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Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of Chinese guideline for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the “Guidelines for the prevention and treatment of dyslipidemia\" were adapted into the “Chinese guideline for Lipid Management\" (henceforth referred to as the new guidelines) by an Experts’ committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with cardiovascular disease (CVD) risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

We report a rare case of 32-year-old female with malignant reninoma complicated by pulmonary metastasis and ATRX mutation (p.G1964*, VAF 23.73%), initially misdiagnosed as renal pelvic carcinoma and treated with radical left nephrectomy and ureterectomy. The patient developed local recurrence and pancreatic head metastasis in January 2025, with stable disease achieved after radiotherapy, EP chemotherapy and toripalimab immunotherapy. Subsequent olaparib targeted therapy led to resolution of renal recurrent tumor, but progressive pancreatic lesion and persistent pulmonary metastasis were observed, suggesting tumor heterogeneity. This case demonstrates the value of NGS in screening actionable molecular targets for rare malignant reninoma; olaparib yields favorable local control for ATRX-mutated malignant reninoma based on synthetic lethality, while the differential response at metastatic sites underscores the need for exploring combination therapies to overcome tumor heterogeneity and drug resistance, providing a clinical reference for precision treatment of this rare disease.

Understanding the electromechanical breakdown mechanisms of polycrystalline ceramics is critical to texture engineering for high‐energy‐density dielectric ceramics. Here, an electromechanical breakdown model is developed to fundamentally understand the electrostrictive effect on the breakdown behavior of textured ceramics. Taking the Na0.5Bi0.5TiO3‐Sr0.7Bi0.2TiO3 ceramic as an example, it is found that the breakdown process significantly depends on the local electric/strain energy distributions in polycrystalline ceramics, and reasonable texture design could greatly alleviate electromechanical breakdown. Then, high‐throughput simulations are performed to establish the mapping relationship between the breakdown strength and different intrinsic/extrinsic variables. Finally, machine learning is conducted on the database from the high‐throughput simulations to obtain the mathematical expression for semi‐quantitatively predicting the breakdown strength, based on which some basic principles of texture design are proposed. The present work provides a computational understanding of the electromechanical breakdown behavior in textured ceramics and is expected to stimulate more theoretical and experimental efforts in designing textured ceramics with reliable electromechanical performances. A comprehensive electromechanical breakdown model is established to investigate the electrostrictive effect on the breakdown behavior of textured ceramics. Based on high‐throughput simulations, machine learning is performed to find the optimization strategy of texture engineering to guide the design of high energy storage performance ceramics.

Electron avalanche breakdown plays a pivotal role in determining the efficiency and reliability of semiconductors and insulators in micro-nanoelectronics and power systems. However, it still remains challenging to understand and control this transient non-equilibrium process. Here, we propose and demonstrate an atomic-scale electron avalanche breakdown model to investigate the dynamic behaviors of excited electrons under extremely high electric fields in various dielectrics ranging from simple oxides to perovskites. Using high-throughput calculations, we establish the relationship maps between ionization energy, bond energy, electron mean free path and breakdown strength, and then excavate their mathematical expressions. On this basis, a high-entropy strategy in BaTiO 3 -based dielectrics with controllable lattice distortion is well designed to regulate the electron avalanche process, which successfully achieves a ~ 250% improvement in the breakdown strength by preventing electrons from acquiring sufficient energy. The atomic-scale understanding of electron avalanche breakdown process provides more refined guidance for atom/defect engineering to break the universal rule of inverse relation between breakdown strength and permittivity in dielectrics. Here the authors propose an atomic-scale electron avalanche breakdown model to investigate the dynamic behaviors of excited electrons under extremely high electric fields in various dielectrics ranging from simple oxides to perovskites.

Dielectric capacitors offer great potential for advanced electronics due to their high power densities, but their energy density still needs to be further improved. High-entropy strategy has emerged as an effective method for improving energy storage performance, however, discovering new high-entropy systems within a high-dimensional composition space is a daunting challenge for traditional trial-and-error experiments. Here, based on phase-field simulations and limited experimental data, we propose a generative learning approach to accelerate the discovery of high-entropy dielectrics in a practically infinite exploration space of over 10 11 combinations. By encoding-decoding latent space regularities to facilitate data sampling and forward inference, we employ inverse design to screen out the most promising combinations via a ranking strategy. Through only 5 sets of targeted experiments, we successfully obtain a Bi(Mg 0.5 Ti 0.5 )O 3 -based high-entropy dielectric film with a significantly improved energy density of 156 J cm −3 at an electric field of 5104 kV cm −1 , surpassing the pristine film by more than eight-fold. This work introduces an effective and innovative avenue for designing high-entropy dielectrics with drastically reduced experimental cycles, which could be also extended to expedite the design of other multicomponent material systems with desired properties. High-entropy ceramic dielectrics show promise for capacitive energy storage but struggle due to vast composition possibilities. Here, the authors propose a generative learning approach for finding high-energy-density high-entropy dielectrics in a practically infinite exploration space of over 10 11 combinations.

This study aimed to investigate the protective effects of the CB2R ligand compound COCA (N-(3-chloro-2-methylphenyl)-5-(4-hydroxyphenyl)-1,2-oxazole-3-carboxamide) against bleomycin (BLM)-induced pulmonary fibrosis in mice. Compound COCA was identified via AI-driven virtual screening from the ChEMBL database. Forty male C57BL/6J mice were randomly divided into five groups: control, model (BLM), low-dose COCA, high-dose COCA, and pirfenidone. Pulmonary fibrosis was induced by intratracheal BLM administration in the model and treatment groups. Pathological evaluation, ELISA, immunofluorescence, and Western blot were conducted.The results showed that COCA significantly alleviated BLM-induced inflammation and fibrosis. ELISA demonstrated decreased serum levels of TNF-α and IL-6 in the treated groups compared to the BLM group ( P < 0.01). Immunofluorescence indicated reduced expression of Col-I and Col-III in the treated groups ( P < 0.01). Western blot analysis revealed an upregulation of CB2R in the BLM group, and enhanced expressions of Nrf2 and Smad7 in the treated groups ( P < 0.01).In conclusion, AI-driven virtual screening enabled the identification of the CB2R ligand COCA, which binds to CB2R, activates the Nrf2/Smad7 pathway, downregulates related cytokines, and plays a therapeutic and protective role in pulmonary fibrosis.

Supported single-atom catalysts (SACs) possess high catalytic activity, selectivity, and atom utilizations. However, the atom coordination environments of SACs are difficult to accurately regulate due to the high complexity of coordination site and local environment of support. Herein, we develop an in-situ electrochemical cation-exchange method to fill the cation vacancies in MnO 2 with Ru single atoms (SAs). This obtained catalyst exhibits high mass activity, which is ∼ 44 times higher than commercial RuO 2 catalyst and excellent stability, superior to the most state-of-the-art oxygen evolution reaction (OER) catalysts. The experimental and theoretical results confirm that the doped Ru can induce charge density redistribution, resulting in the optimized binding of oxygen species, and the strong covalent interaction between Ru and MnO 2 for resisting oxidation and corrosion. This work will provide a new concept in the synthesis of well-defined local environments of supported SAs.

Objective To systematically review and compare the clinical efficacy and impact on fertility function between laparoscopic surgery and methotrexate treatment for tubal pregnancy. Methods Five English databases and four Chinese databases were systematically searched from the database establishment to January 31, 2024, and a meta-analysis was conducted using Review Manager 5.3. Results Ten articles were included, with a total of 1,034 study patients. The meta-analysis showed that compared with a single intramuscular injection of methotrexate, laparoscopic surgery for tubal pregnancy was associated with a significantly higher tubal patency rate [OR = 2.47, 95% CI 1.72–3.53, P  < 0.001]; and a significantly higher spontaneous pregnancy rate [OR = 2.10, 95% CI 1.28–3.46, P  = 0.003]; and a shorter time for serum HCG levels to return to normal [MD = -7.10, 95% CI − 7.84–6.36, P  < 0.001]. However, there was no statistically significant difference in treatment success rate between the two treatment methods [OR = 1.88, 95% CI 0.53–6.69, P  = 0.33], and no statistically significant difference in recurrent EP rate [OR = 1.09, 95% CI 0.41–2.87, P  = 0.87]. Conclusion Compared with a single intramuscular injection of methotrexate, laparoscopic surgery for tubal pregnancy is associated with better fertility function in the future, while the difference in clinical efficacy needs further exploration.

Pyroptosis is triggered by inflammasomes after its activation by various inflammatory stimulations, including lipopolysaccharide (LPS) and improper pH. This may result in programmed death of the affected cell. It is well known that NLRP1 and NLRP3 inflammasomes mediate the production of various cytokines in inflammatory disorders; however, it is still unknown whether NLRP1 and NLRP3 inflammasomes can influence the LPS-induced pyroptosis in the progression of knee osteoarthritis (KOA). In the present study, the correlation between the NLRP inflammasomes and fibroblast-like synoviocytes (FLSs) pyroptosis was investigated in vivo and in vitro. Human synovial samples were collected from KOA patients and the expression of NLRP1 and NLRP3 inflammasomes was analyzed. Human FLS were isolated in vitro and stimulated with LPS. To determine whether NLRP1 and NLRP3 inflammasomes are involved in FLS pyroptosis, NLRP1 and NLRP3 small interfering RNAs (siRNAs) were used. The results showed that the expression of NLRPs and inflammasome-related proteins were upregulated and FLS stimulated with LPS+ATP resulted in cell pyroptosis. However, LPS+ATP-induced pyroptosis was attenuated by NLRP1 and NLRP3 siRNAs. The results of the present study indicate that LPS-induced FLS pyroptosis may be mediated by either NLRP1 or NLRP3 inflammsomes. Overall, based on the data obtained from patients and in vitro cells, the present finsings showed that NLRP1 and NLRP3 inflammasomes are highly involved in the FLS inflammation and pyroptosis. Furthermore, inhibition of NLRP1 and NLRP3 led to a remarkable reduction of pyroptosis-related cytokines. Thus, NLRP1 and NLRP3 inflammasomes may be important in the pathogenesis of OA and may represent a novel therapeutic target.

Transforming growth factor-β（TGF-β） is a key factor in cancer development and progression. TGF-β can suppress tumorigenesis by inhibiting cell cycle progression and stimulating apoptosis in early stages of cancer progression. However, TGF-β can modulate cancer-related processes, such as cell invasion, distant metastasis, and microenvironment modification that may be used by cancer cells to their advantage in late stages. Corresponding mechanisms include angiogenesis promotion, anti-tumor immunity suppression, and epithelial-to-mesenchymal transition（EMT） induction. The correlation between TGF-β expression and cancer prognosis has also been extensively investigated. Results suggest that TGF-β pathway can be targeted to treat cancer; as such, the feasibility of this treatment is investigated in clinical trials.