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The development of an innovative drug is complex and time-consuming, and the drug target identification is one of the critical steps in drug discovery process. Effective and accurate identification of drug targets can accelerate the drug development process. According to previous research, evolutionary and genetic information of genes has been found to facilitate the identification of approved drug targets. In addition, allosteric proteins have great potential as targets due to their structural diversity. However, this information that could facilitate target identification has not been collated in existing drug target databases. Here, we construct a comprehensive drug target database named Genetic and Evolutionary features of drug Targets database (GETdb, http://zhanglab.hzau.edu.cn/GETdb/page/index.jsp). This database not only integrates and standardizes data from dozens of commonly used drug and target databases, but also innovatively includes the genetic and evolutionary information of targets. Moreover, this database features an effective allosteric protein prediction model. GETdb contains approximately 4000 targets and over 29,000 drugs, and is a user-friendly database for searching, browsing and downloading data to facilitate the development of novel targets.

Zr-Y modified silicide coating was deposited on TC4 alloy by the pack cementation process. The microstructure， friction and wear performance， and wear mechanisms of the coating were investigated. The results show that the Zr-Y modified silicide coating has a multi-layer structure， an outer layer consists of TiSi2 and a small amount of ZrSi2， a thin middle layer is TiSi， and an inner layer is a mixture of Ti5Si4 and Ti5Si3. The micro-hardness of the coating is much higher than that of the TC4 substrate and exhibits an obvious decrease tendency from the surface to the interior. The Zr-Y modified silicide coating possesses good anti-wear performance when wearing against GCr15 and Al2O3 balls at a high-temperature of 600 ℃. When wearing against GCr15， the wear rate of the coating is about 3.59×10-5 mm3/（N·m）， which is about 36.6% of that of the TC4 substrate， and the main wear mechanisms are characterized by the adhesive of GCr15 on the coating surface and oxidation wear. When wearing against the Al2O3 ball， the wear rate of the coating is about 9.75×10-5 mm3/（N·m）， which is about 18.9% of that of the TC4 substrate， and the wear mechanisms are fatigue wear， oxidation wear， and adhesion wear.

The sea level in coastal areas of China reached the second highest in 2021, just after that recorded in 2022. External force and dynamic analyses based on tide gauges, satellite observations, reanalysis data and regional numerical outputs were conducted to understand these abnormally high sea levels and determine their possible causes. Results show that the coastal sea level of China had increased at an annual rate of 3.4 ± 0.3 mm during 1980–2021, with an acceleration of 0.06 ± 0.02 mm per year2. The superposition of significant oscillations of quasi-2, 3–7, quasi-9, quasi-11, quasi-19 and 20–30 years contributed to the anomalously high sea levels. The negative-phased El Niño/Southern Oscillation was correlated with the anomalously high sea level and the north‒south anti-phase pattern of the coastal sea level in 2021. Meanwhile, phase lags of 1–4 months occurred with the sea-level response. On a decadal timescale, the Pacific Decadal Oscillation (PDO) was negatively correlated with the anomalous mean sea level (MSL), and the negative-phased PDO contributed to the anomalous sea-level change in 2021. Particularly, the monthly MSL peaked in April and July, and the contribution of wind stress to the anomalously high sea level was 38.5% in the south of the Taiwan Strait in April and 30% along the coast of China in July. These results were consistent with the tide gauge and satellite data. Close agreement was also observed between the coastal sea-level fingerprint and the air and sea surface temperatures.

The relationship between power transmission and reception in AC/DC interconnected power grids is complex， with numerous constraints on grid operation and regulation. Therefore， relying solely on manual expertise to assess the adjustment of power transmission and reception plans presents significant challenges. In response to the precise requirements of market-oriented transactions for adjusting interprovincial power transmission and reception plans， a method for analyzing the feasible domain of interprovincial transmission power is proposed. Firstly， based on the operational characteristics of AC/DC interconnected power grids， the modeling of operational constraints within the feasible scheduling domain is expanded. Subsequently， a model for the feasible domain of interprovincial transmission power is constructed， and solved using the ordered vertex search method. Finally， case studies are conducted based on the actual operational scenarios of the regional power grid in the south， and the effectiveness of the feasible domain for interprovincial transmission power is validated using the computational results of the entire network scheduling and optimization model. The calculation results of the feasible domain provide insight into the limit range of interprovincial transmission power under specific transmission and reception scenarios， thereby providing a reference basis for the verification and adjustment of medium to long-term power transmission and reception plans.

Abstract Background Human patients often experience an episode of serious seizure activity, such as status epilepticus (SE), prior to the onset of temporal lobe epilepsy (TLE), suggesting that SE can trigger the development of epilepsy. Yet, the underlying mechanisms are not fully understood. The low-density lipoprotein receptor related protein (Lrp4), a receptor for proteoglycan-agrin, has been indicated to modulate seizure susceptibility. However, whether agrin-Lrp4 pathway also plays a role in the development of SE-induced TLE is not clear. Methods Lrp4 f/f mice were crossed with hGFAP-Cre and Nex-Cre mice to generate brain conditional Lrp4 knockout mice (hGFAP-Lrp4 −/− ) and pyramidal neuron specific knockout mice (Nex-Lrp4 −/− ). Lrp4 was specifically knocked down in hippocampal astrocytes by injecting AAV virus carrying hGFAP-Cre into the hippocampus. The effects of agrin-Lrp4 pathway on the development of SE-induced TLE were evaluated on the chronic seizure model generated by injecting kainic acid (KA) into the amygdala. The spontaneous recurrent seizures (SRS) in mice were video monitored. Results We found that Lrp4 deletion from the brain but not from the pyramidal neurons elevated the seizure threshold and reduced SRS numbers, with no change in the stage or duration of SRS. More importantly, knockdown of Lrp4 in the hippocampal astrocytes after SE induction decreased SRS numbers. In accord, direct injection of agrin into the lateral ventricle of control mice but not mice with Lrp4 deletion in hippocampal astrocytes also increased the SRS numbers. These results indicate a promoting effect of agrin-Lrp4 signaling in hippocampal astrocytes on the development of SE-induced TLE. Last, we observed that knockdown of Lrp4 in hippocampal astrocytes increased the extracellular adenosine levels in the hippocampus 2 weeks after SE induction. Blockade of adenosine A1 receptor in the hippocampus by DPCPX after SE induction diminished the effects of Lrp4 on the development of SE-induced TLE. Conclusion These results demonstrate a promoting role of agrin-Lrp4 signaling in hippocampal astrocytes in the development of SE-induced development of epilepsy through elevating adenosine levels. Targeting agrin-Lrp4 signaling may serve as a potential therapeutic intervention strategy to treat TLE.

In order to clarify the controlling effect of different packaging materials on common storage pests, the penetration and survival of 7 kinds of high density polyethylene films with different concentrations of deltamethrin by the larvae of 3 common species of stored grain pests (Tribolium castaneum (Herbst), Tribolium confusum Duval and Lasioderma serricorne (Fabricius)) were investigated after being treated by two penetration methods for different times at 27~29 ℃ and 70%~80% RH. The results showed that all the tested new insect-proof films had certain insect resistance capabilities, which were different based on species of stored grain insects. In addition, the insect resistance capability of the 6 kinds of new films containing chemicals was higher than that of the control films after 9 days of treatment, and the anti-penetration rate of 1% A (HDPE particle containing 5% deltamethrin by mass) film, 3% A film, 1% B (HDPE particle containing 5% deltamethrin and 2% isoethers by mass) film and 3% B film was 100% under two penetration modes. The survival rate of all three species larvae decreased with increasing treatment time. After 9 days of parallel penetration treatment, the survival rate of three species of larvae on 3%B film was significantly lower than that of other films, and the survival rate of L. serricorne larvae reduced to 10% at the lowest. According to the penetration resistance and larvae survival rate of the test insects on the films, 3% B film had the best insect control effectiveness.

Chemotherapeutics can induce immunogenic cell death (ICD) in tumor cells, offering new possibilities for cancer therapy. However, the efficiency of the immune response generated is insufficient due to the inhibitory nature of the tumor microenvironment (TME). Here, we developed a pH/reactive oxygen species (ROS) dual-response system to enhance chemoimmunotherapy for melanoma. The system productively accumulated in tumors by specific binding of phenylboronic acid (PBA) to sialic acids (SA). The nanoparticles (NPs) rapidly swelled and released quercetin (QUE) and doxorubicin (DOX) upon the stimulation of tumor microenvironment (TME). The in vitro and in vivo results consistently demonstrated that the NPs improved anti-tumor efficacy and prolonged survival of mice, significantly enhancing the effects of the combination. Our study revealed DOX was an ICD inducer, stimulating immune responses and promoting maturation of dendritic cells (DCs). Additionally, QUE served as a TME regulator by inhibiting the cyclooxygenase-2 (COX2)-prostaglandin E2 (PGE2) axis, which influenced various immune cells, including increasing cytotoxic T cells (CLTs) infiltration, promoting M1 macrophage polarization, and reducing regulatory T cells (Tregs) infiltration. The combination synergistically facilitated chemoimmunotherapy efficacy by remodeling the immunosuppressive microenvironment. This work presents a promising strategy to increase anti-tumor efficiency of chemotherapeutic agents.

Laparoscopic surgery is extensively applied in the treatment of hepatobiliary diseases. Hepatic artery pseudoaneurysm (HAP) is a rare complication following hepatic biliary surgery through laparoscopy. The clinical manifestations of HAP are diverse and can be fatal. Given its severity, rapid assessment and management are crucial to ensuring a good prognosis. Here, we report three cases of HAP; two underwent laparoscopic surgery due to cholelithiasis, and another caused by trauma. The first case exhibited a pseudoaneurysm involving the distal portion of the right hepatic artery main trunk. The second patient had a pseudoaneurysm at the bifurcation of the left and right hepatic arteries. The third case involved a patient with a pseudoaneurysm involving a branch of the right hepatic artery. The main clinical manifestations of all three cases were bleeding from the biliary tract (the first two cases showed postoperative bleeding in the T-tube, while the third case exhibited gastrointestinal bleeding). The final diagnosis was obtained through digital subtraction angiography. The three patients underwent successful transcatheter arterial embolization operation and a follow-up revealed they were disease-free and alive. This article aims to highlight a rare complication of laparoscopic hepatobiliary surgery and share our experience in early diagnosis and treatment of HAP.

Background The number of chronic obstructive pulmonary disease (COPD) patients in China is huge, and respiratory rehabilitation training, as an important part of the management of COPD patients in the stabilization period, can effectively improve their lung function and quality of life, as well as reduce the burden on their families and society. Current data from Europe and the United States have shown that the implementation of respiratory rehabilitation under telemedicine management can improve the lung function and QOL of patients, however, there is a lack of relevant practice in China, especially in the west. Objective To assess the impact of respiratory rehabilitation training via telemedicine management in combination with conventional therapy on improving ventilatory capacity and lung function in elderly patients with moderate-to-severe COPD. Methods This study was a prospective randomized controlled study, enrolling consecutive COPD patients who attended the Fourth People's Hospital of Sichuan Province and five joint community clinics from June 2021 to June 2022. The included patients were randomly divided into the experimental group and control group by simple randomized grouping method using random number table. The control group received traditional long-term regular inhalation bronchodilator and oral medication, and the experimental group was guided by telemedicine on the basis of the treatment plan of the control group. A six-month study was conducted on two groups of patients, lung function, Borg score, 6MWT, and quality of life score (QOL score) were recorded at 1 month before and 1, 3, 6 months after intervention. Results The study subjects were divided into 72 cases in the control group and 73 cases in the experimental group, and there was no significant difference in gender, age and lung function at baseline [the forced expiratory volume in one second/predicted value ratio (FEV1%pred) , and the ratio of the forced expiratory volume in one second to the forced vital capacity (FEV1/FVC) ] between the two groups (P>0.05) . There was an interaction between time and group for dyspnea and mood in FEV1%pred, FEV1/FVC, 6MWT level and QOL score (P

Stored grain is extremely vulnerable to the storage insects during storage and processing. At present, chemical control is still the main method for controlling stored grain insects. However, the increasing resistance of insects caused by long-term use of chemical control raises unprecedented challenges. Insect-repellent packaging, as a traditional and emerging physical insect prevention method, has increasingly attracted widespread attention among people. The types and characteristics of food packaging materials, the types and application of insect-repellent packaging, the research and evaluating methods of insect-repellent packaging at home and abroad, and the problems existing in the practical application of insect-repellent packaging were reviewed, and the development trend of insect-repellent packaging was prospected, so as to provide reference information for the scientific and efficient use of insect-repellent packaging, development of new insect-repellent packaging to control stored grain insects in the future.

Abstract As a new data management paradigm, knowledge graphs can integrate multiple data sources and achieve quick responses, reasoning and better predictions in drug discovery. Characterized by powerful contagion and a high rate of morbidity and mortality, porcine reproductive and respiratory syndrome (PRRS) is a common infectious disease in the global swine industry that causes economically great losses. Traditional Chinese medicine (TCM) has advantages in low adverse effects and a relatively affordable cost of application, and TCM is therefore conceived as a possibility to treat PRRS under the current circumstance that there is a lack of safe and effective approaches. Here, we constructed a knowledge graph containing common biomedical data from humans and Sus Scrofa as well as information from thousands of TCMs. Subsequently, we validated the effectiveness of the Sus Scrofa knowledge graph by the t-SNE algorithm and selected the optimal model (i.e., transR) from six typical models, namely, transE, transR, DistMult, ComplEx, RESCAL and RotatE, according to five indicators, namely, MRR, MR, HITS@1, HITS@3 and HITS@10. Based on embedding vectors trained by the optimal model, anti-PRRSV TCMs were predicted by two paths, namely, VHC-Herb and VHPC-Herb, and potential anti-PRRSV TCMs were identified by retrieving the HERB database according to the pharmacological properties corresponding to symptoms of PRRS. Ultimately, Dan Shen's (Salvia miltiorrhiza Bunge) capacity to resist PRRSV infection was validated by a cell experiment in which the inhibition rate of PRRSV exceeded 90% when the concentrations of Dan Shen extract were 0.004, 0.008, 0.016 and 0.032 mg/mL. In summary, this is the first report on the Sus Scrofa knowledge graph including TCM information, and our study reflects the important application values of deep learning on graphs in the swine industry as well as providing accessible TCM resources for PRRS.

Summary: Biomarker screening is critical for precision oncology. However, one of the main challenges in precision oncology is that the screened biomarkers often fail to achieve the expected clinical effects and are rarely approved by regulatory authorities. Considering the close association between cancer pathogenesis and the evolutionary events of organisms, we first explored the evolutionary feature underlying clinically approved biomarkers, and two evolutionary features of approved biomarkers (Ohnologs and specific evolutionary stages of genes) were identified. Subsequently, we utilized evolutionary features for screening potential prognostic biomarkers in four common cancers: head and neck squamous cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, and lung squamous cell carcinoma. Finally, we constructed an evolution-strengthened prognostic model (ESPM) for cancers. These models can predict cancer patients’ survival time across different cancer cohorts effectively and perform better than conventional models. In summary, our study highlights the application potentials of evolutionary information in precision oncology biomarker screening.

BackgroundThe relationship between serum antinuclear antibody (ANA) and rheumatoid arthritis (RA) remains unknown. Therefore, we aimed to evaluate whether serum ANA was associated with an increased risk of RA in a case–control study.MethodsPatients with rheumatoid arthritis hospitalized at Shandong Provincial Hospital from January 2018 to December 2022 were recruited as the case group, and patients with other types of arthritis and healthy people at the same time were taken as the control group. Antinuclear antibody (ANA) was detected by indirect immunofluorescence assays. Propensity score matching was employed to construct a cohort of patients exhibiting comparable baseline characteristics. The relationship between serum ANA and the risk of rheumatoid arthritis was analyzed by logistic regression analysis.ResultsA total of 1,175 patients with RA and 1,662 control subjects were included in this study. After adjusting for potential confounding factors in the propensity-score matched cohort, the risk of RA gradually increased with rising of ANA titers. When ANA titers were divided into three groups (1:100, 1:320, and 1:1,000), the OR (95% CI) for ANA titers from low to high was 3.95 (3.01, 5.18), 16.63 (9.44, 29.30), and 17.34 (9.53, 31.54), respectively, compared to those when ANA was negative. The ANA patterns closely related to the occurrence of RA include nuclear homogeneous, nuclear speckled, and cytoplasmic speckled. Among them, the positive rate of nuclear homogeneous was the highest, which accounted for 42.64%. The OR (95% CI) of ANA patterns including nuclear homogeneous, nuclear speckled, and cytoplasmic speckled was 16.81 (11.46, 24.65), 3.40 (2.49, 4.63), and 3.09 (1.77, 5.40), respectively.ConclusionThere was a curve relation between ANA titer and RA, and the higher the ANA titer, the higher the probability of RA. However, there was no statistical difference in probability of RA for 1:320 versus 1:1,000 ANA titers. The most important kind of ANA pattern in the blood of RA patients was nuclear homogeneous. These findings suggest that ANA may be a novel risk marker for RA.