CCDC181 is required for sperm flagellum biogenesis and male fertility in mice

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 coiled-coil 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.

Current clinical trials on gastric cancer surgery in China

Gastric cancer(GC)is the leading diagnosed malignancy worldwide,especially in China.Radical surgery is the cornerstone of GC treatment.We reviewed previous clinical trials and aimed to provide an update on the factors related to the surgical treatment of GC.The number of registered clinical trials in the field of GC surgery is rapidly increasing.With the development and popularization of endoscopic,laparoscopic,and robotic techniques,GC surgery has gradually entered a new era of precise minimally invasive surgery.Postoperative quality of life has become a major issue in addition to surgical oncological safety.Although great progress has been made in clinical research on GC in China,there are still deficiencies.Many studies enrolled large numbers of patients,but the research data were not of high quality.The characteristics of GC in China include a high incidence,large population,and large proportion of patients with advanced GC,which provides sufficient reason for studying this disease.There is still a need for well-designed,large,randomized clinical trials to improve our knowledge of the surgical treatment of GC.

Blood-testis barrier and spermatogenesis： lessons From genetically-modified mice

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.

Microscopic oil occurrence in high-maturity lacustrine shales:Qingshankou Formation,Gulong Sag,Songliao Basin

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 1.268×10^(9) t.In this study,field emission scanning electron microscope(FE-SEM),the modular automated processing system(MAPS),pyrolysisgas 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%e79.4%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.

Organic matter occurrence and pore-forming mechanisms in lacustrine shales in China

The evolution of pore structure in shales is affected by both the thermal evolution of organic matter(OM)and by inorganic diagenesis,resulting in a wide variety of pore structures.This paper examines the OM distribution in lacustrine shales and its influence on pore structure,and describes the process of porosity development.The principal findings are:(i)Three distribution patterns of OM in lacustrine shales are distinguished;laminated continuous distribution,clumped distribution,and stellate scattered distribution.The differences in total organic carbon(TOC)content,free hydrocarbon content(S_(1)),and OM porosity among these distribution patterns are discussed.(ii)Porosity is negatively correlated with TOC and plagioclase content and positively correlated with quartz,dolomite,and clay mineral content.(iii)Pore evolution in lacustrine shales is characterized by a sequence of decreasing-increasing-decreasing porosity,followed by continuously increasing porosity until a relatively stable condition is reached.(iv)A new model for evaluating porosity in lacustrine shales is proposed.Using this model,the organic and inorganic porosity of shales in the Permian Lucaogou Formation are calculated to be 2.5%-5%and 1%-6.3%,respectively,which correlate closely with measured data.These findings may provide a scientific basis and technical support for the sweet spotting in lacustrine shales in China.

Laparoendoscopic single-site distal pancreatectomy in pigs

AIM: To explore the technique for laparoendoscopic single-site distal pancreatectomy.

Development of an enzyme immune assay for detecting M2 autoantibodies specific for primary biliary cirrhosis

OBJECTIVE: To develope a new enzyme immune assay (ELISA) for detection of M2 antibody specific for primary biliary cirrhosis (PBC) by using a triple hybrid clone as antigen, which coexpresses the three immunodominant lipoyl domains of PDC-E2, BCOADC-E2 and OGDC-E2 from human sources. METHODS: After expressing autoantigens of PBC in prokaryote by constructing recombinant expressive plasmid successfully, the fusion protein was purified by affinity chromatography. The sera of 17 PBC patients were examined. As controls, the sera of 167 non-PBC patients and the sera of 1225 normal controls aged under 28 were examined. RESULTS: None of the sera from the non-PBC patients or the normal controls was positive for anti-M2 shown by the new ELISA. However, the positivity rate for anti-M2 in the PBC patients was 100% (17/17), as shown by the new ELISA. CONCLUSION: The detection system with a good sensitivity and specificity may be used as a powerful method for the diagnosis of PBC.

Ultrafine eutectic Ti_xSn_y/TiNi composites with high damping capacity

Three kinds of bulk-type ultrafine TixSny/TiNi （TixSny represents Ti3Sn, Ti2Sn, and TisSn3 or Ti6Sns） composites with homogeneous eutectic microstructure were prepared by arc melting. The composites exhibit high damping capacity （tan6 greater than 1 x 10-2） and enhanced mechanical strength （the highest fracture strength is 2.15 GPa）. The damping capacity originates from TiNi and Ti3Sn, while the eutectic contributes to the mechanical strength.

A novel missense mutation of CCDC34 causes male infertility with oligoasthenoteratozoospermia in a consanguineous Pakistani family

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.

Association between MTHFR c.677C>T variant and erectile dysfunction among males attending fertility clinic

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=O.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 routineclinicaldiagnosis.

Semen parameters in men recovered from COVID-19

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.

The molecular control of meiotic double-strand break (DSB) formation and its significance in human infertility

Meiosis is an essential step in gametogenesis which is the key process in sexually reproducing organisms as meiotic aberrations may result in infertility. In meiosis, programmed DNA double-strand break (DSB) formation is one of the fundamental processes that are essential for maintaining homolog interactions and correcting segregation of chromosomes. Although the number and distribution of meiotic DSBs are tightly regulated, still abnormalities in DSB formation are known to cause meiotic arrest and infertility. This review is a detailed account of molecular bases of meiotic DSB formation, its evolutionary conservation, and variations in different species. We further reviewed the mutations of DSB formation genes in association with human infertility and also proposed the future directions and strategies about the study of meiotic DSB formation.

Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families

Multiple morphological abnormalities of the sperm flagella(MMAF)is a specific type of asthenoteratozoospermia,presenting with multiple morphological anomalies in spermatozoa,such as absent,bent,coiled,short,or irregular caliber flagella.Previous genetic studies revealed pathogenic mutations in genes encoding cilia and flagella-associated proteins(CFAPs;e.g.,CFAP43,CFAP44,CFAP65,CFAP69,CFAP70,and CFAP251)responsible for the MMAF phenotype in infertile men from different ethnic groups.However,none of them have been identified in infertile Pakistani males with MMAF.In the current study,two Pakistani families with MMAF patients were recruited.Whole-exome sequencing(WES)of patients and their parents was performed.WES analysis reflected novel biallelic loss-of-function mutations in CFAP43 in both families(Family 1:ENST00000357060.3,p.Arg300Lysfs*22 and p.Thr526Serfs*43 in a compound heterozygous state;Family 2:ENST00000357060.3,p.Thr526Serfs*43 in a homozygous state).Sanger sequencing further confirmed that these mutations were segregated recessively in the families with the MMAF phenotype.Semiquantitative reverse-transcriptase polymerase chain reaction(qRT-PCR)was carried out to detect the effect of the mutation on mRNA of the affected gene.Previous research demonstrated that biallelic loss-of-function mutations in CFAP43 accounted for the majority of all CFAP43-mutant MMAF patients.To the best of our knowledge,this is the first study to report CFAP43 biallelic loss-of-function mutations in a Pakistani population with the MMAF phenotype.This study will help researchers and clinicians to understand the genetic etiology of MMAF better.

Tocolysis Effects of Traditional Chinese Medicine and Their Effective Components

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.

Association between semen collection time and semen parameters:an observational study

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.