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Male infertility is a worldwide health issue, affecting 8%–12% of the global population. Oligoasthenoteratozoospermia (OAT) represents a severe type of male infertility, characterized by reduced sperm count and motility and an increased frequency of sperm with aberrant morphology. Using whole-exome sequencing, this study identified a novel missense mutation (c.848C>A, p.A283E) in the coiled-coil domain-containing 34 gene (CCDC34) in a consanguineous Pakistani family. This rare mutation was predicted to be deleterious and to affect the protein stability. Hematoxylin and eosin staining of spermatozoa from the patient with OAT revealed multiple morphological abnormalities of the flagella and transmission electron microscopy indicated axonemal ultrastructural defects with a lack of outer dynein arms. These findings indicated that CCDC34 plays a role in maintaining the axonemal ultrastructure and the assembly or stability of the outer dynein arms, thus expanding the phenotypic spectrum of CCDC34 missense mutations.

Abstract Gastric cancer (GC) is a highly heterogeneous and aggressive malignant tumor that seriously affects the life safety of people all over the world. Its early manifestations are subtle. The present study aimed to investigate the clinical significance of serum lipid profiles, insulin resistance markers including the triglyceride-glucose (TyG) index and the atherosclerotic index (AI), in GC patients. A retrospective analysis encompassed 215 GC patients and 827 healthy individuals. The study results show that the total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein levels, and the TyG index of GC patients were significantly lower than those of the control group before and after propensity score matching analysis. In the GC group, the levels of CEA, CA199, CA125, and CA724 tumor markers were higher than those in the healthy control group. Patients in advanced stages exhibited lower serum levels of serum lipids and TyG index compared to those in early stages. ROC analysis revealed that the TyG index, CA125, and CA199 combination yielded the highest positive prediction rate for GC at 98.6%. TyG index is significantly associated with the risk of adverse reactions after chemotherapy (OR = 1.104, 95% CI 1.028–1.186, P

Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15–5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.

Abstract Background Laparoscopic colorectal surgery has been proved to have similar oncological outcomes with open surgery. Due to the lack of tactile perception, surgeons may have misjudgments in laparoscopic colorectal surgery. Therefore, the accurate localization of a tumor before surgery is important, especially in the early stages of cancer. Autologous blood was thought a feasible and safe tattooing agent for preoperative endoscopic localization but its benefits remain controversial. We therefore proposed this randomized trial to the accuracy and safety of autogenous blood localization in small, serosa-negative lesion which will be resected by laparoscopic colectomy. Methods The current study is a single-center, open-label, non-inferiority, randomized controlled trial. Eligible participants would be aged 18–80 years and diagnosed with large lateral spreading tumors that could not be treated endoscopically, malignant polyps treated endoscopically that required additional colorectal resection, and serosa-negative malignant colorectal tumors (≤ cT3). A total of 220 patients would be randomly assigned (1:1) to autologous blood group or intraoperative colonoscopy group. The primary outcome is the localization accuracy. The secondary endpoint is adverse events related to endoscopic tattooing. Discussion This trial will investigate whether autologous blood marker achieves similar localization accuracy and safety in laparoscopic colorectal surgery compared to intraoperative colonoscopy. If our research hypothesis is statistically proved, the rational introduction of autologous blood tattooing in preoperative colonoscopy can help improve identification of the location of tumors for laparoscopic colorectal cancer surgery, performing an optimal resection, and minimizing unnecessary resections of normal tissues, thereby improving the patient’s quality of life. Our research data will also provide high quality clinical evidence and data support for the conduction of multicenter phase III clinical trials. Trial registration This study is registered with ClinicalTrials.gov, NCT05597384. Registered 28 October 2022

The process of semen collection plays a key role in the quality of semen specimens. However, the association between semen collection time and semen quality is still unclear. In this study, ejaculates by masturbation from 746 subfertile men or healthy men who underwent semen analysis were examined. The median (interquartile range) semen collection time for all participants was 7.0 (5.0–11.0) min, and the median time taken for semen collection was lower in healthy men than that in subfertile men (6.0 min vs 7.0 min). An increase in the time required to produce semen samples was associated with poorer semen quality. Among those undergoing assisted reproductive technology (ART), the miscarriage rate was positively correlated with the semen collection time. After adjusting for confounders, the highest quartile (Q4) of collection time was negatively associated with semen volume and sperm concentration. A longer time to produce semen samples (Q3 and Q4) was negatively correlated with progressive and total sperm motility. In addition, there was a significant negative linear association between the semen collection time and the sperm morphology. Higher risks of asthenozoospermia (adjusted odds ratio [OR] = 2.06, 95% confidence interval [CI]: 1.31–3.25, P = 0.002) and teratozoospermia (adjusted OR = 1.98, 95% CI: 1.10–3.55, P = 0.02) were observed in Q3 than those in Q1. Our results indicate that a higher risk of abnormal semen parameter values was associated with an increase in time for semen collection, which may be related to male fertility through its association with semen quality.

Abstract Background Gastric cancer is a major public health problem worldwide. Social media has affected public’s daily lives in ways no one ever thought possible. Both TikoTok and its Chinese version Douyin are the most popular short video posting platform. This study aimed to evaluate the quality, accuracy, and completeness of videos for gastric cancer on TikTok and Douyin. Methods The terms “gastric cancer” was searched on TikTok in both English and Japanese, and on Douyin in Chinese. The first 100 videos in three languages (website’s default setting) were checked. QUality Evaluation Scoring Tool (QUEST) and DISCERN as the instrument for assessing the quality of the information in each video. Content was analysed under six categories (aetiology, anatomy, symptoms, preventions, treatments, and prognosis). The educational value and completeness were evaluated with a checklist developed by the researchers. Results A total of 78 videos in English, 63 in Japanese, and 99 in Chinese were analyzed. The types of sources were as follows: 6.4% in English, 4.8% in Japanese, and 57.6% in Chinese for health professionals; 93.6% in English, 95.2% in Japanese, and 3.0% in Chinese for private users; none in English and Japanese, but 39.4% in Chinese for other sources. In all, 20.5% in English, 17.5% in Japanese, and 93.9% in Chinese of videos had useful information about gastric cancer. Among the useful videos, the videos published in Chinese had the highest QUEST(p

Objectives The high frequency of chemotherapy resistance is ultimately responsible for clinical relapse in acute lymphoblastic leukemia (ALL). Nevertheless, the molecular mechanism relevant to glucocorticoid (GC) resistance remains ambiguous. Methods Quantitative real-time polymerase chain reaction and Western blot were performed to detect the expressions of paraoxonase 2 (PON2), Bcl-2 and Bax. shRNA was used to knockdown PON2 expression in SUP-B15 and REH cell. CCK-8 and flow cytometry assay were conducted to monitor the changes of proliferation and apoptosis in ALL cells. The growth of ALL REH cells in vivo was determined using transplanted tumor model. Results This study was designed to identify GC resistance-associated genes by means of the transcriptome chip from the public Gene Expression Omnibus database, and preliminarily investigation of dexamethasone (DEX)-resistance mechanism in ALL. We disclosed that PON2 expression was elevated in ALL patients and especially higher in DEX-resistance ALL patients. Then, cell apoptosis assay suggested that silencing of PON2 dramatically promoted in DEX-resistant ALL cells apoptosis and the activity of Caspase 3 induced by DEX administration. In xenograft tumor model, PON2 knockdown significantly reduced DEX-resistant ALL cells growth in immunodeficient mice. Conclusions Collectively, inhibition of PON2 may represent a novel method to restore the sensitivity of treatment-resistant ALL to GC-induced cell death.

Traditional Chinese medicine (TCM) for anti-abortion is based on the theory of gynecology of TCM, which aims to prevent and treat abdominal pain during pregnancy, fetal leakage, uneasy fetal movement, and fetal atrophy. Because of the complexity of the ingredients of Chinese Materia Medica, and the imprecise intervention mechanism for tocolysis, further investigation about the effects of Chinese herbs and their components on tocolysis by utilizing advanced technologies is required to be made. All the information available about TCM and its effects on pregnant women and fetuses was collected via electronic search using Web of Science, PubMed, and CNKI, and a library search was performed to locate classic herbal medicine books. The active ingredients in TCM were screened with the help of Traditional chinese medicine systems pharmacology database and analysis platform (TCMSP). The keywords being used included herbal names, pharmacology, pregnancy, threatened abortion, and fetus. Modern pharmacological studies have shown that TCM mainly prevents threatened abortion by a direct effect on the pregnant woman's immune system, sex hormones such as estrogen and progesterone, the uterus and the endometrium, and the decidual tissue such as the placenta. It may also address pregnancy complications due to advanced maternal age, infection, polycystic ovary syndrome, diabetes, and mental disorders caused by threat of a miscarriage. TCM protects against spontaneous miscarriage, but its mechanisms are largely unknown. This research applies scientific methods to characterize and examine the effective components of TCM and their application to lower the risk of abortion to the pregnant women and fetuses.

Purpose. Our objective was to compare the value of positron emission tomography/magnetic resonance imaging (PET/MRI) with the new imaging agent [68Ga]Ga-DOTA-FAPI-04 and the traditional imaging agent [18F]FDG for the preoperative diagnosis of gastric cancer. Methods. Forty patients with gastric cancer diagnosed by gastroscopy in gastrointestinal surgery at our hospital from June 2020 to January 2021 were analyzed. All patients underwent simultaneous [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/MRI. The standard uptake value (SUV), fat removal standard uptake value (SUL), and diagnostic sensitivity, specificity, and accuracy for primary and metastatic lesions were compared, and their diagnostic value for different lymph node dissection stages was analyzed. Results. The median age of the patients in this cohort was 68 years. Twenty-nine patients underwent surgery, and 11 patients underwent gastroscopic biopsy. The SUVmax of primary lesions in the FDG group and the FAPI group was 5.74 ± 5.09 and 8.06 ± 4.88, respectively (P0.05). Conclusion. Compared with the traditional imaging agent, [68Ga]Ga-DOTA-FAPI-04 has better diagnostic efficiency but no substantial advantage for preoperative lymph node staging.

The structural integrity of the sperm flagellum is essential for proper sperm function. Flagellar defects can result in male infertility, yet the precise mechanisms underlying this relationship are not fully understood. CCDC181, a coiledcoil domain-containing protein, is known to localize on sperm flagella and at the basal regions of motile cilia. Despite this knowledge, the specific functions of CCDC181 in flagellum biogenesis remain unclear. In this study, Ccdc181 knockout mice were generated. The absence of CCDC181 led to defective sperm head shaping and flagellum formation. Furthermore, the Ccdc181 knockout mice exhibited extremely low sperm counts, grossly aberrant sperm morphologies, markedly diminished sperm motility, and typical multiple morphological abnormalities of the flagella (MMAF). Additionally, an interaction between CCDC181 and the MMAF-related protein LRRC46 was identified, with CCDC181 regulating the localization of LRRC46 within sperm flagella. These findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.

Background. Traditionally, serum CEA and CA19-9 levels are good prognostic factors for gastric cancer. Many gastric cancer patients do not have elevated CEA or CA19-9 levels even at a very advanced stage. This study investigates the significance of the modified Glasgow prognostic score (mGPS) for the survival of gastric cancer patients with normal CEA and CA19-9. Methods. We retrospectively examined 488 curatively resected gastric cancer patients with normal preoperative serum levels of CEA and CA19-9 to evaluate the prognostic ability of mGPS for overall survival. The prognostic significance was analyzed by univariate and multivariate analyses. Results. Age, hemoglobin, white cell count, and neutrophils were each significantly correlated with the mGPS. Multivariate analyses showed that tumor location (HR, 0.803; 95% CI, 0.667–0.966; P=0.020), TNM stage (HR, 2.714; 95% CI, 2.250–3.275; P

Background: Excessive oxidative stress is associated with hypertension in professional high-temperature working conditions. Polyphenols exhibit a cardioprotective effect. Hawthorn contains high amounts of flavonoids, though its effect on hypertension protection has yet to be studied. This study aims to investigate this effect of extract of hawthorn (EH) or its combination with vitamin C (Vit. C) in rats induced by working under a hot environment. Methods: Forty-two male rats were randomly divided into a control group under normal temperature and six treatment groups exposed at 33 ± 1 °C along with 1 h of daily treadmill running. They were orally provided with water, Vit. C (14mg/kg), EH (125, 250, and 500 mg/kg), and EH500 + Vit. C, once a day for four weeks. Results: Both EH and Vit. C alone reduced the systolic and diastolic blood pressure of rats exposed to the heat environment; however, their joint supplementation completely maintained their blood pressure to the normal level throughout the experimental period. No morphological changes were found on the intima of aorta. Moreover, the co-supplementation of EH and Vit. C prevented the changes of heat exposure in inducing oxidative stress markers, such as glutathione peroxidase, catalase, total antioxidant capacity, and nitric oxide; the synergistic action was more effective than either individual treatment of EH and Vit. C. Furthermore, the administration of EH had more potent effects on increasing superoxide dismutase, IL-2, the 70 kilodalton heat shock proteins and high sensitivity C reactive protein, and decreasing serum malondialdehyde and lipofuscin in vascular tissue than those in Vit. C group. Conclusions: A strong synergistic effect of EH and Vit. C on the prevention of hypertension under heat exposure was established, as they inhibited the oxidative stress state. This study also sets up a novel intervention strategy in animal models for investigation on the early phases of hypertension induced by heat exposure.

(1) Background: Chitooligosaccharides (COS) have numerous applications due to their excellent properties. Chitosan hydrolysis using chitosanases has been proposed as an advisable method for COS preparation. Although many chitosanases from various sources have been identified, the cold-adapted ones with high stability are still rather rare but required. (2) Methods: A novel chitosanase named CsnY from marine bacterium Renibacterium sp. Y82 was expressed in Escherichia coli, following sequence analysis. Then, the characterizations of recombinant CsnY purified through Ni–NTA affinity chromatography were conducted, including effects of pH and temperature, effects of metal ions and chemicals, and final product analysis. (3) Results: The GH46 family chitosanase CsnY possessed promising thermostability at broad temperature range (0–50 °C), and with optimal activity at 40 °C and pH 6.0, especially showing relatively high activity (over 80% of its maximum activity) at low temperatures (20–30 °C), which demonstrated the cold-adapted property. Common metal ions or chemicals had no obvious effect on CsnY except Mn2+ and Co2+. Finally, CsnY was determined to be an endo-type chitosanase generating chitodisaccharides and -trisaccharides as main products, whose total concentration reached 56.74 mM within 2 h against 2% (w/v) initial chitosan substrate. (4) Conclusions: The results suggest the cold-adapted CsnY with favorable stability has desirable potential for the industrial production of COS.

Abstract Cystic fibrosis transmembrane conductance regulator (CFTR), known as a cAMP-activated Cl− channel, is widely expressed at the apical membrane of epithelial cells in a wide variety of tissues. Of note, despite the abundant expression of CFTR in mammalian kidney, the role of CFTR in kidney disease development is unclear. Here, we report that CFTR expression is downregulated in the UUO (unilateral ureteral obstruction)-induced kidney fibrosis mouse model and human fibrotic kidneys. Dysfunction or downregulation of CFTR in renal epithelial cells leads to alteration of genes involved in Epithelial-Mesenchymal Transition (EMT) and kidney fibrosis. In addition, dysregulation of CFTR activates canonical Wnt/β-catenin signaling pathways, whereas the β-catenin inhibitor reverses the effects of CFTR downregulation on EMT marker. More interestingly, CFTR interacts with Dishevelled 2 (Dvl2), a key component of Wnt signaling, thereby suppressing the activation of β-catenin. Compared to wild type, deltaF508 mice with UUO treatment exhibit significantly higher β-catenin activity with aggregated kidney fibrogenesis, which is reduced by forced overexpression of CFTR. Taken together, our study reveals a novel mechanism by which CFTR regulates Wnt/β-catenin signaling pertinent to progression of kidney fibrosis and indicates a potential treatment target.

Abstract Background Hepatitis C virus (HCV) core protein and nonstructural protein 4B (NS4B) are potentially oncogenic. Aberrant activation of the Wnt/β-catenin signaling pathway is closely associated with hepatocarcinogenesis. We investigated the effects of HCV type 1b core protein and NS4B on Wnt/β-catenin signaling in various liver cells, and explored the molecular mechanism underlying HCV-related hepatocarcinogenesis. Results Compared with the empty vector control, HCV core protein and NS4B demonstrated the following characteristics in the Huh7 cells: significantly enhanced β-catenin/Tcf-dependent transcriptional activity (F = 40.87, P 0.05), but they did significantly enhance Wnt3a-induced β-catenin/Tcf-dependent transcriptional activity (F = 64.25, P

Occurrence and mobility of shale oil are prerequisites for evaluating shale oil reserves and prioritizing exploration targets, particularly for heterogeneous lacustrine shales. The Qingshankou Formation in the Gulong Sag, Songliao Basin is a classic lacustrine pure shale reservoir that contains abundant shale oil resources. The predicted geological reserves of the shale are 1.268 × 109 t. In this study, field emission scanning electron microscope (FE-SEM), the modular automated processing system (MAPS), pyrolysis-gas chromatography (Py-GC), low-pressure nitrogen gas adsorption (LPNA), Soxhlet extraction, pyrolysis, and 2-D nuclear magnetic resonance (NMR) were integrated to describe the shale oil components, microscopic occurrence, mobility, and the effective pore size distribution. Meanwhile, the related controlling factors are discussed.The shale oil in the Qingshankou Fm exists dominantly in the matrix pores of the clay minerals, with small amounts distributed in the intergranular pores of terrigenous clastic grains, intercrystalline pores of pyrite, intragranular pores of ostracod shells, and micro-fractures. Shale oil is distributed in the pore spaces of variable sizes in different lithofacies. The clay mineral-laminated shales are characterized by the broadest range of pore size and largest volume of pore spaces with shale oil distribution, while the ostracod-laminated shales have limited pore spaces retaining oil. Furthermore, the proposed integrated analysis evaluates the shale oil molecules existing in two states: movable, and adsorbed oil, respectively. The result illustrates that movable oil takes up 30.6%–79.4% of the total residual oil. TOC, mineral composition, and pore structures of the shale joint together to control the states and mobility of the shale oil. TOC values are positively correlated with the quantities of shale oil regardless of the state of oil. The mineral components significantly impact the state of shale oil. Noticeable differences in the states of oil were observed following the changing types of minerals, possibly due to their difference in adsorption capacity and wettability. Clay minerals attract more adsorbed oil than movable oil. Felsic minerals generally decrease the occurrence of total and adsorbed oil. Carbonate plays a positive role in hydrocarbon retention of all the shale oil states. As for the pore structure, the average pore size exerts a critical impact on the total, movable, and adsorbed oil content. The total pore volume and specific surface area of shales play a principal role in controlling the total yields and amounts of adsorbed oil. This research improves the understanding of the occurrence characteristics and enrichment mechanisms of shale oil in terrestrial pure shales and provides a reference for locating favorable shale oil exploration areas. [ABSTRACT FROM AUTHOR]

The blood-testis barrier (BTB) is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of meiotic and postmeiotic germ cells in seminiferous tubes. It is a compound proteinous structure, composed of several types of cell junctions including tight junctions (TJs), adhesion junctions and gap junctions (GJs). Some of the junctional proteins function as structural proteins of BTB and some have regulatory roles. The deletion or functional silencing of genes encoding these proteins may disrupt the BTB, which may cause immunological or other damages to meiotic and postmeiotic cells and ultimately lead to spermatogenic arrest and infertility. In this review, we will summarize the findings on the BTB structure and function from genetically-modified mouse models and discuss the future perspectives.

The biologic studies of human neural crest stem cells (hNCSCs) are extremely challenging due to the limited source of hNCSCs as well as ethical and technical issues surrounding isolation of early human embryonic tissues. On the other hand, vast majority of studies on MycN have been conducted in human tumor cells, thus, the role of MycN in normal human neural crest development is completely unknown. In the present study, we determined the role of MycN in hNCSCs isolated from in vitro-differentiating human embryonic stem cells (hESCs). For the first time, we show that suppression of MycN in hNCSCs inhibits cell growth and cell cycle progression. Knockdown of MycN in hNCSCs increases the expression of Cdkn1a, Cdkn2a and Cdkn2b, which encodes the cyclin-dependent kinases p21CIP1, p16 INK4a and p15INK4b. In addition, MycN is involved in the regulation of human sympathetic neurogenesis, as knockdown of MycN enhances the expression of key transcription factors involved in sympathetic neuron differentiation, including Phox2a, Phox2b, Mash1, Hand2 and Gata3. We propose that unlimited source of hNCSCs provides an invaluable platform for the studies of human neural crest development and diseases.

Hearing loss or ototoxicity is one of the major side effects associated with the use of the antibiotics, particularly aminoglycosides (AGs), which are the most commonly used antibiotics worldwide. However, the molecular and cellular events involved in the antibiotic-induced ototoxicity remains unclear. In the present study, we test the possibility that prestin, the motor protein specifically expressed in the basolateral membrane of outer hair cells (OHCs) in the cochlea with electromotility responsible for sound amplification, may be involved in the process of AG-induced apoptosis in OHCs. Our results from both mice model and cultured cell line indicate a previously unexpected role of prestin, in mediating antibiotic-induced apoptosis, the effect of which is associated with its anion-transporting capacity. The observed downregulation of prestin mRNA prior to detectable apoptosis in OHCs and hearing loss in the antibiotic-treated mice is interesting, which may serve as a protective mechanism against hearing loss induced by AGs in the early stage.

An improved and efficient oxalylation of aryl methyl ketones was accomplished with tert-butyl methyl oxalate. Advantages over conventional methods with dimethyl oxalate were observed in both yield and reaction time.