A male germ-cell-specific ribosome controls male fertility.

Ribosomes are highly sophisticated translation machines that have been demonstrated to be heterogeneous in the regulation of protein synthesis1,2. Male germ cell development involves complex translational regulation during sperm formation3. However, it remains unclear whether translation during sperm formation is performed by a specific ribosome. Here we report a ribosome with a specialized nascent polypeptide exit tunnel, RibosomeST, that is assembled with the male germ-cell-specific protein RPL39L, the paralogue of core ribosome (RibosomeCore) protein RPL39. Deletion of RibosomeST in mice causes defective sperm formation, resulting in substantially reduced fertility. Our comparison of single-particle cryo-electron microscopy structures of ribosomes from mouse kidneys and testes indicates that RibosomeST features a ribosomal polypeptide exit tunnel of distinct size and charge states compared with RibosomeCore. RibosomeST predominantly cotranslationally regulates the folding of a subset of male germ-cell-specific proteins that are essential for the formation of sperm. Moreover, we found that specialized functions of RibosomeST were not replaceable by RibosomeCore. Taken together, identification of this sperm-specific ribosome should greatly expand our understanding of ribosome function and tissue-specific regulation of protein expression pattern in mammals.

Quantitative Phosphoproteomic Profiling of Mouse Sperm Maturation in Epididymis Revealed Kinases Important for Sperm Motility.

Transcriptionally and translationally silent sperm undergo functional maturation during epididymis traverse, which provides sperm ability to move and is crucial for successful fertilization. However, the molecular mechanisms governing sperm maturation remain poorly understood, especially at the protein post-translational modification level. In this study, we conducted a comprehensive quantitative phosphoproteomic analysis of mouse epididymal sperm from different regions (caput, corpus, and cauda) to unveil the dynamics of protein phosphorylation during sperm maturation. We identified 6447 phosphorylation sites in 1407 phosphoproteins, and 345 phosphoproteins were differentially phosphorylated between caput and cauda sperm. Gene ontology and KEGG pathway analyses showed enrichment of differentially phosphorylated proteins in energy metabolism, sperm motility, and fertilization. Kinase substrate network analysis followed by inhibition assay and quantitative phosphoproteomics analysis showed that TSSK2 kinase is important for sperm motility and progressive motility. This study systemically characterized the intricate phosphorylation regulation during sperm maturation in the mouse epididymis, which can be a basis to elucidate sperm motility acquisition, and to offer potential targets for male contraception and the treatment of male infertility.

Lectin-Based SP3 Technology Enables N-Glycoproteomic Analysis of Mouse Oocytes.

N-glycosylation is one of the most universal and complex protein post-translational modifications (PTMs), and it is involved in many physiological and pathological activities. Owing to the low abundance of N-glycoproteins, enrichment of N-glycopeptides for mass spectrometry analysis usually requires a large amount of peptides. Additionally, oocyte protein N-glycosylation has not been systemically characterized due to the limited sample amount. Here, we developed a glycosylation enrichment method based on lectin and a single-pot, solid-phase-enhanced sample preparation (SP3) technology, termed lectin-based SP3 technology (LectinSP3). LectinSP3 immobilized lectin on the SP3 beads for N-glycopeptide enrichment. It could identify over 1100 N-glycosylation sites and 600 N-glycoproteins from 10 µg of mouse testis peptides. Furthermore, using the LectinSP3 method, we characterized the N-glycoproteome of 1000 mouse oocytes in three replicates and identified a total of 363 N-glycosylation sites from 215 N-glycoproteins. Bioinformatics analysis revealed that these oocyte N-glycoproteins were mainly enriched in cell adhesion, fertilization, and sperm-egg recognition. Overall, the LectinSP3 method has all procedures performed in one tube, using magnetic beads. It is suitable for analysis of a low amount of samples and is expected to be easily adaptable for automation. In addition, our mouse oocyte protein N-glycosylation profiling could help further characterize the regulation of oocyte functions.

Bronchopulmonary dysplasia: analysis and validation of ferroptosis-related diagnostic biomarkers and immune cell infiltration features.

BACKGROUND: Early and precise diagnosis of bronchopulmonary dysplasia (BPD) is essential to improve the prognosis of preterm infants with BPD. Studying ferroptosis-related genes for diagnostic markers of BPD was the objective of this study. METHODS: Using the GEO database and the FerrDb database, we obtained the GSE32472 dataset and screened the ferroptosis-related differentially expressed mRNAs (FRDE-mRNAs). By using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), possible biological functions and pathways were identified for FRDE-mRNAs. Three machine learning algorithms (LASSO, SVM-RFE, Random Forest) were used to recognize hub genes, as well as CIBERSORT for exploring the immune landscape of BPD and controls. Functional predictions for hub genes were made using single-gene gene set enrichment analysis (GSEA). RESULTS: Twenty three FRDE-mRNAs were obtained and were mainly involved in autophagy, fatty acid metabolism and ferroptosis. The four hub genes (LPIN1, ACADSB, WIPI1 and SLC7A11) screened were utilized to construct a diagnostic nomogram. The receiver operating characteristic (ROC) curves and calibration curves demonstrateld that the nomogram exhibited good predictive performance. Eight types of immune cell markers differed significantly between BPD and controls. CONCLUSION: We developed a diagnostic model for BPD, which could facilitate the early diagnosis and timely intervention of BPD. IMPACT: The role of ferroptosis in bronchopulmonary dysplasia is rarely reported. The ferroptosis-related genes (LPIN1, ACADSB, WIPI1 and SLC7A11) we identified could serve as early diagnostic biomarkers for BPD. Immune cell infiltration features in BPD and signaling pathways associated with marker genes give new insight into the disease process and provide a basis for further research.

Regulation of Miwi-mediated mRNA stabilization by Ck137956/Tssa is essential for male fertility.

BACKGROUND: Sperm is formed through spermiogenesis, a highly complex process involving chromatin condensation that results in cessation of transcription. mRNAs required for spermiogenesis are transcribed at earlier stages and translated in a delayed fashion during spermatid formation. However, it remains unknown that how these repressed mRNAs are stabilized. RESULTS: Here we report a Miwi-interacting testis-specific and spermiogenic arrest protein, Ck137956, which we rename Tssa. Deletion of Tssa led to male sterility and absence of sperm formation. The spermiogenesis arrested at the round spermatid stage and numerous spermiogenic mRNAs were down-regulated in Tssa-/- mice. Deletion of Tssa disrupted the localization of Miwi to chromatoid body, a specialized assembly of cytoplasmic messenger ribonucleoproteins (mRNPs) foci present in germ cells. We found that Tssa interacted with Miwi in repressed mRNPs and stabilized Miwi-interacting spermiogenesis-essential mRNAs. CONCLUSIONS: Our findings indicate that Tssa is indispensable in male fertility and has critical roles in post-transcriptional regulations by interacting with Miwi during spermiogenesis.

Distribution of ocular biometric parameters and optimal model of anterior chamber depth regression in 28,709 adult cataract patients in China using swept-source optical biometry.

BACKGROUND: The purpose of this study was to evaluate the ocular biometric parameters in adult cataract patients from China and create an anterior chamber depth (ACD) regression model. METHODS: The ocular biometric records of 28,709 right eyes of cataract surgery candidates who were treated at Aier Eye Hospitals in nine cities from 2018 to 2019 were retrospectively analyzed. All measurements were taken with IOLMaster 700. We included patients who were at least 40 years old and were diagnosed with cataract. RESULTS: The mean age of the patients was 68.6 ± 11.0 years. The mean values recorded were as follows: axial length (AL), 24.17 ± 2.47 mm; mean keratometry (Km) value, 44.26 ± 1.70 D; corneal astigmatism (CA), 1.06 ± 0.96 D; ACD, 3.02 ± 0.45 mm; lens thickness (LT), 4.52 ± 0.45 mm; central corneal thickness (CCT), 0.534 ± 0.04 mm; and white to white (WTW) corneal diameter, 11.64 ± 0.46 mm. ACD correlated positively with AL (Spearman coefficient, 0.544) and WTW (0.300), but negatively with LT (-0.660) and age (-0.285) (all P < 0.01). In the multivariate regression analysis of ACD, which included LT, AL, WTW, sex, Km, CCT, and age, there was a reasonable prediction with adjusted R2 = 0.641. CONCLUSIONS: Cataract patients with longer AL and wider WTW have deeper ACD. With increasing age and lens thickening ACD becomes shallower. Based on the standardized coefficients of ACD multivariate regression analysis from the study, LT is the main factor that affects ACD, and is followed by AL.

STYXL1 regulates CCT complex assembly and flagellar tubulin folding in sperm formation.

Tubulin-based microtubule is a core component of flagella axoneme and essential for sperm motility and male fertility. Structural components of the axoneme have been well explored. However, how tubulin folding is regulated in sperm flagella formation is still largely unknown. Here, we report a germ cell-specific co-factor of CCT complex, STYXL1. Deletion of Styxl1 results in male infertility and microtubule defects of sperm flagella. Proteomic analysis of Styxl1-/- sperm reveals abnormal downregulation of flagella-related proteins including tubulins. The N-terminal rhodanese-like domain of STYXL1 is important for its interactions with CCT complex subunits, CCT1, CCT6 and CCT7. Styxl1 deletion leads to defects in CCT complex assembly and tubulin polymerization. Collectively, our findings reveal the vital roles of germ cell-specific STYXL1 in CCT-facilitated tubulin folding and sperm flagella development.

Hospital mortality of blunt abdominal aortic injury (BAAI): a systematic review and meta-analysis.

BACKGROUND: Studies on the mortality of blunt abdominal aortic injury (BAAI) are rare and have yielded inconsistent results. In the present study, we aimed to quantitatively analyse the retrieved data to more accurately determine the hospital mortality of BAAI. METHODS: The Excerpta Medica Database, PubMed, Web of Science and Cochrane Library databases were searched to identify relevant publications without date restrictions. The overall hospital mortality (OHM) of BAAI patients was set as the primary outcome measure. English publications with data that met the selection criteria were included. The quality of all included studies was assessed by the Joanna Briggs Institute checklist and the American Agency for Health Care Quality and Research's cross-sectional study quality evaluation items. After data extraction, a meta-analysis of the Freeman-Tukey double arcsine transformation of data was performed using the Metaprop command in Stata 16 software. Heterogeneity was assessed and reported as a percentage using the I2 index value and as a P value using the Cochrane Q test. Various methods were used to determine the sources of heterogeneity and to analyse the sensitivity of the computation model. RESULTS: Of the 2147 references screened, 5 studies that involved 1593 patients met the selection criteria and were included. There were no low-quality references after assessment. One study that only included 16 juvenile BAAI patients was excluded from the meta-analysis of the primary outcome measure due to high heterogeneity. Due to the low heterogeneity (I2 = 47.6%, P = 0.126 for Q test) that was observed after using the random effects model, the fixed model was subsequently used to pool the effect sizes of the remaining four studies, thus yielding an OHM of 28.8% [95% confidence interval (CI) 26.5-31.1%]. The stability of the model was verified by sensitivity analysis, and Egger's test (P = 0.339) indicated a low level of publication bias. In addition, we also performed meta-analyses and obtained a pooled hospital mortality of operation (13.5%, 95% CI 8.0-20.0%), a pooled hospital mortality of non-operation (28.4%, 95% CI 25.9-31.0%), and a pooled rate of aortic rupture (12.2%, 95% CI 7.0-18.5%) of BAAI. CONCLUSIONS: The present study indicated that BAAI has an OHM of 28.8%, indicating that this disease deserves more attention and research.

Meta-analysis of outcomes from drug-eluting stent implantation in infrapopliteal arteries.

BACKGROUND: Percutaneous drug-eluting stent implantation (DESI) is an emerging and promising treatment modality for infrapopliteal artery diseases (IPADs). This systematic review and meta-analysis summarizes and quantitatively analyzes the outcomes of DESI in IPADs considering the hazard ratio (HR), which is a more accurate and appropriate outcome measure than the more commonly used relative risk and odds ratio. AIM: To explore the superiority of drug-eluting stents (DESs) vs traditional treatment modalities for IPADs. METHODS: The following postoperative indicators were the outcomes of interest: All-cause death (ACD)-free survival, major amputation (MA)-free survival, target lesion revascularization (TLR)-free survival, adverse event (AE)-free survival, and primary patency (PP) survival. The outcome measures were then compared according to their respective HRs with 95% confidence intervals (CIs). The participants were human IPAD patients who underwent treatments for infrapopliteal lesions. DESI was set as the intervention arm, and traditional percutaneous transluminal angioplasty (PTA) with or without bare metal stent implantation (BMSI) was set as the control arm. A systematic search in the Excerpta Medica Database (Embase), PubMed, Web of Science, and Cochrane Library was performed on November 29, 2022. All controlled studies published in English with sufficient data on outcomes of interest for extraction or conversion were included. When studies did not directly report the HRs but gave a corresponding survival curve, we utilized Engauge Digitizer software and standard formulas to convert the information and derive HRs. Then, meta-analyses were conducted using a random-effects model. RESULTS: Five randomized controlled trials and three cohort studies involving 2639 participants were included. The ACD-free and MA-free survival HR values for DESI were not statistically significant from those of the control treatment (P > 0.05); however, the HR values for TLR-free, AE-free, and PP-survival differed significantly [2.65 (95%CI: 1.56-4.50), 1.57 (95%CI: 1.23-2.01), and 5.67 (95%CI: 3.56-9.03), respectively]. CONCLUSION: Compared with traditional treatment modalities (i.e., PTA with or without BMSI), DESI for IPADs is superior in avoiding TLR and AEs and maintaining PP but shows no superiority or inferiority in avoiding ACD and MA.

A systematic review of blunt abdominal aortic injury and analysis of predictors of death.

At present, research on blunt abdominal aortic injury (BAAI) is limited, with the majority being case reports. Consequently, there is a significant knowledge gap concerning this condition. To address this, we conducted a systematic review by extensively searching major databases. We included all literature that provided individual (non-identifiable) data on BAAI patients, irrespective of the study design. Furthermore, we undertook regression analyses to identify predictors of death after BAAI. The search yielded 2,099 results, leading to the inclusion of 102 case reports and one conference abstract. Using the Joanna Briggs Institute (JBI) checklist for assessment, all studies were deemed of medium to high quality. In total, 133 patients were included, with a median age of 34 years, and 73.7% being male. The predominant clinical manifestation was pain, reported in 65.6% of patients. The most frequently observed aortic lesion severity was grade A (intimal tear or intramural hematoma) at 46.9%, and the most common lesion location was zone III (infrarenal aorta) in 88.3% of cases.  The overall mortality after BAAI was 15.3%. Multivariate regression analyses revealed the following predictors of death after BAAI: lower limb ischemia (relative risk [RR] = 7.137, 95% confidence interval [CI] 1.154 - 44.161), cardiopulmonary arrest (RR = 10.250, 95% CI 1.452 - 72.344), and injuries to body parts other than the abdomen and lumbar spine (RR = 2.593, 95% CI 1.189 - 5.655). In conclusion, this review provides a detailed quantitative summary of BAAI's clinical manifestations, diagnosis, treatment, and prognosis, emphasizing its high mortality rate and identifying three critical variables as predictors of death.

Meta-analysis of outcomes from drug-eluting stent implantation in femoropopliteal arteries.

OBJECTIVE: In recent years, studies of drug-eluting stent (DES) for femoropopliteal artery diseases (FPADs) have been gradually published. To explore whether this type of stent is superior to the traditional bare metal stent (BMS), we performed this study. METHODS: A systematic search for randomized controlled trials (RCTs) in Excerpta Medica Database (Embase), PubMed, Web of Science (WOS), and Cochrane Library was performed on November 29, 2022. We innovatively adopted the hazard ratio (HR), the most appropriate indicator, as a measure of the outcomes that fall under the category of time-to-event data. The HRs was extracted directly or indirectly. Then, the meta-analyses using random effects model were performed. The bias risks of included papers were assessed by the Cochrane Risk of Bias 2.0 tool. This study was registered on the PROSPER platform (CRD42023391944) and not funded. RESULTS: Seven RCTs involving 1,889 participants were found. After pooled analyses, we obtained results without propensity on each of the following 3 outcomes of interest: in-stent restenosis (ISR) -free survival, primary patency (PP) survival, and target lesion revascularization (TLR) -free survival (P >0.05, respectively). Because the results of pooled analyses of the other two outcomes of interest (all-cause death free survival and clinical benefit survival) had high heterogeneity both, they were not accepted by us. CONCLUSION: For FPADs, the DES has not yet demonstrated superiority or inferiority to BMS, in the ability to maintain PP, avoid ISR and TLR.

The cognitive dysfunction of claustrum on Alzheimer's disease: A mini-review.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by cognitive deficits and dementia. AD entails predominant pathological characteristics including amyloid beta (Aß) plaque formation, neurofibrillary entanglements, and brain atrophy, which gradually result in cognitive dysfunctions. Studies showed that these pathological changes are found in a myriad of brain structures, including the claustrum (CLA), a nucleus that penetrates deeply into the brain and is extensively interconnected to various brain structures. The CLA modulates many aspects of cognitive functions, with attention, executive function, visuospatial ability, language, and memory in particular. It is also implicated in multiple neuropsychiatric disorders, of which one worthy of particular attention is AD-related cognitive impairments. To inspire novel AD treatment strategies, this review has summarized the CLA functionality in discriminative cognitive dysfunctions in AD. And then propose an array of potential mechanisms that might contribute to the cognitive impairments caused by an abnormal CLA physiology. We advocate that the CLA might be a new promising therapeutic target in combination with existing anti-AD drugs and brain stimulation approaches for future AD treatment.

At-home disposal practices of used insulin needles among patients with diabetes in China: A single-center, cross-sectional study.

Background: Most insulin injections for people with diabetes are administered at home, thus generating many used needles. Unsafe disposal of these at-home needles can lead to needle stick injuries, blood-borne disease transmission, and environmental contamination. Previous studies have shown varying results on the prevalence of and factors associated with safe sharps disposal practices of people with diabetes. Objective: To assess the prevalence of and the factors associated with the safe disposal of used insulin needles among patients with diabetes. Methods: We collected data from 271 insulin-using patients at a tertiary care hospital in China. A self-designed instrument was used to assess sociodemographic data, disease- and treatment-related characteristics, sharps disposal practices, education on diabetes self-management and sharps disposal, and awareness of the potential risks associated with unsafe sharps disposal. Multivariate logistic regression analysis was used to explore factors associated with safe sharps disposal practices. Results: Only 10.3% (28/271) of participants disposed of used at-home insulin needles in a safe manner, and 14.8% (45/271) of participants had received previous instruction on sharps disposal. Previous sharps disposal instruction (AOR = 4.143, 95% CI = 1.642-10.450) and awareness of the risk of blood-borne pathogen transmission (AOR = 3.064, 95% CI = 1.332-7.046) were associated with safe disposal of used insulin needles. Conclusion: In our study, the prevalence of safe sharps disposal practices was low, and a minority of respondents had received previous instruction on sharps disposal. Participants who had previously received instruction and were aware of the risk of blood-borne pathogen transmission were more likely to handle sharps safely. Our study findings suggest that health care professionals should pay attention to sharps disposal practices of patients with diabetes and conduct diabetes education programs that include information on safe sharps disposal methods and potential hazards of unsafe sharps disposal.

Postpartum women's views on human milk banking in a city in Southeast China: a cross-sectional survey.

BACKGROUND: Donor human milk is the best alternative for preterm infants when their mother's own milk is insufficient or unavailable. The development of human milk banks in China started late, and in most of these banks, the amount of donor human milk is insufficient for clinical demand. Moreover, many mothers are reluctant to use donor human milk due to safety concerns. It is important to understand the potential supply and demand of donor human milk before establishing a new human milk bank. This study aimed to understand women's acceptance of human milk banking in Wenzhou, southeastern China. METHODS: A cross-sectional study was conducted in three community health centers in Wenzhou, southeast China, in December 2020. Data were collected from 305 postpartum women selected through convenience sampling. Sociodemographic, perinatal and breastfeeding characteristics, awareness and knowledge of human milk banking and willingness to donate human milk, and to accept donor human milk were assessed. Multivariable logistic regression analysis was used to explore independent predictors of willingness to donate human milk and to accept donor human milk. RESULTS: Only 17% (52/305) of our participants had heard of human milk banking prior to this survey. The prevalence of willingness to donate human milk and use donor human milk in our study was 73.4% (224/305) and 44.6% (136/305), respectively. Employment (adjusted odds ratio [AOR] 2.30; 95% confidence interval [CI] 1.17, 4.50) and human milk banking knowledge (AOR 1.23; 95% CI 1.12, 1.35) were independent predictors of willingness to donate human milk. Monthly household income in the previous year (AOR 2.18; 95% CI 1.17, 4.06), awareness of human milk banking (AOR 2.41; 95% CI 1.24, 4.67) and knowledge of human milk banking (AOR 1.22; 95% CI 1.11, 1.35) were significantly associated with willingness to accept donor human milk. CONCLUSIONS: In our study, awareness of human milk banks among women in the first year postpartum was low. More mothers were willing to donate human milk than to use donor human milk to feed their children. In our study, knowledge of human milk banking was a predictor of both willingness to donate human milk and willingness to use donor human milk. Programs with detailed information on human milk banking are needed to help mothers improve their knowledge and increase acceptance of human milk banking.

Proteomic profiling of the endogenous peptides of MRSA and MSSA.

Staphylococcus aureus is a Gram-positive bacterium that can cause diverse skin and soft tissue infections. Methicillin-resistant Staphylococcus aureus (MRSA) can cause more severe infections than methicillin-susceptible Staphylococcus aureus (MSSA). Nevertheless, the physiological and metabolic regulation of MSSA and MRSA has not been well studied. In light of the increased interest in endogenous peptides and recognition of the important roles that they play, we studied the endogenous peptidome of MSSA and MRSA. We identified 1,065 endogenous peptides, among which 435 were differentially expressed (DE), with 292 MSSA-abundant endogenous peptides and 35 MRSA-abundant endogenous peptides. MSSA-abundant endogenous peptides have significantly enriched "VXXXK" motif of at the C-terminus. MSSA-abundant endogenous peptides are involved in penicillin-binding and immune responses, whereas MRSA-abundant endogenous peptides are associated with antibiotic resistance and increased toxicity. Our characterization of the peptidome of MSSA and MRSA provides a rich resource for future studies to explore the functional regulation of drug resistance in S. aureus and may also help elucidate the mechanisms of its pathogenicity and the development of treatments.

Comparative Analysis of Visual Performance and Optical Quality with a Rotationally Asymmetric Multifocal Intraocular Lens and an Apodized Diffractive Multifocal Intraocular Lens.

PURPOSE: To compare the short-term visual outcomes and intraocular optical performance of a rotationally asymmetric multifocal intraocular lens (MIOL) (SBL-3, Lenstec, Inc., Christ Church, Barbados) and an apodized diffractive MIOL (the Acrysof IQ ResTOR SN6AD1, Alcon Laboratories, Inc., Fort Worth, Texas, United States). METHODS: A prospective, comparative, nonrandomized, and single-center study. Sixty-eight age-related cataract patients (81 eyes) after phacoemulsification cataract surgery and in-the-bag MIOL implantation were enrolled. Thirty-eight eyes received SBL-3, and 43 eyes received SN6AD1. Ophthalmological evaluation included uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), corrected distance visual acuity (CDVA), modulation transfer function (MTF), Strehl ratio (SR), intraocular aberrations (4 mm optical zone), and defocus curve at 3 months postoperatively. The Chinese version of the visual function index-14 (VF-12-CN) and spectacle independence were assessed in all patients. RESULTS: There was no statistically significant difference between groups in postoperative UDVA (p = 0.186). Postoperative UIVA and UNVA were significantly better for the SBL-3 group than for the SN6AD1 group (p < 0.01). Statistically significant differences were revealed in defocus levels from -3.50 D to -4.00 D with better visual acuities for the SBL-3 group (p < 0.01). For intraocular optical quality outcomes, statistically significant differences between groups were observed in RMS of intraocular total aberrations, coma, and trefoil high-order aberrations, presenting significantly higher values of these parameters in the eyes of the SBL-3 group (p < 0.01). Statistically significant differences were revealed in the MTF values at spatial frequencies of 5 and 10 cycles/degree between groups. There were no significant differences in scores of VF-12-CN, and spectacle independence between the groups (p > 0.05). CONCLUSIONS: Both MIOLs were able to successfully restore visual function after cataract surgery. SBL-3 provided better UIVA and UNVA with a wider range of intermediate vision.