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Abstract Observational studies have shown that non-alcoholic fatty liver disease (NAFLD) is strongly associated with metabolic dysfunction. However, there is a paucity of research on whether changes in indicators of serum metabolism contribute to the development of NAFLD. This study was conducted with 4084 participants who underwent healthy physical examinations at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China, in 2022 and 2023. Baseline and follow-up measurements, including anthropometric data, abdominal ultrasound and blood samples were collected. The diagnosis of NAFLD was based on the 2010 Chinese Guidelines on Diagnosis and Treatment of NAFLD. Multiple logistic regression was utilized to analyze the odds ratios (ORs) for the 1-year risk of NAFLD in connection with both baseline metabolic indicators and changes in metabolic indicators observed over the course of 1 year. A total of 3425 study participants who were free of NAFLD at baseline, including 1146 men and 2279 women, were included in the final analysis. The mean age was 34.43 ± 7.20 years. Participants who developed NAFLD were older, male and had higher levels of body mass index (BMI), blood pressure, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free triiodothyronine (fT3), uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and lower levels of high-density lipoprotein cholesterol (HDL-C) and free thyroxine (fT4) (all P values

Abstract Background Addressing presbyopia in the aging population, particularly in non-cataractous patients, remains a challenge. This study evaluates the outcomes of refractive lens exchange (RLE) with AT LISA tri 839MP trifocal intraocular lens (IOL) implantation in a Chinese presbyopic population without cataracts. Methods The study included 164 eyes from 82 patients undergoing bilateral RLE at Peking Union Medical College Hospital. Comprehensive evaluations encompassed visual acuities, refraction, ocular aberrometry, and subjective outcomes via the VF-14 questionnaire. The focus was on postoperative visual performance, refractive outcomes, safety, objective optical quality, and patient satisfaction. Results 100%, 90.2%, and 89.0% of patients achieved binocular UDVA, UNVA, and UIVA of logMAR 0.1 or better at 6 months postoperatively. 97.6% of eyes were within ± 1.00 D of emmetropia postoperatively. Optical quality assessments showed increases in modulation transfer function and Strehl ratios (p

Abstract Background Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates. Case presentation The 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient’s condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management. Conclusion Enhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.

Abstract Background Thyroid eye disease (TED) is an inflammatory process involving lymphocyte-mediated immune response and orbital tissue damage. The anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies produced by B lymphocytes are involved in the activation of orbital fibroblasts and the inflammatory process of orbital tissue damage in TED. The purpose of this study was to explore the role of IGF-1R in the mechanistic connection between orbital fibroblasts and B lymphocytes in TED. Methods Orbital fibroblasts sampled from orbital connective tissues and peripheral B lymphocytes isolated from peripheral blood, which were obtained from 15 patients with TED and 15 control patients, were co-cultured at a ratio of 1:20. The level of IGF-1R expression in orbital fibroblasts was evaluated by flow cytometry and confocal microscopy. Transient B lymphocyte depletion was induced with anti-CD20 monoclonal antibody rituximab, while the IGF-1R pathway was blocked by the IGF-1R binding protein. The expression levels of interleukin-6 (IL-6) and regulated upon activation, normal T cell expressed and secreted (RANTES) in the co-culture model were quantified via ELISA. Results IGF-1R expression was significantly elevated in TED orbital fibroblasts compared to that of controls. A 24-h co-culture of orbital fibroblasts with peripheral B lymphocytes induced elevated expression levels of IL-6 and RANTES in each group (TED patients and controls), with the highest levels occurring in TED patients (T + T group). Rituximab and IGF-1R binding protein significantly inhibited increased levels of IL-6 and RANTES in the co-culture model of TED patients. Conclusions IGF-1R may mediate interaction between orbital fibroblasts and peripheral B lymphocytes; thus, blocking IGF-1R may reduce the local inflammatory response in TED. Rituximab-mediated B lymphocyte depletion played a role in inhibiting inflammatory responses in this in vitro co-culture model, providing a theoretical basis for the clinical application of anti-CD20 monoclonal antibodies in TED.

Abstract Tunability of interfacial effects between two-dimensional (2D) crystals is crucial not only for understanding the intrinsic properties of each system, but also for designing electronic devices based on ultra-thin heterostructures. A prerequisite of such heterostructure engineering is the availability of 2D crystals with different degrees of interfacial interactions. In this work, we report a controlled epitaxial growth of monolayer TaSe2 with different structural phases, 1H and 1 T, on a bilayer graphene (BLG) substrate using molecular beam epitaxy, and its impact on the electronic properties of the heterostructures using angle-resolved photoemission spectroscopy. 1H-TaSe2 exhibits significant charge transfer and band hybridization at the interface, whereas 1 T-TaSe2 shows weak interactions with the substrate. The distinct interfacial interactions are attributed to the dual effects from the differences of the work functions as well as the relative interlayer distance between TaSe2 films and BLG substrate. The method demonstrated here provides a viable route towards interface engineering in a variety of transition-metal dichalcogenides that can be applied to future nano-devices with designed electronic properties.

Abstract Antigen-specific regulatory T cells (Tregs) suppress pathogenic autoreactivity and are potential therapeutic candidates for autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis is associated with autoreactivity to the Smith (Sm) autoantigen and the human leucocyte antigen (HLA)-DR15 haplotype; hence, we investigated the potential of Sm-specific Tregs (Sm-Tregs) to suppress disease. Here we identify a HLA-DR15 restricted immunodominant Sm T cell epitope using biophysical affinity binding assays, then identify high-affinity Sm-specific T cell receptors (TCRs) using high-throughput single-cell sequencing. Using lentiviral vectors, we transduce our lead Sm-specific TCR into Tregs derived from patients with SLE who are anti-Sm and HLA-DR15 positive. Compared with polyclonal mock-transduced Tregs, Sm-Tregs potently suppress Sm-specific pro-inflammatory responses in vitro and suppress disease progression in a humanized mouse model of lupus nephritis. These results show that Sm-Tregs are a promising therapy for SLE.

Abstract Toxic amyloid-beta (Aβ) plaque and harmful inflammation are two leading symptoms of Alzheimer’s disease (AD). However, precise AD therapy is unrealizable due to the lack of dual-targeting therapy function, poor BBB penetration, and low imaging sensitivity. Here, we design a near-infrared-II aggregation-induced emission (AIE) nanotheranostic for precise AD therapy. The anti-quenching emission at 1350 nm accurately monitors the in vivo BBB penetration and specifically binding of nanotheranostic with plaques. Triggered by reactive oxygen species (ROS), two encapsulated therapeutic-type AIE molecules are controllably released to activate a self-enhanced therapy program. One specifically inhibits the Aβ fibrils formation, degrades Aβ fibrils, and prevents the reaggregation via multi-competitive interactions that are verified by computational analysis, which further alleviates the inflammation. Another effectively scavenges ROS and inflammation to remodel the cerebral redox balance and enhances the therapy effect, together reversing the neurotoxicity and achieving effective behavioral and cognitive improvements in the female AD mice model.

Abstract Background Malnutrition and subsequent alterations in body composition (BC), particularly sarcopenia, are common but not yet elucidated in patients with inflammatory bowel disease (IBD); we aimed to detail the changes in BC and the characteristics of co‐occurrence of malnutrition and sarcopenia in IBD patients and to investigate its effect on quality of life. Methods This study was a multicentre, prospective, observational study involving four tertiary referral hospitals in China. The following data were collected from consecutive IBD inpatients: demographic information, medical history, recent weight change, handgrip strength (HGS) and BC parameters by bioelectrical impedance analysis (BIA). Nutritional assessments were performed through stepwise screening (Nutritional Risk Screening 2002) and diagnosis (World Health Organization‐related body mass index [BMI], subjective global assessment, European Society for Clinical Nutrition and Metabolism 2015 and Global Leadership Initiative on Malnutrition [GLIM] criteria). The quality of life was assessed by the Inflammatory Bowel Disease Questionnaire. IBD patients were compared with 1:1 sex‐, age‐ and BMI‐matched healthy controls (MHC). Results A total of 238 IBD patients (177 Crohn's disease [CD] and 61 ulcerative colitis [UC]), 68.5% male, with a mean age of 38.5 ± 14.0 years and a mean BMI of 19.8 ± 3.5 kg/m2, were recruited. Compared with MHC (n = 122), IBD patients showed significant deterioration in BC and physical function, characterized by muscle depletion (appendicular skeletal muscle mass index [ASMI], 8.0 ± 1.3 vs. 6.7 ± 1.2 kg/m2, Δ% −15.0% [−22.0%, −10.0%], P

Abstract Recurring evidence suggests that fasting has extensive antitumor effects in various cancers, including papillary thyroid carcinoma (PTC). However, the underlying mechanism of this relationship with PTC is unknown. In this study, we study the effect of fasting on glycolysis and mitochondrial function in PTC. We find that fasting impairs glycolysis and reduces mitochondrial dysfunction in vitro and in vivo and also fasting in vitro and fasting mimicking diets (FMD) in vivo significantly increase the expression of lncRNA-protein kinase C theta antisense RNA 1 (PRKCQ-AS1), during the inhibition of TPC cell glycolysis and mitochondrial function. Moreover, lncRNA PRKCQ-AS1 was significantly lower in PTC tissues and cells. In addition, PRKCQ-AS1 overexpression increased PTC cell glycolysis and mitochondrial function; PRKCQ-AS1 knockdown has the opposite effect. On further mechanistic analysis, we identified that PRKCQ-AS1 physically interacts with IGF2BPs and enhances protein arginine methyltransferases 7 (PRMT7) mRNA, which is the key player in regulating glycolysis and mitochondrial function in PTC. Hence, PRKCQ-AS1 inhibits tumor growth while regulating glycolysis and mitochondrial functions via IGF2BPs/PRMT7 signaling. These results indicate that lncRNA PRKCQ-AS1 is a key downstream target of fasting and is involved in PTC metabolic reprogramming. Further, the PRKCQ-AS1/IGF2BPs/PRMT7 axis is an ideal therapeutic target for PTC diagnosis and treatment.

Abstract Background IOL fixation without capsular support presents challenges for surgeons. Although innovative techniques were developed to address subluxated IOLs, adjustable IOL fixation methods are seldom reported. We introduce a novel two-way adjustable double-knots intrascleral fixation combined with single sclerotomy looping technique for fixing intraocular lenses (IOL) or IOL-capsular bags. Methods A bent 30-gauge needle threaded with 8 − 0 polypropylene was introduced into the eye. A gripping forceps assisted the haptic looping. Two overhand knots were made with 8 − 0 polypropylene thread. The knots were incarcerated into a scleral tunnel made by a 30-gauge needle, with two ends of the thread left at each side of the tunnel. The IOL was adjusted to the premium position with adequate tension by pulling either end of the threads. The study included 19 eyes with aphakia, subluxated IOL-capsular bags, or subluxated crystalline lenses. The mean followed up period was 18.9 ± 7.1 months with evaluations of uncorrected visual acuity (UCVA), intraocular pressure, slit-lamp examination, and swept-source optical coherence tomography of the anterior segment. Results UCVA increased from 1.28 ± 0.74 at baseline to 0.44 ± 0.51 (logMAR) at final visit (P

Abstract Anaplastic thyroid carcinoma (ATC) is a deadly disease with a poor prognosis. Thus, there is a pressing need to determine the mechanism of ATC progression. The homeobox D9 (HOXD9) transcription factor has been associated with numerous malignancies but its role in ATC is unclear. In the present study, the carcinogenic potential of HOXD9 in ATC was investigated. We assessed the differential expression of HOXD9 on cell proliferation, migration, invasion, apoptosis, and epithelial–mesenchymal transition (EMT) in ATC and explored the interactions between HOXD9, microRNA-451a (miR-451a), and proteasome 20S subunit beta 8 (PSMB8). In addition, subcutaneous tumorigenesis and lung metastasis in mouse models were established to investigate the role of HOXD9 in ATC progression and metastasis in vivo. HOXD9 expression was enhanced in ATC tissues and cells. Knockdown of HOXD9 inhibited cell proliferation, migration, invasion, and EMT but increased apoptosis in ATC cells. The UCSC Genome Browser and JASPAR database identified HOXD9 as an upstream regulator of miR-451a. The direct binding of miR-451a to the untranslated region (3′-UTR) of PSMB8 was established using a luciferase experiment. Blocking or activation of PI3K by LY294002 or 740Y-P could attenuate the effect of HOXD9 interference or overexpression on ATC progression. The PI3K/AKT signaling pathway was involved in HOXD9-stimulated ATC cell proliferation and EMT. Consistent with in vitro findings, the downregulation of HOXD9 in ATC cells impeded tumor growth and lung metastasis in vivo. Our research suggests that through PI3K/AKT signaling, the HOXD9/miR-451a/PSMB8 axis may have significance in the control of cell proliferation and metastasis in ATC. Thus, HOXD9 could serve as a potential target for the diagnosis of ATC. Graphical Abstract

Photoactive artificial nanocatalysts that mimic natural photoenergy systems can yield clean and renewable energy. However, their poor photoabsorption capability and disfavored photogenic electron–hole recombination hinder their production. Herein, we designed two nanocatalysts with various microstructures by combining the tailored self-assembly of the meso-tetra(p-hydroxyphenyl) porphine photosensitizer with the growth of titanium dioxide (TiO2). The porphyrin photoabsorption antenna efficiently extended the absorption range of TiO2 in the visible region, while anatase TiO2 promoted the efficient electron–hole separation of porphyrin. The photo-induced electrons were transferred to the surface of the Pt co-catalyst for the generation of hydrogen via water splitting, and the hole was utilized for the decomposition of methyl orange dye. The hybrid structure showed greatly increased photocatalytic performance compared to the core@shell structure due to massive active sites and increased photo-generated electron output. This controlled assembly regulation provides a new approach for the fabrication of advanced, structure-dependent photocatalysts.

The online monitoring of metal particles in lubricating oil plays an important role in equipment fault diagnosis technology. This paper designs an online wear monitoring warning sensor based on the electromagnetic induction of metal particles in lubricating oil. First, different from the traditional three-coil sensing and detection method, the sensor consists of two excitation coils and one detection coil. In addition, the parallel capacitance and detection capacitance parameters are obtained by COMSOL’s scanning frequency, and the best detection capacitance is 7.53 nF. Second, according to the obtained optimal detection parallel capacitance value, the amplitude data of the particle signal, as well as the ferromagnetic particles above 60 µm and the non-ferromagnetic particles above 80 µm, are obtained. Third, according to the principle of three-coil induction, a mapping relationship model was established between the size range of metal wear particles in lubricating oil. Finally, we set up an oil wear particle platform to verify the sensor performance. The ferromagnetic and non-ferromagnetic particles are divided into multiple size ranges, and the peak-to-peak values of the output signal of different-sized wear particles are measured. We developed a prototype sensor and verified the signal consistency and repeatability of the sensor to wear metal particles. In addition, we used the sensor to test a large number of metal particles of different sizes (14 ferromagnetic particle standard samples with particle sizes ranging from 20.64 to 457.59 µm and ten non-ferromagnetic particle standard samples with particle sizes ranging from 40.52 to 348.07 µm). The experimental results show that the sensor can directly achieve monitoring sensitivity for ferromagnetic particles greater than 64.57 µm and non-ferromagnetic (copper) particles greater than 82.83 µm under the 4.2 mm aperture flow channel. The sensor can effectively realize the sensitivity on monitoring of small ferromagnetic particles and non-ferromagnetic particles, and it is particularly sensitive to small non-ferromagnetic particles.

Abstract The field of two-dimensional (2D) ferromagnetism has been proliferating over the past few years, with ongoing interests in basic science and potential applications in spintronic technology. However, a high-resolution spectroscopic study of the 2D ferromagnet is still lacking due to the small size and air sensitivity of the exfoliated nanoflakes. Here, we report a thickness-dependent ferromagnetism in epitaxially grown Cr2Te3 thin films and investigate the evolution of the underlying electronic structure by synergistic angle-resolved photoemission spectroscopy, scanning tunneling microscopy, x-ray absorption spectroscopy, and first-principle calculations. A conspicuous ferromagnetic transition from Stoner to Heisenberg-type is directly observed in the atomically thin limit, indicating that dimensionality is a powerful tuning knob to manipulate the novel properties of 2D magnetism. Monolayer Cr2Te3 retains robust ferromagnetism, but with a suppressed Curie temperature, due to the drastic drop in the density of states near the Fermi level. Our results establish atomically thin Cr2Te3 as an excellent platform to explore the dual nature of localized and itinerant ferromagnetism in 2D magnets.

This paper designed and developed an online digital imaging excitation sensor for wind power gearbox wear condition monitoring based on an adaptive deep learning method. A digital imaging excitation sensing image information collection architecture for magnetic particles in lubricating oil was established to characterize the wear condition of mechanical equipment, achieving the real-time online collection of wear particles in lubricating oil. On this basis, a mechanical equipment wear condition diagnosis method based on online wear particle images is proposed, obtaining data from an engineering test platform based on a wind power gearbox. Firstly, a foreground segmentation preprocessing method based on the U-Net network can effectively eliminate the interference of bubbles and dark fields in online wear particle images, providing high-quality segmentation results for subsequent image processing, A total of 1960 wear particle images were collected in the experiment, the average intersection union ratio of the validation set is 0.9299, and the accuracy of the validation set is 0.9799. Secondly, based on the foreground segmentation preprocessing of wear particle images, by using the watered algorithm to obtain the number of particles in each size segment, we obtained the number of magnetic particle grades in three different ranges: 4–38 µm, 39–70 µm, and >70 µm. Thirdly, we proposed a method named multidimensional transformer (MTF) network. Mean Square Error (MSE), Root Mean Square Error (RMSE), and Mean Absolute Error (MAE) are used to obtain the error, and the maintenance strategy is formulated according to the predicted trend. The experimental results show that the predictive performance of our proposed model is better than that of LSTM and TCN. Finally, the online real-time monitoring system triggered three alarms, and at the same time, our offline sampling data analysis was conducted, the accuracy of online real-time monitoring alarms was verified, and the gearbox of the wind turbine was shut down for maintenance and repair.

Abstract Hemibarbus maculatus is a globally important species for its value in fisheries and aquaculture. There is relatively little information available about this species' sexual development genes. Therefore, in this study, we used the technology of high‐throughput RNA sequencing (RNA‐seq), to investigate if the ovary and testis' differently expressed genes (DEGs) during sex differentiation in H. maculatus. Our results revealed a total of 43,468,248 and 39,241,362 qualified reads were generated in the female and male libraries, and 32,127 unigenes were assembled via the annotation analysis. Moreover, 17,808 unigenes were found to be DEGs between males and females, with 12,726 up‐ and 5082 downregulated genes in the ovaries and testes, respectively. The transcriptome analysis revealed there are 23 DEGs between ovary and testes of H. maculatus, which may be involved in sex determination. The expression patterns of these genes were validated by quantitative real‐time PCR (qPCR). The results of qPCR were generally consistent with the RNA‐seq results. This work was the first to annotate genes linked with gonadal development and reproduction in H. maculatus using gonadal transcriptome analysis, which provides useful molecular data for a better understanding of sexual development, as well as functional genomics and population genetics studies of H. maculatus.

Abstract Introduction As a CGM-derived indicator, ‘time in range’ (TIR) is emerging as a key indicator for accurate assessment of glycaemic control. However, there is few report focusing on the correlation of TIR with albumuria and renal fuction. The aim of this work was to investigate whether TIR, as well as nocturnal TIR and hypoglycaemic events is related to the presence and severity of albuminuria and decrease of eGFR in type 2 diabetes. Research design and methods A total of 823 patients were enrolled in this study. All patients received continuous glucose monitoring, TIR indicating the percentage of time that blood glucose was in the range of 3.9–10.0 mmol/L. The Spearman analysis was applied to analyze the relationship between TIR (or nocturnal TIR) and ACR. Logistic regression was used to explore whether TIR (or nocturnal TIR) is an independent risk factor for albuminuria. Results The prevalence of albuminuria decreased with increasing TIR quartiles. Binary logistic regression revealed that TIR as well as nocturnal TIR was obviously related to the presence of albuminuria. Multiple regression analysis found that only nocturnal TIR was obviously related to the severity of albuminuria. In our study, eGFR was significantly associated with the number of hypoglycemic events. Conclusions In T2DM patients, TIR and nocturnal TIR is associated with the presence of albuminuria independent of HbA1c and GV metrics. Nocturnal TIR shows better correlation than TIR. The role of TIR especially nocturnal TIR in the evaluation of diabetes kidney disease should be emphasized.

Abstract. Background:. Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys. Methods:. In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand–receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining. Results:. 15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47, RASSF4, EBAG9, IER3, SASH1, SEPTIN7, and NUB1, which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand–receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI. Conclusion:. Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell–cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.

Abstract Background and Aims Multiple sclerosis (MS) is a crippling, chronic, gender‐related disease that causes burdens to individuals and society. China has a considerable and increasing population of MS. We aim to analyze the gender disparities in the burden of MS in China and predict the trends. Methods The study was conducted based on the Global Burden of Disease Study 2019. Data on incidence, prevalence, deaths, and disability‐adjusted life years (DALYs) of MS in China from 1990 to 2019 was descriptively analyzed by year, gender, and age group. The Nordpred package in R (version 4.2.2) was used for age‐period‐cohort analysis to predict the all‐ages numbers and age‐standardized rates of incidence, prevalence, deaths, and DALYs in China from 2020 to 2044. Results The number of prevalent cases of MS in 2019 reached 18,143.56 (95% uncertainty intervals [UI]: 13,997.71–22,658.60) in males and 24,427.11 (95% UI: 18,906.02–30,530.21) in females in China. The peak age of prevalence was shifted from 40–44 years in 1990 to 45–49 years in 2019 in females but remained unchanged in males. In contrast to the increased age‐standardized prevalence rate, the age‐standardized death rate (ASDR) and age‐standardized DALYs rate showed downward trends, which were more significant in females. Different from the global, Chinese males showed lower prevalence but higher deaths and DALYs than females for age‐standardized rates and numbers. In the next 25 years, the patient population will remain large and peak around 44,599.78 in 2025–2029. The ASDR, age‐standardized DALYs rate, and DALYs number were expected to decrease. The improvements in deaths and DALYs will be more significant in females. Conclusion Males with MS had a lower prevalence but higher deaths and DALYs than females in China. The ASDR and age‐standardized DALYs rate have reduced over the past 30 years and were expected to continue decreasing, especially in females. The burden of MS will remain notable in the next 25 years.

Characterizing the operational wear status of mechanical equipment based on online monitoring of metal particles in lubricating oil plays a significant role in the effect of equipment fault diagnosis technology. According to the theoretical analysis of the electromagnetic induction principle and Biot–Savart’s law, combined with the finite element simulation analysis, systematic study and analysis were conducted on the distribution of magnetic field inside a single inductance coil, the coupling relationship between metal particles in lubricating oil, and the inductance coil. This paper analyzed the effects of four important design parameters that were the excitation frequency, the inside diameter of the coil, the turns number of the coil, and the length of the coil. On magnetic field uniformity and monitoring sensitivity, experiments demonstrated that: the correlation between the uniformity of the magnetic field on the testing surface of the sensor inductance coil and the coil radius and length is the highest, followed by the correlation with the number of coil turns. The correlation with the excitation frequency can be ignored in a negligible manner. In addition, experimental results indicated that if the ratio between the inside diameter of the inductance coil and the length of the coil (R/L) was less than 0.41, the magnetic field uniformity would reach over 91%. Meanwhile, results showed that the sensitivity of the sensor to ferromagnetic and non-ferromagnetic particles increased with the decrease in the coil inner diameter and inductance and increased with the increase in the excitation frequency. There is a specific length that can make the sensor coil monitoring, which is the most sensitive.

Abstract Background Apurinic/apyrimidinic endonuclease 1 (APE1) imparts radio-resistance by repairing isolated lesions via the base excision repair (BER) pathway, but whether and how it is involved in the formation and/or repair of DSBs remains mostly unknown. Methods Immunoblotting, fluorescent immunostaining, and the Comet assay were used to investigate the effect of APE1 on temporal DSB formation. Chromatin extraction, 53BP1 foci and co-immunoprecipitation, and rescue assays were used to evaluate non-homologous end joining (NHEJ) repair and APE1 effects. Colony formation, micronuclei measurements, flow cytometry, and xenograft models were used to examine the effect of APE1 expression on survival and synergistic lethality. Immunohistochemistry was used to detect APE1 and Artemis expression in cervical tumor tissues. Results APE1 is upregulated in cervical tumor tissue compared to paired peri-tumor, and elevated APE1 expression is associated with radio-resistance. APE1 mediates resistance to oxidative genotoxic stress by activating NHEJ repair. APE1, via its endonuclease activity, initiates clustered lesion conversion to DSBs (within 1 h), promoting the activation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key kinase in the DNA damage response (DDR) and NHEJ pathway. APE1 then participates in NHEJ repair directly by interacting with DNA- PKcs. Additionally, APE1 promotes NHEJ activity by decreasing the ubiquitination and degradation of Artemis, a nuclease with a critical role in the NHEJ pathway. Overall, APE1 deficiency leads to DSB accumulation at a late phase following oxidative stress (after 24 h), which also triggers activation of Ataxia-telangiectasia mutated (ATM), another key kinase of the DDR. Inhibition of ATM activity significantly promotes synergistic lethality with oxidative stress in APE1-deficient cells and tumors. Conclusion APE1 promotes NHEJ repair by temporally regulating DBS formation and repair following oxidative stress. This knowledge provides new insights into the design of combinatorial therapies and indicates the timing of administration and maintenance of DDR inhibitors for overcoming radio-resistance.

As a structural indicator of dense subgraphs, k-core has been widely used in community search due to its concise and efficient calculation. Many community search algorithms have been expanded on the basis of k-core. However, relevant algorithms often set k values based on empirical analysis of datasets or require users to input manually. Once users are not familiar with the graph network structure, they may miss the optimal solution due to an improper k setting. Especially in attribute social networks, characterizing communities with only k-cores may lead to a lack of semantic interpretability of communities. Consequently, this article proposes a method for identifying the optimal k-core with the greatest attribute score in the attribute social network as the target community. The difficulty of the problem is that the query needs to integrate both structural and textual indicators of the community while fully considering the diversity of attribute scoring functions. To effectively reduce computational costs, we incorporate the topological characteristics of the k-core and the attribute characteristics of entities to construct a hierarchical forest. It is worth noting that we name tree nodes in a way similar to pre-order traversal and can maintain the order of all tree nodes during the forest creation process. In such an attribute forest, it is possible to quickly locate the initial solution containing all query vertices and reuse intermediate results during the process of expanding queries. We conducted effectiveness and performance experiments on multiple real datasets. As the results show, attribute scoring functions are not monotonic, and the algorithm proposed in this paper can avoid scores falling into local optima. With the help of the attribute k-core forest, the actual query time of the Advanced algorithm has improved by two orders of magnitude compared to the BaseLine algorithm. In addition, the average F1 score of our target community has increased by 2.04 times and 26.57% compared to ACQ and SFEG, respectively.

BackgroundKinesin is a molecular motor for transporting “goods” within cells and plays a key role in many types of tumors. The multi-angle study of kinesin at the pan-cancer level is conducive to understanding its role in tumorigenesis and development and clinical treatment potential.MethodsWe evaluated the expression of KIF genes, performed differential analysis by using the R package limma, and explored the pan-cancer prognosis of KIF genes by univariate Cox regression analysis. To evaluate the pan-cancer role of KIF genes as a whole, we defined the KIFscore with the help of gene set variation analysis (GSVA) and explored the KIFscores across normal tissues, tumor cell lines, and 33 tumor types in TCGA. Next, we used spearman correlation analysis to extensively study the correlation between the KIFscore and tumor prognosis and be-tween the KIFscore and clinical indicators. We also identified the relationship between the KIFscore and genomic variation and immune molecular signatures by multiplatform analysis. Finally, we identified the key genes in clear cell renal cell carcinoma (ccRCC) through machine learning algorithms and verified the candidate genes by CCK8, wound healing assay, Transwell assay, and flow cytometry.ResultsIn most cancers, KIFscores are high and they act as a risk factor for cancer. The KIFscore was significantly associated with copy number variation (CNV), tumor mutation burden (TMB), immune subtypes, DNA repair deficiency, and tumor stemness indexes. Moreover, in almost all cancer species, the KIFscore was positively correlated with T cell CD4+ TH2, the common lymphoid pro-genitor, and the T cell follicular helper. In addition, it was negatively correlated with CXCL16, CCL14, TNFSF13, and TNFRSF14 and positively correlated with ULBP1, MICB, and CD276. Machine learning helped us to identify four hub-genes in ccRCC. The suitable gene, KIF14, is highly expressed in ccRCC and promotes tumor cell proliferation, migration, and invasion.ConclusionOur study shows that the KIF genes play an important pan-cancer role and may become a potential new target for a variety of tumor treatments in the future. Furthermore, KIF14, a key molecule in the KIF genes, can provide a new idea for the ccRCC treatment.

BackgroundPrevious studies from our group and other investigators have shown that lung involvement is one of the independent predictors for treatment resistance in patients with myeloperoxidase (MPO)–anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-AAV). However, it is unclear which image features of lung involvement can predict the therapeutic response in MPO-AAV patients, which is vital in decision-making for these patients. Our aim was to develop and validate a radiomics nomogram to predict treatment resistance of Chinese MPO-AAV patients based on low-dose multiple slices computed tomography (MSCT) of the involved lung with cohorts from two centers.MethodsA total of 151 MPO-AAV patients with lung involvement (MPO-AAV-LI) from two centers were enrolled. Two different models (Model 1: radiomics signature; Model 2: radiomics nomogram) were built based on the clinical and MSCT data to predict the treatment resistance of MPO-AAV with lung involvement in training and test cohorts. The performance of the models was assessed using the area under the curve (AUC). The better model was further validated. A nomogram was constructed and evaluated by DCA and calibration curves, which further tested in all enrolled data and compared with the other model.ResultsModel 2 had a higher predicting ability than Model 1 both in training (AUC: 0.948 vs. 0.824; p = 0.039) and test cohorts (AUC: 0.913 vs. 0.898; p = 0.043). As a better model, Model 2 obtained an excellent predictive performance (AUC: 0.929; 95% CI: 0.827–1.000) in the validation cohort. The DCA curve demonstrated that Model 2 was clinically feasible. The calibration curves of Model 2 closely aligned with the true treatment resistance rate in the training (p = 0.28) and test sets (p = 0.70). In addition, the predictive performance of Model 2 (AUC: 0.929; 95% CI: 0.875–0.964) was superior to Model 1 (AUC: 0.862; 95% CI: 0.796–0.913) and serum creatinine (AUC: 0.867; 95% CI: 0.802–0.917) in all patients (all p< 0.05).ConclusionThe radiomics nomogram (Model 2) is a useful, non-invasive tool for predicting the treatment resistance of MPO-AAV patients with lung involvement, which might aid in individualizing treatment decisions.

Abstract In recent years, with the advance of Artificial Intelligence, automatic music composition has been demonstrated. However, there are many music genres and music instruments. For a same piece of music, different music instruments would produce different effects. Invented some 2500 years ago, Guzheng is one of the oldest music instruments in China and the world. It has distinct timbres and patterns that cannot be duplicated by other music instruments. Therefore, it is interesting to see whether AI can compose Guzheng music or alike. In this paper we present a method that can automatically compose and play Guzheng music. First, we collect a number of existing Guzheng music pieces and convert them into Music Instrument Digital Interface format. Second, we use these data to train a Long Short-Term Memory (LSTM) network and use the trained network to generate new Guzheng music pieces. Next, we use the Reinforcement Learning to optimize the LSTM network by adding special Guzheng playing techniques. Comparing to the existing AI methods, such as LSTM and Generative Adversary Network, our new method is more effective in capturing the characteristics of Guzheng music. According to the evaluations from skilled Guzheng players and general audiences, our Guzheng music is very close to the real Guzheng music. The presented method can also be used to automatically compose the music of other Chinese music instruments.

Abstract Background Mesenchymal stromal cells (MSCs) are heterogeneous populations. Heterogeneity exists within the same tissue and between different tissues. Some studies have found enormous heterogeneity in immunomodulatory function among MSCs derived from different tissues. Moreover, the underlying mechanism of heterogeneity in immunomodulatory abilities is still unclear. Methods Foreskin mesenchymal stromal cells (FSMSCs) and human umbilical cord mesenchymal stromal cells (HuMSCs) were isolated and cultured until the third passage. According to the International Association for Cell Therapy standard, we confirmed the cell type. Then, FSMSCs and HuMSCs were cocultured with human peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS) in vitro. Furthermore, the supernatant was sampled for an enzyme-linked immunosorbent assay to investigate the secretion of IL-1β, IL-6, IL-10, TNF-α, and TGF-β1. Finally, we performed single-cell RNA sequencing (scRNA-seq) of FSMSCs and HuMSCs. Results We successfully identified FSMSCs and HuMSCs as MSCs. When cocultured with LPS pretreated PBMCs, FSMSCs and HuMSCs could effectively reduced the secretion of IL-1β and TNF-α. However, FSMSCs stimulated the PBMCs to secrete more IL-10, TGF-β1, and IL-6. Furthermore, 4 cell subsets were identified from integrated scRNA-seq data, including proliferative MSCs (MKI67 +, CD146 low+, NG2 +, PDGFRB − ), pericytes (CD146 high+, PDGFRB +, MKI67 − , CD31 − , CD45 − , CD34 − ), immune MSCs (CXCL12 high+, PTGIS high+, PDGFRB +, CD146 − , MKI67 − ) and progenitor proliferative MSCs (CXCL12 low+, PTGIS low+, PDGFRB +, CD146 − , MKI67 − ). Among them, we found that immune MSCs with strengthened transcriptional activity were similar to pericytes with regard to the degree of differentiated. Various of immune-related genes, gene sets, and regulons were also enriched in immune MSCs. Moreover, immune MSCs were determined to be close to other cell subsets in cell–cell communication analysis. Finally, we found that the proportion of immune MSCs in foreskin tissue was highest when comparing the subset compositions of MSCs derived from different tissues. Conclusions FSMSCs show better immunomodulatory capacity than HuMSCs in vitro. Moreover, immune MSCs may play a vital role in the heterogeneity of immunoregulatory properties. This study provides new insights suggesting that immune MSCs can be isolated to exert stable immunoregulatory functions without being limited by the heterogeneity of MSCs derived from different tissues.

As part of vehicle to everything (V2X) environments, intelligent connected vehicles (ICVs) generate a large amount of data, which can be exploited securely and effectively through decentralized techniques such as federated learning (FL). Existing FL systems, however, are vulnerable to attacks and barely meet the security requirements for real-world applications. If malicious or compromised ICVs upload inaccurate or low-quality local model updates to the central aggregator, they may reduce the accuracy of the global model, thereby reducing drivers safety and efficiency. This paper aims to alleviate these concerns by presenting BV-ICVs, a blockchain-enabled and privacy-preserving FL framework for ICVs in an edge-envisioned V2X environment. This system uses Zero-Knowledge Succinct Non-Interactive Argument of Knowledge (zkSNARKs) verification that is compiled as smart contracts to prevent malicious, compromised or even rational ICVs from uploading unreliable, erroneous or low-quality model updates. The verification process is embedded within the consensus of the underlying permissioned blockchain, which maximizes both the efficiency of the process and the utilization of computer resources. As demonstrated by discussions, security analysis, and numerical results, BV-ICVs reduced data poisoning attacks and increased the privacy protection and accuracy of FL.

Abstract Near‐infrared‐II (NIR‐II) ferroptosis activators offer promising potentials in in vivo theranostics of deep tumors, such as glioma. However, most cases are nonvisual iron‐based systems that are blind for in vivo precise theranostic study. Additionally, the iron species and their associated nonspecific activations might trigger undesired detrimental effects on normal cells. Considering gold (Au) is an essential cofactor for life and it can specifically bind to tumor cells, Au(I)‐based NIR‐II ferroptosis nanoparticles (TBTP‐Au NPs) for brain‐targeted orthotopic glioblastoma theranostics are innovatively constructed. It achieves the real‐time visual monitoring of both the BBB penetration and the glioblastoma targeting processes. Moreover, it is first validated that the released TBTP‐Au specifically activates the effective heme oxygenase‐1‐regulated ferroptosis of glioma cells to greatly extend the survival time of glioma‐bearing mice. This new ferroptosis mechanism based on Au(I) may open a new way for the fabrication of advanced and high‐specificity visual anticancer drugs for clinical trials.

Precipitation is an essential element in earth system research, which greatly benefits from the emergence of Satellite Precipitation Products (SPPs). Therefore, assessment of the accuracy of the SPPs is necessary both scientifically and practically. The Integrated Multi-Satellite Retrievals for GPM (IMERG) is one of the most widely used SPPs in the scientific community. However, there is a lack of comprehensive evaluation for the performance of the newly released IMERG Version 07, which is essential for determining its effectiveness and reliability in precipitation estimation. In this study, we compare the IMERG V07 Final Run (V07_FR) with its predecessor IMERG V06_FR across scales from January 2016 to December 2020 over the globe (cross-compare their similarities and differences) and a focused study on mainland China (validate against 2481 rain gauges). The results show that: (1) Globally, the annual mean precipitation of V07_FR increases 2.2% compared to V06_FR over land but decreases 5.8% over the ocean. The two SPPs further exhibit great differences as indicated by the Critical Success Index (CSI = 0.64) and the Root Mean Squared Difference (RMSD = 3.42 mm/day) as compared to V06_FR to V07_FR. (2) Over mainland China, V06_FR and V07_FR detect comparable precipitation annually. However, the Probability of Detection (POD) improves by 5.0%, and the RMSD decreases by 3.7% when analyzed by grid cells. Further, the POD (+0%~+6.1%) and CSI (+0%~+8.8%) increase and the RMSD (−11.1%~0%) decreases regardless of the sub-regions. (3) Under extreme rainfall rates, V07_FR measures 4.5% lower extreme rainfall rates than V06_FR across mainland China. But V07_FR tends to detect more accurate extreme precipitation at both daily and event scales. These results can be of value for further SPP development, application in climatological and hydrological modeling, and risk analysis.

Cardiac substructure segmentation is a prerequisite for cardiac diagnosis and treatment, providing a basis for accurate calculation, modeling, and analysis of the entire cardiac structure. CT (computed tomography) imaging can be used for a noninvasive qualitative and quantitative evaluation of the cardiac anatomy and function. Cardiac substructures have diverse grayscales, fuzzy boundaries, irregular shapes, and variable locations. We designed a deep learning-based framework to improve the accuracy of the automatic segmentation of cardiac substructures. This framework integrates cardiac anatomical knowledge; it uses prior knowledge of the location, shape, and scale of cardiac substructures and separately processes the structures of different scales. Through two successive segmentation steps with a coarse-to-fine cascaded network, the more easily segmented substructures were coarsely segmented first; then, the more difficult substructures were finely segmented. The coarse segmentation result was used as prior information and combined with the original image as the input for the model. Anatomical knowledge of the large-scale substructures was embedded into the fine segmentation network to guide and train the small-scale substructures, achieving efficient and accurate segmentation of ten cardiac substructures. Sixty cardiac CT images and ten substructures manually delineated by experienced radiologists were retrospectively collected; the model was evaluated using the DSC (Dice similarity coefficient), Recall, Precision, and the Hausdorff distance. Compared with current mainstream segmentation models, our approach demonstrated significantly higher segmentation accuracy, with accurate segmentation of ten substructures of different shapes and sizes, indicating that the segmentation framework fused with prior anatomical knowledge has superior segmentation performance and can better segment small targets in multi-target segmentation tasks.

Small-diameter round timber is a kind of by-product mainly from the thinning operation of the plantations. It is plentiful and inexpensive, and is generally destined for non-structural applications. The small-diameter round timber is rarely used as structural members. This study was aimed to provide an innovative but simple way to use the small-diameter round timber as structural members. Three kinds of composite members were developed to be used in light frame wood construction, i.e. the built-up studs, the wood-steel joists and the wood-steel roof trusses. The shearwalls and diaphragms made of the developed composite members were also examined. To facilitate the fabrication, the configurations of these members were described in details. Efforts were also made to investigate the structural performances of these members via full-scale tests. It was found that the developed composite members could be used as substitutes of dimension lumber in the framework of light frame construction. The developed members could be also pre-fabricated as standard components in a mill and assembled on site. As a result, application of small-diameter round timber as structural members developed would be an efficient way to increase use of forest resource from plantation and lower the construction cost of light frame buildings.

This paper introduces the four stages of the construction of China’s social credit system. In combination with the characteristics of the institutional system, this paper describes the specific practices adopted by the Chinese government to promote the construction of the social credit system from six aspects, namely, governing government integrity, business and social ethics and judicial integrity, building the credit information platform, developing third-party credit service institutions and credit service markets, and constructing the social credit system demonstration cities. It argues that the construction of China’s credit system has the problems of insufficient rule of law, imperfect credit platform construction, and difficult credit repair. These problems will be gradually solved in the new phase of the social credit system’s construction starting from 2021, and China will continue to develop and improve its social credit system in the process of solving problems.

Leprosy, caused by Mycobacterium leprae, rarely affects children younger than 5 years. Here, we studied a multiplex leprosy family that included monozygotic twins aged 22 months suffering from paucibacillary leprosy. Whole genome sequencing identified three amino acid mutations previously associated with Crohn's disease and Parkinson's disease as candidate variants for early onset leprosy: LRRK2 N551K, R1398H and NOD2 R702W. In genome-edited macrophages, we demonstrated that cells expressing the LRRK2 mutations displayed reduced apoptosis activity following mycobacterial challenge independently of NOD2. However, employing co-immunoprecipitation and confocal microscopy we showed that LRRK2 and NOD2 proteins interacted in RAW cells and monocyte-derived macrophages, and that this interaction was substantially reduced for the NOD2 R702W mutation. Moreover, we observed a joint effect of LRRK2 and NOD2 variants on Bacillus Calmette-Guérin (BCG)-induced respiratory burst, NF-κB activation and cytokine/chemokine secretion with a strong impact for the genotypes found in the twins consistent with a role of the identified mutations in the development of early onset leprosy.

IntroductionDiabetic kidney disease (DKD) is a long-term complication of diabetes and causes renal microvascular disease. It is also one of the main causes of end-stage renal disease (ESRD), which has a complex pathophysiological process. Timely prevention and treatment are of great significance for delaying DKD. This study aimed to use bioinformatics analysis to find key diagnostic markers that could be possible therapeutic targets for DKD.MethodsWe downloaded DKD datasets from the Gene Expression Omnibus (GEO) database. Overexpression enrichment analysis (ORA) was used to explore the underlying biological processes in DKD. Algorithms such as WGCNA, LASSO, RF, and SVM_RFE were used to screen DKD diagnostic markers. The reliability and practicability of the the diagnostic model were evaluated by the calibration curve, ROC curve, and DCA curve. GSEA analysis and correlation analysis were used to explore the biological processes and significance of candidate markers. Finally, we constructed a mouse model of DKD and diabetes mellitus (DM), and we further verified the reliability of the markers through experiments such as PCR, immunohistochemistry, renal pathological staining, and ELISA.ResultsBiological processes, such as immune activation, T-cell activation, and cell adhesion were found to be enriched in DKD. Based on differentially expressed oxidative stress and inflammatory response-related genes (DEOIGs), we divided DKD patients into C1 and C2 subtypes. Four potential diagnostic markers for DKD, including tenascin C, peroxidasin, tissue inhibitor metalloproteinases 1, and tropomyosin (TNC, PXDN, TIMP1, and TPM1, respectively) were identified using multiple bioinformatics analyses. Further enrichment analysis found that four diagnostic markers were closely related to various immune cells and played an important role in the immune microenvironment of DKD. In addition, the results of the mouse experiment were consistent with the bioinformatics analysis, further confirming the reliability of the four markers.ConclusionIn conclusion, we identified four reliable and potential diagnostic markers through a comprehensive and systematic bioinformatics analysis and experimental validation, which could serve as potential therapeutic targets for DKD. We performed a preliminary examination of the biological processes involved in DKD pathogenesis and provide a novel idea for DKD diagnosis and treatment.

Salt structures are crucial targets in oil and gas seismic exploitation so that one fast, automatic and accurate method is necessary for accelerating salt structure identification in the exploitation process. With the development of machine-learning algorithms, geophysical scientists adopt machine-learning models to solve problems. Most machine-learning models in geophysics require mass data in the model training. However, the number of seismic images is limited and the class-imbalance is often existed in actuality, causing the machine-learning algorithms to be difficult to apply in exploitation projects. To overcome the challenge of the seismic images’ volume, this work collects a two-dimensional (2D) seismic images dataset and trains several U-net models with the methods of inversion and multiple distillation. Moreover, self-distillation is introduced to boost the model’s performance. A test using a public seismic dataset and the case of salt detection in the Hith evaporite in southern United Arab Emirates and western Oman shows the distillation method is able to identify salt structures automatically and accurately, which has great potential for application in actual exploitation.

The interplay between reduced dimensionality and interactions in monolayer transition metal dichalcogenides has been of great research interest. Here the authors report an insulating dimer ground state in 1T-IrTe2, driven by the combined effect of the charge density wave instability and local atomic bond formation.

AIM: To identify and characterize the 100 most influential articles in the field of myopia over the last decades. METHODS: Articles on myopia published between January 1975 and March 2020 were searched through the Web of Science Core Collection database. Two independent authors reviewed and determined the 100 most cited articles. The characteristics of each eligible article were recorded, including authors, institutions, countries, journals, publication date, total citations (TCs), annual citations (ACs), research focus and article type. RESULTS: The top 100 most influential articles were published between 1983 and 2016, with 1999 as the most prolific year. The mean number of TCs was 288 (range: 193-537) and the mean number of ACs was 19 (range: 7-109). Treatment and epidemiology of myopia were the most important research focus. These articles were published in 21 journals led by Ophthalmology (29%) followed by Investigative Ophthalmology & Visual Science (23%). The number of ACs for articles published in the last ten years was significantly higher than that for the other most-cited articles (44 vs 16, Mann-Whitney U test P

Investigation of the swelling pressure of buffer/backfill materials is a critical aspect in the design of high-level radioactive waste (HLW) disposal repositories. In this study, to clarify the swelling pressure–suction relation for compacted bentonite upon the hydration path, constant-volume swelling pressure tests with suction control were conducted. The swelling pressure–suction curves indicated that the swelling pressure of the specimens increased significantly with increasing dry density, while the shape of the curves during hydration depended on the dry density. Moreover, the swelling pressure–suction curves exhibited a distinction between unsaturated and saturated segments divided by the critical saturated state (CSS) curve, which proves the unique existence of a CSS curve in the stress space independent of the stress path. With the introduction of the CSS curve into the s–p space, the conventional stress space of unsaturated soil could expand to that of unsaturated expansive soil. The results obtained in this study could provide the mechanical parameters for the construction of disposal repositories. In addition, the stress space with CSS curve proposed in this study provides a new approach to building constitutive models of bentonite materials.

Query auto-completion (QAC) serves as a critical functionality in contemporary textual search systems by generating real-time query completion suggestions based on a user’s input prefix. Despite the prevalent use of language models (LMs) in QAC candidate generation, LM-based approaches frequently suffer from overcorrection issues during pair-wise loss training and efficiency deficiencies. To address these challenges, this paper presents a novel framework—discriminator-enhanced knowledge distillation (Dis-KD)—for the QAC task. This framework combines three core components: a large-scale pre-trained teacher model, a lightweight student model, and a discriminator for adversarial learning. Specifically, the discriminator aids in discerning generative-level differences between the teacher and the student models. An additional discriminator score loss is amalgamated with the traditional knowledge-distillation loss, resulting in enhanced performance of the student model. Contrary to the stepwise evaluation of each generated word, our approach assesses the entire generation sequence. This method alleviates the prevalent overcorrection issue in the generation process. Consequently, our proposed framework boasts improvements in model accuracy and a reduction in parameter size. Empirical results highlight the superiority of Dis-KD over established baseline methods, with the student model surpassing the teacher model in QAC tasks for sub-word languages.

Abstract Purpose To assess the accuracy of biometric parameters measured by anterior segment optical coherence tomography (AS-OCT) and partial coherence interferometry (PCI) in prediction of effective lens position (ELP) compared with previous formulas in PACG patients. Methods 121 PACG eyes were randomly divided into training set (85 eyes) and validation set (36 eyes) with same procedure including AS-OCT, PCI, phacoemulsification and IOL implantation surgery. Preoperative anterior chamber depth (pre-ACD), scleral spur depth (SSD), scleral spur width (SSW), lens vault (LV) and cornea thickness (CT) were measured from AS-OCT image. Axial length (AL) and corneal power (K) were measured by PCI. All the 7 parameters were analyzed by multiple linear regression in training set and a statistic regression formula was developed. In validation set, one-way ANOVA was applied to compare the new regression formula with Sanders-Retzlaff-Kraff theoretic (SRK/T), Holladay 1, Haigis, and a regression formula developed in previous study. Results The coefficient of determination (R2) of different parameter combinations are 0.19 (pre-ACD, AL), 0.25 (AL, K) and 0.49 (SSD, AL, SSW) in training set. In validation set, the correlation between predicted and measured ELP are: new formula (R2 = 0.50, P = 0.9947) Holladay 1 (R2 = 0.12, P

As a typical underwater robot, the robotic fish has been a hot topic of research in terms of the swimming control method and the reduction of energy consumption. Body flexibility and passive designs have been proven to be effective approaches for improving the swimming performance of robotic fishes. However, the addition of passive structures or motions of these approaches makes it more difficult to control the movement of robotic fish. In this paper, we proposed a deep reinforcement learning-based method for online learning control of a robotic eel with multiple passive structures. First, we designed a robotic eel with two wire-driven segments and two complaint bodies made of elastic material. Second, a simulation model of the robotic eel was built and the validity of the model was tested. Following that, the neural network was trained in simulation and deployed directly on the robotic eel, which was controlled without an underlying control model or strategy and directly online by the neural network. Finally, extensive experiments verified the effectiveness of our control method, which offers a valuable and potential solution for robots difficult to model and control.

Acute lung injury (ALI) is the most common complication of sepsis. Intravenous injection of HUMSCs can regulate the level of circulating endothelial cytokines and alleviate lung injury in juvenile septic rats. In this study, we performed proteomic and phosphorylated proteomic analysis of lung tissue of juvenile septic rats after Human Umbilical Cord Mesenchymal Stem Cells (HUMSCs) intervention for the first time, and screened the potential proteins and pathways of HUMSCs for therapeutic effect. The 4D proteome quantitative technique was used to quantitatively analyze the lung tissues of septic rats 24 hours (3 biological samples) and 24 hours after HUMSCs intervention (3 biological samples). A total of 213 proteins were identified as differentially expressed proteins, and 971 phosphorylation sites changed significantly. Based on the public database, we analyzed the functional enrichment of these proteins and phosphorylated proteins. In addition, Tenascin-C may be the key differential protein and ECM receptor interaction pathway may be the main signal pathway by using various algorithms to analyze the protein-protein interaction network. Phosphorylation analysis showed that tight junction pathway was closely related to immune inflammatory reaction, and EGFR interacted most, which may be the key differential phosphorylated protein. Finally, 123 conserved motifs of serine phosphorylation site (pS) and 17 conserved motifs of threonine (pT) phosphorylation sites were identified by motif analysis of phosphorylation sites. Results from proteomics and phosphorylated proteomics, the potential new therapeutic targets of HUMSCs in alleviating lung injury in juvenile septic rats were revealed.

BackgroundSeveral lines of evidence implicate that there are distinct differences between patients with myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) antibody double-seropositive patients (DPPs) and single-positive patients. Hence, we conducted a retrospective study from a single center in China to analyze the clinical and pathological features, and prognosis of DPPs.Methods109 patients with MPO-ANCA-associated vasculitis (MPO-AAV), 20 DPPs and 23 patients diagnosed with anti-GBM disease from a large center in China were included in this study. The ratio of patients with renal biopsy in three groups were 100%, 50% and 100%, respectively. Their clinical and pathological characteristics, and outcomes were analyzed. The intensity of immune deposits in the kidney at diagnosis was detected by immunofluorescence (IF). Furthermore, multivariate Cox hazard model analysis was used to assess the clinical and histological predictors of end-stage renal disease (ESRD) and death for DPPs.ResultsIn our study, we found that patients in the DPPs group were older than the other two groups (p = 0.007, MPO-AAV vs. DPPs; p < 0.001, DPPs vs. anti-GBM). The DPPs group had a higher value of serum creatinine (p = 0.041) and lower estimated glomerular filtration rate (eGFR) (p = 0.032) compared with MPO-AAV patients. On the contrary, the DPPs group had a lower serum creatinine (p = 0.003) compared with patients with anti-GBM group. The proportion of patients with cardiac system involvement in the DPPs group was higher than anti-GBM patients (p = 0.014). Cellular crescents could be generally observed in renal biopsy of DPPs and patients with anti-GBM glomerulonephritis. In addition, Bowman’s capsule rupture was more common in DPPs than MPO-AAV patients (p = 0.001). MPO-AAV had a better renal and overall survival outcome than DPPs (p < 0.001). There was no significant difference of renal and overall survival outcome between DPPs and patients with anti-GBM disease. The incidence of ESRD in DPPs was negatively associated with lymphocyte count (HR 0.153, 95% CI 0.027 to 0.872, p = 0.034) and eGFR (HR 0.847, 95% CI 0.726 to 0.989, p = 0.036). Elevated serum creatinine was confirmed as a risk factor of both renal (HR 1.003, 95% CI 1.000 to 1.005, p = 0.019) and patient survival in DPPs (HR1.461, 95% CI 1.050 to 2.033, p = 0.024).ConclusionIn summary, compared with anti-GBM disease, DPPs tended to involve multi-organ damage rather than limited to the kidney. It is highlighted that serologic DPPs have a worse renal and patient prognosis than MPO-AAV. Moreover, we found that the risk factors of renal survival of DPPs include low lymphocyte count, elevated serum creatinine and reduced eGFR, and serum creatinine can predict patient survival.

Objective: To analyze the role of serum sortilin in coronary artery calcification (CAC) and cardiovascular and cerebrovascular events (CCE) in maintenance hemodialysis (MHD) patients. Methods: One hundred eleven patients with MHD ≥3 months were included in this study. The general data, clinical features, hematological data, and medication history of the patients were recorded. Eighty-five cases were examined by vascular color Doppler ultrasound, cardiac color Doppler ultrasound, lateral lumbar radiography, and coronary artery calcification score. The patients were followed up for a median time of 45 months. The primary endpoint was CCE or death from a vascular event, and the role of sortilin in this process was analyzed. Results: Among 85 MHD patients, 51 cases (60.00%) had different degrees of CAC. There were significant differences in diabetes, dialysis time, serum phosphorus, calcium-phosphorus product, medical history of phosphate binders, sortilin, and carotid artery plaque between 4 different degrees of calcification groups (p < 0.05). Logistic regression analysis showed that diabetes (OR = 5.475; 95% CI: 1.794–16.71, p = 0.003), calcium-phosphorus product (OR = 2.953; 95% CI: 1.198–7.279, p = 0.019), and sortilin (OR = 1.475 per 100 pg/mL; 95% CI: 1.170–1.858, p = 0.001) were independent risk factors for CAC. During the follow-up, 28 cases of 111 patients (25.23%) suffered from CCE. There were significant differences in CCE between mild, moderate, and severe CAC groups and noncalcification groups (p < 0.05). Cox regression analysis showed that diabetes mellitus (HR 3.424; 95% CI: 1.348–8.701, p = 0.010), CAC (HR 5.210; 95% CI: 1.093–24.83, p = 0.038), and serum sortilin (HR = 8.588; 95% CI: 1.919–38.43, p = 0.005) were independent risk factors for CCE. Besides, we proposed a cutoff value of 418 pg/mL for serum sortilin level, which was able to predict the occurrence of CCE with 75.0% sensitivity and 71.9% specificity. The area under the curve was 0.778 (95% CI: 0.673–0.883). Conclusion: Sortilin is newly found to be independently associated with CAC and CCE in MHD patients.

To date, the pathogenesis of hepatitis B virus (HBV)-associated membranous nephropathy (MN) remains elusive. This study aimed to decipher the etiopathogenesis of HBV-associated MN by performing single-cell RNA sequencing (scRNA-seq) of kidney biopsy specimens from a patient with HBV-associated MN and two healthy individuals. We generated 4,114 intrarenal single-cell transcriptomes from the HBV-associated MN patient by scRNA-seq. Compared to healthy individuals, podocytes in the HBV-associated MN patient showed an increased expression of extracellular matrix formation-related genes, including HSPA5, CTGF, and EDIL3. Kidney endothelial cells (ECs) in the HBV-associated MN were enriched in inflammatory pathways, including NF-kappa B signaling, IL-17 signaling, TNF signaling and NOD-like receptor signaling. Gene ontology (GO) functional enrichment analysis and Gene Set Variation Analysis (GSVA) further revealed that differentially expressed genes (DEGs) of ECs from the HBV-associated MN patients were enriched in apoptotic signaling pathway, response to cytokine and leukocyte cell-cell adhesion. The up-regulated DEGs in glomerular ECs of HBV-associated MN patients were involved in biological processes such as viral gene expression, and protein targeting to endoplasmic reticulum. We further verified that the overexpressed genes in ECs from HBV-associated MN were mainly enriched in regulation of protein targeting to endoplasmic reticulum, exocytosis, viral gene expression, IL-6 and IL-1 secretion when compared with anti-phospholipase A2 receptor (PLA2R)-positive idiopathic membranous nephropathy (IMN). The receptor-ligand crosstalk analysis revealed potential interactions between endothelial cells and other cells in HBV-associated-MN. These results offer new insight into the pathogenesis of HBV-associated MN and may identify new therapeutic targets for HBV-associated MN.

Teacher emotion has become an important issue in English language teaching as it is a crucial construct in understanding teachers' responses to institutional policies. The study explored teachers' emotion labor and its impact on teachers' pedagogical decision-making in English for Specific Purposes (ESP) teaching in a university of Traditional Chinese Medicine (TCM) in China. Drawing on a poststructural perspective, the study examined data from two rounds of semi-structured interviews, policy documents and teaching artifacts. The analysis of data revealed that the major emotion labor facing the participants revolved around students' disengagement in class. Teachers experienced mixed feelings of anticipation, disappointment, anger, and empathy toward students and distanced themselves from institutional feeling rules enforcing objective assessment of students' performance and punishing students for lack of engagement in class. The study found that teacher emotion labor served as the site for their pedagogical modifications. ESP teachers' beliefs in the importance of attending to students' needs become a powerful discourse in supporting teachers to strategically subvert institutional feeling rules and critically reflect on the dysfunctions of curriculum, orienting teachers' agentic actions in modifying pedagogical practices. We thus underscore this empowering discourse as the bridge to connect teachers' policy negotiation and their actual classroom practices. We also highlight teachers' pedagogical decision-making as a process of the interactions of teacher emotion, teachers' reflexive practices, and power relations. The study ended by suggesting more longitudinal research where teachers' beliefs as previously appropriated discourses could be examined comprehensively as they were both the construct of emotion labor and the potential subverting power in supporting teachers' pedagogical decision-making in policy negotiation.

The task of multi-hop question generation (QG) seeks to generate questions that require a complex reasoning process that spans multiple sentences and answers. Beyond the conventional challenges of what to ask and how to ask, multi-hop QG necessitates sophisticated reasoning from dispersed evidence across multiple sentences. To address these challenges, a knowledge graph-enhanced language model (KGEL) has been developed to imitate human reasoning for multi-hop questions.The initial step in KGEL involves encoding the input sentence with a pre-trained GPT-2 language model to obtain a comprehensive semantic context representation. Next, a knowledge graph is constructed using the entities identified within the context. The critical information in the graph that is related to the answer is then utilized to update the context representations through an answer-aware graph attention network (GAT). Finally, the multi-head attention generation module (MHAG) is performed over the updated latent representations of the context to generate coherent questions. Human evaluations demonstrate that KGEL generates more logical and fluent multi-hop questions compared to GPT-2. Furthermore, KGEL outperforms five prominent baselines in automatic evaluations, with a BLEU-4 score that is 27% higher than that of GPT-2.