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Qingru Niu,1– 3,* Chuanmiao Lin,1– 3,* Shuqing Yang,1– 3 Shuxuan Rong,1– 3 Junbin Wei,1– 3 Tingting Zhao,1– 3 Yingying Peng,1– 3 Zhilan Cheng,1– 3 Yunyi Xie,1– 3 Yan Wang1– 3 1Hospital of Stomatology, Guanghua School of Stomatology, Guangzhou, People’s Republic of China; 2Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunyi Xie; Yan Wang, Email xieyy59@mail2.sysu.edu.cn; wang93@mail.sysu.edu.cnPurpose: Periodontitis is a chronic infectious disease characterized by progressive inflammation and alveolar bone loss. Forkhead box O1 (FoxO1), an important regulator, plays a crucial role in maintaining bone homeostasis and regulating macrophage energy metabolism and osteogenic differentiation of mesenchymal stem cells (MSCs). In this study, FoxO1 was overexpressed into small extracellular vesicles (sEV) using engineering technology, and effects of FoxO1-overexpressed sEV on periodontal tissue regeneration as well as the underlying mechanisms were investigated.Methods: Human periodontal ligament stem cell (hPDLSCs)-derived sEV (hPDLSCs-sEV) were isolated using ultracentrifugation. They were then characterized using transmission electron microscopy, Nanosight, and Western blotting analyses. hPDLSCs were treated with hPDLSCs-sEV in vitro after stimulation with lipopolysaccharide, and osteogenesis was evaluated. The effect of hPDLSCs-sEV on the polarization phenotype of THP-1 macrophages was also evaluated. In addition, we measured the reactive oxygen species (ROS) levels, adenosine triphosphate (ATP) production, mitochondrial characteristics, and metabolism of hPDLSCs and THP-1 cells. Experimental periodontitis was established in vivo in mice. HPDLSCs-sEV or phosphate-buffered saline (PBS) were injected into periodontal tissues for four weeks, and the maxillae were collected and assessed by micro-computed tomography, histological staining, and small animal in vivo imaging.Results: In vitro, FoxO1-overexpressed sEV promoted osteogenic differentiation of hPDLSCs in the inflammatory environment and polarized THP-1 cells from the M1 phenotype to the M2 phenotype. Furthermore, FoxO1-overexpressed sEV regulated the ROS level, ATP production, mitochondrial characteristics, and metabolism of hPDLSCs and THP-1 cells in the inflammatory environment. In the in vivo analyses, FoxO1-overexpressed sEV effectively promoted bone formation and inhibited inflammation.Conclusion: FoxO1-overexpressed sEV can regulate osteogenesis and immunomodulation. The ability of FoxO1-overexpressed sEV to regulate inflammation and osteogenesis can pave the way for the establishment of a therapeutic approach for periodontitis. Keywords: periodontal ligament stem cells, small extracellular vesicles, periodontitis, bone homeostasis, mitochondrial function

Xiaoxia Ding,1 Shisong Rong,2 Yu Wang,1 Dong Li,1 Liang Wen,1 Bo Zou,1 Dongxiao Zang,1 Kemi Feng,3 Yuanbo Liang,3 Fenghua Wang,4 Gang Zhai1 1Department of Ophthalmology, Fushun Eye Hospital, Fushun, Liaoning, People’s Republic of China; 2Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear, Boston, MA, USA; 3Department of Ophthalmology, the Affiliated Eye Hospital, School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 4Department of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Science Key Laboratory, Beijing, People’s Republic of ChinaCorrespondence: Gang Zhai, Fushun Eye Hospital, No. 1 Hupo Street, Xinfu District, Fushun, Liaoning, 113008, People’s Republic of China, Email fsgangzhai@163.comAim: To report the prevalence of depression and its association with vision-related quality of life and social support in a type 2 diabetes mellitus (T2DM) population.Methods: Patients were recruited from a community-based study, Fushun Diabetic Retinopathy Cohort Study (FS-DIRECT), conducted between July 2012 and May 2013 in China. Depression was assessed using the Centre for Epidemiological Studies Depression Scale (CES-D). Vision-related quality of life was evaluated using the Visual Function Questionnaire-25 (VFQ-25). Social support was captured with the Social Support Rating Scale (SSRS). Generalized linear models were used to estimate the individual and joint association of VFQ-25 composite score (VFQCS) and SSRS score (SSRSS) with depression.Results: A total of 1618 subjects (60.9% female) aged 61.69 ± 8.72 years in an urban district of Jiangjun Street, Fushun City, Liaoning province, Northeast China from July 2012 to May 2013 were recruited, of which, 23.36% (95% CI: 21.30– 25.42%) were identified with depression. Every 14.1 increase in VFQ-25 composite score decreased the risk of depression by half (OR = 0.5; 95% CI: 0.4– 0.6); with the elevation of 10.0 SSRS score the risk of depression decreased by 40% (OR = 0.6; 95% CI: 0.5– 0.7). Patients with the VFQCS less than 91.3 and SSRSS less than 38.0 had 5.9 times more risk of depression (OR = 5.9; 95% CI: 3.6– 9.7). Age (over 60 years) (OR = 0.6; 95% CI: 0.4– 0.9) and medical history of cardiovascular disease (OR = 1.7; 95% CI: 1.1– 2.5) were independently correlated with depression symptom.Conclusion: The prevalence of depression is high among patients with T2DM in urban district in northeast China. Vision-related quality of life and social support scores are significantly associated with depression. Measures should be taken to screen depressive symptoms in patients with type 2 diabetes patients. These patients need to be intervened with appropriate and effective treatment as early as possible. Meanwhile, behavioral health specialists should guide the patient to get and use social support sources effectively.Keywords: diabetic retinopathy, depression, quality of vision, Visual Function Questionnaire-25, Social Support Rating Scale

Abstract Introduction Oral submucosal fibrosis is a potentially life-threatening oral disease that significantly impacts physiological functions such as speech and swallowing while also diminishing the quality of life for patients. Currently, the mainstream treatment for oral submucosal fibrosis in clinical practice involves invasive glucocorticoid drugs such as injection therapy. However, this method often leads to intraoperative pain, anxiety, fear, and poor medical experience due to associated side effects. Methods There is an urgent need to actively explore new drugs and relatively noninvasive approaches for the treatment of oral submucosal fibrosis in order to enhance patients’ medical experience and compliance. This has become a focal point of attention in clinical research. After conducting an extensive literature search, it was discovered that curcumin, a natural polyphenolic compound, exhibits potent anti-tumor, anti-inflammatory, antioxidant, anti-metastatic and anti-angiogenic properties. Moreover, curcumin holds significant clinical potential in the prevention and treatment of various diseases such as oral submucosal fibrosis. Conclusion This review presents a comprehensive elaboration encompassing the action mechanisms, biological activity, potential applications, and clinical characteristics of curcumin in the management of oral submucosal fibrosis, aiming to provide diagnostic insights and novel therapeutic perspectives for its prevention and treatment.

Abstract Chimeric antigen receptor T (CAR-T) cell therapy has greatly improved the prognosis of relapsed and refractory patients with large B-cell lymphoma (LBCL). Early identification and intervention of patients who may respond poorly to CAR-T cell therapy will help to improve the efficacy. Ninety patients from a Chinese cohort who received CAR-T cell therapy and underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans at the screening stage (median time to infusion 53.5 days, range 27–176 days), 1 month and 3 months after CAR-T cell infusion were analyzed, with RNA-sequencing conducted on 47 patients at the screening stage. Patients with maximum diameter of the largest lesion (Dmax)

Polysaccharide nano-selenium (polysaccharide selenium nanoparticles, Polysaccharide-SeNPs) exhibits unique properties and biological functions, offering limitless potential and promising applications in various fiels such as medicine, food and pharmacology. This review mainly focuses on the structure and properties of polysaccharides, nano-selenium (selenium nanoparticles, SeNPs) and the complementary combination of polysaccharides and SeNPs. SeNPs utilizes the hydrogen or Se-O bonds on its surface, thereby achieving dispersion and stability. The article provides a summary of the preparation conditions, methods, and optimization strategies for Polysaccharide-SeNPs. Currently, chemical synthesis methods are commonly used to produce Polysaccharide-SeNPs, with auxiliary techniques such as ultrasound, vacuum, high pressure, or enzymes employed to enhance yield or biological activity. Furthermore, the article reviews representative biological effects of Polysaccharide-SeNPs reported in the international literature over the past five years. Finally, emphasis is placed on the application and progress of Polysaccharide-SeNPs in the fields of medicine, food, pharmaceuticals, and health products. The study of Polysaccharide-SeNPs expands new perspectives in the field of traditional Chinese medicine, particularly polysaccharides derived from Chinese herbal medicine, providing a valuable reference for exploring novel and highly biologically active "selenium-shaped" entities.

Abstract Osteogenesis imperfecta (OI) is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding type I collagen. While it is well known that OI reflects defects in the activity of bone-forming osteoblasts, it is currently unclear whether OI also reflects defects in the many other cell types comprising bone, including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility. Here, we find that numbers of skeletal stem cells (SSCs) and skeletal arterial endothelial cells (AECs) are augmented in Col1a2 oim/oim mice, a well-studied animal model of moderate to severe OI, suggesting that disruption of a vascular SSC niche is a feature of OI pathogenesis. Moreover, crossing Col1a2 oim/oim mice to mice lacking a negative regulator of skeletal angiogenesis and bone formation, Schnurri 3 (SHN3), not only corrected the SSC and AEC phenotypes but moreover robustly corrected the bone mass and spontaneous fracture phenotypes. As this finding suggested a strong therapeutic utility of SHN3 inhibition for the treatment of OI, a bone-targeting AAV was used to mediate Shn3 knockdown, rescuing the Col1a2 oim/oim phenotype and providing therapeutic proof-of-concept for targeting SHN3 for the treatment of OI. Overall, this work both provides proof-of-concept for inhibition of the SHN3 pathway and more broadly addressing defects in the stem/osteoprogenitor niche as is a strategy to treat OI.

Abstract Purpose This study aimed to examine the correlation between different dominant follicle proportions (DFPs) and outcomes of in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) among patients classified under POSEIDON Groups 3 and 4, who underwent gonadotropin-releasing hormone antagonist (GnRH-ant) protocols. Additionally, it sought to determine the optimal DFP threshold for trigger timing. Methods A retrospective analysis was performed on patients classified under POSEIDON Groups 3 (n = 593) and 4 (n = 563) who underwent GnRH-ant protocols for controlled ovarian hyperstimulation (COH) between 2016 and 2022. These patients were categorized into two groups based on their DFPs, defined as the ratio of ≥ 18-mm dominant follicles to ≥ 12-mm follicles on the trigger day (DFP ≤ 40% and DFP ≥ 40%). Statistical analyses, including restricted cubic spline (RCS) and multivariate logistic regression, were employed to assess the relationship between DFP and IVF/ICSI outcomes. Results Demographic characteristics of patients were similar across groups. In POSEIDON Groups 3 and 4, DFP > 40 was associated with a significant decrease in the number (No.) of oocytes retrieved, cleaved embryos, and available embryos. Moreover, following the GnRH-ant cycle, the clinical pregnancy and live birth rates in fresh embryo transfer (ET) were notably reduced in the DFP > 40 group compared with the DFP ≤ 40 group, whereas no significant differences were observed in the pregnancy outcomes of the first frozen-thawed embryo transfer (FET) between the groups. In POSEIDON Group 3, the cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLRB) were significantly higher in the DFP ≤ 40 subgroup than in the DFP > 40 subgroup, with a notable decrease in CLRB observed with increasing DFP levels. However, in POSEIDON Group 4, no significant differences in CCPR and CLRB were found between the groups. Logistic regression analysis identified age and the No. of oocytes retrieved as pivotal factors influencing CLRB in Group 4. Conclusion For patients in POSEIDON Group 3, maintaining a DFP ≤ 40 mm is crucial to achieve optimal laboratory and pregnancy outcomes by avoiding delayed triggering. However, for patients in POSEIDON Group 4, age remains a critical factor influencing CLRB regardless of DFP, although a higher No. of oocytes retrieved and available embryos with DFP ≤ 40 is beneficial.

Abstract Background Air pollution poses a significant threat to global public health. While broad mitigation policies exist, an understanding of the economic consequences, both in terms of health benefits and mitigation costs, remains lacking. This study systematically reviewed the existing economic implications of air pollution control strategies worldwide. Methods A predefined search strategy, without limitations on region or study design, was employed to search the PubMed, Scopus, Cochrane Library, Embase, Web of Science, and CEA registry databases for studies from their inception to November 2023 using keywords such as “cost–benefit analyses”, “air pollution”, and “particulate matter”. Focus was placed on studies that specifically considered the health benefits of air pollution control strategies. The evidence was summarized by pollution control strategy and reported using principle economic evaluation measurements such as net benefits and benefit–cost ratios. Results The search yielded 104 studies that met the inclusion criteria. A total of 75, 21, and 8 studies assessed the costs and benefits of outdoor, indoor, and mixed control strategies, respectively, of which 54, 15, and 3 reported that the benefits of the control strategy exceeded the mitigation costs. Source reduction (n = 42) and end-of-pipe treatments (n = 15) were the most commonly employed pollution control methodologies. The association between particulate matter (PM) and mortality was the most widely assessed exposure-effect relationship and had the largest health gains (n = 42). A total of 32 studies employed a broader benefits framework, examining the impacts of air pollution control strategies on the environment, ecology, and society. Of these, 31 studies reported partially or entirely positive economic evidence. However, despite overwhelming evidence in support of these strategies, the studies also highlighted some policy flaws concerning equity, optimization, and uncertainty characterization. Conclusions Nearly 70% of the reviewed studies reported that the economic benefits of implementing air pollution control strategies outweighed the relative costs. This was primarily due to the improved mortality and morbidity rates associated with lowering PM levels. In addition to health benefits, air pollution control strategies were also associated with other environmental and social benefits, strengthening the economic case for implementation. However, future air pollution control strategy designs will need to address some of the existing policy limitations.

Abstract Background Pain management is an important part of nursing care for children. The objective of this study was to systematically assess the impact of virtual reality (VR) technology on alleviating the pain and anxiety experienced by children during venipuncture procedures. Methods This study searched Pubmed, Web of Sciences, Scopus, The Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Embase, Medline, China National Knowledge Infrastructure (CNKI), Wanfang, Weipu and China biomedical databases on the randomized controlled trials (RCTs) of virtual reality technology for relieving pain and anxiety associated with venous puncture for children up to July 6, 2024. Risk of bias tool recommended by Cochrane library was used to evaluate the RCT quality. RevMan 5.3 software was used for statistical analysis. Results A total of 10 RCTs involving 874 children were included. 429 children received VR intervention during vein puncture. VR was beneficial to reduce the children’s self-reported pain scores [SMD=-0.48, 95% CI (− 0.61, − 0.35)], children’s caregivers reported needle-related pain level [SMD=-0.93, 95% CI (-1.45, − 0.42)], children’s self-reported anxiety scores [SMD=-0.45, 95% CI (− 0.65, − 0.25)], children’s caregivers reported needle-related anxiety level [SMD=-0.47, 95% CI (− 0.73, − 0.21)]. Egger regression tests indicated that there were no publication biases in the synthesized outcomes (all P > 0.05). Conclusions VR technology has been shown to effectively mitigate the pain and anxiety experienced by children during venipuncture. Despite the positive findings, more research is needed to better understand the role of VR in children undergoing venipuncture.

Abstract Background Lung cancer (LC) is currently the number one malignancy death rate disease in China, and its disease burden is serious. The study aimed to analyze trends of LC and its risk factor attributable disease in China from 1990 to 2019 and predict the next 41 years. Methods The average annual percentage change (AAPC) was used to analyze the trend of LC and its risk factor attributable incidence, deaths, and disability‐adjusted life years (DALYs) rate in China from 1990 to 2019, collected in the Global Burden of Disease 2019. Cochran–Armitage trends examine trends in lung cancer disease burden by sex, age, and attributable risk factor groups in China from 1990 to 2019. In addition, based on data on death and DALYs rate due to LC and its risk factors between 1990 and 2019, an autoregressive integrated moving average (ARIMA) model was developed to predict the change in the trend of burden of disease due to LC and its risk factors over the next 41 years, and the model was evaluated using the model parameters root mean square error, mean absolute error, and mean absolute percentage error. Results From 1990 to 2019, the incidence, mortality and DALYs of LC were all increased. Among the eight risk factors associated with lung cancer, the DALYs rate and mortality rate of lung cancer risk factors for Chinese residents increased from 1990 to 2019, except for household air pollution from solid fuels and diet low in fruit, which showed a decrease; among them, the DALYs rate and mortality rate due to ambient particulate matter pollution showed the greatest increase with AAPC values of 2.880 and 3.310, respectively, while DALYs and mortality rates due to household air pollution from solid fuels showed the largest decreases, with AAPC values of −4.755 and −4.348, respectively. The results of the ARIMA model predictions show that both the mortality rate and the rate of DALYs for lung cancer are increasing yearly, and it is predicted that the rate of DALYs for lung cancer by 2060 will reach 740.095/100 000 and the mortality rate will reach 35.151/100 000. It is expected that by 2060, the top four risk factors for lung cancer in China will be, in order of DALYs rate and mortality rate, smoking, ambient particulate matter pollution, high fasting plasma glucose (HFPG), and secondhand smoke, with HFPG showing the greatest increase. Conclusions The LC burden increased from 1990 to 2019 in China, the LC burden that could be attributed to HFPG will continue to increase in the next 40 years, and will be the third most factor by 2060. Targeted interventions are warranted to facilitate the prevention of LC and improvement of health‐related quality of life patients with LC.

Abstract Purpose To investigate the impact of antibiotic treatment for chronic endometritis (CE) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycles and the relevant clinical risk factors associated with CE. Methods A retrospective cohort analysis was conducted on 1352 patients who underwent hysteroscopy and diagnostic curettage at Nanjing Maternal and Child Health Hospital from July 2020 to December 2021. All patients underwent CD138 immunohistochemical (IHC) testing to diagnose CE, and a subset of them underwent FET after hysteroscopy. Patient histories were collected, and reproductive prognosis was followed up. Results Out of 1088 patients, 443 (40.7%) were diagnosed with CE. Univariate and multivariate binary logistic regression analyses revealed that parity ≥ 2, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, hydrosalpinx, endometrial polyps, a history of ≥ 2 uterine operations, and RIF were significantly associated with an elevated risk of CE (P 0.05). Conclusion Infertile patients with a history of parity ≥ 2, hydrosalpinx, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, endometrial polyps, a history of ≥ 2 uterine operations, and RIF are at an increased risk of CE; these patients should be recommended to undergo hysteroscopy combined with CD138 examination before embryo transfer. Antibiotic treatment can improve the reproductive outcomes of FET in patients with CE, especially those with RIF.

Highlights A large-scale metabolic adaptation in M1-polarized macrophages compared with M2 macrophages, along with multiple altered metabolite parameters that can serve as potential targets, have been discussed. Nanomaterial-based repurposing of macrophage metabolism and its applications are systematically summarized and illustrated using representative examples. Potential challenges, additional information about future research objectives, and priorities of nanomaterial-based macrophage immunotherapy are highlighted.

Stress-induced anisotropy has been applied for FeSiBCuNb nanocrystalline alloy ribbons in transformers with large direct current (DC) component. However, the physical mechanism of anisotropy induced by stress annealing during crystallization remains controversial. Here, a systematic study was conducted on the microstructure, residual stress state, dynamic domain structure and properties of the stress-annealed FeSiBCuNb nanocrystalline ribbons. Present results demonstrate that, the increase of the applied stress greatly increases the residual tensile stress and induces lattice distortion, which acts as pinning site during magnetization, resulting in enhanced domain-wall energy and narrower wall width. Meanwhile, stress annealing promotes the flattening of hysteresis loops and decreases the effective permeability, which improves the DC-bias characteristics of the ribbons, thereby promoting the transition from “hard saturation” to “soft saturation” behavior. Also, stress-induced grain refinement is beneficial to obtaining high hardness. Owing to the stress-induced anisotropy, the stress-annealed sample with applied stress of 113 MPa exhibits excellent combined properties, including low constant effective permeability of 438 at wide frequency range (1 kHz–8 MHz), high DC-bias capability of 74% (30 Oe), low power loss of 49 kW/m3 (100 mT, 100 kHz), and high hardness of 644 HV. This discovery provides an insightful understanding of stress-induced anisotropy mechanism on the high-performance Fe-based nanocrystalline alloys.

Abstract The tunable properties of halide perovskite/two dimensional (2D) semiconductor mixed-dimensional van der Waals heterostructures offer high flexibility for innovating optoelectronic and photonic devices. However, the general and robust growth of high-quality monocrystalline halide perovskite/2D semiconductor heterostructures with attractive optical properties has remained challenging. Here, we demonstrate a universal van der Waals heteroepitaxy strategy to synthesize a library of facet-specific single-crystalline halide perovskite/2D semiconductor (multi)heterostructures. The obtained heterostructures can be broadly tailored by selecting the coupling layer of interest, and can include perovskites varying from all-inorganic to organic-inorganic hybrid counterparts, individual transition metal dichalcogenides or 2D heterojunctions. The CsPbI2Br/WSe2 heterostructures demonstrate ultrahigh optical gain coefficient, reduced gain threshold and prolonged gain lifetime, which are attributed to the reduced energetic disorder. Accordingly, the self-organized halide perovskite/2D semiconductor heterostructure lasers show highly reproducible single-mode lasing with largely reduced lasing threshold and improved stability. Our findings provide a high-quality and versatile material platform for probing unique optoelectronic and photonic physics and developing further electrically driven on-chip lasers, nanophotonic devices and electronic-photonic integrated systems.

Abstract Background Investigating the spatial distribution of muscle activity would facilitate understanding the underlying mechanism of spasticity. The purpose of this study is to investigate the characteristics of spastic muscles during passive stretch and active contraction by high-density surface electromyography (HD-sEMG). Methods Fourteen spastic hemiparetic subjects and ten healthy subjects were recruited. The biceps brachii (BB) muscle activity of each subject was recorded by HD-sEMG during passive stretch at four stretch velocities (10, 60, 120, 180˚/s) and active contraction at three submaximal contraction levels (20, 50, 80%MVC). The intensity and spatial distribution of the BB activity were compared by the means of two-way analysis of variance, independent sample t-test, and paired sample t-test. Results Compared with healthy subjects, spastic hemiparetic subjects showed significantly higher intensity with velocity-dependent heterogeneous activation during passive stretch and more lateral and proximal activation distribution during active contraction. In addition, spastic hemiparetic subjects displayed almost non-overlapping activation areas during passive stretch and active contraction. The activation distribution of passive stretch was more distal when compared with the active contraction. Conclusions These alterations of the BB activity could be the consequence of deficits in the descending central control after stroke. The complementary spatial distribution of spastic BB activity reflected their opposite motor units (MUs) recruitment patterns between passive stretch and active contraction. This HD-sEMG study provides new neurophysiological evidence for the spatial relationship of spastic BB activity between passive stretch and active contraction, advancing our knowledge on the mechanism of spasticity. Trial registration ChiCTR2000032245.

Colorectal carcinoma (CRC) is one of the most common malignancies, though there are no effective therapeutic regimens at present. This study aimed to investigate the inhibitory effects of mannooligosaccharides extracted from coconut meal (CMOSs) on the proliferation and migration of human colorectal cancer HCT116 cells in vitro. The results showed that CMOSs exhibited significant inhibitory activity against HCT116 cell proliferation in a concentration-dependent manner with less cytotoxic effects on the Vero normal cells. CMOSs displayed the ability to increase the activation of caspase-8, –9, and –3/7, as well as the generation of reactive oxygen species (ROS). Moreover, CMOSs suppressed HCT116 cell migration in vitro. Interestingly, treatment of human microvascular endothelial cells (HMVECs) with CMOSs resulted in the inhibition of cell proliferation, cell migration, and capillary-like tube formation, suggesting its anti-vascular angiogenesis. In summary, the results of this study indicate that CMOSs could be a valuable therapeutic candidate for CRC treatment.

Abstract Breast cancer patients may initially benefit from cytotoxic chemotherapy but experience treatment resistance and relapse. Chemoresistant breast cancer stem cells (BCSCs) play a pivotal role in cancer recurrence and metastasis, however, identification and eradication of BCSC population in patients are challenging. Here, an mRNA‐based BCSC signature is developed using machine learning strategy to evaluate cancer stemness in primary breast cancer patient samples. Using the BCSC signature, a critical role of polyamine anabolism in the regulation of chemotherapy‐induced BCSC enrichment, is elucidated. Mechanistically, two key polyamine anabolic enzymes, ODC1 and SRM, are directly activated by transcription factor HIF‐1 in response to chemotherapy. Genetic inhibition of HIF‐1‐controlled polyamine anabolism blocks chemotherapy‐induced BCSC enrichment in vitro and in xenograft mice. A novel specific HIF‐1 inhibitor britannin is identified through a natural compound library screening, and demonstrate that coadministration of britannin efficiently inhibits chemotherapy‐induced HIF‐1 transcriptional activity, ODC1 and SRM expression, polyamine levels, and BCSC enrichment in vitro and in xenograft and autochthonous mouse models. The findings demonstrate the key role of polyamine anabolism in BCSC regulation and provide a new strategy for breast cancer treatment.

Percutaneous coronary intervention (PCI) is currently the main method for treating coronary artery stenosis, but the incidence of restenosis after PCI is relatively high. Restenosis, the narrowing of blood vessels by more than 50% of the normal diameter after PCI, severely compromises the therapeutic efficacy. Therefore, preventing postinterventional restenosis is important. Vascular restenosis is mainly associated with endothelial injury, the inflammatory response, the proliferation and migration of vascular smooth muscle cells (VSMCs), excessive deposition of extracellular matrix (ECM) and intimal hyperplasia (IH) and is usually prevented by administering antiproliferative or anti-inflammatory drugs through drug-eluting stents (DESs); however, DESs can lead to uncontrolled drug release. In addition, as extracorporeal implants, they can cause inflammation and thrombosis, resulting in suboptimal treatment. Therefore, there is an urgent need for a drug carrier with controlled drug release and high biocompatibility for in vivo drug delivery to prevent restenosis. The development of nanotechnology has enabled the preparation of nanoparticle drug carriers with low toxicity, high drug loading, high biocompatibility, precise targeting, controlled drug release and excellent intracellular delivery ability. This review summarizes the advantages of nanoparticle drug carriers for treating vascular restenosis, as well as how nanoparticles have improved targeting, slowed the release of therapeutic agents, and prolonged circulation in vivo to prevent vascular restenosis more effectively. The overall purpose of this review is to present an overview of nanoparticle therapy for vascular restenosis. We expect these findings to provide insight into nanoparticle-based therapeutic approaches for vascular restenosis.

ABSTRACT Objective Researches on the epidemiology of various respiratory pathogens at multiple testing points in the pediatric population are limited, and these are crucial for the prevention of respiratory tract infections in children. Methods We obtained 1788 upper respiratory tract swabs from children exhibiting symptoms of respiratory infection (notably fever with a body temperature exceeding 38.5°C) across five hospitals in Guangdong between November 2020 and June 2022. We used the multiplex probe amplification (MPA) PCR testing to identify 11 respiratory viruses and subsequently analyzed the prevalence characteristics of these pathogens among febrile children in hospitals. Results The overall detection rate of the pathogens was 58.1% (1039/1788). Human rhinovirus (HRV) exhibited the highest detection rate at 19.0% (339/1788), succeeded by human parainfluenza virus (HPIV), human adenovirus (HAdV), and respiratory syncytial virus (RSV). The positivity and coinfection rates were higher in children aged 5 years and below compared to those above 5 years. Moreover, a distinct pathogen spectrum was observed across different age groups. Hospitalized patients demonstrated a significantly higher positivity and coinfection rate compared to outpatients. During COVID‐2019, RSV appeared a counter‐seasonal trend. Conclusion Respiratory viral infections in children display distinct characteristics concerning age, hospitalization status, and seasonality. Children under the age of 5 and minor patients admitted to hospitals at least be tested for RSV, HRV, HPIV, and HAdV. The epidemiological patterns of RSV in the post‐epidemic period require ongoing surveillance.

IntroductionAs a malignant hematological disease, the incidence of acute myeloid leukemia (AML) has exhibited an upward trend in recent years. Nevertheless, certain limitations persist in the treatment of AML. Sperm-associated antigen 6 (SPAG6) has been implicated in the onset and progression of various human cancers, with its expression levels significantly elevated in AML. Consequently, we undertook a series of experiments to investigate the role and underlying mechanisms of SPAG6 in AML cell lines.MethodsIn the in vitro experiments of this study, DEPs and GO and KEGG enrichment analysis subsequent to SPAG6 down-regulation were detected by TMT. CCK8 was employed to determine cell viability. The levels of apoptosis and ROS were measured by flow cytometry. In the in vivo experiments, a xenografted tumor model was constructed, and the expression of SPAG6 and GSTP1 in tumor tissues was detected by IHC.ResultsUltimately, our findings indicated that over-expression of SPAG6 promoted cell growth and decreased reactive oxygen species (ROS) and malondialdehyde levels. Furthermore, SPAG6 knockdown was found to diminish mitochondrial membrane potential and facilitate cell apoptosis. In vivo, SPAG6 could also promote tumor growth, suggesting that SPAG6 may serve as a pro-tumor factor. In addition, daunorubicin (DNR) may cause oxidative stress and initiate apoptosis, resulting in oxidative damage to AML cells. However, the overexpression of SPAG6 may attenuate the efficacy of DNR. This was due to SPAG6 promoted GSTP1 expression, thereby reducing ROS levels. Simultaneously, the elevation of GSTP1 and JNK complex may reduce the expression of p-JNK and inhibit the activation of JNK pathway, which might inhibit cell apoptosis.DiscussionIn conclusion, our experiments suggested that upregulated SPAG6 might mitigate the pro-apoptotic effects of DNR through ROS/JNK MAPK axis in a GSTP1-dependent manner.

BackgroundDNA damage induced by chemotherapy has duality. It affects the efficacy of chemotherapy and constrains its application. An increasing number of studies have shown that traditional Chinese medicine (TCM) is highly effective in reducing side-effects induced by chemotherapy due to its natural, non-toxic and many sourced from food. Recent advancements have demonstrated survival rates are improved attributable to effective chemotherapy. DNA damage is the principal mechanism underlying chemotherapy. However, not all instances of DNA damage are beneficial. Chemotherapy induces DNA damage in normal cells, leading to side effects. It affects the efficacy of chemotherapy and constrains its application.ObjectivesThis review aims to summarize the dual nature of DNA damage induced by chemotherapy and explore how TCM can mitigate chemotherapy-induced side effects.ResultsThe review summarized the latest research progress in DNA damage caused by chemotherapy and the effect of alleviating side effects by TCM. It focused on advantages and disadvantages of chemotherapy, the mechanism of drugs and providing insights for rational and effective clinical treatment and serving as a basis for experiment. In this review, we described the mechanisms of DNA damage, associated chemotherapeutics, and their toxicity. Furthermore, we explored Chinese herb that can alleviate chemotherapy-induced side-effects.ConclusionWe highlight key mechanisms of DNA damage caused by chemotherapeutics and discuss specific TCM herbs that have shown potential in reducing these side effects. It can provide reference for clinical and basic research.

With the advancement of Fuel Cell Vehicles (FCVs), detecting hydrogen leaks is critically important in facilities such as hydrogen refilling stations. Despite its significance, the dynamic response performance of hydrogen sensors in confined spaces, particularly under ceilings, has not been comprehensively assessed. This study utilizes a catalytic combustion hydrogen sensor to monitor hydrogen leaks in a confined area. It examines the effects of leak size and placement height on the distribution of hydrogen concentrations beneath the ceiling. Results indicate that hydrogen concentration rapidly decreases within a 0.5–1.0 m range below the ceiling and declines more gradually from 1.0 to 2.0 m. The study further explores the attenuation pattern of hydrogen concentration radially from the hydrogen jet under the ceiling. By normalizing the radius and concentration, it was determined that the distribution conforms to a Gaussian model, akin to that observed in open space jet flows. Utilizing this Gaussian assumption, the model is refined by incorporating an impact reflux term, thereby enhancing the accuracy of the predictive formula.

Oceanic water quality monitoring is essential for environmental protection, resource management, and ecosystem vitality. Optical remote sensing from space plays a pivotal role in global surveillance of oceanic water quality. However, the spatial resolution of current ocean color data products falls short of scrutinizing intricate small-scale marine features. This study introduces a hybrid model that fuses MODIS (Moderate Resolution lmaging Spectroradiometer) ocean color products with Sentinel-2 ‘s remote sensing reflectance data to generate high-resolution ocean color imagery, specifically investigating the diffuse attenuation coefficient at a wavelength of 490 nm (Kd490). To address the intricacies of coastal environments, we propose two complementary strategies to improve the accuracy of inversion. The first strategy leverages MODIS ocean color products alongside a geographic segmentation model to perform distinct inversions for separate marine zones, enhancing spatial resolution and specificity in coastal regions. The second strategy bolsters model interpretability during training by integrating predictions from conventional physical models into a Random Forest-based Regression Ensemble (RFRE) model. This study focuses on the coastal regions surrounding the Beibu Gulf, near Hainan Island in China. Our findings exhibit a strong concordance with MODIS products, achieving a monthly average coefficient of determination (R²) of 0.90, peaking at 0.97, and sustaining a monthly average root-mean-square error (RMSE) of less than 0.02. These results substantiate the model’s efficacy. Moreover, the annual trend analysis and localized assessment of the reconstructed Kd490 offer nuanced insights that surpass MODIS data, establishing a robust foundation for high-resolution water quality monitoring in coastal zones.

Summary: A disclosed technique employs electrochemical dehydrogenative cross-coupling to create organophosphates, utilizing phosphites compounds with arenols. Inorganic iodide salts serve dual roles as redox catalysts and electrolytes in an undivided cell, omitting the need for external oxidants or bases. Initial mechanistic investigations indicate the reaction unfolds via an electro-oxidative radical pathway, facilitating the formation of P–O bonds, leading to the generation of oxygen radicals in the formation of acetylaminophenol. This environmentally friendly approach offers excellent tolerance to various functional groups, achieves high yields (up to 95% isolated yield), and accommodates a wide range of substrates, showcasing its utility for practical synthesis applications.

ObjectivesProgrammed death-ligand 1 (PD-L1) is the only Food and Drug Administration-approved biomarker for monitoring response to immune checkpoint inhibitor (ICI) therapy in patients with lung adenocarcinoma. Understanding the nuances of molecular phenotypes, clinical attributes, and PD-L1 expression levels in primary and metastatic lung adenocarcinoma may help predict response to therapy and assist in the clinical management of lung adenocarcinoma.MethodsA total of 235 primary and metastatic lesion specimens from patients with non-small cell lung cancer (NSCLC) an institution in Shandong, China were analyzed. PD-L1 expression was assessed by immunohistochemistry using the 22C3 antibody, and the molecular phenotype was determined by next-generation sequencing of 450 genes. The molecular phenotypes of the primary and metastatic lesions were compared.ResultsElevated PD-L1 expression was significantly associated with advanced and metastatic disease (P = 0.001). The distribution of PD-L1 expression varied based on the anatomical location, showing a higher frequency of elevated PD-L1 expression in distal metastases than in the primary tumor. Metastatic lesions exhibited a higher proportion of carcinogenic pathway gene alterations and a greater number of DNA damage-repair pathway gene alterations than the primary lesions. Notably, CDKN2A copy number deletions were more prevalent in metastatic lesions than in primary lesions. Clinical data stemming from research conducted at the Memorial Sloan Kettering Cancer Center revealed an association between the absence of CDKN2A expression and a poorer prognosis in stage I lung adenocarcinoma.ConclusionSamples of metastatic tumors exhibited a higher proportion of elevated PD-L1 expression, a greater number of pathway alterations, and a higher occurrence of CDKN2A copy number deletions than primary samples. This highlights the importance of reinforcing the clinical management and follow-up of patients with CDKN2A deficiency, particularly within the subset of stage I lung adenocarcinoma.

Background: The climate change scenario has witnessed an increase in extreme temperature events (ETEs), including heat waves and cold spells, and a heightened occurrence of compounding with fine particulate matter (PM2.5). However, the impact of this phenomenon on the sensitivity to thyroid hormones (THs) in humans is unclear, especially in a group as specific as schizophrenia. Methods: A longitudinal study was constructed using longitudinal measurements of thyroid function in schizophrenia in the Anhui Mental Health Center. The latent growth mixture model was applied to assess the optimal trajectory of change in impaired THs sensitivity. We then used logistic regression to explore associations between heat waves, cold spells, and PM2.5 with impaired THs sensitivity trajectories in the total population and different gender and age subgroups. Furthermore, the effect of the frequency, intensity, and duration of ETEs in the above associations was explored, as well as an assessment of the interaction between ETEs and PM2.5. Results: Among 931 participants, we identified two classifications of trajectories of impaired THs sensitivity: “Low-stable” (n = 836, 89.80 %) and “Rise-slight down” (n = 95, 10.20 %). Logistic regression showed significant associations between each additional day of heat waves (≥3 days with temperature thresholds above the 95th percentile) and cold spells (≥3 days with temperature thresholds below the 5th percentile) and “Rise-slight down” trajectory, with odds ratios (95 % confidence intervals) of 1.06 (1.02, 1.10) and 1.19 (1.14, 1.24), respectively, and the strength of this association increased with the intensity and duration of ETEs. Subgroup analyses indicated that the association was more pronounced in males and the age group above 40 years. Furthermore, PM2.5 was found to interact with heat waves, with high concentrations exacerbating the effects of heat waves. Conclusions: Our findings suggest that mitigating both ETEs and PM2.5 exposures may bring health co-benefits in preventing thyroid impairment in schizophrenia.

Epoxy resin composites are a type of polymer-based materials with wide application scopes. A mass of fillers was added to improve thermal properties which may degrades mechanical properties at the same time. In addition, the common heat-curing process takes several hours to completely cure. To improve the performance of epoxy resin composites of low-content fillers, we prepare UV-heat dually curable epoxy resin with silicate ester. The overall curing time of UV-heat curing process is about half of the traditional thermal-curing process. The breakdown voltage of epoxy resin modified by silicate ester is up to 181 MV/m, which is increased by 50 % compared to pure epoxy resin. The silicate ester curing agent can react with both epoxy resin and silica fillers and can thus improve the dispersion of the fillers in the matrix and enhance the interaction between fillers and the resin. As a result, the coefficient of thermal expansion (CTE) of the composites was greatly reduced. The CTE of silicate ester-modified epoxy resin composites is 93 ppm/K and 137 ppm/K over the temperature range below and above its Tg, respectively, which is 25 % lower than those of normal epoxy resin composites.

To characterize the chromosomes of the four species of Polygonatum Miller, 1754, used in traditional Chinese medicine, P. cyrtonema Hua, 1892, P. kingianum Collett et Hemsley, 1890, P. odoratum (Miller, 1768) Druce, 1906, and P. sibiricum Redouté, 1811, and have an insight into the karyotype variation of the genus Polygonatum, fluorescence in situ hybridization (FISH) with 5S and 45S rDNA oligonucleotide probes was applied to analyze the karyotypes of 9 populations of the four species. Detailed molecular cytogenetic karyotypes of the 9 populations were established for the first time using the dataset of chromosome measurements and FISH signals of 5S and 45S rDNA. Four karyotype asymmetry indices, CVCI, CVCL, MCA and Stebbins’ category, were measured to elucidate the asymmetry of the karyotypes and karyological relationships among species. Comparison of their karyotypes revealed distinct variations in the karyotypic parameters and rDNA patterns among and within species. The basic chromosome numbers detected were x = 9, 11 and 13 for P. cyrtonema, x = 15 for P. kingianum, x = 10 and 11 for P. odoratum, and x = 12 for P. sibiricum. The original basic chromosome numbers of the four species were inferred on the basis of the data of this study and previous reports. All the 9 karyotypes were of moderate asymmetry and composed of metacentric, submetacentric and subtelocentric chromosomes or consisted of two of these types of chromosomes. Seven populations have one locus of 5S rDNA and two loci of 45S rDNA, and two populations added one 5S or 45S locus. The karyological relationships among the four species revealed by comparison of rDNA patterns and PCoA based on x, 2n, TCL, CVCI, MCA and CVCL were basically accordant with the phylogenetic relationships revealed by molecular phylogenetic studies. The mechanisms of both intra- and inter-specific dysploidy in Polygonatum were discussed based on the data of this study and literature.

Abstract Gastric cancer is one of the most common malignant tumors, and chemotherapy is the main treatment for advanced gastric cancer. However, chemotherapy resistance leads to treatment failure and poor prognosis in patients with gastric cancer. Multidrug resistance (MDR) is a major challenge that needs to be overcome in chemotherapy. According to recent research, ferroptosis activation is crucial for tumor therapeutic strategies. In this work, we explored the solution to chemoresistance in gastric cancer by investigating the effects of the Chinese medicine monomer baicalin on ferroptosis. Baicalin with different concentrations was used to treat the parent HGC27 and drug-resistant HGC27/L cells of gastric cancer. Cell viability was measured by CCK8, and synergistic effects of baicalin combined with oxaliplatin were evaluated using Synergy Finder software. The effects of baicalin on organelles and cell morphology were investigated using projective electron microscopy. Iron concentration, MDA production and GSH inhibition rate were measured by colorimetry. ROS accumulation was detected by flow cytometry. The ferroptosis-related genes (IREB2, TfR, GPX4, FTH1), P53, and SLC7A11 were analysed by Western blot, and the expression differences of the above proteins between pretreatment and pretreatment of different concentrations of baicalin, were assayed in both parental HGC27 cells and Oxaliplatin-resistant HGC27/L cells. Mechanically, Baicalin disrupted iron homeostasis and inhibits antioxidant defense, resulting in iron accumulation, lipid peroxide aggregation, and specifically targeted and activated ferroptosis by upregulating the expression of tumor suppressor gene p53, thereby activating the SLC7A11/GPX4/ROS pathway mediated by it. Baicalin activates ferroptosis through multiple pathways and targets, thereby inhibiting the viability of oxaliplatin-resistant gastric cancer HGC27/L cells and enhancing the sensitivity to oxaliplatin chemotherapy.

Abstract Background Knee osteoarthritis (KOA) characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults. The pathophysiology of KOA remains poorly understood, as it involves complex mechanisms that result in the same outcome. Consequently, researchers are interested in studying KOA and require appropriate animal models for basic research. Chinese herbal compounds, which consist of multiple herbs with diverse pharmacological properties, possess characteristics such as multicomponent, multipathway, and multitarget effects. The potential benefits in the treatment of KOA continue to attract attention. Purpose This study aims to provide a comprehensive overview of the advantages, limitations, and specific considerations in selecting different species and methods for KOA animal models. This will help researchers make informed decisions when choosing an animal model. Methods Online academic databases (e.g., PubMed, Google Scholar, Web of Science, and CNKI) were searched using the search terms “knee osteoarthritis,” “animal models,” “traditional Chinese medicine,” and their combinations, primarily including KOA studies published from 2010 to 2023. Results Based on literature retrieval, this review provides a comprehensive overview of the methods of establishing KOA animal models; introduces the current status of advantages and disadvantages of various animal models, including mice, rats, rabbits, dogs, and sheep/goats; and presents the current status of methods used to establish KOA animal models. Conclusion This study provides a review of the animal models used in recent KOA research, discusses the common modeling methods, and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

Abstract The COVID-19 pandemic has provided valuable lessons that deserve deep thought to prepare for the future. The decay pattern of surface contamination by SARS-CoV-2 RNA in the residences of COVID-19 patients is important but still unknown. We collected 2,233 surface samples from 21 categories of objects in 141 residences of COVID-19 patients in Shanghai when attacked by the omicron variant in spring 2022. Several characteristics of the patients and their residences were investigated to identify relevant associations. The decay of contamination was explored to determine the persistence. Approximately 8.7% of the surface samples were tested positive for SARS-CoV-2 RNA. The basin, water tap, and sewer inlet had the highest positive rates, all exceeding 20%. Only time was significantly associated with the level of surface contamination with SARS-CoV-2, showing a negative association. The decrease fit a first-order decay model with a decay rate of 0.77 ± 0.07 day−1, suggesting a 90% reduction in three days. Positive associations between the cumulative number of newly diagnosed patients in the same building and the positive rate of SARS-CoV-2 RNA in the public corridor were significant during the three days. Our results, in conjunction with the likely lower infectivity or viability, demonstrate that fomite transmission played a limited role in COVID-19 spread. The time determined SARS-CoV-2 RNA contamination, which was reduced by three days. This study is the first to show the decay patterns of SARS-CoV-2 contamination in real residential environments, providing insight into the patterns of transmission, as well as community-based prevention and control of similar threats.

Abstract Importance The first meta-analysis focused only on gonadotropin-releasing hormone (GnRH) antagonists, which helped determine the effect of delay trigger on pregnancy outcomes. Objective To evaluate the impact of delay trigger compared with standard trigger in normal responders undergoing GnRH antagonist protocol in improving pregnancy outcomes. Methods Studies published before April 2023 in PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, VIP and CBM databases were searched. Randomized controlled trials (RCTs) and cohort studies conducted in normal responders reporting the efficacy of delay trigger using GnRH antagonist protocol were included. Data were combined to calculate mean differences (MD) for continuous variables and odd ratios (OR) for categorical variables with their corresponding 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran’s Q test. Results Endpoints, including clinical pregnancy rate (CPR), live birth rate (LBR), the number of oocyte retrievals and embryos, and fertilization rate, were analyzed. Six (6) clinical studies (4 RCTs and 2 cohort studies) with 1,360 subjects were included. The pooled results showed that the number of oocyte retrievals (MD: 1.20, 95% CI: 1.10, 1.30, p

Abstract New concept for the development of supramolecular assemblies from intricate interactions between different classes of biomacromolecules (polysaccharides, proteins and lipids) is yet to come, due to their intrinsic chemical and structural complexity and incompatibility. Herein, we report an interaction mechanism among multiple biomacromolecules, and the structural and digestive properties of their assemblies using amylose (AM), lauric acid (LA), and β‐lactoglobulin (βLG) as exemplars. AM, LA, and βLG interact to form a water‐soluble ternary complex through van der Waals forces between AM and LA and high affinity binding between AM and βLG, which can further assemble into uniform‐sized, semi‐crystalline nanospheres under certain thermodynamic conditions. These nanospheres are substantially resistant to amylolysis, thus can be well utilized by gut microbiota, including increasing short‐chain fatty acid levels and shaping bacterial communities. Illustrating the complexation of AM, LA, and βLG and their assemblies from disorder to order, this work offers potential rationale of assemblies for multiple biomacromolecules driven by non‐covalent interactions and substantial potentials for supramolecular biomaterials development.

Abstract 2D magnetic materials hold substantial promise in information storage and neuromorphic device applications. However, achieving a 2D material with high Curie temperature (TC), environmental stability, and multi‐level magnetic states remains a challenge. This is particularly relevant for spintronic devices, which require multi‐level resistance states to enhance memory density and fulfil low power consumption and multi‐functionality. Here, the synthesis of 2D non‐layered triangular and hexagonal magnetite (Fe3O4) nanosheets are proposed with high TC and environmental stability, and demonstrate that the ultrathin triangular nanosheets show broad antiphase boundaries (bAPBs) and sharp antiphase boundaries (sAPBs), which induce multiple spin precession modes and multi‐level resistance. Conversely, the hexagonal nanosheets display slip bands with sAPBs associated with pinning effects, resulting in magnetic‐field‐driven spin texture reversal reminiscent of “0” and “1” switching signals. In support of the micromagnetic simulation, direct explanation is offer to the variation in multi‐level resistance under a microwave field, which is ascribed to the multi‐spin texture magnetization structure and the randomly distributed APBs within the material. These novel 2D magnetite nanosheets with unique spin textures and spin dynamics provide an exciting platform for constructing real multi‐level storage devices catering to emerging information storage and neuromorphic computing requirements.

The motor temperature distribution characteristics help to understand the working condition of the unit, thus improving efficiency. Currently, the motors are gradually being used at high altitudes. However, the plateau region has low air pressure, thin air and large differences in humidity. There is a lack of research on the effect of its complex and special working environment on motor temperature. Therefore, in this study, the numerical analysis of the motor temperature field is carried out from the novel perspective of plateau characteristics. In this paper, the finite volume method is used to analyse the flow-heat-solid coupling of a 20 MW motor. By comparing and verifying the experimental data with the simulation data, it is found that the error between the two is within 5 %. In order to have a more comprehensive picture of the motor's operation in the plateau environment, the temperature effects of different air pressure, air intake and relative humidity on the motor were investigated. The results of the study show that air pressure changes have a large effect on the temperature of the stator structure. The temperature decreases when the air pressure increases and the temperature difference decreases gradually with the increase of air pressure. The largest temperature difference in the stator structure occurs when the air pressure increases from 10 kPa to 40 kPa. The change in air intake has a positive effect on the stator structure temperature, which decreases when the air intake increases. After simulation calculations, it was found that the best heat dissipation effect was achieved in the range of air intake between 3.5 m/s and 4.5 m/s. Relative humidity has a minimal effect on the stator structure temperature. The conclusions of this paper can provide certain theoretical reference for the temperature change law of the motor under plateau operation, which is of great significance to improve the comprehensive hydraulic performance.

IntroductionTo characterize the influence of female-specific hormones on women’s thyroid function, the study investigated the influence of extra progestin from oral contraceptives on inducing thyroid dysfunction.MethodsSixty female Wistar rats were divided into six groups based on levonorgestrel or desogestrel administration as the main active agents: control, low (0.0039 mg*20-fold), medium (0.0039 mg*100-fold), high (0.0318 mg*100-fold) levonorgestrel (pure product); and low (0.0083 mg*20-fold) and high (0.0083 mg*100-fold) desogestrel (pure product). Progestin was administered by gavage every 4 days for 1 month. Statistical analysis was performed using one-way analysis of variance and the Kruskal–Wallis test.ResultsFollowing levonorgestrel gavage, serum free T4 and thyroidstimulating hormone levels were significantly lower in the experimental group than that in the control group (p=0.013 and 0.043). After desogestrel gavage, the serum free T4 and free T3 levels were lower in the experimental group than that in the control group (p=0.019 and 0.030). Thyroid hormone antibody concentrations were lower in rats administered levonorgestrel and desogestrel than that in control rats. Moreover, exposure to progestin upregulated the expression of the thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid.DiscussionProgestin stimulation enhanced the proliferation of follicular epithelial cells in rat thyroid tissues. Progestin exposure could cause thyroid dysfunction by upregulating the transcription of thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid, thus inducing pathomorphological changes in rats’ thyroid.

In order to explore the species and population distribution of endophytic fungi in Camellia luteoflora, as well as their inhibitory effects on plant pathogenic fungi, this study used tissue separation method to isolate and purify endophytic fungi in C. luteoflora. These fungi were identified based on morphology and molecular biology, and their diversity was evaluated through statistical analysis. The strains with antibacterial activity were screened out by the plate confrontation method. The results were as follows: (1) A total of 261 strains of endophytic fungi were isolated from 324 C. luteoflora tissue samples, belonging to 1 phylum, 5 classes, 9 orders, and 22 genera. The dominant genera were Colletotrichum, Diaporthe and Pestalotiopsis with isolation frequencies of 21.84%, 16.86% and 10.34%, respectively. (2) The distribution of endophytic fungi in C. luteoflora varied in different seasons. The highest number of strains was isolated in winter (72 strains, accounting for 27.59%, belonging to 16 genera), 62 strains were isolated in spring (belonging to 13 genera), 59 strains were isolated in summer (belonging to 15 genera), and 68 strains were isolated in autumn (belonging to 13 genera). The Shannon-Wiener index (H′), Simpson index (D), Pielou's evenness index (E), and Margalef's richness index (M) were the highest in winter. The similarity of endophytic fungal species between spring and winter was higher, and the similarity between summer and autumn was higher. (3) The distribution of endophytic fungi also varied in different parts of C. luteoflora. The stems had the most abundant endophytic fungi, with 102 strains accounting for 39.08% (belonging to 15 genera), 61 strains were isolated from the roots (belonging to 10 genera), and 98 strains were isolated from the leaves (belonging to 15 genera). The H′, D, E, and M were highest in the stems, and the endophytic fungal species in the leaves were most similar to those in the stems. (4) The plate confrontation results showed that among the 35 tested endophytic fungi, 26 endophytic fungi had inhibitory effects on at least one plant pathogenic fungi, accounting for 74.29%, among which CJ-Ⅱ-2, XY-V-3, QY-Ⅱ-4, QJ-Ⅲ-2 and DJ-I-2 had inhibitory effects on eight plant pathogen fungi to varying degrees. XY-V-3 had the best inhibitory effect on eight plant pathogenic fungi, and the inhibitory rate was higher than 50%. XY-V-3 and QJ-Ⅲ-2 have higher inhibitory rate than 50% on two strains of pathogenic fungi in C. luteoflora, which had the potential to control disease of C. luteoflora. To sum up, the diversity of endophytic fungi in C. luteoflora is rich, and some of the strains have higher effect of inhibiting plant pathogenic fungi, which lay a foundation for the research and development of biological control products and the disease control of C. luteoflora.

Abstract Recent work by our laboratory and others indicates that co-display of multiple antigens on protein-based nanoparticles may be key to induce cross-reactive antibodies that provide broad protection against disease. To reach the ultimate goal of a universal vaccine for seasonal influenza, a mosaic influenza nanoparticle vaccine (FluMos-v1) was developed for clinical trial (NCT04896086). FluMos-v1 is unique in that it is designed to co-display four recently circulating haemagglutinin (HA) strains; however, current vaccine analysis techniques are limited to nanoparticle population analysis, thus, are unable to determine the valency of an individual nanoparticle. For the first time, we demonstrate by total internal reflection fluorescence microscopy and supportive physical–chemical methods that the co-display of four antigens is indeed achieved in single nanoparticles. Additionally, we have determined percentages of multivalent (mosaic) nanoparticles with four, three, or two HA proteins. The integrated imaging and physicochemical methods we have developed for single nanoparticle multivalency will serve to further understand immunogenicity data from our current FluMos-v1 clinical trial.

Abstract The Ciona intestinalis voltage-sensing phosphatase (Ci-VSP) is a membrane protein containing a voltage-sensing domain (VSD) that is homologous to VSDs from voltage-gated ion channels responsible for cellular excitability. Previously published crystal structures of Ci-VSD in putative resting and active conformations suggested a helical-screw voltage sensing mechanism in which the S4 helix translocates and rotates to enable exchange of salt-bridge partners, but the microscopic details of the transition between the resting and active conformations remained unknown. Here, by combining extensive molecular dynamics simulations with a recently developed computational framework based on dynamical operators, we elucidate the microscopic mechanism of the resting-active transition at physiological membrane potential. Sparse regression reveals a small set of coordinates that distinguish intermediates that are hidden from electrophysiological measurements. The intermediates arise from a noncanonical helical-screw mechanism in which translocation, rotation, and side-chain movement of the S4 helix are only loosely coupled. These results provide insights into existing experimental and computational findings on voltage sensing and suggest ways of further probing its mechanism.