Search

Abstract The cell death and survival paradox in various biological processes requires clarification. While spore development causes maternal cell death in Bacillus species, the involvement of other cell death pathways in sporulation remains unknown. Here, we identified a novel ArsR family transcriptional regulator, CdsR, and found that the deletion of its encoding gene cdsR causes cell lysis and inhibits sporulation. To our knowledge, this is the first report of an ArsR family transcriptional regulator governing cell death. We found that CdsR directly repressed lrgAB expression. Furthermore, lrgAB overexpression resulted in cell lysis without sporulation, akin to the cdsR mutant, suggesting that LrgAB, a holin-like protein, induces cell death in Bacillus spp. The lrgAB mutation increases abnormal cell numbers during spore development. In conclusion, we propose that a novel repressor is vital for inhibiting LrgAB-dependent cell lysis.

Abstract This mediation analysis aimed to investigate the associations among areal bone mineral density, mobility-related brain atrophy, and specific gait patterns. A total of 595 participants from the Taizhou Imaging Study, who underwent both gait and bone mineral density measurements, were included in this cross-sectional analysis. We used a wearable gait tracking device to collect quantitative gait parameters and then summarized them into independent gait domains with factor analysis. Bone mineral density was measured in the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of brain regions related to mobility were computed using FreeSurfer. Lower bone mineral density was found to be associated with higher gait variability, especially at the site of the lumbar spine (β = 0.174, FDR = 0.001). Besides, higher gait variability was correlated with mobility-related brain atrophy, like the primary motor cortex (β = 0.147, FDR = 0.006), sensorimotor cortex (β = 0.153, FDR = 0.006), and entorhinal cortex (β = 0.106, FDR = 0.043). Bidirectional mediation analysis revealed that regional brain atrophy contributed to higher gait variability through the low lumbar spine bone mineral density (for the primary motor cortex, P = 0.018; for the sensorimotor cortex, P = 0.010) and the low lumbar spine bone mineral density contributed to higher gait variability through the primary motor and sensorimotor cortices (P = 0.026 and 0.010, respectively).

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9), the last member of the proprotein convertase family, functions as a classic regulator of low-density lipoprotein (LDL) by interacting with low-density lipoprotein receptor (LDLR). Recent studies have shown that PCSK9 can affect the occurrence and development of tumors and can be used as a novel therapeutic target. However, a comprehensive pan-cancer analysis of PCSK9 has yet to be conducted. Methods The potential oncogenic effects of PCSK9 in 33 types of tumors were explored based on the datasets of The Cancer Genome Atlas (TCGA) dataset. In addition, the immune regulatory role of PCSK9 inhibition was evaluated via in vitro cell coculture and the tumor-bearing mouse model. Finally, the antitumor efficacy of targeted PCSK9 combined with OVA-II vaccines was verified. Results Our results indicated that PCSK9 was highly expressed in most tumor types and was significantly correlated with late disease stage and poor prognosis. Additionally, PCSK9 may regulate the tumor immune matrix score, immune cell infiltration, immune checkpoint expression, and major histocompatibility complex expression. Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Combining PCSK9 inhibitors could enhance the efficacies of OVA-II tumor vaccine monotherapy. Conclusions Conclusively, our pan-cancer analysis provided a more comprehensive understanding of the oncogenic and immunoregulatory roles of PCSK9 and demonstrated that targeting PCSK9 could increase the efficacy of long peptide vaccines by upregulating DC infiltration and MHC-II expression on the surface of tumor cells. Summary This study reveals the critical oncogenic and immunoregulatory roles of PCSK9 in various tumors and shows the promise of PCSK9 as a potent immunotherapy target.

Abstract Creating circularly polarized organic afterglow system with elevated triplet energy levels, suppressed non-radiative transitions, and effective chirality, which are three critical prerequisites for achieving blue circularly polarized afterglow, has posed a formidable challenge. Herein, a straightforward approach is unveiled to attain blue circularly polarized afterglow materials by covalently self-confining isolated chiral chromophore within polymer matrix. The formation of robust hydrogen bonds within the polymer matrix confers a distinctly isolated and stabilized molecular state of chiral chromophores, endowing a blue emission band at 414 nm, lifetime of 3.0 s, and luminescent dissymmetry factor of ~ 10−2. Utilizing the synergistic afterglow and chirality energy transfer, full-color circularly polarized afterglow systems are endowed by doping colorful fluorescent molecules into designed blue polymers, empowering versatile applications. This work paves the way for the streamlined design of blue circularly polarized afterglow materials, expanding the horizons of circularly polarized afterglow materials into various domains.

Abstract The rational use and conversion of energy are the primary means for achieving the goal of carbon neutrality. MXenes can be used for photothermal conversion, but their opaque appearance limits wider applications. Herein, we successfully develop visible-light transparent and UV-absorbing polymer composite film by solution blending the MXene with polyethylene and then vacuum pressing. The resulting film could be quickly heated to 65 °C under 400 mW cm−2 light irradiation and maintained over 85% visible-light transmittance as well as low haze (

Abstract Swine acute diarrhea syndrome coronavirus (SADS-CoV), an emerging Alpha-coronavirus, brings huge economic loss in swine industry. Interferons (IFNs) participate in a frontline antiviral defense mechanism triggering the activation of numerous downstream antiviral genes. Here, we demonstrated that TRIM25 overexpression significantly inhibited SADS-CoV replication, whereas TRIM25 deficiency markedly increased viral yield. We found that SADS-CoV N protein suppressed interferon-beta (IFN-β) production induced by Sendai virus (SeV) or poly(I:C). Moreover, we determined that SADS-CoV N protein interacted with RIG-I N-terminal two caspase activation and recruitment domains (2CARDs) and TRIM25 coiled-coil dimerization (CCD) domain. The interaction of SADS-CoV N protein with RIG-I and TRIM25 caused TRIM25 multimerization inhibition, the RIG-I-TRIM25 interaction disruption, and consequent the IRF3 and TBK1 phosphorylation impediment. Overexpression of SADS-CoV N protein facilitated the replication of VSV-GFP by suppressing IFN-β production. Our results demonstrate that SADS-CoV N suppresses the host IFN response, thus highlighting the significant involvement of TRIM25 in regulating antiviral immune defenses.

Abstract Depression is a mood disorder mainly clinically characterized by significant and persistent low spirits. Chronic stress is the leading cause of depression. However, traditional medicine has severe side effects in treating depression, ineffective treatment, and easy recurrence. Therefore, it is of great significance to prevent depression in the environment of chronic stress. In this study, aromatherapy was used for the prevention of depression. To solve the defects of intense volatility and inconvenience in using essential oils, we designed bionic nano-aromatic drugs and adhered them to the wallpaper. Inspired by the moldy wallpaper, we successively prepared the morphology-bionic nano-aromatic drugs, the function-bionic nano-aromatic drugs, and the bionic plus nano-aromatic drugs by referring to the morphology of microorganisms and substances in bacterial biofilms. Bionic nano-aromatic drugs remarkably promoted their adhesion on wallpaper. Molecular dynamics simulation explored its molecular mechanism. The essential oils, which were slowly released from the bionic nano-aromatic drugs, showed excellent biosecurity and depression prevention. These sustainedly released essential oils could significantly increase monoamine neurotransmitters in the brain under a chronic stress environment and had excellent neuroprotection. Besides, the bionic nano-aromatic drugs with simple preparation process and low cost had excellent application potential.

Abstract Purpose This study aims to provide a comprehensive overview of anesthesia management strategies employed in pediatric lung transplantation. Methods A retrospective analysis was conducted on data from 14 pediatric patients who underwent lung transplantation at the Wuxi Center between September 2019 and November 2022. Patient demographics, surgical particulars, airway management, utilization of extracorporeal support, fluid administration, blood gas and electrolyte profiles, and postoperative outcomes were systematically documented and subsequently summarized. Results Of the 14 patients, 7 received extracorporeal membrane oxygenation (ECMO) and 1 received cardiopulmonary bypass (CPB). The average operation time was 303 ± 53 min, with the median extubation time of 26 h. The entirety of pediatric lung transplant procedures was executed successfully, resulting in the discharge of thirteen patients postoperatively. Regrettably, one patient died due to infectious shock on the fourth postoperative day. Conclusion The achievement of successful pediatric lung transplantation necessitates effective perioperative anesthesia management, with a focal emphasis on circulatory control. Real-time measurements serve as the cornerstone for decision-making. Proactive administration of vasoactive agents is integral to sustaining hemodynamic stability. The judicious assessment of ECMO necessity is paramount, favoring central ECMO during the surgical intervention.

Abstract Background Becoming a first-level discipline in China means access to more educational resources. The development of medical humanities in China has been going on for more than 40 years, and some medical schools have set up master’s and doctoral programs in medical humanities. The demand for medical humanities-related knowledge in China is also growing after COVID-19. However, medical humanities is only a second-level discipline and receives limited resources to meet the needs of society. This study aims to establish a system of indicators that can assess whether the medical humanities has a first-level discipline and provide a basis for its upgrading to a first-level. Methods A Delphi technique was used, with the panel of expert expressing their views in a series of two questionnaires. A coefficient of variation of less than 0.2 indicates expert agreement. Result A total of 25 experts participated in this Delphi study. Consensus was reached on 11 first-grade indices and 48 s-grade indices. The authoritative coefficient(Cr) of the experts was 0.804, which indicates that the experts have a high level of reliability. Conclusion This study provides a reliable foundation for the evaluation of medical humanities maturity.

Abstract Linear ubiquitination catalyzed by HOIL-1-interacting protein (HOIP), the key component of the linear ubiquitination assembly complex, plays fundamental roles in tissue homeostasis by executing domain-specific regulatory functions. However, a proteome-wide analysis of the domain-specific interactome of HOIP across tissues is lacking. Here, we present a comprehensive mass spectrometry-based interactome profiling of four HOIP domains in nine mouse tissues. The interaction dataset provides a high-quality HOIP interactome resource with an average of approximately 90 interactors for each bait per tissue. HOIP tissue interactome presents a systematic understanding of linear ubiquitination functions in each tissue and also shows associations of tissue functions to genetic diseases. HOIP domain interactome characterizes a set of previously undefined linear ubiquitinated substrates and elucidates the cross-talk among HOIP domains in physiological and pathological processes. Moreover, we show that linear ubiquitination of Integrin-linked protein kinase (ILK) decreases focal adhesion formation and promotes the detachment of Shigella flexneri-infected cells. Meanwhile, Hoip deficiency decreases the linear ubiquitination of Smad ubiquitination regulatory factor 1 (SMURF1) and enhances its E3 activity, finally causing a reduced bone mass phenotype in mice. Overall, our work expands the knowledge of HOIP-interacting proteins and provides a platform for further discovery of linear ubiquitination functions in tissue homeostasis.

Abstract Background Gait disturbance is common in older adults with vascular diseases. However, how carotid atherosclerosis affects gait remains poorly understood. The objectives were to investigate the associations between carotid intima-media thickness and specific gait performances and explore the potential role of brain structure in mediating these associations. Methods A cross-sectional analysis of data from the Taizhou Imaging Study was conducted, including 707 individuals who underwent both gait and carotid ultrasound examinations. Gait assessments include the Timed-Up-and-Go test, the Tinetti test, and quantitative gait assessment using a wearable device. Quantitative parameters were summarized into independent gait domains with factor analysis. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of fifteen brain regions related to motor function (primary motor, sensorimotor), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules), executive control function (dorsolateral prefrontal cortex, anterior cingulate), memory (hippocampus, entorhinal cortex), motor imagery (precuneus, parahippocampus, posterior cingulated cortex), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) were computed using FreeSurfer and the Desikan-Killiany atlas. Mediation analysis was conducted with carotid intima-media thickness as the predictor and mobility-related brain regions as mediators. Results Carotid intima-media thickness was found to be associated with the Timed-Up-and-Go performance (β = 0.129, p = 0.010) as well as gait performances related to pace (β=-0.213, p

In this paper, Cinnamomum cassia polysaccharide (CCP) was extracted and purified, and its physicochemical properties, antioxidant and hypoglycemic activities were investigated. The polysaccharide yield was optimized by the response surface test with three conditions: Temperature, time and liquid-solid ratio. Then the physicochemical properties of purified CCP were investigated by high performance liquid chromatography, thermogravimetric analysis and other methods, meanwhile, its antioxidant and hypoglycemic activities were tested in vitro. Results indicated that the optimum extraction conditions as follow: Extraction temperature 90 ℃, extraction time 2.5 h, liquid-solid ratio 20:1 (mL/g), extraction twice, under these conditions, the average yield was 3.22%. The relative molecular weight of CCP was 1.95×106 Da, the total sugar content was 90.11%±1.24%, and it was stable within 230 ℃. Both Fourier-transform infrared and nuclear magnetic hydrogen spectra showed that CCP had α, β-glycosidic bonds and other structures, in addition, Congo red staining showed that it might not have triple helix structure. Activity assays showed that CCP had good scavenging effect on DPPH·, ABTS+∙, ·OH, with IC50 values of 0.191, 2.835 and 3.221 mg/mL, respectively, and the total reducing power value of the polysaccharide at 6 mg/mL was 1.18. In addition, CCP also had inhibitory activity against α-amylase and α-glucosidase, with IC50 values of 0.189 and 0.340 mg/mL. In this study, a high molecular weight Cinnamomum cassia polysaccharide was extracted and purified, which had good antioxidant and hypoglycemic activities, which may provide a basis for the functional development and utilization of Cinnamomum cassia.

In order to improve the antioxidant activity of Zizania latifolia polysaccharides, sulfate it and explore the optimum modification conditions. Polysaccharides was extracted by water extraction and alcohol precipitation method from Zizania latifolia, then it was separated and purified to obtain a new type of water-soluble polysaccharide. Using formamide as solvent, polysaccharides were sulfated by sulfur trioxide-pyridine method. The degree of substitution (DS) was set as the examination index, the optimal sulfonation conditions were selected by response surface method. Through the free radical scavenging rate trial in vitro, compared with natural polysaccharides, to explore the changes of antioxidant activity of sulfated polysaccharides in vitro. The results showed that the optimum reaction conditions obtained as polysaccharide 100 mg, time 4 h, temperature 70 ℃, sulfur trioxide-pyridine complex 2.6 g. The optimum DS was 1.79. Thermogravimetric analysis showed that the fastest weight loss rate of Zizania latifolia polysaccharides was 16.48% at 46.38 ℃, and the sulfated polysaccharides was 2.92% at 65.04 ℃. In the antioxidant test in vitro, the IC50 of free radical scavenging ability of Zizania latifolia polysaccharides to DPPH·, ·OH and ABTS+· were 3.49, 3.28 and 12.70 mg/mL respectively. The sulfated polysaccharides of Zizania latifolia polysaccharides were 0.39, 1.00 and 1.82 mg/mL respectively, and the positive control (VC) was 0.069, 0.17 and 0.077 mg/mL respectively. In summary, sulfation modification can enhance the thermal stability of Zizania latifolia polysaccharides and enhance its free radical scavenging ability to some extent.

Asphalt binder is susceptible to aging from heat, air and sunlight exposure during service, leading to pavement distresses. This study aimed to improve the aging resistance of asphalt using zinc oxide-silicate (ZOS) composites. ZOS containing 2–8 wt% ZnO were synthesized via a one-step sol-gel method and incorporated into an unmodified 70/100 penetration grade asphalt binder. The rheological properties and aging characteristics were evaluated before and after rolling thin film oven and pressure aging vessel protocols. Dynamic shear rheometry showed increased complex modulus and decreased phase angle for ZOS-modified binders, indicating improved rutting resistance. Aging indices revealed the 6% ZOS composite had the least susceptibility to oxidative aging. FTIR analysis confirmed the formation of carbonyl and sulfoxide functional groups during aging, which were mitigated by ZOS addition. Scanning electron microscopy visualized nano-scaled ZnO particles dispersed within the silica matrix and asphalt binder. The ZOS composites delayed the aging rate through physicochemical interactions between ZnO and the asphalt medium. An optimum ZOS dosage of 4–6% was found to enhance the anti-aging properties. The renewable silica-supported ZnO composites show potential as cost-effective modifiers for improving asphalt durability.

To ensure the stability of broken surrounding rock under the influence of advance abutment pressure and the reliability of support system, the 21104 working face of Hulusu Coal Mine is taken as the research background. By means of theoretical calculation, numerical simulation and field measurement, a mechanical model of the elastic foundation beam for the deformation of the super front roof is established, the influencing factors of the bending deformation of the roof, the leading bearing pressure and the main controlling factors of the concentration coefficient are determined, and the advance grouting anchor cable reinforcement technology for broken surrounding rock is proposed. The results show that the roof elastic modulus only affects the roof deflection above the roadway, and the side elastic modulus controls the overall bending deformation of the roof. The advanced support pressure and concentration coefficient show a rapid increase followed by a slow increase trend with the advancement of the working face, and finally tend to stabilize. There is a 35 m high stress area in the grouting anchor cable reinforcement test face, the anchor cable has a high abundance coefficient, the surrounding rock deformation is low (

Abstract Background Long‐term overgrazing has led to severe degradation of grasslands, posing a significant threat to the sustainable use of grassland resources. Methods Based on the investigation of changes in functional traits and photosynthetic physiology of Stipa breviflora under no grazing, moderate grazing, and heavy grazing treatments, the changes in expression patterns of genes and proteins associated with different grazing intensities were assessed through integrative transcriptomic and proteomic analyses. Results Differentially expressed genes and proteins were identified under different grazing intensities. They were mainly related to RNA processing, carbon metabolism, and secondary metabolite biosynthesis. These findings suggest that long‐term grazing leads to molecular phenotypic plasticity, affecting various biological processes and metabolic pathways in S. breviflora. Correlation analysis revealed low correlation between the transcriptome and the proteome, indicating a large‐scale regulation of gene expression at the posttranscriptional and translational levels during the response of S. breviflora to grazing. The expression profiles of key genes and proteins involved in photosynthesis and phenylpropanoid metabolism pathways suggested their synergistic response to grazing in S. breviflora. Conclusions Our study provides insight into the adaptation mechanisms of S. breviflora to grazing and provides a scientific basis for the development of more efficient grassland protection and utilization practices.

In order to solve the problem of poor permeability enhancement effect caused by disorderly expansion of coal cracks in traditional presplitting blasting, the influence of different opening angles of shaped charge blasting cartridge on permeability enhancement effect of coal seam was studied. By establishing the theoretical model of micro element closure of shaped charge hood, the velocity and mass changes of shaped charge jet were analyzed when the angle of shaped charge hood decreased; On this basis, the mechanism of penetration enhancement by shaped charge blasting is analyzed. A two-way loading gas-solid coupling blasting similar simulation experiment system was built in the laboratory, which can analyze the experimental model from multiple angles of coal macro crack and strain data. The common blasting and different shaped energy opening angle blasting simulation experiments were carried out on the test block of coal containing gas. The results show that the use of shaped charge can effectively guide the directional development of cracks in the opening direction of shaped charge compared with ordinary blasting; With the decrease of the angle of the shaped charge hood, the crack formed after shaped charge blasting is smoother in the direction of energy accumulation, the crack width also increases, and the section of the test block is smoother; According to the inversion results of the super dynamic strain gauge, the peak compressive stress of 60°, 80° and 100° shaped charge blasting at No. 1 measuring point is 1.52 times, 1.26 times and 1.08 times that of ordinary blasting, respectively, and the time to reach the peak stress of 60° shaped charge blasting is the shortest, indicating that with the reduction of the opening of the shaped charge cover, the upward energy concentration phenomenon is more obvious. Four different angles of shaped charge blasting were compared and analyzed by ANSYS/LS-DYNA software. The simulation results show that the effective stress of the shaped charge jet formed initially by 60° shaped charge blasting is the largest, and the crack generated in the direction of shaped charge blasting is the longest. The test and simulation results show that better blasting effect can be obtained by using 60° shaped charge. The research results have certain reference significance for the permeability enhancement of shaped charge blasting in soft and high gas coal seam.

Over the past two decades, (K0.5Na0.5)NbO3 (KNN)-based lead-free piezoelectric ceramics have made significant progress. However, attaining a high electrostrain with remarkable temperature stability and minimal hysteresis under low electric fields has remained a significant challenge. To address this long-standing issue, we have employed a collaborative approach that combines defect engineering, phase engineering, and relaxation engineering. The LKNNS-6BZH ceramic, when sintered at Tsint = 1170 ℃, demonstrates an impressive electrostrain with a d33∗ value of 0.276% and 1379 pm·V–1 under 20 kV·cm–1, which is comparable to or even surpasses that of other lead-free and Pb(Zr,Ti)O3 ceramics. Importantly, the electrostrain performance of this ceramic remains stable up to a temperature of 125 ℃, with the lowest hysteresis observed at 9.73% under 40 kV·cm–1. These excellent overall performances are attributed to the presence of defect dipoles involving VA′–VO∙∙ and BNb′–VO∙∙, the coexistence of R–O–T multiphase, and the tuning of the trade-off between long-range ordering and local heterogeneity. This work provides a lead-free alternative for piezoelectric actuators and a paradigm for designing piezoelectric materials with outstanding comprehensive performance under low electric fields.

Abstract Background Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) recommended for the patients with subsolid nodule in early lung cancer stage is not routinely. The clinical value and impact in patients with EGFR mutation on survival outcomes is further needed to be elucidated to decide whether the application of EGFR-TKIs was appropriate in early lung adenocarcinoma (LUAD) stage appearing as subsolid nodules. Materials and methods The inclusion of patients exhibiting clinical staging of IA-IIB subsolid nodules. Clinical information, computed tomography (CT) features before surgical resection and pathological characteristics including tertiary lymphoid structures of the tumors were recorded for further exploration of correlation with EGFR mutation and prognosis. Results Finally, 325 patients were enrolled into this study, with an average age of 56.8 ± 9.8 years. There are 173 patients (53.2%) harboring EGFR mutation. Logistic regression model analysis showed that female (OR = 1.944, p = 0.015), mix ground glass nodule (OR = 2.071, p = 0.003, bubble-like lucency (OR = 1.991, p = 0.003) were significant risk factors of EGFR mutations. Additionally, EGFR mutations were negatively correlated with TLS presence and density. Prognosis analysis showed that the presence of TLS was associated with better recurrence-free survival (RFS)(p = 0.03) while EGFR mutations were associated with worse RFS(p = 0.01). The RFS in patients with TLS was considerably excel those without TLS within EGFR wild type group(p = 0.018). Multivariate analyses confirmed that EGFR mutation was an independent prognostic predictor for RFS (HR = 3.205, p = 0.037). Conclusions In early-phase LUADs, subsolid nodules with EGFR mutation had specific clinical and radiological signatures. EGFR mutation was associated with worse survival outcomes and negatively correlated with TLS, which might weaken the positive impact of TLS on prognosis. Highly attention should be paid to the use of EGFR-TKI for further treatment as agents in early LUAD patients who carrying EGFR mutation.

Abstract All-solid-state batteries with non-flammable solid electrolytes offer enhanced safety features, and show the potential for achieving higher energy density by using lithium metal as the anode. Among various solid electrolytes, sulfides are favored for their high room-temperature ionic conductivity and low-temperature processing. However, making large-scale thin electrolyte films via pressing sulfide powder is still challenging. A polymer has recently been introduced as a binder or framework to obtain a flexible thin sulfide-based composite electrolyte film with high ionic conductivity. In this Review, we initially discuss the ionic transport mechanism of sulfide/polymer composite electrolyte films. Then, the preparation methods and the properties of sulfide-based composite electrolytes are introduced in detail, and the advantages and disadvantages of each method are also analyzed. We later discuss the application of composite electrolyte films in all-solid-state batteries. Finally, we provide a perspective on the future development direction of sulfide-based composite electrolyte films.

Abstract Background The treatment for colon adenocarcinoma (COAD) faces challenges in terms of immunotherapy effectiveness due to multiple factors. Because of the high tumor specificity and immunogenicity, neoantigen has been considered a pivotal target for cancer immunotherapy. Therefore, this study aims to identify and predict the potential tumor antigens of MUC somatic mutations (MUCmut) in COAD. Methods Three databases of TCGA, TIMER2.0, and cBioPortal were used for a detailed evaluation of the association between MUCmut and multi-factors like tumor mutation burden (TMB), microsatellite instability (MSI), prognosis, and the tumor microenvironment within the context of total 2242 COAD patients. Next, TSNAdb and the differential agretopicity index (DAI) were utilized to predict high-confidence neopeptides for MUCmut based on 531 COAD patients’ genomic information. DAI was calculated by subtraction of its predicted HLA binding affinity of the MUCmut peptide from the corresponding wild-type peptide. Results The top six mutation frequencies (14 to 2.9%) were from MUC16, MUC17, MUC5B, MUC2, MUC4 and MUC6. COAD patients with MUC16 and MUC4 mutations had longer DFS and PFS. However, patients with MUC13 and MUC20 mutations had shorter OS. Patients with the mutation of MUC16, MUC5B, MUC2, MUC4, and MUC6 exhibited higher TMB and MSI. Moreover, these mutations from the MUC family were associated with the infiltration of diverse lymphocyte cells and the expression of immune checkpoint genes. Through TSNAdb 1.0/NetMHCpan v2.8, 452 single nucleotide variants (SNVs) of MUCmut peptides were identified. Moreover, through TSNAdb2.0/NetMHCpan v4.0, 57 SNVs, 1 Q-frame shift (TS), and 157 short insertions/deletions (INDELs) of MUCmut were identified. Finally, 10 high-confidence neopeptides of MUCmut were predicted by DAI. Conclusions Together, our findings establish the immunogenicity and therapeutic potential of mutant MUC family-derived neoantigens. Through combining the tools of TSNAdb and DAI, a group of novel MUCmut neoantigens were identified as potential targets for immunotherapy.

In this article, the experimental and finite element analysis is utilized to investigate the quasi-static compression features of sandwich constructions built with tapered tubes. 3D printing technology was utilized to create the hollow centers of the tapering tubes, with and without corrugations. The results demonstrate that the energy absorption (EA) and specific energy absorption (SEA) of the single corrugated tapered tube sandwich are 51.6% and 19.8% higher, respectively, than those of the conical tube sandwich. Furthermore, the results demonstrate that energy absorbers can benefit from corrugation in order to increase their efficiency. Additionally, the tapered corrugated tubes’ resistance to oblique impacts was studied. Compared to a straight tube, the tapered tube is more resistant to oblique loads and has a lower initial peak crushing force (PCF), according to numerical simulations. After conducting a parametric study, it was discovered that the energy absorption performance of the sandwich construction is significantly affected by the amplitude, number of corrugations, and wall thickness. EA and SEA of DTS with corrugation number of 8 increased by 17.4% and 29.6%, respectively, while PCF decreased by 9.2% compared to DTS with corrugation number of 10.

ABSTRACT: The development of efficient perovskite light-emitting diodes (PeLEDs) relies strongly on the fabrication of perovskite films with rationally designed structures (grain size, composition, surface, etc.). Therefore, an understanding of structure-performance relationships is of vital importance for developing high-performance perovskite devices, particularly for devices with in-situ fabricated perovskite nanocrystal films. In this study, we reveal the vertical structure of an in-situ fabricated quasi-two-dimensional perovskite film. By combining time-of-flight secondary ion mass spectrometry, energy dispersive spectroscopy, grazing incidence wide-angle X-ray scattering (GIWAXS), and low-temperature photoluminescence spectra, we illustrate that the resulting in-situ fabricated DPPA2Csn-1Pbn(Br0.3I0.7)3n+1 (DPPA+: 3,3-diphenylpropylammonium) film has a gradient structure with a very thin layer of ligands on the surface, predominantly small-n domains at the top, and predominantly large-n domains at the bottom owing to the solubility difference of the precursors. In addition, GIWAXS measurements show that the domain of n = 2 on the top layer has an ordered in-plane alignment. Based on the understanding of the film structure, we developed an in-situ fabrication process with ligand exchange to achieve efficient pure red PeLEDs at 638 nm with an average external quantum efficiency (EQE) of 7.4%. The optimized device had a maximum luminance of 623 cd/m2 with a peak EQE of 9.7%.

Abstract Background Thymus mongolicus (family Lamiaceae) is a Thyme subshrub with strong aroma and remarkable environmental adaptability. Limited genomic information limits the use of this plant. Results Chromosome-level 605.2 Mb genome of T. mongolicus was generated, with 96.28% anchored to 12 pseudochromosomes. The repetitive sequences were dominant, accounting for 70.98%, and 32,593 protein-coding genes were predicted. Synteny analysis revealed that Lamiaceae species generally underwent two rounds of whole genome duplication; moreover, species-specific genome duplication was identified. A recent LTR retrotransposon burst and tandem duplication might play important roles in the formation of the Thymus genome. Using comparative genomic analysis, phylogenetic tree of seven Lamiaceae species was constructed, which revealed that Thyme plants evolved recently in the family. Under the phylogenetic framework, we performed functional enrichment analysis of the genes on nodes that contained the most gene duplication events (> 50% support) and of relevant significant expanded gene families. These genes were highly associated with environmental adaptation and biosynthesis of secondary metabolites. Combined transcriptome and metabolome analyses revealed that Peroxidases, Hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferases, and 4-coumarate-CoA ligases genes were the essential regulators of the phenylpropanoid–flavonoid pathway. Their catalytic products (e.g., apigenin, naringenin chalcone, and several apigenin-related compounds) might be responsible for the environmental tolerance and aromatic properties of T. mongolicus. Conclusion This study enhanced the understanding of the genomic evolution of T. mongolicus, enabling further exploration of its unique traits and applications, and contributed to the understanding of Lamiaceae genomics and evolutionary biology.

Abstract IgG4-related disease (IgG4-RD) has complex clinical manifestations ranging from fibrosis and inflammation to deregulated metabolism. The molecular mechanisms underpinning these phenotypes are unclear. In this study, by using IgG4-RD patient peripheral blood mononuclear cells (PBMCs), IgG4-RD cell lines and Usp25 knockout mice, we show that ubiquitin-specific protease 25 (USP25) engages in multiple pathways to regulate fibrotic and inflammatory pathways that are characteristic to IgG4-RD. Reduced USP25 expression in IgG4-RD leads to increased SMAD3 activation, which contributes to fibrosis and induces inflammation through the IL-1β inflammatory axis. Mechanistically, USP25 prevents ubiquitination of RAC1, thus, downregulation of USP25 leads to ubiquitination and degradation of RAC1. Decreased RAC1 levels result in reduced aldolase A release from the actin cytoskeleton, which then lowers glycolysis. The expression of LYN, a component of the B cell receptor signalosome is also reduced in USP25-deficient B cells, which might result in B cell activation deficiency. Altogether, our results indicate a potential anti-inflammatory and anti-fibrotic role for USP25 and make USP25 a promising diagnostic marker and potential therapeutic target in IgG4-RD.

Abstract. Background:. Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA. Methods:. The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4+) T-cell counts, CD8+ T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. Results:. The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6–6.5 copies/reaction) with linearity over a 5-log10-unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8–16.6 copies/reaction) with linearity over a 3-log10-unit range. Total HIV DNA in CD4+ T cells was positively associated with integrated HIV DNA (r = 0.76, P

[Objective] The structural reliability of the transmission shaft of guideway rubber-tyred train is crucial to the safety of train operation. During the ice and snow test on a certain urban rail transit line, the guideway rubber-tyred train failed several times resulting from the fracture of the transmission shaft. Therefore, it is necessary to analyze the fracture causes of the transmission shaft and optimize its design. [Method] The causes of the fracture of the transmission shaft are analyzed from two aspects: macroscopic detection of the failure shaft section, physical and chemical detection of the failure material. A wireless torque test system is used to test the real-time load of the transmission shaft between stations 5-6 and stations 5-7 on the line. The test results are analyzed, and the structure of the transmission shaft is optimized. The strength test on the optimized transmission shaft bench and the fatigue test on the optimized transmission shaft are carried out respectively. [Result & Conclusion] The causes of transmission shaft fracture are identified as the overload brittle fracture of cross shaft and fatigue fracture of double coupling bushing. The test results from the above two line sections show that all the maximum torques of the shaft occur when the vehicle is slipping. Though the actual torque of transmission shaft is less than the designed maximum working torque, the impact energy on the shaft is much larger than the torque change value under normal working conditions because the torque changes within a very short time. The measures that are taken to optimize the transmission shaft structure are as follows: increasing the shaft diameter of the cross shaft, increasing the chamfer angle of the cross shaft arc transition, and further reducing the stress concentration. The strength of the shaft shoulder of the double coupling bushing is increased by adding the reinforcing rib on it. The strength test on the optimized transmission shaft bench shows that it meets the design requirements and passes its fatigue test.

Abstract Recently, the development of natural polysaccharides for ameliorating immunity and gut metabolism has attracted extensive attention. This study used Holothuria leucospilota polysaccharides (HLP) to explore the improvement mechanism in ulcerative colitis rats on perspectives of immunity and metabolism. The results showed that HLP increased goblet cells’ number and the content of tight junction proteins (zona occludens 1 and occludin) and improved intestinal barrier permeability. The levels of immune cytokines (IL‐4, IL‐6, IL‐10, IL‐18, TNF‐α, and IL‐1β) and the activity of oxidative stress‐related enzymes (superoxide dismutase, catalase, malondialdehyde, and glutathione peroxidase) were regulated. HLP regulated the related genes and proteins expression of immune cytokines, MAPK, and NLRP3 inflammasome. Furthermore, HLP treatment increased the concentration of short‐chain fatty acids (SCFAs) and regulated serum metabolic disorders by regulating amino acid metabolism, SCFA metabolism, and energy metabolism. These results provide a new perspective for developing HLP as a promising functional food for preventing and mitigating colitis.

Abstract Background The presence of heterogeneity is a significant attribute within the context of ovarian cancer. This study aimed to assess the predictive accuracy of models utilizing quantitative 18F-FDG PET/CT derived inter-tumor heterogeneity metrics in determining progression-free survival (PFS) and overall survival (OS) in patients diagnosed with high-grade serous ovarian cancer (HGSOC). Additionally, the study investigated the potential correlation between model risk scores and the expression levels of p53 and Ki-67. Methods A total of 292 patients diagnosed with HGSOC were retrospectively enrolled at Shengjing Hospital of China Medical University (median age: 54 ± 9.4 years). Quantitative inter-tumor heterogeneity metrics were calculated based on conventional measurements and texture features of primary and metastatic lesions in 18F-FDG PET/CT. Conventional models, heterogeneity models, and integrated models were then constructed to predict PFS and OS. Spearman’s correlation coefficient (ρ) was used to evaluate the correlation between immunohistochemical scores of p53 and Ki-67 and model risk scores. Results The C-indices of the integrated models were the highest for both PFS and OS models. The C-indices of the training set and testing set of the integrated PFS model were 0.898 (95% confidence interval [CI]: 0.881–0.914) and 0.891 (95% CI: 0.860–0.921), respectively. For the integrated OS model, the C-indices of the training set and testing set were 0.894 (95% CI: 0.871–0.917) and 0.905 (95% CI: 0.873–0.936), respectively. The integrated PFS model showed the strongest correlation with the expression levels of p53 (ρ = 0.859, p

Abstract Background and objective The effectiveness of immunosuppressive and corticosteroid treatments for Immunoglobulin A (IgA) nephropathy (IgAN) remains thoroughly evaluated. We undertook a meta-analysis to investigate the efficacy and safety of low-dose corticosteroids plus leflunomide for progressive IgA nephropathy. Methods Eligible studies were obtained from PubMed, Embase, and Cochrane Library databases. We also searched the references of the included studies. Our protocol followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Eligibility criteria were defined using a PICOS framework. Results Our study included three articles presenting 342 patient cases. Findings revealed that low-dose corticosteroids combined with the leflunomide group were effective in relieving urine protein excretion (UPE) [mean difference (MD) = -0.35, 95% confidence interval (CI): -0.41 to -0.30, P 0.05). Regarding safety, low-dose corticosteroids combined with leflunomide significantly reduced the risk of serious adverse events [odds ratio (OR): 0.11, 95% CI: 0.01 to 0.91, P = 0.04]. Besides, no significant differences were observed between the two groups in the incidence of respiratory infection, abnormal liver function, diarrhea, herpes zoster, alopecia, pruritus, insomnia, pneumonia, diabetes, and urinary tract infection (P > 0.05). Conclusions Low-dose corticosteroids combined with leflunomide are a safe and effective treatment for progressive IgA nephropathy. Trial registration The PROSPERO registration number is CRD42022361883.

For the first time, the underwater wet wire and arc directed energy deposition (UW-WADED) multi-tracks deposition layers with favorable morphology were obtained. The forming characteristics of single-track UW-WADED were determined through response surface methodology. It was found that the power function curve provided the best fit for the profile of single-track UW-WADED owing to its changing plumpness value. Subsequently, the formation characteristics of multi-track UW-WADED with varying intervals were investigated. The deposition layer exhibited the flattest surface and the least root-mean-square deviation, measuring 321.79 μm when the interval was 8 mm. The dynamic process of UW-WADED was unveiled through X-ray high-speed images, leading to the formulation of UW-WADED droplet force model. As the arc bubble expanded, the horizontal component of the air drag force pointed to the opposite side of the molten pool and was the principal factor for the droplets to become spatters in UW-WADED. The mechanism of the defect formation was also revealed. The accumulation of the molten pool on the previous deposition layer coupled with the downflow of the molten slag were the inducers of slag inclusion defect while the exorbitant molten pool increased the likelihood of molten pool explosion and subsequent spatter formation.

Abstract Subthalamic nucleus deep brain stimulation (STN-DBS) has the potential to delay Parkinson’s disease (PD) progression. Whether oxidative stress participates in the neuroprotective effects of DBS and related signaling pathways remains unknown. To address this, we applied STN-DBS to mice and monkey models of PD and collected brain tissue to evaluate mitophagy, oxidative stress, and related pathway. To confirm findings in animal experiments, a cohort of PD patients was recruited and oxidative stress was evaluated in cerebrospinal fluid. When PD mice received STN stimulation, the mTOR pathway was suppressed, accompanied by elevated LC3 II expression, increased mitophagosomes, and a decrease in p62 expression. The increase in mitophagy and balance of mitochondrial fission/fusion dynamics in the substantia nigra caused a marked enhancement of the antioxidant enzymes superoxide dismutase and glutathione levels. Subsequently, fewer mitochondrial apoptogenic factors were released to the cytoplasm, which resulted in a suppression of caspase activation and reservation of dopaminergic neurons. While interfaced with an mTOR activator, oxidative stress was no longer regulated by STN-DBS, with no neuroprotective effect. Similar results to those found in the rodent experiments were obtained in monkeys treated with chronic STN stimulation. Moreover, antioxidant enzymes in PD patients were increased after the operation, however, there was no relation between changes in antioxidant enzymes and motor impairment. Collectively, our study found that STN-DBS was able to increase mitophagy via an mTOR-dependent pathway, and oxidative stress was suppressed due to removal of damaged mitochondria, which was attributed to the dopaminergic neuroprotection of STN-DBS in PD.

Abstract The micro-scale gas adsorption–desorption characteristics determine the macro-scale gas transport and production behavior. To reveal the three-dimensional stress state-induced gas adsorption–desorption characteristics in coal-bearing shale reservoirs from a micro-scale perspective, the coal-bearing shale samples from the Dongbaowei Coal Mine in the Shuangyashan Basin were chosen as the research subject. Isothermal adsorption–desorption experiments under three-dimensional stress state were conducted using the low field nuclear magnetic resonance (L-NMR) T 2 spectrum method to simulate the in-situ coal-bearing shale gas adsorption–desorption process. The average effective stress was used as the equivalent stress indicator for coal-bearing shale, and the integral of nuclear magnetic resonance T 2 spectrum amplitude was employed as the gas characterization indicator for coal-bearing shale. A quantitative analysis was performed to examine the relationship between gas adsorption in coal-bearing shale and the average effective stress. And a quantitative analysis was performed to examine the relationship between the macroscopic and microscopic gas quantities of coal-bearing shale. Experimental findings: (1) The adsorption–desorption process of coal-bearing shale gas follows the L-F function model and the D-A-d function model respectively with respect to the amount of gas and the average effective stress. (2) There is a logarithmic relationship between the macroscopic and microscopic gas quantities of coal-bearing shale during the adsorption–desorption process. This quantitatively characterizes the differences in the curves, which may be related to the elastic–plastic deformation, damage and fracture of the micropores in coal-bearing shale, as well as the hysteresis of gas desorption and the stress field of the gas occurrence state.

Abstract Next generation sequencing (NGS) is typically used to reveal tumor gene variation feature for targeted therapy of various types of human cancers, including non-small cell lung cancer (NSCLC). Here, we report the role and potential applicable value of combining DNA and RNA sequencing in gene variation detection in NSCLC. 386 NSCLC patients with stage II-IV were enrolled and detected using NGS sequencing of DNA and RNA panels that covered all well-documented target driver genes from the Chinese Society of Clinical Oncology (CSCO). The rate of epidermal growth factor receptor (EGFR) single nucleotide variation (SNV)/indel, mesenchymal-epithelial transition factor (MET) copy number variation (CNV) and anaplastic lymphoma kinase (ALK) fusion were 52.1%, 4.1% and 6.0% in the NSCLC cohort. The landscapes of SNV/indel, CNV and gene fusion in the cohort were depicted as well. Meanwhile, we assessed detection efficacy of DNA and RNA sequencing in gene fusion. Detected number and types of gene fusion using the RNA sequencing were better than those using the DNA sequencing. Gene fusion with intergenic region was only detected by DNA sequencing and MET exon 14 skipping (METΔex14) was more easily identified by RNA sequencing. Finally, we investigated clinical correlations of SNV/indel/CNV/fusion with clinicopathologic features in the NSCLC cohort. Taken together, RNA sequencing significantly complements deficiency of DNA sequencing for gene fusion, which cooperatively presents comprehensive and reliable gene variation features and facilitate the identification of potential drug targets for NSCLC patients.

Abstract Diabetic foot ulcer (DFU), a serious complication of diabetes, remains a clinical challenge. MicroRNAs affect inflammation and may have therapeutic value in DFU. Here, we find that an miR-221-3p mimic reduces the inflammatory response and increases skin wound healing rates in a mouse model of diabetes, whereas miR-221-3p knockout produced the opposite result. In human keratinocytes cells, miR-221-3p suppresses the inflammatory response induced by high glucose. The gene encoding DYRK1A is a target of miR-221-3p. High glucose increases the expression of DYRK1A, but silencing DYRK1A expression decreases high glucose–induced inflammatory cytokine release via dephosphorylation of STAT3, a substrate of DYRK1A. Application of miR-221-3p mimic to human keratinocytes cells not only decreases DYRK1A expression but also inhibits high glucose–induced production of inflammatory cytokines to promote wound healing. This molecular mechanism whereby miR-221-3p regulates inflammation through the DYRK1A/STAT3 signaling pathway suggests targets and therapeutic approaches for treating DFU.

Sacrificial metallic coatings are an effective strategy for mitigating corrosion in steel operating in industrial environments. This review article focuses on examining the protection mechanism of zinc-aluminum-magnesium (Zn-Al-Mg) coatings on steel substrates. Specifically, it investigates the effects of various elements and their corrosion products on the corrosion resistance of Zn-Al-Mg coatings. Furthermore, this review summarizes the formation mechanisms of various specialized corrosion modes that occur following the corrosion of Zn-Al-Mg coatings, based on previous experimental findings. It also includes suggestions for further research areas that could contribute to the development of highly corrosion-resistant and long-lasting coatings. These suggestions are based on published laboratory and field test results available in literature.

Abstract Background Approximately 30% of post-operative breast cancer patients develop shoulder joint movement disorders affecting routine upper limb movement. This study discusses the impact of a neuromuscular joint facilitation (NJF) method on the physical function of breast cancer patients experiencing shoulder dysfunction during chemotherapy after radical surgery. Methods This study included 162 female patients who have unilateral breast cancer in a cancer hospital in China. They developed shoulder joint mobility disorders during chemotherapy within 1–3 months postoperatively. These patients were divided into three groups: NJF, conventional rehabilitation (conventional group), and control groups. The clinical examination included the maximum passive and active range of motion (ROM) of the shoulder (flexion, extension, abduction, adduction, and external and internal rotation). Other evaluations included a pain score using a visual analog scale (VAS), grip strength, and supraspinatus muscle thickness. All tests were evaluated pre-and post-intervention. Results The NJF group showed a significant increase in all shoulder ROM angles post-intervention. In the conventional group, all other ROM values increased significantly, except passive external rotation ROM. In the control group, all other ROM values increased significantly, except passive and active external rotation ROM. All three groups had decreased VAS scores, increased grip strength, and supraspinatus muscle thickness post-intervention during active abduction. In the control group, the supraspinatus contraction rate decreased significantly at 60° and 90° abduction post-intervention compared to that at pre-intervention. Conclusion This study revealed that NJF during chemotherapy had positive clinical intervention effects, improving shoulder joint mobility disorders, pain, grip strength, and external rotation following radical breast cancer surgery. Clinical trial registration Chinese Clinical Trial Registry; https://www.chictr.org.cn/ (ChiCTR2300073170), registered (03/07/2023).

ABSTRACT Aims This research aimed to investigate the specific mechanism of methyltransferase like 3 (METTL3) in the progression of diabetic kidney disease (DKD). Materials and Methods The model of diabetic kidney disease was established with HK‐2 cells and mice in vitro and in vivo. The N6 methyladenosine (m6A) contents in the cells and tissues were detected with a commercial kit and the m6A levels of PTEN induced putative kinase 1 (PINK2) were detected with a MeRIP kit. The mRNA and protein levels were determined with RT‐qPCR and western blot. The ROS, TNF‐α, and IL‐6 levels were assessed with ELISA. The cell proliferative ability was measured by a CCK‐8 assay and cell apoptosis was determined with TUNEL staining. The HE and Masson staining was performed to observe the renal morphology. The RIP assay was conducted to detect the interaction between METTL3/YTHDF2 and PINK1. Results The m6A content and METTL3 levels were prominently elevated in diabetic kidney disease. METTL3 silencing promoted the cell growth and the expression of LC3 II, PINK1, and Parkin, while inhibiting the cell apoptosis and the expression of LC3 I and p62 in the high glucose (HG) stimulated HK‐2 cells. METTL3 silencing also decreased the ROS, TNF‐α, and IL‐6 levels in diabetic kidney disease. PINK1 silencing neutralized the function of sh‐METTL3 in the HG stimulated HK‐2 cells. The HE and Masson staining showed that METTL3 silencing alleviated the kidney injury induced by DKD. METTL3 silencing decreased the m6A levels of PINK1, while increased the mRNA levels of PINK1 which depended on YTHDF2. Conclusions METTL3 silencing could inhibit the progression of diabetic nephropathy in vivo and in vitro by regulating the m6A modification of PINK1, which depends on YTHDF2. Our research lays the theoretical foundation for the precise treatment of diabetic kidney disease and the development of targeted drugs in the future.

Rapidly increasing urbanization in recent decades has elevated the subway as the primary public transportation mode in metropolitan areas. Indoor air quality (IAQ) inside subways is an important factor that influences the health of commuters and subway workers. This review discusses the subway IAQ in different cities worldwide by comparing the sources and abundance of particulate matter (PM2.5 and PM10) in these environments. Factors that affect PM concentration and chemical composition were found to be associated with the subway internal structure, train frequency, passenger volume, and geographical location. Special attention was paid to air pollutants, such as transition metals, volatile/semi-volatile organic compounds (VOCs and SVOCs), and bioaerosols, due to their potential roles in indoor chemistry and causing adverse health impacts. In addition, given that the IAQ of subway systems is a public health issue worldwide, we calculated the Gini coefficient of urban subway exposure via meta-analysis. A value of 0.56 showed a significant inequity among different cities. Developed regions with higher per capita income tend to have higher exposure. By reviewing the current advances and challenges in subway IAQ with a focus on indoor chemistry and health impacts, future research is proposed toward a sustainable urban transportation systems.

Purpose Research on bone metastasis in esophageal cancer (EC) is relatively limited. Once bone metastasis occurs in patients, their prognosis is poor, and it severely affects their quality of life. Currently, there is a lack of convenient tumor markers for early identification of bone metastasis in EC. Our research aims to explore whether neutrophil-lymphocyte ratio (NLR) can predict bone metastasis in patients with EC. Methods Retrospective analysis of clinical indicators was performed on 604 patients with EC. They were divided into groups based on whether or not there was bone metastasis, and the patients’ coagulation-related tests, blood routine, tumor markers and other indicators were collected. The receiver operating characteristic curve (ROC) were used to determine the predictive ability of parameters such as NLR for bone metastasis in EC, and univariate and multivariate logistic regression analyses were conducted to determine the impact of each indicator on bone metastasis. Using binary logistic regression to obtain the predictive probability of NLR combined with tumor markers. Results ROC curves analysis suggested that the area under the curve (AUC) of the NLR was 0.681, with a sensitivity of 79.2% and a specificity of 52.6%, which can be used as a predictive factor for bone metastasis in EC. Multivariate logistic regression analysis showed that high NLR (odds ratio [OR]: 2.608, 95% confidence interval [CI]: 1.395-4.874, P = 0.003) can function as an independent risk factor for bone metastasis in patients with EC. Additionally, high PT, high APTT, high FDP, high CEA, high CA724, low hemoglobin, and low platelet levels can also predict bone metastasis in EC. When NLR was combined with tumor markers, the area under the curve was 0.760 (95% CI: 0.713-0.807, P

BackgroundCerebral syphilitic gumma is a rare intracranial infectious disorder. Without a clear history of syphilis and comprehensive serological examinations, it’s challenging to diagnose it accurately prior to surgery through routine magnetic resonance imaging (MRI). Advanced neuroimaging techniques have been widely used in diagnosing brain tumors, yet there’s limited report on their application in cerebral syphilitic gumma. This report presents a case of an elderly male patient with cerebral syphilitic gumma and analyzes its characteristics of advanced neuroimaging.Case presentationA 68-year-old male patient was admitted to our institution presenting with bilateral hearing loss complicated with continuing headaches without obvious cause. Laboratory tests indicated positive treponema pallidum. Conventional MRI showed nodules closely related to the adjacent meninges in bilateral temporal lobes. The patient underwent surgical resection of the nodule in the right temporal lobe due to the mass effect and the final pathological diagnosis revealed cerebral syphilitic gumma.ConclusionsWith the return of syphilis in recent years, accurate diagnosis of cerebral syphilitic gumma is a matter of great urgency. Advanced neuro-MRI can serve as a significant complement to conventional MRI examination.

ObjectiveMeige syndrome (MS) is an adult-onset segmental dystonia for which no satisfactory remedy currently exists. Our team developed a novel surgical approach called bilateral trigeminal/facial nerve combing (BTFC). This study aimed to evaluate the outcomes of patients who underwent BFTC (Clinical Trial Registry Number: ChiCTR2000033481).MethodWe assigned 22 patients with MS to undergo BTFC. The primary outcome was assessed using the movement subscale of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-M) at 12 months postoperatively. The second outcome was evaluated using the Medical Outcome Study (MOS) 36-item Short Form Health Survey (SF-36), the dysfunction subscale of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-D), and the sub-item scores of the BFMDRS-M. Safety outcomes included the House-Brackmann (HB) functional grading score and the visual analog scale (VAS) for facial numbness.ResultsAt the final follow-up at 12 months, the BFMDRS-M showed a mean improvement of 70.7% from baseline. Mean scores of the BFMDRS-M sub-motor (including the eyes, mouth, and speech/swallowing) improved by 65.6, 81.00, and 60%, respectively. The median score of the total BFMDRS-D score was 0.70 ± 1.17 compared with 1.86 ± 2.21 at baseline. There were no serious operative complications in this population. The quality of life of the patients significantly improved (P < 0.05).ConclusionBFTC has proven to be effective in relieving the symptoms of Meige syndrome. This novel surgical approach offers a new alternative treatment for patients who have failed to respond to medications, botulinum toxin injections, and deep brain stimulation (DBS).Clinical Trial Registrationhttps://www.chictr.org.cn/bin/project/edit?pid=54567, ChiCTR2000033481.

As a chemotherapy agent, doxorubicin is used to combat cancer. However, cardiotoxicity has limited its use. The existing strategies fail to eliminate doxorubicin-induced cardiotoxicity, and an in-depth exploration of its pathogenesis is in urgent need to address the issue. Endoplasmic reticulum stress (ERS) occurs when Endoplasmic Reticulum (ER) dysfunction results in the accumulation of unfolded or misfolded proteins. Adaptive ERS helps regulate protein synthesis to maintain cellular homeostasis, while prolonged ERS stimulation may induce cell apoptosis, leading to dysfunction and damage to tissue and organs. Numerous studies on doxorubicin-induced cardiotoxicity strongly link excessive activation of the ERS to mechanisms including oxidative stress, calcium imbalance, autophagy, ubiquitination, and apoptosis. The researchers also found several clinical drugs, chemical compounds, phytochemicals, and miRNAs inhibited doxorubicin-induced cardiotoxicity by targeting ERS. The present review aims to outline the interactions between ERS and other mechanisms in doxorubicin-induced cardiotoxicity and summarize ERS’s role in this type of cardiotoxicity. Additionally, the review enumerates several clinical drugs, phytochemicals, chemical compounds, and miRNAs targeting ERS for considering therapeutic regimens that address doxorubicin-induced cardiotoxicity.

Estimations of the patterns and controls of soil organic carbon (SOC) could provide instructive insights into the potential impact of future global change on soil carbon (C). In this work, we combined GeoDetector and random forest (RF) to estimate SOC stocks in Chinese grassland ecosystems with uncertainty assessments, and identified a network of cross-correlated environmental covariates for determining SOC based on a dataset collected from 813 sampling sites (0–20 cm) collected from 2000 to 2014. We predicted that 17.50 Pg C was stored in Chinese grasslands to a depth of 20 cm and that the average SOC density was 4.69 kg C/m−2(−|−). The effectiveness of using RF to predict SOC was demonstrated by an accuracy assessment based on 10-fold cross-validation, with a ratio of performance to deviation (RPD) of 2.89. The SOC stocks in southern China were lower than those in northern China. A high SOC density was found in northeastern China and on the Qinghai–Tibet Plateau. Soil properties had the strongest direct effect on SOC. Climate was significantly negatively associated with SOC and indirectly affected SOC via its effect on soil properties. Topography had a significant direct impact on vegetation, but its direct effect on SOC was relatively weak. This study emphasizes the patterns and heterogeneity of SOC stocks as well as the relative significance of climate, vegetation, soil characteristics, topography, and their complex interrelationships in controlling SOC. These results may provide a theoretical foundation for developing sustainable management systems and calibrating C process models.

This study explores the mechanism by which obstructive jaundice (OJ) induces liver damage through pyroptosis. We induced OJ in rats via bile duct ligation and assessed liver damage using serum biochemical markers and histological analysis of liver tissue. Pyroptosis was investigated through immunofluorescence, ELISA, Western blot, and quantitative RT-PCR techniques. Additionally, we examined intestinal function and fecal microbiota alterations in the rats using 16S rDNA sequencing. In vitro experiments involved co-culturing Kupffer cells and hepatocytes, which were then exposed to bile and lipopolysaccharide (LPS). Our findings indicated that OJ modified the gut microbiota, increasing LPS levels, which, in conjunction with bile, initiated a cycle of inflammation, fibrosis, and cell death in the liver. Mechanistically, OJ elevated necrotic markers such as ATP, which in turn activated pyroptotic pathways. Increased levels of pyroptosis-related molecules, including NLRP3, caspase-1, gasdermin D, and IL-18, were confirmed. In our co-cultured cell model, bile exposure resulted in cell death and ATP release, leading to the activation of the NLRP3 inflammasome and its downstream effectors, caspase-1 and IL-18. The combination of bile and LPS significantly intensified pyroptotic responses. This study is the first to demonstrate that LPS and bile synergistically exacerbate liver injury by promoting necrosis and pyroptosis, unveiling a novel mechanism of OJ-associated hepatic damage and suggesting avenues for potential preventive or therapeutic interventions.

The diagnosis and treatment of bacterial infections in the medical and public health field in the 21st century remain significantly challenging. Artificial Intelligence (AI) has emerged as a powerful new tool in diagnosing and treating bacterial infections. AI is rapidly revolutionizing epidemiological studies of infectious diseases, providing effective early warning, prevention, and control of outbreaks. Machine learning models provide a highly flexible way to simulate and predict the complex mechanisms of pathogen-host interactions, which is crucial for a comprehensive understanding of the nature of diseases. Machine learning-based pathogen identification technology and antimicrobial drug susceptibility testing break through the limitations of traditional methods, significantly shorten the time from sample collection to the determination of result, and greatly improve the speed and accuracy of laboratory testing. In addition, AI technology application in treating bacterial infections, particularly in the research and development of drugs and vaccines, and the application of innovative therapies such as bacteriophage, provides new strategies for improving therapy and curbing bacterial resistance. Although AI has a broad application prospect in diagnosing and treating bacterial infections, significant challenges remain in data quality and quantity, model interpretability, clinical integration, and patient privacy protection. To overcome these challenges and, realize widespread application in clinical practice, interdisciplinary cooperation, technology innovation, and policy support are essential components of the joint efforts required. In summary, with continuous advancements and in-depth application of AI technology, AI will enable doctors to more effectivelyaddress the challenge of bacterial infection, promoting the development of medical practice toward precision, efficiency, and personalization; optimizing the best nursing and treatment plans for patients; and providing strong support for public health safety.