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The potential protective mechanisms of MT on hepatic OS in PCOS. MT could lead to a decrease in autophagy, presenting a decrease of LC3 and an increase of P62 in the PCOS liver. Increased P62 could reduce Nrf2 ubiquitination and increase its nuclear translocation and activation through direct interaction with Keap1. Thus, MT ultimately activated the Keap1-Nrf2 pathway, promoting nuclear Nrf2 expression to reduce hepatic OS. Abstract The elevated level of hepatic oxidative stress (OS) in polycystic ovary syndrome (PCOS) is one of the important causes of liver abnormalities. Therefore, decreasing the level of hepatic OS in PCOS is beneficial in reducing the risk of PCOS-related liver diseases. Melatonin (MT) is recognized as a potent antioxidant. Nevertheless, the efficacy of MT in alleviating hepatic OS associated with PCOS is yet to be established, and the precise mechanisms through which MT exerts its antioxidant effects remain to be fully elucidated. The aim of this study was to explore the potential mechanisms by which MT reduces hepatic OS in PCOS. First, we detected elevated OS levels in PCOS samples. Subsequently, with MT pretreatment, we discovered that MT could significantly diminish the levels of OS, liver triglycerides, total cholesterol, alanine aminotransferase, and aspartate aminotransferase, while concurrently ameliorating mitochondrial structural damage in the PCOS liver. Furthermore, we identified elevated autophagy levels in the liver of PCOS rats and an inhibition of the Keap1–Nrf2 pathway. Through MT pretreatment, the expression of LC3 was significantly decreased, while the Keap1–Nrf2 pathway was activated. Our study showed that MT could affect the Nrf2 pathway dependent on the P62/LC3 autophagy pathway, thereby attenuating hepatic OS in PCOS. These findings offer novel insights and research avenues for the study of PCOS-related liver diseases.

Abstract Early and accurate diagnosis of focal liver lesions is crucial for effective treatment and prognosis. We developed and validated a fully automated diagnostic system named Liver Artificial Intelligence Diagnosis System (LiAIDS) based on a diverse sample of 12,610 patients from 18 hospitals, both retrospectively and prospectively. In this study, LiAIDS achieved an F1-score of 0.940 for benign and 0.692 for malignant lesions, outperforming junior radiologists (benign: 0.830-0.890, malignant: 0.230-0.360) and being on par with senior radiologists (benign: 0.920-0.950, malignant: 0.550-0.650). Furthermore, with the assistance of LiAIDS, the diagnostic accuracy of all radiologists improved. For benign and malignant lesions, junior radiologists’ F1-scores improved to 0.936-0.946 and 0.667-0.680 respectively, while seniors improved to 0.950-0.961 and 0.679-0.753. Additionally, in a triage study of 13,192 consecutive patients, LiAIDS automatically classified 76.46% of patients as low risk with a high NPV of 99.0%. The evidence suggests that LiAIDS can serve as a routine diagnostic tool and enhance the diagnostic capabilities of radiologists for liver lesions.

Objective To understand the experience and problems of nurses participating in new media health science popularization. Methods Using the qualitative research method of phenomenology, semi-structured interviews were conducted with 14 nurses who participated in the production and promotion of new media health science popularization. Results The real experience of nurses participating in new media health science popularization included 4 themes and 13 sub-themes. The 4 themes included: the improvement of nurses' sense of professional value; the improvement of nurses' new media health science popularization ability; the difficulties of nurses in new media health science popularization; perception Patients have complex science needs. Conclusion Nurses had benefited experience and encountered some difficulties in participating in new media health science popularization. Managers should integrate resources, improve the support system, encourage nurses to participate in new media health science popularization, enhance their sense of professional value and comprehensive ability, and build satisfaction High-quality new media health science popularization works with complex needs of patients. (目的 了解护士参与新媒体健康科普的体验及存在问题。方法 采用现象学质性研究方法, 对14名全流程参与新媒体健康科普制作和推广的护士进行半结构式访谈。结果 护士参与新媒体健康科普真实体验包括4个主题和13个亚主题, 4个主题包括: 护士职业价值感提升; 护士新媒体健康科普能力提升; 护士在新媒体健康科普中的困难; 感知到患者存在复杂科普需求。结论 护士参与新媒体健康科普存在获益体验, 也遇到一些困难。管理者应整合资源, 完善支持系统, 促进护士参与新媒体健康科普的同时, 提升其职业价值感及综合能力, 构建满足患者复杂需求的高质量新媒体健康科普作品。)

The incidence of leiomyosarcoma (LMS) is about 4–5/100,000 individuals per year. LMSs occurring in the small bowel are even rarer, and their preoperative diagnosis is very difficult. We described two patients with pathologically confirmed small bowel LMS and analyzed their clinical and medical imaging features. Similar cases reported in English in Pubmed database over the past decade were reviewed and summarized. These tumors were categorized by the growth direction and relationship with the intestinal lumen into three types: intraluminal (n = 10), intermural (n = 3), and extraluminal (n = 7). Notably, among the three types of LMS, the intramural leiomyosarcoma stands out as a noteworthy subtype. Emerging evidence suggests that smaller tumor size (< 5 cm) and the intraluminal type may serve as favorable prognostic indicators, while the extraluminal type is associated with relatively poor prognosis. Furthermore, the integration of imaging features with CA125 and LDH biomarkers holds promise for potential diagnostic value in LMS.

Summary: Although the small GTPase RAB37 acts as an organizer of autophagosome biogenesis, the upstream regulatory mechanism of autophagy via guanosine diphosphate (GDP)-guanosine triphosphate (GTP) exchange in maintaining retinal function has not been determined. We found that retinitis pigmentosa GTPase regulator (RPGR) is a guanine nucleotide exchange factor that activates RAB37 by accelerating GDP-to-GTP exchange. RPGR directly interacts with RAB37 via the RPGR-RCC1-like domain to promote autophagy through stimulating exchange. Rpgr knockout (KO) in mice leads to photoreceptor degeneration owing to autophagy impairment in the retina. Notably, the retinopathy phenotypes of Rpgr KO retinas are rescued by the adeno-associated virus-mediated transfer of pre-trans-splicing molecules, which produce normal Rpgr mRNAs via trans-splicing in the Rpgr KO retinas. This rescue upregulates autophagy through the re-expression of RPGR in KO retinas to accelerate GDP-to-GTP exchange; thus, retinal homeostasis reverts to normal. Taken together, these findings provide an important missing link for coordinating RAB37 GDP-GTP exchange via the RPGR and retinal homeostasis by autophagy regulation.

Background: Neural crest cells constitute a distinct set of multipotent cells that undergo migration along predefined pathways, culmination in the differentiation into a plethora of cell types, including components of the pharyngeal cartilage. The neurocranium is composite structure derived from both cranial neural crest and mesoderm cells, whereas the pharyngeal skeletal elements-including the mandibular and branchial arches-are exclusively formed by craniofacial neural crest cells. Previous studies have elucidated the critical involvement of the chemokine signaling axis Cxcl12b/Cxcr4a in craniofacial development in zebrafish (Danio rerio). Nonetheless, the function contribution of Cxcl12a and Cxcr4b-the homologous counterparts of Cxcl12b and Cxcr4a-remain largely unexplored.Methods: In the present study, mutant lines for cxcl12a and cxcr4b were generated employing CRISPR/Cas9 system. Temporal and spatial expression patterns of specific genes were assessed using in situ hybridization and dual-color fluorescence in situ hybridization techniques. High-resolution confocal microscopy was utilized for in vivo imaging to detect the pharyngeal arch or pouch patterning. Additionally, cartilage formation within the craniofacial region was analyzed via Alcian blue staining, and the proliferation and apoptosis rates of craniofacial neural crest cells were quantified through BrdU incorporation and TUNEL staining.Results: Our data reveals that the deletion of the chemokine gene cxcl12a results in a marked diminution of pharyngeal cartilage elements, attributable to compromised proliferation of post-migratory craniofacial neural crest cells. Subsequent experiments confirmed that Cxcl12a and Cxcl12b exhibit a synergistic influence on pharyngeal arch and pouch formation.Conclusion: Collectively, the present investigation furnishes compelling empirical evidence supporting the indispensable role of Cxcl2a in craniofacial cartilage morphogenesis, albeit cxcr4b mutants exert a minimal impact on this biological process. We delineate that Cxcl12a is essential for chondrogenesis in zebrafish, primarily by promoting the proliferation of craniofacial neural crest cells. Furthermore, we proposed a conceptual framework wherein Cxcl12a and Cxcl12b function synergistically in orchestrating both the pharyngeal arch and pouch morphogenesis.

Introduction The NICHE trial showed remarkable results of neoadjuvant immunotherapy in colorectal cancer patients with mismatch repair (MMR) deficiency (dMMR). However, rectal cancer patients with dMMR accounted for only 10% of case. The therapeutic effect is unsatisfactory in MMR-proficient patients. Oxaliplatin has been demonstrated to induce immunogenic cell death (ICD), which may improve the therapeutic effect of programmed cell death 1 blockade; however, a maximum tolerated dose is required to induce ICD. Arterial embolisation chemotherapy provides drugs locally and can easily reach the maximum tolerated dose, which could be a significant method for delivering chemotherapeutic agents. Therefore, we designed a multicenter, prospective, single-arm, phase II study.Methods and analysis First, recruited patients will receive neoadjuvant arterial embolisation chemotherapy (NAEC) with oxaliplatin 85 mg/m2 and 3 mg/m2. After 2 days, three cycles of immunotherapy with intravenous tislelizumab (200 mg/body, day 1) will be initiated at an interval of 3 weeks. From the second cycle of immunotherapy, the XELOX regimen will be added. 3 weeks after neoadjuvant therapy finished, the operation will be initiated. Neoadjuvant Arterial Embolization Chemotherapy Combined PD-1 Inhibitor for Locally Advanced Rectal Cancer (NECI) Study combined arterial embolisation chemotherapy, immunotherapy and systemic chemotherapy. Based on this combination therapy, the maximum tolerated dose could easily be reached, and ICD could be induced by oxaliplatin easily. To our knowledge, the NECI Study is the first multicenter, prospective, single-arm, phase II clinical trial to assess the efficacy and safety of NAEC combined with tislelizumab and systemic chemotherapy in locally advanced rectal cancer. This study is expected to provide a new neoadjuvant therapeutic regimen for locally advanced rectal cancer.Ethics and dissemination The Human Research Ethics Committee of the Fourth Affiliated Hospital of Zhejiang University School of Medicine approved this study protocol. The results will be published in peer-reviewed journals and presented at appropriate conferences.Trial registration number NCT05420584.

A series of GO/g-C3N4 aerogel materials were prepared by the methods of ultrasonic peeling, solution cross-linking and freeze-drying, and the proportion of raw materials were optimized. The materials were characterized by SEM, XRD, and UV-vis absorption spectrum. The photocatalytic activity was evaluated by the degradation of unsymmetrical dimethylhydrazine (UDMH) wastewater. The pure g-C3N4 aerogel was dominated by mesoporous structure. As the graphene oxide (GO) ratio increases, the layered structure and macroporous structure of the material gradually increase, and all show strong adsorption performance. When the mass fraction of GO is 25%, the photocatalytic degradation of UDMH wastewater is the best and the performance is stable after 5 cycles, the photocatalytic activity is only reduced by 7.15%. Through the study on the energy band structure, characterization of photoelectric effect and PL spectrum, the results show that the g-C3N4 molecular orbital energy level and band gap (Eg) were impacted by the cross-linking between the π-π bond of GO layers and the aromatic ring of g-C3N4, which improve the response performance to visible light. The metallic properties of GO facilitate the rapid separation of photogenerated electron-hole pairs and improve the photocatalytic activity. According to the band gap calculation and the intrinsic molecular orbital of the material, the main active species for GOCN photocatalytic degradation of UDMH wastewater are ·O-2 and h+.

Abstract Folliculogenesis is essential for production of female gametes in vertebrates. However, the molecular mechanisms underlying follicle development, particularly apoptosis regulation in ovary, remain elusive. Here, we generated sox3 knockout zebrafish lines using CRISPR/Cas9. sox3 knockout led to follicle development retardation and a reduced fecundity in females. Comparative analysis of transcriptome between sox3 −/− and wild-type ovaries revealed that Sox3 was involved in pathways of ovarian steroidogenesis and apoptosis. Knockout of sox3 promoted follicle apoptosis and obvious apoptosis signals were detected in somatic cells of stages III and IV follicles of sox3 −/− ovaries. Moreover, Sox3 can bind to and activate the promoter of cyp19a1a. Up-regulation of Cyp19a1a expression promoted 17β-estradiol synthesis, which inhibited apoptosis in follicle development. Thus, Sox3 functions as a regulator of Cyp19a1a expression, via 17β-E2 linking apoptosis suppression, which is implicated in improving female fecundity.

A cardiomyocyte differentiation in vitro system from zebrafish embryos remains to be established. Here, we have determined pluripotency window of zebrafish embryos by analyzing their gene-expression patterns of pluripotency factors together with markers of three germ layers, and have found that zebrafish undergoes a very narrow period of pluripotency maintenance from zygotic genome activation to a brief moment after oblong stage. Based on the pluripotency and a combination of appropriate conditions, we established a rapid and efficient method for cardiomyocyte generation in vitro from primary embryonic cells. The induced cardiomyocytes differentiated into functional and specific cardiomyocyte subtypes. Notably, these in vitro generated cardiomyocytes exhibited typical contractile kinetics and electrophysiological features. The system provides a new paradigm of cardiomyocyte differentiation from primary embryonic cells in zebrafish. The technology provides a new platform for the study of heart development and regeneration, in addition to drug discovery, disease modeling, and assessment of cardiotoxic agents.

C24H24Cu2N8O12S2, monoclinic, P21/c (no. 14), a = 10.4668(12) Å, b = 10.1315(12) Å, c = 14.9315(17) Å, β = 94.608(5)°, V = 1578.3(3) Å3, Z = 2, Rgt(F) = 0.0268, wRref(F2) = 0.0796, T = 296 K.

The pharmacokinetic profile of freeze-dried cyclosporine A-Eudragit S100 nanoparticles (CyA-S100-NP)was studied with a random two-way crossover study in dogs. The drug blood concentration was determined by internal standard HPLC method after oral administration of CyA-S100-NP and Neoral. Pharmacokinetics parameters were calculated by 3P97 program. The concentration-time data were fitted as a two-compartment open model. The AUC of CyA-S100-NP was higher than that of Neoral(P

To further study the effects of low temperature and high strain rate on the tensile behaviors of hydroxyl-terminated polybutadiene (HTPB) propellant, an INSTRON testing machine was applied for carrying out the uniaxial tensile tests at low temperatures and room temperature after storage at low temperatures. The strain rates are in the range of 0.40 to 85.71 s−1. Scanning electron microscope (SEM) was used for examining the failure mechanisms of HTPB propellant under the test conditions. The results reveal that HTPB propellant is still capable of large deformation at lower strain rates and low temperatures in the glass transition and glass state. The characteristics of stress-strain curves at room temperature after storage at low temperatures are the same with that directly obtained at room temperature. The effect of strain rate on the elastic modulus E at various temperatures is almost the same. However, the effect of strain rate on the maximum tensile stress σm becomes weak with decreasing temperature. Furthermore, the strain εm is nearly independence of the strain rate at higher strain rates and the lowest test temperature in glass state. Continuously decreasing temperature can more easily cause the extensive brittle fracture of AP particles, even at lower strain rates. The temperature changes from room temperature to low temperature and then from low temperature to room temperature in a short time cannot influence the failure mechanism of HTPB propellant at room temperature and high strain rate.

Chronic wounds, especially non-healing wounds, significantly affect patients' quality of life and raise the costs of therapy. Wound healing is a complicated process involving interdependent stages, which may be impaired and delayed by infections with multi-drug resistant pathogens. Current medical strategies for wound healing, especially the treatment of non-healing wounds, exert limited therapeutic effects, thus become a dramatic challenge for modern medicine. There has been growing interest in exploring complementary approaches to enhance the wound healing process, and complementary therapy using herbs and their related products has gained increasing attention. Apart from skin wounds, dermal pathological changes caused by UV irradiation, may also benefit from such complementary therapy. The antimicrobial, anti-inflammatory, antioxidant, analgesic and collagen-promoting properties of extract from Rosmarinus officinalis L. (rosemary) have all been considered to contribute to the beneficial effects on different stages and multiple aspects of skin recovery after various wounds or UV irradiation. This review aims to summarize the applications and their underlying mechanisms of rosemary as part of the complementary therapy for injured and UV-irradiated skin based on the currently available evidence. The medicinal properties of rosemary and its application in wound dressing are first discussed, followed by summarization of its application in different types of wounds. A conclusion is reached and future directions are discussed. As research in this area continue to evolve, rosemary-derived products may become an integral part of holistic wound care strategies, offering a complementary approach to conventional treatments. The properties of REO for the enhancement of skin healing process. For the antimicrobial property, REO exhibited activity against Gram-positive, Gram-negative bacteria, virus and fungi, particularly having a high antibacterial potency against MDR pathogens. For the anti-inflammatory property, REO prevented phosphorylation of MAPKs, suppressed the activation of NF-κB and decreased expressions of iNOS and COX-2. The antioxidant activity is associated with direct elimination of ROS and a significant reduction in DNA lesions, caspase-3 and -9 activity and IL-6 secretion. The analgesic property was attributed to its anti-neuroinflammation and neuroprotection, as indicated by the attenuation of markers of glia activation (Iba1, GFAP), inflammatory factors (TNF-ɑ, iNOS, TLR4) and apoptotic mediators (Bax, cleaved caspase-3 and caspase-9) in spinal cords. The collagen-promoting property refers to the enhanced collagen fibers and reduced number of senescent cells, leading to an accelerated wound healing. So far, the application of REO has been tested in a wide range of wounds and UV-irradiated skin, including excisional and incisional wounds, burns, diabetic wounds, pressure ulcer and sunburn. [ABSTRACT FROM AUTHOR]

A large variety of metal fuels is usually added to the modern solid rocket propellants to improve the propellant energy and motor specific impulse and to suppress high frequency unstable combustion. Among them, aluminum is the most common additive. The combustion process of aluminum can significantly affect the combustion characteristics of a solid rocket motor. In this paper, the SPH (Smoothed Particle Hydrodynamics) method is used to simulate the combustion process of aluminum particles. First, the SPH discrete equations with an evaporation combustion model are derived. On this basis, the evaporation combustion process of aluminum particles is numerically simulated. The results show that when aluminum particles are heated and evaporated in a static flow field, an alumina shell will be formed on the surface, and further thermal expansion will cause the alumina shell to break. The molten aluminum will spray out, and an aluminum cap will be formed on the surface. The "microburst process" will be similar to the gel droplet. In the convective environment, the flame structure of aluminum particles will be obviously peach shaped, which will wrap aluminum particles at the bottom. The simulation results are consistent with the experimental results. [ABSTRACT FROM AUTHOR]