we investigate the function and internal mechanism of Rab27A in NSCLC. Results show that Rab27A is overexpressed in NSCLC, and regulates the tumor proliferation, migration, invasion, and cell motility in vitro and in vivo, and is negatively regulated by miR-124. Further research reveals that upregulated Rab27A can induce the production of IFNα in the medium by mediating exosome secretion. Then IFNα activates TYK2/STAT/HSPA5 signaling to promote NSCLC cell proliferation and metastasis. This process can be suppressed by TYK2 inhibitor Cerdulatinib. These results suggest that Rab27A is involved in the pathogenesis of NSCLC by regulating exosome secretion and downstream signaling, and inhibitors targeting this axis may become a promising strategy in future clinical practice.

Abstract The high-frequency pulse flow, equivalent to the natural frequency of rocks, is generated by a self-excited oscillating cavity to achieve resonance rock-breaking. The flow field and oscillating mechanism of the self-excited oscillating cavity were simulated using the large eddy simulation method of Computational Fluid Dynamics (CFD). A field-scale testing apparatus was developed to investigate the impulse characteristics and verify the simulation results. The results show that the fluid at the outlet at the tool is deflected due to the pulse oscillation of the fluid. The size and shape of low-pressure vortices constantly change, leading to periodic changes in fluid impedance within the oscillating cavity. The impulse frequency reaches its highest point when the length–diameter ratio is 0.67. As the length–diameter ratio increases, the tool pressure loss also increases. Regarding the cavity thickness, the impulse frequency of the oscillating cavity initially decreases, then increases, and finally decreases again. Moreover, both the impulse frequency and pressure loss increase with an increase in displacement. The numerical simulation findings align with the experimental results, thus confirming the validity of the theoretical model. This research provides theoretical guidance for the practical application of resonance rock-breaking technology.

Abstract DNA is a danger signal sensed by cGAS to engage signaling through STING to activate innate immune functions. The best-studied downstream responses to STING activation include expression of type I interferon and inflammatory genes, but STING also activates other pathways, including apoptosis. Here, we report that STING-dependent induction of apoptosis in macrophages occurs through the intrinsic mitochondrial pathway and is mediated via IRF3 but acts independently of gene transcription. By intersecting four mass spectrometry datasets, we identify SAM68 as crucial for the induction of apoptosis downstream of STING activation. SAM68 is essential for the full activation of apoptosis. Still, it is not required for STING-mediated activation of IFN expression or activation of NF-κB. Mechanistic studies reveal that protein trafficking is required and involves SAM68 recruitment to STING upon activation, with the two proteins associating at the Golgi or a post-Golgi compartment. Collectively, our work identifies SAM68 as a STING-interacting protein enabling induction of apoptosis through this DNA-activated innate immune pathway.

Abstract Photon-initiated photoacoustic streaming (PIPS) with an Er: YAG laser has been introduced in root canal treatment to improve irrigation and facilitate the removal of bacteria in the root canal system. This study aimed to compare the antibacterial effectiveness of two different root canal irrigation techniques, conventional needle irrigation (CNI) and PIPS, using 1% sodium hypochlorite (NaOCl), in the treatment of teeth with apical periodontitis. Sixty patients with a total of sixty teeth affected by apical periodontitis were included in this study. The teeth underwent root canal therapy, and after mechanical instrumentation, they were randomly assigned to two groups (n = 30) based on the final irrigation protocol: CNI or PIPS with 1% NaOCl. Bacterial suspensions in the root canals were evaluated using Adenosine 5’-triphosphate (ATP) assay kit after mechanical instrumentation and after final irrigation. Then, a follow-up was conducted after 7 days. The results revealed that final irrigation significantly reduced ATP values in both the CNI and PIPS groups (P

ObjectiveThe risk factors of PJK (proximal junctional kyphosis) related to AIS (adolescent idiopathic scoliosis) are inconsistent due to heterogeneity in study design, diagnostic criteria, and population. Therefore, the meta-analysis was conducted to investigate the factors affecting PJK after posterior spinal fusion for AIS patients.MethodsWe implemented a systematic search to obtain potential literature relevant to PJK in AIS surgery. Then, a meta-analysis was performed to assess the incidence of PJK and its risk factors.ResultsWe retrieved 542 articles, and 24 articles were included. The PJK incidence was 17.67%. The use of hooks at UIV (upper instrumented vertebrae) (p = 0.001) could prevent PJK. Before surgery, the larger TK (thoracic kyphosis) (p

Background: Previous studies showed that MSCs could mitigate damage in the pancreas during acute pancreatitis (AP). However, acute mortality associated with AP was more often a result of persistent failure of remote organs, rather than local damage, especially in severe acute pancreatitis (SAP), and the effect of MSCs may vary depending on their origin. Methods: An SAP model was induced in 8-week C57BL/6 J male mice by retrograde injection of 5 % sodium taurocholate solution through the bile duct. SAP mice were divided into the SAP group, UC-MSCs group, and BMSCs group, which were treated with saline, 1 × 106 UC-MSCs, and 1 × 106 BMSCs respectively, through the tail vein. After treatment, serum markers, inflammation, and morphology were assessed in the pancreas, kidneys, lungs, and hearts. Results: MSCs infusion ameliorated the systemic inflammatory response in SAP mice. In the MSCs-treated SAP mice, local tissue injury and inflammation response in the pancreas were alleviated. But more importantly, the renal and lung injury were all significantly and drastically mitigated, and the levels of pro-inflammatory factors such as IL-6, MCP-1, IL-1β, and TNF-α in the kidney, lung and heart were sharply decreased. In terms of origin, UC-MSCs exhibited superior efficacy compared with BMSCs. Furthermore, compared to the normal control mice, UC-MSCs showed an earlier appearance, higher distribution densities, and longer duration of presence in the injured tissue. Conclusions: This study provides compelling evidence supporting the therapeutic potential of MSCs in SAP treatment and particularly their ability to mitigate multi-organ failure. Our results also suggested that UC-MSCs may offer greater advantages over BMSCs in SAP therapy.

Abstract BackgroundThe core Healthy Days measures were used to track the population-level health status in the China Chronic Disease and Risk Factor Surveillance; however, they were not easily combined to create a summary of the overall health-related quality of life (HRQOL), limiting this indicator’s use. ObjectiveThis study aims to develop a summary score based on the Chinese version of the core Healthy Days measures (HRQOL-5) and apply it to estimate HRQOL and its determinants in a Chinese population. MethodsFrom November 2018 to May 2019, a multistage stratified cluster survey was conducted to examine population health status and behavioral risk factors among the resident population older than 15 years in Weifang City, Shandong Province, China. Both exploratory factor analyses and confirmatory factor analyses were performed to reveal the underlying latent construct of HRQOL-5 and then to quantify the overall HRQOL by calculating its summary score. Tobit regression models were finally carried out to identify the influencing factors of the summary score. ResultsA total of 26,269 participants (male: n=13,571, 51.7%; mean age 55.9, SD 14.9 years) were included in this study. A total of 71% (n=18,663) of respondents reported that they had excellent or very good general health. One summary factor was extracted to capture overall HRQOL using exploratory factor analysis. The confirmatory factor analysis further confirmed this one-factor model (Tucker-Lewis index, comparative fit index, and goodness-of-fit index >0.90; root mean square error of approximation 0.02). Multivariate Tobit regression analysis showed that age (β=–0.06), educational attainments (primary school: β=0.72; junior middle school: β=1.46; senior middle school or more: β=2.58), average income (≥¥30,000 [US $4200]: β=0.69), physical activity (β=0.75), alcohol use (β=0.46), self-reported disease (β=−6.36), and self-reported injury (β=–5.00) were the major influencing factors on the summary score of the HRQOL-5. ConclusionsThis study constructs a summary score from the HRQOL-5, providing a comprehensive representation of population-level HRQOL. Differences in summary scores of different subpopulations may help set priorities for health planning in China to improve population HRQOL.

The interior of a high-voltage cable causes a state of extrusion due to thermomechanical effects; the resulting stress and deformation can easily lead to the destruction of the cable structure. Aiming at the problem, we establish an electromagnetic–thermal–force field model of a high voltage cable. By considering the influence of temperature on the material properties, a bidirectional couple simulation of electromagnetic and thermal fields is established. The thermal load excitation is introduced into the structural field, and the simulation calculation of thermal strain and thermal stress of the axial and radial layers is realized. The influence of ambient temperature, load current, and circulating current defect factors on the thermal–force characteristics of each layer of the cable is studied. The results show that the response of the insulating layer to the thermomechanical effect is the most significant, and its characteristic change law shows the nonlinear trend. In addition, the thermal strain of the cable has an approximate axial symmetry; the axial thermomechanical effect is significantly higher than the radial direction. The maximum axial and radial deformations of the cable when running at full load are 1.21 and 0.16 mm respectively. Among the three influencing factors, the impact of circulating current defects on the thermomechanical effect of cables is the most obvious. The thermomechanical effect of the cable approximately is positively related to the square of the circulating current defect factors, the load current, and the ambient temperature.

Osteocytes are terminally differentiated cells derived from osteoblasts and are deeply embedded within the bone matrix. They play a critical role in bone remodeling by generating a lacuno-canalicular network (LCN) and controlling the transport of nutrients. Due to the absence of blood vessels within the bone matrix, it is widely believed that osteocytes develop in a hypoxic environment. However, the mechanisms of osteocytogenesis and the role of oxygen sensing in this process remain unclear. Hypoxia-inducible factors (HIFs) are major transcriptional factors involved in oxygen sensing. Previous studies have shown that accumulation of HIFs in osteoblasts leads to abnormal bone remodeling, potentially linked with the alterations of the LCN network. Specifically, HIF-1α is hypothesized to play a more significant role in regulating bone remodeling compared to HIF-2α. Therefore, we investigated the functions of HIF-1α in dendrite formation and the establishment of the LCN network during osteocytogenesis. Immunostaining and scanning electron microscopy revealed that the E11 protein aggregates to form a ring structure that defines the site for dendrite initiation. This process is followed by activation of the ERM/RhoA pathway and recruitment of matrix metalloproteinase 14 (MMP14) to facilitate extracellular matrix degradation, enabling dendrite elongation. However, both hypoxic treatment and overexpression of HIF-1α impair ring formation, resulting in reduced ERM/RhoA activity and decreased matrix degradation capability. These findings suggest that abnormal HIF-1α activity in local areas could contribute to impaired LCN network formation and abnormal bone remodeling observed in bone diseases such as osteopenia and aging.

Porcine circovirus types 2 (PCV2) and 3 (PCV3) are the two most prevalent porcine circoviruses in China, all of which can infect swine herds and cause serious diseases. To detect coinfection with PCV2 and PCV3, primers and probes for duplex PCV2 and PCV3 real-time PCR were designed to target their cap genes based on the constructed plasmids pUC57-PCV2 and pUC57-PCV3. The established duplex PCV2 and PCV3 real-time PCRs were specific to PCV2 and PCV3 and showed no cross-reactions with other porcine viral pathogens. The limit of detection was 5 and 50 copies for the PCV2 and PCV3 plasmids, respectively. The intra- and interassay repeatability had coefficients of variation below 3 %. The established methods were used to analyze clinical samples from Liaoning and Jilin provinces of China. The coinfection rates of PCV2 and PCV3 in pigs extensively fed in Liaoning and Jilin, large-scale farmed pigs in Liaoning and large-scale farmed pigs in Jilin were 15.0 % (6/40), 36.7 % (11/30) and 35.4 % (62/175), respectively. This study established a useful duplex PCV2 and PCV3 real-time PCR method that can be used for the detection of PCV2 and PCV3 in local clinical samples.

Purpose This study elucidates the rationale, implementation, values, and challenges of the Synergized Quality Improvement Program in Teacher Education (SQIPTE)—the first policy specifically dedicated to the development of teaching staff since the founding of the People's Republic of China. Design/Approach/Methods After introducing the primary structure and rationale of the SQIPTE, this study reviews the existing data and research to explain why the program focuses on local normal colleges and determine how it could be implemented more effectively. Findings In establishing group-based assistance under the principle of “1 + M + N” (M ≥ N), the SQIPTE seeks to make normal colleges the primary force in the education of rural teachers and explores a collaborative operating mechanism to this end. Evidence suggests that this innovative program will provide new practical experience for the collaborative development and quality improvement of teachers. Originality/Value This study reviews the SQIPTE as a new Chinese intervention to improve the quality of rural teachers. There is strong evidence to suggest that this innovative program will inspire the construction of collaborative operating mechanisms incorporating multiple resources for teacher education systems across different areas.

Mechanical stirring can promote uniform distribution of crude oil temperature and increase the heating rate, but the effect is different for different heating methods in crude oil storage tank. In this paper, jet heating and tubular heating are used as the heating methods in the tank, the physical and mathematical models under the synergy of two heating methods and mechanical stirring are established, FVM and SIMPLE algorithm are used to numerical calculate. The results show that mechanical stirring can enhance the flow of crude oil in the tank, affect greatly the temperature and velocity fields of crude oil and improve uniformity of the temperature field. Mechanical stirring has more significant effect on tubular heating for the 1000 m3 actual oil storage tank. For tubular heating, mechanical stirring can increase the crude oil average velocity 13.8 times, heating rate by 0.123 °C/h, heating efficiency by 8.37 % and reduce the temperature variance by 92.03 % during 2h of heating. At the same time, the indicators of economic benefits for different heating methods are put forward, and the order of energy consumption per unit temperature rise is obtained: Tubular heating > Jet heating > Jet heating and stirring > Tubular heating and stirring.

Abstract Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1, Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation.

The purpose of this study was to assess the factors affecting caudal screw loosening after spinopelvic fixation for adult patients with spinal deformity. This meta-analysis calculated the weighted mean difference (WMD) and odds ratio (OR) using Review Manager ver. 5.3 (RevMan; Cochrane, London, UK). The loosening group was older than the control group (WMD, 2.17; 95% confidence interval [CI], 0.48–3.87; p=0.01). The S2 alar-iliac (S2AI) could prevent the caudal screw from loosening (OR, 0.43; 95% CI, 0.20–0.94; p=0.03). However, gender distribution (p=0.36), the number of fusion segments (p=0.24), rod breakage (p=0.97), T-score (p=0.10), and proximal junctional kyphosis (p=0.75) demonstrated no difference. Preoperatively, only pelvic incidence (PI) in the loosening group was higher (WMD, 5.08; 95% CI, 2.71–7.45; p

Abstract Photovoltaic (PV) modules are prone to short circuits, open circuits, cracks, which can bring serious harmful effects. It is difficult to establish the corresponding PV fault models to diagnose the status of PV strings. The paper proposes a machine learning‐based stacking classifier (MLSC) for accurate fault diagnosis of PV strings. Specifically, for the operating state of PV modules, the parameter sensitivity algorithm is used to analyze the impact of characteristic factors on the characteristics of PV modules. Then based on the characteristic factors (irradiance, temperature, current, and power), MLSC is proposed to realize the accurate fault diagnosis of PV strings. This structure of MLSC is to integrate all kinds of classifiers by stacking to play the characteristics of each classifier. It combines the characteristics of various types of machine learning algorithms to improve the overall classification effect by using the advantages of each classifier. Finally, experiments reveal that MLSC improves the accuracy of PV fault diagnosis.

Interferometric Synthetic Aperture Radar (InSAR) enables the efficient retrieval of surface elevation and has extensive applications in terrain mapping. Dual/multi-channel InSAR techniques utilize the differences in the elevation ambiguity of different InSAR channels (i.e., baselines and frequencies) to perform Phase Unwrapping (PU). This enables the effective application of InSAR in regions with abrupt terrain changes. In response to the growing demand for efficient and precise PU, this study leverages deep learning and proposes a dual/multi-channel joint PU network, i.e., Multi-Channel-Joint-UNet (MCJ-UNet), which effectively combines multi-channel phase characteristics and their mutual constraint relationships. The proposed network is constructed based on the dual-channel (i.e., dual-frequency and dual-baseline) InSAR observation configuration. It can also be extended to multi-channel InSAR. The core concept of the proposed method can be summarized as follows. First, the method transforms the elevation ambiguity estimation problem in PU into semantic segmentation, and the UNet network is employed to accomplish the segmentation processing. Second, the squeeze-and-excitation module is introduced to dynamically adjust the information weights, enhancing the network’s perception of the required information across different channels. Third, a phase residual optimization loss function is employed in the context of multi-channel joint constraints to achieve network tuning. In addition, to mitigate the effect of edge detail errors in semantic segmentation results on PU performance, a self-correcting approach for PU errors based on multi-channel joint constraints is proposed. The proposed MCJ-UNet is verified by computer simulations based on simulated and real terrains and experiments based on real TerraSAR-X data.

Genetic transformation has been a cornerstone in plant molecular biology research and molecular design breeding, facilitating innovative approaches for the genetic improvement of trees with long breeding cycles. Despite the profound ecological and economic significance of conifers in global forestry, the application of genetic transformation in this group has been fraught with challenges. Nevertheless, genetic transformation has achieved notable advances in certain conifer species, while these advances are confined to specific genotypes, they offer valuable insights for technological breakthroughs in other species. This review offers an in-depth examination of the progress achieved in the genetic transformation of conifers. This discussion encompasses various factors, including expression vector construction, gene-delivery methods, and regeneration systems. Additionally, the hurdles encountered in the pursuit of a universal model for conifer transformation are discussed, along with the proposal of potential strategies for future developments. This comprehensive overview seeks to stimulate further research and innovation in this crucial field of forest biotechnology.

Abstract Objective To analyze the changes of plantar pressure in amateur marathon runners with flexor halluics longus (FHL) tendon injury using the Medtrack-Gait plantar pressure measurement system, and to explore whether the plantar pressure data can be used as an index for the diagnosis of injury. Methods A total of 39 healthy amateur marathon runners without any ankle joint symptoms were recruited. Dynamic and static plantar pressure data were measured using the pressure plate of Medtrack-Gait. According to MRI imaging findings, whether the FHL tendon was injured or not was judged, and the dynamic and static data were divided into the injury group and control group. The data with statistically significant differences between the two groups were used to make the receiver operating characteristic (ROC) curve. Result The maximum contact area (PA) of the first metatarsal(M1) region, the maximum load-bearing peak value (PW) and the time pressure integral (PMPTI) of the second metatarsal(M2) region in the injury group were lower than those in the control group, respectively (P

Abstract Purpose The choice of continuous renal replacement therapy (CRRT) anticoagulation program for patients at high risk of bleeding has always been a complex problem in clinical practice. Clinical regimens include regional citrate anticoagulation (RCA) and nafamostat mesylate (NM). This study aimed to evaluate the efficacy and safety of these two anticoagulants for CRRT in patients at high risk of bleeding to guide their clinical use better. Patients and methods Between January 2021 and December 2022, 307 patients were screened for this study. Forty-six patients were finally enrolled: 22 in the regional citrate anticoagulation group and 24 in the nafamostat mesylate group. We collected patients’ baseline characteristics, laboratory indicators before CRRT, and CRRT-related data. We then performed a statistical analysis of the data from both groups of patients. Results In our study, the baseline characteristics did not differ significantly between the two groups; the baseline laboratory indicators before CRRT of patients in the two groups were not significantly different. The duration of CRRT was 600 min in the regional citrate anticoagulation (RCA) group, 615 min in the nafamostat mesylate (NM) group; the success rate was 90.7% in the RCA group, and 85.6% in the NM group, the anticoagulant efficacy between the two groups was comparable. There was no significant difference in the safety of anticoagulation between the two groups. We used Generalized Estimating Equations (GEE) to test whether different anticoagulation methods significantly affected the success rate of CRRT and found no statistical difference between RCA and NM. Conclusion Our study suggests that nafamostat mesylate's anticoagulant efficacy and safety are not inferior to regional citrate anticoagulation for continuous renal replacement therapy in patients at high risk of bleeding.

Abstract Emerging evidence reveals associations between metabolic syndrome (MetS) and psychiatric disorders (PDs), although causality remains uncertain. Consequently, we conducted Mendelian randomization (MR) to systematically evaluate the causality between MetS and PDs. Linkage disequilibrium score regression estimated the heritability of PDs and their genetic correlations with MetS. In primary analyses, the main model employed inverse variance weighting method, with sensitivity analyses using various MR models to ensure robustness. Replication MR analyses, involving cohorts distinct from those in the primary analyses, were performed to validate the generalizability of the findings. Multivariable MR analyses were carried out to account for genetically predicted body mass index (BMI). As a result, genetic correlations of MetS with attention-deficit/hyperactivity disorder(ADHD), anorexia nervosa(ANO), major depressive disorder(MDD), and schizophrenia were identified. Causal effects of MetS on ADHD (OR: 1.59 [95% CI:1.45–1.74]), ANO (OR: 1.42 [95% CI:1.25–1.61]), MDD(OR: 1.23 [95% CI: 1.13–1.33]), and the effects of ADHD (OR: 1.03 [95% CI: 1.02–1.04]) and ANO (OR: 1.01 [95% CI: 1.01–1.02]) on MetS were observed in primary analyses. Results from sensitivity analyses and replication analyses were generally consistent with the primary analyses, confirming the robustness and generalizability of the findings. Associations between MetS and ADHD, as well as ANO persisted after adjusting for BMI, whereas the statistical significance of the association between MetS and MDD was no longer observable. These results contribute to a deeper understanding of the mechanisms underlying PDs, suggesting potential modifiable targets for public prevention and clinical intervention in specific PDs related to metabolic pathways.

Abstract Background Smoking is a significant public health concern in China and a leading cause of lung cancer deaths among adults. This study aims to employ three methods to estimate smoking-attributable lung cancer mortality among Chinese adults from 2000 to 2020. Methods Population attributable fractions (PAFs) of lung cancer deaths caused by smoking were estimated using lagged smoking prevalence, Peto-Lopez, and dose–response relationship methods, separately. Smoking exposure was obtained from national tobacco surveys in China, and relative risks (RR) were derived from a meta-analysis of state-of-the-art studies among the Chinese population. Finally, we estimated the sex- and age-stratified smoking-attributable lung cancer deaths in Chinese population in 2000, 2005, 2010, 2015, and 2020. Results The PAFs estimated using 5- and 10-year lagged smoking prevalence method (45–47%) and Peto-Lopez method (46–47%) were similar, while PAFs calculated using the dose–response method were highest (47–58%). The PAFs were consistently higher in males than in females. Age-specific PAFs estimated by lagged smoking prevalence method (54–60%) and the Peto-Lopez method (57–61%) in males were similar and relatively stable, with slight decreases in older populations, while the dose–response relationship-based PAFs increased with age and fluctuated by year. By using the above methods, smoking-attributable lung cancer deaths were estimated to be 134,100, 134,600, 136,600, and 155,300 in 2000 increasing to 310,300, 301,100, 306,000, and 314,700 in 2020, respectively. Conclusion The estimation from dose–response methods could better reflect the smoking effect, however, high-quality data and accurate estimation of parameters are necessary.

CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases. CD36 was recently found to be widely expressed in various cell types in the nervous system, including endothelial cells, pericytes, astrocytes, and microglia. CD36 mediates a number of regulatory processes, such as endothelial dysfunction, oxidative stress, mitochondrial dysfunction, and inflammatory responses, which are involved in many central nervous system diseases, such as stroke, Alzheimer’s disease, Parkinson’s disease, and spinal cord injury. CD36 antagonists can suppress CD36 expression or prevent CD36 binding to its ligand, thereby achieving inhibition of CD36-mediated pathways or functions. Here, we reviewed the mechanisms of action of CD36 antagonists, such as Salvianolic acid B, tanshinone IIA, curcumin, sulfosuccinimidyl oleate, antioxidants, and small-molecule compounds. Moreover, we predicted the structures of binding sites between CD36 and antagonists. These sites can provide targets for more efficient and safer CD36 antagonists for the treatment of central nervous system diseases.

Abstract The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.

The filamentous fungus Trichoderma reesei is widely used for the production of lignocellulolytic enzymes in industry. XYR1 is the major transcriptional activator of cellulases and hemicellulases in T. reesei. However, rational engineering of XYR1 for improved lignocellulolytic enzymes production has been limited by the lack of structure information. Here, alanine 873 was identified as a new potential target for the engineering of XYR1 based on its structure predicted by AlphaFold2. The mutation of this residue to tyrosine enabled significantly enhanced production of xylanolytic enzymes in the medium with cellulose as the carbon source. Moreover, xylanase and cellulase production increased by 56.7- and 3.3-fold, respectively, when glucose was used as the sole carbon source. Under both conditions, the improvements of lignocellulolytic enzyme production were higher than those in the previously reported V821F mutant. With the enriched hemicellulases and cellulases, the crude enzymes secreted by the A873Y mutant strain produced 51 % more glucose and 52 % more xylose from pretreated corn stover than those of the parent strain. The results provide a novel strategy for engineering the lignocellulolytic enzyme-producing capacity of T. reesei, and would be helpful for understanding the molecular mechanisms of XYR1 regulation.

AbstractPurpose To evaluate dry eye and anterior segment inflammation after small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK), and investigate their association.Methods This prospective and observational study included 96 eyes from 48 myopic patients. The evaluation was performed at baseline, postoperative day 1, week 1, month 1 and month 3. Outcome measures included anterior chamber flare, bulbar redness (BR), limbal redness (LR), ocular surface disease index (OSDI), tear meniscus height (TMH), the first and average noninvasive breakup time (NIBUT-1, NIBUT-a), fluorescein breakup time (FBUT), corneal fluorescein staining (CFS), and Schirmer I. Generalized estimating equations (GEEs) were applied to explore the correlation between flare and ocular surface parameters.Results Flare increased significantly in both groups at day 1 and week 1 and then returned to baseline at month 1. In both groups, BR decreased on day 1 and then gradually increased towards the baseline. In FS-LASIK, LR was lower than baseline at day 1 and month 3. An increase in OSDI was found in the SMILE group on day 1, and in the FS-LASIK group at day 1 to month 1. NIBUT-1 and NIBUT-a decreased significantly on day 1 in both groups. At month 3, NIBUT-a did not return to baseline in FS-LASIK. CFS increased significantly at week 1 in both groups. All parameters were comparable between SMILE and FS-LASIK except for OSDI and NIBUT-a. Time and spherical equivalent showed a correlation with flare.Conclusions Both SMILE and FS-LASIK induced elevated anterior chamber flare and dry eye. However, flare might not be considered a factor determining perioperative dry eye.Key MessagesDry eye disease is common after corneal refractive surgery. Signs and symptoms of dry eye disease persist longer after FS-LASIK compared with SMILE.Both FS-LASIK and SMILE transiently disrupted blood-aqueous barrier integrity, leading to anterior segment inflammation.Anterior chamber flare might not be considered a factor explaining perioperative dry eye, other biomarkers remain for future exploration.

With large-scale wind power connected to the power grid, accurate short-term wind power forecasting has become a key technology for safe, economic power grid operation. Therefore, a short-term wind power forecasting and uncertainty analysis method based on the FCM-WOA-ELM-GMM was proposed. Fuzzy C-means (FCM) was used to cluster the numerical weather prediction (NWP) and wind farm power data, and the data points with similar meteorological information are classified into one class. Using the rapid convergence and high convergence accuracy of the whale optimization algorithm (WOA), the input weight and hidden layer threshold of the extreme learning machine (ELM) model were optimized to improve the ELM calculation speed and forecasting accuracy. The WOA-ELM model was trained using the clustered NWP and wind farm power data and the short-term wind power was projected using the trained forecasting model. To accurately calculate the forecasting error probability density distribution, the Gaussian mixture model (GMM) was applied and the wind power forecast confidence intervals under different climatic conditions and time scales were calculated. The forecasting accuracies of the WOA-ELM, ELM, PSO-LSSVM, LSSVM, LSTM, PSO-BP, and WNN models were compared and analyzed, and the RMSE values of the 4-h forecasting results in April were as follows: WOA-ELM, 5.95%; ELM, 26.73%; PSO-LSSVM, 3.78%; LSSVM, 5.19%; LSTM, 23.71%; PSO-BP, 15.63%; and WNN, 23.23%. The RMSE values of 24-h forecasting results in April were: WOA-ELM, 6.62%; ELM, 19.86%; PSO-LSSVM, 9.91%; LSSVM, 13.73%; LSTM, 23.69%; PSO-BP, 14.08%; and WNN, 20.11%. The RMSE values of 72-h forecasting results in April were as follows: WOA-ELM, 5.24%; ELM, 13.64%; PSO-LSSVM, 12.03%; LSSVM, 13.67%; LSTM, 16.61%; PSO-BP, 15.46%; and WNN, 20.22%. According to the calculation results, under different climatic conditions and forecasting time scales, the forecasting accuracy of the FCM-WOA-ELM-GMM model is higher than those of the other models.

Yuanbaoshancha (YBSC) is characterized as a new wild tea relative morphologically and phytochemically distinguished from the closest wild tea plants Rongjiangcha (Camellia yungkiangensis, RJC) and Tulecha (Camellia costata, TLC). YBSC young leaves contain higher tea polyphenol and theobromine contents but lower caffeine and theanine as compared with RJC, TLC, and other tea landraces and modern cultivars. The major alkaloid detected in YBSC, TLC, and RJC is theobromine while caffeine is a minor; the primary catechins in YBSC leaves are non-galloylated catechins, significantly different from Camellia sinensis and other low-caffeine tea resources. The unique phytochemical profiles featured YBSC black tea with extremely lower caffeine and higher theobromine, as well as unique flavors and health benefits. This botanical characterization of YBSC and two related low-caffeine wild tea resources lays a foundation for future better utilization for the production of a highly valuable natural low-caffeine/high-theobromine tea. Chemical compounds: Caffeine (PubChem CID: 2519); Theobromine (PubChem CID: 5429); Catechins (PubChem CID: 9064); Epigallocatechin gallate (PubChem CID: 65064); Theanine (PubChem CID: 439378); Jasmone (PubChem CID: 1549018); cis-3-Hexenyl hexanoate (PubChem CID: 5352543); Hexyl 2-methylbutanoate (PubChem CID: 24838).

A newly developed microseismic (MS) monitoring system was employed in the Tianshan-Shengli tunnel to detect MS activities and then predict and provide early warning of rockburst disasters. The system not only has the advantages of accuracy of artificial analysis but also real-time analysis and warnings. The positioning accuracy for MS events is approximately 5–10 m. A new sensor installation scheme was proposed to achieve fast sensor installation and recovery, taking advantage of semicircular steel tubes and hose clamps. In addition, the rockburst risk level prediction criteria adopted multiple evaluation indexes such as MS event energy and moment magnitude and number, and it revealed that the evolution of maximum energy has a good positive correlation with that of maximum moment magnitude through analyzing the monitored MS events. It also showed that the rockburst generally occurred 2 days after the rock mass was exposed by the tunnel boring machine (TBM) tail shield and belonged to the delayed rockburst category, according to the field statistical results. The preliminary application cases indicated that the rockburst prediction and early warning based on MS monitoring agree with the site survey results. Therefore, the new MS monitoring system is a reliable tool for predicting and providing early warnings of rockburst disasters.

ABSTRACT Through a long-term micro-area positioning experiment (2006-2017), the precise fertilization locations of spring maize (Zea mays L.) in Jilin, China, were investigated using an embedded cement bucket pot. The effects of different fertilization placements and additional application of organic manure on maize yield, biomass, grain nutrient uptake, and soil fertility were examined. Six treatments were designed: base fertilizer + topdressing shallow application (BF1TD1); base fertilizer deep + topdressing shallow application (BF2TD1); base fertilizer + topdressing deep application (BF1TD2); base fertilizer deep + topdressing deep application (BF2TD2); base fertilizer + topdressing + organic manure shallow application (BF1TD1 + OS); and base fertilizer + topdressing shallow application + organic manure deep application (BF1TD1 + OD). After 12 years of continuous experimentation, the findings revealed that BF2TD2, BF1TD1 + OS, and BF1TD1 + OD exhibited 10.59 %, 25.17 %, and 29.34 % higher average yields than BF1TD1, respectively. Deep topdressing was more beneficial in increasing maize yield and nutrient accumulation, and additionally, increasing the use of organic fertilizer enhanced plant biomass and nutrient uptake. Over the 12 years considered, the soil organic matter in the 0-20 cm and 20-40 cm layers increased by 45.96 % and 80.61 %, respectively, and the soil pH increased from 0.38 to 0.48. In general, the deep application of organic manure was more beneficial for soil retention as it can increase soil fertility in the 0-40 cm layer. Considering the high yield and nutrient absorption and utilization of maize, technical advancement for soil fertilizer in whole-field tillage layers was crucial.

BackgroundPostpartum depression (PPD) is the most common mental illness affecting women after childbirth, and working mothers may be faced with unique challenges. This study aimed to examine the depression status among working postpartum women in 1 year of childbirth and explore the relationship between occupational factors and PPD in urban Beijing, China.MethodsA cross-sectional survey of 554 postpartum women was conducted among ten community health service centers in six urban districts of Beijing, China. Sociodemographic, occupational, childbirth and postpartum information were collected. Depression status was obtained using the Edinburgh Postnatal Depression Scale. Prevalence of postpartum depression (PPD) was assessed in relation to occupational characteristics, and influencing factors were analyzed through logistic regression.ResultsOf the postpartum women, 29.42% met the criteria for depression. PPD prevalence was significantly higher among women employed in commercial enterprises (39.81%). The analysis of influencing factors showed that age, family or personal monthly income, maternity leave, feeding methods, and postpartum care affected the psychological health of occupational women after childbirth.ConclusionPPD prevalence is notably elevated among women employed in commercial enterprises, and specific risk factors contribute to its occurrence. These findings highlight the need for targeted interventions to address these risk factors and prevent PPD in this population.

The aim of this study was to expose anti-obesity effect of Gnaphalium affine (GA) and its underlying mechanism by combining biochemical analysis, 16S rRNA sequencing and untargeted metabolomics. The results showed GA alleviated high-fat diet (HFD)-mediated oxidative stress, fat accumulation and inflammation. Moreover, GA improved gut barrier and immunity in HFD-fed mice through up-regulating tight junction protein, decreasing Lipopolysaccharide (LPS) level and inhibiting pro-inflammatory makers production in LPS/ toll-like receptor 4 (TLR4) / Myd88 / NF-κB pathway. Additionally, GA and its extracts altered composition and metabolism of gut microbiota. GA promoted abundances of Dubosiella and decreased abundance of Alistipes in HFD-fed mice, which were closely linked to 5-Hydroxy-6,7-dimethoxylflavone from GA and levels of weight, inflammatory markers, gut microbial metabolites of mice. Collectively, GA offers its anti-obesity properties through regulating gut microbiota by mucosal barrier functions, indicating that GA and its natural compounds hold great potential as a functional food ingredient.

With the tertiary oil recovery in the oilfield, the content of aging oil emulsion with high water content and complex components has become more prevalent, so it is crucial for aging oil to break the emulsification. In this paper, the experimental laws of water content are explored under the conditions of different transducer input powers through the ultrasonic reforming of aging oil, and the microscopic topography, particle size, components, etc. of oil samples before and after the irradiation of ultrasound are characterized through the microscopic analysis, particle size analysis and component analysis and other ways. The results show that the oil samples achieve the effect of demulsification and dehydration in the presence of ultrasonic cavitation effect, with a maximum dehydration rate of 98.24 %, and that the dehydration rate follows an “M−type” trend with the increase of power. The results of microscopic and particle size analyses demonstrate that ultrasonic irradiation destabilizes the oil–water interfacial membrane, and causes droplets of different sizes to collide, agglomerate, and settle. It was also observed that the droplets of the emulsion system are more evenly distributed and the intervals are increased. Furthermore, we hypothesize that ultrasound may be less irreversible in demulsification and dehydration of aging oil.

The blotched snakehead (Channa maculata) is a freshwater species of economic importance, widely distributed throughout Southeast Asia and Southern China. The comprehension of genetic regulatory mechanisms underlying growth traits, particularly body weight, is paramount for the advancement and economic viability of blotched snakehead aquaculture. Despite its importance, limited investigations have been undertaken regarding the growth properties of this species. To enhance our grasp of the genetic regulation mechanisms dictating growth traits and identify pertinent genetic loci, the inaugural genome-wide association study (GWAS) was executed. In this study, eight growth traits of 500 blotched snakeheads were measured and whole genome resequencing (WGS) were conducted. Genetic parameters were estimated for the eight traits, revealing moderate to high heritability (0.2245–0.5184) for seven traits, while one exhibited low heritability (0.1081). A comprehensive set of 2, 225, 993 high-quality SNPs were identified in the 500 blotched snakehead individuals, and the mixed linear model in GEMMA was applied for GWAS analysis. A total of 51 significant SNPs related to the seven growth traits were identified, and 112 genes were obtained by scanning 50 kb upstream and downstream regions. Thirteen genes harboring significant SNP sites were considered as important candidate genes, and these genes were associated with organelle formation, signal transduction, cell proliferation, and muscle growth. Notably, the HS6ST1 gene was significantly associated with body weight, body length and total length, designating it as a key candidate gene. This investigation makes a substantive contribution to our comprehension of the genetic architecture governing growth traits in the blotched snakehead, establishing a robust foundation for future initiatives in molecular marker-assisted selection and breeding strategies.

The effects of dietary emodin supplementation on the growth, gut health, and gut microbiota of common carp (Cyprinus carpio) were evaluated in this study. The basal diet (CONTROL group) was supplemented with 5 g/kg (EMODIN 5 group), 10 g/kg (EMODIN 10 group) and 20 g/kg (EMODIN 20 group) emodin for 6 weeks. Compared with the CONTROL alone group, the EMODIN 10 and EMODIN 20 groups of common carp had a significantly increased weight gain rate (WG%), specific growth rate (SGR%), and condition factor ratio (CF%) and decreased feed conversion ratio (FCR). The activities of intestinal digestive enzymes, including α-amylase (AMS), protease (PRT) and lipase (LPS), were also significantly increased in the emodin group (EMODIN 10 and EMODIN 20). Emodin also enhanced intestinal barrier function by increasing the length of intestinal villi, the number of goblet cells, and expression of the occludin gene. The dominant gut probiotics Cetobacterium and Actinobacteriota_unclassified were significantly enriched in the emodin group, while Aeromonas abundance was depleted, indicating that the intestinal barrier health of the emodin-treated carp improved. We also observed elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), catalase (CAT) and superoxide dismutase (T-SOD) activities, and malondialdehyde (MDA) levels were reduced in the serum of the treatment group, which means that the fish's immunity was improved. There was functional enrichment of gut microbiota immune system pathways in the emodin group, which highlights the importance of gut immunity. Network pharmacology analysis showed that the NF-κB signaling pathway was significantly enriched in the intestine-immunity axis. Accordingly, RTPCR showed that emodin affected the intestinal expression of NF-κB signaling pathway-related immune factors in artificially infected fish, including decreased NF-κB, IL-6 and TNF-α expression and increased TLR22 expression. Correlation analysis showed that downregulated NF-κB expression upon emodin addition (EMODIN 20) was related to increased Cetobacterium abundance. Therefore, dietary emodin supplementation may enhance intestinal immune defense by regulating the intestinal microbiota, which promotes common carp growth.

DNA methylation indicates the individual’s aging, so-called Epigenetic clocks, which will improve the research and diagnosis of aging diseases by investigating the correlation between methylation loci and human aging. Although this discovery has inspired many researchers to develop traditional computational methods to quantify the correlation and predict the chronological age, the performance bottleneck delayed access to the practical application. Since artificial intelligence technology brought great opportunities in research, we proposed a perceptron model integrating a channel attention mechanism named PerSEClock. The model was trained on 24,516 CpG loci that can utilize the samples from all types of methylation identification platforms and tested on 15 independent datasets against seven methylation-based age prediction methods. PerSEClock demonstrated the ability to assign varying weights to different CpG loci. This feature allows the model to enhance the weight of age-related loci while reducing the weight of irrelevant loci. The method is free to use for academics at www.dnamclock.com/#/original.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a serious type of hemorrhagic stroke. It is very important to predict the prognosis at early phase. In this work, we intend to characterize early changes in peripheral blood cells after aSAH and explore the association between peripheral blood cells and clinical outcomes after aSAH. Methods: aSAH patients admitted between December 2019 and September 2022 were enrolled. A retrospective observational study was performed. Total leukocytes, monocytes, neutrophils, erythrocytes, lymphocytes and platelets counts were recorded on the day of admission (day 1), day 3, day 5 and day 7. Statistical tests included Chi-square test, analysis of variance and multivariate logistic regression (MLR) models. 197 patients were analyzed. Results: Leukocytes and neutrophils were higher in poor outcome groups from day 1 to day 7 and in delayed cerebral ischemia (DCI) groups from day 3 to day 7. Lymphocytes were higher at day 5 and day 7 in good outcome groups and no DCI groups. Neutrophil-to-lymphocyte ratio (NLR) was lower from day 3 to day 7 in good outcome groups and no DCI groups. Erythrocytes were higher from day 3 to day 7 in good outcome groups and no DCI groups. Lymphocytes were negatively related to poor outcomes on day 1 (OR = 0.457), indicating higher lymphocytes predicted good outcomes, Neutrophils were positively related to poor outcomes on day 3 (OR = 3.003) indicating higher neutrophils predicted poor outcomes. Lymphocytes were negatively related to DCI on day 5 (OR = 0.388) indicating higher lymphocytes predicted no DCI, Erythrocytes were negatively related to DCI on day 5 (OR = 0.335) and day 7 (OR = 0.204) indicating higher erythrocytes predicted no DCI. The improved ability of neutrophils, lymphocytes and erythrocytes to predict DCI or poor functional outcomes were revealed by ROC curve analysis. Conclusions: The dynamic changes of peripheral blood cell counts were related to poor functional outcomes and DCI after aSAH. Elevated neutrophils, leukocytes, NLR, and decreased lymphocytes, erythrocytes were accompanied by DCI and poor outcome. Neutrophils, lymphocytes and erythrocytes counts could be beneficial to predict DCI and outcomes after aSAH.

Abstract T cells engineered to express chimeric antigen receptors (CARs) with specificity toward tumor cells have led to promising outcomes in patients with hematological malignancies. Nevertheless, the application of CAR‐T cell therapy in solid tumors encounters several obstacles. These include tumor heterogeneity and immune escape, T cell exhaustion and restricted infiltration into the tumors that affect the therapeutic efficacy of CAR‐T cells, as well as “on‐target, off‐tumor” toxicities that can lead to severe and even fatal adverse events. In recent years, clinical trials and new approaches of CAR‐T cell therapy for solid tumors have made certain progress. Here, we update the outcomes of related clinical trials and summarize engineered strategies aiming to improve the efficacy and therapeutic safety of CAR‐T cells based on experimental and clinical studies.

RNA editing plays an extensive role in the initiation and progression of cancer. However, the overall profile and molecular functions of RNA editing in different ovarian cancer subtypes have not been fully characterized and elucidated. Here, we conducted a study on RNA editing in four cohorts of ovarian cancer subtypes through large-scale parallel reporting and bioinformatics analysis. Our findings revealed that RNA editing patterns exhibit subtype-specific characteristics within cancer subtypes. The expression pattern of ADAR and the number of differential editing sites varied under different conditions. CCOC and EOC exhibited significant editing deficiency, whereas HGSC and MOC displayed significant editing excess. The sites within the turquoise module of the coedited network also revealed their correlation with ovarian cancer. In addition, we identified an average of over 40,000 cis-edQTLs in the four subtypes. Finally, we explored the association between RNA editing and drug response, uncovering several potentially effective editing-drug pairs (EDP) and suggesting the conceivable utility of RNA editing sites as therapeutic targets for cancer treatment. Overall, our comprehensive study has identified and characterized RNA editing events in various subtypes of ovarian cancer, providing a new perspective for ovarian cancer research and facilitating the development of medical interventions and treatments.

The effect of underwater noise environment generated by equipment in industrial recirculating aquaculture systems (RAS) on fish is evident. However, different equipment generate noise in various frequency ranges. Understanding the effects of different frequency ranges noise on cultured species is important for optimizing the underwater acoustic environment in RAS. Given this, the effects of underwater noise across various frequency bands in RAS on the growth, physiology, and collective behavior of juvenile largemouth bass (Micropterus salmoides) were comprehensively evaluated here. In this study, three control groups were established: low-frequency noise group (80–1000 Hz, 117 dB re 1μPa RMS), high-frequency noise group (1–19 kHz, 117 dB re 1μPa RMS), and ambient group. During a 30-day experiment, it was found that: 1) industrial RAS noise with different frequency bands all had a certain inhibitory effect on the growth of fish, which the weight gain rate and product of length and depth of caudal peduncle in the ambient group were significantly higher than those of the two noise groups, with the low-frequency noise group showing significantly lower values than the high-frequency noise group; 2) industrial RAS noise had a certain degree of adverse effect on the digestive ability of fish, with the low-frequency noise group being more affected; 3) industrial RAS noise affected the collective feeding behavior of fish, with the collective feeding signal propagation efficiency and feeding intensity of the noise groups being significantly lower than those of the ambient group, and the high-frequency noise group performing better than the low-frequency noise group as a whole therein. From the above, the underwater noise across different frequency bands generated by equipment operation in industrial RAS both had an impact on juvenile largemouth bass, with the low-frequency noise group being more severely affected.