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Abstract In this paper, we selected representative electric buses (EBs) and diesel buses as research cases, aiming to explore a localized method suitable for various vehicle types that can be implemented in any region to measure the carbon emissions of urban buses throughout the lifecycle. We take into account the influence of seasonal factors over the lifecycle. We fully consider the production, assembly, and recycling stages of vehicle systems. We construct a model for estimating CO2 emissions during the fuel cycle. We analyze and compare the impacts of the optimized power grid structure on the lifecycle CO2 emissions of the two types of buses. The results indicate that seasonal factors affect both bus types' energy consumption, with EBs being more sensitive. Carbon emissions primarily stem from manufacturing the body, chassis, and notably, the lithium‐ion batteries, with the latter having a pronounced impact on EBs. A decrease in coal power generation from 71% to 21% in the grid reduced EB fuel‐cycle emissions by 70.7%. Although EBs are sensitive to seasonal factors, they still have the greatest potential for carbon reduction, depending on the proportion of clean energy in the power grid and the production processes of vehicle components.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulators may attenuate PCSK9-induced low-density lipoprotein receptor (LDLR) degradation in lysosome and promote the clearance of circulating low-density lipoprotein cholesterol (LDL-C). A novel series of tetrahydroprotoberberine derivatives (THPBs) were designed, synthesized, and evaluated as PCSK9 modulators for the treatment of hyperlipidemia. Among them, eight compounds exhibited excellent activities in downregulating hepatic PCSK9 expression better than berberine in HepG2 cells. In addition, five compounds 15, 18, 22, (R)-22, and (S)-22 showed better performance in the low-density lipoprotein, labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl-indocarbocyanine perchlorate (DiI-LDL) uptake assay, compared with berberine at the same concentration. Compound 22, selected for in vivo evaluation, demonstrated significant reductions of total cholesterol (TC) and LDL-C in hyperlipidemic hamsters with a good pharmacokinetic profile. Further exploring of the lipid-lowering mechanism showed that compound 22 promoted hepatic LDLR expression in a dose-dependent manner in HepG2 cells. Additional results of human ether-à-go-go related gene (hERG) inhibition assay indicated the potential druggability for compound 22, which is a promising lead compound for the development of PCSK9 modulator for the treatment of hyperlipidemia. Key words: PCSK9, Tetrahydroprotoberberine derivatives, Low-density lipoprotein cholesterol, Lipid-lowering, PCSK9 expression, Low-density lipoprotein receptor, Total cholesterol, Hyperlipidemia hamster

Metabolomics has great potential to process accessible biofluids through high-throughput and quantitative analysis for radiation biomarker screening. This study focused on the potential radiation responsive metabolites in rat plasma and the dose-response relationships. In the discovery stage, 20 male Sprague–Dawley rats were exposed to 0, 1, 3 and 5 Gy of cobalt-60 gamma rays at a dose rate of 1 Gy/min. Plasma samples were collected at 72 h after exposure and analyzed using liquid chromatography mass spectrometry based on non-targeted metabolomics. In the verification stage, 50 additional rats were exposed to 0, 1, 2, 3, 5 and 8 Gy of gamma rays. The concentrations of candidate metabolites were then analyzed using targeted metabolomics methods. Fifteen candidate radiation responsive metabolites were identified as potential radiation metabolite biomarkers. Metabolic pathways, such as linoleic acid metabolism and glycerophospholipid metabolism pathways, were changed after irradiation. Six radiation responsive metabolites, including LysoPC(20:2), LysoPC(20:3), PC(18:0/22:5), L-palmitoylcarnitine, N-acetylornithine and butyrylcarnitine, had good dose-response relationships ( R 2 > 0.80). The area under the curve of the panel of the 6 radiation responsive metabolites was 0.923. The radiation exposure metabolomics biomarkers and dose-response curves may have potential for rapid dose assessment and triage in nuclear and radiation accidents.

In this study, the bond-slip behavior between textile reinforced concrete (TRC)-confined concrete and rebars both at ambient temperature and after ISO 834 standard fire was investigated experimentally through pull-out tests. The failure modes, ultimate load, average ultimate bonding stress and energy consumption were obtained and discussed. Effects of rebar diameters (12 mm, 14 mm and 16 mm), bonding lengths (2.5d, 5d and 7.5d) and high-temperature exposure durations (30 min and 60 min) on the bonding behavior between TRC-confined concrete and rebars were examined emphatically. It was observed that the damage modes of specimens changed from pull-out failure at ambient temperature into splitting failure for both TRC-confined specimens and companion unconfined specimens exposed to high temperatures. The results obtained demonstrated that both the ultimate load and the average ultimate bonding stress can be significantly improved by the utilization of TRC jackets after 30 min exposure, and the increment of the average ultimate bonding stress can reach up to 90% as compared to those unconfined specimens. However, the enhancement of TRC jackets became unobvious after 60 min. Finally, based on test results and Prigogine's dissipative structure theory, the energy analysis of bond-slip curves was evaluated to verify the enhancement of TRC jackets quantitatively. [ABSTRACT FROM AUTHOR]

Abstract Aberrant repair underlies the pathogenesis of pulmonary fibrosis while effective strategies to convert fibrosis to normal regeneration are scarce. Here, we found that thyroid hormone is decreased in multiple models of lung injury but is essential for lung regeneration. Moreover, thyroid hormone receptor α (TRα) promotes cell proliferation, while TRβ fuels cell maturation in lung regeneration. Using a specific TRβ agonist, sobetirome, we demonstrate that the anti-fibrotic effects of thyroid hormone mainly rely on TRβ in mice. Cellularly, TRβ activation enhances alveolar type-2 (AT2) cell differentiation into AT1 cell and constrains AT2 cell hyperplasia. Molecularly, TRβ activation directly regulates the expression of KLF2 and CEBPA, both of which further synergistically drive the differentiation program of AT1 cells and benefit regeneration and anti-fibrosis. Our findings elucidate the modulation function of the TRβ-KLF2/CEBPA axis on AT2 cell fate and provide a potential treatment strategy to facilitate lung regeneration and anti-fibrosis.

Abstract PANoptosis is engaged in the program of immune response and carcinogenicity. Nonetheless, the actual impacts of PANoptosis on clinical management and oncology immunity in hepatocellular carcinoma (HCC) are not fully grasped. RNA-seq-derived computations were conducted to sort out the molecular subtypes and elucidate the disparities based on PANoptosis molecules. Single-cell sequencing (scRNA-seq) tools including Cytotrace and Addmodulescore were extracted to characterize diversification potency and quantify the PANoptosis motion. Transcriptional factors were inferred by the pySCENIC package and Cellchat program scrutinized the intercellular exchange across cell compartments. The PANoptosis score system originated by incorporating 10 machine learning algorithms and 101 compositions to project clinical results and deteriorate tendencies. Circulatory PANoptosis-associated protein HSP90AA1 was determined by enzyme-linked immunosorbent assay (ELISA). HCC individuals could be categorized into low- and high-PANoptosis groups with diverse biogenic and pharmacotherapy heterogeneity. Individuals in the elevated PANoptosis subtype were characterized as “hot tumor” conveying the increased presence of immunogenicity while reiterating an explicit negative connection with tumor stemness. Compared to immune and stromal cells, cancerous cells showcased decreased PANoptosis and heightened PANoptosis malignant cell subgroups might be tied to a substantial level of genomic expression of SREBF2, JUND, GATAD1, ZBTB20, SMAD5 and implied a more aggressive potential. The PANoptosis index, derived from machine learning, has been established to provide succinct frameworks for predicting outcomes and clarified the noteworthy utility of conventional regimens, as the differentiated power of HCC occurred together with vascular invasion and hepatocellular adenoma (HCA). The experiment confirmed that the circulating HSP90AA1 was aberrantly augmented in HCC patients, thus demonstrating its potential as a discriminatory biomarker. We systematically deciphered the molecular and immune ecosystem traits of PANoptosis in bulk and scRNA-seq degrees, which may deliver advantageous insights for customized treatment, awareness of the pathological process and prognosis scrutiny for HCC patients.

Abstract We discover an intrinsic dipole Hall effect in a variety of magnetic insulating states at integer fillings of twisted MoTe2 moiré superlattice, including topologically trivial and nontrivial ferro-, antiferro-, and ferri-magnetic configurations. The dipole Hall current, in linear response to in-plane electric field, generates an in-plane orbital magnetization M ∥ along the field, through which an AC field can drive magnetization oscillation up to THz range. Upon the continuous topological phase transitions from trivial to quantum anomalous Hall states in both ferromagnetic and antiferromagnetic configurations, the dipole Hall current and M ∥ have an abrupt sign change, enabling contact-free detection of the transitions through the magnetic stray field. In configurations where the linear response is forbidden by symmetry, the dipole Hall current and M ∥ appear as a crossed nonlinear response to both in-plane and out-of-plane electric fields. These magnetoelectric phenomena showcase fascinating functionalities of insulators from the interplay between magnetism, topology, and electrical polarization.

Abstract Ovarian cancer, the second most leading cause of gynecologic cancer mortality worldwide, is challenged by chemotherapy resistance, presenting a significant hurdle. Pyroptosis, an inflammation-linked programmed cell death mediated by gasdermins, has been shown to impact chemoresistance when dysregulated. However, the mechanisms connecting pyroptosis to chemotherapy resistance in ovarian cancer are unclear. We found that cytokine receptor-like factor 1 (CRLF1) is a novel component of mTORC2, enhancing AKT Ser473 phosphorylation through strengthening the interaction between AKT and stress-activated protein kinase interacting protein 1 (SIN1), which in turn inhibits the mitogen-activated protein kinase kinase kinase 5 (ASK1)-JNK-caspase-3-gasdermin E pyroptotic pathway and ultimately confers chemoresistance. High CRLF1-expressing tumors showed sensitivity to AKT inhibition but tolerance to cisplatin. Remarkably, overexpression of binding-defective CRLF1 variants impaired AKT-SIN1 interaction, promoting pyroptosis and chemosensitization. Thus, CRLF1 critically regulates chemoresistance in ovarian cancer by modulating AKT/SIN1-dependent pyroptosis. Binding-defective CRLF1 variants could be developed as tumor-specific polypeptide drugs to enhance chemotherapy for ovarian cancer.

Abstract Background Inadequate nerve regeneration and an inhibitory local microenvironment are major obstacles to the repair of spinal cord injury (SCI). The activation and differentiation fate regulation of endogenous neural stem cells (NSCs) represent one of the most promising repair approaches. Metformin has been extensively studied for its antioxidative, anti-inflammatory, anti-aging, and autophagy-regulating properties in central nervous system diseases. However, the effects of metformin on endogenous NSCs remains to be elucidated. Methods The proliferation and differentiation abilities of NSCs were evaluated using CCK-8 assay, EdU/Ki67 staining and immunofluorescence staining. Changes in the expression of key proteins related to ferroptosis in NSCs were detected using Western Blot and immunofluorescence staining. The levels of reactive oxygen species, glutathione and tissue iron were measured using corresponding assay kits. Changes in mitochondrial morphology and membrane potential were observed using transmission electron microscopy and JC-1 fluorescence probe. Locomotor function recovery after SCI in rats was assessed through BBB score, LSS score, CatWalk gait analysis, and electrophysiological testing. The expression of the AMPK pathway was examined using Western Blot. Results Metformin promoted the proliferation and neuronal differentiation of NSCs both in vitro and in vivo. Furthermore, a ferroptosis model of NSCs using erastin treatment was established in vitro, and metformin treatment could reverse the changes in the expression of key ferroptosis-related proteins, increase glutathione synthesis, reduce reactive oxygen species production and improve mitochondrial membrane potential and morphology. Moreover, metformin administration improved locomotor function recovery and histological outcomes following SCI in rats. Notably, all the above beneficial effects of metformin were completely abolished upon addition of compound C, a specific inhibitor of AMP-activated protein kinase (AMPK). Conclusion Metformin, driven by canonical AMPK-dependent regulation, promotes proliferation and neuronal differentiation of endogenous NSCs while inhibiting ferroptosis, thereby facilitating recovery of locomotor function following SCI. Our study further elucidates the protective mechanism of metformin in SCI, providing new mechanistic insights for its candidacy as a therapeutic agent for SCI.

Abstract Background Acute gouty arthritis (AGA) is classified as ‘arthritis’ in traditional Chinese medicine (TCM) theory. Shirebi granules (SGs), derived from the classic prescription SiMiaoWan, exerts satisfying therapeutic efficacy in ameliorating AGA clinically. However, the underlying mechanisms of SGs against AGA remain unclarified. Methods AGA-related biological processes, signal pathways and biomarker genes were mined from the GEO database through bioinformatics. SGs components were systematically recognized using the UPLC-Q-TOF–MS/MS. A correlation network was established based on the biomarker genes and the chemical components, from which the signal pathway used for further study was selected. Finally, we established an AGA model using SD rats injected with monosodium urate (MSU) in the ankle joint for experimental validation. A combination of behavioral tests, H&E, safranin O- fast green, western blotting, and immunofluorescence were employed to reveal the mechanism of action of SGs on AGA. Results The deterioration of AGA was significantly related to the imbalance between immunity and inflammation, neutrophil chemotaxis and inflammatory factor activation. HDAC5, PRKCB, NFκB1, MPO, PRKCA, PIK3CA were identified to be the candidate targets of SGs against AGA, associated with neutrophil extracellular traps (NETs) signal pathway. Animal experiments demonstrated that SGs effectively repaired cartilage damage, blocked TLR4 activation, and inhibited the expression of NETs indicators and inflammatory factors. In addition, SGs prominently alleviated joint redness and swelling, improved joint dysfunction, inhibited inflammatory infiltration of AGA rats. Conclusion Our data reveal that SGs may effectively alleviate the disease severity of AGA by suppressing NETs-promoted imbalance between immunity and inflammation.

Oleanolic acid (OA) is a five-ring triterpenoid compound, which is widely present in plants. Due to a wide range of pharmacological activities, oleanolic acid has attracted more and more attention. However, oleanolic acid is insoluble in water and has low bioavailability, which limits its clinical application. In this review, we focus on summarizing the anti-cancer activity and mechanism of the A ring or C-28 carboxyl modified derivatives of OA since 2015, to determine the strength of its anti-cancer effectiveness and evaluate whether it could be used as a clinical anti-cancer drug. [ABSTRACT FROM AUTHOR]

【Objective】 Brackish waters including saline groundwater and treated wastewater have been increasingly used as a complimentary irrigation water resource in regions where freshwater is scarce. In the paper we investigate the effect of various concentrations of saltine irrigation water on photosynthetic characteristics of winter jujube. 【Method】 The experiment was conducted in 2020 in a jujube orchard, with the winter jujubes irrigated by mixtures of saltine groundwater and freshwater at concentrations of 1 (S1), 2 (S2), 3 (S3), 4 (S4) and 5 g/L (S5), respectively. In each treatment, we measured the spaciotemporal changes in soil water and salt, as well as the photosynthetic traits of the jujubes. 【Result】 Net photosynthetic rate, transpiration and stomatal conductance of the plant leaves varied with irrigation salinity nonlinearly, all peaking in S3 or S4. Compared with other treatments, S3 and S4 reduced the SPAD, maximum fluorescence and maximum quantum efficiency significantly. Compared to S1, S3 and S4 increased the apparent quantum efficiency, maximum net photosynthetic rate, light compensation point, and dark respiration rate, but reduced the light saturation point. These indicate that, although S3 and S4 reduced the range of available light intensity, they improved the physiological activity and efficient photosynthesis of the jujube leaves. 【Conclusion】 Irrigating the winter jujubes with saline water at concentration of 1-3 g/L during the fruit enlargement period can prevent light reaction inhibition and promote efficient photosynthesis. However, irrigation with water salinity exceeding 4 g/L led to salinity stress, thereby significantly reducing light energy utilization efficiency. To minimize soil salt accumulation and improve growth and development of the winter jujube, maintaining irrigation water salinity around 3 g/L is most beneficial.

Abstract The primary objective of this study was to compare short-term outcomes between Intracorporeal ileocolic anastomosis (IIA) and extracorporeal ileocolic anastomosis (EIA) after laparoscopic right hemicolectomy in patients with visceral obesity. The secondary objective was to identify risk factors associated with prolonged postoperative ileus (PPOI) after laparoscopic right hemicolectomy. This single-center retrospective study analyzed visceral obesity patients who underwent laparoscopic right hemicolectomy for primary bowel cancer between January 2020 and June 2023. Patients were categorized into IIA and EIA groups based on the type of anastomosis, and a 1:1 propensity score-matched analysis was performed. A total of 129 patients were initially included in this study, with 45 patients in each group following propensity score matching. The IIA group had significantly longer anastomosis times (p

Abstract Background Sperm storage capacity (SSC) determines the duration of fertility in hens and is an important reproduction trait that cannot be ignored in production. Currently, the genetic mechanism of SSC is still unclear in hens. Therefore, to explore the genetic basis of SSC, we analyzed the uterus-vagina junction (UVJ) of hens with different SSC at different times after insemination by RNA-seq and Ribo-seq. Results Our results showed that 589, 596, and 527 differentially expressed genes (DEGs), 730, 783, and 324 differentially translated genes (DTGs), and 804, 625, and 467 differential translation efficiency genes (DTEGs) were detected on the 5th, 10th, and 15th days after insemination, respectively. In transcription levels, we found that the differences of SSC at different times after insemination were mainly reflected in the transmission of information between cells, the composition of intercellular adhesion complexes, the regulation of ion channels, the regulation of cellular physiological activities, the composition of cells, and the composition of cell membranes. In translation efficiency (TE) levels, the differences of SSC were mainly related to the physiological and metabolic activities in the cell, the composition of the organelle membrane, the physiological activities of oxidation, cell components, and cell growth processes. According to pathway analysis, SSC was related to neuroactive ligand-receptor interaction, histidine metabolism, and PPAR signaling pathway at the transcriptional level and glutathione metabolism, oxidative phosphorylation, calcium signaling pathway, cell adhesion molecules, galactose metabolism, and Wnt signaling pathway at the TE level. We screened candidate genes affecting SSC at transcriptional levels (COL4A4, MUC6, MCHR2, TACR1, AVPR1A, COL1A1, HK2, RB1, VIPR2, HMGCS2) and TE levels(COL4A4, MUC6, CYCS, NDUFA13, CYTB, RRM2, CAMK4, HRH2, LCT, GCK, GALT). Among them, COL4A4 and MUC6 were the key candidate genes differing in transcription, translation, and translation efficiency. Conclusions Our study used the combined analysis of RNA-seq and Ribo-seq for the first time to investigate the SSC and reveal the physiological processes associated with SSC. The key candidate genes affecting SSC were screened, and the theoretical basis was provided for the analysis of the molecular regulation mechanism of SSC.

Abstract The Nernst effect is a fundamental thermoelectric conversion phenomenon that was deemed to be possible only in systems with magnetic field or magnetization. In this work, we propose a novel dynamical chiral Nernst effect that can appear in two-dimensional van der Waals materials with chiral structural symmetry in the absence of any magnetic degree of freedom. This unconventional effect is triggered by time variation of an out-of-plane electric field, and has an intrinsic quantum geometric origin linked to not only the intralayer center-of-mass motion but also the interlayer coherence of electronic states. We demonstrate the effect in twisted homobilayer and homotrilayer transition metal dichalcogenides, where the strong twisted interlayer coupling leads to sizable intrinsic Nernst conductivities well within the experimental capacity. This work suggests a new route for electric control of thermoelectric conversion.

The extracellular matrix (ECM) regulates carcinogenesis by interacting with cancer cells via cell surface receptors. Discoidin Domain Receptor 2 (DDR2) is a collagen‐activated receptor implicated in cell survival, growth, and differentiation. Dysregulated DDR2 expression has been identified in various cancer types, making it as a promising therapeutic target. Additionally, cancer cells exhibit mechanosensing abilities, detecting changes in ECM stiffness, which is particularly important for carcinogenesis given the observed ECM stiffening in numerous cancer types. Despite these, whether collagen‐activated DDR2 signaling and ECM stiffness‐induced mechanosensing exert similar effects on cancer cell behavior and whether they operate through analogous mechanisms remain elusive. To address these questions, we performed bulk RNA sequencing (RNA‐seq) on human SH‐SY5Y neuroblastoma cells cultured on collagen‐coated substrates. Our results show that DDR2 downregulation induces significant changes in the cell transcriptome, with changes in expression of 15% of the genome, specifically affecting the genes associated with cell division and differentiation. We validated the RNA‐seq results by showing that DDR2 knockdown redirects the cell fate from proliferation to senescence. Like DDR2 knockdown, increasing substrate stiffness diminishes cell proliferation. Surprisingly, RNA‐seq indicates that substrate stiffness has no detectable effect on the transcriptome. Furthermore, DDR2 knockdown influences cellular responses to substrate stiffness changes, highlighting a crosstalk between these two ECM‐induced signaling pathways. Based on our results, we propose that the ECM could activate DDR2 signaling and mechanosensing in cancer cells to orchestrate their cell fate through distinct mechanisms, with or without involving gene expression, thus providing novel mechanistic insights into cancer progression.

It has been proven that robot-assisted rehabilitation training can effectively promote the recovery of upper-limb motor function in post-stroke patients. Increasing patients’ active participation by providing assist-as-needed (AAN) control strategies is key to the effectiveness of robot-assisted rehabilitation training. In this paper, a greedy assist-as-needed (GAAN) controller based on radial basis function (RBF) network combined with 3 degrees of freedom (3-DOF) potential constraints was proposed to provide AAN interactive forces of an end-effect upper limb rehabilitation robot. The proposed 3-DOF potential fields were adopted to constrain the tangential motions of three kinds of typical target trajectories (one-dimensional (1D) lines, two-dimensional (2D) curves and three-dimensional (3D) spirals) while the GAAN controller was designed to estimate the motor capability of a subject and provide appropriate robot-assisted forces. The co-simulation (Adams-Matlab/Simulink) experiments and behavioral experiments on 10 healthy volunteers were conducted to validate the utility of the GAAN controller. The experimental results demonstrated that the GAAN controller combined with 3-DOF potential field constraints enabled the subjects to actively participate in kinds of tracking tasks while keeping acceptable tracking accuracies. 3D spirals could be better in stimulating subjects’ active participation when compared to 1D and 2D target trajectories. The current GAAN controller has the potential to be applied to existing commercial upper limb rehabilitation robots.

In the present review, we focused on recent translational and clinical discoveries in asthma immunology, facilitating phenotyping and stratified or personalized interventions for patients with this condition. The immune processes behind chronic inflammation in asthma exhibit marked heterogeneity, with diverse phenotypes defining discernible features and endotypes illuminating the underlying molecular mechanisms. In particular, two primary endotypes of asthma have been identified: “type 2-high,” characterized by increased eosinophil levels in the airways and sputum of patients, and “type 2-low,” distinguished by increased neutrophils or a pauci-granulocytic profile. Our review encompasses significant advances in both innate and adaptive immunities, with emphasis on the key cellular and molecular mediators, and delves into innovative biological and targeted therapies for all the asthma endotypes. Recognizing that the immunopathology of asthma is dynamic and continuous, exhibiting spatial and temporal variabilities, is the central theme of this review. This complexity is underscored through the innumerable interactions involved, rather than being driven by a single predominant factor. Integrated efforts to improve our understanding of the pathophysiological characteristics of asthma indicate a trend toward an approach based on disease biology, encompassing the combined examination of the clinical, cellular, and molecular dimensions of the disease to more accurately correlate clinical traits with specific disease mechanisms.

Abstract The precise mechanism underlying the therapeutic effects of dihydroartemisinin (DHA) in alleviating colitis remains incompletely understood. A strong correlation existed between the elevation of glial fibrillary acidic protein (GFAP)+/S100 calcium binding protein B (S100β)+ enteric glial cells (EGCs) in inflamed colonic tissues and the disruption of the intestinal epithelial barrier (IEB) and gut vascular barrier (GVB) observed in chronic colitis. DHA demonstrated efficacy in restoring the functionality of the dual gut barrier while concurrently attenuating intestinal inflammation. Mechanistically, DHA inhibited the transformation of GFAP+ EGCs into GFAP+/S100β+ EGCs while promoting the differentiation of GFAP+/S100β+ EGCs back into GFAP+ EGCs. Furthermore, DHA induced apoptosis in GFAP+/S100β+ EGCs by inducing cell cycle arrest at the G0/G1 phase. The initial mechanism is further validated that DHA regulates EGC heterogeneity by improving dysbiosis in colitis. These findings underscore the multifaceted therapeutic potential of DHA in ameliorating colitis by improving dysbiosis, modulating EGC heterogeneity, and preserving gut barrier integrity, thus offering promising avenues for novel therapeutic strategies for inflammatory bowel diseases.

Background: Dyslipidemia has been implicated in autoimmunity; however, its association with myasthenia gravis (MG) prognosis is unclear. We aimed to investigate the correlation between baseline lipid profiles and risk of MG worsening. Methods: This 7-year retrospective cohort study conducted at a Chinese hospital included 264 adult patients with MG. Data on baseline lipids, 1-year worsening, and covariates, including demographics, MG characteristics, comorbidities, and treatments were extracted. Results: Univariate and multivariate logistic regression analyses failed to show a significant association between the risk of 1-year MG worsening and any of the seven blood lipid-related indicators. However, the subsequent non-linear analysis revealed an inflection point in the risk curve of ln[lipoprotein(a)], at 4.06 (58 nmol/L). The lipoprotein(a) levels on the left side of the inflection point presented a positive significant correlation with the risk of MG worsening (relative risk [RR]: 6.06, 95 % confidence interval [CI]: 1.00–38.57), whereas those on the right side of the inflection point demonstrated no significant correlation (RR: 0.86, 95 % CI: 0.55–1.34). Conclusions: Except for lipoprotein(a) levels being associated with worsening of myasthenia gravis, most lipid parameters were not associated with changes in the clinical course and severity of myasthenia gravis.we observed that lower levels of lipoprotein(a) were associated with a better prognosis in the interval 7–58 nml/L, whereas beyond this interval this was not observed, suggesting dyslipidemia may impact MG prognosis. Further studies are required to validate these findings.

Purpose: To investigate the correlation between the marginal bone height of implants in the posterior maxilla of patients with periodontal disease and the inclination of cusp, providing a theoretical basis for the occlusal design of implant restorations in such patients. Methods: A total of 80 patients with periodontal disease who underwent implant restoration in the posterior maxilla (55 men and 25 women; mean age 56.66 ± 12.70 years) were selected, with a total of 80 implant restorations (one implant restoration per patient). In addition to recording the main research factor of the inclination of cusp, general patient information, implant characteristics and restoration characteristics were taken, and retrospective analysis of the case data and imaging data of the 80 patients from over 3 years was conducted. Cone beam computed tomography was performed preoperatively and 3 years after implant loading to measure and calculate the marginal bone height of the implants using the One Volume Viewer software. Correlation analysis was performed to determine the relationship between the inclination of the cusp and marginal bone height. Results: There was a positive correlation between the inclination of cusp and the marginal bone height of the implants, with a correlation coefficient of 0.661 (p

Summary: Pyroptosis, a pro-inflammatory form of programmed cell death, is crucial for host defense against pathogens and danger signals. Proteolytic cleavage of gasdermin proteins B–E (GSDMB–GSDME) is well established as a trigger for pyroptosis, but the intracellular activation mechanism of GSDMA remains elusive. Here, we demonstrate that severe starvation induces pyroptosis through phosphorylation-induced activation of GSDMA. Nutrient stresses stimulate GSDMA activation via phosphorylation mediated by Unc-51-like autophagy-activating kinase 1 (ULK1). Phosphorylation of Ser353 on human GSDMA by ULK1 or the phospho-mimetic Ser353Asp mutant of GSDMA liberates GSDMA from auto-inhibition, facilitating its membrane targeting and initiation of pyroptosis. To further validate the significance of GSDMA phosphorylation, we generated a constitutively active mutant Ser354Asp of mouse Gsdma, which induced skin inflammation and hyperplasia in mice, reminiscent of phenotypes with activated Gsdma. This study uncovers phosphorylation of GSDMA as a mechanism underlying pyroptosis initiation and cellular response to nutrient stress.

The synthesis of pseudo-healthy images, involving the generation of healthy counterparts for pathological images, is crucial for data augmentation, clinical disease diagnosis, and understanding pathology-induced changes. Recently, Generative Adversarial Networks (GANs) have shown substantial promise in this domain. However, the heterogeneity of intracranial infection symptoms caused by various infections complicates the model's ability to accurately differentiate between pathological and healthy regions, leading to the loss of critical information in healthy areas and impairing the precise preservation of the subject's identity. Moreover, for images with extensive lesion areas, the pseudo-healthy images generated by these methods often lack distinct organ and tissue structures. To address these challenges, we propose a three-stage method (localization, inpainting, synthesis) that achieves nearly perfect preservation of the subject's identity through precise pseudo-healthy synthesis of the lesion region and its surroundings. The process begins with a Segmentor, which identifies the lesion areas and differentiates them from healthy regions. Subsequently, a Vague-Filler fills the lesion areas to construct a healthy outline, thereby preventing structural loss in cases of extensive lesions. Finally, leveraging this healthy outline, a Generative Adversarial Network integrated with a contextual residual attention module generates a more realistic and clearer image. Our method was validated through extensive experiments across different modalities within the BraTS2021 dataset, achieving a healthiness score of 0.957. The visual quality of the generated images markedly exceeded those produced by competing methods, with enhanced capabilities in repairing large lesion areas. Further testing on the COVID-19-20 dataset showed that our model could effectively partially reconstruct images of other organs.

Introduction Haemodialysis (HD) patients usually engage in a low level of physical activities, which could impact the prognosis and mortality of this group. Fitness Qigong Baduanjin, a physical exercise from traditional Chinese Medicine, is known to have benefit in chronic heart failure patients and peritoneal dialysis patients. However, researches about Baduanjin in HD patients are currently limited. So, the aim of the study is to investigate the current exercise intensity of HD patients and its influencing factors, and to explore the effects of Baduanjin on HD patients.Methods and analysis This prospective, non-blinded, randomised controlled trial will enrol patients with end-stage kidney disease who were stable on HD for more than 3 months. All eligible participants will be randomly divided into the intervention group undergoing Baduanjin and the control group without Baduanjin in a 1:1 ratio. The intervention group is required to perform Baduanjin two times per day, starting 30 min after breakfast and dinner, 45 min per session for a total of a 6 month, starting from 10 June 2024. Information such as laboratory biochemical examination indicators, radiological examination results and related scales and questionnaires will be collected at baseline, 1 month follow-up, 3 month follow-up and 6 month follow-up. All statistical tests are conducted through the two-tailed test, and a p-value≤0.05 will be considered statistically significant for the difference being tested. The description of quantitative indicators will be used in calculating the number of cases, mean, SD, median and IQR method. The classification indicators will be used to describe the number of cases and percentages (frequency and frequency rate).Ethics and dissemination The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (V20230521). The results will be reported in a peer-reviewed journal and a relevant academic conference.Trail registration ChiCTR2300074659.

BackgroundThis study aims to assess the causal relationship between immune cell characteristics and malignant tumors of bone and articular cartilage, focusing on the mediating role of metabolites. Using Mendelian randomization, we evaluated these relationships based on genetic variations to identify potential biomarkers and therapeutic targets.MethodsA two-sample Mendelian randomization analysis was conducted using GWAS data for immune cell features and 1,400 metabolites to investigate direct and mediating effects. Effective instrumental variables (IVs) were selected, and statistical analyses—including inverse variance weighting (IVW), weighted median, and mode-based methods—were performed using R software. This approach enabled the assessment of direct causal relationships as well as the potential mediating role of metabolites in the association between immune cell features and malignancies.ResultsSignificant causal relationships were identified between 26 immune phenotypes and the risk of malignant tumors of bone and articular cartilage. Notably, the HLA DR+ NK cell phenotype SSC-A showed a positive correlation with the risk of these malignancies. Further analysis revealed causal relationships with 67 metabolites, 38 of which were positively correlated and 29 negatively correlated. Mediation analysis highlighted the role of immune surveillance and metabolic dysregulation in tumor development, as evidenced by the association between the immune phenotype SSC-A on HLA DR+ NK cells and the metabolite 5-hydroxyhexanoate.ConclusionThe findings suggest significant causal relationships between immune phenotypes and malignant tumors of bone and articular cartilage, with metabolites potentially mediating these relationships. These insights lay the groundwork for further research and could contribute to the development of new biomarkers and treatment strategies.

Host remodeling of decellularized extracellular matrix (dECM) material through the appropriate involvement of immune cells is essential for achieving functional organ/tissue regeneration. As many studies have focused on the role of macrophages, only few have evaluated the role of regulatory T cells (Tregs) in dECM remodeling. In this study, we used a mouse model of traumatic muscle injury to determine the role of Tregs in the constructive remodeling of vascular-derived dECM. According to the results, a certain number of Tregs could be recruited after dECM implantation. Notably, using anti-CD25 to reduce the number of Tregs recruited by the dECM was significantly detrimental to material remodeling based on a significant reduction in the number of M2 macrophages. In addition, collagen and elastic fibers, which maintain the integrity and mechanical properties of the material, rapidly degraded during the early stages of implantation. In contrast, the use of CD28-SA antibodies to increase the number of Tregs recruited by dECM promoted constructive remodeling, resulting in a decreased inflammatory response at the material edge, thinning of the surrounding fibrous connective tissue, uniform infiltration of host cells, and significantly improved tissue remodeling scores. The number of M2 macrophages increased whereas that of M1 macrophages decreased. Moreover, Treg-conditioned medium further enhanced material-induced M2 macrophage polarization in vitro. Overall, Treg is an important cell type that influences constructive remodeling of the dECM. Such findings contribute to the design of next-generation biomaterials to optimize the remodeling and regeneration of dECM materials.