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Background. Infertility is a global medical and social problem that affects human health and social development. At present, about 15% of couples of the right age in the world are infertile. As all we know, genetic defects are the most likely underlying cause of the pathology. ATP5D is also known as the delta subunit of mitochondrial ATP synthase. Mitochondria maintain sperm vitality, capacitation, acrosome reaction, and DNA integrity through ATP. Mitochondrial damage can trigger energy synthesis disorders, resulting in decreased sperm quality and function or even disappearance. The specific role of ATP5D in regulation of the male reproductive system remains elusive. Methods. In this study, semen from normal and infertile males were collected and their indicators were examined by analysis of routine sperm parameters; ATP5D protein content in semen was examined by ELISA. Singer sequencing was used to detect whether there was a mutated of ATP5D in semen. Meanwhile, ATP5D knockout (KO) and knockin (KI) male mice were selected at 8-12 weeks of age and mated with adult wild-type (WT) female mice for more than two months to assess their fertility and reproductive ability. Morphological changes in tissues such as testes and epididymis were observed by HE staining; spermatozoa were taken from the epididymis of the mice; sperm counts were performed and morphological changes were observed by Diff-Quik staining. Results. The results showed that the expression of ATP5D in infertile males was significantly lower than that in normal males ( P < 0.001 ) and the normal morphology rate of spermatozoa was much lower than that of normal males, and the sequencing results showed no mutations. The animal reproductive experiments showed no significant changes in the number of fertility in KO/KI mice compared with WT mice, but the duration of fertility was significantly longer ( P = 0.02 ). The testicular cells in KO mice were loosely arranged and disorganized, the lumen was larger, the interstitial cells were atrophied, and the number of spermatozoa was reduced and the malformation rate was higher in WT males. This suggests that ATP5D is an essential protein for sperm formation and fertility in male mice and may be used as a biomarker of male fertility. Conclusion. This study found ATP5D correlated with male infertility and the expression levels were significantly reduced in the seminal plasma of all male infertile patients without gene mutations. KO male significantly prolonged fertility time and impaired testicular histomorphology. This suggests that ATP5D may be associated with spermatogenic function and fertility in male mice and may be used as a biomarker for male fertility. Future studies are required to elucidate the potential mechanisms. The trial registration number is KLL-2021-266.

Insomnia is a common sleep complaint among patients who had a stroke and has been recognized as an independent risk factor for cognitive impairment. However, the relationship between poststroke insomnia and cognitive impairment over time is under-researched. Therefore, we examined the association between poststroke insomnia and the risk of cognitive impairment.Stroke participants who had a stroke and were 20 years and older.This multicenter hospital-based retrospective cohort study with a 13-year follow-up period (2004-2017). The diagnosis of stroke, insomnia, and cognitive impairment was based on the International Classification of Diseases. The study participants who experienced a stroke were divided into two cohorts: those who also had insomnia and those who did not have insomnia. A Cox proportional-hazards regression model was used.A total of 1,775 patients with a mean age of 67.6 years were included. Of these patients, 146 and 75 patients were diagnosed with insomnia and cognitive impairment during the follow-up period, respectively. The cumulative incidence of cognitive impairment in the stroke with insomnia cohort was significantly lower than that in the stroke without insomnia cohort (log-rank test,Patients who had a stroke and were diagnosed with insomnia exhibited a substantial increased risk of cognitive impairment over time.

This study investigated natural gamma emitting radionuclides 40K and 226Ra in rice consumed in Taiwan. Thirty rice samples, collected from local markets, included 24 local rice and 6 imported rice samples. Radionuclide activities were 24.05 ± 10.21 and 0.62 ± 0.61 Bq/kg for 40Kand 226Ra for all rice samples. The activity of each radionuclide was insignificantly different for local and imported samples (p = 0.33 and 0.52 for 40K and 226Ra, respectively). The annual effective doses from rice consumption were estimated to be 6.80 ± 2.89 and 7.86 ± 7.81 μSv/y for 40K and 226Ra, respectively, and the sum ingestion dose of 226Ra and 40K was 14.66 ± 8.57 μSv/y. These values were one order of magnitude less than the 290 μSv/y world average of the ingestion exposure from natural sources. The results suggest that rice consumption in Taiwan is radiologically safe for the investigated radionuclides.

This review summarizes chemical tools for cell engineering, introduces their wide application in diagnosis and therapy, and discusses the challenges and opportunities in precision medicine.

Mn2−xCrxSb2 epitaxial thin films were grown on perovskite oxide single-crystal substrates using the molecular beam epitaxy technique. A magnetic phase diagram has been established for Mn2−xCrxSb2 films in the low doping region.

The Eastern Staging System, which was specially developed for patients undergoing surgical resection for hepatocellular carcinoma (HCC), has been proposed for more than ten years. To prospectively validate the predictive accuracy of the Eastern staging on long-term survival after HCC resection.Patients who underwent hepatectomy for HCC from 2011 to 2020 at 10 Chinese hospitals were identified from a prospectively collected database. The survival predictive accuracy was evaluated and compared between the Eastern Staging with six other staging systems, including the JIS, BCLC, Okuda, CLIP, 8th AJCC TNM, and HKLC staging.Among 2365 patients, the 1-, 3-, and 5-year overall survival rates were 84.2%, 64.5%, and 52.6%, respectively. Among these seven staging systems, the Eastern staging was associated with the best monotonicity of gradients (linear trend χUsing a large multicenter prospectively collected database, the Eastern Staging was found to show the best predictive accuracy on long-term overall survival in patients with resectable HCC than the other 6 commonly-used staging systems.

Hypertension is a significant risk factor of cardiovascular diseases (CVDs) with high prevalence worldwide, the current treatment has multiple adverse effects and requires continuous administration. The glucagon-like peptide-1 receptor (GLP-1R) agonists have shown great potential in treating diabetes mellitus, neurodegenerative diseases, obesity and hypertension. Butyric acid is a potential target in treating hypertension. Yet, the application of GLP-1 analogue and butyric acid in reducing blood pressure and reversing ventricular hypertrophy remains untapped. In this study, we combined the therapeutic capability of GLP-1 and butyric acid by transforming Clostridium butyricum (CB) with recombinant plasmid pMTL007 encoded with hGLP gene to construct the engineered probiotics Clostridium butyricum-pMTL007-GLP-1 (CB-GLP-1). We used spontaneous hypertensive rat (SHR) models to evaluate the positive effect of this strain in treating hypertension. The results revealed that the intragastric administration of CB-GLP-1 had markedly reduced blood pressure and improved cardiac marker ACE2, AT2R, AT1R, ANP, BNP, β-MHC, α-SMA and activating AMPK/mTOR/p70S6K/4EBP1 signalling pathway. The high-throughput sequencing further demonstrated that CB-GLP-1 treatments significantly improved the dysbiosis in the SHR rats via downregulating the relative abundance of Porphyromonadaceae at the family level and upregulating Lactobacillus at the genus level. Hence, we concluded that the CB-GLP-1 greatly improves blood pressure and cardiomegaly by restoring the gut microbiome and reducing ventricular hypertrophy in rat models. This is the first time using engineered CB in treating hypertension, which provides a new idea for the clinical treatment of hypertension.

The ecological stoichiometry theory provides a framework to understand organism fitness and population dynamics based on stoichiometric mismatch between organisms and their resources. Recent studies have revealed that different soil animals occupy distinct multidimensional stoichiometric niches (MSNs), which likely determine their specific stoichiometric mismatches and population responses facing resource changes. The goals of the present study are to examine how long-term forest plantations affect multidimensional elemental contents of litter and detritivores and the population size of detritivores that occupy distinct MSNs. We evaluated the contents of 10 elements of two detritivore taxa (lumbricid earthworms and julid millipedes) and their litter resources, quantified their MSNs and the multidimensional stoichiometric mismatches, and examined how such mismatch patterns influence the density and total biomass of detritivores across three forest types spanning from natural forests (oak forest) to plantations (pine and larch forests). Sixty-year pine plantations changed the multidimensional elemental contents of litter, but did not influence the elemental contents of the two detritivore taxa. Earthworms and millipedes exhibited distinct patterns of MSNs and stoichiometric mismatches, but they both experienced severer stoichiometric mismatches in pine plantations than in oak forests and larch plantations. Such stoichiometric mismatches led to lower density and biomass of both earthworms and millipedes in pine plantations. In other words, under conditions of low litter quality and severe stoichiometric mismatches in pine plantations, detritivores maintained their body elemental contents but decreased their population biomass. Our study illustrates the success in using the multidimensional stoichiometric framework to understand the impact of forest plantations on animal population dynamics, which may serve as a useful tool in addressing ecosystem responses to global environmental changes.生态化学计量理论为研究生态系统不同组分间的元素流动提供了基本框架，消费者-资源之间化学元素比的错配直接影响了有机体生长和种群动态。不同土壤动物类群存在化学计量生态位上的分化，这导致不同动物类群应对食物资源变化时会产生不同程度的元素错配。 本研究基于北京东灵山三种森林类型(天然辽东栎次生林和人工种植油松林和落叶松林)开展调查，测量了两种土壤动物分解者类群(正蚓科蚯蚓和马陆)及其生境中的凋落物的十种化学元素含量，量化了分解者和凋落物之间的化学计量错配程度，并评估了化学元素错配如何影响两种分解者的密度和生物量。 研究发现，六十年油松林种植显著改变了凋落物化学元素组成，但并未显著改变两种分解者的化学元素含量。在三种森林中，蚯蚓和马陆具有明显的化学计量生态位分化，从而展示不同的元素错配模式；但两种分解者在油松林中均受到更为严重的化学计量错配程度，这种错配导致两种分解者在油松林中密度和生物量更小。整体上，在具有较低凋落物质量的油松林中，分解者维持了体内元素含量但降低了种群生物量。 本研究展示了在多维度化学计量理论框架下探究人工林种植对土壤动物种群动态影响的可行性，该理论框架可作为一种有效的工具来探究生态系统如何响应全球环境变化。.

Circular intuitionistic fuzzy (C-IF) sets are an up-and-coming tool for enforcing indistinct and imprecise information in variable and convoluted decision-making situations. C-IF sets, as opposed to typical intuitionistic fuzzy sets, are better suited for identifying the evaluation data with uncertainty in intricate realistic decision situations. The architecture of the technique for order preference by similarity to ideal solutions (TOPSIS) provides powerful evaluation tools to aid decision-making in intuitionistic fuzzy conditions. To address appraisal issues associated with decision analysis involving extremely convoluted information, this paper propounds a novel C-IF TOPSIS approach in the context of C-IF uncertainty. This research makes three significant contributions. First, based on the three- and four-term operating rules, this research introduces C-IF Minkowski distance measures, which are new generalized representations of distance metrics applicable to C-IF values and C-IF sets. Such general C-IF distance metrics can alleviate the constraints of established C-IF distance measures, provide usage resiliency through parameter settings, and broaden the applicability of metric analysis. Second, unlike existing C-IF TOPSIS methods, this research fully utilizes C-IF information characteristics and extends the core structure of the classic TOPSIS to C-IF contexts. With the newly developed C-IF Minkowski metrics, this study faithfully demonstrates the trade-off evaluation and compromise decision rules in the TOPSIS framework. Third, this research builds on the core strengths of the pioneered C-IF Minkowski distance measures to create innovative C-IF TOPSIS techniques utilizing four different combinations, including displaced and fixed anchoring frameworks, as well as three- and four-term representations. Such a refined C-IF TOPSIS methodology can assist decision-makers in proactively addressing increasingly sophisticated decision-making problems in practical settings. Finally, this research employs two innovative prioritization algorithms to address a site selection issue of large-scale epidemic hospitals to illustrate the superior capabilities of the C-IF TOPSIS methodology over some current related approaches.

The improvement of treatment for patients with 'driver-gene-negative' lung adenocarcinoma (LUAD) remains a critical problem to be solved. We aimed to explore the role of methylation of N6 adenosine (m6A)-related long noncoding RNA (lncRNA) in stratifying 'driver-gene-negative' LUAD risk. Patients negative for mutations in EGFR, KRAS, BRAF, HER2, MET, ALK, RET, and ROS1 were identified as 'driver-gene-negative' cases. RNA sequencing was performed in 46 paired tumors and adjacent normal tissues from patients with 'driver-gene-negative' LUAD. Twenty-three m6A regulators and relevant lncRNAs were identified using Pearson's correlation analysis. K-means cluster analysis was used to stratify patients, and a prognostic nomogram was developed. The CIBERSORT and pRRophetic algorithms were employed to quantify the immune microenvironment and chemosensitivity. We identified two clusters highly consistent with the prognosis based on their unique expression profiles for 46 m6AlncRNAs. A risk model constructed from nine m6A lncRNAs could stratify patients into high- and low-risk groups with promising predictive power (C-index = 0.824), and the risk score was an independent prognostic factor. The clusters and risk models were closely related to immune characteristics and chemosensitivity. Additional pan-cancer analysis using the nine m6AlncRNAs showed that the expression of DIO3 opposite strand upstream RNA (DIO3OS) is closely related to the immune/stromal score and tumor stemness in a variety of cancers. Our results show that m6AlncRNAs are a reliable prognostic tool and can aid treatment decision-making in 'driver-gene-negative' LUAD. DIO3OS is associated with the development of various cancers and has potential clinical applications.

RNA therapeutics is an emerging field that widens the range of treatable targets and would improve disease outcome through bypassing the antibiotic bactericidal targets to kill Mycobacterium tuberculosis (M.tb).We screened for microRNA with immune-regulatory functions against M.tb by next generation sequencing of peripheral blood mononuclear cells, followed by validation in an independent cohort.Twenty three differentially expressed microRNAs were identified between 12 active pulmonary TB patients and 4 healthy subjects, and 35 microRNAs before and after 6-month anti-TB therapy. Enriched predicted target pathways included proteoglycan, HIF-1 signaling, longevity-regulating, central carbon metabolism, and autophagy. We validated miR-431-3p down-regulation and miR-1303 up-regulation accompanied with corresponding changes in their predicted target genes in an independent validation cohort of 46 active TB patients, 30 latent TB infection subjects, and 24 non-infected healthy subjects. In vitro experiments of transfections with miR-431-3p mimic/miR-1303 short interfering RNA in THP-1 cells under ESAT-6 stimuli showed that miR-431-3p and miR-1303 were capable to augment and suppress autophagy/apoptosis/phagocytosis of macrophage via targeting MDR1/MMP16/RIPOR2 and ATG5, respectively.This study provides a proof of concept for microRNA-based host-directed immunotherapy for active TB disease. The combined miR-431-3p over-expression and miR-1303 knock-down revealed new vulnerabilities of treatment-refractory TB disease.

Despite the rapid development of immunotherapy, low response rates, poor therapeutic outcomes and severe side effects still limit their implementation, making the augmentation of immunotherapy an important goal for current research. DNA, which has principally been recognized for its functions of encoding genetic information, has recently attracted research interest due to its emerging role in immune modulation. Inspired by the intrinsic DNA-sensing signaling that triggers the host defense in response to foreign DNA, DNA or nucleic acid-based immune stimulators have been used in the prevention and treatment of various diseases. Besides that, DNA vaccines allow the synthesis of target proteins in host cells, subsequently inducing recognition of these antigens to provoke immune responses. On this basis, researchers have designed numerous vehicles for DNA and nucleic acid delivery to regulate immune systems. Additionally, DNA nanostructures have also been implemented as vaccine delivery systems to elicit strong immune responses against pathogens and diseased cells. This review will introduce the mechanism of harnessing DNA-mediated immunity for the prevention and treatment of diseases, summarize recent progress, and envisage their future applications and challenges.