Cadherin-18 loss in prospermatogonia and spermatogonial stem cells enhances cell adhesion through a compensatory mechanism.

Extracellular membrane proteins are crucial for mediating cell attachment, recognition, and signal transduction in the testicular microenvironment, particularly germline stem cells. Cadherin 18 (CDH18), a type II classical cadherin, is primarily expressed in the nervous and reproductive systems. Here, we investigated the expression of CDH18 in neonatal porcine prospermatogonia (ProSGs) and murine spermatogonial stem cells (SSCs). Disruption of CDH18 expression did not adversely affect cell morphology, proliferation, self-renewal, or differentiation in cultured porcine ProSGs, but enhanced cell adhesion and prolonged cell maintenance. Transcriptomic analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell adhesion. To further elucidate the function of CDH18 in germ cells, Cdh18 knockout mice were generated, which exhibited normal testicular morphology, histology, and spermatogenesis. Transcriptomic analysis showed increased expression of genes associated with adhesion, consistent with the observations in porcine ProSGs. The interaction of CDH18 with ß-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 deficiency. Collectively, these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse SSCs. Understanding this regulatory mechanism provides significant insights into the testicular niche.

Global burden of osteoarthritis: Prevalence and temporal trends from 1990 to 2019.

OBJECTIVE: To investigate the age-standardized prevalence rate (ASPR) and temporal trends for hip, knee, hand, and other osteoarthritis (OA) at a global, continental, and national level. DESIGN: The estimates and 95% uncertainty intervals (UIs) for case number and ASPR of OA were derived from the Global Burden of Diseases Study (GBD) 2019. The joinpoint regression analysis was utilized to examine the temporal trends from 1990 to 2019. RESULTS: In 2019, the global ASPR of hip, knee, hand, and other OA was 400.95 (95% UI: 312.77-499.41), 4375.95 (95% UI: 3793.04-5004.9), 1726.38 (95% UI: 1319.91-2254.85), and 745.62 (95% UI: 570.16-939.8). As for the ASPR of hip OA, hand OA, and other OA, Europe and America had higher rates than Asia and Africa, and Asia was second only to America in knee OA ASPRs. The period 1990-2019, the ASPR at global level dropped significantly for hand OA (AAPC = -0.4%, 95% CI: -0.47 to -0.34) and increased significantly for hip OA (AAPC = 0.43%, 95% CI: 0.39-0.46), knee OA (AAPC = 0.17%, 95% CI: 0.09-0.24) and other OA (AAPC = 0.16%, 95% CI: 0.15-0.17). Different continents, countries, and periods demonstrated significant changes. CONCLUSIONS: Globally, America has the highest OA burden and Asia has a higher knee OA burden. Appropriate prevention and control measures to reduce modifiable risk factors are needed to reduce the burden of OA.

Hippocampal Crhr1 conditional gene knockout ameliorated the depression-like behavior and pathological damage in male offspring mice caused by chronic stress during pregnancy.

Numerous studies have demonstrated that chronic stress during pregnancy (CSDP) can induce depression and hippocampal damage in offspring. It has also been observed that high levels of corticotropin-releasing hormone (CRH) can damage hippocampal neurons, and intraperitoneal injection of a corticotropin releasing hormone receptor 1 (CRHR1) antagonist decreases depression-like behavior and hippocampal neuronal damage in a mouse depression model. However, whether CSDP causes hippocampal damage and depression in offspring through the interaction of CRH and hippocampal CRHR1 remains unknown and warrants further investigation. Therefore, hippocampal Crhr1 conditional gene knockout mice and C57/BL6J mice were used to study these questions. Depression-related indexs in male offspring mice were examined using the forced swim test (FST), sucrose preference test (SPT), tail suspension test (TST) and open field test (OFT). Serum CRH levels were measured by enzyme-linked immunosorbent assay (ELISA). Golgi-Cox staining was used to examine the morphological changes of hippocampal neuronal dendrites. Neuronal apoptosis in the hippocampal CA3 regions was detected by terminal deoxynucleotidy transferase dUTP nick end labeling (TUNEL) staining. The levels of mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR) and protein kinase B (AKT) proteins were measured by Western blot analysis. This study showed that CSDP induces depression-like behavior, hippocampal neuronal dendrite damage and apoptosis in male offspring mice. Conditional gene knockout of hippocampal Crhr1 in mice reduced CSDP-induced depression-like behavior, hippocampal neuronal dendrite damage and apoptosis in male offspring, and counteracted the CSDP-induced decreased expression of p-Akt and mTOR activity in male offspring hippocampus. These findings demonstrated that CSDP might inhibit the Akt/mTOR pathway by increasing the levels of CRH, leading to increased CRH-mediated activation of hippocampal CRHR1, thereby inducing synaptic impairment and apoptosis in hippocampal neurons, which in turn leads to depression-like behavior in offspring.

Thermophilic and mesophilic digestion of high-solid oily food waste: How to ensure long-term and stable continuous operation?

Commonly high lipid in food waste confronts anaerobic digestion with improved energy production and also inhibition risk from the intermediate long chain fatty acids (LCFAs). Combined with operation challenges from anaerobic digestion of food waste itself, coping strategies are necessitated to ensure stable operation for oily food waste (OFW). A parallel thermophilic (TD) and mesophilic digestion (MD) of high-solid OFW was conducted and operated continuously for a long term. It was clarified that challenges were mainly from acidification, trace metal deficiency and LCFA inhibition. Acidification resulted in an abrupt pH decline to even below 6.00, and over 75% drop of biogas production rate. In addition to the requirements of saturated strong alkali to maintain an appropriate range, supplementation of trace metals were proven effective in counteracting the sharp decrease of biogas production rate. The TD was observed more competent in coping with the acidification than the MD, while the TD needed more supplementation of trace metals at approximately 0.10 mg Fe/g chemical oxygen demand (COD)added, 0.01 mg Co/g CODadded and 0.01 mg Ni/g CODadded. The TD was more adaptable in LCFA conversion due to the stronger ability of overcoming the palmitic acid (C16:0) accumulation. The MD experienced a prolonged recovery period owing to LCFA inhibition shortly after acidification. Similar operation performance was ultimately achieved for the TD and MD by the counteractions, with a methane yield and volatile solids (VS) removal efficiency at about 0.60 L/g VSadded and 75.0%, respectively. In summary, combined pH control and trace metal supplementation, and prevention and recovery of LCFA inhibition were necessary for the stability insurance of a long-term continuous digestion of oily food waste.

Mendelian Randomization Analysis of Circulating Cytokines and Risk of Autoimmune Neuroinflammatory Diseases.

Background: Cytokines act a vital role in autoimmune neuroinflammatory diseases (ANDs) with undetermined causal relationships. Mendelian randomization (MR) analysis was performed to estimate the causal effects of circulating levels of cytokines on the risk of ANDs. Methods: The causal relationship between 34 circulating cytokines and 4 kinds of ANDs, including multiple sclerosis (MS), neuromyelitis optica (NOM), chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) were explored using four methods of MR analysis. MR-PRESSO, MR-Egger regression methods and Cochran's Q statistic were utilized to identify the instrumental variables (IVs) with potential pleiotropy and heterogeneity. The Bonferroni correction was used for multiple group comparisons. P-value less than 3.68E-04 (0.05/ (34*4)) was considered statistically significant. Results: Negative causal effects of circulating levels of interleukin (IL)-8 (OR = 0.648, 95% CI: 0.494-0.851, P = 0.002) on risk of MS, chemokine (C-C Motif) ligand (CCL)-5 (OR = 0.295, 95% CI: 0.103-0.841, P = 0.022) and stem cell growth factor-beta (SCGF-ß) (OR = 0.745, 95% CI: 0.565-0.984, P = 0.038) on risk of CIDP, as well as positive causal effects of circulating levels of IL-2 receptor α (IL-2Rα) (OR = 1.216, 95% CI: 1.120-1.320, P = 3.20E-06) and chemokine C-X-C motif ligand (CXCL)-10 (OR = 1.404, 95% CI: 1.094-1.803, P = 0.008) on MS were observed. Nevertheless, only IL-2Rα still had a causal effect on MS after Bonferroni correction. Conclusion: The results identify a genetically predicted causal effect of IL-2Rα, IL-8 and CXCL-10 on MS, CCL-5 and SCGF-ß on CIDP.

Trends and cross-country inequalities in the global burden of osteoarthritis, 1990-2019: A population-based study.

OBJECTIVE: To evaluate the trends and cross-country inequalities of global osteoarthritis (OA) burden over the last 30 years, and further predicted its changes to 2035. METHODS: The estimates and 95 % uncertainty intervals (UIs) for incidence, prevalence, and disability-adjusted life-years (DALYs) of OA were extracted from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. We described OA epidemiology at global, regional, and national levels, analyzed 1990-2019 trends in OA burden from overall, local, and multi-dimension scopes, decomposed OA burden according to population size, age structure, and epidemiologic changes, quantified cross-country inequalities in OA burden using standard health equity methods recommended by World Health Organization, and predicted changes of OA burden to 2035. RESULTS: GBD 2019 estimated 527,811,871 (95 % UIs: 478,667,549 to 584,793,491) prevalent cases, 41,467,542 (95 % UIs: 36,875,471 to 46,438,409) incident cases and 18,948,965 (95 % UIs: 9,571,298 to 37,659,660) DALYs cases of OA worldwide in 2019, with the highest cases in East Asia and highest age-standardized rate (ASR) in high-income North America. The global burden of OA increased overall from 1990 to 2019 with the fastest growth observed in the first decade of the 21st century. Decomposition analysis revealed that OA knee (62.78 %), women (60.47 %), and middle sociodemographic index (SDI) quintile (32.35 %) were responsible for the most significant DALYs, whose changes were primarily driven by population growth and aging. A significant increase in SDI-related inequalities was detected, and the gap in DALYs between the highest SDI country and the lowest SDI country increased from 179.5 [95 % confidence interval (CI): 149.3-209.8] per 100,000 in 1990 to 341.9 (95 % CI: 309.5-374.4) per 100,000 in 2019. Notably, although the ASR of incidence, prevalence, and DALYs of OA was predicted to decrease annually from 2020 to 2035, the case number of these metrics was predicted to keeping increasing, with predicted values of 52,870,737 [95 % credible interval (Crl): 39,330,063 to 66,411,411], 727,532,373 (95 % Crl: 542,765,783 to 912,298,962), and 25,986,983 (95 % Crl: 19,216,928 to 32,757,038) in 2035, respectively. CONCLUSIONS: As a major public health issue, the global burden of OA showed an overall increasing trend from 1990 to 2019, which was primarily driven by population growth and aging. Countries with high SDI shouldered disproportionately high OA burden, and the SDI-related inequalities across countries exacerbated over time. This study highlighted great challenges in the control and management of OA, including both growing case number and distributive inequalities worldwide, which may be instructive for better making public health policy and reasonably allocating medical source.

Emerging biologic frontiers for Sjogren's syndrome: Unveiling novel approaches with emphasis on extra glandular pathology.

Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest in biologic therapies for pSS, FDA approval has proven challenging due to trial complications. This review addresses the absence of a molecular-target-based approach to biologic therapy development and highlights novel research on drug targets and clinical trials. A literature search identified potential pSS treatment targets and recent advances in molecular understanding. Overlooking extraglandular symptoms like fatigue and depression is a notable gap in trials. Emerging biologic agents targeting cytokines, signal pathways, and immune responses have proven efficacy. These novel therapies could complement existing methods for symptom alleviation. Improved grading systems accounting for extraglandular symptoms are needed. The future of pSS treatment may involve gene, stem-cell, and tissue-engineering therapies. This narrative review offers insights into advancing pSS management through innovative biologic interventions.

MicroRNAs as Key Regulators in RA and SLE: Insights into Biological Functions.

MicroRNAs (miRNAs) are non-coding RNA molecules that bind to mRNAs to regulate gene expression. Since changes in miRNA expression levels have been found in a variety of autoimmune illnesses, miRNAs are important in autoimmune diseases. MiRNAs serve not only as pathogenic factors and biomarkers for autoimmune diseases but also as important targets for disease therapeutics. Although miRNA-based treatments are still in the research stage, in-depth investigations into the biological functions of miRNAs have significantly enhanced our understanding of their mechanisms in autoimmune diseases. The purpose of this review is to summarize the biological functions of miRNAs, their roles in rheumatoid arthritis and systemic lupus erythematosus, therapeutic strategies, and challenges.

Ammonia stripping by in situ biogas self-circulation to upgrade continuous thermophilic and mesophilic digestion of hydrothermal high-solid sludge.

High-solid anaerobic digestion of hydrothermal sewage sludge has been developed. In order to upgrade the process by focusing on ammonia inhibition, a simply-equipped stripping system without additional alkali or heat supply was introduced by in situ biogas self-circulation. As the determined limit of total ammonia nitrogen at 1500 mg/L and 1000 mg/L for the mesophilic (MAD) and thermophilic anaerobic digestion (TAD) respectively and stripping rate at 5 L/min, continuous MAD and TAD was conducted in parallel. The stripping system successfully polished up the ammonia inhibition, and methanogenic capability of the TAD was promoted to approximately 90.0 % of the potential. Intermittent stripping mode proved usable. More frequent stripping was inevitable for the TAD as compared to the MAD. Hydraulic retention time below 20 d resulted in failure of the stripping mode due to rapid ammonia generation. Overall, this technology was practical in upgrading high-solid sludge digestion by effective ammonia control.

Cross-cultural adaptation and construct validity of the Chinese Version of Visual Vertigo Analogue Scale by using structural equation modeling.

BACKGROUND: Visual vertigo (VV) is a disease characterized by various visual signal-induced discomforts, including dizziness, unsteady balance, activity avoiding, and so forth. Distinguishing it from other kinds of dizziness is important because it needs the combination of visual training and vestibular rehabilitation together. However, there is no appropriate tool to diagnose VV in China, thus we would like to introduce an effective tool to China. OBJECTIVE: The aim of this study was to establish the reliability and validity of the Chinese version of visual vertigo analogue scale (VVAS-CH) and to achieve its crosscultural adaptation in order to promote its further usage in China. METHODS: A total of 1681 patients complaining of vertigo or dizziness were enrolled and they were asked to complete the VVAS-CH. The cross-cultural adaptation, reliability and construct validity of the VVAS-CH were determined. RESULTS: Split-half reliability was 0.939, showing a good reliability. Factor analysis identified only one common factor for the nine items that explained 64.83% of the total variance. Most fit indices reached acceptable levels, proving the good fit of the VVAS-CH model. CONCLUSIONS: The VVAS-CH validated in this study can be used as an effective tool for diagnosing and evaluating VV in patients whose native language is Chinese.

Sorafenib Resistance Contributed by IL7 and MAL2 in Hepatocellular Carcinoma Can Be Overcome by Autophagy-Inducing Stapled Peptides.

Drug resistance poses a great challenge in systemic therapy for hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms associated with resistance to anti-cancer drugs, such as Sorafenib, remain unclear. In this study, we use transposon insertional mutagenesis to generate Sorafenib-resistant HCC cell lines in order to identify potential drug resistant causative genes. Interleukin 7 (IL7) and mal, T cell differentiation protein 2 (MAL2) were identified as candidate genes that promote survival by activating JAK/STAT and PI3K/AKT signaling pathways. Sorafenib-resistant cells exhibited higher clonogenic survival and lower drug sensitivity due to IL7 and MAL2 upregulation. Higher anti-apoptotic effect, clonogenic survival and increased PI3K/AKT/STAT3 activities were observed in IL7 and MAL2 co-overexpressing cells compared with controls or cells overexpressing IL7 or MAL2 individually. Given the critical role of MAL2 in endocytosis, we propose that MAL2 might facilitate the endocytic trafficking of IL7 and its cognate receptors to the plasma membrane, which leads to upregulated JAK/STAT and PI3K/AKT signaling pathways and Sorafenib resistance. Additionally, our previous studies showed that an autophagy-inducing stapled peptide promoted the endolysosomal degradation of c-MET oncogene and overcame adaptive Sorafenib resistance in c-MET+ HCC cells. In this study, we demonstrate that these stapled peptides readily induced autophagy and inhibited the proliferation of both wild-type and Sorafenib-resistant HCC cells co-overexpressing both IL7 and MAL2. Furthermore, these peptides showed synergistic cytotoxicity with Sorafenib in drug-resistant HCC cells co-overexpressing both IL7 and MAL2. Our studies suggest that targeting autophagy may be a novel strategy to overcome IL7/MAL2-mediated Sorafenib resistance in HCC.

Awareness of Hospice Care Among Community-Dwelling Elderly Participants.

Background and Purpose: The main goal of hospice care is to improve the quality of life for people who are at the end-of-life phase. However, investigations on the awareness of hospice care among community-dwelling elderly participants are limited. This work aimed to reveal the awareness status of hospice care and explore the factors influencing the awareness rate among elderly participants. Methods: A questionnaire survey was conducted among individuals aged 60 years and above. Results: A total of 4,969 individuals aged 60 years and above were randomly selected from 48 primary medical institutions in Handan. The awareness rate of hospice care in the baseline survey was 19.3% (n = 959). All included individuals were divided into two groups in accordance with their awareness of hospice care. The awareness of hospice care among participants with low educational level, living alone, and afraid of talking about death was low (p < .05). Implications for Practice: The level of awareness of hospice care among community-dwelling elderly participants is low. The influencing factors included educational level, living status, and fear of talking about death. The community-dwelling elderly participants' awareness of hospice care must be improved. It is recommended that public medical education and training should be enhanced to improve knowledge and awareness of hospice care among community-dwelling elderly residents with low educational level, living alone, and afraid of talking about death.

Transposon delivery for CRISPR-based loss-of-function screen in mice identifies NF2 as a cooperating gene involved with the canonical WNT signaling molecular class of hepatocellular carcinoma.

Various molecular subclasses of hepatocellular carcinoma (HCC) exists, with many novel cooperating oncogenes and tumor suppressor genes involved in its tumorigenesis. The emerging importance of WNT signaling in HCC has been established. However, the intricate genetic mechanisms involved in this complex signaling pathway remains to be elucidated. Importantly, while some cooperating genes have been identified, there are still many unknown genes associated with catenin beta 1 (CTNNB1)-induced HCC. Mutations in both oncogenes and tumor suppressor genes are required for HCC tumorigenesis. The emergence of the CRISPR/Cas9 system has allowed researchers now to target both alleles efficiently. In this novel study, the Sleeping Beauty transposon system was used as a gene delivery system in vivo to stably integrate an expression cassette that carry pools of gRNAs and overexpress a mutant version of CTNNB1 into the hepatocyte genome. We identified 206 candidate genes that drive HCC tumorigenesis in the context of WNT signaling activation and, neurofibromin 2 (NF2) gene, a known tumor suppressor gene with clinical relevance was validated in this proof-of-principle study.

T cell receptor ß repertoires in patients with COVID-19 reveal disease severity signatures.

Background: The immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity. Methods: In this study, we employed high-throughput T cell receptor (TCR) ß repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes. Results: We observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression. Conclusions: Our study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR ß repertoires in monitoring disease development and indicating disease severity.

Epstein-Barr virus-induced infection-associated hemophagocytic lymphohistiocytosis with acute liver injury: A case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory reaction, which is rare and life-threatening. According to the pathogen, HLH is divided into genetic and acquired. The most common form of acquired HLH is infection-associated HLH, of which Herpes viruses, particularly Epstein-Barr virus (EBV), are the leading infectious triggers. However, it is difficult to distinguish between simple infection with EBV and EBV-induced infection-associated HLH since both can destroy the whole-body system, particularly the liver, thereby increasing the difficulty of diagnosis and treatment. CASE SUMMARY: This paper elaborates a case about EBV-induced infection-associated HLH and acute liver injury, aiming to propose clinical guides for the early detection and treatment of patients with EBV-induced infection-associated HLH. The patient was categorized as acquired hemophagocytic syndrome in adults. After the ganciclovir antiviral treatment combined with meropenem antibacterial therapy and methylprednisolone inhibition to inflammatory response, gamma globulin enhanced immunotherapy, the patient recovered. CONCLUSION: From the diagnosis and treatment of this patient, attention should be paid to routine EBV detection and a further comprehensive understanding of the disease as well as early recognition and early initiation are keys to patients' survival.

Huang-Lian-Jie-Du decoction alleviates depressive-like behaviors in dextran sulfate sodium-induced colitis mice via Trem2/Dap12 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian-Jie-Du decoction (HLJD), a traditional Chinese medicine prescription, has been implicated as effective in treating colitis, depression and inflammation-related diseases. Whether HLJD decoction could ameliorate colitis-induced depression was still unknown and the underlying mechanism was needed to be clarified. AIM OF THE STUDY: Our study aimed to explore the effect and the underlying mechanism of HLJD treatment on colitis-induced depression and the involvement of the inflammatory factors and microglial-activated related genes. MATERIALS AND METHODS: The chronic colitis model was established by treating male mice with 1% dextran sulfate sodium (DSS) for 8 weeks. One week after DSS-treated, HLJD decoction was administered orally with 2 and 4 g/kg daily for 7 weeks. Behavior tests (Open field/Elevated plus maze/Novel object recognition) and TUNEL staining were then assessed. The expression of inflammatory-related genes and microglial dysregulation were measured by RT-PCR and the expression of Trem2, Danp12 and Iba1 were assessed by immunofluorescence methods. RESULTS: Depressive-like behaviors were observed in mice treated with DSS, which suffered colitis. Compared to normal control (NC-V) mice, the density of TUNEL + cells in the habenula (Hb), hippocampus (HIP), and cortex were significantly higher in colitis (DSS-V) mice, especially in Hb. Compared to NC-V and several brain regions, the expression levels of the Il-1ß, Il-10 and Dap12 mRNA were significantly increased in the lateral habenula (LHb) of colitis mice. Moreover, the expression of Trem2, Dap12 and Iba1 were increased in LHb of DSS-V mice. HLJD treatment could alleviate depressive-like behaviors, reduce the density of TUNEL + cells in Hb and the expression of Il-6, Il-10 and Dap12 mRNA in LHb of DSS-V mice. The overexpression of Trem2, Dap12 and Iba1 in LHb of DSS-V mice were reversed after HLJD treatment. CONCLUSION: These results reveal LHb is an important brain region during the process of colitis-induced depression. HLJD treatment could alleviates depressive-like behaviors in colitis mice via inhibiting the Trem2/Dap12 pathway in microglia of LHb, which would contribute to the precise treatment. It provides a potential mechanistic explanation for the effectiveness of HLJD treatment in colitis patients with depression.

[Effects and mechanism of p53 gene deletion on energy metabolism during the pluripotent transformation of spermatogonial stem cells].

Previous studies have shown that long-term spermatogonial stem cells (SSCs) have the potential to spontaneously transform into pluripotent stem cells, which is speculated to be related to the tumorigenesis of testicular germ cells, especially when p53 is deficient in SSCs which shows a significant increase in the spontaneous transformation efficiency. Energy metabolism has been proved to be strongly associated with the maintenance and acquisition of pluripotency. Recently, we compared the difference in chromatin accessibility and gene expression profiles between wild-type (p53+/+) and p53 deficient (p53-/-) mouse SSCs using the Assay for Targeting Accessible-Chromatin with high-throughput sequencing (ATAC-seq) and transcriptome sequencing (RNA-seq) techniques, and revealed that SMAD3 is a key transcription factor in the transformation of SSCs into pluripotent cells. In addition, we also observed significant changes in the expression levels of many genes related to energy metabolism after p53 deletion. To further reveal the role of p53 in the regulation of pluripotency and energy metabolism, this paper explored the effects and mechanism of p53 deletion on energy metabolism during the pluripotent transformation of SSCs. The results of ATAC-seq and RNA-seq from p53+/+ and p53-/- SSCs revealed that gene chromatin accessibility related to positive regulation of glycolysis and electron transfer and ATP synthesis was increased, and the transcription levels of genes encoding key glycolytic enzymes and regulating electron transport-related enzymes were markedly increased. Furthermore, transcription factors SMAD3 and SMAD4 promoted glycolysis and energy homeostasis by binding to the chromatin of the Prkag2 gene which encodes the AMPK subunit. These results suggest that p53 deficiency activates the key enzyme genes of glycolysis in SSCs and enhances the chromatin accessibility of genes associated with glycolysis activation to improve glycolysis activity and promote transformation to pluripotency. Moreover, SMAD3/SMAD4-mediated transcription of the Prkag2 gene ensures the energy demand of cells in the process of pluripotency transformation and maintains cell energy homeostasis by promoting AMPK activity. These results shed light on the importance of the crosstalk between energy metabolism and stem cell pluripotency transformation, which might be helpful for clinical research of gonadal tumors.

Excess methane production and operation stability for anaerobic digestion of oily food waste controlled by mixing intensity: Focusing on heterogeneity of long chain fatty acids.

Long chain fatty acids (LCFAs) are the key intermediate of anaerobic digestion of oily food waste, not completely soluble in a water-dominant anaerobic system due to their long hydrocarbon chains with hydrophobic property. Their effective concentration affects release of high methanogenic potential and system stability. A long-term continuous anaerobic digestion of oily food waste demonstrated excess methane production of even more than feedstock in an anaerobic continuous stirred tank reactor (CSTR). Assuming feedstock COD at 100%, approximately 120% of COD as methane could be achieved. Oil floating and crystallization with Ca salt resulting from the distribution heterogeneity of LCFAs in the CSTR were found responsible for the excess methane production. Moreover, slow conversion and accumulation of saturated LCFAs with relatively lower solubility played an important role as well. Compared with unsaturated oleic (C18:1) and linoleic acids (C18:2), around twice slower methane production rate and longer lag time could be observed for those saturated LCFAs. Mixing intensity was proved to be a critical controlling factor for methanogenesis and stability possibly by affecting interaction between oil/LCFAs and anaerobes to change effective lipid loading.

Edible HIPE-Gels and oleogels formed by synergistically combining natural triterpenoid saponin and citrus dietary fiber.

High-internal-phase emulsion gels (HIPE-Gels) and oleogels were successfully fabricated through synergistically combination of natural triterpenoid Quillaja saponin (QS) and citrus dietary fiber (CDF). The amphiphilic QS significantly lowered the oil-water interface tension; whereas CDF could form compact structure at the interface as well as in the bulk under a hydrogen-bonding interaction with saponin. The combination endowed the emulsion gels with enhanced performance, such as decreasing droplet size, strengthening gel network structure and better viscoelastic. At a very low QS of 0.045 %, stable HIPE-Gels can be produced with 0.3 % CDF, which mainly attributing to the highly viscoelastic fiber networks in continuous phase and thus actively trap the QS-coated emulsion droplets. Consequently, the robust HIPE-Gels were applied as soft template to fabricate oleogels with controlled by QS and CDF loading. These findings proved an effective strategy towards structuring edible liquid oil into healthy gels for alternating saturated and trans fats in foods.

Electro-acupuncture treatment ameliorates intestinal inflammatory injury in cerebral ischemia-reperfusion rats via regulating the balance of Treg / γδ T cells.

Electro-acupuncture (EA) has an anti-inflammatory role in ischemic stroke, but whether the protective effect of EA involves the regulation of the intestine barrier and Treg/ γδ T cells is unclear. Cerebral ischemia-reperfusion (I/R) injury was induced by middle cerebral artery occlusion(MCAO) for 2 h followed by reperfusion for 24 h. The rats have treated with EA at the "Baihui" acupoint(GV20). Triphenyl tetrazolium chloride (TTC) staining and Longa neurologic score were performed to evaluate the outcomes after ischemic stroke. Inflammatory factor expression levels in the serum, ischemic hemisphere brain, and small intestine were detected by ELISA or RT-qPCR. Additionally, the morphology change of the small intestine was evaluated by analyzing villus height and smooth muscle thickness. Meanwhile, the expression of tight-junction proteins, including Zonula Occludens-1 (ZO-1), Occludin, and Claudin-1, were detected to evaluate the impact of EA on mucosal permeability in the small intestine. The percentages of regulatory T cells (Tregs) (CD45+CD4+Foxp3+) and γδ T cells (CD45+CD4-γδ T+) were measured to assess the effect of EA on intestinal T cells. EA decreased the brain infarction volume and intestine barrier injury in ischemic stroke rats. At the same time, it effectively suppressed the post-stroke inflammation in the brain and small intestine. More importantly, EA treatment increased the percentage of Tregs in the small intestine while reducing the rate of γδ T cells, and ultimately increased the ratio of Treg/ γδ T cells. These results demonstrated that EA ameliorated intestinal inflammation damage by regulating the Treg/ γδ T cell polarity shift and improving the intestine barrier integrity in rats with I/R injury. This may be one of the mechanisms underlying the anti-ischemic injury effects of acupuncture on stroke.