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Abstract The damnification of mitochondrion is often considered to be an important culprit of inflammatory bowel disease (IBD), however, there are fewer reports of mechanisms of mitochondria-mediated IBD treatment. Therefore, we first proposed to reboot mitochondrial energy metabolism to treat IBD by capturing the double-sided factor of ROS and creatine (Cr)-assisted energy adjustment. Herein, an oral Cr-modified selenium-based hyaluronic acid (HA) nanogel (HASe-Cr nanogel) was fabricated for treatment of IBD, through ROS elimination and energy metabolism upgradation. More concretely, due to IBD lesion-specific positive charge and the high expression of CD44, HASe-Cr nanogel exhibited dual targeted inflammatory bio-functions, and ROS-driven degradation properties in high-yield ROS levels in inflammation areas. As expected, multifunctional HASe-Cr nanogel could effectively ameliorate IBD-related symptoms, such as mitochondrial biological function restoration, inhibition of M1-like macrophage polarization, gut mucosal reconstruction, microbial ecological repair, etc., thus excellently treating IBD. Overall, the proposed strategy underlined that the great potentiality of HASe-Cr nanogel by restarting mitochondrial metabolic energy in colitis lesions, providing new a pavement of mitochondrion-mediated colitis treatment in clinical applications.

Abstract The metastasis or recurrence of rhabdomyosarcoma (RMS) is the primary cause of tumour-related deaths. Patients with high-risk RMS have poor prognosis with a 5-year overall survival rate of 20–30%. The lack of specific drug-targeted therapy and chemotherapy resistance are the main reasons for treatment failure. Drugs or molecular target inhibitors can induce the pyroptosis of tumour cells or increase their sensitivity to chemotherapy, making pyroptosis an effective strategy for antitumour therapies. Pyroptosis is mediated by gasdermin (GSDM) family members. Here, we found that the expression of NLRP3, caspase-1, caspase-3, GSDMD and GSDME in RMS was remarkably lower than that in skeletal muscle tissues. Nigericin and dactinomycin in RMS cells achieved their regulatory effect on pyroptosis through the NLRP3/caspase-1/GSDMD pathway and caspase-3/GSDME pathway, respectively. Necrosulfonamide reversed the pyroptosis-related changes induced by nigericin, and siGSDME converted the dactinomycin-induced pyroptosis into apoptosis. Additionally, GEFT inhibited the GSDMD and GSDME pyroptosis pathways, thereby promoting the progression and drug resistance of RMS. Mouse xenograft and tumour analysis confirmed that nigericin and dactinomycin can effectively improve the therapeutic effect of RMS by activating the pyroptosis pathway. To the best of our knowledge, this study was the first to focus on pyroptosis in RMS. Overall, our investigation demonstrated that nigericin and dactinomycin play therapeutic roles in tumours by promoting RMS cell pyroptosis. Interference with GEFT and drug combination can exert a great inhibitory effect on tumours.

Abstract Epithelial–mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells plays key roles in the pathogenesis of multiple vitreoretinal diseases, leading to profound and permanent vision loss. Circular RNAs (circRNAs) are widespread and functional endogenous RNAs that could regulate gene expression in eukaryotes. The functions of circRNAs in mediating EMT has been reported in several diseases. In the current study, we investigated the role of circRNA HIPK3 (circHIPK3) in EMT process of RPE cells (RPE-EMT). circHIPK3 is one abundant circRNA generated from the second exon of HIPK3 mRNA. We found that circHIPK3 expression was significantly increased in TGF-β1-induced RPE-EMT model. Silencing of circHIPK3 attenuated TGF-β1-induced RPE-EMT process, whereas forced expression of circHIPK3 could trigger EMT in RPE cells. Mechanistically, circHIPK3 regulates RPE-EMT process via sponging multiple microRNAs (miRNAs). This study provides novel insights into the mechanism of RPE-EMT. Targeting circHIPK3 might serve as a therapeutic strategy in RPE-EMT associated vitreoretinal diseases.

Abstract The present study was undertaken to investigate the therapeutic effect and underlying mechanisms of lumbrokinase (LK) on diabetic kidney disease (DKD). Kidney tissue samples from DKD patients and normal controls were collected from hospitals. The type 2 diabetic nephropathy model was induced in db/db mice. The mice were then randomly divided into a model group (DM group) and an LK group. db/m mice were used as the control group (Con group). After 12 weeks of treatment with LK (234 KU/kg/day), biochemical parameters were tested, and pathological changes in the kidney were observed under a light microscope. The epithelial-to-mesenchymal transition (EMT), mRNA m6A methylation proteins, and activated TGF-β1/Smad pathway components were assessed by western blot or immunofluorescence in DKD patients, model mice, and high glucose-stimulated HK-2 cells. We found that the m6A eraser METTL3 was expressed at low levels in DKD patients, model mice, and high glucose-stimulated HK-2 cells. METTL3 overexpression reversed the high glucose-induced activation of the TGF-β1/Smad pathway and EMT through snail in vitro. However, LK can restore the expression of the m6A-modifying enzyme METTL3 in vivo and in vitro, suppressed EMT, and alleviated renal interstitial fibrosis by downregulating snail. Overall, LK ameliorated renal fibrosis through the regulation of Snail via m6A RNA METTL3.

Abstract Colorectal cancer (CRC) development involves a series of molecular events that drive the progression from normal colorectal epithelium to adenoma and eventually to invasive carcinoma. While the involvement of extrachromosomal circular DNAs (ecDNAs) in cancer genome remodeling has been established, their specific roles in CRC formation remain unclear. Using Circle-Sequencing and whole transcriptomic sequencing, we comprehensively profile circular DNAs and transcriptomes in healthy individuals, colorectal adenoma, and CRC patients. Our delineate analyses characterize the key circular DNAs involved in oncogene expression through the normal-adenoma–carcinoma continuum and highlight that immune response-related pathways and cell cycle pathways, are the dominat events in CRC progression. Notably, chr8 ecDNA 64950741–114379093 exhibits robust up-regulation during CRC progression. Further validation in a new cohort of 50 CRC patients confirms the higher expression of chr8 ecDNA 64950741–114379093 and its strong correlation with poor prognosis. Thus, these findings provide unprecedented insights into the landscape of circular DNAs in CRC and highlights the potential of chr8 ecDNA 64950741–114379093 as a promising biomarker and therapeutic target for CRC management.

Abstract Understanding tumor cell heterogeneity and plasticity is crucial for overcoming drug resistance. Single-cell technologies enable analyzing cell states at a given condition, but catenating static cell snapshots to characterize dynamic drug responses remains challenging. Here, we propose scStateDynamics, an algorithm to infer tumor cell state dynamics and identify common drug effects by modeling single-cell level gene expression changes. Its reliability is validated on both simulated and lineage tracing data. Application to real tumor drug treatment datasets identifies more subtle cell subclusters with different drug responses beyond static transcriptome similarity and disentangles drug action mechanisms from the cell-level expression changes.

Abstract Background The interplay between infertility and intimate partner violence (IPV) is a pressing global health issue, yet qualitative evidence on this phenomenon is limited. In order to measure and prevent IPV, it is pivotal to explore and integrate perceptions and experiences from those women with infertility themselves on IPV definition and its phenomenal manifestations in the context of infertility. Methods This study is undertaken as part of a year-long ethnographic research based at a reproductive medicine center in Beijing, China from July 2022 to July 2023. Individual interviews with women attending ART outpatient clinics and with clinicians involved in infertility treatment were conducted. Grounded Theory methodology was used to guide data analysis, which entailed a three-step analytical approach. Results A total of 37 women and five clinicians were interviewed. Incomplete conceptualization of IPV and high mental stress among patients were evident. IPV against women with infertility has been shown to be a specific and severe form of IPV. The phenomenal manifestation of IPV in the context of infertility often takes the form of psychological abuse, including stonewalling, threats of divorce, and non-compliance with ART treatment. Conclusion The study revealed that the burden of fertility disproportionately falls on women, often intensified by the involvement of other family and cultural norms, exacerbating gender inequalities and IPV risks. Findings from this study calls for an immediate and comprehensive response in healthcare practice. IPV screening, health education, and structural interventions should be introduced to prevent and mitigate this issue.

Abstract Background Activation of pericytes leads to renal interstitial fibrosis, but the regulatory mechanism of pericytes in the progression from AKI to CKD remains poorly understood. CD36 activation plays a role in the progression of CKD. However, the significance of CD36 during AKI-CKD, especially in pericyte, remains to be fully defined. Methods GEO and DISCO database were used to analyze the expression of CD36 in pericyte during AKI-CKD; IRI to conduct AKI-CKD mouse model; Hypoxia/Reoxygenation (H/R) to induce the cell model; RT-qPCR and Western blotting to detect gene expression; IP and confocal-IF to determine the core fucosylation (CF) level of CD36. Flow cytometry (AV/PI staining) to detect the cell apoptosis and JC-1 staining to react to the change of mitochondrial membrane potential. Results During AKI to CKD progression, CD36 expression in pericytes is higher and may be influenced by CF. Moreover, we confirmed the positive association of CD36 expression with pericyte-myofibroblast transition and the progression of AKI-CKD in an IRI mouse model and hypoxia/reoxygenation (H/R) pericytes. Notably, we discovered that FUT8 upregulates both CD36 expression and its CF level, contributing to the activation of the mitochondrial-dependent apoptosis signaling pathway in pericytes, ultimately leading to the progression of AKI-CKD. Conclusion These results further identify FUT8 and CD36 as potential targets for the treatment in the progression of AKI-CKD.

Abstract Generally, invasive treatment is contraindication for patients with severe thrombocytopenia, because it may increase risk of bleeding. However, many early hepatocellular carcinoma (HCC) patients with cirrhosis have platelet counts (PC) less than 50 × 109/L due to hypersplenism. These patients are often accompanied by hepatic insufficiency, which makes hepatectomy impossible, and local thermal ablation (LTA) has become a major treatment. The aim of our study is to investigate the correlation between severe thrombocytopenia and bleeding after LTA in HCC patients with cirrhosis, and evaluate risk factors of bleeding. 473 patients with cirrhosis who underwent LTA for HCC from 2016 to 2020 were enrolled, and 709 ablations were performed in total. Based on preoperative PC, cases were divided into three groups, namely, group A (PC > 50 × 109/L), group B (30 × 109/L

Abstract The long-term health impacts of niacin are still debated, and the association between dietary niacin and mortality risk in populations hasn’t been extensively explored. This study included 26,746 US adults aged 20 years or older from the National Health and Nutrition Examination Survey 2003–2018, with a median follow-up of 9.17 years. During this period, there were 3,551 all-cause deaths, including 1,096 cardiovascular deaths. Cox models were used to compare hazard ratios (HRs) for mortality among participants grouped into different dietary niacin intake quartiles. Participants with the highest dietary niacin intake had a lower risk of all-cause mortality (HR 0.74, 95%CI 0.63–0.86) compared to those in the lowest intake quartile. For cardiovascular mortality, the HR was 0.73 (95%CI 0.57–0.95) in the highest niacin intake quartile. A dose-response relationship was revealed between dietary niacin intake and mortality by restricted cubic spline. Subgroup analysis showed a significant interaction between dietary niacin intake and diabetes concerning all-cause mortality (P = 0.046). In this population-based cohort study, higher dietary niacin intake correlates with lower risk of all-cause and cardiovascular mortality among US adults. The influence of niacin intake on all-cause mortality appears to be more significant in non-diabetic individuals compared to those with diabetes.

Abstract Background Patients with gastrointestinal cancer have a higher risk of malnutrition and postoperative infection. Objective To investigate the nutritional status of patients with gastrointestinal cancers and factors for postoperative infections. Method Based on the nutritional risk status, 294 patients with gastrointestinal tumours were divided into a nutritional risk group and a non-nutritional risk group, and the differences between the two groups were compared. Results Among the included patients, 128 were at preoperative nutritional risk (43.54%); there were significant differences between the two groups in terms of age (66.25 ± 11.73 vs. 58.36 ± 10.41 years, P 3, history of alcohol consumption and surgical time of > 6 h have a higher risk of postoperative infections.

Abstract LiNi x Co y Mn1-x-y O2 (0 < x, y

Abstract Crystalline silica (CS) particle exposure leads to silicosis which is characterized as progressive fibrosis. Fibroblasts are vital effector cells in fibrogenesis. Emerging studies have identified immune sentinel roles for fibroblasts in chronic disease, while their immune-modulatory roles in silicosis remain unclear. Herein, we show that group 2 innate lymphoid cell (ILC2) conversion to ILC1s is closely involved in silicosis progression, which is mediated by activated fibroblasts via interleukin (IL)−18. Mechanistically, Notch3 signaling in mechanics-activated fibroblasts modulates IL-18 production via caspase 1 activity. The mouse-specific Notch3 knockout in fibroblasts retards pulmonary fibrosis progression that is linked to attenuated ILC conversion. Our results indicate that activated fibroblasts in silicotic lungs are regulators of ILC2–ILC1 conversion, associated with silicosis progression via the Notch3–IL-18 signaling axis. This finding broadens our understanding of immune-modulatory mechanisms in silicosis, and indicates potential therapeutic targets for lung fibrotic diseases.

Objective: Distraction osteogenesis (DO) has been widely used to treat bone defects as its effectiveness in bone regeneration. Currently, distraction devices for establishing DO models are mainly developed for rats or large animals. However, a mouse DO model is in great need for in-depth mechanistic investigations using various transgenic mice. The current study reports the development of a reproducible murine DO model. Methods: A mini-titanium lengthener was designed and fabricated. The mini-lengthener was applied on the murine femur with four threaded pins using a designed clamp as the drilling and insertion guide. After transverse osteotomy using a Gigli saw, and after 5 days of latency, DO procedures started at 0.3 mm/day for 10 days, and the consolidation period was left for 28 days. The bone formation was monitored by radiography and histology. Potential effects on animal locomotion during DO were also measured by behavior tests. Results: Separated bone segments maintained good alignment during the entire DO phases. New bone formation was found as early as the end of the distraction phase. Active bone remodeling was found between the separated bone segments at late distraction and early consolidation phases. At the mature consolidation phase, bone remodeling was mainly observed in the contact cortical bone. Mice underwent DO procedure did not have significant impairment in their locomotion. Conclusion: We have successfully developed a murine femoral DO model, which may be used to study the biological processes of DO. We also developed the mini-lengthener and the guide clamp to ensure the standardization and reproducibility of the mouse DO model.The translational potential of this article: Current study reports the development of a murine femoral DO model. A well-established murine DO model will facilitate further investigations of the biological mechanisms of DO in various transgenic and normal mice.

In this paper, the directional modification behavior of rare earth Ce on sulfide inclusions in steel is studied by thermodynamic calculation and experiment methods, and the mechanism of directional modification of rare earth Ce on sulfide inclusions in U71Mn heavy rail steel is proved. The results show that U71Mn heavy rail steel contained more large-sized inclusions and their distribution is more concentrated without the addition of rare earth Ce element. After the addition of rare earth Ce element, the average size of sulfur-containing inclusions in the steel decrease from 5.22 μm to 1.85 μm, and the number density of sulfur-containing inclusions in the steel increase from 83.65 mm−2 to 217.68 mm−2, indicating that the number of sulfur-containing inclusions in the steel increases after the addition of Ce element, and more small-sized sulfur-containing inclusions will form in the steel. The addition of rare earth Ce element can effectively reduce the existence of large-sized inclusions in the steel and modify large-sized inclusions into small-sized inclusions.

Abstract Ceria (CeO2) is a widely used oxide catalyst, yet the nature of its active sites remains elusive. This study combines model and powder catalyst studies to elucidate the structure-activity relationships in ceria-catalyzed CO activation and hydrogenation. Well-defined ceria clusters are synthesized on planar CeO2(111) and exhibit dynamic and tunable ranges of Ce coordination numbers, which enhance their interaction with CO. Reduced ceria clusters (e.g., Ce3O3) bind CO strongly and facilitate its dissociation, while near-stoichiometric clusters (e.g., Ce3O7) adsorb CO weakly and promote oxidation via carbonate formation. Unlike planar ceria surfaces, supported ceria clusters exhibit dynamic properties and enhanced catalytic activity, that mimic those of powder ceria catalysts. Insight from model studies provide a method to quantify active sites on powder ceria and guide further optimization of ceria catalysts for syngas conversion. This work marks a leap toward model-guided catalyst design and highlights the importance of site-specific catalysis.

Abstract. Background:. Liver cancer remains the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide, causing a heavy burden globally. An updated assessment of the global epidemiology of the liver cancer burden that addresses geographical disparities is necessary to better understand and promote healthcare delivery. Methods:. Data were extracted from the GLOBOCAN 2022 database, including the number, crude, and age-standardized rates of incidence and mortality at the global, country, continent, and human development index (HDI) regional levels. Age-standardized rates (incidence and mortality) per 100,000 person-years were adjusted based on the Segi-Doll World standard population. The mortality-to-incidence ratios (MIR) for each region and country were calculated. The HDI and gross national income (GNI) for 2022 were obtained, and a Pearson correlation analysis was conducted with the incidence, mortality, and MIR. Results:. In 2022, approximately 866,136 new liver cancer cases and 758,725 related deaths were recorded worldwide, with a global MIR of 0.86. Males had a disproportionately higher burden than females across all levels, and the highest burden was observed in the elderly population. Geographically, the regions with the highest incidence rates included Micronesia, Eastern Asia, and Northern Africa, and the regions with the highest mortality rates included Northern Africa, Southeastern Asia, Eastern Asia, and Micronesia. Notably, Mongolia had a strikingly high burden compared to other countries. The highest MIR was observed in North America and the lowest in Africa. Negative associations of HDI and GNI with liver cancer mortality and MIR were identified, irrespective of sex. Conclusions:. The current liver cancer burden underscores the presence of remarkable geographic heterogeneity, which is particularly evident across countries with varying HDI levels, highlighting the urgent need to prioritize health accessibility and availability to achieve health inequities.

Abstract Background The evaluation of lateral ankle laxity remains challenging when diagnosing chronic lateral ankle instability (CLAI). Several studies have reported that internal rotation of the talus as an indicator of rotational lateral ankle laxity (RLAL) increases in patients with CLAI. However, there is no established method for detecting and evaluating the RLAL. This study aimed to report a novel method for evaluating the RLAL in the gravity stress position by measuring the talofibular distance (TFD) using ultrasonography (US) and show the normative value of the TFD. Methods The TFDs in the subjects with healthy ankles were prospectively measured 10 mm distal to the ankle joint in the neutral ankle position and gravity stress position using US. The differences in the TFD between the two ankle positions were evaluated. The differences in the TFD by gender and ankle laterality were also evaluated. Results A total of 52 healthy ankles of 28 subjects (mean age, 24.0 ± 1.6; male/female, 12/16) were finally included. There was a significant difference in the TFD between the neutral ankle position (6.9 ± 0.9 mm) and gravity stress position (9.0 ± 0.9 mm) (p

Abstract UBE2C, a ubiquitin-conjugating enzyme, functions as an oncogene in different types of human cancers. Nonetheless, the exact influence of UBE2C on the development of HCC via regulation of ubiquitination remains uncertain. Here, we found that UBE2C displayed elevated levels of expression in HCC and was associated with an unfavorable prognosis, as evidenced by the analysis of the TCGA database and the examination of clinical specimens. The role of UBE2C in HCC revealed its ability to promote the growth and metastasis of HCC. Mechanistically, UBE2C activated Notch signaling, as evidenced by the upregulation of N1ICD and Hes1, crucial components of the Notch pathway, and activation of the RBP-JK luciferase reporter by UBE2C. Finally, rescue experiments demonstrated that the oncogenic role of UBE2C was eliminated through treatment with the Notch inhibitor DAPT, while overexpression of N1ICD alleviated the anticarcinogenic impact of knockdown of UBE2C. Altogether, the results of our study indicate that UBE2C plays a role in the activation of Notch signaling and could potentially serve as a viable target for therapeutic interventions in HCC.

Abstract Addressing the imbalance between exploration and exploitation, slow convergence, local optima Traps, and low convergence precision in the Northern Goshawk Optimizer (NGO): Introducing a Multi-Strategy Integrated Northern Goshawk Optimizer (MINGO). In response to challenges faced by the Northern Goshawk Optimizer (NGO), including issues like the imbalance between exploration and exploitation, slow convergence, susceptibility to local optima, and low convergence precision, this paper introduces an enhanced variant known as the Multi-Strategy Integrated Northern Goshawk Optimizer (MINGO). The algorithm tackles the balance between exploration and exploitation by improving exploration strategies and development approaches. It incorporates Levy flight strategies to preserve population diversity and enhance convergence precision. Additionally, to avoid getting trapped in local optima, the algorithm introduces Cauchy mutation strategies, improving its capability to escape local optima during the search process. Finally, individuals with poor fitness are eliminated using the crossover strategy of the Differential Evolution algorithm to enhance the overall population quality. To assess the performance of MINGO, this paper conducts an analysis from four perspectives: population diversity, balance between exploration and exploitation, convergence behavior, and various strategy variants. Furthermore, MINGO undergoes testing on the CEC-2017 and CEC-2022 benchmark problems. The test results, along with the Wilcoxon rank-sum test results, demonstrate that MINGO outperforms NGO and other advanced optimization algorithms in terms of overall performance. Finally, the applicability and superiority of MINGO are further validated on six real-world engineering problems and a 3D Trajectory planning for UAVs.

Abstract Background Pitt–Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder that results from variants of TCF4 gene. PTHS follows an autosomal dominant inheritance pattern and the underlying pathological mechanisms of this disease are still unclear. Methods Whole-genome sequencing (WGS) was conducted to screen for potential pathogenic variant in a boy highly suspected of having a genetic disorder. PCR and Sanger sequencing were used to verify the effects of the variant. Serum TCF4 levels were measured by ELISA. Results We present a 4-year and 3-month-old Chinese boy clinically and molecularly diagnosed with PTHS. The proband experienced global development delay, and the preliminary clinical diagnosis was cerebral palsy. WGS identified a de novo heterozygous variant: c.*1A > G in the 3’UTR of the TCF4 gene as a potential cause of his condition. The variant was verified to cause aberrant mRNA splicing by PCR and the aberrant splicing was confirmed by Sanger sequencing. Conclusion The study identified and demonstrated the pathogenicity of a novel 3’UTR site TCF4 variant for the first time. This research enhances understanding of pathogenetic mechanisms of PTHS and aids genetic counseling and diagnosis.

Abstract Background At present, the relationship between the Triglyceride-glucose index (TyG index) and Acute kidney injury (AKI) in traumatic brain injury patients in the Intensive Care Unit (ICU) is still unclear. Currently, the relationship between TyG index and AKI occurred within 7 days in the ICU is a highly researched and trending topic. Objective In this study, we conducted in-depth exploration of the relationship between the development of AKI in traumatic brain injury (TBI) patients in the ICU and changes in TyG index, as well as its relevance. Methods A cross-sectional study was conducted with a total of 492 individuals enrolled in the Medical Information Mart for Intensive Care IV(MIMIC-IV) database. Multivariate model logistic regression, smoothed curve fitting and forest plots were utilized to confirm the study objectives. The predictive power of the TyG index for outcome indicators was assessed using subject work characteristics (ROC) curves. As well as comparing the Integrated Discriminant Improvement Index and the Net Reclassification Index of the traditional forecasting model with the addition of the TyG index. Results Of all eligible subjects, 55.9% were male and the incidence of AKI was 59.3%. There was a statistically significant difference in the incidence of AKI within 7 days in the ICU between the different TyG index groups. The difference between TyG index and the risk of AKI within 7 days in the ICU remained significant after adjustment for logistic multifactorial modeling (OR = 2.07, 95% CI = 1.41–3.05, P

Abstract Simplified rapid hydration has been proven to be non-inferior to standard hydration in preventing contrast-associated acute kidney injury among chronic kidney disease patients undergoing coronary angiography. The current investigation aimed to further confirm the feasibility and safety of the newly proposed hydration method-simplified rapid hydration (SH) in each risk stratification by Mehran risk score (MRS). Eligible patients (n = 954) randomized to the SH group and standard hydration group were allocated into 2 groups based on MRS: low to moderate-risk and high to very high-risk groups. Primary endpoints were the incidence of contrast-associated acute kidney injury (CA-AKI) and acute heart failure (AHF) (SH vs standard hydration). Secondary endpoints included serum creatinine (Scr), blood urea nitrogen (BUN), cystatin-C (Cys-C), and C-reactive protein (CRP) at 24 h, 48 h, and 72 h after PCI procedure, and the incidence of major adverse cardiac events (MACE). MRS was associated with a higher incidence of CA-AKI (OR = 1.101, 95%CI 1.049–1.156, P

The Carboniferous strata in the northeastern Junggar Basin are an important exploration field for natural gas in the basin. However, volcanic rocks have long been the primary exploration target. In contrast, the exploration and research of clastic rocks associated with source formations have been largely overlooked, resulting in an insufficient understanding of the reservoir forming conditions and exploration potential of Carboniferous clastic rocks. Through the evaluation of Carboniferous source rocks, effective source stove characterization, clastic reservoir evaluation, oil and gas source correlation, and reservoir formation model construction in this region, three key findings have been made. First, the Carboniferous in the northeastern Junggar Basin has developed three sets of high-quality gas source rocks: the Dishuiquan Formation, the Songkalsu B Member, and the Shiqiantan Formation. These formations correspond to three hydrocarbon source centers: the Sannan–Dishuiquan Sag, the Wucaiwan Sag–Dajing area, and the Dongdao Haizi Sag–Baijiahai High. Second, the Carboniferous system in the northeast has developed multiple types of large-scale reservoirs, including sand conglomerates, sandstones, turbidites, dolomitic rocks, and shale. These reservoirs are generally characterized by low porosity to ultra-low porosity and low permeability to ultra-low permeability reservoirs. There is a dissolution pore development zone at depths of 2900–4500 m. Third, a comparison of oil and gas sources reveals that all three sets of gas source rocks contribute to the natural gas found in the northeast, with obvious characteristics of near-source reservoir formation. The Carboniferous clastic rocks host two types of natural gas reservoirs: unconventional and conventional near-source reservoirs. It is predicted that there is an orderly accumulation pattern of shale gas, tight sandstone gas, and conventional natural gas reservoirs. This study reveals that the Carboniferous clastic rock source and reservoir configuration in the northeastern Junggar Basin is highly favorable, and the natural gas reservoirs in source and near-source clastic rocks represent important exploration directions.

Abstract The poor corrosion resistance of magnesium limits its clinical applications. Accordingly, in the present study, carbon ions were incorporated into a AZ31b magnesium alloy surface via carbon plasma immersion ion-implantation to improve its corrosion resistance and biocompatibility. The surface morphology and properties of the modified alloy were evaluated by field-emission scanning electron microscopy, water contact angle measurement, Raman scattering, X-ray photoelectron spectroscopy, and energy dispersive X-ray spectroscopy. Furthermore, compositional depth profiles were obtained by glow discharge optical emission spectroscopy, revealing a Gaussian-like distribution of carbon concentration. Electrochemical and hydrogen-evolution analysis demonstrated the successfully improved corrosion resistance of the AZ31b Mg alloy, while its biocompatibility was demonstrated by MTT and cell-adherence assays.

Abstract The three-stranded DNA-RNA triplex hybridization is involved in various biological processes, including gene expression regulation, DNA repair, and chromosomal stability. However, the DNA-RNA triplex mediating mechanisms underlying tumorigenesis remain to be fully elucidated. Here, we show that peptidylprolyl isomerase A (PPIA) serves as anchor to recruit GAU1 lncRNA by interacting with exon 4 of GAU1 and enhances the formation of SENP5/GAU1 DNA-lncRNA triplex. Intriguingly, TFR4 region of GAU1 exon 3 and TTS4 region of SENP5 promoter DNA constitute fragments forming the SENP5/GAU1 triplex. The SENP5/GAU1 triplex subsequently triggers the recruitment of the methyltransferase SET1A to exon 1 of GAU1, leading to the enrichment of H3K4 trimethylation and the activation of SENP5 transcription for driving the tumorigenesis of gastric cancer in vitro and in vivo. Our study reveals a mechanism of PPIA-guided SENP5/GAU1 DNA-lncRNA triplex formation in tumorigenesis and providing a concept in the dynamics of isomerase assisted DNA-RNA hybridization.

Abstract Smooth metal microspheres with uniform sizes are ideal for constructing particle-arrayed anisotropic conductive films (ACF), but synthesis is hindered by challenges in controlling anisotropic metal growth. Here, we present a positioned transient-emulsion self-assembly and laser-irradiation strategy to fabricate pure gold microsphere arrays with smooth surfaces and uniform sizes. The fabrication involves assembling gold nanoparticles into uniform colloidosomes within a pre-designed microhole array, followed by rapid transformation into well-defined microspheres through laser heating. The gold nanoparticles melt and merge in a layer-by-layer manner due to the finite skin depth of the laser, leading to a localized photothermal effect. This strategy circumvents anisotropic growth, enables tunable control of microsphere size and positioning, and is compatible with conventional lithography. Importantly, these pure gold microspheres exhibit stable conductivity under deep compression, offering promising applications in soldering micro-sized chips onto integrated circuits.

Denitrification, anaerobic ammonium oxidation (Anammox), and ferric iron reduction coupled with anaerobic ammonium oxidation (Feammox) are the nitrogen removal pathways in natural ecosystems. In this study, the differences between these three nitrogen removal pathways in a Phragmites australis covered site (LW), artificial grassland covered site (CD), poplar covered site (YD), and topsoil tillage after harvesting reed site (GD) in the Yinchuan Yellow River wetland were investigated using isotope tracing, metagenome, and quantitative polymerase chain reaction (Q-PCR) techniques. No 30N2 accumulation was detected in 15NH4+ addition incubations, indicating that Feammox was weak in all sites, which is consistent with a low abundance of the Feammox functional bacteria Acidimiprobiaceae sp. A6. The denitrification rates were 0.36 (LW), 0.5 (CD), 0.76 (YD) and 0.12 (GD) mg N/kg/day. The Anammox rates were 0.18 (LW) and 0.26 (GD) mg N/kg/day; other sites did not detect Anammox rate. Denitrification was the dominant pathway except for the CD site. The YD site had the highest abundance of denitrification genes, which was consistent with the denitrification rate.

Abstract Background LDL receptor‐related protein‐1 (LRP1) is a cell‐surface receptor that functions in diverse physiological pathways. We previously demonstrated that hepatocyte‐specific LRP1 deficiency (hLRP1KO) promotes diet‐induced insulin resistance and increases hepatic gluconeogenesis in mice. However, it remains unclear whether LRP1 regulates hepatic glycogenesis. Methods Insulin signaling, glycogenic gene expression, and glycogen content were assessed in mice and HepG2 cells. The pcDNA 3.1 plasmid and adeno‐associated virus serotype 8 vector (AAV8) were used to overexpress the truncated β‐chain (β∆) of LRP1 both in vitro and in vivo. Results On a normal chow diet, hLRP1KO mice exhibited impaired insulin signaling and decreased glycogen content. Moreover, LRP1 expression in HepG2 cells was significantly repressed by palmitate in a dose‐ and time‐dependent manner. Both LRP1 knockdown and palmitate treatment led to reduced phosphorylation of Akt and GSK3β, increased levels of phosphorylated glycogen synthase (GYS), and diminished glycogen synthesis in insulin‐stimulated HepG2 cells, which was restored by exogenous expression of the β∆‐chain. By contrast, AAV8‐mediated hepatic β∆‐chain overexpression significantly improved the insulin signaling pathway, thus activating glycogenesis and enhancing glycogen storage in the livers of high‐fat diet (HFD)‐fed mice. Conclusion Our data revealed that LRP1, especially its β‐chain, facilitates hepatic glycogenesis by improving the insulin signaling pathway, suggesting a new therapeutic strategy for hepatic insulin resistance‐related diseases.

Abstract Background Lung adenocarcinoma (LUAD) with lymph node (LN) metastasis is linked to poor prognosis, yet the underlying mechanisms remain largely undefined. This study aimed to elucidate the immunogenomic landscape associated with LN metastasis in LUAD. Methods We employed broad-panel next-generation sequencing (NGS) on a cohort of 257 surgically treated LUAD patients to delineate the molecular landscape of primary tumors and identify actionable driver-gene alterations. Additionally, we used multiplex immunohistochemistry (mIHC) on a propensity score-matched cohort, which enabled us to profile the immune microenvironment of primary tumors in detail while preserving cellular metaclusters, interactions, and neighborhood functional units. By integrating data from NGS and mIHC, we successfully identified spatial immunogenomic patterns and developed a predictive model for LN metastasis, which was subsequently validated independently. Results Our analysis revealed distinct immunogenomic alteration patterns associated with LN metastasis stages. Specifically, we observed increased mutation frequencies in genes such as PIK3CG and ATM in LN metastatic primary tumors. Moreover, LN positive primary tumors exhibited a higher presence of macrophage and regulatory T cell metaclusters, along with their enriched neighborhood units (p

Abstract Multiple sclerosis (MS) is an autoimmune disorder caused by chronic inflammatory reactions in the central nervous system. Currently, little is known about the changes of plasma proteomic profiles in Chinese patients with MS (CpwMS) and its relationship with the altered profiles of multi-omics such as metabolomics and gut microbiome, as well as potential molecular networks that underlie the etiology of MS. To uncover the characteristics of proteomics landscape and potential multi-omics interaction networks in CpwMS, Plasma samples were collected from 22 CpwMS and 22 healthy controls (HCs) and analyzed using a Tandem Mass Tag (TMT)-based quantitative proteomics approach. Our results showed that the plasma proteomics pattern was significantly different in CpwMS compared to HCs. A total of 90 differentially expressed proteins (DEPs), such as LAMP1 and FCG2A, were identified in CpwMS plasma comparing to HCs. Furthermore, we also observed extensive and significant correlations between the altered proteomic profiles and the changes of metabolome, gut microbiome, as well as altered immunoinflammatory responses in MS-affected patients. For instance, the level of LAMP1 and ERN1 were significantly and positively correlated with the concentrations of metabolite L-glutamic acid and pro-inflammatory factor IL-17 (Padj

The inferior creep ductility of Inconel 718 (IN718) fabricated by selective laser melting (SLM), which is unable to meet aerospace material specification (≥4%), limits its engineering application. Despite persistent optimization efforts in the SLM process and post-heat treatment, this issue remains unresolved. This study involved SLM fabrication of the modified IN718 with trace amounts of LaB6 and/or P, followed by homogenization and double aging heat treatment. The addition of trace LaB6 notably influenced the recrystallized grain structure and carbide precipitation at grain boundaries, while trace P addition had minimal impact. All samples exhibited similar γ′ and γ″ strengthening precipitates. Creep tests conducted at 650°C/690 MPa revealed that the individual modification of LaB6 showed limited improvement in creep performance and P showed no improvement, but the combined addition of LaB6 and P led to a substantial enhancement in creep performance, especially reaching as high as 8.6% creep strain. This remarkable improvement in creep ductility is unlikely to arise from the altered grain structure and grain boundary precipitates induced by LaB6 but predominantly arises from the synergistic effect of P and B in enhancing resistance to crack propagation during the third stage of creep.

Abstract In forensic genetics, utilizing massively parallel sequencing (MPS) to analyze short tandem repeats (STRs) has demonstrated several advantages compared to conventional capillary electrophoresis (CE). Due to the current technical limitations, although flanking region polymorphisms had been mentioned in several previous studies, most studies focused on the core repeat regions of STRs or the variations in the adjacent flanking regions. In this study, we developed an MPS system consisting of two sets of multiplex PCR systems to detect not only the STR core repeat regions but also to observe variants located at relatively distant positions in the flanking regions. The system contained 42 commonly used forensic STRs, including 21 autosomal STRs (A-STRs) and 21 Y-chromosomal STRs (Y-STRs), and a total of 350 male individuals from a Chinese Han population were genotyped. The length and sequence variants per locus were tallied and categorized based on length (length-based, LB), sequence without flanking region (core repeat regions sequence-based, RSB), and sequence with flanking region (core repeat and flanking regions sequence-based, FSB), respectively. Allele frequencies, Y-haplotype frequencies, and forensic parameters were calculated based on LB, RSB, and FSB, respectively, to evaluate the improvement in discrimination power, heterozygosity, and effectiveness of forensic systems. The results suggested the sequence variations have more influence on A-STRs and could improve the identification ability of MPS-STR genotyping. Concordance between MPS and CE methods was confirmed by using commercial CE-based STR kits. The impact of flanking region variations on STR genotype analysis and potential factors contributing to discordances were discussed. A total of 58 variations in the flanking regions (53 SNPs/SNVs and 5 InDels) were observed and most variations (48/58) were distributed in A-STRs. In summary, this study delved deeper into the genetic information of forensic commonly used STR and advanced the application of massively parallel sequencing in forensic genetics.

Abstract Real-time location tracking is essential for personal security in industrial scenes, e.g. monitoring worker safety in power substations. Ultra wideband (UWB) technology is suitable for indoor positioning thanks to its high penetration capability, high ranging accuracy and low power consumption. However, UWB based trilateration positioning requires high workload for field deployment of base stations. Indoor complex topology results in multipath and non-line of sight (NLOS) conditions of UWB signals, and degrades the positioning performance in terms of accuracy and reliability. This paper proposes a three-dimensional (3D) area recognition solution by integrating UWB time of flight (TOF) ranging and barometer measurements. The proposed solution utilizes a multi-tier distributed joint probabilistic inference model, which accomplishes the indoor 3D area recognition exploiting multiple clustering and prediction algorithms of machine learning. The field experiments showed that the proposed method can achieve an accuracy of 3D area recognition of more than 99.2%. The proposed method improves the computing efficiency by 93%. The errors of improved differential barometric height estimation method are less than 1 m, which means a success rate of 100% for floor identification, given a floor separation of 3–4 m. The proposed solution is suitable for personnel security applications of industrial scenes, which requires reliable real-time area information rather than just coordinates.

Abstract Background Neoadjuvant chemotherapy (NAC) is an effective treatment for locally advanced breast cancer (BC). However, there are no effective biomarkers for evaluating its efficacy. CDR1-AS, well known for its important role in tumorigenesis, is a famous circular RNA involved in the chemosensitivity of cancers other than BC. However, the predictive role of CDR1-AS in the efficacy and prognosis of NAC for BC has not been fully elucidated. We herein aimed to clarify this role. Methods The present study included patients treated with paclitaxel-cisplatin-based NAC. The expression of CDR1-AS was detected by real-time quantitative reverse transcription polymerase chain reaction testing. The predictive value of CDR1-AS expression was examined in pathological complete response (pCR) after NAC using logistic regression analysis. The relationship between CDR1-AS expression and survival was demonstrated using the Kaplan–Meier method, and tested by log-rank test and Cox proportional hazards regression model. Results The present study enrolled 106 patients with BC. Multivariate logistic regression analysis revealed that CDR1-AS expression was an independent predictive factor for pCR (odds ratio [OR] = 0.244; 95% confidence interval [CI] 0.081–0.732; p = 0.012). Furthermore, pCR benefits with low CDR1-AS expression were observed across all subgroups. The Kaplan–Meier curves and log-rank test suggested that the CDR1-AS high-expression group showed significantly better disease-free survival (DFS; log-rank p = 0.022) and relapse-free survival (RFS; log-rank p = 0.012) than the CDR1-AS low-expression group. Multivariate analysis revealed that CDR1-AS expression was an independent prognostic factor for DFS (adjusted HR = 0.177; 95% CI 0.034–0.928, p = 0.041), RFS (adjusted HR = 0.061; 95% CI 0.006–0.643, p = 0.020), and distant disease-free survival (adjusted HR = 0.061; 95% CI 0.006–0.972, p = 0.047). Conclusions CDR1-AS may be a potential novel predictive biomarker of pCR and survival benefit in patients with locally advanced BC receiving NAC. This may help identify specific chemosensitive individuals and build personalized treatment strategies.

Abstract Non-alcoholic fatty liver disease (NAFLD) is becoming a significant global public health threat. Seabuckthorn (Hippophae rhamnoides L.) has been used in traditional Chinese medicine (TCM). The hypolipidemic effects of Seabuckthorn polysaccharides (SP) against high-fat diets (HFD)-induced NAFLD were systematically explored and compared with that of Bifidobacterium lactis V9 (B. Lactis V9). Results showed that HFD-induced alanine transaminase (ALT) and aspartate aminotransferase (AST) levels decreased by 2.8-fold and 4.5-fold, respectively, after SP supplementation. Moreover, the alleviating effect on hepatic lipid accumulation is better than that of B. Lactis V9. The ACC and FASN mRNA levels were significantly reduced by 1.8 fold (P

The interfacial behaviors between protective coatings and substrate single-crystal superalloys significantly impact their service performances. This work focuses on the elements interdiffusion and microstructural evolution at the interface between a NiCrAlY coating and a series of high-Mo Ni3Al-based single-crystal superalloys, through the coupled phase-field simulations and DICTRA kinetics calculations of their model systems. The critical roles of Al and Cr played in the microstructural evolution at coating/superalloy interface have been confirmed, which requires the appropriate content decreases of Al and Cr in the coating at 1100 °C. However, the addition of Mo reduces the driving force of element diffusion from coating to substrate by increasing the activities of Al and Cr in superalloy. Moreover, increasing the Mo content in superalloy from 8 wt% to 10 wt% could also counteract the promoting effect of Al on Ni mobility and mitigate the γ′ coarsening and detrimental TCP precipitation. Therefore, the effects of Mo enable the reasonable increase of Al content in coating to better balance the interfacial stability and oxidation resistance of coated superalloy, besides its advantage in reducing the anisotropy of TCP precipitate. The obtained interfacial evolution mechanisms resulting from the phase transformation thermodynamics and element interdiffusion kinetics are expected to aid the coating design for advanced single-crystal superalloys servicing at ultra-high temperature.

Abstract The spatial co-presence of aberrant long non-coding RNAs (lncRNAs) and abnormal coding genes contributes to malignancy development in various tumors. However, precise coordinated mechanisms underlying this phenomenon in tumorigenesis remains incompletely understood. Here, we show that Prohibitin 2 (PHB2) orchestrates the transcription of an oncogenic CASC15-New-Isoform 2 (CANT2) lncRNA and the coding tumor-suppressor gene CCBE1, thereby accelerating melanoma tumorigenesis. In melanoma cells, PHB2 initially accesses the open chromatin sites at the CANT2 promoter, recruiting MLL2 to augment H3K4 trimethylation and activate CANT2 transcription. Intriguingly, PHB2 further binds the activated CANT2 transcript, targeting the promoter of the tumor-suppressor gene CCBE1. This interaction recruits histone deacetylase HDAC1 to decrease H3K27 acetylation at the CCBE1 promoter and inhibit its transcription, significantly promoting tumor cell growth and metastasis both in vitro and in vivo. Our study elucidates a PHB2-mediated mechanism that orchestrates the aberrant transcription of lncRNAs and coding genes, providing an intriguing epigenetic regulatory model in tumorigenesis.

BackgroundTo identify new intervention targets, we explored the correlation between cytokines and the development of refractory status epilepticus (RSE) in patients with severe viral encephalitis (SVE).MethodsWe examined the characteristics of 14 cytokines in the cerebrospinal fluid (CSF) and serum, analyzing their correlation with acute symptomatic seizures and prognosis. Furthermore, we conducted a dynamic analysis of differences and correlations in the expression of cytokines among patients with SVE without seizures, those with controlled seizures, and those with RSE.ResultsWe included 161 patients with SVE; the incidence of seizures was 55.2%, and the mortality rate was 5.5%. Notably, 18.9% of these patients developed RSE, with a mortality rate of 20%. During the early stage of SVE, CSF interleukin (IL)-6 and IL-8 levels were significantly higher, declining over time and affecting the prognosis. CSF IL-6 and IL-8 levels were significantly elevated in the RSE group compared to patients without seizures and with controlled seizures, decreasing gradually and independently of serum cytokine levels. CSF IL-8 and age were independent risk factors for RSE, with clinical utility.ConclusionsPatients with SVE exhibit intrathecal cytokine storms, primarily characterized by elevated levels of IL-6 and IL-8, which influence prognosis. The strong and persistent hyperinflammation underscored by CSF IL-6 and IL-8 is associated with the occurrence and development of RSE; thus, CSF IL-8 and age are independent risk factors for SVE with RSE, indicating potential anti-inflammatory intervention targets.

Summary: The mechanism by which Wnt signaling, an essential pathway controlling development and disease, stabilizes β-catenin has been a subject of debate over the last four decades. Casein kinase 1α (CK1α) functions as a pivotal negative regulator of this signaling pathway, initiating the events that destabilize β-catenin. However, whether and how CK1α activity is regulated in Wnt-off and Wnt-on states remains poorly understood. We now show that CK1α activity requires its association with the α catalytic subunit of protein phosphatase 2A (PPP2CA) on AXIN, the scaffold protein of the β-catenin destruction complex. Wnt stimulation induces the dissociation of PPP2CA from CK1α, resulting in CK1α autophosphorylation and its consequent inactivation. Moreover, autophosphorylated CK1α is enriched in a subset of colorectal cancers (CRCs) harboring constitutive Wnt activation. Our findings identify a mechanism by which Wnt stimulation inactivates CK1α, filling a critical gap in our understanding of Wnt signaling, with relevance for CRC.

Systemic lupus erythematosus (SLE) is a chronic inflammatory and autoimmune disease with multiple tissue damage. However, the pathology remains elusive, and effective treatments are lacking. Multiple types of programmed cell death (PCD) implicated in SLE progression have recently been identified. Although ferroptosis, an iron-dependent form of cell death, has numerous pathophysiological features similar to those of SLE, such as intracellular iron accumulation, mitochondrial dysfunction, lipid metabolism disorders and concentration of damage associated-molecular patterns (DAMPs), only a few reports have demonstrated that ferroptosis is involved in SLE progression and that the role of ferroptosis in SLE pathogenesis continues to be neglected. Therefore, this review elucidates the potential intricate relationship between SLE and ferroptosis to provide a reliable theoretical basis for further research on ferroptosis in the pathogenesis of SLE.

Abstract Nanoparticle (NP) arrays, particularly those with plasmonic properties, have diverse applications in electronics, photonics, catalysis, and biosensing, but their precise and scalable fabrication remains challenging. In this work, a facile chemical‐based strategy is presented for the fabrication of precise NP patterns using a combination of soft thermal nanoimprinting and template‐directed assembly. The approach enables the creation of well‐defined NP arrays with single‐particle resolution and yields over 99%, covering a diverse range of NP sizes from 30 to 150 nm. These patterns can be transferred onto various substrates including semiconductors, insulators, 2D materials, and flexible polymers, maintaining high uniformity and repeatability for over 60 cycles with minimal degradation. Moreover, the method enables the fabrication of extensive NP arrays up to 1 cm2 with a positional accuracy of ±11 nm for 30 nm NPs. As a result, the obtained silver NP arrays exhibit ultranarrow surface lattice resonances with a linewidth of 4 nm and a quality factor (Q) of 216. The method offers new avenues for the creation of plasmonic NP arrays for flexible and wearable devices.

This study aimed to investigate the pharmacokinetics of difloxacin in pigeons following oral (PO), intramuscular (IM), and intravenous (IV) administration. Thirty pigeons were randomly divided into three groups (IM, IV, and PO; n = 10 per group). Difloxacin was administered at 10 mg/kg body weight (BW) via each route. Blood samples were collected at various intervals from 0 to 48 h, and plasma was analyzed for difloxacin concentrations using a validated high-performance liquid chromatography (HPLC) method. Pharmacokinetic parameters were determined using Phoenix software and a non-compartmental analysis (NCA) approach. After PO and IM administration, peak plasma concentrations (Cmax) were observed as 1.81 ± 0.47 and 6.52 ± 1.62 μg/mL, occurring at 2.60 ± 0.97 and 0.63 ± 0.24 h, respectively. Bioavailability (F) was 38.35 % ± 10.45 % for PO and 90.25 % ± 26.14 % for IM administration. Following IV administration, difloxacin was widely distributed, with a volume of distribution (VZ) of 2.52 ± 0.65 L/kg and a steady-state volume of distribution (VSS) of 1.87 ± 0.27 L/kg. Difloxacin exhibited slow elimination, with elimination half-lives (t1/2λzs) of 1.61 ± 0.3, 2.64 ± 0.64, and 4.27 ± 1.14 h after IM, PO, and IV administration, respectively. Based on the AUC/MIC ratios calculated here, the current IM or IV administration at 10 mg/kg BW is effective against bacterial infections with MIC values ≤ 0.1 μg/mL, while the current oral dose (10 mg/kg BW) may be insufficient, particularly for infections caused by pathogens with MIC values exceeding 0.1 μg/mL.

We demonstrate the nonreciprocal transmission of magnonic frequency combs (MFCs) in a dissipative cavity-magnonic system. We utilize the recently emerged pump-induced magnon (PIM) mode in YIG spheres to generate an MFC, as the PIM mode exhibits excellent nonlinearity under coherent pumping. Meanwhile, the dissipative cavity magnonic device is prepared to critical bound states in the continuum (BIC), providing clear nonreciprocity. Based on the different absorption efficiencies of the device in two opposite directions, we have demonstrated a clear difference in the number of frequency comb teeth for forward and reverse transmission, showcasing the ability to generate unidirectional combs. The nonreciprocal MFCs can be systematically tuned by modulating the detuning of the pump and BIC, the magnon and cavity modes, as well as the pump and perturbation tone. This research promotes the combination of MFCs and functional non-Hermitian cavity-magnon electronic devices, realizing new applications for nonreciprocal magnonic devices.

ABSTRACT Objective Currently, chimeric antigen receptor T‐cell (CART) therapy represents a highly effective approach for relapsed/refractory B‐cell lymphomas. However, it also carries treatment‐related risks. Limited data are available on the risks associated with CART therapy in patients with gastrointestinal involvement in B‐cell lymphomas. Therefore, we conducted a retrospective cohort study to address this gap in knowledge. Methods During the period from May 2019 to August 2022, a total of 26 patients recurrent/refractory with recurrent/refractory B‐cell lymphoma involving the gastrointestinal tract enrolled. Pathology confirmed CD19 antigen expression in tumor tissues. The disease status of patients who failed multiple lines of therapy was progressive disease (PD). Before CART cell infusion, patients received an FC regimen (fludarabine and cyclophosphamide) lymphodepletion. Quantitative PCR and flow cytometry were adopted for monitoring CART cell kinetics and function, with a focus on gastrointestinal AEs during treatment. The overall response rate (ORR) of the 26 patients was 61.5% (16/26), while the complete response rate (CR) was 23.1% (6/26). Their median follow‐up time was 22.49 months, while the medians of overall survival (OS) and progression‐free survival (PFS) were 10.88 and 5.47 months, respectively. The 1‐year OS and PFS rates were 45% and 42.3%, respectively. The prevalence of gastrointestinal complications was 21/26 (80.7%), including gastrointestinal hemorrhage in 11/26 (42.3%), emesis and diarrhea in 9/26 (34.6%), as well as intestinal obstruction in 2/26 (7.7%). A total of three patients (3/26, 11.5%) died of gastrointestinal hemorrhage. The gastrointestinal hemorrhage group exhibited markedly lower ORR and inferior OS compared to the non‐hemorrhage group. Conclusion Generally, the CART cell therapy is valid in relapsed/refractory B‐cell lymphoma with gastrointestinal involvement, but gastrointestinal bleeding is a unique risk factor that requires special attention, particularly in patients with high gastrointestinal tumor burden, as it is associated with poor efficacy and survival.

BackgroundNecrotizing pneumonia is a serious complication of Mycoplasma pneumoniae infection, especially in pediatric patients. Although necrotizing pneumonia is a rare condition, the occurrence of unilateral necrosis in two entire lobe tissues is even rarer. This case study presents a 5-year-old male child with necrotizing pneumonia caused by Mycoplasma pneumoniae, describing the clinical features, laboratory abnormalities, and radiographic findings associated with this condition, particularly the rare occurrence of unilateral necrosis in two entire lobe tissues.Case presentationThe patient presented with a 14-day history of fever and cough, accompanied by paroxysmal cough with continuous sounds, congested throat, increased respiratory effort, and abnormal lung findings on physical examination. Laboratory investigations revealed elevated white blood cell count, increased inflammatory markers, elevated liver enzymes, coagulation dysfunction, and hypoalbuminemia. Imaging studies showed the presence of pleural effusion and progressive necrotizing pneumonia, including the rare occurrence of unilateral necrosis affecting both entire lobe tissues.ConclusionNecrotizing pneumonia caused by Mycoplasma pneumoniae infection can present with prolonged fever, elevated inflammatory markers, pleural effusion, and progressive necrosis of lung tissue, with the occurrence of necrosis observed unilaterally in both entire lobe tissues is even rarer. Monitoring D-dimer levels is essential for evaluating the possibility of necrotizing pneumonia. Early recognition and appropriate management are crucial to improve outcomes in these patients.

Abstract The terrestrial ring current consists of particles with energy from several keV to 100 s of keV, and its enhancement will result in magnetic field depression, known as geomagnetic storms. The ring current is mainly composed of H+, O+, He+, and electrons, and there has been a longstanding debate regarding their relative contributions. In this study, we employed a multi‐output convolutional neural network to predict the storm‐time ring current plasma pressures of these particles. Taking solar wind parameters, interplanetary magnetic field (IMF) data, and geomagnetic indices with a time history of 3 days as input parameters, the model shows good performances for electron plasma pressure, H+ plasma pressure, He+ plasma pressure, and O+ plasma pressure in both quiet‐time and storm‐time periods, with high correlation coefficients and small root mean square errors between the measured and the predicted values. Our model successfully captures ring current enhancement during the storm main phase and species‐dependent decay during the recovery phase. Moreover, the model's ability to predict plasma pressures of different species simultaneously facilitates a comparative analysis of their respective contributions to the ring current. The storm event where our model was applied demonstrates that during the storm, the contribution of H+ decreases but still dominates, while the contribution of O+ increases dramatically, and electrons and He+ also play roles in some localized regions. The application of this model is in line with previous observations and simulations, which can be utilized for quantitative analysis of storm‐time ring current dynamics.

ABSTRACT As one of the most sensitive and fragile alpine ecosystems in the Qilian Mountains, the alpine meadow holds significant scientific importance in understanding the changes in the characteristics of soil bacterial community in response to altitude and aspect variations. In our study, we analyzed the composition, diversity, and function of soil bacterial communities in alpine meadows at different altitudes and aspects and their relationship with environmental factors. Our results indicate that altitude and aspect orientation significantly influences the diversity index and composition of soil bacterial communities. Specifically, the Shannon and Chao1 indices of soil bacteria initially increased and then decreased with increasing altitude, with the Shannon index being lower in shady aspects compared to sunny aspects, and the Chao1 index being lower in sunny aspects above an altitude of 3400 m compared to shady aspects at the exact altitudes. Using Linear Discriminant Analysis Effect Size analysis, we identified 77 bacterial species in the research area, with key ecological functions primarily associated with nitrification, aerobic ammonia oxidation, and chitinolysis. Furthermore, we found that soil water content and Urease were the main factors influencing bacterial community composition. Our findings underscore the significant impact of altitude orientation on bacterial communities in alpine grasslands, emphasizing the importance of considering bacterial differences in evaluating alpine grassland health.