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Abstract Little is known about the long-term effectiveness of risk-based treat-to-target cholesterol-lowering interventions on cardiovascular risk. Here, we show the emulated effectiveness of guideline-recommended low-density and non-high-density lipoprotein cholesterol-lowering interventions using the absolute risk reduction (ARR) and the restricted mean event-free time-based number needed to treat (NNT). With 5,375 participants, the 29-year risks for cardiovascular disease (CVD), all-cause mortality, and atherosclerotic CVD were 18.6%, 25.6%, and 17.7%, respectively. Long-term treat-to-target interventions showed significant reductions in CVD (ARR −2.3%, 95%CI −3.4% to −0.8%; NNT 115), all-cause mortality (−3.0%, −4.3% to −1.8%; 95), and atherosclerotic CVD (−2.6%, −3.5% to −1.2%; 104). Such effects appear more pronounced in women, smokers, and those with body mass index

Abstract Craniofacial structure and dental hard tissue used to be researched on by traditional imaging tools such as light microscope, electron microscope and micro-CT. Due to the limitations of imaging principle, resolution and 3D rendering reconstruction technique, traditional imaging tools are constrained for presenting fine structure and precise measurements. Here a brand-new imaging equipment–3D X-ray microscope is introduced to realize a more efficient scanning by demonstrating the comparison of the craniofacial structures and dental hard tissue of diabetes and normal DBA mouse. To explore a higher resolution, more efficient imaging measurement and 3D reconstruction method on craniofacial structure and dental hard tissue. The study included 12 DBA mice which were divided into two groups (control group and diabetes group). The heads were separated and scanned by 3D X-ray microscope, after which regions of interest were selected, followed by measurement and 3D reconstruction based on microscope attached software Dragonfly pro©. Hemi-mandibles were collected for enamel mineral density assessment supported by QRM-MicroCT-HA phantom. Data was submitted to paired t-tests at a 95% confidence level. The automatic assessed enamel thickness of diabetes mice decreased on average, whereas the rest of manual measurements and automatic assessed density showed no statistical difference. We constructed HA phantom assisted enamel density procedure in Dragonfly software. Craniofacial structure and dental hard tissue were well-presented both in 2D slide and 3D reconstruction viewport by 3D X-ray microscope which can be routinely used as craniofacial structure and dental hard tissue imaging tool.

Abstract Background Rimegepant, a small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, is indicated for acute and preventive migraine treatment in the United States and other countries. However, there is a lack of prospective real-world evidence for the use of rimegepant in Chinese migraine patients. Methods This was a single-arm, prospective, real-world study. While taking rimegepant to treat migraine attacks as needed, eligible participants were asked to record their pain intensity, functional ability, and accompanying symptoms for a single attack at predose and 0.5, 1, 2, 24, and 48 h postdose via a digital platform. Adverse events (AEs) during the rimegepant treatment period were recorded and analysed. The percentages of participants who experienced moderate to severe pain at predose and 0.5, 1, 2, 24, and 48 h postdose were assessed. Additionally, the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose were analysed. In addition, the total cohort (full population, FP) was stratified into a prior nonresponder (PNR) group to observe the effectiveness and safety of rimegepant for relatively refractory migraine and a rimegepant and eptinezumab (RE) group to observe the effectiveness and safety of the combination of these drugs. Results By November 24th, 2023, 133 participants (FP, n = 133; PNR group, n = 40; RE group, n = 28) were enrolled, and 99 participants (FP, n = 99; PNR group, n = 30; RE group, n = 23) were included in the analysis. Rimegepant was effective in treating migraine in the FP and both subgroups, with a significant decreasing trend in the percentages of participants experiencing moderate to severe pain postdose (p

Introduction: Lecithin cholesterol acyltransferase (LCAT) plays a crucial role in acyl-esterifying cholesterol in plasma, which is essential for reverse cholesterol transport (RCT). Previous studies indicated that its activity on both α and β lipoproteins interpret its effects on lipoproteins for many controversial investigations of atherosclerosis. Objectives: To better understand the relationship between LCAT, diet-induced dyslipidemia and atherosclerosis, we developed a double knockout (LCAT−/−&LDLR−/−, DKO) hamster model to evaluate the specific role of LCAT independent of LDL clearance effects. Methods: Plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and free cholesterol (FC) levels were measured using biochemical reagent kits. FPLC was performed to analyze the components of lipoproteins. Apolipoprotein content was assessed using western blotting (WB). The hamsters were fed a high cholesterol/high fat diet (HCHFD) to induce atherosclerosis. Oil Red O staining was employed to detect plaque formation. Peritoneal macrophages were studied to investigate the effects of LCAT on cholesterol uptake and efflux. Results: On HCHFD, DKO hamsters exhibited significantly elevated levels of TG and FC, while HDL-C was nearly undetectable without affecting TC levels, as compared to low-density lipoprotein receptor (LDLR)-deficient (LDLR−/−, LKO) hamsters. Lipoprotein profiling revealed a marked increase in plasma chylomicron/very low-density lipoprotein (CM/VLDL) fractions, along with an unexpected reduction in LDL fraction in DKO hamsters. Furthermore, DKO hamsters displayed aggravated atherosclerotic lesions in the aorta, aortic root, and coronary artery relative to LKO hamsters, attributed to a pro-atherogenic lipoprotein profile and impaired cholesterol efflux in macrophages. Conclusions: Our study demonstrates the beneficial role of LCAT in inhibiting atherosclerotic development and highlights the distinctive lipid metabolism characteristics in hamsters with familial hypercholesterolemia.

[Objective] The Qinghai-Tibetan Plateau is an important ecological barrier in China, and alpine meadows are an important part of it, and the function of soil and water conservation is an important ecological service function of alpine meadows. Therefore, it is of great significance to carry out the study of soil erosion process in alpine meadows on the Tibetan Plateau to reduce anthropogenic disturbance of soil erosion and to safeguard the ecological security of the southwest region. [Methods] In this study, five different types of slopes, namely, undegraded, mildly degraded, moderately degraded, bare slopes and artificially restored slopes in alpine meadows of the Tibetan Plateau, were selected to analyze the process of flow and sand production on degraded and restored slopes under different rainfall intensities, and to reveal the relationship between the erosion mechanism and water-sand relationship between degraded slopes and restored slopes with artificial vegetation through the simulated rainfall test in the field. [Results] (1) The initial flow production time is relatively short on the undegraded slopes of alpine meadows and the restored slopes with artificial vegetation because of their dense root system, and the water infiltration ability is relatively weak; while on the mildly degraded slopes, the lateral flow and vertical infiltration ability are relatively strong, and the initial flow production time is relatively long. (2) Under regular rainfall conditions (30 and 60 mm/h), the flow rate of mildly degraded slopes is the smallest, and the flow reduction benefit is the highest, reaching 77.13%, the flow rate of artificially restored slopes is close to that of undegraded slopes and is slightly higher than that of mildly degraded slopes; the cumulative flow rate of bare soil slopes is the largest, and it is significantly higher than other slopes; the flow rate of undegraded slopes under extreme rainfall conditions (90 mm/h) is surging, only lower than that of bare slopes and significantly higher than other slopes. Under extreme rainfall conditions (90 mm/h), the flow rate of undegraded slopes increased, which was only lower than that of bare slopes and significantly higher than that of artificially restored slopes. (3) Under regular rainfall conditions (30 and 60 mm/h), the sand reduction benefit of the artificially restored vegetated slopes was the highest, reaching 81.97% and 89.82%, followed by the undegraded slopes, and with the increase of the degradation degree of the vegetation, the sand reduction benefit was gradually reduced; however, under extreme rainfall conditions, the sand reduction benefit of the artificially restored vegetation and the undegraded slopes was almost the same, and the sand production of the moderately degraded slopes was higher than the undegraded slopes, which is significantly higher than the other slopes. However, under extreme rainfall conditions, the sand reduction benefits of artificially restored vegetation and undegraded slopes are almost the same, while the sand production of moderately degraded slopes is 4.59 times of that of undegraded slopes. [Conclusion] The results of these studies can provide important scientific basis for vegetation restoration and ecological security in alpine meadow area.

[Objective] With the intensified influence of climate change and human activities, the climate and underlying surface conditions of the basins have changed. Accurately simulating the process of soil moisture change and analyzing its influencing factors are of great significance for regional water resource management and vegetation construction. [Methods] The Weihe River Basin in the Loess Plateau was taken as the research object. Based on the ABCD hydrological model, the EFAST method was used to analyze the parameter sensitivity of the model, and the constant parameter and time-varying parameter models were constructed. The runoff depth and soil water storage simulation accuracy of different parameter models were compared. The effects of climate change and vegetation restoration on soil water storage changes in the Weihe River Basin were discussed, and the dominant factors of soil water storage changes were clarified. [Results] The proportional parameter of soil water layer recharge groundwater c was the most sensitive, followed by the groundwater storage coefficient d, the upper limit parameter b of the sum of actual evapotranspiration and soil water storage, and the tendency parameter a of runoff that before the soil is completely saturated was the least sensitive. Compared with the ABCD constant parameter model, the time-varying parameter model increased the values of NSE, KGE, and R2 of the runoff depth simulation results by 19%, 10%, and 19%, respectively, and the NSE, KGE, and R2 of the verification period increased by 7%, 7%, and 9%, respectively. The time-varying parameter model significantly improved the runoff depth simulation results. The srtongest correlation between soil water storage in the Weihe river basin and ERA 5-Land 0-100 cm soil layer based on time-varying parameter model simulation, and the change process of the two agreed well. The degree of different influencing factors on the change of soil water storage in the Weihe River Basin from strong to weak was potential evapotranspiration>precipitation>NDVI. [Conclusion] The research results provide a scientific basis for water resources planning and management and vegetation construction in this area and they also provide references for soil water storage research in other similar areas.

Currently, China is undergoing a comprehensive transition toward a digital society, which has placed renewed emphasis on the need for robust national-level digital management capabilities. Identity management serves as a foundational support for the construction of Digital China and social security in the new era, with direct implications for national, social, and individual security. This study explores the major challenges faced by the digital identity system in supporting digital society governance, analyzes the current status and key problems of digital identity management, proposes the development goal and major tasks of building a secure and reliable digital social identity management system, and clarifies the trend of key technologies in establishing a digital identity system with Chinese characteristics. Furthermore, we propose the following suggestions: (1) strengthening toplevel design to formulate the development strategy and implementation roadmap of digital identity, (2) improving related laws and regulations, (3) establishing a digital identity management system with a hybrid architecture featuring centralized management and distributed authentication, (4) strengthening digital identity supervision capabilities, (5) enhancing the standard management of participants, (6) fostering ecological cooperation, and (7) actively engaging in global governance, thus to promote the development of the digital identity system and facilitate the long-term and stable development of digital society administration.

Abstract A power system can be regarded as a cyber‐physical system with physical power networks and a cyber system based on increasing engagement with information communication technologies for smart grid functionalities for more efficient operations and control. Non‐intrusive load monitoring (NILM), an emerging smart‐grid technology, can be used to better understand the electricity usage profile and composition of smart meters using advanced data analysis algorithms. Although NILM enables various smart grid services, wider applications of NILM require addressing the challenges regarding cyber security and data privacy risks. Anomaly detection in appliance data is one of the most effective measures against potential cyber intrusions from a data perspective. This study proposes a framework of anomaly detection‐based learning algorithms to identify the anomalous periods of electricity loading data, which may be a subject for potential cyber‐attacks. Comparison studies with the hidden Markov model are performed to validate the proposed approaches. The simulation results show that these anomaly detection‐based learning algorithms work well and can precisely determine anomalous loading periods. Moreover, these trained models perform well on the testing dataset without prior knowledge of the data, providing the possibility of the real‐time assessment of power‐ loading states. The proposed framework can also be used to develop protective measures to ensure secure system operation and user data privacy.

Hexafluoroisobutylene (HFIB) is an important compound widely used in semiconductor lithography materials, refrigerants, fluorine coatings, and pharmaceutical intermediates in the fluorination industry. Owing to its toxicity, the occupational exposure in the workplace, especially for pregnant woman is the concern and there is still lack of the data of HFIB toxicity on pregnancy and fetal development. Here, for the first time, we investigated the effects of HFIB on pregnant rats and fetal development. The pregnant rats were exposed to different doses of HFIB (0 ppm, 27.2 ppm, 53.5 ppm, 105.6 ppm) via whole-body inhalation for the period of organogenesis, which from implantation (gestation day 5) to the day prior to scheduled caesarean section (gestation day 19). The results showed that the pregnant rats exposed to 105.6 ppm HFIB displayed systemic toxicity, including a decrease in body weight and food consumption, as well as tracheal inflammation, pulmonary interstitial inflammation and renal tubular swelling. Moreover, reduced fetal and placental weights, delayed ossification, and a reduced number of ossification centers were observed in fetuses delivered by pregnant rats exposed to 105.6 ppm. These effects were attributed to severe maternal weight loss. In addition, it would be useful to note that no whole-body, visceral or skeletal congenital malformations were observed. However, HFIB exposure at 53.5 ppm showed no significant adverse effects on pregnant rats and fetuses. These findings demonstrate that 105.6 ppm HFIB is a toxic concentration, while 53.5 ppm HFIB is the no-observed-adverse-effect concentration (NOAEC) for both pregnancy and fetal development. This study for the first time to provide evidence for the health risk of HFIB exposure on pregnancy and fetal development.

ABSTRACT: China has abundant local duck resource populations, and evaluating the characteristics of these breeds will help improve development and utilization. In this study, we conducted the first investigations of growth and slaughter performance on Sichuan Shelduck (n = 240), an endangered duck local breed. The average body weight is 1497.91 g at 90 d of age. According to the growth curve through data recorded every 2 wk, we observed a low relative growth rate (RGR) for the early growth stage. The RGR shows a decreasing trend with age increasing in the stage from 0 to 56 d of age. The SNP-based heritability estimation showed the growth rate has a relatively high heritability, indicating high genetic stability for this trait. In the correlation analysis, the percentage of leg muscle is positively correlated with the absolute growth rate (AGR) at 28 to 42 d of age, whereas it is negatively correlated with the earlier stages, exhibiting a time-specific correlation result. Additionally, genome-wide association studies (GWAS) identified PCSK6, TOX2, and TOMM7 as potential candidate genes influencing AGR (42–56) and AGR (56–90), while the candidate genes of slaughter traits were PTP4A2, FAM110B, TOX, UBXN2B, and FCHSD2. These results provide an important reference for further understanding the genetic basis of growth and meat production performance of Sichuan Shelduck.

Objective Unintentional injuries constitute a significant global public health issue with significant social and economic costs. Previous evidence suggests ambient temperatures are associated with unintentional injury occurrences. However, the impacts of ambient temperature on unintentional injury economic burden have received little research attention. The objective of the study was to examine the association between ambient temperature and economic burden of unintentional injury.Design Time-stratified case-crossover study.Setting This study was performed at Tianjin Hospital, the largest trauma centre in Tianjin, by applying a hospital-based time-stratified case-crossover study.Participants The 12 241 patients admitted with unintentional injuries and meteorological data were collected in Tianjin, China in 2021.Primary and secondary outcome The association between ambient temperature and unintentional injury hospitalisation was evaluated with a distributed lag non-linear model, further temperature-attributable economic burden of unintentional injuries was quantified, and adjusted for demographic characteristics, injury mechanism and injury location of injury.Results The temperatures below 11.5°C were significantly associated with the increased risk of unintentional injury hospitalisation in Tianjin, in 2021. The effect was maximised on the current day. The relatively low temperature was responsible for 25.44% (95% CI 13.74, 33.09) of unintentional injury patients, and was associated with the number of unintentional injury patients (3114, 95% CI 1608, 4036). The relatively low temperature was associated with the excess economic burden for unintentional injury (¥197.52 million, 95% CI 102.00, 256.00; about 27.10 million dollars), accounting for 26.49% of the total economic burden. The cold temperatures generally had greater impacts on males (¥136.46 million, 95% CI 83.28, 172.42; about 18.67 million dollars) and the elderly (¥74.35 million, 95% CI 14.87, 102.14; about 10.24 million dollars).Conclusion The temperature was associated with approximately 3000 unintentional injury patients and ¥200 million (27 million dollars), accounting for 26% of the total economic burden in Tianjin, 2021.

PV hosting capacity of a practical three-phase unbalanced distribution network is expected to increase, thus increasing safe PV penetration and speeding up the decarbonization of power systems. However, power unbalances and bus voltage violations are two major obstacles limiting further increases in the PV hosting capacity. With the popularization of electric vehicles (EVs), EV charging stations (EVCSs) as controllable loads can effectively provide grid ancillary services, which helps enhance the PV hosting capacity. In this regard, this paper proposes a hierarchical control method for EVCSs in an unbalanced network, consisting of central day-ahead scheduling and local real-time dynamic control. It is novel that the local control capability of EVCSs is reserved in the central scheduling. A three-phase day-ahead EV charging scheduling optimization model is developed to reduce the power unbalance and the bus voltage violation, and in turn, improve the PV hosting capacity. Moreover, active power transfer and voltage droop control are developed as two ancillary service functions for local real-time control responding to dynamic network operating conditions. Numerical simulations verify the effectiveness of the proposed method in enhancing PV hosting capacity and providing grid ancillary services.

ABSTRACT: The primary feathers of ducks have important economic value in the poultry industry. This study quantified the primary feather phenotype of Nonghua ducks, including the primary feathers' length, area, distribution of black spots, and feather symmetry. And genome-wide association analysis was used to screen candidate genes that affect the primary feather traits. The genome-wide association study (GWAS) results identified the genetic region related to feather length (FL) on chromosome 2. Through Linkage disequilibrium (LD) analysis, candidate regions (chr2: 115,246,393–116,501,448 bp) were identified and were further annotated to 5 genes: MRS2, GPLD1, ALDH5A1, KIAA0319, and ATP9B. Secondly, candidate regions related to feather black spots were identified on chromosome 21. Through LD analysis, the candidate regions (chr21: 163,552–2,183,853 bp) were screened and further annotated to 47 genes. Among them, STK4, CCN5, and YWHAB genes were related to melanin-related pathways or pigment deposition, which may be key genes affecting the distribution of black spots on feathers. In addition, we also screened 125 genes on multiple chromosomes that may be related to feather symmetry. Among them, significant SNPs on chromosome 1 were further identified as candidate regions (chr1: 142,118,209–142,223,605 bp) through LD analysis and annotated into 2 genes, TGFBRAP1 and LOC113839965. These results reported the genetic basis of the primary feather from multiple phenotypes, and offered valuable insights into the genetic basis for the growth and development of duck feathers and feather color pattern.

C16H15FN2O, monoclinic, Pc (no. 7), a = 12.3610(11) Å, b = 15.1269(17) Å, c = 8.1382(6) Å, β = 106.411(9)°, V = 1459.7(2) Å3, Z = 4, R gt(F) = 0.0565, wR ref(F 2) = 0.1315, T = 293 K.

With the widespread integration of distributed energy sources into low-voltage distribution networks, the demands for operational flexibility and absorptive capacity of distribution grids have been continuously increasing. The use of low-voltage flexible interconnection devices to interconnect independently operated low-voltage distribution substations helps to avoid frequent operations of traditional voltage regulation and reactive power compensation devices. Considering the high cost of flexible interconnection devices, a method is proposed to plan the siting and capacity of low-voltage flexible interconnection devices in coordination with traditional voltage-reactive power regulation devices. Firstly, the topology and operational mode of the low-voltage flexible interconnection devices are analyzed, and their power flow model is established. Subsequently, a dual-layer planning model is formulated for optimizing the configuration of low-voltage flexible interconnection devices. The upper-layer planning aims to minimize the annual comprehensive cost, while the lower-layer planning takes into account a time-series model for voltage-reactive power coordination control. The objectives of the lower-layer planning are to minimize operation costs and voltage deviations. The optimal solution for the distribution network system's flexible interconnection scheme and operational mode is obtained through alternating iterations of particle swarm optimization and mixed-integer second-order cone programming algorithms. Finally, a case study is conducted on the IEEE 33-node test system to validate the effectiveness of the proposed dual-layer planning algorithm. The results indicate that the proposed method can effectively reduce the excessive deployment of flexible interconnection devices while simultaneously decreasing the operational costs caused by frequent fluctuations in distributed energy sources. The method of convexifying and linearizing the model significantly enhances the solution efficiency.

The cold winter weather in northern China influences the dietary habits of its residents, contributing to a heightened risk of cardiovascular disorders, such as hypertension and coronary heart disease. Key factors include low vegetable consumption and high salt and fat intakes. This study aims to investigate the relationships between northern dietary nutrient intake in northern China and cardiovascular disorders during the winter season.

Abstract Power system dynamic security assessment (DSA) has long been essential for protecting the system from the risk of cascading failures and wide‐spread blackouts. The machine learning (ML) based data‐driven strategy is promising due to its real‐time computation speed and knowledge discovery capacity. However, ML algorithms are found to be vulnerable against well‐designed malicious input samples that can lead to wrong outputs. Adversarial attacks are implemented to measure the vulnerability of the trained ML models. Specifically, the targets of attacks are identified by interpretation analysis that the data features with large SHAP values will be assigned with perturbations. The proposed method has the superiority that an instance‐based DSA method is established with interpretation of the ML models, where effective adversarial attacks and its mitigation countermeasure are developed by assigning the perturbations on features with high importance. Later, these generated adversarial examples are employed for adversarial training and mitigation. The simulation results present that the model accuracy and robustness vary with the quantity of adversarial examples used, and there is not necessarily a trade‐off between these two indicators. Furthermore, the rate of successful attacks increases when a greater bound of perturbations is permitted. By this method, the correlation between model accuracy and robustness can be clearly stated, which will provide considerable assistance in decision making.

Abstract Objective This study aimed to evaluate enamel surface integrity and time consumed during residual cement removal after bracket debonding using different adhesive removal burs with and without a dental loupe. Material and Methods Sixty human-extracted premolars were collected, cleaned, mounted, and prepared for orthodontic bracket bonding. Teeth were randomly divided into three main groups (n = 20) based on the adhesive removal method: tungsten carbide system (TC), sof-lex discs system (SD), and diamond system (DB) groups. Then, each group was subdivided into two subgroups (naked eye and magnifying loupe subgroups). The brackets were bonded and then debonded after 24 h, and the Adhesive Remnant Index (ARI) was assessed. The adhesive remnants were removed by different systems, and the final polishing was performed by Silicone OneGloss. The enamel surface roughness was evaluated before bracketing (T0), after residual cement removal (T1), and finally after polishing (T2) using surface Mitutoyo SJ-210 profilometry and Scanning Electron Microscopy (SEM) to determine the Enamel Damage Index (EDI) score. The time consumed for adhesive removal was recorded in seconds. Results The Kruskal Wallis test showed a statistically significant difference in roughness values at T1 compared to T2 between subgroups (p

Abstract This letter introduces an ultra‐low‐power temperature sensor utilizing dynamic leakage‐suppression (DLS) logic and thoroughly analyses its working principle. The sensor effectively tackles the weak pull‐up challenge inherent in DLS logic ensuring its compatibility with standard digital logic. By capitalizing on the super cut‐off attribute of DLS logic, the frontend of the sensor achieves ultra‐low power consumption, without compromising on measurement precision or the breadth of the temperature range. The digital part of the proposed utilizes the output frequency of the sensor's frontend as the clock source, in conjunction with an external 50 Hz reference clock, achieving a low overall power consumption. The frontend of the temperature sensor was fabricated using a 180 nm process, occupying a minimal area of 374 μm2. The digital part of the circuit is implemented using FPGA. Following a two‐point calibration and system error removal, the sensor, operating at a supply voltage of 0.8 V, demonstrated a 3δ error of ±0.54 ∘C across the temperature range of −20 to 125 ∘C. At 25 ∘C, the resolution figure of merit of the sensor was 0.037 pJ K2, with a maximum voltage sensitivity of 4.2 ∘C/V.

PurposeTo develop a predictive model using machine learning for levothyroxine (L-T4) dose selection in patients with differentiated thyroid cancer (DTC) after resection and radioactive iodine (RAI) therapy and to prospectively validate the accuracy of the model in two institutions.MethodsA total of 266 DTC patients who received RAI therapy after thyroidectomy and achieved target thyroid stimulating hormone (TSH) level were included in this retrospective study. Sixteen clinical and biochemical characteristics that could potentially influence the L-T4 dose were collected; Significant features correlated with L-T4 dose were selected using machine learning random forest method, and a total of eight regression models were established to assess their performance in prediction of L-T4 dose after RAI therapy; The optimal model was validated through a two-center prospective study (n=263).ResultsSix significant clinical and biochemical features were selected, including body surface area (BSA), weight, hemoglobin (HB), height, body mass index (BMI), and age. Cross-validation showed that the support vector regression (SVR) model was with the highest accuracy (53.4%) for prediction of L-T4 dose among the established eight models. In the two-center prospective validation study, a total of 263 patients were included. The TSH targeting rate based on constructed SVR model were dramatically higher than that based on empirical administration (Rate 1 (first rate): 52.09% (137/263) vs 10.53% (28/266); Rate 2 (cumulative rate): 85.55% (225/263) vs 53.38% (142/266)). Furthermore, the model significantly shortens the time (days) to achieve target TSH level (62.61 ± 58.78 vs 115.50 ± 71.40).ConclusionsThe constructed SVR model can effectively predict the L-T4 dose for postoperative DTC after RAI therapy, thus shortening the time to achieve TSH target level and improving the quality of life for DTC patients.

Total pressure gain is an important parameter in RDC engineering applications. Many factors affect the total pressure gain, such as the area ratio of the outlet to the inlet (A8/A3.1) and type of fuel. In this study, convergent–divergent slot and Tesla valve inlet configurations were adopted. Three convergent nozzles were used, and the ratios of the outlet area to the combustor cross-sectional area (A8/A3.2) were 0.65, 0.5, and 0.25, respectively. The experiments were conducted at mass flow rate of 1.5 kg/s, 1.3 kg/s, and 1.0 kg/s. The combustion efficiency and total pressure gain were calculated using the temperature increase and Mach-corrected static pressure (MCSP). When A8/A3.2 is 0.25, most of the propagation modes are longitudinal pulsed detonations (LPD). The combustion efficiency increased with the equivalence ratio within the range of the detonation boundary. A model was developed to describe the relationship between combustion efficiency and total pressure gain. Once the configuration of the RDC is fixed, a proportional relationship exists between the combustion efficiency and total pressure gain. Improving combustion efficiency enhances the total pressure gain.

This long-term study protocol aims to compare the clinical outcomes of patients with severe lower limb trauma undergoing orthoplastic and orthopedic surgeries, focusing on their physical and psychological status. Patients with lower limb injuries and open fractures have been recruited since October 2019 and will be followed up until October 2024. The patients will be divided into two groups: (1) Orthoplastic group, where single-stage debridement, fixation, and soft tissue repair will be performed, and (2) Orthopedic group, where soft tissue repair will be done in a delayed-stage. The follow-up period will be one year, during which clinical data, limb function recovery, psychological scores, and health-related quality of life (HRQOL) will be evaluated to assess postoperative recovery and clinical outcomes. Additional clinical data, such as socio-demographic information, baseline features, Enneking score, Visual Analogue Scale (VAS) score, two-point discrimination score, and blood test parameters will also be collected. The 36-Item Short Form Health Survey (SF-36) will be used to evaluate HRQOL, while the Post-traumatic Stress Disorder Checklist (PCL) will assess the severity of self-reported post-traumatic stress disorder. The results of this study will provide valuable insights into prognostically relevant targets and contribute to improving the management and outcomes of patients with lower limb injuries and open fractures, who often face challenges related to limb disability and potential amputation postoperatively, significantly impacting their psychological and physical well-being.

To investigate the parameter characteristics of permanent magnet synchronous motor (PMSM) speed sensorless vector control system and capture the noise matrices quickly and accurately in the speed estimation process of the extended Kalman filter for PMSM, The recursive least square method with forgetting factor is proposed to determine the actual parameters of the system, and then a new variable-scale chaotic particle swarm optimization (VCPSO) algorithm is put forward to accurately obtain the system noise matrix and the measurement noise matrix. The simulation results show that noise matrix optimization of extended Kalman filter by employing VCPSO algorithm under actual motor parameters is better than those employing standard PSO or chaotic PSO algorithms with faster speed and higher accuracy.

To reduce carbon emissions associated with substantial concrete usage in construction and achieve the objectives of green and low-carbon construction, this study innovatively develops a low-carbon binary material by adding limestone powder (LP) and silica fume (SF) into the conventional cement-based material, enhancing the comprehensive utility value of LP. The experimental results show that the addition of 15% LP and 5% SF increases the yield stress of the mortar yet substantially reduces the plastic viscosity to 2.84 Nmm·min, representing a 44.5% decrease compared to pure cement slurry. This reduction is conducive to long-distance pumping of the cement-based material. Moreover, the addition of 5% SF compensates for the 18.8% (mid-stage, 28-d) and 15.8% (late-stage, 90-d) strength loss in mortar caused by LP while simultaneously improving the strength of the co-mixed system by 10.4% (mid-stage) and 10.8% (late-stage). In the early-stage measurements of the LP-SF binary cement-based materials, it is observed that while SF slightly increases the hydration heat release, LP suppresses the early hydration heat release. Therefore, the total heat release observed in the 15% LP and 5% SF group after 72 h is only 254 J/g, demonstrating favorable temperature control and crack prevention effects. In addition, X-ray diffraction (XRD) and thermogravimetric/differential thermogravimetric (TG/DTG) phase analysis reveal a notable increase of 53.56% in CH consumption. Besides, the weight loss on ignition of C-S-H crystals increases, indicating that the secondary hydration of LP and the pozzolanic reaction of SF promote the production of C-S-H in the system. Combined with the late-stage strength and water absorption characteristics, it is concluded that the system exhibits good mechanical properties and compactness. This study presents a use of mixed proportion that enables excellent mechanical properties, good pumping performance, and low hydration heat. Moreover, the analysis indicates that the carbon emission of each cubic meter of the as-developed mortar is reduced by approximately 16.7–23.9%, promoting the efficient and clean utilization of LP and SF.

Abstract Lake‐effect snow (LES) storms, characterized by heavy convective precipitation downwind of large lakes, pose significant coastal hazards with severe socioeconomic consequences in vulnerable areas. In this study, we investigate how devastating LES storms could evolve in the future by employing a storyline approach, using the LES storm that occurred over Buffalo, New York, in November 2022 as an example. Using a Pseudo‐Global Warming method with a fully three‐dimensional two‐way coupled lake‐land‐atmosphere modeling system at a cloud‐resolving 4 km resolution, we show a 14% increase in storm precipitation under the end‐century warming. This increase in precipitation is accompanied by a transition in the precipitation form from predominantly snowfall to nearly equal parts snowfall and rainfall. Through additional simulations with isolated atmospheric and lake warming, we discerned that the warmer lake contributes to increased storm precipitation through enhanced evaporation while the warmer atmosphere contributes to the increase in the storm's rainfall, at the expense of snowfall. More importantly, this shift from snowfall to rainfall was found to nearly double the area experiencing another winter hazard, Rain‐on‐Snow. Our study provides a plausible future storyline for the Buffalo LES storm, focusing on understanding the intricate interplay between atmospheric and lake warming in shaping the future dynamics of LES storms. It emphasizes the importance of accurately capturing the changing lake‐atmosphere dynamics during LES storms under future warming.

It is essential to recognize efficient heterogeneous catalysts for environmental remediation that can eliminate organic contaminants or transform them into beneficial byproducts. Herein, we have designed and developed a gold nanoparticle based green nanocomposite material templated over the Curcuma longa extract. The Au NPs/C. longa nanomaterial was thoroughly characterized by FT-IR and UV–Vis spectroscopy followed by FE-SEM, EDX, TEM and XRD analysis. Subsequently, towards the wastewater treatment, it demonstrated excellent potential in the reduction of water contaminant toxic organic dyes like methylene blue (MB), methyl orange (MO), and 4-nitrophenol (4-NP) following excellent kinetics, as monitored by UV–Vis spectrophotometer. The reaction followed a pseudo-first order kinetics. The robustness of the nanocatalyst was justified by reusability studies, and hot filtration test and the catalytic activity did not substantially decline over the course of seven cycles. Towards the assessment of biological activity of Au NPs/C. longa nanocomposite antioxidant capacity was evaluated first using the DPPH radical scavenging method. Further, the study was extended in the investigation of anti-lung cancer properties against a number of standard lung cancer cell lines, viz., NCI-H661, NCI-H1975, NCI-H1573, and NCI-H1563 following MTT colorimetric in vitro studies. Curcuma longa-modified Au NPs are thought to have potential biological activities because of their exceptional capacity to produce reactive oxygen species (ROS).

In order to investigate the effect of low-temperature air cooling on the postmortem energy metabolism and meat quality of yellow-feathered broilers during mixed cooling (first water cooling and then air cooling), 85-day-old broilers were slaughtered and divided into three groups: treatment (water cooling at 0–4 ℃ followed by air cooling at −8, −18, −25 or −31 ℃), control (traditional water cooling at 0–4 ℃) and traditional mixed cooling (water cooling at 0–4 ℃ followed by air cooling at 0–4 ℃) groups. Finally, all carcasses were cooled to an internal temperature of 4 ℃, and the optimal air cooling temperature was determined by measuring cooling rate, pH, energy metabolism and quality indexes. The results showed that the cooling time of air cooling at −25 and −31 ℃ was 2 537 and 2 272 s, respectively, which was shortened by 27.78% and 35.33% compared with the traditional water cooling and by 51.87% and 56.90% compared with the traditional mixed cooling, respectively. Air cooling at −25 and −31 ℃ delayed the decrease in pH, reduced the drip loss and cooking loss of broiler breast muscle, significantly increased the shear force and the content of immobilized water compared with the control group (P < 0.05). Compared with the other groups, the activities of muscle hexokinases, phosphate-3-phosphate dehydrogenase and lactate dehydrogenase in the air cooling treatments at −25 and −31 ℃ were lower, and the consumptions of adenosine triphosphate (ATP) and glycogen, the production of lactic acid and adenosine monophosphate (AMP) and AMP/ATP ratio were the smallest (P < 0.05). The above findings showed that air cooling at −25 and −31 ℃ significantly inhibited the rate of anaerobic glycolysis during the early postmortem period in chicken meat, delayed the rate of pH decline, and effectively improved muscle water retention. From the perspective of industrial energy saving, −25 ℃ is determined as the best temperature for air cooling treatment.

The accumulation and release of energy in coal are closely linked to rock burst, with energy transfer being a key parameter for evaluating bursting liability. This study constructs an energy transfer model under energy source disturbance conditions, where we establish a relationship between impact energy index and elastic energy index, propose the proportion of energy φ, introduce the concept of energy transfer efficiency β based on an energy dissipation model during the transfer process, develop an evaluation method for bursting liability by multiplying two efficiency parameters η=βφ. We conducted experiments to identify bursting liability of 11 coal layers from 3 pairs of coal mines, whose reliability was verified by referencing results from 79 layered impact tendency identifications in other coal mines. Results show that 1)the proportion of energy release φ has boundary conditions with physical significance for ground pressure; 2)there is negative correlation between the efficiency β and Poisson's ratio which can model boundary conditions; 3)calculation results of the energy transfer index η show high consistency(88.61 %)with bursting liability identification results, reflecting the bursting liability of coal bodies. It can serve as a basis for evaluating "*" outcomes and is an effective indicator suitable for existing systems used to evaluate bursting liability.

This letter proposes a reliable transfer learning (RTL) method for pre-fault dynamic security assessment (DSA) in power systems to improve DSA performance in the presence of potentially related unknown faults. It takes individual discrep-ancies into consideration and can handle unknown faults with incomplete data. Extensive experiment results demonstrate high DSA accuracy and computational efficiency of the proposed RTL method. Theoretical analysis shows RTL can guarantee system performance.

ObjectiveTuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disease involving multiple organ system. Renal angiomyolipoma (RAML) is a leading cause of death for adult TSC patients. Our study aims at investigating the clinical manifestations of TSC-RAML to enable clinicians to have a better understanding of the disease in Chinese patients.MethodsWe reviewed retrospectively the data collected from patients with TSC-RAML in Peking Union Medical College Hospital from January 2014 to January 2023. We also collected information about the age, gender, imageological examination, RAML stage, and comorbidities.ResultsA total of 186 TSC-RAML patients were registered, 65 of whom were males and 121 were females(male-to-female ratio 1∶1.86). The median age of all patients was 31 years old. Totally, 117 cases (62.9%)of RAML were rated stage 6. Twenty-two cases (11.8%) had a history of tumor rupture and bleeding. Research shows statistical differences between high and low grade on RAML rupture bleeding(P=0.0475). Angiofibromas/fibrous cephalic plaque (155/186, 83.3%), subependymal nodules(103/146, 70.5%), lymphangioleiomyomatosis (102/157, 65.0%), hypomelanotic macules (114/186, 61.3%), and shagreen patch (83/186, 44.6%)were the most common clinical manifestations. All patients with lymphangioleiomyomatosis(LAM) were female(P < 0.0001).ConclusionsFemale patients predominated TSC-RAML patients. Most RAML were in stage 6. About 11.8% cases had a history of tumor rupture and hemorrhage. The higher grade meant the higher proportion of tumor rupture and hemorrhage. Dermatological and nervous lesions were the most common comorbidities. All patients with LAM in this study were female.

Tumor-derived exosomes have been shown to play a key role in organ-specific metastasis, and the androgen receptor regulates prostate cancer (PCa) progression. It is unclear whether the androgen receptor regulates the recruitment of prostate cancer cells to the bone microenvironment, even bone metastases, through exosomes. Here, we found that exosomes isolated from PCa cells after knocking down androgen receptor (AR) or enzalutamide treatment can facilitate the migration of prostate cancer cells to osteoblasts. In addition, AR silencing or treatment with the AR antagonist enzalutamide may increase the expression of circular RNA-deoxyhypusine synthase (circ-DHPS) in PCa cells, which can be transported to osteoblasts by exosomes. Circ-DHPS acts as a competitive endogenous RNA (ceRNA) against endogenous miR-214-3p to promote C-C chemokine ligand 5 (CCL5) levels in osteoblasts. Increasing the level of CCL5 in osteoblasts could recruit more PCa cells into the bone microenvironment. Thus, blocking the circ-DHPS/miR-214-3p/CCL5 signal may decrease exosome-mediated migration of prostate cancer cells to osteoblasts.

Abstract A new concept of Battery Doctor is proposed for the next generation battery health assessment, first, the comprehensive assessment framework integrating the multiple health indices is formulated, where the bottom‐up assessment hierarchy is used to provide the holistic health indicator from the battery cell to the large‐format battery. Second, several options for defining a uniform indicator state of X is provided to effectively measure the battery health, which contributes to promoting the health assessment from state of charge and stage of health to state of X. Finally, the future challenges and opportunities of developing the battery doctor are disclosed from three different viewpoints, which is to incentivize the technology breakthrough for the next generation battery health assessment.

This paper proposes a three-step joint rate optimization method for intelligent reflecting surface (IRS)-assisted coal mine wireless communication systems. Different from terrestrial IRS-assisted communication scenarios, in coal mines, IRSs can be installed flexibly on the tops of rectangular tunnels to address the issues of signals being blocked and interfered with by mining equipment. Therefore, it is necessary to optimize the IRS deployment position, the transmit power and IRS phase shifts to achieve the maximum effective achievable rate at user stations equipped with the proposed system. However, due to the complex channel models of coal mines, the optimization problem of IRS deployment position is non-convex. To solve this problem, two auxiliary variables along with logarithmic operations and Taylor approximation are introduced. On this basis, a three-step joint rate optimization involving the transmit power, IRS phase shifts and IRS deployment position is proposed to maximize the effective achievable rates at the user station. The simulation results show that compared with other rate optimization schemes, the effective achievable rates at the user station using the proposed joint rate optimization scheme can be improved by approximately 12.32% to 54.17% for different parameter configurations. It is also pointed out that the deployment position of the IRS can converge to the same optimal position independent of the initial deployment position. Moreover, we investigate the effects of the roughness of the tunnel walls in a coal mine on the effective achievable rates at the user station, and the simulation results indicate that the proposed three-step joint rate optimization scheme performs better in the coal mine scenario regardless of the roughness.

Mine water inflow is a significant safety concern in coal mine operations. Accurately predicting the volume of mine water inflow is vital for ensuring mine safety and environmental protection. This study focused on the Laohutai mining area in Liaoning, China, to reduce the reliance on hydrogeological parameters in the mine water inflow prediction process. An integrated approach combining grid search (GS) with the Seasonal Autoregressive Integrated Moving Average (SARIMA) and Long Short-Term Memory (LSTM) model was proposed, and its results were compared with Visual MODFLOW. The grid search was used to optimize the SARIMA model, modeling the linear component of nine years of water inflow data, with the remaining six months of data used for model validation. Subsequently, the prediction residuals from the SARIMA model were input into the LSTM model to capture the nonlinear features in the data and enhance the generalization capability and stability of the LSTM model by introducing Dropout, EarlyStopping, and the Adam optimizer. This model effectively handles long-term trends and seasonal fluctuations in the data while overcoming limitations in capturing periodicity and trends in complex time series data. The results indicated that the GC-SARIMA-LSTM model performs better than the Visual MODFLOW numerical simulation software in predicting mine water inflow. Therefore, without hydrogeological parameters, the GC-SARIMA-LSTM model can serve as an effective tool for short-term prediction, advancing the application of deep learning in coal mine water inflow forecasting and providing reliable technical support for mine water hazard prevention.

While tunnel boring machines (TBMs) tunneling in clayey strata, the adhered excavated soil on the cutterhead and cutting tools tends to form mudcake after compaction and consolidation. Mudcake can obstruct the cutterhead openings and rendering the cutting tools ineffective, leads to a substantial reduction in advance rate. Dispersants are recognized as an effective method for the disintegration of mudcakes. A novel set of equipment, comprising a mudcake compression device and a mudcake disintegration apparatus, is developed for assessing mudcake disintegration properties. The results showed that mudcakes underwent a tripartite disintegration process in water, including an initial stage, a rapid disintegration stage, and a stable stage. In the initial stage, the mudcakes absorbed water before disintegration, resulting in marginal changes in the weight of the disintegrated mudcakes. In the rapid disintegration stage, the weight of the disintegrated mudcakes increased quickly. During the stable stage, the weight of the disintegrated mudcakes remained relatively constant. The submersion of mudcakes in a dispersant solution substantially increased the rate of disintegration. Greater dispersant concentration corresponded to an increase in the disintegration rate. No weight gain was observed in mudcakes during the initial disintegration stage. When mudcakes disintegrated in a bentonite slurry, the weight of the disintegrated mudcakes initially decreased and then stabilized. The weight of the disintegrated mudcakes turned negative, indicating an increase in the weight of mudcakes. This suggested that bentonite significantly hindered mudcake disintegration.

Abstract Lithium‐Sulfur (Li‐S) batteries as the next‐generation battery system have an ultrahigh theoretical energy density. However, the limited conversion of polysulfides in sulfur cathodes deteriorates the performance of Li‐S batteries. In this study, we develop a novel titanium nitride (TiN) catalyst for sulfur cathodes via atomic layer deposition (ALD). The synthesized ALD‐TiN catalyst shows controllable ultrafine particle size (

Background: The aim of this study was to investigate the effect of DNA methylation of Fork Head Box O3 (FOXO3a) on the process of epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). Methods: The expressions of FOXO3a, DNA methyltransferase 1 (DNMT1), METTL3, and EMT-related proteins (E-cadherin and N-cadherin) were measured. The influence of 5-Aza-dC and DNMT1 on the methylation level in the promoter region of FOXO3a was examined through the application of methylation-specific PCR (MSP). Chromatin immunoprecipitation (ChIP) was employed to detect binding between DNMT1 and the FOXO3a promoter. Methylated RNA immunoprecipitation (MeRIP) was utilized to evaluate the level of DNMT1 N6-methyladenosine (m6A) methylation. The assessment of cell viability and invasion abilities of A549 cells was performed using Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. NSCLC xenograft mouse models were established by subcutaneously injected treated A549 cells into nude mice. Results: The expression levels of DNMT1 and DNA methylation level FOXO3a were found to be significantly increased, whereas FOXO3a expression was considerably decreased in NSCLC cell lines and NSCLC tumor tissues. Both 5-Aza-dC treatment and DNMT1 knockdown resulted in the down-regulation of DNA methylation levels of FOXO3a while simultaneously up-regulating the expression of FOXO3a. A ChIP assay demonstrated that DNMT1 has the ability to bind to the promoter region of FOXO3a. Furthermore, the knockdown of DNMT1 promoted E-cadherin expression, but inhibited expression of N-cadherin, cell viability, and invasion ability. However, the knockdown of FOXO3a hindered the effect of DNMT1 knockdown on EMT, cell viability, and invasion ability of A549 cells. This was evidenced by decreased E-cadherin expression and increased N-cadherin expression, as well as increased cell viability and invasion ability. Increased expression of DNMT1 resulted from m6A methylation of DNMT1, which was mediated by METTL3. Overexpression of DNMT1 decreased of E-cadherin expression while increased N-cadherin expression, cell viability, and invasion ability in METTL3-shRNA treated A549 cells. In xenograft mouse models, DNMT1 knockdown significantly reduced tumor volumes and tumor weight. DNMT1 knockdown upregulated the expression of FOXO3a and E-cadherin, while downregulated N-cadherin expression in vivo. Conclusion: METTL3-mediated m6A methylation of DNMT1 up-regulates FOXO3a promoter methylation, thereby promoting the progression of NSCLC.

When the opening rate of the cutter head of tunnel boring machines is insufficient for the removal of excavated soil in a timely manner, the soil tends to accumulate in front of the cutter head and inside the earth or slurry chamber, leading to mud caking. High-pressure water jetting is an effective method for removing mud cakes. This study explored the influence of high-pressure water jet parameters on the efficiency of mud cake cleaning by using highly weathered argillaceous siltstone as experimental materials. Mud cake compaction equipment and high-pressure water jetting devices were developed. In addition, the impact of jetting parameters such as jet pressure and flow rate on the mud cake cutting performance was investigated. The results indicated that with an increase in the erosion distance, the cutting width of the mud cake first increased and then gradually decreased to zero, while the cutting depth progressively diminished. Under the same jet pressure, when the flow rate increased from 49.1 L/min to 110 L/min, the cutting width of the high-pressure water jet increased. With further increase in the flow rate from 110 L/min to 202.8 L/min, the cutting width decreased and the cutting depth increased. Under the same jet flow, the increase in water pressure resulted in greater cutting width and depth.

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine characterized by a compromised intestinal epithelial barrier. Mucin glycans are crucial in preserving barrier function during bacterial infections, although the underlying mechanisms remain largely unexplored. Methods A cohort comprising 15 patients diagnosed with UC and 15 healthy individuals was recruited. Stool samples were collected to perform 16S rRNA gene sequencing, while biopsy samples were subjected to nanocapillary liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) to assess O-glycosylation. Gene expression was evaluated through qPCR analysis and Western blotting. Furthermore, animal experiments were conducted to investigate the effects of Escherichia coli and/or O-glycan inhibitor benzyl-α-GalNAc on the development of colitis in mice. Results Our findings revealed that the mucus barrier was disrupted during the early stages of UC, while the MUC2 protein content remained unaltered. Additionally, a noteworthy reduction in the o-glycosylation of MUC2 was observed, along with significant changes in the intestinal microbiota during the early stages of UC. These changes included a decrease in intestinal species richness and an increase in the abundance of Escherichia coli (E. coli). Moreover, subsequent to the administration of galactose or o-glycan inhibitor to intestinal epithelial cells, it was observed that the cell culture supernatant had the ability to modify the proliferation and adhesive capacity of E. coli. Furthermore, when pathogenic E. coli or commensal E. coli were cocultured with intestinal epithelium, both strains elicited activation of the NF-KB signaling pathway in epithelial cells and facilitated the expression of serine protease in comparison to the untreated control. Consistently, the inhibition of o-glycans has been observed to enhance the pathogenicity of E. coli in vivo. Furthermore, a correlation has been established between the level of o-glycans and the development of ulcerative colitis. Specifically, a reduction in the O-glycan content of MUC2 cells has been found to increase the virulence of E. coli, thereby compromising the integrity of the intestinal epithelial barrier. Conclusions Together, there exist complex interactions between the intestinal epithelium, o-glycans, and the intestinal microbiota, which may inform the development of novel therapeutic strategies for the treatment of ulcerative colitis.

Objective To investigate the occurrence and outcomes of immune-related adverse events (irAEs) in the clinical application of programmed cell death protein 1 (PD-1) inhibitors. Methods A retrospective cohort studies was performed on 456 patients with malignant tumors treated with PD-1 inhibitors from March 2020 to November 2022, and the types, grades and prognosis of adverse skin reactions were observed. Results In the cohort, 101 patients experienced irAEs. There were 71 (70.29%) patients having reactive cutaneous capillary endothelial proliferation (RCCEP), including 15 cases of grade 2 and 56 cases of grade 1, most of whom did not receive special treatment and a small number of whom had hemangioma regression after apatinib treatment; 22 (21.7%) patients developing itchy skin, including 4 cases of grade 2 and 18 cases of grade 1, with the symptoms disappearing within 1 week after topical glucocorticoid and oral antihistamine treatment; 15 (14.8%) patients experiencing maculopapular rash, including 9 cases of grade 1 and 6 cases of grade 2 of skin adverse reactions, which were greatly improved after symptomatic treatment with emollients, topical glucocorticoids and oral antihistamines; 4 (3.9%) cases of vitiligo-like depigmentation, including 1 case of grade 2 and 3 cases of grade 1, all of which did not receive special treatment; 1 case of toxic epidermal necrolysis (TEN), and the skin lesions were improved after ICU supportive therapy and hormonal antibiotic administration; and 1 case of psoriasis at grade 3 skin reaction, and the lesions were improved after intravenous glucocorticoid drugs. Conclusion Among the irAEs events after PD-1 inhibitor treatment, the adverse skin reactions are mainly grade 1~3, and grade 4 or above are rare. After symptomatic treatment of irAEs, most symptoms can be relieved. Early identification and full management of skin adverse events can prevent the deterioration of lesions, and irAEs are generally safe and controllable.

Abstract Objectives The aim of the study was to evaluate the efficacy and safety of allogeneic umbilical cord-derived mesenchymal stem cells (TH-SC01) for complex perianal fistula in patients with Crohn’s disease (CD). Methods This was an open-label, single-arm clinical trial conducted at Jinling Hospital. Adult patients with complex treatment-refractory CD perianal fistulas (pfCD) were enrolled and received a single intralesional injection of 120 million TH-SC01 cells. Combined remission was defined as an absence of suppuration through an external orifice, complete re-epithelization, and absence of collections larger than 2 cm measured by magnetic resonance imaging (MRI) at 24 weeks after cell administration. Results A total of 10 patients were enrolled. Six patients (60.0%) achieved combined remission at 24 weeks. The number of draining fistulas decreased in 9 (90.0%) and 7 (70.0%) patients at weeks 12 and 24, respectively. Significant improvement in Perianal Crohn Disease Activity Index, Pelvic MRI-Based Score, Crohn Disease Activity Index, and quality of life score were observed at 24 weeks. No serious adverse events occurred. The probability of remaining recurrence-free was 70% at week 52. Conclusion The study demonstrated that local injection of TH-SC01 cells might be an effective and safe treatment for complex treatment-refractory pfCD after conventional and/or biological treatments fail (ClinicalTrials.gov ID, NCT04939337). Trial Registration: The study was retrospectively registered on www.ClinicalTrials.gov (NCT04939337) on June 25, 2021.

Abstract Daqing Oilfield as the world’s largest application area of alkali–surfactant–polymer (ASP) flooding, in recent years, with the increase in aging wells, the eccentric wear and deformation of sucker rod and pipe during oil production has become more and more serious. In order to study the effect of emulsion lubrication in ternary composite flooding on eccentric wear of sucker rod and tubing, this paper establishes a calculation model for the depth of tubing wear under different emulsion lubrication conditions through indoor friction and wear experiments combined with White and Dawson wear efficiency theory. Based on this, the finite element method is used to predict the safe wear life of tubing under different component emulsion lubrication. The results show that compared to intact oil pipes, the residual internal pressure strength of oil pipes with defects decreases, and stress concentration occurs at the edges and middle of the defects. The wear life of oil pipes decreases with the increase in pump depth and wear coefficient under emulsion lubrication. The water content and alkali concentration have the most significant effects on the wear life of oil pipes under emulsion lubrication conditions. The safe wear life of sucker rod pipes under emulsion lubrication with a water content of 75% will be increased by 37.8% compared to those in emulsion lubrication with a water content of 95%, and under emulsion lubrication with an alkali concentration of 500 mg/l, the safe wear life will be increased by 50.6% compared to those in emulsion lubrication with a concentration of 2000 mg/l. The research results can provide theoretical and technical support for oilfield enterprises to reduce rod and pipe wear in ASP flooding oil wells, improve the pump inspection cycle of pumping wells, and ensure the safety of oil well work.

Abstract Prostate development and regeneration depend on prostate stem cell function, the delicate balance of stem cell self-renewal and differentiation. However, mechanisms modulating prostate stem cell function remain poorly identified. Here, we explored the roles of Yes-associated protein 1 (YAP) in prostate stem cells, prostate development and regeneration. Using YAPfl/fl, CD133-CreER mice, we found that stem cell-specific YAP-deficient mice had compromised branching morphogenesis and epithelial differentiation, resulting in damaged prostate development. YAP inhibition also significantly affected the regeneration process of mice prostate, leading to impaired regenerated prostate. Furthermore, YAP ablation in prostate stem cells significantly reduced its self-renewal activity in vitro, and attenuated prostate regeneration of prostate grafts in vivo. Further analysis revealed a decrease in Notch and Hedgehog pathways expression in YAP inhibition cells, and treatment with exogenous Shh partially restored the self-renewal ability of prostate sphere cells. Taken together, our results revealed the roles of YAP in prostate stem cell function and prostate development and regeneration through regulation of the Notch and Hedgehog signaling pathways.

Rhubarb is a significant medicinal herb in China. Its adulteration or fabrication is common in the market. Consequently, it is necessary to establish a comprehensive identification method to accurately identify genuine rhubarb and its adulterants. In this study, the sequences of chloroplast genes rps3-rpl22 and rpl16 from three genuine rhubarbs (Rheum tanguticum, Rh. palmatum and Rh. officinale) and their adulterants (Rumex japonicus and Rumex spp.) were amplified, sequenced and subjected to genetic analyses. The genetic distances for rps3-rpl22 and rpl16 between genuine rhubarbs and their adulterants showed that there was an evident barcoding gap, which allowed the adulterants to be distinguished from the genuine rhubarbs, as demonstrated by a neighbor joining tree. Additionally, Rh. officinale could be distinguished from the other two genuine rhubarbs. The anthraquinone, sennoside, polysaccharide and protein contents were analyzed in seven rhubarbs using high-performance liquid chromatography and ultraviolet spectrophotometry. Cluster and principal component analyses results showed that Rh. tanguticum and Rh. palmatum could be effectively distinguished. The study suggests that DNA barcoding based on rps3-rpl22 and rpl16 sequences coupled with multiple-indicator quantification can be successfully applied to identify rhubarb species and distinguish among the three genuine rhubarbs, and this can provide a scientific foundation for rhubarb quality assurance.

Underground gas storage (UGS) is a beneficial economic method of compensating for the imbalance between natural gas supply and demand. This paper addresses the problem of a lack of research on the two-phase distribution pattern and seepage law during the water–gas alternated flooding in gas storage reservoirs. The study constructed a three-dimensional digital core of the aquifer reservoir based on Computed Tomography (CT) scanning technology, and extracted the connecting pore structure to establish the tetrahedral mesh model. A two-phase microscopic seepage model was established based on the Volume of Fluid (VOF)method, and microscopic gas and gas–liquid two-phase unsaturated microscopic seepage simulation was carried out. The results show that the effective reservoir capacity increases with the increase in the number of alternated flooding cycles. The irreducible water is mainly distributed in the dead-end of the pore space and small pore throats, and the residual gas is mainly distributed as a band in the gas–water interface and the dead-end of the pore space of the previous round. The reservoir capacity can be increased by appropriately increasing the intensity of injection and extracting and decreasing the pressure of the reservoir.

Alfalfa is a perennial herbaceous forage legume that is significantly and adversely affected by monocropping. Crop rotation is the most effective measure to overcome continuous cropping obstacles. However, the mechanisms of how bacterial communities are affected and the potential links between these effects and cropping systems remain poorly understood. Based on a long-term field experiments with continuous alfalfa and forage crops with alfalfa rotation in the black soil region of the western Songnen Plain in Northeast China, the alterations in soil bacterial community structure using high-throughput sequencing of the 16S rRNA gene and soil chemical properties and enzyme activities were analyzed. The alfalfa–forage oats–silage maize–alfalfa and alfalfa–silage maize–forage oats–alfalfa system significantly increase the levels of total phosphorus and available phosphorus, and promote the activities of acid phosphatase, β-glucosidase, leucine aminopeptidase, and N-acetyl-β-glucosaminidase in comparison to continuous alfalfa. While alfalfa crop rotation did not affect the α-diversity of soil bacteria, it significantly altered the bacterial community composition and structure. Some key taxa are significantly enriched in the crop rotation system soils, including Bacillus, Sphingobium, Paenibacillus, Hydrogenispora, Rubrobacter, Haliangium, and Rubellimicrobium. Additionally, crop rotation with alfalfa increased the stability and complexity of the soil bacterial co-occurrence network. Based on our findings, we recommend promoting the alfalfa–forage oats–silage maize–alfalfa and alfalfa–silage maize–forage oats–alfalfa rotation systems as ideal practices for overcoming the challenges associated with continuous cropping of alfalfa. These systems not only enhance soil nutrient content and enzyme activities but also foster a beneficial microbial community, ultimately improving soil functionality and crop performance.

The open-circuit voltage (OCV) curve has a significant influence on the accuracy of the state of charge (SOC) estimation based on equivalent circuit models (ECMs). However, OCV curves are tested through offline experiments and are hard to be very accurate because they constantly change with the test method’s ambient temperature and aging status. Recently, researchers have attempted to improve the accuracy of OCV curves by increasing the volume of sample data or updating/reconstructing the curve combined with practical operation data. Still, prior offline tests are essential, and experimental errors inevitably exist. Consequently, a SOC estimation method without any offline OCV tests might be an efficient route to improve the accuracy of SOC. According to this idea, this paper presents a novel method for SOC estimation, which is based on online OCV curve construction. Meanwhile, a stepwise multi-timescale parameter identification algorithm is designed to improve the interpretability and precision of the estimated ECM parameters. The results demonstrate that the maximum SOC estimation error is only 0.05% at 25 °C, indicating good robustness under various ambient temperatures and operational conditions.

A high strength and ductile Mg-Gd-Y-Zn-Zr alloy was designed and fabricated. The local strain evolution of the alloys during plastic deformation was analyzed using high-resolution digital image correlation (DIC). The results showed that the β particles, nano-sized γ’ phases, and LPSO phases were distributed in the as-extruded alloy and a bimodal microstructure was exhibited, including elongated un-dynamic recrystallized grains and fine dynamic recrystallized grains. With increasing extrusion ratio, the grain size remained, with the volume fraction of dynamic recrystallization of the as-extruded alloy increasing from 30% to 75%, and the as-extruded alloy exhibited a high strength-ductility synergy, which is attributed to the grain refinement, extensive β particles, and elongated block-shaped LPSO phases. The strain evolution analysis showed that a strain-transfer from un-DRXed regions to adjacent DRXed regions and LPSO phases can promote uniform plastic deformation, which tends to improve the ductility of the alloy.