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Abstract Background In locally advanced rectal cancer (LARC), optimizing neoadjuvant strategies, including the addition of concurrent chemotherapy and dose escalation of radiotherapy, is essential to improve tumor regression and subsequent implementation of anal preservation strategies. Currently, dose escalation studies in rectal cancer have focused on the primary lesions. However, a common source of recurrence in LARC is the metastasis of cancer cells to the proximal lymph nodes. In our trial, we implement simultaneous integrated boost (SIB) to both primary lesions and positive lymph nodes in the experimental group based on magnetic resonance-guided adaptive radiotherapy (MRgART), which allows for more precise (and consequently intense) targeting while sparing neighboring healthy tissue. The objective of this study is to evaluate the efficacy and safety of MRgART dose escalation to both primary lesions and positive lymph nodes, in comparison with the conventional radiotherapy of long-course concurrent chemoradiotherapy (LCCRT) group, in the neoadjuvant treatment of LARC. Methods This is a multi-center, randomized, controlled phase III trial (NCT06246344). 128 patients with LARC (cT3-4/N+) will be enrolled. During LCCRT, patients will be randomized to receive either MRgART with SIB (60–65 Gy in 25–28 fractions to primary lesions and positive lymph nodes; 50–50.4 Gy in 25–28 fractions to the pelvis) or intensity-modulated radiotherapy (50–50.4 Gy in 25–28 fractions). Both groups will receive concurrent chemotherapy with capecitabine and consolidation chemotherapy of either two cycles of CAPEOX or three cycles of FOLFOX between radiotherapy and surgery. The primary endpoints are pathological complete response (pCR) rate and surgical difficulty, while the secondary endpoints are clinical complete response (cCR) rate, 3-year and 5-year disease-free survival (DFS) and overall survival (OS) rates, acute and late toxicity and quality of life. Discussion Since dose escalation of both primary lesions and positive nodes in LARC is rare, we propose conducting a phase III trial to evaluate the efficacy and safety of SIB for both primary lesions and positive nodes in LARC based on MRgART. Trial registration The study was registered at ClinicalTrials.gov with the Identifier: NCT06246344 (Registered 7th Feb 2024).

Objective The Mesozoic strata in the Halahatang-Hade area of the Tabei Uplift belt, Tarim Basin, cover an area of more than 30 000 km2. It has a large monoclinic background, with active hydrocarbon displays and great exploration potential, but no exploration breakthrough have been made for many years. The discovery of the adjacent SINOPEC mining area promoted exploration in the area. Methods Based on the newly obtained 3D seismic data and a regional geological overview, the oil source conditions, structural and evolutionary characteristics of strike-slip faults, and formation and sealing conditions of lithologic traps were systematically analysed, and the reservoir formation pattern and favourable exploration directions in this area were clarified. Results In this area, fluvial-delta sedimentary systems developed in the Mesozoic, including a NE-SW-trended delta sand-body developed during the Triassic, the SE-NW-directed shallow water delta sand-bodies developed during the Early Jurassic and Cretaceous, and a large scale of continuous braided river sand-body developed during Late Cretaceous. The study area had experienced three uplift episodes and five faulting episodes. The Triassic-Jurassic fault system accompanied by the Palaeozoic fault system show NE-SW-striked in echelon. The front edge of the Cretaceous and Jurassic shallow water deltas was spliced with a single body or multiple bodies covered with mudstone to form lateral occlusion, which combined with an upwards-dipping fault to form a lithology-fault trap. The Triassic striped sand-body spread in the southeast direction and formed lithology, and the mudstone shading outside the channel at the bend of the large river channel formed a lithological trap. Hydrocarbon sourced from Palaeozoic palaeo-accumulations, migrated through Palaeozoic-Ordovician faults, and directly or successively charged into the Mesozoic trap through the Mesozoic fault. Conclusion Based on the hydrocarbon accumulation model, it is believed that the potential exploration areas in the study area mainly include the Jurassic-Cretaceous Shushan River formation Delta front lithological reservoir of the northern strike-slip zone, the delta front sand-body on the north side of the Triassic, and the southern channel sand-body lithological trap, and the northern Triassic descending area covered with small fan lithological traps. The three controlling factors, fault assemblage, sand-body distribution, and mantled mudstone shielding, and their effective allocation are important for guaranteeing the formation of favourable lithologic and lithologic fault combination traps in the large slope areas of the Tabei Uplift belt. The research results point out the direction of further hydrocarbon exploration in this area and are important for guiding hydrocarbon reservoir exploration of lithologic and lithologic fault combination traps in other areas.

There is a growing amount of research that highlights the significant connection between the development of colitis and both metabolic imbalance and the inflammatory response. Tagatose, an inherent sweetening agent and alternative to sugar, plays a crucial role in the biosynthesis of several chemicals and metabolic pathways in living organisms. However, the specific biochemical mechanism via which tagatose hinders colitis is still not understood. According to recent study, tagatose plays a crucial role in safeguarding the integrity of tight junctions inside the intestinal mucosal barrier. Furthermore, it is crucial to acknowledge the presence of a correlation between the severity of inflammatory bowel disease (IBD) and the occurrence of colorectal cancer (CRC), chemically-induced colitis in rodents, and reduced blood levels of tagatose. The treatment of tagatose resulted in a decrease in intestinal mucosal injury in mice with colitis, regardless of whether it was caused by dextran sodium sulfate (DSS) or spontaneous colitis in IL-10-/- mice and C3H/HeJBir mice. The introduction of tagatose in a colitis model triggers a cascade of events, wherein it hinders the expulsion of cathepsin B and enhances lysosomal cohesiveness. The aforementioned method successfully inhibits the activity of myosin light chain kinase (MLCK) in the context of intestinal epithelial damage, hence impeding the deterioration of tight junction integrity and the initiation of mitochondrial dysfunction. In summary, the outcomes of the study have provided empirical evidence that substantiates the beneficial effects of tagatose in mitigating the progression of colitis. The ability to prevent the disruption of the intestinal barrier is responsible for this achievement. Hence, tagatose has promise as a therapeutic adjunct for the management of colitis.

Benggang, an erosional phenomenon located in southern China, exhibits distinctive characteristics that can have profound ecological and agricultural consequences as well as pose risks to human life. Previous investigations have primarily focused on elucidating the relationships between the physical and chemical attributes of soils collected from Benggang. However, the precise role of free iron oxides in the surface properties of Benggang soil and its contribution to the formation of Benggang remains largely unexplored. In this study, we aim to investigate the role of free iron oxides in Benggang soil by removing them and subsequently introducing goethite to evaluate their impact on the soil’s surface properties. Our results reveal a decrease in the surface charge density of soil colloidal particles with increasing soil depth. Specifically, the uppermost red soil layer exhibits the highest value, followed by the sandy soil and the lowermost clastic layer. Upon removing free iron oxide, we documented reductions of 44.28% (red soil), 20.62% (sandy soil), and 8.70% (clastic layer) in the surface charge density of colloidal particles. The red soil layer presented an over 18-fold increase compared to the initial linear shrinkage, followed by the sandy soil and clastic layer. Notably, the addition of goethite to the iron oxide-free soil layers resulted in the recovery of approximately 81.93%, 121.13%, and 104.35% of the initial surface charge density, respectively. Moreover, significant changes in volume shrinkage were observed, with approximately 97.54% (red soil), 94.75% (sandy soil), and 89.72% (clastic layer) of the initial values being influenced. These findings underscore the substantial influence of free iron oxide on the physicochemical properties of Benggang soil and contribute to a comprehensive understanding of the erosive mechanisms underlying Benggang formation.

Revolutionary agricultural structural reforms in the supply chain and cutting-edge institutional mechanisms are pivotal in catalyzing a quantum leap in food production. China’s focus on achieving self-sufficiency in grain production for domestic security necessitates structural reforms in the agricultural supply chain and innovative institutional mechanisms. The emergence of socialized agricultural institutions plays a pivotal role in providing essential services to smallholder farmers. However, a dearth of studies evaluating the efficacy of these services in enhancing grain production exists. This study aims to fill this gap by analyzing provincial panel data from China spanning 2011 to 2020 to evaluate the impact of Agricultural Socialized Services (ASS) development levels on grain production. Employing panel and panel threshold models for empirical analysis, the research investigates how this impact varies between major grain-producing regions and non-major grain-producing regions. Findings indicate a significant positive effect of ASS on grain production, with a correlation coefficient of 1.3555. While its impact is less pronounced in grain-producing regions, it proves beneficial in non-grain regions. Moreover, the transfer of farmland use rights amplifies ASS’s influence on grain production, with a threshold value of 33.18%. The study concludes by outlining policy implications from various perspectives, providing practical recommendations for policymakers and stakeholders in the agricultural sector.

Abstract Background Calcification is a common phenomenon in both benign and malignant thyroid nodules. However, the clinical significance of calcification remains unclear. Therefore, we explored a more objective method for distinguishing between benign and malignant thyroid calcified nodules. Methods This retrospective study, conducted at two centers, involved a total of 631 thyroid nodules, all of which were pathologically confirmed. Ultrasound image sets were employed for analysis. The primary evaluation index was the area under the receiver-operator characteristic curve (AUROC). We compared the diagnostic performance of deep learning (DL) methods with that of radiologists and determined whether DL could enhance the diagnostic capabilities of radiologists. Results The Xception classification model exhibited the highest performance, achieving an AUROC of up to 0.970, followed by the DenseNet169 model, which attained an AUROC of up to 0.959. Notably, both DL models outperformed radiologists (P

As an important means to enhance oil recovery, ternary composite flooding (ASP flooding for short) technology has achieved remarkable results in Daqing Oilfield. Alkalis, surfactants and polymers are mixed in specific proportions and injected into the reservoir to give full play to the synergistic effect of each component, which can effectively enhance the fluidity of crude oil and greatly improve the oil recovery. At present, the technology for further improving oil recovery after ternary composite flooding is not mature and belongs to the stage of technical exploration. The presence of alkaline substances significantly alters the reservoir’s physical properties and causes considerable corrosion to the equipment used in its development. This is detrimental to both the environment and production. Therefore, it is necessary to develop green displacement control agents. In the reservoir environment post-ASP flooding, 2-(methylamino)ethyl methacrylate and glycidyl methacrylate were chosen as monomers to synthesize a polymer responsive to alkali, and then grafted with cellulose nanocrystals to form microspheres of alkali-resistant swelling hydrogel. Cellulose nanocrystals (CNCs) modified with functional groups and other materials were utilized to fabricate hydrogel microspheres. The product’s structure was characterized and validated using Fourier transform infrared spectroscopy and X-ray diffraction. The infrared spectrum revealed characteristic absorption peaks of CNCs at 1165 cm−1, 1577 cm−1, 1746 cm−1, and 3342 cm−1. The diffraction spectrum corroborated the findings of the infrared analysis, indicating that the functional modification occurred on the CNC surface. After evaluating the swelling and erosion resistance of the hydrogel microspheres under various alkaline conditions, the optimal particle size for compatibility with the target reservoir was determined to be 6 μm. The potential of cellulose-based gel microspheres to enhance oil recovery was assessed through the evaluation of Zeta potential and laboratory physical simulations of oil displacement. The study revealed that the absolute value of the Zeta potential for gel microspheres exceeds 30 in an alkaline environment with pH values ranging from 7 to 14, exhibiting a phenomenon where stronger alkalinity correlates with a greater absolute value of Zeta potential. The dispersion stability spans from good to excellent. The laboratory oil displacement simulation experiment was conducted using a cellulose-based gel microsphere system following weak alkali ASP flooding within the pH value range from 7 to 10. The experimental interventions yielded recovery rates of 2.98%, 3.20%, 3.31%, and 3.38%, respectively. The study indicates that cellulose-based gel microspheres exhibit good adaptability in alkaline reservoirs. This research offers a theoretical foundation and experimental approaches to enhance oil recovery techniques post-ASP flooding.

Abstract Background Sarcopenia is commonly seen in the older adults and increases in incidence with age, also in Parkinson’s disease (PD). Although research has indicated that the development of sarcopenia in patients with PD may be related to both motor symptoms and non-motor symptoms (NMS), the precise relationship between the two conditions remains unclear. Therefore, we aimed to investigate the incidence of sarcopenia in patients with PD and its association with NMS. Methods The study included 123 patients with PD and 38 age- and sex-matched healthy controls (HC). All participants were evaluated for sarcopenia using the 2019 Asian Sarcopenia Diagnostic Criteria, and patients with PD underwent standard assessments of motor symptoms and NMS. Multiple logistic regression and receiver operating characteristic (ROC) curve analyses were used to examine the association between sarcopenia and NMS in patients with PD. Results The incidence of sarcopenia was significantly higher in patients with PD than in HC (26.8% vs. 10.4%, p = 0.046). Multiple logistic regression analysis revealed that poorer sleep quality (odds ratio [OR]: 1.245; 95% confidence interval [CI]: 1.011–1.533; p = 0.040) and fatigue (OR: 1.085, 95% CI: 1.006–1.170, p = 0.034) were independently associated with sarcopenia. ROC analysis indicated that the optimal cut-off value for Pittsburgh Sleep Quality Index (PSQI) scores was 10, with 72.7% sensitivity and 74.4% specificity (area under the curve [AUC] = 0.776, 95% CI: 0.683–0.868, p

IntroductionThis study emphasizes the importance of agricultural efficiency for food security and income generation, especially among smallholder rice farmers in southern China. Limited access to essential agricultural services hinders productivity in this region. The study highlights the significant potential of agricultural socialized services (ASS) in improving the technical efficiency of smallholder rice production.MethodsTo analyze the impact of ASS on technical efficiency in rice production, we focused on tillage, transplanting, crop protection, and harvest operations. We employed stochastic frontier analysis and collected data from smallholder farmers in Hunan, Jiangxi, and Zhejiang provinces. By estimating the technical efficiency of rice production, we aimed to assess the relationship between ASS and smallholder farmers’ technical efficiency.Results and discussionThe results of our analysis revealed that ASS significantly enhance the technical efficiency of rice production among smallholder farmers by supporting agricultural practices such as transplanting, crop protection, and harvest operations. However, we found that the impact of ASS on tillage operations was not statistically significant. Participation in ASS enhances smallholders’ access to modern production techniques, resources, and knowledge, leading to improved technical efficiency. These services also empower smallholder rice producers to adopt sustainable farming practices, access credit, financing, and market information, and promote collective action and cooperation, ultimately influencing technical efficiency.ConclusionThis study emphasizes the potential of ASS in improving the technical efficiency of smallholder rice production in southern China. Policymakers and agricultural organizations can use these insights to design interventions that promote efficient practices, enhance productivity, support livelihoods, and ensure food security in the region.

IntroductionEmergency medical rescue plays a vital role in alleviating the harm of all kinds of emergencies to people's physical and mental health and life safety. The current emergency medical teams (EMTs) formation model is not unified. We focused on the disadvantages of the bricolage mode of China EMTs and put forward empirical-based countermeasures to improve the emergency management ability of EMTs.MethodsFrom March to September 2022, 23 leaders of EMTs in North China (Tianjin) were selected by objective sampling method to conduct one-to-half structured in-depth interviews. Nvivo12.0 software was used for three-level coding. The disadvantages of the bricolage model of EMT were analyzed.ResultsBased on the three-level coding, 150 initial concepts, 36 sub-coding, 17 main coding, six categories, and two core categories were sorted out. Management structure, internal stability, and support are recognized as the crucial elements armed with the EMTs.DiscussionThe bricolage EMTs have disadvantages such as a chaotic management structure, weak internal stability, and inadequate support. It is necessary to construct full-time EMTs that incorporate a standardized personnel admission mechanism, full-time training and exercise mechanism, diversified incentive mechanism, and multi-agent cooperation mechanism, etc.

Abstract Background Hydroxychloroquine (HCQ) is recommended as a treatment for IgA nephropathy (IgAN) to control proteinuria. The long-term effects of HCQ compared to systemic corticosteroid therapy remain unclear. Methods We conducted a retrospective case‒control study at Peking University First Hospital. Thirty-nine patients with IgAN who received HCQ for at least 24 months without corticosteroids (CSs) or other immunosuppressive agents were included. Thirty-nine matched patients who received systemic CS therapy were selected using propensity score matching. Clinical data over a 24-month period were compared. Results In the HCQ group, the level of proteinuria decreased from 1.72 [1.44, 2.35] to 0.97 [0.51, 1.37] g/d (-50.5 [-74.0, -3.4] %, P

Objective: The effect of processing on the volatile fractions of different parts of the flowers of Camellia liberofilamenta was investigated. Methods: Different parts of the whole flowers, petals and stamens of C. liberofilamenta were processed by spreading, microwave killing and drying to make dry samples, separately, and then the effect of processing on volatile components extracted from different parts of the flowers. Results: A total of 73 kinds of volatile substances were identified, which were mainly alcohols, aldehydes, ketones, esters, acids, terpenes and others, and alcohols and aldehydes were the main volatile compounds. In terms of the type and quantity of volatile substances, the effect of processing on whole flower was greater than that on stamen and petal. Linalsol, methyl endolaurate and methyl acetate were negatively correlated to the volatile components of the tea. Alcohols and aldehydes contributed significantly to the volatile components of the whole dry flower, C6 volatile compounds contributed significantly to the volatile components of the petals, and carotenoid degraded volatile compounds contributed significantly to the volatile components of the stamens. Conclusion: There are some differences in the types and relative contents of volatile substances in different parts of stamens, petals and whole flower, and the main contribution volatile substances are different. The influence of processing on whole flower is greater than that of stamens and petals.

Abstract Background Measurement of the Chinese burden of disease with disability-adjusted life-years (DALYs) requires disability weight (DW) that quantify health losses for all non-fatal consequences of disease and injury. The Global Burden of Disease (GBD) 2013 DW study indicates that it is limited by lack of geographic variation in DW data and by the current measurement methodology. We aim to estimate DW for a set of health states from major diseases in the Wuhan population. Methods We conducted the DW measurement study for 206 health states through a household survey with computer-assisted face-to-face interviews and a web-based survey. Based on GBD 2013 DW study, paired comparison (PC) and Population health equivalence (PHE) method was used and different PC/PHE questions were randomly assigned to each respondent. In statistical analysis, the PC data was analyzed by probit regression. The probit regression results will be anchored by results from the PHE data analyzed by interval regression on the DW scale units between 0 (no loss of health) and 1 (loss equivalent to death). Results A total of 2610 and 3140 individuals were included in the household and web-based survey, respectively. The results from the total pooled data showed health state “mild anemia” (DW = 0.005, 95% UI 0.000–0.027) or “allergic rhinitis (hay fever)” (0.005, 95% UI 0.000–0.029) had the lowest DW and “heroin and other opioid dependence, severe” had the highest DW (0.699, 95% UI 0.579–0.827). A high correlation coefficient (Pearson’s r = 0.876; P

Human pharyngeal squamous cell carcinoma (HPSCC) is the most common malignancy in the head and neck region, characterized by high mortality and a propensity for metastasis. Fucoxanthin, a carotenoid isolated from brown algae, exhibits pharmacological properties associated with the suppression of tumor proliferation and metastasis. Nevertheless, its potential to inhibit HPSCC proliferation and metastasis has not been fully elucidated. This study represents the first exploration of the inhibitory effects of fucoxanthin on two human pharyngeal squamous carcinoma cell lines (FaDu and Detroit 562), as well as the mechanisms underlying those effects. The results showed dose-dependent decreases in the proliferation, migration, and invasion of HPSCC cells after fucoxanthin treatment. Further studies indicated that fucoxanthin caused a significant reduction in the expression levels of proteins in the phosphoinositide 3−kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, as well as the downstream proteins matrix metalloproteinase (MMP)−2 and MMP−9. Specific activators of PI3K/AKT reversed the effects of fucoxanthin on these proteins, as well as on cell proliferation and metastasis, in FaDu and Detroit 562 cells. Molecular docking assays confirmed that fucoxanthin strongly interacted with PI3K, AKT, mTOR, MMP−2, and MMP−9. Overall, fucoxanthin, a functional food component, is a potential therapeutic agent for HPSCC.

Abstract Background Colorectal cancer (CRC) is one of the most common cancers worldwide. Comprehensive data on the economic burden of CRC at a population‐level is critical in informing policymaking, but such data are currently limited in China. Methods From a societal perspective, the economic burden of CRC in 2019 was estimated, including direct medical and nonmedical expenditure, disability, and premature‐death‐related indirect expenditure. Data on disease burden was taken from the GBD 2019 and analyzed using a prevalence‐based approach. The per‐person direct expenditure and work loss days were from a multicenter study; the premature‐death‐related expenditure was estimated using a human capital approach. Projections were conducted in different simulated scenarios. All expenditure data were in Chinese Yuan (CNY) and discounted to 2019. Results In 2019, the estimated overall economic burden of CRC in China was CNY170.5 billion (0.189% of the local GDP). The direct expenditure was CNY106.4 billion (62.4% of the total economic burden), 91.4% of which was a direct medical expenditure. The indirect expenditure was CNY64.1 billion, of which 63.7% was related to premature death. The predicted burden would reach CNY560.0 billion in 2030 given constant trends for disease burden; however, it would be alternatively reduced to

Compared to conventional vertical wells, horizontal wells with Ultra-Long horizontal sections greatly increase the oil drainage area and can significantly increase oil and gas production from individual wells. In order to analyze the limit of horizontal well extension, an extension limit model was developed, which takes into account formation, rated pump pressure, rated pressure and string buckling, and is used to predict the limit of horizontal well extension under different constraints. The results show that increasing the inside and outside diameter of drill pipe can effectively reduce pressure loss and facilitate the extension of the horizontal section while keeping the hole size unchanged. As the cuttings density, cuttings diameter, mud density, mud performance, pump rates, and ROP increase, the limit extension length of the horizontal section gradually decreases. As the WOB, RPM, friction factor increase, the torque gradually increases and the limit extension length of the horizontal section gradually decreases. Selecting the right combination of drilling tools can reduce the torque, which is beneficial for mechanical extension. This study is instructive for the limit of horizontal well extension with ultra-long horizontal sections in the field.

Decarbonization of the power sector in China is an essential aspect of the energy transition process to achieve carbon neutrality. The power sector accounts for approximately 40% of China’s total CO2 emissions. Accordingly, collaborative optimization in power generation expansion planning (GEP) simultaneously considering economic, environmental, and technological concerns as carbon emissions is necessary. This paper proposes a collaborative mixed- integer linear programming optimization approach for GEP. This minimizes the power system’s operating cost to resolve emission concerns considering energy development strategies, flexible generation, and resource limitations constraints. This research further analyzes the advantages and disadvantages of current GEP techniques. Results show that the main determinants of new investment decisions are carbon emissions, reserve margins, resource availability, fuel consumption, and fuel price. The proposed optimization method is simulated and validated based on China’s power system data. Finally, this study provides policy recommendations on the flexible management of traditional power sources, the market-oriented mechanism of new energy sources, and the integration of new technology to support the attainment of carbon-neutral targets in the current energy transition process.

Glioblastoma multiforme (GBM) is the most aggressive and deadliest type of brain tumor with a > >th he most aggressive and deadliest type of brain tumor witnear-infrared fluorescent dye, but it is hard to directly target brain tumor. Therefore, our study aimed to develop a new carrier for ICG to accurately visualize cancer tissue during surgery. Exosomes were isolated from culture U-87 MG cells, then loaded with Indocyanine green (ICG) and conjugated with RGERPPR peptide (RGE) (R-exo-ICG). The parameters of R-exo-ICG were analyzed and injected into tumor-bearing nude mice to evaluate its anti-tumor effect. R-exo-ICGs were nano size, and completely released ICG within 24 h. RGE modification increased cell uptake of exosomes, and induced cell apoptosis through activating Caspase 3 signaling pathway after laser irradiation. Moreover, R-exo-ICG was largely accumulated in the brain tumor in vivo, and inhibited tumor growth in tumor-bearing mice. RGE-conjugated exosomes that loaded ICG could target brain tumor in mice and significantly inhibited tumor growth in mice, which suggested that R-exo-ICG might serve as a novel approach for GBM treatment.

BackgroundImmunoglobulin A nephropathy (IgAN) is one of the leading causes of end-stage kidney disease (ESKD). Many studies have shown the significance of pathological manifestations in predicting the outcome of patients with IgAN, especially T-score of Oxford classification. Evaluating prognosis may be hampered in patients without renal biopsy.MethodsA baseline dataset of 690 patients with IgAN and an independent follow-up dataset of 1,168 patients were used as training and testing sets to develop the pathology T-score prediction (Tpre) model based on the stacking algorithm, respectively. The 5-year ESKD prediction models using clinical variables (base model), clinical variables and real pathological T-score (base model plus Tbio), and clinical variables and Tpre (base model plus Tpre) were developed separately in 1,168 patients with regular follow-up to evaluate whether Tpre could assist in predicting ESKD. In addition, an external validation set consisting of 355 patients was used to evaluate the performance of the 5-year ESKD prediction model using Tpre.ResultsThe features selected by AUCRF for the Tpre model included age, systolic arterial pressure, diastolic arterial pressure, proteinuria, eGFR, serum IgA, and uric acid. The AUC of the Tpre was 0.82 (95% CI: 0.80–0.85) in an independent testing set. For the 5-year ESKD prediction model, the AUC of the base model was 0.86 (95% CI: 0.75–0.97). When the Tbio was added to the base model, there was an increase in AUC [from 0.86 (95% CI: 0.75–0.97) to 0.92 (95% CI: 0.85–0.98); P = 0.03]. There was no difference in AUC between the base model plus Tpre and the base model plus Tbio [0.90 (95% CI: 0.82–0.99) vs. 0.92 (95% CI: 0.85–0.98), P = 0.52]. The AUC of the 5-year ESKD prediction model using Tpre was 0.93 (95% CI: 0.87–0.99) in the external validation set.ConclusionA pathology T-score prediction (Tpre) model using routine clinical characteristics was constructed, which could predict the pathological severity and assist clinicians to predict the prognosis of IgAN patients lacking kidney pathology scores.

Introduction: IgA nephropathy (IgAN) is a leading cause of end-stage renal disease. The exact pathogenesis of IgAN is not well defined, but some genetic studies have led to a novel discovery that the (immuno)proteasome probably plays an important role in IgAN. Methods: We firstly analyzed the association of variants in the UBE2L3 region with susceptibility to IgAN in 3,495 patients and 9,101 controls, and then analyzed the association between lead variant and clinical phenotypes in 1,803 patients with regular follow-up data. The blood mRNA levels of members of the ubiquitin-proteasome system including UBE2L3 were analyzed in peripheral blood mononuclear cells from 53 patients and 28 healthy controls. The associations between UBE2L3 and the expression levels of genes involved in Gd-IgA1 production were also explored. Results: The rs131654 showed the most significant association signal in UBE2L3 region (OR: 1.10, 95% CI: 1.04–1.16, p = 2.29 × 10−3), whose genotypes were also associated with the levels of Gd-IgA1 (p = 0.04). The rs131654 was observed to exert cis-eQTL effects on UBE2L3 in various tissues and cell types, particularly in immune cell types in multiple databases. The UBE2L3, LUBAC, and proteasome subunits were highly expressed in patients compared with healthy controls. High expression levels of UBE2L3 were not only associated with higher proteinuria (r = 0.34, p = 0.01) and lower eGFR (r = −0.28, p = 0.04), but also positively correlated with the gene expression of LUBAC and other proteasome subunits. Additionally, mRNA expression levels of UBE2L3 were also positively correlated with IL-6 and RELA, but negatively correlated with the expression levels of the key enzyme in the process of glycosylation including C1GALT1 and C1GALT1C1. Conclusion: In conclusion, by combined genetic association and differed expression analysis of UBE2L3, our data support a role of genetically conferred dysregulation of the (immuno)proteasome in regulating galactose-deficient IgA1 in the development of IgAN.

In this research, a new type of spring steel with ultra-high strength and toughness was designed, and its mechanical properties and microstructure under different heat treatment processes were studied. The results show that the optimal heat treatment process for the steel is oil quenching at 890 °C for 40 min, followed by tempering at 400 °C for 1 h. Its mechanical properties have an optimal combination of 1865MPa tensile strength, a yield strength of 1662 MPa, an elongation of 11.5%, a cross-sectional shrinkage of 51.5%, and a Charpy impact energy of 43.7 J at room temperature. With increasing austenitizing temperature, the austenite grain size increases, the martensite lath becomes thicker, and the strength decreases. With increasing tempering temperature, the lath boundary of martensite becomes blurred, the strength decreases, and the plasticity improves. In addition, it was found that during tempering at higher temperature (450 °C), large particle inclusions and secondary cracks appeared in the fractured surface, and a large number of carbides precipitated, leading to the brittleness of tempered martensite.