Genetic variation and evolutionary characteristics of Echovirus 11: new variant within genotype D5 associated with neonatal death found in China.

Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. From 2018 to 2023, a surge in severe neonatal cases and fatalities linked to a novel variant of genotype D5 was documented in China, France, and Italy. However, the prevention and control of E11 variants have been hampered by limited background data on the virus circulation and genetic variance. Therefore, the present study investigated the circulating dynamics of E11 and the genetic variation and molecular evolution of genotype D5 through the collection of strains from the national acute flaccid paralysis (AFP) and hand, foot, and mouth disease (HFMD) surveillance system in China during 2000-2022 and genetic sequences published in the GenBank database. The results of this study revealed a prevalent dynamic of E11 circulation, with D5 being the predominant genotype worldwide. Further phylogenetic analysis of genotype D5 indicated that it could be subdivided into three important geographic clusters (D5-CHN1: 2014-2019, D5-CHN2: 2016-2022, and D5-EUR: 2022-2023). Additionally, variant-specific (144) amino acid mutation sites and positive-selection pressure sites (132, 262) were identified in the VP1 region. Cluster-specific recombination patterns were also identified, with CVB5, E6, and CVB4 as the major recombinant viruses. These findings provide a preliminary landscape of E11 circulation worldwide and basic scientific data for further study of the pathogenicity of E11 variants.

Towards an actionable One Health approach.

BACKGROUND: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. MAIN TEXT: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. CONCLUSIONS: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.

Magnetic Nanoparticle-Based Microfluidic Platform for Automated Enrichment of High-Purity Extracellular Vesicles.

Extracellular vesicles (EVs) are available in various biological fluids and have highly heterogeneous sizes, origins, contents, and functions. Rapid enrichment of high-purity EVs remains crucial for enhancing research on EVs in tumors. In this work, we present a magnetic nanoparticle-based microfluidic platform (ExoCPR) for on-chip isolation, purification, and mild recovery of EVs from cell culture supernatant and plasma within 29 min. The ExoCPR chip integrates bubble-driven micromixers and immiscible filtration assisted by surface tension (IFAST) technology. The bubble-driven micromixer enhances the mixing between immunomagnetic beads and EVs, eliminating the need for manual pipetting or off-chip oscillatory incubation. The high-purity EVs were obtained after passing through the immiscible phase interface where hydrophilic or hydrophobic impurities nonspecifically bound to SIMI were removed. The ExoCPR chip had a capture efficiency of 75.8% and a release efficiency of 62.7% for model EVs. We also demonstrated the powerful performance of the ExoCPR in isolating EVs from biological samples (>90% purity). This chip was further employed in clinical plasma samples and showed that the number of GPC3-positive EVs isolated from hepatocellular carcinoma patients was significantly higher than that of healthy individuals. This ExoCPR chip may provide a promising tool for EV-based liquid biopsy and other fundamental research.

Di-(2-ethylhexyl) phthalate exacerbates abnormalities of testicular development in F1 males via inhibition the Wnt/ß-catenin signaling pathway.

The theory of "Developmental Origins of Health and Disease (DOHaD)" espouses that environmental exposures to toxicants during critical developmental stages can affect health outcomes in adulthood. Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that can be transferred to developing organisms via the placenta and breast milk as an environmental endocrine disruptor. We herein implemented a cross-fostering model to decipher the contributions of prenatal vs. postnatal exposure to low or high dose DEHP (30 or 500 mg/kg-bw•d) on reproductive outcomes in male offspring and the underlying mechanism of action. Unexpectedly, we observed that postnatal DEHP exposure programmed weight gain in a dose-dependent manner, in-utero exposure to high dose DEHP appeared to constitute a significant factor in the weight loss of male offspring. Moreover, in the low dose group, offspring of control that were suckled by DEHP dams (CC-DE) generated a considerable number of adverse reproductive outcomes compared with the offspring of DEHP that were suckled by control dams (DE-CC), based on histopathologic alterations in the testis, blockage of sex hormone secretion, and transcriptional inhibition of steroid-hormone-related factors in the hypothalamic-pituitary-testicular (HPT) axis. However, DE-CC group affected reproductive dysfunction in male offspring more so than CC-DE in the high dose group. Mechanistically, DEHP contributed to the inhibition of steroidogenesis by perturbing the Wnt/ß-catenin-signaling pathway. These studies confirm the sensitivity window in which future reproductive outcomes in offspring are influenced following developmental exposure to DEHP at two different dosages, and reveals a critical role for the Wnt/ß-catenin signaling pathway in DEHP-induced male reproductive disorders.

Superiority of Percutaneous Endoscopic Gastrostomy Over Nasogastric Feeding for Stroke-Induced Severe Dysphagia: A Comparative Study.

BACKGROUND Patients with dysphagia due to stroke may require enteral feeding using either a nasogastric (NG) feeding tube or a percutaneous endoscopic gastrostomy (PEG) tube. This study aimed to compare outcomes from NG tube and PEG tube feeding in 40 patients with severe dysphagia due to stroke. MATERIAL AND METHODS We enrolled 40 patients admitted to the hospital from April 2019 to December 2022 due to severe stroke dysphagia, who were divided into the gastrostomy group (20 patients) and the nasogastric feeding group (20 patients) in accordance with the random number table method. Percutaneous endoscopic gastrostomy was performed in both groups and we assessed differences in swallowing function, nutritional recovery, safety, and hope levels. RESULTS Standardized Swallowing Assessment (SSA) scores in both groups clearly decreased after the intervention, but there was greater reduction in the gastrostomy group (P<0.001). Both groups had distinct improvements of the levels of a variety of nutritional indicators after the intervention, but there was greater improvement in the gastrostomy group (P<0.001). The gastrostomy group also had fewer overall complications (P<0.001). Herth Hope Scale scores in both groups were significantly increased after intervention, and the gastrostomy group had a larger increase that the nasogastric feeding group (P<0.001). CONCLUSIONS Compared with nasogastric tube feeding, percutaneous endoscopic gastrostomy has advantages in SSA score, protein level, and Herth Hope Scale in the treatment of stroke patients with dysphagia.

Tackling global health security by building an academic community for One Health action.

BACKGROUND: One Health approach is crucial to tackling complex global public health threats at the interface of humans, animals, and the environment. As outlined in the One Health Joint Plan of Action, the international One Health community includes stakeholders from different sectors. Supported by the Bill & Melinda Gates Foundation, an academic community for One Health action has been proposed with the aim of promoting the understanding and real-world implementation of One Health approach and contribution towards the Sustainable Development Goals for a healthy planet. MAIN TEXT: The proposed academic community would contribute to generating high-quality scientific evidence, distilling local experiences as well as fostering an interconnected One Health culture and mindset, among various stakeholders on different levels and in all sectors. The major scope of the community covers One Health governance, zoonotic diseases, food security, antimicrobial resistance, and climate change along with the research agenda to be developed. The academic community will be supported by two committees, including a strategic consultancy committee and a scientific steering committee, composed of influential scientists selected from the One Health information database. A workplan containing activities under six objectives is proposed to provide research support, strengthen local capacity, and enhance global participation. CONCLUSIONS: The proposed academic community for One Health action is a crucial step towards enhancing communication, coordination, collaboration, and capacity building for the implementation of One Health. By bringing eminent global experts together, the academic community possesses the potential to generate scientific evidence and provide advice to local governments and international organizations, enabling the pursuit of common goals, collaborative policies, and solutions to misaligned interests.

China's application of the One Health approach in addressing public health threats at the human-animal-environment interface: Advances and challenges.

Background: Due to emerging issues such as global climate change and zoonotic disease pandemics, the One Health approach has gained more attention since the turn of the 21st century. Although One Health thinking has deep roots and early applications in Chinese history, significant gaps exist in China's real-world implementation at the complex interface of the human-animal-environment. Methods: We abstracted the data from the global One Health index study and analysed China's performance in selected fields based on Structure-Process-Outcome model. By comparing China to the Belt & Road and G20 countries, the advances and gaps in China's One Health performance were determined and analysed. Findings: For the selected scientific fields, China generally performs better in ensuring food security and controlling antimicrobial resistance and worse in addressing climate change. Based on the SPO model, the "structure" indicators have the highest proportion (80.00%) of high ranking and the "outcome" indicators have the highest proportion (20.00%) of low ranking. When compared with Belt and Road countries, China scores above the median in almost all indicators (16 out of 18) under the selected scientific fields. When compared with G20 countries, China ranks highest in food security (scores 72.56 and ranks 6th), and lowest in climate change (48.74, 11th). Conclusion: Our results indicate that while China has made significant efforts to enhance the application of the One Health approach in national policies, it still faces challenges in translating policies into practical measures. It is recommended that a holistic One Health action framework be established for China in accordance with diverse social and cultural contexts, with a particular emphasis on overcoming data barriers and mobilizing stakeholders both domestically and globally. Implementation mechanisms, with clarified stakeholder responsibilities and incentives, should be improved along with top-level design.

Reveal the mechanisms of prescriptions for liver cancer' treatment based on two illustrious senior TCM physicians.

OBJECTIVE: To explore the core herbs of two illustrious senior Traditional Chinese Medicine (TCM) Physicians for the treatment of liver cancer, and to further clarify the gene targets and pathway mechanisms of liver cancer that the core prescription (CP) may regulate. METHODS: We used the patient information of two illustrious senior TCM physicians from the Affiliated Hospital of Shandong University of Traditional Chinese Medicine and the Affiliated Hospital of Capital Medical University as the database. The CP was analyzed using the community network algorithm. The pathway mechanism was analyzed using network pharmacology method. And the prognostic survival genes were identified using Single factor cox regression analysis. Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP), Herb, Online Mendelian Inheritance in Man (OMIM), Genecards, Kyoto Encyclopedia of Genes and Genomes (KEGG), Genomic Data Commons (GDC), The Cancer Genome Atlas (TCGA), Gephi and R were used to mine CP, building a pathway network diagram. All the analyses were visualized. RESULTS: We found that the CP consistes of Huangqi (), Danshen (), Shuihonghuazi (), Baihuasheshecao (), Banzhilian (), and Ezhu (), which were attributed to the two physicians respectively. The CP played an anti-cancer role through such pathways as signal transduction, energy metabolism, immune system and other pathways, covering a total of 112 pathways and 176 herb-disease-related genes. Fourteen genes have a significant impact on the prognosis and survival of liver cancer. CONCLUSION: Based on the liver cancer cases of two illustrious senior TCM physicians, we obtained the CP through data mining. The CP may mainly exert anti-cancer effects by inhibiting inflammatory response, angiogenesis, and enhancing the body's immune response. We screened out 14 genes in the CP that may be related to the prognosis of liver cancer, and these genes may play an important regulatory role in the prognosis of liver cancer.

Immunomagnetic Separation Method Integrated with the Strep-Tag II System for Rapid Enrichment and Mild Release of Exosomes.

Exosomes are important participants in numerous pathophysiological processes and hold promising application value in cancer diagnosis, monitoring, and prognosis. However, the small size (40-160 nm) and high heterogeneity of exosomes make it still challenging to enrich exosomes efficiently from the complex biological fluid microenvironment, which has largely restricted their downstream analysis and clinical application. In this work, we introduced a novel method for rapid isolation and mild release of exosomes from the cell culture supernatant. A Strep-tag II-based immunomagnetic isolation (SIMI) system was constructed by modifying the capture antibodies onto magnetic nanoparticles through specific and reversible recognition between Strep-Tactin and Strep-tag II. Due to their high affinity and binding selectivity, exosomes could be isolated within 38 min with an isolation efficiency of 82.5% and a release efficiency of 62%. Compared with the gold-standard ultracentrifugation, the SIMI system could harvest nearly 59% more exosomes from the 293 T cell culture medium with shorter isolation time and higher purity. In addition, cellular uptake assay indicated that exosomes released from magnetic nanoparticles could maintain their high biological activity. These superior characteristics show that this novel method is a fast, efficient, and nondestructive exosome isolation tool and thus could potentially be further utilized in various exosome-related applications, e.g., disease diagnosis and drug delivery.

The analysis of risk factors for accidental parathyroid resection during thyroid surgery: a retrospective analysis of 1775 patients.

PURPOSE: The present study discussed the effects of accidental parathyroid resection on hypoparathyroidism and investigated the risk factors associated with accidental parathyroid resection. METHODS: Clinical data from patients who have undergone thyroidectomy at a university hospital in the period from November 2018 and October 2020 were entered into the database and analyzed. Risk factors for accidental parathyroid resection were recorded. RESULTS: A total of 1775 cases were included in this study. The analysis showed that lymph-node dissection (p < 0.001), T staging (p = 0.037), and treatment group (p < 0.001) were independent risk factors for accidental parathyroid resection. Different treatment groups were important risk factors for accidental parathyroid resection. There were significant differences between the professional and non-professional groups in the following aspects: accidental parathyroid resection (p < 0.001), Scope (p < 0.001), T stage (p = 0.009), N stage (p < 0.001), range of lymph-node dissection (p < 0.001), number of lymph nodes dissected in central area (p < 0.001), and number of lymph-node metastases in the central region (p < 0.001). CONCLUSIONS: The causes of accidental parathyroid resection are multifactorial. The predictors for accidental parathyroid resection include lymph-node dissection in the central region, T staging, as well as the operating surgeons' experience.

Surprising leopard restoration in fragmented ecosystems reveals connections as the secret to conservation success.

The Chinese Loess Plateau has been the cradle of Chinese civilization and the main human settlement in China for thousands of years, where anthropogenic activities are believed to have deeply eroded natural landscapes. After decades of minimal leopard sighting in forests of northern China, due to serious human interference, we recently discovered that the leopard population is recovering. This finding provides hope for successful biodiversity conservation in human-dominated ecosystems. To understand the mechanism of leopard return into such a highly fragmented landscape, we applied the concept of ecological networks (ENs) to identify key factors promoting leopard restoration and quantify the ecological links among habitats. We first determined the existence of a healthy leopard population in the study area based on the size of its home range and presence of breeding individuals. We then innovatively used the relationship between species richness and top predators to generate ENs, and found that the connectivity of ENs had a significant positive interaction with leopard survival. Our study validates the effectiveness of establishing ecologically connected habitats for leopard protection, and highlights the importance of applying ENs for conservation planning in highly fragmented ecosystems. This study provides a successful case for the protection of top predators in human-dominated landscapes.

Large extracellular vesicles in bovine follicular fluid inhibit the apoptosis of granulosa cell and stimulate the production of steroid hormones.

The cargo carried by extracellular vesicles (EVs) plays an important physiological role in their corresponding target organs or target tissue cells. Extracellular vesicles are classified into large extracellular vesicles (LEVs) and small extracellular vesicles (SEVs) according to their diameters. Since different subtypes contain different contents, their roles are also different. In this study, the morphology and size of LEVs were analyzed by transmission electron microscopy and nanoparticle size, and the marker proteins of LEVs (CD63, GP96, TSG101, ALB) were identified by western blot, and high-purity LEVs were obtained. Through the uptake of extracellular vesicles by purified ovarian granulosa cells and the determination of granulosa cell viability, cell apoptosis, and steroid hormone production, the result indicated that LEVs significantly enhanced cell viability (P < 0.05), reduced the rate of granulosa cell apoptosis (P < 0.05). Meanwhile, LEVs promoted the secretion of estradiol in granulosa cells (P < 0.05). This study provides a reference for the in-depth study of the function of follicular fluid extracellular vesicle subtypes and the research on the regulation of extracellular vesicles on follicle and oocyte development.

Short video users' personality traits and social sharing motivation.

Purpose/significance: Studying the correlation between short video users' personality traits and their sharing motivation can enrich the theoretical research on social sharing motivation and provide a reference for short-video content management and platform construction. Methods/process: Based on uses and gratifications theory and personality traits theory, a structural model affecting short-video users' sharing motivations was proposed. A total of 579 valid questionnaires were collected from a social network, and the proposed hypotheses were tested using SPSS and Amos software. Results/conclusion: The results show that the personality traits of short-video users affect their sharing motivation and that their specific sharing motivation also differ due to their personality traits. At the same time, the research results also confirm the Matthew effect of "the rich getting richer" and the social compensation effect of "the poor getting richer" in the context of social platforms that host short videos.

TRIP13/FLNA Complex Promotes Tumor Progression and Is Associated with Unfavorable Outcomes in Melanoma.

Cutaneous melanoma is a high-grade malignant tumor originating from skin melanocytes with high risk of recurrence and metastasis. Further study on the mechanism of melanoma development is urgently needed. Here, we performed a bioinformatic analysis to identify critical genes in melanoma using public datasets in the Gene Expression Omnibus database. Among these differentially expressed genes, thyroid hormone receptor interactor 13 (TRIP13) has been reported to exert an important role in the development of various tumors, while its role in melanoma remains unclear. We selected TRIP13 as a candidate gene for further study. TRIP13 expression in clinical specimens was evaluated by immunohistochemistry, and its association with patient prognosis was analyzed by the Kaplan-Meier method and log-rank test. MV3 and A2058 melanoma cells were transfected with lentiviral vector to overexpress or knockdown TRIP13 expression level, and then, its biological function was studied using a series of in vitro and in vivo assays. RNA sequencing, co-immunoprecipitation, and mass spectrometry were used to identify the underlying mechanism of TRIP13. The results of this study exhibited that TRIP13 expression was upregulated in melanoma tissue compared with normal tissues, and high levels of TRIP13 were closely correlated with poor prognoses of melanoma patients. Elevated TRIP13 promoted the invasion and migration of melanoma cells in vitro and enhanced lung metastasis in vivo, without an influence on tumor growth. Importantly, elevated TRIP13 promoted the epithelial-mesenchymal transition (EMT) of melanoma cells, indicating a higher metastatic potential of these cells. Mechanically, TRIP13 physically interacted with filamin A (FLNA) and then activated the PI3K/AKT pathway to transcriptional activation of EMT-related genes. The present study revealed that TRIP13 is a novel prognostic biomarker and potential therapeutic target for melanoma treatment.

Breast metastasis of cervical cancer: A case report and systematic literature review.

It has been reported that extramammary malignant tumors metastasize to the breast, but cervical cancer metastasis to the breast is very rare. At present, there are only dozens of reports about cervical cancer metastasis to breast in the world. It is difficult to distinguish between primary breast cancer and metastatic breast cancer. We report a 44-year-old woman who underwent surgery, chemotherapy, and radiotherapy for cervical cancer 5 years ago. Then, she was hospitalized for finding a left breast mass measured 2.9 × 2.7 cm in chest CT. Pathological examination combined with immunohistochemical staining showed that the mass came from the cervix. Then, the patient received systematic chemotherapy and interstitial brachytherapy (IB) for the breast mass and got a great result. Cervical cancer rarely metastasizes to the breast. In this case, we confirmed the diagnosis of breast mass by histopathological examination and immunohistochemistry. IB achieved a good result in the treatment of the breast mass. We hope to provide reference of prognosis and treatment when facing this situation by presenting this case.

Novel compound heterozygous mutation of SLC12A3 in Gitelman syndrome co-existent with hyperthyroidism: A case report and literature review.

BACKGROUND: Gitelman syndrome (GS) is a rare inherited autosomal recessive tubulopathy, characterized clinically by hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis, and is caused by an inactivating mutation in SLC12A3. GS is prone to misdiagnosis when occurring simultaneously with hyperthyroidism. It is important to consider the possibility of other diseases when hyperthyroidism is combined with hypokalemia, which is difficult to correct. CASE SUMMARY: A female patient with hyperthyroidism complicated with limb weakness was diagnosed with thyrotoxic hypokalemic periodic paralysis for 4 mo. However, the patient's serum potassium level remained low despite sufficient potassium replacement and remission of hyperthyroidism. GS was confirmed by whole exome and Sanger sequencing. Gene sequencing revealed compound heterozygous mutations of c.488C>T (p.Thr163Met), c.2612G>A (p.Arg871His), and c.1171_1178dupGCCACCAT (p.Ile393fs) in SLC12A3. Protein molecular modeling was performed to predict the effects of the identified missense mutations. All three mutations cause changes in protein structure and may result in abnormal protein function. All previously reported cases of GS coexisting with autoimmune thyroid disease are reviewed. CONCLUSION: We have identified a novel compound heterozygous mutation in SLC12A3. The present study provides new genetic evidence for GS.

Laurolitsine ameliorates type 2 diabetes by regulating the hepatic LKB1-AMPK pathway and gut microbiota.

BACKGROUND: Type 2 diabetes mellitus (DM) is a highly prevalent chronic metabolic disease. Effective antidiabetic drugs are needed to improve and expand the available treatments. Using the ob/ob diabetic mouse model, we previously demonstrated that the alkaloid-rich extract from Litsea glutinosa bark (CG) has potent antidiabetic effects and that laurolitsine (LL) is the richest alkaloid in CG. PURPOSE: We conducted a systematic investigation of the antidiabetic effects and potential mechanisms of LL in vitro and in vivo. METHODS: The antidiabetic effects of LL and its mechanisms of action were explored in HL-7702 hepatocytes in vitro and in db/db mice in vivo by a series of experiments, including cellular toxicity analysis, glucose consumption analysis, serum/liver biochemical analysis, pathological examinations, Western blots, RNA-seq analysis, and gut microbiota analysis. RESULTS: LL stimulated glucose consumption and activated AMP-activated protein kinase (AMPK) without inducing lactic acid production or cytotoxicity in vitro. LL had potent antidiabetic effects with hypoglycemic activity in vivo. It improved insulin resistance, glucose tolerance and lipid metabolism; protected liver, renal and pancreatic functions; and promoted weight loss in db/db mice. Transcriptomic analysis suggested that the antidiabetic effects of LL involved the regulation of mitochondrial oxidative phosphorylation. We further demonstrated that LL effectively activated the hepatic liver kinase B1 (LKB1)/AMPK pathway by regulating the ADP/ATP ratio. Simultaneously, LL significantly modulated the gut microbial community, specifically decreasing the abundances of Mucispirillum schaedleri and Anaerotruncus_sp_G3_2012, which might also contribute to its antidiabetic effects. CONCLUSION: These results suggest that LL is a promising antidiabetic drug candidate that may improve glucolipid metabolism via modulation of the hepatic LKB1/AMPK pathway and the gut microbiota.

Preliminary design for establishing compost maturity by using the spectral characteristics of five organic fertilizers.

The maturity of compost is involved in the availability of nutrients to crops and improvement of soil properties after fertilization. In the past, the determination of composts maturity mostly required analysis in the laboratory previously and it must consume a lot of time and cost. This study was conducted to use Fourier Transform Infrared (FTIR) spectroscopy and solid 13C Nuclear Magnetic Resonance (13C NMR) spectroscopy to understand the mature characteristics of five type of common composts. The FTIR analysis showed that all composts contained aromatic groups. In addition, the surface of five composts contained the functional groups including hydroxyl group, carboxyl group, amino group etc. However, these functional groups changed along with maturity degree. It is recognized that the aliphatic group located at 2930 cm-1 and 2850 cm-1 showed a decreasing peak, and amino acid at 1385 cm-1 was disappearing gradually due to the decomposition of organic matter by bacteria. There may be used to identify the maturity degree of composts. Increase of aromatic group at 1650 cm-1, carboxy (-COOH) and phenolic OH group at 1385 cm-1 may prove the full maturity of composts. 13C NMR analysis showed that five type of matured composts are mainly consisted with aliphatic groups and aromatic groups. The surfaces of the composts contained C-O bonds (ester, ethers, carbohydrate and other functional groups), COO- (carboxyl and ester carbons) and C=O bond (aldehydes and ketones). The strength of different absorptive characteristics of FTIR and 13C NMR may be a clue to identify the maturity of composts for the design of detective instruments in the future.