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Abstract Mitophagy, a form of selective autophagy that removes damaged or dysfunctional mitochondria, plays a crucial role in maintaining mitochondrial and cellular homeostasis. Recent findings suggest that defective mitophagy is closely associated with various diseases, including breast cancer. Moreover, a better understanding of the multifaceted roles of mitophagy in breast cancer progression is crucial for the treatment of this disease. Here, we will summarize the molecular mechanisms of mitophagy process. In addition, we highlight the expression patterns and roles of mitophagy-related signaling molecules in breast cancer progression and the potential implications of mitophagy for the development of breast cancer, aiming to provide better therapeutic strategies for breast cancer treatment.

Abstract Background The cardiometabolic index (CMI) is a novel metric for assessing cardiometabolic health and type 2 diabetes mellitus (DM), yet its relationship with insulin resistance (IR) and prediabetes (preDM) is not well-studied. There is also a gap in understanding the nonlinear associations between CMI and these conditions. Our study aimed to elucidate these associations. Methods We included 13,142 adults from the National Health and Nutrition Examination Survey (NHANES) 2007–2020. CMI was calculated by multiplying the triglyceride-to-high density lipoprotein cholesterol (TG/HDL-C) by waist-to-height ratio (WHtR). Using weighted multivariable linear and logistic regression explored the relationships of CMI with glucose metabolism markers, IR, preDM, and DM. Nonlinear associations were assessed using generalized additive models (GAM), smooth curve fittings, and two-piecewise logistic regression. Results Multivariate regression revealed positive correlations between CMI and glucose metabolic biomarkers, including FBG (β = 0.08, 95% CI: 0.06–0.10), HbA1c (β = 0.26, 95% CI: 0.22–0.31), FSI (β = 4.88, 95% CI: 4.23–5.54), and HOMA-IR (β = 1.85, 95% CI: 1.56–2.14). There were also significant correlations between CMI and increased risk of IR (OR = 3.51, 95% CI: 2.94–4.20), preDM (OR = 1.49, 95% CI: 1.29–1.71), and DM (OR = 2.22, 95% CI: 2.00-2.47). Inverse nonlinear L-shaped associations were found between CMI and IR, preDM, and DM, with saturation inflection points at 1.1, 1.45, and 1.6, respectively. Below these thresholds, increments in CMI significantly correlated with heightened risks of IR, preDM, and DM. Conclusions CMI exhibited inverse L-shaped nonlinear relationships with IR, preDM, and DM, suggesting that reducing CMI to a certain level might significantly prevent these conditions.

Background Promoting the construction of county-level medical communities is a crucial measure for establishing a hierarchical medical system. While the domestic academic community has conducted extensive theoretical and empirical research in this field, there is a lack of comprehensive summaries of existing research findings. This study uses bibliometric methods to systematically review the progress of related literature in this field, providing insights and references for the high-quality development of county-level medical communities. Objective To conduct a visual analysis of the literature on county-level medical communities in China, exploring research hotspots and frontier trends in this field. Methods Using the China National Knowledge Infrastructure (CNKI) database, literature related to county-level medical communities published between 2016 and 2023 was retrieved on February 25, 2024. CiteSpace software was employed for bibliometric visualization analysis of the literature, focusing on publication years, authors and institutions, keyword co-occurrence, clustering, timeline distribution, and burst detection. Results A total of 481 articles were included. The publication volume in this field has been increasing, driven by policy factors, with 65 articles (13.51%) published between 2016 and 2019, 167 articles (34.72%) published between 2020 and 2021, and 249 articles (51.77%) published between 2022 and 2023. The top three authors in terms of publication volume were CHEN Yingchun, WANG Fang, and ZHENG Ying, each with 8 articles. The top two keywords in terms of centrality and cluster size are "medical community" and "hierarchical medical system". The timeline distribution indicated that "hierarchical medical system" was the earliest and most sustained research hotspot in this field. Additionally, clusters such as "integration of medical prevention" "performance evaluation" "countermeasures" and "patients" emerged as research hotspots. Burst detection revealed that "medical insurance fund" "chronic disease" "management model" "development strategy" and "rural doctors" were recent research hotspots and future directions in this field. Conclusion Key research hotspots in the field of county-level medical communities include the construction of hierarchical medical systems, focusing on chronic diseases and the integration of public health services, and exploring performance evaluation pathways. Future research trends indicate a strong focus on deepening policy research, using county-level medical community construction to promote the establishment of hierarchical medical systems, advancing innovation in the integration of medical prevention, enhancing performance evaluation, and optimizing internal management.

Highly efficient photocatalysts have been developed for the degradation of contaminated water under visible light. In this study, N-doped TiO2 (N-TiO2) and metal-free graphitic carbon nitride (g-C3N4) composites with various Ti/C molar ratios were prepared with the simple mixing-calcining method. The samples were characterized by X-ray diffraction, scanning electron microscopy, ultraviolet–visible diffuse reflectance spectroscopy, and photoluminescence spectroscopy. The photocatalytic activity of N-TiO2/g-C3N4 in the degradation of Rhodamine B (RhB) was investigated, and the electrochemical method was used to determine the origin of the enhanced photoactivity of N-TiO2/g-C3N4. The results showed that N-TiO2 nanoparticles were dispersed on the surface of g-C3N4 and formed a stable heterojunction structure with g-C3N4. The heterojunction between the two semiconductors could effectively prevent the recombination of photogenerated electrons and holes and improve the photocatalytic efficiency of the photocatalyst under visible light irradiation. The photocatalyst exhibited high stability, and the RhB degradation rate was still higher than 82.3% after five cycles.

Abstract Rare earth ions with d-f transitions (Ce3+, Eu2+) have emerged as promising candidates for electroluminescence applications due to their abundant emission spectra, high light conversion efficiency, and excellent stability. However, directly injecting charge into 4f orbitals remains a significant challenge, resulting in unsatisfied external quantum efficiency and high operating voltage in rare earth light-emitting diodes. Herein, we propose a scheme to solve the difficulty by utilizing the energy transfer process. X-ray photoelectron spectroscopy and transient absorption spectra suggest that the Cs3CeI6 luminescence process is primarily driven by the energy transfer from the I2-based self-trapped exciton to the Ce-based Frenkel exciton. Furthermore, energy transfer efficiency is largely improved by enhancing the spectra overlap between the self-trapped exciton emission and the Ce-based Frenkel exciton excitation. When implemented as an active layer in light-emitting diodes, they show the maximum brightness and external quantum efficiency of 1073 cd m−2 and 7.9%, respectively.

Abstract Human cases of avian influenza virus (AIV) infections are associated with an age-specific disease burden. As the influenza virus N2 neuraminidase (NA) gene was introduced from avian sources during the 1957 pandemic, we investigate the reactivity of N2 antibodies against A(H9N2) AIVs. Serosurvey of healthy individuals reveal the highest rates of AIV N2 antibodies in individuals aged ≥65 years. Exposure to the 1968 pandemic N2, but not recent N2, protected against A(H9N2) AIV challenge in female mice. In some older adults, infection with contemporary A(H3N2) virus could recall cross-reactive AIV NA antibodies, showing discernable human- or avian-NA type reactivity. Individuals born before 1957 have higher anti-AIV N2 titers compared to those born between 1957 and 1968. The anti-AIV N2 antibodies titers correlate with antibody titers to the 1957 N2, suggesting that exposure to the A(H2N2) virus contribute to this reactivity. These findings underscore the critical role of neuraminidase immunity in zoonotic and pandemic influenza risk assessment.

Multiple microgrid (MG) distribution systems are facing challenges owing to variations in the operational statuses of the individual MGs, which experience voltage and current fluctuations during transient interconnections. The impedances of the interconnecting lines further exacerbate the unevenness of power distribution among the MGs, hence threatening the operational stability of the system. To achieve flexible and seamless interconnections between multiple MGs, we fully analyzed the interconnected structures and operation modes of the MGs; then, we designed a transient switching control method based on investigation of the transient interconnection processes to ensure smooth transition of the MGs. Additionally, to balance the power distribution among the interconnected MGs, a voltage–current-based coordinated power control strategy was synthesized using advanced synchronized fixed-frequency technology. Simulation case studies were conducted, and the results indicate that the proposed coordinated power control scheme effectively facilitated instantaneous interconnections between the isolated regions, thereby avoiding voltage disturbances and current surges. Furthermore, it efficiently equalized and distributed the output power from the distributed energy sources, thereby enhancing the operational flexibilities and stabilities of the MGs and distribution system.

Chlorinated polyethylene （CPE) flame retardant composites were prepared with CPE as the matrix material and sepiolite as flame retardant, and the effects of the addition amount of sepiolite on cu-ring characteristics, physical and mechanical properties, and flame retardance were studied. The results showed that with the increase in the addition amount of sepiolite, tensile strength, tear strength, modulus at 100%, modulus at 300%, and Shore A hardness of the composites increased significantly; the addition of sepiolite improved limiting oxygen index of the CPE flame retardant composites, reduced the maximum heat release rate and total heat release during combustion of the composites, prolonged the ignition time of the composites, reduced the absolute content of carbon monoxide and carbon dioxode, and decreased the smoke emission.

Abstract Cancer-associated fibroblasts (CAFs), the main stromal component of the tumor microenvironment (TME), play multifaceted roles in cancer progression through paracrine signaling, exosome transfer, and cell interactions. Attractively, recent evidence indicates that CAFs can modulate various forms of regulated cell death (RCD) in adjacent tumor cells, thus involving cancer proliferation, therapy resistance, and immune exclusion. Here, we present a brief introduction to CAFs and basic knowledge of RCD, including apoptosis, autophagy, ferroptosis, and pyroptosis. In addition, we further summarize the different types of RCD in tumors that are mediated by CAFs, as well as the effects of these modes of RCD on CAFs. This review will deepen our understanding of the interactions between CAFs and RCD and might offer novel therapeutic avenues for future cancer treatments.

Objective To analyze and summarize the types, incidence rates and relevant influencing factors of adverse events (AEs) after high-intensity focused ultrasound ablation of gynecological diseases and provide reference and basis for handling such events in clinical practice.Method We searched PubMed, Cochrane Library, Web of Science and Embase databases to retrieve all literature since its establishment until February 2024. We evaluated the quality of included literature and publication bias and conducted a meta-analysis of single group rates for various AEs using Stata 17.0.Results This systematic review finally included 41 articles. We summarized 34 kinds of AEs in 7 aspects and conducted a single group rate meta-analysis and sub-group analysis of 16 kinds of AEs. Among the common AEs of High-Intensity Focused Ultrasound (HIFU), the incidence of lower abdominal pain/pelvic pain is 36.1% (95% CI: 24.3%∼48.8%), vaginal bleeding is 20.6% (95% CI: 13.9%∼28.0%), vaginal discharge is 14.0% (95% CI: 9.6%∼19.1%), myoma discharge is 24% (95% CI: 14.6%∼34.8%), buttock pain is 10.8% (95% CI: 6.0%∼16.5%) and sacral pain is 10% (95% CI: 8.8%∼11.2%). Serious complications include uterine rupture, necrotic tissue obstruction requiring surgical intervention, third degree skin burns and persistent lower limb pain or movement disorders.Conclusion The common AEs after HIFU surgery are mostly mild and controllable, and the incidence of serious complications is extremely low. By reasonable prevention and active intervention, these events can be further reduced, making it a safe and effective treatment method. It is a good choice for patients who crave noninvasive treatment or have other surgical contraindications.

BackgroundsUlcerative colitis (UC) is a form of chronic inflammatory bowel disease, and UC diagnosis rates continue to rise throughout the globe. The research and development of new drugs for the treatment of UC are urgent, and natural compounds are an important source. However, there is a lack of systematic summarization of natural compounds and their mechanisms for the treatment of UC.MethodsWe reviewed the literature in the databases below from their inception until July 2023: Web of Science, PubMed, China National Knowledge Infrastructure, and Wanfang Data, to obtain information on the relationship between natural compounds and UC.ResultsThe results showed that 279 natural compounds treat UC through four main mechanisms, including regulating gut microbiota and metabolites (Mechanism I), protecting the intestinal mucosal barrier (Mechanism II), regulating intestinal mucosal immune response (Mechanism III), as well as regulating other mechanisms (Mechanism Ⅳ) such as cellular autophagy modulation and ferroptosis inhibition. Of these, Mechanism III is regulated by all natural compounds. The 279 natural compounds, including 62 terpenoids, 57 alkaloids, 52 flavonoids, 26 phenols, 19 phenylpropanoids, 9 steroids, 9 saponins, 8 quinonoids, 6 vitamins, and 31 others, can effectively ameliorate UC. Of these, terpenoids, alkaloids, and flavonoids have the greatest potential for treating UC. It is noteworthy to highlight that a total of 54 natural compounds exhibit their therapeutic effects by modulating Mechanisms I, II, and III.ConclusionThis review serves as a comprehensive resource for the pharmaceutical industry, researchers, and clinicians seeking novel therapeutic approaches to combat UC. Harnessing the therapeutic potential of these natural compounds may significantly contribute to the improvement of the quality of life of patients with UC and promotion of disease-modifying therapies in the future.

Abstract With the comprehensive understanding of microorganisms and the rapid advances of physiochemical engineering and bioengineering technologies, scientists are advancing rationally‐engineered bacteria as emerging drugs for treating various diseases in clinical disease management. Engineered bacteria specifically refer to advanced physiochemical or genetic technologies in combination with cutting edge nanotechnology or physical technologies, which have been validated to play significant roles in lysing tumors, regulating immunity, influencing the metabolic pathways, etc. However, there has no specific reviews that concurrently cover physiochemically‐ and genetically‐engineered bacteria and their derivatives yet, let alone their distinctive design principles and various functions and applications. Herein, the applications of physiochemically and genetically‐engineered bacteria, and classify and discuss significant breakthroughs with an emphasis on their specific design principles and engineering methods objective to different specific uses and diseases beyond cancer is described. The combined strategies for developing in vivo biotherapeutic agents based on these physiochemically‐ and genetically‐engineered bacteria or bacterial derivatives, and elucidated how they repress cancer and other diseases is also underlined. Additionally, the challenges faced by clinical translation and the future development directions are discussed. This review is expected to provide an overall impression on physiochemically‐ and genetically‐engineered bacteria and enlighten more researchers.

ABSTRACT The upper and lower respiratory tract may share microbiome because they are directly continuous, and the nasal microbiome contributes partially to the composition of the lung microbiome. But little is known about the upper and lower airway microbiome of early postoperative lung transplant recipients (LTRs). Using 16S rRNA gene sequencing, we compared paired nasal swab (NS) and bronchoalveolar lavage fluid (BALF) microbiome from 17 early postoperative LTRs. The microbiome between the two compartments were significantly different in Shannon diversity and beta diversity. Four and eight core NS‐associated and BALF‐associated microbiome were identified, respectively. NS samples harbored more Corynebacterium, Acinetobacter, and Pseudomonas, while BALF contained more Ralstonia, Stenotrophomonas, Enterococcus, and Pedobacter. The within-subject dissimilarity was higher than the between-subject dissimilarity, indicating a greater impact of sampling sites than sampling individuals on microbial difference. There were both difference and homogeneity between NS and BALF microbiome in early postoperative LTRs. High levels of pathogens were detected in both samples, suggesting that both of them can reflect the diseases characteristics of transplanted lung. The differences between upper and lower airway microbiome mainly come from sampling sites instead of sampling individuals.IMPORTANCELung transplantation is the only therapeutic option for patients with end-stage lung disease, but its outcome is much worse than other solid organ transplants. Little is known about the NS and BALF microbiome of early postoperative LTRs. Here, we compared paired samples of the nasal and lung microbiome from 17 early postoperative LTRs and showed both difference and homogeneity between the two samples. Most of the “core” microbiome in both NS and BALF samples were recognized respiratory pathogens, suggesting that both samples can reflect the diseases characteristics of transplanted lung. We also found that the differences between upper and lower airway microbiome in early postoperative LTRs mainly come from sampling sites instead of sampling individuals.

Abstract Background Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. Methods From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. Results A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151–3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421–3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186–2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. Conclusion GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

With the increasing integrations of renewable energy resources into distribution networks (DNs) and microgrids (MGs), the imperative for an effective market scheduling mechanism becomes paramount to enhance the operational safety, reliability, and economic efficiency of distribution grids. Taking advantage of bi-level programming theory, this study meticulously formulates a comprehensive optimization scheduling model for the multi-MGs distribution network. The upper-level optimization objective is to minimize both the operational losses and total costs of the DN. Concurrently, the lower-level optimization pursues the maximization of daily operational revenue for MGs. Recognizing the pervasive impact of the inherent uncertainty associated with renewable energy sources on system safety and reliability, a cutting-edge scenario-based stochastic planning framework is introduced. The methodology integrates a heuristic matrix matching approach to effectively handle the intricate challenges posed by uncertainties from wind and photovoltaic generations. Moreover, in addressing the proposed nonlinear models, a sophisticated method is employed, utilizing the second-order cone relaxation and linearization methods. These methods meticulously transform the upper and lower-level models into second-order cone planning and mixed-integer linear programming issues, respectively. Finally, the proposed methodologies are rigorously scrutinized and validated with intricate case studies, providing a nuanced understanding of their efficacy. The empirical results underscore the theoretical feasibility and superiority of the proposed scheduling scheme. Notably, the operational performance of the DN as well as the economic viability of multiple MGs can also be significantly improved.

Exosomes are extracellular vesicles comprising bilayer phospholipid membranes and are secreted by eukaryotic cells. They are released via cellular exocytosis, contain DNA, RNA, proteins, and other substances, and participate in various cellular communications between tissues and organs. Since the discovery of exosomes in 1983, animal-derived exosomes have become a research focus for small-molecule drug delivery in biology, medicine, and other fields owing to their good biocompatibility and homing effects. Recent studies have found that plant-derived exosome-like nanovesicles (PELNVs) exhibit certain biological effects, such as anti-inflammatory and anti-tumor abilities, and have minimal toxic side effects. Because they are rich in active lipid molecules with certain pharmacological effects, PELNVs could be novel carriers for drug delivery. In this review, the biological formation and effects, isolation, and extraction of PELNVs, as well as characteristics of transporting drugs as carriers are summarized to provide new ideas and methods for future research on plant-derived exosome-like nanovesicles.

Umbilical cord-derived mesenchymal stem cells for regenerative therapy are a promising treatment option for chronic illnesses. Umbilical cord-derived mesenchymal stem cells offer several advantages over other sources, which makes them an attractive option in tissue repair and regeneration. This clinical study describes a 1-year follow-up on the safety and tolerance of umbilical cord-derived mesenchymal stem cell therapy on nine patients in Malaysia. Patients were assessed for adverse effects, and liver function tests were carried out on both pre- and post-treatments. Umbilical cord-derived mesenchymal stem cells’ effectiveness and safety were assessed by follow-up evaluations. All nine patients responded positively towards umbilical cord-derived mesenchymal stem cell therapy, without any adverse effects. After umbilical cord-derived mesenchymal stem cell therapy, a significant improvement was observed in liver functioning test outcomes, as haematological parameters and tumour markers were stable. The present study concludes that umbilical cord-derived mesenchymal stem cell therapy is well tolerated by Malaysian patients; however, further clinical screening must be done over a large number of patients population.

Objective: Dysregulation of covalently closed circular RNAs (circRNAs) has been associated with neurological disorders, the role of circHIVP2 in Parkinson's disease (PD) and its molecular mechanism is not well understood. Methods: 127 patients with PD and 85 healthy people were enrolled. RT-qPCR was employed to examine the levels of circHIVEP2. ROC curve to explore the diagnostic. Mpp+ induced the SH-SY5Y to construct an in vitro PD cell model. Cell viability, apoptosis, and secretion levels of inflammatory factors were analyzed by CCK-8, flow cytometry, and ELISA assay. CircHIVEP2 targets miRNA predicted by bioinformatics database and validated by the dual luciferase reporter and RIP assays. Results: CircHIVEP2 was typically lower in PD patients than in controls. CircHIVEP2 has certain specificity and sensitivity to recognize PD patients from healthy individuals. miR-485-3p, a target miRNA of circHIVEP2, was significantly elevated in PD patients. Additionally, MPP+ induction reduced cell viability and promoted apoptosis and inflammatory factor overproduction. However, overexpression of circHIVEP2 significantly inhibited the effects of MPP+, but this inhibition was significantly attenuated by elevated miR-485-3p. Conclusion: circHIVEP2 is a potential diagnostic biomarker for PD, and its upregulation mitigated MPP+-induced nerve damage and inflammation and this may be through targeted by the miR-485-3p.