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Abstract The comprehensive study of the relationship between lymph node metastasis (LNM) and its associated factors in patients with concurrent papillary thyroid carcinoma (PTC) and Hashimoto’s thyroiditis (HT) remains insufficient. Building upon the initial investigation of factors associated with LNM in patients with concurrent PTC and HT, we further analyzed the complex relationships between different severity indicators of LNM and these associated factors. This study included patients confirmed PTC with HT who underwent total thyroidectomy at Xiangya Hospital, from January 2020 to December 2021. A total of 271 patients from 2020 were used as the training set, and 300 patients from 2021 as the validation set. Univariate analysis and regression modeling were used to identify key factors associated with LNM. Model reliability was assessed using the area under the receiver operating characteristic curve (AUC). Network analysis was employed to explore associations between LNM severity and its related factors. The regression model indicated that age, calcification, free triiodothyronine (FT3), and tumor maximum diameter (TMD) are independent factors for LNM. The severity model showed free thyroxine (FT4) and hemoglobin (Hb) are independent protective factors for the region and quantity of LNM, respectively, while TMD is an independent risk factor for both. Network analysis revealed TMD has a closer relationship with LNM severity compared to other associated factors. This study innovatively combined regression models and network analysis to investigate factors related to LNM in patients with PTC and HT, providing a theoretical basis for predicting preoperative LNM in future clinical practice.

Abstract Background The effect of neoadjuvant immunotherapy on minimally invasive gastrectomy (MIG) in older patients with gastric cancer remains controversial. This study aimed to evaluate the safety, and efficacy of MIG for older patients who underwent neoadjuvant chemotherapy and immunotherapy (NICT). Methods The clinical data of 726 older patients aged over 65 years who underwent upfront MIG or MIG after NICT in the Department of General Surgery, Chinese PLA General Hospital First Medical Center between Jan 2020 and Nov 2023 were retrospectively analyzed. Propensity score-matched (PSM) analysis at a ratio of 1:2 was performed to reduce bias from confounding patient-related variables, short- and long-term outcomes were compared between the two groups. Results The baseline characteristics were comparable between 61 patients in the NICT-MIG group and 114 patients in the MIG group after PSM (P > 0.05). The major pathological response (MPR) rate and pathological complete response (pCR) rate were 44.2% and 21.3%, respectively, in the NICT-MIG group. Patients in the NICT-MIG group had longer operation times (P = 0.005) and postoperative days (P = 0.030) than those in the MIG group. No significant differences were found in intraoperative bleeding, number of retrieved lymph nodes, first flatus day, R0 resection rate, overall postoperative complication (POC) morbidity, severe POC morbidity, 2-year overall, and recurrence-free survival between the MIG and NICT-MIG groups (P > 0.05). Multivariate logistic analysis revealed that an estimated blood loss > 200 mL (P = 0.010) and a lymphocyte-to-monocyte ratio (LMR) ≤ 3.25 (P = 0.006) were independent risk factors for POCs after MIG in older patients. Conclusion The safety, and efficacy of NICT-MIG were comparable to those of upfront MIG in older patients with GC. Patients with an estimated blood loss > 200 mL or an LMR ≤ 3.25 should be carefully evaluated for an increased risk of POCs in older patients who undergo MIG. Trial registration Chinese Clinical Trial Registry (Registration Number: ChiCTR2400086827).

Abstract Background Depression acts as a noteworthy worldwide public health challenge. Identifying accessible biomarkers is crucial for early diagnosis and intervention. The relationship between depression in adult Americans and the neutrophil to high-density lipoprotein cholesterol ratio (NHR) was investigated in this research. Methods The relationship between NHR and depressive symptoms was analyzed utilizing National Health and Nutrition Examination Survey data from 2005 to 2018 and the Patient Health Questionnaire-9. The study included 33,871 participants with complete NHR and depression data. Adjusted multivariable logistic regression models were used to account for possible confounders, and subgroup analyses were conducted to investigate effect changes. Results Elevated NHR levels were positively correlated with a heightened risk of depression (OR = 1.03, 95% CI: 1.01–1.05, P

Feature selection (FS) is a promising pre-processing step before performing most data engineering tasks. The goal of it is to select the optimal feature subset with promising quality from the original high-dimension feature space. The Salp Swarm Algorithm (SSA) has been widely used as the optimizer for FS problems. However, with the increase of dimensionality of original feature sets, the FS problems propose significant challenges for SSA. To solve these issues that SSA is easy to fall into local optimum and have poor convergence performance, we propose a multi-swarm SSA (MSSA) to solve the FS problem. In MSSA, the salp swarm was divided into three sub-swarms, the followers updated their positions according to the optimal leader of the corresponding sub-swarm. The design of multi-swarm and multi-exemplar were beneficial to maintain the swarm diversity. Moreover, the updating models of leaders and followers were modified. The salps learn from their personal historical best positions, which significantly improves the exploration ability of the swarm. In addition, an adaptive perturbation strategy (APS) was proposed to improve the exploitation ability of MSSA. When the swarm stagnates, APS will perform the opposition-based learning with the lens imaging principle and the simulated binary crossover strategy to search for promising solutions. We evaluated the performance of MSSA by comparing it with 14 representative swarm intelligence algorithms on 10 well-known UCI datasets. The experimental results showed that the MSSA can obtain higher convergence accuracy with a smaller feature subset.

Abstract Pain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management is crucial for individuals suffering from pain. However, the current methods for pain assessment and treatment fall short of clinical needs. Benefiting from advances in neuroscience and biotechnology, the neuronal circuits and molecular mechanisms critically involved in pain modulation have been elucidated. These research achievements have incited progress in identifying new diagnostic and therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting the stage for the subsequent contents. The review next delves into the molecular mechanisms underlying pain disorders, including gene mutation, epigenetic modification, posttranslational modification, inflammasome, signaling pathways and microbiota. To better present a comprehensive view of pain research, two prominent issues, sexual dimorphism and pain comorbidities, are discussed in detail based on current findings. The status quo of pain evaluation and manipulation is summarized. A series of improved and innovative pain management strategies, such as gene therapy, monoclonal antibody, brain-computer interface and microbial intervention, are making strides towards clinical application. We highlight existing limitations and future directions for enhancing the quality of preclinical and clinical research. Efforts to decipher the complexities of pain pathology will be instrumental in translating scientific discoveries into clinical practice, thereby improving pain management from bench to bedside.

Dynamin-related protein 1 (DRP1) plays crucial roles in mitochondrial and peroxisome fission. However, the mechanisms underlying the functional regulation of DRP1 in adipose tissue during obesity remain unclear. To elucidate the metabolic and pathological significance of diminished DRP1 in obese adipose tissue, we utilized adipose tissue–specific DRP1 KO mice challenged with a high-fat diet. We observed significant metabolic dysregulations in the KO mice. Mechanistically, DRP1 exerts multifaceted functions in mitochondrial dynamics and endoplasmic reticulum (ER)-lipid droplet crosstalk in normal mice. Loss of function of DRP1 resulted in abnormally giant mitochondrial shapes, distorted mitochondrial membrane structure, and disrupted cristae architecture. Meanwhile, DRP1 deficiency induced the retention of nascent lipid droplets in ER, leading to perturbed overall lipid dynamics in the KO mice. Collectively, dysregulation of the dynamics of mitochondria, ER, and lipid droplets contributes to whole-body metabolic disorders, as evidenced by perturbations in energy metabolites. Our findings demonstrate that DRP1 plays diverse and critical roles in regulating energy metabolism within adipose tissue during the progression of obesity.

Coalbed methane (CBM) development and underground coal gasification (UCG) are important sources for coal-based natural gas production in China, and coal and CBM resources are abundant in the inclined coalbed development area of the Xinjiang foreland thrust belt. To deeply analyze the feasibility of coordinated development of CBM and UCG in inclined coal seams, the existing key technologies of CBM and UCG and their significances for coordinated development of CBM- UCG was systematically analyzed, the advantages, the technical routes, major problems and future research directions of coordinated development of CBM and UCG in inclined coal seams were also elaborated, the major problems faced and the direction of future research were proposed, and the following understanding was obtained. ① The coordinated development of CBM-UCG under the “CBM development dredging effect”, “UCG thermal desorption effect”, and “UCG mining pressure releasing effect” can form a virtuous cycle of mutual promotion. ② The coordinated development technology routes was proposed, such as vertical wells + inclined well along coal seam with “first drainage and then gasification”, multiple inclined wells along the coal seam with “simultaneous drainage and gasification”, directional L-typed CBM wells + UCG wells along the coal seam direction with “simultaneous gasification and drainage”, UCG wells along inclined wells in the lower coal + directional L-typed CBM wells in the upper coal seam with “first drainage, then gasification, and then drainage again”, and the “well factory” arrangement of complex well type. ③ The coordinated development of CBM and UCG faces theoretical issues such as weak theoretical foundation research on geological constituency evaluation, unclear expansion range of UCG thermal action under the condition of fracture network, and the undetermined range of rock movement and pressure relief in the UCG process of inclined coal seams. It also faces the engineering issues such as coordinated development of CBM-UCG “well factory” drilling technology, coordinated development of CBM wells and UCG wells production system, coordinated development of CBM and UCG wells geodynamic measurement and control, and the sealing and high-temperature-resistant protection of CBM wells. ④ It is necessary to strengthen the study on the evaluation of geological site selection for the coordinated development of CBM and UCG in inclined coal seams, the theoretical research on the development dynamics, and the pioneering experimental study on engineering coordination technology, so as to ensure that the coordinated development is safe, orderly, controllable and efficient.

Abstract Background MicroRNA-200b-3p (miR-200b-3p) plays a pivotal role in inflammatory responses and is implicated in various inflammatory disorders. In this study, we aim to explore the role of miR-200b-3p in the inflammatory response in heart failure (HF). Methods Patients diagnosed with heart failure and age-matched healthy controls were studied. Peripheral blood samples from participants were collected for RNA-seq analysis to explore the expression profile of miR-200b-3p. The predictive value of miR-200b-3p and ZEB1 in the prognosis of heart failure was evaluated by analyzing the receiver operating characteristic (ROC) curve. Bioinformatics analysis and double luciferase reporter gene analysis were used to confirm the interaction between miR-200b-3p and ZEB1. Real-time quantitative polymerase chain reaction (QRT-PCR) was used to detect the expression levels of miR-200b-3p and ZEB1 in cardiopulmonary bypass. Additionally, the effects of miR-200b-3p on myocardial cell line (H9c2) injury were evaluated by enzyme-linked immunosorbent assay (ELISA). Results In the extracardiac circulation of HF patients, miR-200b-3p expression was significantly reduced, while ZEB1 levels were notably elevated. Analysis of the ROC curve revealed that miR-200b-3p and ZEB1 have predictive value in the prognosis of HF patients. The double luciferase reporter experiment demonstrated that miR-200b-3p binds to ZEB1 and inhibits its expression. Overexpression of miR-200b-3p demonstrated a remarkable ability to alleviate inflammation and inhibit the damage to myocardial cells in vivo. Conclusion MiR-200b-3p can target and inhibit ZEB1, reducing the inflammatory reaction of myocardial cells. The miR-200b-3p/ZEB1 network may be helpful in preventing and treating HF.

Abstract Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p

In order to compare and analyze the on-site desorption performance and numerical simulation desorption performance of low coalification reservoir coal core, the on-site gas content of coal core of a coalbed methane (CBM) well in Xinjiang was measured, and a numerical model of coal core in undersaturated reservoir with adsorbed gas is established, and based on this, the loss gas content calculation method was analyzed. The results show that the loss gas, desorption gas and residual gas contents calculated by the desorption numerical model of the unsaturated coal core (adsorbed gas saturation 54.77%, 77.51%, and 99.79%, respectively) were close to the corresponding results measured in the field (error

The Xinjiang Uygur Autonomous Region has presented the expected resource conditions and work foundations for a large-scale coalbed methane (CBM) exploration and development, which shows that its CBM resources below the depth of 2000 m are 7.5 trillion m3, 450 CBM wells have been constructed, and the annual gas production has approached to 80 million m3. Xinjiang has put forward the goal of the annual CBM production of 2.5 billion m3 in 2025. Therefore, the large-scale and efficient development of CBM in Xinjiang has become an urgent and significant demand. In this paper, the main research progresses of Xinjiang CBM made in five key technical fields have been systematically summarized, including the CBM enrichment model and area optimization technology, the prediction and detection technology for sweet spot distribution, the technological strategy of the accelerated rolling development and rapid increase of reserves and productions, the geological adaptation technology system, and the cooperative exploration and development of CBM with coal, oil and gas. Then, the potential breakthrough directions have been analyzed and proposed. Research has shown that the coal reservoirs in Xinjiang show the unique geological characteristics of CBM, including widely developed multi-thick coal seams, low rank coal development, the frequent occurrence of steep coal seams, the significant deformation and structural control of coal bodies, complex hydrologic and outcrop conditions, and the gas-bearing and physical properties with three “low” (low gas content, methane concentration, and gas saturation) and five “high” (high gas intensity, porosity, stress change, reservoir pressure change, and permeability change). The Xinjiang CBM has multiple genetic types and enrichment models, including biogenic mechanism, thermogenic mechanism, and biogenic-thermogenic composite genetic mechanism, etc., and their corresponding enrichment models. Biogenic gas reservoirs or biogenic gas contribute widely. The distribution and occurrence patterns of CBM in Xinjiang show some significant differences between foreland basin and intermountain basin. Therefore, the first breakthrough direction is to innovate and form the scientific evaluation based on the principle of “two separation” (low-rank and middle- and high-rank; shallow and deep coal) and “two combination” (geological and engineering evaluation; multivariate data) and the precise target optimization technology based on “machine learning + three-dimensional geological modeling”. The sweet spot of deep CBM/CMG (coal measure gas) in Xinjiang is mainly the uplift of the depression in the basin, the depression of the uplift in the basin, and the slope around the basin margin. The potential well location is the structurally high position, and the potential reservoir is the fissure-developed primary structure coal seam or pore and fissure-developed coal bearing sand conglomerate reservoir. Then, the second breakthrough direction is the sweet spot prediction and exploration technology for deep CBM/CMG based on “new method of geophysics, rock physics and rock mechanics stratigraphy” and “new concept of geological and engineering sweet spot”. The basic principles of the accelerated rolling development are low-risk, short-cycle, high-efficiency, and multi-batch project deployment. The technical strategies of the rapid increase of CBM reserves and productions in the middle and shallow coal seams include the new well layout and construction in the new optimized block and the old well reconstruction for the increase of CBM production in the mature block. While this strategy for the deep coal seam is to give priority to deployment and development in the sweet spot in the deep but gentle slope in the large basin and the uplift in the basin. Then, the third breakthrough direction is the engineering deployment methods and technical strategies for the scientific accelerated rolling development, and efficient and rapid increase of the gas reserves and productions. The important progresses have been made in the engineering technologies of Xinjiang CBM, such as the differential optimization and deployment of the well type and pattern, the drilling and cementing with a low reservoir damage, the high reliability logging and well testing, the efficient staged fracturing with the multi-well types, and the drainage control with the low casing pressure and controlled pressure. The fourth breakthrough direction is to develop and construct a geological adaptability technology system for a large-scale and efficient exploration and development of CBM in Xinjiang. For the middle and shallow CBM and coal cooperative exploration and development, the gas extraction followed by coal mining, the co-extraction of CBM and coal, and the co-extraction of CBM and in-situ oil-rich coal should be conducted. For the deep CBM, oil, and gas cooperative exploration and development, the development of coal measure superimposed gas reservoir, the co-exploration and co-extraction of CBM and CMG, and the exploration and development of the whole petroleum system in coal-bearing sequence should be conducted. These cooperative exploration and development of deep CBM, oil, and gas is the fifth breakthrough direction, whose developments have been considered and explored. The results of this study are expected to provide the technical support and engineering decision reference for a large-scale and efficient exploration and development of CBM in Xinjiang.

The lithology and pore structure of conglomerate reservoir in the Mahu sag, China, are complex, which makes it difficult to identify reservoir fluids. In this study, the body relaxation characteristics of crude oil at different temperatures were obtained from block crude oil samples, and two simulated oil samples with different body relaxation characteristics were used to conduct experiments. The saturated water, bound water, and saturated oil states of some conglomerate samples were quickly established by vacuum compression saturation, high-speed centrifugation, and vacuum saturation simulation of oil, and the fluid and different simulated oil-water saturation states were analyzed by nuclear magnetic resonance (NMR) experiments. The experimental results showed that the distribution range of the water-saturated core NMR T2 spectrum is mainly affected by surface relaxation. The NMR spectra of saturated oil with different viscosity values are different from those of saturated water because of the relaxation property of the oil phase. The samples of this experiment indicated that the difference is more obvious when the oil is thinner. The distribution pattern of the oil-bearing NMR results was affected by the relaxation of the oil phase, surface relaxation, pore structure, and wettability. With consideration of the relaxation characteristics of the oil samples, the NMR T2 spectra of two oil-saturated conglomerates were analyzed by multi-component Gaussian fitting, and the relaxation signals of the oil phase were evaluated quantitatively.

ObjectiveAuditory hallucinations are the most frequently occurring psychotic symptom in schizophrenia. Continuous theta burst stimulation (cTBS) has been used as an adjuvant treatment for auditory hallucinations. This meta-analysis focused on randomized controlled clinical trials (RCTs) to assess the efficacy of adjuvant cTBS on auditory hallucinations in schizophrenia.MethodsWe performed a comprehensive search of four international databases from their inception to January 14, 2024, to identify relevant RCTs that assessed the effects of adjuvant cTBS on auditory hallucinations. The key words included “auditory hallucinations”, “continuous theta burst stimulation” and “transcranial magnetic stimulation”. Inclusion criteria included patients with auditory hallucinations in schizophrenia or schizoaffective disorder. The Revised Cochrane risk-of-bias tool for randomized trials (RoB1) were used to evaluate the risk of bias and the Review Manager Software Version 5.4 was employed to pool the data.ResultsA total of 4 RCTs involving 151 patients with auditory hallucinations were included in the analysis. The Cochrane risk of bias of these studies presented “low risk” in all items. Preliminary analysis showed no significant advantage of adjuvant cTBS over sham stimulation in reducing hallucinations [4 RCTs, n = 151; SMD: -0.45 (95%CI: -1.01, 0.12), P = 0.13; I2 = 61%]. Subgroup analysis revealed that patients treated with adjuvant cTBS for more than 10 stimulation sessions and total number of pulses more than 6000 [3 RCTs, n = 87; SMD: -4.43 (95%CI: -8.22, -0.63), P = 0.02; I2 = 47%] had a statistically significant improvement in hallucination symptoms. Moreover, the rates of adverse events and discontinuation did not show any significant difference between the cTBS and sham group.ConclusionsAlthough preliminary analysis did not revealed a significant advantage of adjuvant cTBS over sham stimulation, subgroup analysis showed that specific parameters of cTBS appear to be effective in the treatment of auditory hallucinations in schizophrenia. Further large-scale studies are needed to determine the standard protocol of cTBS for treating auditory hallucinations.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024534045.

Accumulating evidence has proved the close association between alterations in gut microbiota and resistance to chemotherapeutic drugs. However, the potential roles of gut microbiota in regulating oxaliplatin sensitivity in gastric cancer (GC) have not been investigated before. We first found that antibiotic treatment diminished the therapeutic efficacy of oxaliplatin in a GC mouse model. Importantly, this effect could be transmitted to germ-free mice via fecal microbiota transplantation, indicating a potential role of gut microbiota modulation in oxaliplatin efficacy. Further, metagenomics data showed that Akkermansia muciniphila (A. muciniphila) ranked first among the bacterial species with decreased relative abundances after antibiotic treatment. Metabolically active A. muciniphila promotes oxaliplatin efficacy. As shown by metabolomics analysis, the metabolic pattern of gut microbiota was disrupted with significantly downregulated levels of pentadecanoic acid (PEA), and the use of PEA significantly promoted oxaliplatin efficacy. Mechanistically, FUBP1 positively regulated aerobic glycolysis of GC cells to hinder the therapeutic efficacy of oxaliplatin. A. muciniphila-derived PEA functioned as an inhibitory factor of glycolysis by directly antagonizing the activity of FUBP1, which potentiated GC responses to oxaliplatin. Our research suggested a key role for intestinal A. muciniphila and its metabolite PEA in promoting oxaliplatin efficacy, thus providing a new perspective for probiotic and prebiotic intervention in GC patients during chemotherapy.

IntroductionThe combination of neoadjuvant immunotherapy and chemotherapy (NICT) has become a common treatment regimen for locally advanced gastric cancer (LAGC). However, the safety and efficacy of radical gastrectomy following NICT (NICT-G) remain controversial. This study aimed to analyze the risk factors influencing postoperative complications (POCs) after NICT-G. Additionally, it aimed to construct a nomogram to provide a clinical reference for predicting POCs.MethodsThis study included 177 patients who received NICT-G at the Chinese PLA General Hospital First Medical Center from January 2020 to January 2024. Univariable and multivariable logistic regression models were used to evaluate the risk factors influencing POCs, and a nomogram model was constructed. To evaluate the discrimination and accuracy of the nomogram model, the area under the receiver operating characteristic curve (AUC) and the calibration curve were measured.ResultsIn 177 patients who received NICT-G, the pathological complete response and major pathological response rates were 15.8% and 45.2%, respectively, whereas the rates of the overall and severe treatment-related adverse events were 71.8% and 15.8%, respectively. In addition, 43 (24.3%) patients developed overall POCs (Clavien–Dindo classification ≥ II). Univariable and multivariable logistic analyses showed that age ≥70 years, greater estimated blood loss, platelet/lymphocyte ratio (PLR) ≤196, neutrophil/lymphocyte ratio (NLR) >1.33, non-R0 resection, and body mass index (BMI) < 18.5 kg/m2 were independent risk factors for overall POCs (p < 0.05). The nomogram model developed using the abovementioned variables showed that the AUC (95% confidence interval [CI]) was 0.808 (95% CI): 0.731–0.885 in predicting the POC risk. The calibration curves showed that the prediction curve of the nomogram was a good fit for the actual POCs (Hosmer–Lemeshow test: χ2 = 5.76, P = 0.451).ConclusionThe independent risk factors for overall POCs in the NICT-G were age ≥ 70 years, greater estimated blood loss, PLR ≤ 196, NLR > 1.33, non-R0 resection, and BMI < 18.5 kg/m2. The nomogram model developed based on the abovementioned indicators showed better accuracy in predicting the POC risk.

Inflammasomes are sensors that detect cytosolic microbial molecules or cellular damage, and in response they initiate a form of lytic regulated cell death called pyroptosis. Inflammasomes signal via homotypic protein-protein interactions where CARD or PYD domains are crucial for recruiting downstream partners. Here, we screened these domains from NLR family proteins, and found that the PYD domain of NLRP6 and NLRP12 could activate caspase-1 to induce cleavage of IL-1β and GSDMD. Inflammasome reconstitution verified that full length NLRP6 and NLRP12 formed inflammasomes in vitro, and NLRP6 was more prone to auto-activation. NLRP6 was highly expressed in intestinal epithelial cells (IEC), but not in immune cells. Molecular phylogeny analysis found that NLRP12 was closely related to NLRP3, but the activation mechanisms are different. NLRP3 was highly expressed in monocytes and macrophages, and was modestly but appreciably expressed in neutrophils. In contrast, NLRP12 was specifically expressed in neutrophils and eosinophils, but was not detectable in macrophages. NLRP12 mutations cause a periodic fever syndrome called NLRP12 autoinflammatory disease. We found that several of these patient mutations caused spontaneous activation of caspase-1 in vitro, which likely causes their autoinflammatory disease. Different cell types have unique cellular physiology and structures which could be perturbed by a pathogen, necessitating expression of distinct inflammasome sensors to monitor for signs of infection.

The treatment of primary Sjögren’s syndrome (pSS) coexisting with neuromyelitis optica spectrum disorder (NMOSD) using protein-A immunoadsorption combined with immunosuppressive therapy has rarely been reported. Herein, we present the case of a 35-year-old female diagnosed with pSS concomitant with NMOSD (pSS-NMOSD) who demonstrated a positive response to protein-A immunoadsorption after failing to respond to therapy comprising high-dose intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIG). Within one week of receiving three sessions of immunoadsorption combined with immunosuppressive treatment, the patient’s clinical symptoms (blurred vision, paraparesis, and dysfunctional proprioception) significantly improved. Additionally, a rapid decrease in the circulating levels of Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG), immunoglobulin (Ig) A, IgG, IgM, erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were observed. Magnetic resonance imaging (MRI) further revealed a significant reduction in the lesions associated with longitudinal extensive transverse myelitis. During the follow-up period, prednisolone was gradually tapered to a maintenance dose of 5-10 mg/day, whereas mycophenolate mofetil (MMF) was maintained at 1.0-1.5 g/day. The patient’s condition has remained stable for four years, with no signs of recurrence or progression observed on imaging examination. Therefore, this case suggests that protein A immunoadsorption may represent a potentially effective therapeutic option for patients with pSS-NMOSD who are refractory to conventional treatments.

ObjectiveIn this study, we aimed to determine the relationships among perceived social support, mindful self-care, and resilience in a sample of nurses in three provinces of China.MethodsA cross-sectional study was conducted in seven hospitals in Guangdong, Guizhou, and Henan provinces between August and October, 2023; the provinces are located in south, southwest, and central China. A total of 389 nurses were surveyed using a self-designed sociodemographic characteristics questionnaire and the Chinese versions of Multidimensional Scale of the Perceived Social Support, Brief-Mindful Self-Care Scale and the 10-item Connor-Davidson Resilience Scale (CD-RISC-10).ResultsOf the 389 nurses, the majority were women (n = 365; 93.8%), aged 26–35 years (n = 244; 62.7%) and had bachelor’s degrees (n = 337; 86.6%), had worked for 10–20 years (n = 136; 35%), with junior professional titles (n = 331; 85.1%), and had a monthly income in the range 3,001–6,000 yuan in CNY (n = 239; 61.4%). Nurses’ resilience was measured using the CD-RISC-10, which ranges from 10 to 40 points. And average score of nurses’ resilience was (23.94 ± 6.95). Multiple linear regression showed that scores for resilience were higher among nurses who had higher educational attainment (95% confidence interval: 0.568–3.024, p

The evolutionary analysis showed that the GF14 family was conserved, however, there was limited evidence linking GF14s to plant height. In our investigations, we discovered a co-expression relationship between ZmGF14s and functionally characterized genes linked to plant height. In the co-expression network, we identified ZmGF14-3, a gene expression exhibiting a positive correlation with plant height in three maize varieties, we postulated that this gene could be intimately linked to plant height development. Subsequently, we cloned ZmGF14-3 from the maize B73 inbred line and overexpressed it in Arabidopsis, resulting in markedly dwarfed transgenic phenotypes. Measurements of endogenous phytohormones disclosed a significant reduction in concentrations of Gibberellic Acid 7 (GA7) and Indole-3-Acetic Acid (IAA) in the overexpressed Arabidopsis, furthermore, qPCR results highlighted a pronounced decrease in the expression levels of plant height-related genes when compared to the wild type, therefore, it is plausible to posit that ZmGF14-3 plays a pivotal role in regulating the growth and development of maize through interactions with various phytohormone-related genes. Thus, delving into the potential interactions between ZmGF14-3 and these genes holds the promise of yielding valuable insights into the molecular mechanisms underpinning plant height development in maize.

Background and purpose: Our previous research discovered that cinnamamide derivatives are a new type of potential cardioprotective agents myocardial ischemia-reperfusion (MIR) injury, among which Compound 10 exhibits wonderful beneficial action in vitro. However, the exact mechanism of Compound 10 still needs to be elucidated. Experimental approach: The protective effect of Compound 10 was determined by detecting the cell viability and LDH leakage rate in H9c2 cells subjected to H2O2. Alterations of electrocardiogram, echocardiography, cardiac infarct area, histopathology and serum myocardial zymogram were tested in MIR rats. Additionally, the potential mechanism of Compound 10 was explored through PCR. Network pharmacology and Western blotting was conducted to monitor levels of proteins related to autophagic flux and mTOR, autophagy regulatory substrate, induced by Compound 10 both in vitro and in vivo, as well as expressions of Sirtuins family members. Key results: Compound 10 significantly ameliorated myocardial injury, as demonstrated by increased cell viability, decreased LDH leakage in vitro, and declined serum myocardial zymogram, ST elevation, cardiac infarct area and improved cardiac function and microstructure of heart tissue in vivo. Importantly, Compound 10 markedly enhanced the obstruction of autophagic flux and inhibited excessive autophagy initiation against MIR by decreased ATG5, Rab7 and increased P-mTOR and LAMP2. Furthermore, Sirt1 knockdown hindered Compound 10’s regulation on mTOR, leading to interrupted cardiac autophagic flux. Conclusions and implications: Compound 10 exerted cardioprotective effects on MIR by reducing excessive autophagy and improving autophgic flux blockage. Our work would take a novel insight in seeking effective prevention and treatment strategies against MIR injury.

Objectives The efficacy of transjugular intrahepatic portosystemic shunt (TIPS) plus extrahepatic collateral embolisation (TIPS+E) in reducing rebleeding and hepatic encephalopathy (HE) post-TIPS was recently reported in a meta-analysis, but further validation is essential. This study aims to confirm the effectiveness of TIPS+E using real-world data.Methods The multicentre retrospective cohort included 2077 patients with cirrhosis who underwent TIPS±E (TIPS: 631, TIPS+E: 1446) between January 2010 and December 2022. Regression and propensity score matching (PSM) were used to adjust for baseline characteristic differences. After PSM, clinical outcomes, including rebleeding, HE, survival and further decompensation (FDC), were analysed. Baseline data from all patients contributed to the construction of prognostic models.Results After PSM, 1136 matched patients (TIPS+E: TIPS=568:568) were included. TIPS+E demonstrated a significant reduction in rebleeding (HR 0.77; 95% CI 0.59 to 0.99; p=0.04), HE (HR 0.82; 95% CI 0.68 to 0.99; p=0.04) and FDC (HR 0.85; 95% CI 0.73 to 0.99; p=0.04), comparing to TIPS. Significantly, TIPS+E also reduced rebleeding, HE and FDC in subgroup of using 8 mm diameter stents and embolising of gastric varices+spontaneous portosystemic shunts (GV+SPSS). However, there were no differences in overall or subgroup survival analysis. Additionally, the random forest models showed higher accuracy and AUROC comparing to other models. Controlling post-TIPS portal pressure gradient (pPPG) within 7 mm Hg

Objective: To analyze the clinical features and genetic etiology of a patient with developmental and epileptic encephalopathy. Methods: The clinical information and peripheral blood of the patient and their family members were collected before the whole exome sequencing analysis was performed and Sanger sequencing was employed to verify the potential variant. Results: The patient presented with epilepsy and cerebral palsy with his parents, brother, and sister being all healthy. Whole exome sequencing analysis revealed that the child carried the paternal c.823del (p. R275Gfs*31) heterozygous variant and the maternal c.2456del (p.V819Gfs*190) heterozygous variant of the CACNA1B gene. Pedigree verification found that the elder brother and amniotic fluid of fetus in womb carried the paternal c.823del heterozygous variant, and the elder sister carried the maternal c.2456del heterozygous variant, which conformed to the law of autosomal recessive inheritance. Neither of these two variants has been reported in the literature and has not been included in the Genomic Mutation Frequency Database (gnomAD); according to the American Academy of Medical Genetics and Genomics Variation Grading Guidelines (ACMG), both variants are classified as pathogenic variants (PVS1+PM2-Supporting + PM3). Conclusion: This study reported the first case of a child with neurodevelopmental disorder and epilepsy caused by a new compound heterozygous variant of the CACNA1B gene in China, clarified its genetic etiology, enriched the mutation spectrum and disease spectrum of CACNA1B gene, and provided a basis for prenatal diagnosis of the family.

Memristive devices such as resistive switching memories and artificial synapses have emerged as promising technologies to overcome the technological challenges associated with the von Neumann bottleneck. Recently, lead halide perovskites have drawn substantial research attention as the candidate material for memristors and artificial synapses due to their unique optoelectronic properties, solution processability, and mechanical flexibility. However, the toxicity of lead‐containing species has raised major concerns for health and the environment, which makes it crucial to transition from lead‐based to lead‐free materials for practical applications. Herein, the recent progress of lead‐free metal halides including perovskites and perovskite analogs for resistive memory and artificial synapse is reviewed. Initially, the fundamentals of lead‐free materials and switching mechanisms are introduced. Next, the material design, fabrication technique, and device performance are summarized and critically evaluated for each metal halide species. Finally, the challenges of the lead‐free metal halides toward memristors and artificial synapses are outlined and discussed, and some potential research directions for future study are proposed.

Abstract How cells coordinate cell cycling with cell survival and death remains incompletely understood. Here, we show that cell cycle arrest has a potent suppressive effect on ferroptosis, a form of regulated cell death induced by overwhelming lipid peroxidation at cellular membranes. Mechanistically, cell cycle arrest induces diacylglycerol acyltransferase (DGAT)–dependent lipid droplet formation to sequester excessive polyunsaturated fatty acids (PUFAs) that accumulate in arrested cells in triacylglycerols (TAGs), resulting in ferroptosis suppression. Consequently, DGAT inhibition orchestrates a reshuffling of PUFAs from TAGs to phospholipids and re-sensitizes arrested cells to ferroptosis. We show that some slow-cycling antimitotic drug–resistant cancer cells, such as 5-fluorouracil–resistant cells, have accumulation of lipid droplets and that combined treatment with ferroptosis inducers and DGAT inhibitors effectively suppresses the growth of 5-fluorouracil–resistant tumors by inducing ferroptosis. Together, these results reveal a role for cell cycle arrest in driving ferroptosis resistance and suggest a ferroptosis-inducing therapeutic strategy to target slow-cycling therapy-resistant cancers.

Abstract In this paper, we propose the fine-grained geospatial knowledge graph (FineGeoKG), which can capture the neighboring relations between geospatial objects. We call such neighboring relations strong geospatial relations (SGRs) and define six types of SGRs. In FineGeoKG, the vertices (or entities) are geospatial objects. The edges (or relations) can have “sgr” labels together with properties, which are used to quantify SGRs in both topological and directional aspects. FineGeoKG is different from WorldKG, Yago2Geo, and other existing geospatial knowledge graphs, since its edges can capture the spatial coherence among geospatial objects. To construct FineGeoKG efficiently, the crucial problem is to find out SGRs. We improve the existing geospatial interlinking algorithm in order to find out SGRs faster. To answer SGR queries efficiently, we design an index to organize the SGR edges and improve the binary join method for subgraph matching. We conduct experiments on the real datasets and the experimental results show that the proposed algorithm is more efficient than the baseline algorithms. We also demonstrate the usefulness of FineGeoKG by presenting the results of complicated spatial queries which focus on structural and semantic information. Such queries can help researchers (for example, ecologists) find groups of objects following specific spatial patterns.

Abstract Background Regenerative techniques combined with core decompression (CD) are commonly used to treat osteonecrosis of the femoral head (ONFH). However, no consensus exists on regeneration therapy combined with CD that performs optimally. Therefore, we evaluated six regenerative therapies combined with CD treatment using a Bayesian network meta-analysis (NMA). Methods We searched PubMed, Embase, Cochrane Library, and Web of Science databases. Six common regeneration techniques were categorized into the following groups with CD as the control group: (1) autologous bone graft (ABG), (2) autologous bone graft combined with bone marrow aspirate concentrate (ABG + BMAC), (3) bone marrow aspirate concentrate (BMAC), (4) free vascular autologous bone graft (FVBG), (5) expanded mesenchymal stem cells (MSCs), and (6) platelet-rich plasma (PRP). The conversion rate to total hip arthroplasty (THA) and progression rate to femoral head necrosis were compared among the six treatments. Result A total of 17 literature were included in this study. In the NMA, two of the six treatment strategies demonstrated higher response in preventing the progression of ONFH than CD: MSCs (odds ratio [OR]: 0.098, 95% confidence interval [CI]: 0.0087–0.87) and BMAC (OR: 0.27, 95% CI: 0.073–0.73). Additionally, two of the six treatment strategies were effective techniques in preventing the conversion of ONFH to THA: MSCs (OR: 0.062, 95% CI: 0.0038–0.40) and BMAC (OR: 0.32, 95% CI: 0.1–0.074). No significant difference was found among FVBG, PRP, ABG + BMAC, ABG, and CD in preventing ONFH progression and conversion to THA (P > 0.05). Conclusions Our NMA found that MSCs and BMAC were effective in preventing ONFH progression and conversion to THA among the six regenerative therapies. According to the surface under the cumulative ranking value, MSCs ranked first, followed by BMAC. Additionally, based on our NMA results, MSCs and BMAC following CD may be necessary to prevent ONFH progression and conversion to THA. Therefore, these findings provide evidence for the use of regenerative therapy for ONFH.

Abstract Objective Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal activation of the type I interferon (IFN) pathway, which results in tissue inflammation and organ damage. We explored the role of the RhoA GTPase in the type I IFN activation pathway to provide a potential basis for targeting GTPase signaling for the treatment of SLE. Methods Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls, and the mRNA expression levels of RhoA and IFN-stimulated genes were measured by SYBR Green quantitative reverse transcriptase-polymerase chain reaction. IFN-a-stimulated response element (ISRE)-luciferase reporter gene assays and Western blotting were conducted to assess the biologic function of RhoA. An enzyme-linked immunoassay (ELISA) measured C-X-C motif chemokine ligand 10 (CXCL10) protein expression. Results Our studies demonstrate that the expression of RhoA in the PBMCs of SLE subjects was significantly higher than in healthy controls and positively correlated with type I IFN scores and type I IFN-stimulated gene (ISGs) expression levels. SiRNA-mediated knockdown of RhoA and the RhoA/ROCK inhibitor Y27632 reduced the activity of the type I IFN-induced ISRE, the signal transducer and activator of transcription 1 (STAT-1) phosphorylation, and the expression of CXCL10 and 2′-5′-oligoadenylate synthetase 1 (OAS1). Finally, we verified that Y27632 could significantly down-regulate the OAS1 and CXCL10 expression levels in the PBMCs of SLE patients. Conclusion Our study shows that RhoA positively regulates the activation of the type I IFN response pathway. Reducing the expression level of RhoA inhibits the abnormal activation of the type I IFN system, and the RhoA/ROCK inhibitor Y27632 decreases aberrant type I IFN signaling in SLE PBMCs, suggesting the possibility of targeting the RhoA GTPase for the treatment of SLE.

Abstract Background The ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) (NHHR) serves as a reliable lipid indicator associated with atherogenic characteristics. Studies have indicated a potential connection between suicidality and lipid metabolism. This research aims to investigate any possible association between the NHHR and the emergence of suicidal ideation within the confines of the study. Methods This study examined the association between NHHR levels and suicidal ideation using data from the National Health and Nutrition Examination Survey (NHANES), conducted in the United States spanning 2005 and 2016. Calculation of the NHHR corresponds to the proportion of HDL-C to Non-HDL-C. The Patient Health Questionnaire-9’s ninth question was implemented for assessing suicidal ideation. Using subgroup analysis, smooth curve fitting, and multivariate logistic regression analysis, the research was conducted. Results Encompassing a cohort of 29,288 participants, the analysis identified that 3.82% of individuals reported suicidal ideation. After using multivariable logistic regression and thorough adjustments, elevated NHHR levels were significantly and positively associated with a heightened likelihood of suicidal ideation, according to the findings (odds ratio [OR] = 1.06; 95% confidence interval [CI]: 1.02–1.11; P = 0.0048). Despite extensive adjustment for various confounding factors, this relationship remained consistent. An inverted U-shaped curve was utilized to illustrate the link between NHHR and suicidal ideation among nonsmokers; the curve’s inflection point was situated at 7.80. Subgroup analysis and interaction tests (all P for interaction > 0.05) demonstrated that there was no significant influence of the following variables on this positive relationship: age, sex, race, body mass index, education level, married status, hypertension, diabetes, and smoking status. Conclusion Significantly higher NHHR levels were associated with an elevated likelihood of suicidal ideation. Based on these results, it is probable that NHHR may serve as a predictive indicator of suicidal ideation, emphasizing its potential utility in risk assessment and preventive strategies.

Synthetic aperture LiDAR can generate point cloud data, which is widely used in 3-D scene reconstruction. However, existing point cloud object recognition methods are vulnerable to adversarial attacks, and such attacks are difficult to transfer to the physical world. Even if adversarial perturbations are added to physical objects, they are easily detectable by other sensors. Our proposed method includes two modules, R-D and D-R, which generate more concealed adversarial point cloud samples by modifying digital and physical features. The R-D module maps real-world entities to point cloud data in the digital world and generates adversarial samples by modifying signal amplitude values. The D-R module constructs adversarial objects by modifying the surface diffuse reflectance of the target object based on ray tracing and correspondences between digital and physical features. Our method is evaluated through experiments on attack effectiveness, robustness after subsampling and transferability, demonstrating its effectiveness, and achieving new state-of-the-art performance.

Abstract Background Despite several surgical options, there remains no consensus regarding the optimal approach for osteonecrosis of the femoral head (ONFH), a prevalent and refractory disease. To determine the most suitable treatment modality, we compared randomized controlled trials (RCTs) that evaluated multiple surgical treatments for ONFH using a Bayesian network meta-analysis (NMA). Methods The outcomes of 11 different surgical treatments were assessed using NMA comparisons of the rate of progression of femoral head necrosis, the rate of conversion to total hip arthroplasty, and improvement of the Harris hip score (HHS). A random effects model was used to analyze the odds ratio (OR) or mean difference, and risk of bias was assessed using the Cochrane risk of bias assessment tool for randomized trials. The confidence of the results was assessed using the confidence in network meta-analysis tool. Results A total of 18 RCTs were included in the meta-analysis. Compared with core decompression (CD), the forest plot showed that autologous bone grafting (ABG), free fibula grafting (FFG), vascularized bone grafting (VBG), autologous bone grafting combined with bone marrow aspirate concentrate (ABG + BMAC), and biomaterial grafting combined with vascularized bone grafting (BMG + VBG) delayed ONFH progression. Among them, ABG + BMAC showed the most promising results (OR 0.019; 95% confidence interval [CI] 0.0012–0.25). However, upon comparing CD with different surgical modalities, no significant differences were found in preventing total hip arthroplasty. Furthermore, we cannot draw conclusions regarding the HHS due to attribution and high heterogeneity across the studies. Conclusion Overall, ABG, VBG, FFG, ABG + BMAC, and BMG + VBG showed significant results in preventing ONFH progression compared with that shown by CD. Based on the surface under the cumulative ranking, ABG + BMAC was the most effective. Moreover, all treatments involving bone grafting were found to be effective, possibly indicating the necessity of its use in the treatment of ONFH.

This review summarizes the sclerotic zone's pathophysiology, characterization, formation process, and impact on femoral head necrosis. The sclerotic zone is a reaction interface formed during the repair of femoral head necrosis. Compared with normal bone tissue, the mechanical properties of the sclerotic zone are significantly enhanced. Many factors influence the formation of the sclerotic zone, including mechanics, bone metabolism, angiogenesis, and other biological processes. The sclerotic zone plays an essential role in preventing the collapse of the femoral head and can predict the risk of the collapse of the femoral head. Regulating the formation of the sclerotic zone of the femoral head has become a direction worthy of study in treating femoral head necrosis.

Background: Studies dedicated to exploring the incidence of atrial fibrillation (AF) in patients with concurrent depression and heart failure with preserved ejection fraction (HFpEF) are scarce. The impact of antidepressant therapy on AF risk within this population remains unclear. Our current study aimed to investigate the link between depression and AF risk in HFpEF patients and to assess the influence of antidepressant medication on the development of AF. Methods: We utilized Kaplan-Meier estimates to determine the event-free status for AF and applied the Log-rank test for comparative analysis between groups. The associations were quantified using univariate and multivariate Cox proportional hazards regression models, with results expressed as hazard ratios (HR) and 95% confidence intervals (CI). Results: Among the 784 patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, 29.1% (228) were identified with major depression. After adjusting for significant confounders, compared with mild depression, major depression at baseline was not linked to the incidence of AF (adjusted HR = 0.82, 95% CI: 0.46–1.49). Additionally, compared with controls, antidepressant use at baseline did not significantly influence the risk of incident AF in patients with HFpEF and major depression (adjusted HR = 0.41, 95% CI: 0.08–2.10). Conclusions: The presence of major depression at baseline did not elevate the risk of incident AF among individuals with HFpEF. Additionally, the use of antidepressants showed no correlation with an increased rate of AF among HFpEF patients with comorbid major depression. Clinical Trial Registration: URL: https://clinicaltrials.gov/study/NCT00094302. Unique identifier: NCT00094302.

Achieving complete magnetization switching is a significant challenge in the electrical control of magnetic devices. In this paper, we propose a structure called bicomponent multiferroic nanomagnet (BMN) to study strain-mediated magnetization switching behavior. The BMN consists of a complete piezoelectric layer and a magnetostrictive layer made of bicomponent magnetic materials. Our team successfully developed a dynamic model for the magnetization of BMNs. By micromagnetic simulation, the results show that the strict requirements for a precise applied voltage period can be overcome in such a BMN, and a 180° magnetization switching can be achieved with only a square-wave voltage signal and a pulse width (tth) larger than 0.5 ns, given that the amplitude of the voltage is 60 mV. In addition, we also investigated the tolerance window of material composition and geometry, and proved that BMNs have sufficient error margins and the switching rate of BMNs can reach 1.67 GHz within the error margins at room temperature. Our proposed BMN device has a simple structure and low energy consumption as it does not require precise piezoelectric layer design or stringent voltage clocking requirements. The energy consumption per switching is only 7.3 aJ. These findings provide significant guidance for the design of nanomagnetic logic and memory devices and lay a strong foundation for the application of strain-mediated magnetization switching technology.

Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of and activate GSDMB, C, D, and E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis of the gasdermin family. A gene duplication of GSDMA in the common ancestor of caecilian amphibians, reptiles, and birds gave rise to GSDMA–D in mammals. Uniquely in our tree, amphibian, reptile, and bird GSDMA group in a separate clade than mammal GSDMA. Remarkably, GSDMA in numerous bird species contain caspase-1 cleavage sites like YVAD or FASD in the linker. We show that GSDMA from birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with the GSDMD C-terminal domain to confer the specificity of this interaction, whereas we show that bird caspase-1 uses a stereotypical tetrapeptide sequence to confer specificity for bird GSDMA. Our results reveal an evolutionarily stable association between caspase-1 and the gasdermin family, albeit a shifting one. Caspase-1 repeatedly changes its target gasdermin over evolutionary time at speciation junctures, initially cleaving GSDME in fish, then GSDMA in amphibians/reptiles/birds, and finally GSDMD in mammals.

ObjectiveAccumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD.Method50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations.ResultsPatients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups (P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes (B = -0.610, t = -5.299, P < 0.001).ConclusionLower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.

Abstract Background The clinical profiles of recurrent retroperitoneal liposarcoma (RLS) need to be explored. The recurrence patterns of RLS are controversial and ambiguous. Methods A total of 138 patients with recurrent RLS were finally recruited in the study. The analysis of overall survival (OS) and recurrence-free survival (RFS) was performed by Kaplan‒Meier analysis. To identify independent prognostic factors, all significant variables on univariate Cox regression analysis (P ≤ 0.05) were subjected to multivariate Cox regression analysis. The corresponding nomogram model was further built to predict the survival status of patients. Results Among patients, the 1-, 3-, and 5-year OS rates were 70.7%, 35.9% and 30.9%, respectively. The 1-, 3- and 5-year RFS rates of the 55 patients who underwent R0 resection were 76.1%, 50.8% and 34.4%, respectively. The multivariate analysis revealed that resection method, tumor size, status of pathological differentiation, pathological subtypes and recurrence pattern were independent risk factors for OS or RFS. Patients with distant recurrence (DR) pattern usually had multifocal tumors (90.5% vs. 74.7%, P

Microalloying is of great importance for the property modulation of lightweight high-strength aluminum alloys. Little is known, however, about the properties and micromechanisms of Al–Mg–Si alloys microalloyed with Sn and Sc. In this work, the property changes of Al–0.5Mg–0.4Si (wt%) alloys induced by 0.1Sn and 0.1Sn–0.1Sc (wt%) additions and underlying alloying mechanisms are revealed by atomic-scale transmission electron microscopy and first-principles calculations. The results show that the Sn–Sc coaddition results in a decreased diameter and an increased number density of the Sc-containing constituent particles of Mg2Si and Mg2(Si,Sn), as compared to the sole Sn addition. The featured Si-site columns in β'', B′ and β′ structures can be occupied by Sn and Sc. Substantial peak-aging β'' needles with confined cross-sectional coarsening are observed for the Sn–Sc containing alloy compared to the Sn containing alloy. The modified constituent particles and precipitates improve the plasticity and strength of peak-aging Al–Mg–Si–Sn–Sc alloy. The elevated peak-aging corrosion resistance and over-aging thermal stability of Al–Mg–Si–Sn–Sc alloy are associated with the sparse Sc-containing Mg2(Si,Sn) grain boundary precipitates and low strain filed of Al matrix around the β′ containing Sn/Sc, respectively. The obtained results are hoped to guide the design of high-performance Al alloys.

Abstract Current source is an indispensable component of magnetorheological (MR) systems. Though MR fluid has a phase change as fast as in 1 ms, the response of MR damper (MRD) to generate the damping force may be two orders of magnitude longer. Therefore, the rapid response of current source is a key to realize the real-time semi-active control of MR devices. This study proposes a programmable high-speed, low-cost current source exclusively for MR devices based on the synergy between supercapacitor and Buck converter (i.e., SSBC current source). SSBC current source features a strategy consisting of a lifting phase of supercapacitor and a following maintaining phase of Buck converter. Specifically, the high power density of supercapacitor contributes to rapidly lifting/raising the initial current, and then, like a “relay race”, the expected output is maintained through a Buck converter. Theoretical modeling and experiments are performed systematically. The response times (@ 95% of expected outputs) measured are 0.44, 0.84 and 1.88 ms for the outputs of 3, 6 and 9 A, respectively; these values are highlighted as the fastest level in this field. Besides, the response can be up to 24.6 and 43.7 times faster than the cases using supercapacitor and Buck converter to directly drive the MRD, respectively. SSBC current source is employed to generate a sequence of currents/magnetic inductions, only four variables of which need to be controlled programmatically: the order of lifting and maintaining phases, switching time of lifting phase, PWM duty cycle of Buck converter and duration of maintaining phase. The response time stability is verified by 100 cycles of on/off tests, showing a fluctuation of only 1.1%, which indicates a very reliable high-speed response. This study provides an exclusive power supply with a novel strategy for MR devices, which is believed to be an important promotion for MR technologies.

Abstract Traditional total mesorectal excision (TME) for rectal cancer requires partial resection of Denonvilliers’ fascia (DVF), which leads to injury of pelvic autonomic nerve and postoperative urogenital dysfunction. It is still unclear whether entire preservation of DVF has better urogenital function and comparable oncological outcomes. We conducted a randomized clinical trial to investigate the superiority of DVF preservation over resection (NCT02435758). A total of 262 eligible male patients were randomized to Laparoscopic TME with DVF preservation (L-DVF-P group) or resection procedures (L-DVF-R group), 242 of which completed the study, including 122 cases of L-DVF-P and 120 cases of L-DVF-R. The initial analysis of the primary outcomes of urogenital function has previously been reported. Here, the updated analysis and secondary outcomes including 3-year survival (OS), 3-year disease-free survival (DFS), and recurrence rate between the two groups are reported for the modified intention-to-treat analysis, revealing no significant difference. In conclusion, L-DVF-P reveals better postoperative urogenital function and comparable oncological outcomes for male rectal cancer patients.

Abstract PTP4A1 (Protein tyrosine phosphatase 4A1) is a protein tyrosine phosphatase that regulates a range of pro-oncogenic signaling pathways. Here, we report a novel role for PTP4A1 in oral squamous cell carcinoma (OSCC) growth and development. We show that PTP4A1 is frequently overexpressed in OSCC cells and tissues compared to adjacent non-tumor tissue. In OSCC, the overexpression of PTP4A1 increased cell growth and invasion in vitro, and enhanced tumor progression in vivo. At the molecular level, PTP4A1 was found to regulate mitochondrial metabolic reprogramming to enhance the invasive capacity of OSCC cells. Mechanistically, these effects were mediated through binding to pyruvate kinase isoenzyme M2 (PKM2) to promote its expression and aconitase 2 (ACO2) to enhance its degradation. Together, these data reveal PTP4A1 as a viable target for OSCC therapeutics.

Land cover products provide the key inputs for terrestrial change monitoring and modeling. Numerous land cover products have been generated in the past few decades, but their performance on the southeastern Tibetan Plateau remains unclear. This study analyzed 15 land cover products for consistency through compositional similarity and overlay analyses. Additionally, 1305 validation samples from four datasets were employed to construct confusion matrices to evaluate their accuracy. The results indicate the following: (1) Land cover products exhibit relatively high consistency in 62.92% of the region. (2) Land cover products are strongly influenced by terrain fluctuations, showing lower consistency at elevation below 200 m and instability in land cover classification with increasing elevation, particularly between 2800–4400 m and 4800–5400 m. (3) The accuracy for forest, water, and snow/ice is relatively high. However, there is a relatively lower accuracy for wetland and shrubland, necessitating more field samples for reference to improve classification. (4) The average values of the four validation datasets show that the overall accuracy of the 15 products ranges from 50.97% to 73.50%. For broad-scale studies with lower resolution requirements, the CGLS-LC100 product can be considered. For studies requiring a finer scale, a combination of multiple land cover products should be utilized. ESRI is recommended as a reference for built-up land, while FROM-GLC30 can be used for cropland, although misclassification issues should be noted. This study provides valuable insights for analyzing land cover types on plateaus to refine classification. It also offers guidance for selecting suitable land cover products for future research in this region.

Polyploids are essential in plant evolution and species formation, providing a rich genetic reservoir and increasing species diversity. Complex polyploids with higher ploidy levels often have a dosage effect on the phenotype, which can be highly detrimental to gametes, making them rare. In this study, offspring plants resulting from an autoallotetraploid (RRRC) derived from the interspecific hybridization between allotetraploid Raphanobrassica (RRCC, 2n = 36) and diploid radish (RR, 2n = 18) were obtained. Fluorescence in situ hybridization (FISH) using C-genome-specific repeats as probes revealed two main genome configurations in these offspring plants: RRRCC (2n = 43, 44, 45) and RRRRCC (2n = 54, 55), showing more complex genome configurations and higher ploidy levels compared to the parental plants. These offspring plants exhibited extensive variation in phenotypic characteristics, including leaf type and flower type and color, as well as seed and pollen fertility. Analysis of chromosome behavior showed that homoeologous chromosome pairing events are widely observed at the diakinesis stage in the pollen mother cells (PMCs) of these allopolyploids, with a range of 58.73% to 78.33%. Moreover, the unreduced C subgenome at meiosis anaphase II in PMCs was observed, which provides compelling evidence for the formation of complex allopolyploid offspring. These complex allopolyploids serve as valuable genetic resources for further analysis and contribute to our understanding of the mechanisms underlying the formation of complex allopolyploids.

The contents of alkali and alkaline earth metals are higher in Zhundong coal, and there are serious problems of slagging and fouling during the combustion process. Therefore, it is of great significance to reveal the mechanism of slagging and fouling in the boiler of Zhundong coal. In this paper, first-principle calculations based on density functional theory are used to study the competition mechanism of alkaline metal oxides during the combustion process in Zhundong coal by establishing the Na2O(110)/CaO(100)-SiO2(100) double-layer interface model. The results show that the bond lengths of the surface of Na2O(110) and CaO(100) with SiO2(100) after adsorption were generally lengthened and the value of bond population became smaller, which formed a stable binding energy during the reaction. The electron loss of Na is 0.05 e, the electron loss of Ca is 0.03 e, and the electron loss of Na2O is greater than that of CaO. The charge transfer on the surface of Na2O with SiO2 is obviously higher than that of CaO and the orbital hybridization on the surface of CaO with SiO2 is weaker than that on the surfaces of Na2O with SiO2. Na2O is easier to react with SiO2 than CaO. The adsorption energies on the surface of Na2O and CaO with SiO2 are −5.56 eV and −0.72 eV, respectively. The adsorption energy of Na2O is higher than that of CaO, indicating that Na2O is more prone to adsorption reactions and formation of Na-containing minerals and other minerals, resulting in more serious slagging. In addition, the XRD analyses at different temperatures showed that Na-containing compounds appeared before Ca-containing ones, and the reaction activity of Na2O is stronger than that of CaO in the reaction process. The experimental results have good agreement with the calculation results. This provides strong evidence to reveal the slagging and fouling of Zhundong coal.

Quasi-bound state in the continuum (QBIC) can effectively enhance the interaction of terahertz (THz) wave with matter due to the tunable high-Q property, which has a strong potential application in the detection of low-concentration biological samples in the THz band. In this paper, a novel THz metamaterial sensor with a double-chain-separated resonant cavity structure based on QBIC is designed and fabricated. The process of excitation of the QBIC mode is verified and the structural parameters are optimized after considering the ohmic loss by simulations. The simulated refractive index sensitivity of the sensor is up to 544 GHz/RIU, much higher than those of recently reported THz metamaterial sensors. The sensitivity of the proposed metamaterial sensor is confirmed in an experiment by detecting low-concentration lithium citrate (LC) and bovine serum albumin (BSA) solutions. The limits of detection (LoDs) are obtained to be 0.0025 mg/mL (12 μM) for LC and 0.03125 mg/mL (0.47 μM) for BSA, respectively, both of which excel over most of the reported results in previous studies. These results indicate that the proposed THz metamaterial sensor has excellent sensing performances and can well be applied to the detection of low-concentration biological samples.

Abstract Background Mitochondrial metabolism has been proposed as an attractive target for breast cancer therapy. The discovery of new mechanisms underlying mitochondrial dysfunction will facilitate the development of new metabolic inhibitors to improve the clinical treatment of breast cancer patients. DYNLT1 (Dynein Light Chain Tctex-Type 1) is a key component of the motor complex that transports cellular cargo along microtubules in the cell, but whether and how DYNLT1 affects mitochondrial metabolism and breast cancer has not been reported. Methods The expression levels of DYNLT1 were analyzed in clinical samples and a panel of cell lines. The role of DYNLT1 in breast cancer development was investigated using in vivo mouse models and in vitro cell assays, including CCK-8, plate cloning and transwell assay. The role of DYNLT1 in regulating mitochondrial metabolism in breast cancer development is examined by measuring mitochondrial membrane potential and ATP levels. To investigate the underlying molecular mechanism, many methods, including but not limited to Co-IP and ubiquitination assay were used. Results First, we found that DYNLT1 was upregulated in breast tumors, especially in ER + and TNBC subtypes. DYNLT1 promotes the proliferation, migration, invasion and mitochondrial metabolism in breast cancer cells in vitro and breast tumor development in vivo. DYNLT1 colocalizes with voltage-dependent anion channel 1 (VDAC1) on mitochondria to regulate key metabolic and energy functions. Mechanistically, DYNLT1 stabilizes the voltage-dependent anion channel 1 (VDAC1) by hindering E3 ligase Parkin-mediated VDAC1 ubiquitination and degradation. Conclusion Our data demonstrate that DYNLT1 promotes mitochondrial metabolism to fuel breast cancer development by inhibiting Parkin-mediated ubiquitination degradation of VDAC1. This study suggests that mitochondrial metabolism can be exploited by targeting the DYNLT1-Parkin-VDAC1 axis to improve the ability of metabolic inhibitors to suppress cancers with limited treatment options, such as triple-negative breast cancer (TNBC).

The problems caused by microbiologically influenced corrosion (MIC) have become increasingly prominent, which has caused very serious economic losses. The research on the mechanism and protective measures of MIC is becoming more and more important. In this paper, combined with the unique environment of the circulating water cooling system, the influence of the unique environmental factors of the system on MIC is analyzed. Several kinds of bacteria known to cause microbial corrosion are summarized, including sulfate-reducing bacteria, nitrate-reducing bacteria, iron oxidizing bacteria, etc. The current MIC mechanisms and related research progress are reviewed. Several common MIC monitoring methods are summarized. The commonly used protection methods and the ideas of MIC technologies in the recent stage are listed. Finally, the future research direction of the MIC is prospected.

Objective. Large-scale studies on the characteristics and management of abdominal trauma in megacities in China are lacking. The aim of this study was to analyze and present the clinical patterns and treatment status of abdominal trauma in regional medical centers. Methods. Cases of abdominal trauma treated at seven medical centers in Beijing from 2010 to 2021 were collected. Clinical information about age, sex, injury cause, geographic distribution, abbreviated injury scale/injury severity score (AIS/ISS) value, injury-hospital time, preoperative time, surgically identified organ injuries, type of surgery, causes of reoperation and 90-day mortality was included in this study. Clinical characteristics, treatment methods, and short-term prognoses (90-days survival) were compared between blunt abdominal trauma (BAT) and penetrating abdominal trauma (PAT) cases. Non-normally distributed data are described as medians (IQR), and the Mann‒Whitney U test was performed; qualitative data were analyzed using the X2 test. Univariate and multivariate survival analyses were performed by the Cox proportional hazards model. Results. A total of 553 patients (86.98% male) with a median age of 36.50 (27.00–48.00) years were included. The BAT group had a significantly higher proportion of serious injury (P=0.001), lower initial hemoglobin level (P=0.001), and a lower laparoscopy surgery rate (P=0.044) compared to the PAT group. Additionally, more BAT cases were from the area around Beijing (P=0.008) and a longer injury-regional hospital time (10.47 (5.18–22.51) hours vs. 7.00 (3.80–15.38) hours, P=0.001). In the hollow viscus injury subgroup, the BAT group had a significantly longer injury-regional hospital time and preoperative time compared to the PAT group (injury-regional hospital time: 10.23 (6.00–21.59) hours vs. 7.07 (3.99–13.85) hours, P=0.002; preoperative time: 3.02 (2.01–5.58) hours vs. 2.81 (1.85–3.63) hours, P=0.047). The overall 90-day mortality was 11.9%, and longer injury-regional hospital time (HR: 1.01, 95% CI: 1.00–1.02, P=0.008), receipt of ICU treatment (HR: 4.69, 95% CI: 2.54–8.65, P=0.001), and severe ISSs (ISS > 25 vs. ISS

Abstract With the advance of artificial intelligence technology, large language models such as ChatGPT are drawing substantial interest in the healthcare field. A growing body of research has evaluated ChatGPT's performance in various medical departments, yet its potential in pediatrics remains under‐studied. In this study, we presented ChatGPT with a total of 4160 clinical consultation questions in both English and Chinese, covering 104 pediatric conditions, and repeated each question independently 10 times to assess the accuracy of its responses in pediatric disease treatment recommendations. ChatGPT achieved an overall accuracy of 82.2% (95% CI: 81.0%–83.4%), with superior performance in addressing common diseases (84.4%, 95% CI: 83.2%–85.7%), offering general treatment advice (83.5%, 95% CI: 81.9%–85.1%), and responding in English (93.0%, 95% CI: 91.9%–94.1%). However, it was prone to errors in disease definitions, medications, and surgical treatment. In conclusion, while ChatGPT shows promise in pediatric treatment recommendations with notable accuracy, cautious optimism is warranted regarding the potential application of large language models in enhancing patient care.