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Endometriosis (EMs) is an estrogen-dependent chronic inflammatory disease. While apoptosis resistance (evidenced by Bcl-2 upregulation and Bax/caspase-3 downregulation) remains a hallmark of EMs, recent studies reveal a paradoxical coexistence of aberrant apoptotic activation (Fas/FADD/Caspase-8) and inflammatory PANoptosis in ectopic lesions, suggesting novel therapeutic targets for this complex disorder. GEO database mining revealed PANoptosis-related genes in EMs, which was experimentally validated through clinical and animal studies demonstrating the critical role of Fas/FADD/Caspase-8/RIPK1 signaling. Curcumol, the active component of Curcuma zedoaria rhizomes, exhibited strong binding affinity to Fas/RIPK1 in molecular docking and dynamics simulations, and effectively alleviated EMs progression by modulating this pathway, providing novel therapeutic insights for EMs management.

To systematically evaluate the efficacy and safety of blood-invigorating and stasis-resolving Chinese herbal medicines (BISMs) when combined with conventional clinical therapy for endometriosis, and to provide evidence-based guidance for clinical decision-making. Eight databases (CNKI, WanFang, VIP, SinoMed, PubMed, EMBASE, Cochrane Library, and Web of Science) were searched from inception to 16 June 2025 for randomized controlled trials (RCTs). Two reviewers independently screened studies, extracted data, and assessed risk of bias using a modified Cochrane tool. A random-effects network meta-analysis under a frequentist framework was performed with Stata 17.0 (mvmeta command). Surface under the cumulative ranking curve (SUCRA) values were used to rank interventions. Primary outcomes were overall clinical efficacy, pain visual analog scale (VAS), sex hormones (E2, FSH, LH), serum CA125, endometriotic cyst diameter, recurrence rate, and incidence of adverse events. A total of 107 RCTs were included. 1. Global efficacy: BISMs plus modern medical therapy significantly improved overall response; the combination of Guizhi Fuling pills/capsules with biomedicine ranked first (SUCRA = 87.4%). 2. Symptom relief: Regimens such as Sanjie Zhentong capsules and Xiaojin pills provided an additional 1-2-point reduction in VAS compared with modern medical therapy alone. 3. Hormonal regulation: Bushen Huoxue Sanyu decoction, Dan'e Fukang paste, and Gongliuxiao capsules showed prominent reductions in E2, FSH, and/or LH.4. Inflammation and lesion control: Danggui Shaoyao powder and Shaofu Zhuyu granules ranked highest for lowering CA125 and shrinking cyst diameter. 5. Recurrence and safety: Xiaojin pills, Bushen Huoxue Sanyu decoction, and Shaofu Zhuyu granules markedly reduced recurrence, while Dan'e Fukang paste, Guizhi Fuling pills/capsules, and Sanjie Zhentong capsules were associated with fewer adverse events. Funnel plots revealed no evident publication bias. Combining BISMs with conventional modern medical treatment offers superior multidimensional benefits-pain alleviation, hormonal balance, inflammatory control, cyst reduction, and recurrence prevention-over modern medical therapy alone, with a favorable safety profile. Among the evaluated regimens, Guizhi Fulingpills/capsules, Dan'e Fukang paste, Shaofu Zhuyu granules, and Gongliuxiao capsules demonstrated the most consistent overall performance. High-quality, large-scale RCTs with long-term follow-up are warranted to confirm and refine these findings.

The extensive research of two-dimensional layered materials has revealed that valleys, as energy extrema in momentum space, could offer a new degree of freedom for carrying information. Based on this concept, researchers have predicted valley-Hall topological insulators that could support valley-polarized edge states at non-trivial domain walls. Recently, several kinds of photonic and sonic crystals have been proposed as classical counterparts of valley-Hall topological insulators. However, direct experimental observation of valley-polarized edge states in photonic crystals has remained difficult until now. Here, we demonstrate a designer surface plasmon crystal comprising metallic patterns deposited on a dielectric substrate, which can become a valley-Hall photonic topological insulator by exploiting the mirror-symmetry-breaking mechanism. Topological edge states with valley-dependent transport are directly visualized in the microwave regime. The observed edge states are confirmed to be fully valley-polarized through spatial Fourier transforms. Topological protection of the edge states at sharp corners is also experimentally demonstrated. The photonic valley-Hall effect can enable the unidirectional propagation of edge states, but often require covers which shield the states from direct measurement. Here, Wu et al. realize photonic valley-Hall effect using designer surface plasmons, enabling the direct observation of topological states.

Background/Aims: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets.Methods: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options.Results: In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018–1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk of primary sclerosing cholangitis (PSC;1.193, 1.048– 1.357). On the other hand, CFHR1 (0.621, 0.497–0.776) and CFHR2 (0.824, 0.703–0.965) were inversely associated with the risk of alcohol-related cirrhosis. There were also significant inverse associations between C8 gamma chain (C8G) and PSC (0.832, 0.707–0.979), as well as the risk of metabolic dysfunction-associated steatotic liver disease (1.167, 1.036–1.314). Additionally, C1S (0.111, 0.018–0.672), C7 (1.631, 1.190–2.236), and CFHR2 (1.279, 1.059–1.546) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network.Conclusions: Our study suggests that certain complement components, including C1S, C1QC, CFHR1, CFHR2, CFHR5, C7, and C8G, might play a role in non-viral liver diseases and could be potential targets for drug development.

Background Most genetic skeletal disorders (GSD) were complex, disabling and life-threatening without effective diagnostic and treatment methods. However, its impacts on health system have not been well studied. The study aimed to systematically evaluate the health-care utilization and economic burden in GSD patients. Methods The patients were derived from 2018 Nationwide Inpatient Sample and Nationwide Readmissions Database. GSD patients were extracted based on International Classification of Diseases-10th revision codes. Results A total of 25,945 (0.12%) records regarding GSD were extracted from all 21,400,282 records in NIS database. GSD patients were likely to have significantly longer length of stay (6.50 ± 0.08 vs. 4.63 ± 0.002, P  < 0.001), higher total charges ($85,180.97 ± 1,239.47 vs. $49,884.26 ± 20.99, P  < 0.001), suffering more procedure, diagnosis and transferring records in comparison to patients with common conditions. GSD patients had a significantly higher 30-day all-cause readmission rate based on Nationwide Readmissions Database. Conclusions The heavy health-care utilization and economic burden emphasized the urgency for policy leaders, scientific and pharmaceutical researchers, health care providers and employers to identify innovative ways and take effective measurements immediately, and eventually to help improve the care, management, and treatment of these devastating diseases.

IntroductionThis study aimed to examine the risk of common diseases among people with pre-diabetes and explored the relationship between pre-diabetes and multimorbidity (in this case, two or more comorbid diseases).MethodsAn observational multicohort study using data from the UK Biobank database and the National Inpatient Sample (NIS) database (2016–2018) was conducted. We analysed 461 535 participants and 17 548 442 patients aged 18 years or older from both databases, of whom 14.0% and 0.7% were diagnosed with pre-diabetes, respectively. A total of 76 common diseases of various body systems were selected as adverse health outcomes for analysis.ResultsAmong 64 523 individuals with pre-diabetes in the UK Biobank, the mean age was 60 years, 35 304 (54.7%) were female. There were 24 non-overlapping diseases associated with pre-diabetes with significant multiple test results in both databases, and most of them are circulatory system diseases. Compared with normoglycaemia, the confounder-adjusted HR in the UK Biobank for pre-diabetes was 1.46 (95% CI 1.43 to 1.49) for accompanying complex multimorbidity (ie, four or more pre-diabetes-related diseases), the corresponding confounder-adjusted OR in the NIS study was 10.03 (95% CI 9.66 to 10.40).ConclusionPre-diabetes was associated with a significantly higher risk of multimorbidity. Pre-diabetes, thus, might represent an important target for multimorbidity prevention, and stronger emphasis on its management seems necessary to reduce the risk of the development of multiple comorbidities, especially before the onset of overt diabetes.

Poly-ion complex (PIC) integrating non-antibiotic theranostics holds great promise in the combat against drug-resistant bacteria. Photosensitizers with aggregation-induced emission (AIE) characteristic are particularly intriguing theranostic agents, but incorporating them into antibacterial PIC to enable both fluorescence and reactive oxygen species (ROS) generation turn-on deems a great challenge. Here we report the development of a PIC that can dually boost the fluorescence and ROS generation in the presence of pathogen bacteria. The PIC is constructed based on an anionic polydiacetylene poly(deca-4,6-diynedioic acid) (PDDA), which completely degrades in the presence of ROS. A cationic polymer quaternized poly(2-(dimethylamino)ethyl methacrylate) (PQDMA) that can disrupt bacterial membrane is co-loaded together with a highly efficient AIE photosensitizer TPCI in the PIC. PIC is nonfluorescent initially in that PDDA can quench the AIE of TPCI in PIC. When pathogenic bacteria are present, they can disturb the assembly of PIC to release TPCI, the fluorescence of which turns on sensitively to indicate the existence of bacteria. The on-demand irradiation can be subsequently applied to excite TPCI, which generates ROS to degrade PDDA and deform the PIC. As a result, TPCI and PQDMA are completely released to eliminate bacteria through a synergy of turned-on photodynamic therapy (PDT) and membrane disruption. The highly efficient detection and inhibition against both Gram-negative and Gram-positive bacteria have validated this polydiacetylene-based PIC system as an effective non-antibiotic antibacterial theranostic platform as well as a new strategy to enable “turn-on” fluorescence sensing and imaging of AIE fluorophores.

Rare endocrine diseases (RED) often pose chronic and life-threatening challenges, yet their economic costs and societal impact remains have not been precisely quantified. We obtained patient data from the 2018 Nationwide Inpatient Sample (NIS) and the Nationwide Readmissions Database (NRD), identifying RED patients through International Classification of Diseases, 10th revision codes. The difference of economic burden between RED patients and the control group, including hospital length of stay, hospitalisation costs, and readmission rates, was assessed using chi-square tests. We extracted 638 083 (2.98%) RED-related records from the NIS database. Compared to patients with common conditions, RED patients showed an exceedingly high burden of disease, including significantly extended hospital stays (P < 0.05), elevated total charges (P < 0.05), and heightened mortality rates (P < 0.05). They also had a substantially increased 30-day all-cause readmission rate based on the NRD database (P < 0.05). Although the different subgroups of RED patients had varying patterns of health care utilisation and economic burdens, they all surpassed those of patients with common conditions. There is a need for novel strategies aimed at mitigating the substantial RED-related burdens borne by individuals, families, and society in general, as well as funding for research and clinical trials.

Background/Aims: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets. Methods: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options. Results: In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018-1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk of primary sclerosing cholangitis (PSC;1.193, 1.048-1.357). On the other hand, CFHR1 (0.621, 0.497-0.776) and CFHR2 (0.824, 0.703-0.965) were inversely associated with the risk of alcohol-related cirrhosis. There were also significant inverse associations between C8 gamma chain (C8G) and PSC (0.832, 0.707-0.979), as well as the risk of metabolic dysfunction-associated steatotic liver disease (1.167, 1.036-1.314). Additionally, C1S (0.111, 0.018-0.672), C7 (1.631, 1.190-2.236), and CFHR2 (1.279, 1.059-1.546) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network. Conclusions: Our study suggests that certain complement components, including C1S, C1QC, CFHR1, CFHR2, CFHR5, C7, and C8G, might play a role in non-viral liver diseases and could be potential targets for drug development. (Clin Mol Hepatol 2024;30:80-97)

For most acoustic metamaterials, once they have been fabricated, their operating frequencies and functions cannot be adjusted, which is an intrinsic barrier for development of realistic applications. The study to overcome this limit has become a significant issue in acoustic metamaterial engineering. Although with the advance of metamaterials in the past two decades, a series of methods such as electric or magnetic control have been proposed, most of them can only work in the condition of no fluid passage. Some metamaterials with large transmission losses have been proposed, but the sounds are essentially reflected rather than absorbed. Here, to overcome this intrinsic difficulty, we propose a ventilated sound absorber that can be manually tuned in a large range after being manufactured. During the tuning which is achieved through an intricately designed slider, high-performance absorption and ventilation are both ensured. The tunable ventilated sound absorber is demonstrated experimentally and the effective model of coupled lossy oscillators can be employed to understand its mechanism. The manually tunable ventilated metamaterial has the potential application values in various complicated pipe systems that require frequency adjustment and it also establishes the foundation for future development of active tunable ventilated acoustic metamaterials.