Effects of long-term running on the structure and biochemical composition of knee cartilage in males: a cross-sectional study.

Background: Running has been widely recognized as a beneficial activity for improving physical fitness, but it can also increase the risk of running-related injuries (RRIs). This study aims to assess the impact of long-term running on the structural and biochemical composition of the knee. Methods: This study recruited a total of 32 participants, including 16 male recreational runners, aged 28-49 years, with a running experience of 2-7 years, and 16 matched sedentary controls. Magnetic resonance (MR) scans of T2* mapping and three-dimensional double-echo steady-state (3D-DESS) were performed on all participants. The volumes, thickness, and T2* values of joint articular cartilage were obtained via automatic segmentation software. Results: Compared with the sedentary controls, runners exhibited significant increases in the volumes of both the femoral medial articular cartilage and the tibial medial articular cartilage. Additionally, there were significant increases in the thickness of several cartilage regions, including femoral medial cartilage, femoral medial articular cartilage, femoral medial thickness, femoral lateral cartilage, and tibial medial articular cartilage. Notably, the T2* values in the femoral lateral and tibial lateral cartilage of runners decreased significantly, while those in the patellar cartilage and medial tibial cartilage increased significantly. Runner pace was negatively correlated with the overall knee cartilage thickness (r=-0.556; P=0.02), femoral cartilage thickness (r=-0.533; P=0.03), and volume (r=-0.532; P=0.03) but positively correlated with the T2* value of the patellar cartilage (r=0.577; P=0.01). Conclusions: Our study suggests that long-term mechanical stress from running may lead to increased thickness and volume in certain knee joint cartilage regions, possibly enhancing the functional adaptability of knee cartilage. The varying changes in T2* value in the tibial and fibular cartilage areas may indicate differing adaptability to pressure.

HSF5 Deficiency Causes Male Infertility Involving Spermatogenic Arrest at Meiotic Prophase I in Humans and Mice.

Meiosis is a specialized cell division process that generates gametes for sexual reproduction. However, the factors and underlying mechanisms involving meiotic progression remain largely unknown, especially in humans. Here, it is first showed that HSF5 is associated with human spermatogenesis. Patients with a pathogenic variant of HSF5 are completely infertile. Testicular histologic findings in the patients reveal rare postmeiotic germ cells resulting from meiotic prophase I arrest. Hsf5 knockout (KO) mice confirms that the loss of HSF5 causes defects in meiotic recombination, crossover formation, sex chromosome synapsis, and sex chromosome inactivation (MSCI), which may contribute to spermatocyte arrest at the late pachytene stage. Importantly, spermatogenic arrest can be rescued by compensatory HSF5 adeno-associated virus injection into KO mouse testes. Mechanistically, integrated analysis of RNA sequencing and chromatin immunoprecipitation sequencing data revealed that HSF5 predominantly binds to promoters of key genes involved in crossover formation (e.g., HFM1, MSH5 and MLH3), synapsis (e.g., SYCP1, SYCP2 and SYCE3), recombination (TEX15), and MSCI (MDC1) and further regulates their transcription during meiotic progression. Taken together, the study demonstrates that HSF5 modulates the transcriptome to ensure meiotic progression in humans and mice. These findings will aid in genetic diagnosis of and potential treatments for male infertility.

Challenges and perspectives of tobacco cessation in special groups of patients and populations.

During the first 2 years of the coronavirus disease 2019 pandemic, health systems worldwide were put under extreme pressure, and healthcare professionals had to manage unprecedented health crises as well as provide healthcare services to an increased number of patients. Therefore, public health policies with respect to smoking and education of the general population regarding the harmful effects of active and second-hand smoking may not have received adequate attention during this period. More specifically, certain subpopulations suffering from chronic diseases may not have received adequate information about the effects of smoking on the course and outcome of their disease; high-level, evidence-based pharmaceutical therapies; and the potential for follow-up. However, adequate education and awareness regarding short- and long-term health benefits from smoking cessation for the general population as well as special subgroups remains of utmost importance. Healthcare professionals should understand that it is only through high-quality evidence and results from independent studies that they will be able to provide their expertise and scientific knowledge concerning newer tobacco products and their effects on human health.

MiR-93 alleviates DEHP plasticizer-induced neurotoxicity by negatively regulating TNFAIP1 and inhibiting ubiquitin-mediated degradation of CK2ß.

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is widely used in various products, such as plastic packaging in food industries. As an environmental endocrine disruptor, it induces adverse effects on brain development and function. However, the molecular mechanisms by which DEHP induces learning and memory impairment remain poorly understood. Herein, we found that DEHP impaired learning and memory in pubertal C57BL/6 mice, decreased the number of neurons, downregulated miR-93 and the ß subunit of casein kinase 2 (CK2ß), upregulated tumor necrosis factor-induced protein 1 (TNFAIP1), and inhibited Akt/CREB pathway in mouse hippocampi. Co-immunoprecipitation and western blotting assays revealed that TNFAIP1 interacted with CK2ß and promoted its degradation by ubiquitination. Bioinformatics analysis showed a miR-93 binding site in the 3'-untranslated region of Tnfaip1. A dual-luciferase reporter assay revealed that miR-93 targeted TNFAIP1 and negatively regulated its expression. MiR-93 overexpression prevented DEHP-induced neurotoxicity by downregulating TNFAIP1 and then activating CK2/Akt/CREB pathway. These data indicate that DEHP upregulates TNFAIP1 expression by downregulating miR-93, thus promoting ubiquitin-mediated degradation of CK2ß, subsequently inhibiting Akt/CREB pathway, and finally inducing learning and memory impairment. Therefore, miR-93 can relieve DEHP-induced neurotoxicity and may be used as a potential molecular target for prevention and treatment of related neurological disorders.

Population-based genetic analysis in infertile men reveals novel mutations of ADAD family members in patients with impaired spermatogenesis.

The testis-specific adenosine deaminase domain-containing (ADAD) protein family, including ADAD1 and ADAD2, has been confirmed to be essential in mouse male fertility. However, the roles of ADAD1 and ADAD2 in human reproductive biology are unclear. Herein, whole-exome sequencing was conducted for 337 infertile patients to detect pathogenic variants in ADAD1 and ADAD2. Importantly, a novel deleterious biallelic variant of NM_001159285.2:c.1408G > T (p.V470F) and NM_001159285.2:c.1418A > G (p.E473G) in ADAD1 and a pathogenic homozygous missense variant of NM_001145400.2:c.1381C > T (p.R461W) in ADAD2 were identified in this infertile cohort with frequencies of 0.29 (1/337) and 0.59% (2/337), respectively. Electron microscopy revealed an abnormal morphology and severely disorganized ultrastructure of sperm from the patients. Immunofluorescence and western blotting showed a sharp decrease in ADAD1 and ADAD2 expression in sperm from the patients. Mechanistically, bioinformatics analysis suggested that ADAD2 interacts with DNAH17. Furthermore, we demonstrated that the expression of DNAH17 was markedly downregulated in the sperm of patients harboring ADAD2 variants. In addition, the expression of several autophagy regulators was significantly disrupted in the sperm of patients harboring ADAD2 variants. In conclusion, we identified novel ADAD1 and ADAD2 variants in three infertile patients from a large infertile cohort, first providing evidence that ADAD1 and ADAD2 variants might be a candidate genetic cause of human male infertility. Moreover, an important new dimension to our understanding of the genotype-phenotype correlations between the ADAD gene family and male infertility in humans has been uncovered, providing valuable information for the genetic diagnosis of male infertility.

Sequencing of the ZMYND15 gene in a cohort of infertile Chinese men reveals novel mutations in patients with teratozoospermia.

BACKGROUND: The information of ZMYND15 in human reproduction is very limited, resulting in the unclear link between ZMYND15 variants and male infertility. METHODS: Whole exome sequencing and Sanger sequencing to identify the potential pathogenic variation of ZMYND15 in infertile men, Papanicolaou staining and electron microscopy to investigate the spermatozoa morphology, western blotting and immunofluorescence staining to confirm the pathogenicity of the identified variants, and proteomic analysis and coimmunoprecipitation to clarify the potential molecular mechanism. RESULTS: A total of 31 ZMYND15 variants were identified in 227 infertile patients. Three deleterious biallelic variants, including a novel compound heterozygous variant of c.1105delG (p.A369Qfs*15) and c.1853T>C (p.F618S), a new homozygous splicing mutation of c.1297+5G>A and a reported homozygous nonsense mutation of c.1209T>A (p.Y403*), were detected in three affected individuals with oligoasthenoteratozoospermia, showing a biallelic pathogenic mutation frequency of 1.3% (3/227). No biallelic pathogenic mutation was found in 692 fertile men. Morphology analysis showed abnormalities in sperm morphology in the patients harbouring ZMYND15 mutations. Western blotting and immunofluorescence staining confirmed the nearly absent ZMYND15 expression in the sperm of the patients. Mechanistically, ZMYND15 might regulate spermatogenesis by interacting with key molecules involved in sperm development, such as DPY19L2, AKAP4 and FSIP2, and might also mediate the expression of the autophagy-associated protein SPATA33 to maintain sperm individualisation and unnecessary cytoplasm removal. CONCLUSION: Our findings broaden the variant and phenotype spectrum of ZMYND15 in male infertility, and reveal the potential signalling pathway of ZMYND15 regulating spermatogenesis, finally confirming the essential role of ZMYND15 in human fertility.

Deficiency of cancer/testis antigen gene CT55 causes male infertility in humans and mice.

The Cancer/Testis Antigen (CTA) genes comprise a group of genes whose expression under physiological conditions is restricted to the testis but is activated in many human cancers. Depending on the particular expression pattern, the CTA genes are speculated to play a role in spermatogenesis, but evidence is limited thus far. Here, we reported patients with a hemizygous nonsense mutation in cancer-testis antigen 55 (CT55) suffering from male infertility with extreme disruption in sperm production, morphology, and locomotion. Specifically, the insufficiency of sperm individualization, excessive residue of unnecessary cytoplasm, and defects in acrosome development were evident in the spermatozoa of the patients. Furthermore, mouse models with depletion of Ct55 showed accelerated infertility with age, mimicking the defects in sperm individualization, unnecessary cytoplasm removal, and meanwhile exhibiting the disrupted cumulus-oocyte complex penetration. Mechanistically, our functional experiments uncovered CT55 as a new autophagic manipulator to regulate spermatogenesis via selectively interacting with LAMP2 and GABARAP (which are key regulators in the autophagy process) and further fine-tuning their expression. Therefore, our findings revealed CT55 as a novel CTA gene involved in spermatogenesis due to its unprecedented autophagy activity.

Iron-doped novel Co-based metal-organic frameworks for preparation of bifunctional catalysts with an amorphous structure for OER/HER in alkaline solution.

A novel two-dimensional Co-MOF material {[Co(dptz)2(oba)2]·(DMF)2}n is prepared using mixed organic ligands, which exhibits both OER (oxygen evolution reaction) and HER (hydrogen evolution reaction) catalytic performance. The integration of an Fe dopant and amorphous interface into Co-MOF to improving the electrocatalytic performance of pristine MOFs (metal-organic frameworks) is demonstrated and the origin of the remarkable electrocatalytic performance of the catalyst is elucidated. The comprehensive characterization data of Fe@Co-MOFs illustrate that there is a crystallinity transition during the doping of Co-MOF, which increases the electron transfer rate of the material and ensures increased exposure of the ligand unsaturated active site on the surface, and modulates the electronic structure of the Co center in a synergistic manner. As a result, the optimized catalytic Fe@Co-MOF-3 with an amorphous structure exhibits outstanding electrocatalytic performance for the OER, with only 248 mV at a current density of 50 mA cm-2 and excellent stability after 11 h of testing in alkaline solution. Not only that, the HER was achieved with a low overpotential of 150 mV at 10 mA cm-2. The present work indicates that the as-synthesized Co-MOF and Fe@Co-MOFs offer prospects in developing electrocatalysts for water splitting.

Monthly Motivational Interview Counseling and Nicotine Replacement Therapy for Smoking Parents of Pediatric Patients: A Randomized Controlled Trial.

Background: Parental smoking is the dominant source of passive smoke exposure in the pediatric population. The current randomized controlled trial (RCT) study aimed to evaluate the effectiveness of a multi-component smoking reduction intervention in parental smoking reduction and children's environmental tobacco smoke exposure reduction in clinical settings. Methods: A single-blinded, 6-month randomized controlled trial recruited smoking parents (N = 210) of children who attended the pediatric wards or clinics at the Prince of Wales Hospital. Participants allocated to the intervention group (n = 105) received monthly motivational interviews on smoking reduction with emphasis on health hazards related to children's passive smoke exposure, 8-week nicotine replacement therapy, and referral to smoking cessation service if the parents preferred. The control group (n = 105) received simple verbal advice on smoking cessation. Primary outcomes were parental urine cotinine validated and self-reported ≥50% smoking reduction rates at 6 months. Results: Smoking parents in the intervention group had significantly more biochemically validated ≥50% smoking reduction than the control: 27.1 vs. 10.0% (OR = 3.34, 95% CI: 1.16-9.62, P = 0.02). The rate of self-reported ≥50% smoking reduction was also significantly higher in the intervention group than the control: 51.9 vs. 20.2% (OR = 4.40, 95% CI: 2.38-8.12, P < 0.001). For secondary outcomes, the rate of parental self-reported smoking cessation was higher in the intervention arm: 10.5 vs. 1.0% (OR = 12.17, 95% CI: 1.54-96.07, P < 0.001), however, no differences were detected in biochemically validated cessation and changes in children's passive smoke exposure between the groups. Conclusion: Monthly smoking reduction counseling together with nicotine replacement therapy is more effective than simple verbal cessation advice in the smoking reduction for parents of pediatric patients. However, this study did not demonstrate differences in smoking cessation or reduction in children's passive smoke exposure with a 6-month follow-up. Achievement of a smoke-free environment remains challenging. Trial Registration: Clinicaltrials.gov, identifier: NCT03879889.

Radiographic measurement of the posterior tibial slope in normal Chinese adults: a retrospective cohort study.

BACKGROUND: Measurement of the posterior tibial slope (PTS) angle has important applications in total knee replacement surgery, high tibial osteotomy, and anterior cruciate ligament reconstruction. This study aimed to determine the mean PTS of knee joints in healthy Chinese adults, and provide data to guide knee surgery in China. METHODS: A retrospective analysis of 1257 (n = 1233, 50.4% male) plain X-ray films of participants aged 25-59 years was performed. The picture archiving and communication system was used for PTS measurement. The PTS was defined as the angle between the vertical line of the tangent of the anterior tibial cortex of the proximal tibia, and the tangent line of the tibial cortex. Two imaging physicians conducted the PTS measurements independently, and both the inter- and intraclass correlation coefficients (ICCs) were calculated. RESULTS: The mean PTS value was 7.68 ± 3.84° (range: 0-21°). The left PTS was significantly smaller in males than in females (7.22 ± 3.89 vs 8.05 ± 3.60; P = 0.005). Additionally, the PTS in participants aged 25-29 years was significantly larger than that in the other age groups (Left side: 8.64 ± 3.73 vs 6.92 ± 3.42, 7.42 ± 3.75, 7.53 ± 3.98; P <  0.001 and Right side: 8.68 ± 3.84 vs 7.48 ± 4.21, 7.13 ± 3.64, 7.66 ± 3.80; P = 0.004). There were no significant differences in PTS between the left and right sides. Two-way analysis of variance suggested that the differences in PTS between age groups were not affected by sex. The interobserver ICC was 0.91 (95% confidence interval [CI]: 0.85-0.94), and the intraobserver ICC was 0.90 (95% CI: 0.82-0.94). CONCLUSIONS: This study demonstrated that there were significant differences in PTS based on sex and age, highlighting the need to provide individualized treatment for knee surgery. It provided valuable information regarding the normal PTS values in Chinese adults and presented regionalised data to guide knee surgery.

Environmental tobacco smoke and carotid intima-media thickness in healthy children and adolescents: a systematic review.

Thicker carotid intima-media thickness (CIMT) has been a valid predictor for atherosclerosis development. A significant association between environmental tobacco smoke (ETS) and thickening of CIMT has been demonstrated in adults, whereas such association has scarcely been reviewed in paediatric population. The dominate electronic databases, including MEDLINE (Ovid), PubMed, Embase, CINAHL, Web of Science, Scopus, were searched from inception. Reference lists of retrieved articles were further scanned as to avoid any missing literatures. Newcastle-Ottawa scale was used to assess the quality of the included studies. Qualitative synthesis analyses were performed on the selected studies. 331 articles were retrieved, and 4 were finally selected. All four studies investigated the association between postnatal ETS and CIMT in children, and three of them reported a statistically significant positive association. Three studies investigated the association between prenatal maternal ETS and CIMT, and one of the three found a positive association. Two studies explored the association between postnatal maternal ETS and CIMT, one reported a positive association. Two studies used serum cotinine measurement to quantify ETS and demonstrated potential dose-response relationship with CIMT. ETS exposure may play an independent role in the development of cardiovascular risks in healthy children and adolescents. In the consideration of the great burden of respiratory and cardiovascular diseases, there is an urgent need of effective surveillance for paediatric population's ETS exposure to reduce smoke exposure.

Parental Knowledge, Attitude, and Practice on Tobacco Use, Smoking Cessation, and Children's Environmental Tobacco Smoke Exposure.

Background: Environmental tobacco smoke (ETS) exposure in children ranks one of the major public health problems in our time. Poor parental knowledge, attitude, and practice (KAP) on ETS often contribute to worse exposure of the kids. Thus, we aimed to document parental KAP regarding tobacco use, smoking cessation and children's ETS exposure, and to analyse how knowledge and attitude relate to practice. Methods: Self-administered KAP questionnaires were distributed to smoking parents recruited from the pediatric unit at the Prince of Wales Hospital, which provides pediatric service to a population of 1.2 million in Hong Kong. The 60-item questionnaire had a range of 0-38 for knowledge, 0-44 for attitude, and 0-40 for practice. Descriptive analyses were performed for KAP response, regression analyses were performed for the exploration of associations and identification of predictive indicators. Results: 145 smoking parents (mean age: 38.0 ± 6.7 yrs.; male: 85.5%) were included. Less than half (39.3%) of them reported a smoke-free policy at home. Among those parents who had private cars, less than half (45.2%) of them had smoke-free policy in their car that they never smoked in the car. Only 25.5% of the participants correctly answered ≥70% of the knowledge questions, and 11.8 % of the participants gave favorable responses to ≥70% of the attitude questions. The total knowledge and the total attitudes score were positively associated (r = 0.49, 95% CI: 0.35-0.79, p < 0.001), yet they were only modestly correlated with parental practice on children's ETS exposure. By multivariate regressions, potential predictive factors for more favorable parental KAP included higher household income, lower parental nicotine dependence level and breastfeeding practice. Conclusions: Parental KAP related to tobacco use and children's ETS exposure needs improvement to address the significant gap between recommended and actual practice. The weak association between knowledge and practice suggested that parental education alone is not adequate to combat ETS exposure in children.

Household environmental tobacco smoke exposure in healthy young children in Hong Kong: Prevalence and risk factors.

BACKGROUND: Environmental tobacco smoke (ETS) exposure attributable respiratory illness burden is huge in paediatric population. Understanding the epidemiology of ETS exposure is important to guide health promotion planning. Therefore, we designed this study to determine the prevalence of household ETS exposure in healthy young children under 2 years of age in Hong Kong, and to explore risk factors associated with the exposure. Our secondary goal was to characterise children's exposure profile to maternal smoking. METHODS: A secondary analysis was performed based on the data collected from our 2013-2014 territory-wide cross-sectional pneumococcal carriage surveillance study, with a sample size of 1541. We conducted descriptive analysis for exposure prevalence, univariate and multivariate analysis for identification of risk factors. RESULTS: 1541 children (mean age: 11.2 ± 6.4 months, male: 50.7%) were included in the analysis. The overall prevalence of current household ETS exposure was 31.5%, prevalence of prenatal and postnatal maternal smoking was 3.5% and 1.6% respectively. Independent factors associated with children's ETS exposure were: never breastfed (AOR: 1.48, 95% CI: 1.13-1.93, p = 0.004); prenatal maternal smoking (AOR: 7.46, 95% CI: 2.73-20.39, p< 0.001); overcrowding of household living place (AOR: 3.17, 95% CI: 2.02-4.96, P< 0.001); lower household income (AOR: 1.34, 95% CI: 1.04-1.72, p = 0.02). Interestingly, children residing in Kowloon (AOR: 1.66, 95% CI: 1.19-2.33, p = 0.003) and New Territories West (AOR: 1.54, 95% CI: 1.11-2.15, p = 0.01) were associated with exposure compared with children residing in Hong Kong Island. CONCLUSION: Exposure to household ETS is prevalent among Hong Kong young children, particularly in children with maternal unfavourable behaviour and lower socioeconomic status. The identified risk factors should be considered while tobacco control interventions and legislations are planned.

Associations of household environmental tobacco smoke exposure with respiratory symptoms and utilisation of medical services in healthy young children in Hong Kong.

INTRODUCTION: Young children are especially vulnerable to environmental tobacco smoke (ETS) exposure. This study was carried out to determine whether household ETS exposure was associated with respiratory symptoms and medical service utilisation among Hong Kong healthy children in their first eighteen months of age. METHODS: A secondary analysis was done on the data obtained from our previous cross-sectional territory-wide pneumococcal carriage surveillance study in Hong Kong in 2013-2014. All measures were reported by caregivers. Univariable and multivariable analyses were performed to examine the associations between ETS exposure and outcome measures. Covariates included children's sex, age, body mass index z score, history of breastfeeding, gestational age at birth, birthweight, maternal age, living region, overcrowding of living area, household income, child care attendance, and presence of siblings. Additional adjustment for season and households' respiratory symptoms were made to ascertain the association between ETS and children's respiratory symptoms. RESULTS: The analysis included 1541 children (mean age: 11.2 ± 6.4 months; males: 50.7%). Current household ETS exposure (AOR=1.30; 95% CI: 1.00- 1.66; p=0.050) and postnatal maternal smoking (AOR=2.21; 95% CI: 1.06-4.64; p=0.035) were independently and significantly associated with all-cause doctor consultation in the past 3 months. Children living with more than one household smoker were more likely to have all-cause doctor consultation compared with the non-exposed children (AOR=1.70; 95% CI: 1.04-2.77, p=0.028). Postnatal maternal smoking was associated with all-cause hospitalisation in the past 3 months (AOR=2.48; 95% CI: 1.05-5.86; p=0.039). Children living in a household, where the daily consumption by household smokers was more than 20 cigarettes, were more likely to have respiratory symptoms compared with non-exposed children (AOR=1.99; 95% CI: 1.12-3.52; p=0.016). CONCLUSIONS: Household ETS exposure in young children was associated with respiratory symptoms and all-cause outpatient or inpatient medical service utilisation. The associations were potentially dose-dependent.