The common link between sleep apnea syndrome and osteoarthritis: a literature review.

Patients with Osteoarthritis (OA) often also suffer from Sleep Apnea Syndrome (SAS), and many scholars have started to notice this link, although the relationship between the two is still unclear. In this review, we aim to summarize the current literature on these two diseases, integrate evidence of the OA and OSA connection, explore and discuss their potential common mechanisms, and thus identify effective treatment methods for patients with both OA and SAS. Some shared characteristics of the two conditions have been identified, notably aging and obesity as mutual risk factors. Both diseases are associated with various biological processes or molecular pathways, including mitochondrial dysfunction, reactive oxygen species production, the NF-kB pathway, HIF, IL-6, and IL-8. SAS serves as a risk factor for OA, and conversely, OA may influence the progression of SAS. The effects of OA on SAS are underreported in the literature and require more investigation. To effectively manage these patients, timely intervention for SAS is necessary while treating OA, with weight reduction being a primary requirement, alongside combined treatments such as Continuous positive airway pressure (CPAP) and medications. Additionally, numerous studies in drug development are now aimed at inhibiting or clearing certain molecular pathways, including ROS, NF-KB, IL-6, and IL-8. Improving mitochondrial function might represent a viable new strategy, with further research into mitochondrial updates or transplants being essential.

Mechanisms of minor pole-mediated spindle bipolarization in human oocytes.

Spindle bipolarization, the process of a microtubule mass transforming into a bipolar spindle, is a prerequisite for accurate chromosome segregation. In contrast to mitotic cells, the process and mechanism of spindle bipolarization in human oocytes remains unclear. Using high-resolution imaging in more than 1800 human oocytes, we revealed a typical state of multipolar intermediates that form during spindle bipolarization and elucidated the mechanism underlying this process. We found that the minor poles formed in multiple kinetochore clusters contribute to the generation of multipolar intermediates. We further determined the essential roles of HAUS6, KIF11, and KIF18A in spindle bipolarization and identified mutations in these genes in infertile patients characterized by oocyte or embryo defects. These results provide insights into the physiological and pathological mechanisms of spindle bipolarization in human oocytes.

Altered sleep onset transition in depression: Evidence from EEG activity and EEG functional connectivity analyses.

OBJECTIVE: Sleep disorders constitute a principal diagnostic criterion for depression, potentially reflecting the abnormal persistence of brain activity during the sleep onset (SO) transition. Here, we sought to explore the differences in the dynamic changes in the EEG activity and the EEG functional connectivity (FC) during the SO transition in depressed patients. METHODS: Overnight polysomnography recordings were obtained from thirty-two depressed patients and thirty-three healthy controls. The multiscale permutation entropy (MSPE) and EEG relative power were extracted to characterize EEG activity, and weighted phase lag index (WPLI) was calculated to characterize EEG FC. RESULTS: The intergroup differences in EEG activity of relative power and MSPE were reversed near SO, which attributed to slower rates of change among depressed patients. Regarding the characteristics of the EEG FC network, depressed patients exhibited significantly higher inter-hemispheric and interregional WPLI values in both delta and alpha bands throughout the SO transition, concomitant with different dynamic properties in the delta band FC. During the process after SO, patients exhibited increased inter-hemispheric long-range links, whereas controls showed more intra-hemispheric ones. Finally, we found significant correlations in the dynamic changes between different EEG measures. CONCLUSIONS: Our research revealed that the abnormal changes during the SO transition in depressed patients were manifested in both homeostatic and dynamic aspects, which were reflected in EEG FC and EEG activity, respectively. SIGNIFICANCE: These findings may elucidate the mechanism underlying sleep disorders in depression from the perspective of neural activity.

Insulin promotes the bone formation capability of human dental pulp stem cells through attenuating the IIS/PI3K/AKT/mTOR pathway axis.

BACKGROUND: Insulin has been known to regulate bone metabolism, yet its specific molecular mechanisms during the proliferation and osteogenic differentiation of dental pulp stem cells (DPSCs) remain poorly understood. This study aimed to explore the effects of insulin on the bone formation capability of human DPSCs and to elucidate the underlying mechanisms. METHODS: Cell proliferation was assessed using a CCK-8 assay. Cell phenotype was analyzed by flow cytometry. Colony-forming unit-fibroblast ability and multilineage differentiation potential were evaluated using Toluidine blue, Oil red O, Alizarin red, and Alcian blue staining. Gene and protein expressions were quantified by real-time quantitative polymerase chain reaction and Western blotting, respectively. Bone metabolism and biochemical markers were analyzed using electrochemical luminescence and chemical colorimetry. Cell adhesion and growth on nano-hydroxyapatite/collagen (nHAC) were observed with a scanning electron microscope. Bone regeneration was assessed using micro-CT, fluorescent labeling, immunohistochemical and hematoxylin and eosin staining. RESULTS: Insulin enhanced the proliferation of human DPSCs as well as promoted mineralized matrix formation in a concentration-dependent manner. 10- 6 M insulin significantly up-regulated osteogenic differentiation-related genes and proteins markedly increased the secretion of bone metabolism and biochemical markers, and obviously stimulated mineralized matrix formation. However, it also significantly inhibited the expression of genes and proteins of receptors and receptor substrates associated with insulin/insulin-like growth factor-1 signaling (IIS) pathway, obviously reduced the expression of the phosphorylated PI3K and the ratios of the phosphorylated PI3K/total PI3K, and notably increased the expression of the total PI3K, phosphorylated AKT, total AKT and mTOR. The inhibitor LY294002 attenuated the responsiveness of 10- 6 M insulin to IIS/PI3K/AKT/mTOR pathway axis, suppressing the promoting effect of insulin on cell proliferation, osteogenic differentiation and bone formation. Implantation of 10- 6 M insulin treated DPSCs into the backs of severe combined immunodeficient mice and the rabbit jawbone defects resulted in enhanced bone formation. CONCLUSIONS: Insulin induces insulin resistance in human DPSCs and effectively promotes their proliferation, osteogenic differentiation and bone formation capability through gradually inducing the down-regulation of IIS/PI3K/AKT/mTOR pathway axis under insulin resistant states.

Effect of lumbosacral transitional vertebra on developmental alterations of the hip: a quantitative investigation of the lumbo-pelvic-hip complex via whole-body computed tomography.

Background: Lumbosacral transitional vertebra (LSTV) is a common spinal variant, with the reported prevalence varying from 8.1% to 36%. LSTV has been shown to alter the lumbo-pelvic parameters and reduce the benefits of total hip arthroplasty, but the specific effects of LSTV on hip development remain unclear. The aim of this study was thus to investigate the impact of LSTV on developmental alterations of the hip. Methods: A total of 310 individuals were categorized into three groups according to whole-body computed tomography (CT) imaging: a group with sacralization of 23 presacral vertebrae (PSV) (n=102), a group with lumbarization of 25 PSV (n=108), and a normal control group with 24 PSV (n=100). Quantitative parameters of the lumbo-pelvic-hip complex (LPHC) including lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), axial and sagittal acetabular anteversion angle (AAA), center-edge (CE) angle, Sharp angle, and femoral neck-shaft angle (FNSA) were measured and analyzed. Statistical analyses were used to compare the differences of these quantitative parameters among the three groups and to assess the relationship between hip and lumbar-pelvic parameters. Results: Significant differences between each pair of three groups and the LSTV subgroups were only found in the sagittal AAA (left side: P=0.008; right side: P<0.001), with no differences found for the other parameters. Compared to the normal group (24 PSV), both the 23 PSV and 25 PSV groups exhibited increased values in the sagittal AAA, especially in the right side of the 23 PSV group. Only the sagittal AAA showed low-to-moderate positive correlations with pelvic parameters of PI (r=0.195-0.429; P=0.001-0.08) and PT (r=0.239-0.605; P=0.001-0.03). Conclusions: Variations of LSTV are correlated with the hip anatomical development via LPHC transmission and may potentially reduce the sagittal acetabular coverage, particularly in the 23 PSV subtype on the right side.

Acupuncture plus topiramate placebo versus topiramate plus sham acupuncture for the preventive treatment of chronic migraine: A single-blind, double-dummy, randomized controlled trial.

BACKGROUND: Acupuncture has been used for the treatment of chronic migraine, but high-quality evidence is scarce. We aimed to evaluate acupuncture's efficacy and safety compared to topiramate for chronic migraine. METHODS: This double-dummy randomized controlled trial included participants aged 18-65 years diagnosed with chronic migraine. They were randomly assigned (1:1) to receive acupuncture (three sessions/week) plus topiramate placebo (acupuncture group) or topiramate (50-100 mg/day) plus sham acupuncture (topiramate group) over 12 weeks, with the primary outcome being the mean change in monthly migraine days during weeks 1-12. RESULTS: Of 123 screened patients, 60 (mean age 45.8, 81.7% female) were randomly assigned to acupuncture or topiramate groups. Acupuncture demonstrated significantly greater reductions in monthly migraine days than topiramate (weeks 1-12: -2.79 [95% CI: -4.65 to -0.94, p = 0.004]; weeks 13-24: -3.25 [95% CI: -5.57 to -0.92, p = 0.007]). No severe adverse events were reported. CONCLUSIONS: Acupuncture may be safe and effective for treating chronic migraine. The efficacy of 12 weeks of acupuncture was sustained for 24 weeks and superior to that of topiramate. Acupuncture can be used as an optional preventive therapy for chronic migraine. TRIAL REGISTRATION: ISRCTN.org Identifier 13563102.

Investigation of the anatomic risk factors in acute anterior cruciate ligament ruptures to develop ramp lesions of the medial meniscus by quantitative MRI.

OBJECTIVE: To investigate the anatomic risk factors of knee in patients with acute non-contact anterior cruciate ligament (aACL) ruptures to develop ramp lesions. METHODS: A total of 202 subjects were retrospectively divided into three groups: (1) aACL ruptures combined with ramp lesions group (n = 76); (2) isolated ACL ruptures group (n = 56) and (3) normal controls group (n = 70). Quantitative morphological parameters on MRI were measured including: diameter of medial femoral condyle (MFC), anterior-posterior length and depth of medial tibial plateau (MTP AP length and depth), lateral posterior tibial slope (LPTS) and medial posterior tibial slope (MTPS), asymmetry of LPTS and MPTS (LMPTS), lateral meniscal slope (LMS), and medial meniscal slope (MMS). RESULTS: The MTP AP length, MTP AP length/MFC diameter ratio, MTP depth, LPTS and the asymmetry of LMPTS showed significant differences among the three groups (p < 0.001). The risk factors associated with the ramp lesions including a longer MTP AP length (OR 1.17, 95% CI 1.00-1.44, p = 0.044), increased MTP depth (OR 1.91, 95% CI 1.22-3.00, p = 0.005) and lager ratio (OR 1.11, 95% CI 1.01-1.22, p = 0.036). The highest AUC was the MTP AP length/MFC diameter ratio (0.74; 95% CI, 0.66-0.82). The combination model increased higher accuracy (0.80; 95% CI, 0.72-0.88). CONCLUSION: Several bony anatomic characteristics of the knee, especially the morphology of medial tibia plateau, are additional risk factors for aACL ruptures to develop ramp lesions. CRITICAL RELEVANCE STATEMENT: Predictive anatomic risk factors of the knee for patients with acute non-contact anterior cruciate ligament (aACL) ruptures to develop ramp lesions, especially the morphology of medial tibia plateau, are detectable by MRI. KEY POINTS: Ramp lesion development can complicate aACL ruptures and requires specific treatment. Longer AP length and increased MTP depth are risk factors for concurrent ramp lesions. Identification of ramp lesions allows for the most appropriate treatment.

Assessment of bidirectional relationships between hypothyroidism and endometrial cancer: a two-sample Mendelian randomization study.

Objective: Hypothyroidism, characterized by reduced thyroid hormone levels, and endometrial cancer, a prevalent gynecological malignancy, have been suggested to have a potential association in previous observational studies. However, the causal relationship between them remains uncertain. This study aimed to investigate the causal relationship between hypothyroidism and endometrial cancer using a bilateral Mendelian randomization approach. Methods: A bidirectional two-sample Mendelian randomization study was conducted using summary statistics from genome-wide association studies to identify genetic variants associated with hypothyroidism and endometrial cancer. The inverse variance weighting method was used as the main analysis, and sensitivity analyses were conducted to validate the MR results. Results: The results of our analysis did not support a causal effect of hypothyroidism (OR: 0.93, p=0.08) or autoimmune hypothyroidism (OR: 0.98, p=0.39) on endometrial cancer risk. In the reverse MR analysis, we did not find a significant causal effect of endometrial cancer on hypothyroidism (OR: 0.96, p=0.75) or autoimmune hypothyroidism (OR: 0.92, p=0.50). Based on subgroup analysis by pathological subtypes of endometrial cancer, the above findings were further substantiated (all p-value >0.05). Conclusions: Our Mendelian randomization analysis suggests a lack of causal association between hypothyroidism and endometrial cancer. To gain a deeper understanding of this association, it is essential to conduct large-scale randomized controlled trials in the future to validate our findings.

Association Between Sleep Apnea Syndrome and Osteoarthritis: Insights from Bidirectional Mendelian Randomization and Bioinformatics Analysis.

Background: Sleep apnea syndrome(SAS) and osteoarthritis (OA) are two prevalent diseases that often coexist, but the causal relationship between them remains unclear. In light of this, our team utilizes Mendelian Randomization and bioinformatics analysis methods to investigate the potential association between the two diseases. Methods: In this study, we utilized GWAS data pertaining to SAS and OA to assess the causal relationship between the two diseases through Mendelian randomization (MR) analysis. We then employed transcriptomic data to perform differential gene identification, WGCNA, shared gene determination, functional enrichment analysis, and colocalization analysis, all designed to further elucidate the mechanisms underlying the association between the two diseases. In the end, we utilized Mendelian randomization (MR) analysis again to delve deeper into the relationship between the two diseases and immune cells. Results: Our research findings indicate that SAS is a risk factor for OA (p = 0.000004), knee OA (p = 0.0000001) and hip OA(p = 0.001). Furthermore, OA (p = 0.000195), knee OA (p = 0.001) are significant risk factors for SAS. However, there is no clear evidence that hip OA (p = 0.892) is a risk factor for SAS. Interestingly, the genes shared between OA and SAS are significantly enriched in leukocyte migration, leukocyte chemotaxis. Moreover, colocalization analysis suggests that the genes JUNB, COL8A1, FOSB, and IER2 may be key genes associated with both diseases. Furthermore, 57 immune cell phenotypes are associated with SAS, 95 with OA, and 6 shared between both diseases. Conclusion: This research confirmed the bidirectional causal relationship between SAS and OA. Notably, the 4 genes (JUNB, COL8A1, FOSB, IER2) and 6 immune phenotypes are crucial for both diseases, these provide hopeful targets for future interventions against these two diseases.

CCDC28A deficiency causes sperm head defects, reduced sperm motility and male infertility in mice.

Mature spermatozoa with normal morphology and motility are essential for male reproduction. The epididymis has an important role in the proper maturation and function of spermatozoa for fertilization. However, factors related to the processes involved in spermatozoa modifications are still unclear. Here we demonstrated that CCDC28A, a member of the CCDC family proteins, is highly expressed in testes and the CCDC28A deletion leads to male infertility. We found CCDC28A deletion had a mild effect on spermatogenesis. And epididymal sperm collected from Ccdc28a-/- mice showed bent sperm heads, acrosomal defects, reduced motility and decreased in vitro fertilization competence whereas their axoneme, outer dense fibers, and fibrous sheath were all normal. Furthermore, we found that CCDC28A interacted with sperm acrosome membrane-associated protein 1 (SPACA1) and glycogen synthase kinase 3a (GSK3A), and deficiencies in both proteins in mice led to bent heads and abnormal acrosomes, respectively. Altogether, our results reveal the essential role of CCDC28A in regulating sperm morphology and motility and suggesting a potential marker for male infertility.

Automatic Sleep Staging Based on Contextual Scalograms and Attention Convolution Neural Network Using Single-Channel EEG.

Single-channel EEG based sleep staging is of interest to researchers due to its broad application prospect in daily sleep monitoring recently. We proposed using contextual scalograms as input and developed a convolutional neural network with attention modules named Co-ScaleNet for sleep staging. The contextual scalograms were obtained by combining the same color channels of three original RGB scalograms from consecutive epochs, and a simple and efficient data augmentation was designed according to their various forms. The Co-ScaleNet consists of two main parts. Firstly, three parallel convolutional branches with attention modules correspondingly extract and fuse features from contextual scalograms at the top layers. The remaining part is a stack of lightweight blocks. We achieved an overall accuracy of 87.0% for healthy individuals, 84.7% for depressed patients. And we obtained comparable performance on the public Sleep-EDFx (82.8%), ISRUC (84.6%) and SHHS datasets (87.7%), including a high recall of N1. The contextual scalograms of R channel as input achieved the best performance, which conform to the features of interest in visual scoring. The attention modules improved the recall of N1 and N3. Overall, the contextual scalograms provided a novel scheme for both contextual information extraction and data augmentation. Our study successfully expanded its application to depression datasets, as well as patients with sleep apnea, demonstrating its wide applicability.

Non-small cell lung cancer cells with uncommon EGFR exon 19delins variants respond poorly to third-generation EGFR inhibitors.

BACKGROUND: This study compared the clinical efficacy of first-, second-, and third-generation tyrosine kinase inhibitors (TKIs) in previously untreated non-small cell lung cancer (NSCLC) patients harboring uncommon epidermal growth factor receptor (EGFR) exon 19delins variants. METHODS: We retrospectively analyzed the clinical outcomes of NSCLC patients with EGFR exon 19delins mutations who were treated with third- and first-generation EGFR TKIs. In vitro and in vivo studies were conducted to verify the sensitivity of these mutations to distinct generations of TKIs. Molecular simulation was used to investigate the structural characteristics of the EGFR mutant molecules. RESULTS: In a multicenter cohort of 1,526 patients, 37 (2.4 %) had uncommon EGFR 19delins mutations. Twenty-four patients were treated with first-generation EGFR TKIs, and third-generation TKIs were administered to ten patients as frontline therapy. Patients carrying EGFR exon 19delins mutations who were given third-generation TKIs exhibited comparatively shorter progression-free survival (PFS) and overall survival (OS) in relation to those who received first-generation EGFR inhibitors; median PFS: 6.9 months vs. 19.1 months (p < 0.001), Median OS: 19.1 months vs. 32.6 months (p < 0.001). In vivo and in vitro studies revealed that uncommon EGFR 19delins variants exhibit limited sensitivity to third-generation EGFR inhibitors in contrast to first- and second-generation EGFR inhibitors. The molecular binding affinity of third-generation EGFR TKIs toward uncommon EGFR 19delins mutations was less than that of first- and second-generation EGFR inhibitors. CONCLUSIONS: Uncommon EGFR 19delins variants respond poorly to third-generation EGFR inhibitors in NSCLC. Uncommon EGFR 19delins mutations may serve as an unfavorable predictive factor for the efficacy of third-generation EGFR TKI therapy, offering potential guidance for future clinical decision-making.

Oncostatin M/Oncostatin M Receptor Signal Induces Radiation-Induced Heart Fibrosis by Regulating SMAD4 in Fibroblast.

PURPOSE: Radiation-induced heart fibrosis (RIHF) is a severe consequence of radiation-induced heart damage (RIHD) leading to impaired cardiac function. The involvement of oncostatin M (OSM) and its receptor (OSMR) in RIHD remains unclear. This study aimed to investigate the specific mechanism of OSM/OSMR in RIHF/RIHD. METHODS AND MATERIALS: RNA sequencing was performed on heart tissues from a RIHD mouse model. OSM levels were assessed in serum samples obtained from patients receiving thoracic radiation therapy (RT), as well as in RIHF mouse heart tissues and serum using enzyme-linked immunosorbent assay. Fiber activation was evaluated through costimulation of primary cardiac fibroblasts and NIH3T3 cells with RT and OSM, using Western blotting, immunofluorescence, and quantitative Polymerase Chain Reaction (qPCR). Adeno-associated virus serotype 9-mediated overexpression or silencing of OSM specifically in the heart was performed in vivo to assess cardiac fibrosis levels by transthoracic echocardiography and pathologic examination. The regulatory mechanism of OSM on the transcription level of SMAD4 was further explored in vitro using mass spectrometric analysis, chromatin immunoprecipitation-qPCR, and DNA pull-down. RESULTS: OSM levels were elevated in the serum of patients after thoracic RT as well as in RIHF mouse cardiac endothelial cells and mouse serum. The OSM rate (post-RT/pre-RT) and the heart exposure dose in RT patients showed a positive correlation. Silencing OSMR in RIHF mice reduced fibrosis, while OSMR overexpression increased fibrotic responses. Furthermore, increased OSM promoted histone acetylation (H3K27ac) in the SMAD4 promoter region, influencing SMAD4 transcription and subsequently enhancing fibrotic response. CONCLUSIONS: The findings demonstrated that OSM/OSMR signaling promotes SMAD4 transcription in cardiac fibroblasts through H3K27 hyperacetylation, thereby promoting radiation-induced cardiac fibrosis and manifestations of RIHD.

Effect of lumbosacral transitional vertebrae on sagittal balance of lumbo-pelvic complexity assessed by quantitative whole-body CT imaging.

Background: The variation at the lumbosacral junction certainly results in occult alignment changes in the lumbo-pelvic complexity (LPC). This retrospective case-control study aims to investigate the influences of lumbosacral transitional vertebrae (LSTV) on sagittal lumbo-pelvic balance assessment and provide some recommendations for preoperative imaging evaluation. Methods: Based on whole-body computed tomography (CT) images, a total of 210 individuals with complete segmentation anomalies of LSTV were included and divided into 23 presacral vertebrae (PSV) (sacralization, n=102), 25 PSV (lumbarization, n=108). The control group with 24 PSV (normal, n=100) was matched by age and gender. Sagittal lumbo-pelvic parameters including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), sacral table angle (STA), sacral kyphosis (SK), and pelvic radius (PR) were measured at the ontogenetical S1 (Ontog S1) level and the morphological S1 (Morph S1), respectively. These parameters were compared using t-test, Kruskal-Wallis H test and post hoc test. Spearman's rank correlation coefficient and linear regression were used to investigate the association of lumbo-pelvic parameters with LSTV types and measurement levels. Results: All the parameters at the Ontog S1 differed significantly from those at the Morph S1 (all P<0.001). At the Ontog S1 level, PI, PT, SS, and LL were negatively correlated with vertebrae counts; SK and PR were positively correlated with vertebrae counts (all P<0.001). Instead, reverse results were obtained at the Morph S1 level. The measurement level and vertebrae counts were independent influence factors for the measurement of PI, PT, SS, SK, and PR (all P<0.05). Compared with the measured values of the matched controls, the variability of most lumbo-pelvic parameters (PI, SS, LL, STA, SK, PR values of 25 PSV subgroup, and PI, PT, SS, LL, STA values of 23 PSV subgroup) at the Morph S1 level were significantly smaller than that at the Ontog S1. The measurements of PT, SS, LL, and PR were less influenced by the measurement level and vertebrae counts than those of PI and SK. Conclusions: Morph S1 is more recommended for the measurements of most lumbo-pelvic parameters in patients with LSTV. The parameters (PT, SS, LL, STA, PR) are shown more stable and recommended to help reduce the effects caused by LSTV.

Reflecting on the cardiac toxicity in non-small cell lung cancer in the era of immune checkpoint inhibitors therapy combined with thoracic radiotherapy.

In recent years, immune checkpoint inhibitors (ICIs) have become a widely used treatment for non-small cell lung cancer (NSCLC), and the combination with traditional radiotherapy (RT) has shown significant potential in prolonging patient survival. However, both thoracic RT and ICIs can lead to cardiac toxicity, including radiation-induced heart damage (RIHD) and immunotherapy-related heart damage (IRHD). It still remains uncertain whether the combination of thoracic RT and immunotherapy will exacerbate acute or late cardiovascular (CV) toxicity and incidence. In this review, we summarize safety data from relevant clinical studies regarding CV toxicity for the combination therapy in NSCLC patients, explore the underlying synergetic mechanisms and common risk factors, and proposed treatment and management strategies. We hope to increase emphasis on the long-term assessment of CV toxicity risks associated with the combination therapy, and reduce the incidence of CV deaths resulting from such regimens.

ARRDC5 deficiency impairs spermatogenesis by affecting SUN5 and NDC1.

Sperm with normal morphology and motility are essential for successful fertilization, and the strong attachment of the sperm head-tail coupling apparatus to the nuclear envelope during spermatogenesis is required to ensure the integrity of sperm for capacitation and fertilization. Here, we report that Arrdc5 is associated with spermatogenesis. The Arrdc5 knockout mouse model showed male infertility characterized by a high bent-head rate and reduced motility in sperm, which led to capacitation defects and subsequent fertilization failure. Through mass spectrometry, we found that ARRDC5 affects spermatogenesis by affecting NDC1 and SUN5. We further found that ARRDC5 might affect the vesicle-trafficking protein SEC22A-mediated transport and localization of NDC1, SUN5 and other head-tail coupling apparatus-related proteins that are responsible for initiating the attachment of the sperm head and tail. We finally performed intracytoplasmic sperm injection as a way to explore therapeutic strategies. Our findings demonstrate the essential role and the underlying molecular mechanism of ARRDC5 in anchoring the sperm head to the tail during spermatogenesis.

Ectopic expression of human TUBB8 leads to increased aneuploidy in mouse oocytes.

Aneuploidy seriously compromises female fertility and increases incidence of birth defects. Rates of aneuploidy in human eggs from even young women are significantly higher than those in other mammals. However, intrinsic genetic factors underlying this high incidence of aneuploidy in human eggs remain largely unknown. Here, we found that ectopic expression of human TUBB8 in mouse oocytes increases rates of aneuploidy by causing kinetochore-microtubule (K-MT) attachment defects. Stretched bivalents in mouse oocytes expressing TUBB8 are under less tension, resulting in continuous phosphorylation status of HEC1 by AURKB/C at late metaphase I that impairs the established correct K-MT attachments. This reduced tension in stretched bivalents likely correlates with decreased recruitment of KIF11 on meiotic spindles. We also found that ectopic expression of TUBB8 without its C-terminal tail decreases aneuploidy rates by reducing erroneous K-MT attachments. Importantly, variants in the C-terminal tail of TUBB8 were identified in patients with recurrent miscarriages. Ectopic expression of an identified TUBB8 variant in mouse oocytes also compromises K-MT attachments and increases aneuploidy rates. In conclusion, our study provides novel understanding for physiological mechanisms of aneuploidy in human eggs as well as for pathophysiological mechanisms involved in recurrent miscarriages.

Optimal combination periprosthetic vasculature visualization and metal artifact reduction by spectral computed tomography using virtual monoenergetic images in total hip arthroplasty.

OBJECTIVES: To investigate the optimal parameters of spectral CT for preferably visualizing the periprosthetic vasculature and metal artifact reduction (MAR) in total hip arthroplasty (THA). METHODS: A total of 34 THA of 30 patients were retrospectively included. Image reconstructions included conventional image (CI), CI combined with MAR (CIMAR), and virtual monoenergetic images (VMI) combined with MAR (VMIMAR) at 50-120 keV. The attenuation and standard deviation of the vessel and artifact, and the width of artifact were measured. Qualitative scoring was evaluated including the vascular contour, the extent of artifact, and overall diagnostic evaluation. RESULTS: The attenuation, noise of the vessel and artifact, and the width of artifact decreased as the energy level increased (p < 0.001). The downtrend was relatively flat at 80-120 keV, and the vascular attenuation dropped to 200 HU at 90 keV. The qualitative rating of vascular contour was significantly higher at CIMAR (3.47) and VMIMAR 60-80 keV (2.82-3.65) compared with CI (2.03) (p ≤ 0.029), and the highest score occurred at 70 and 80 keV (3.65 and 3.56). The score of the extent of artifact was higher at VMIMAR 80 keV than CIMAR (3.53 VS 3.12, p = 0.003). The score of the overall diagnostic evaluation was higher at VMIMAR 70 and 80 keV (3.32 and 3.53, respectively) than CIMAR (3.12) (p ≤ 0.035). CONCLUSION: Eighty kiloelectron volts on VMIMAR, providing satisfactorily reduced metal artifacts and improved vascular visualization, can be an optimal recommended parameter of spectrum CT for the assessment of periprosthetic vasculature in THA patients. CRITICAL RELEVANCE STATEMENT: The metal artifact is gradually reducing with increasing energy level; however, the vascular visualization is worsening. The vascular visualization is terrible above 100 keV, while the vessel is disturbed by artifacts below 70 keV. The best performance is found at 80 keV. KEY POINTS: • VMIMAR can provide both reduced metal artifacts and improved vascular visualization. • Eighty kiloelectron volts on VMIMAR performs best in vascular visualization of total hip arthroplasty patients. • Energy spectrum CT is recommended for routine use in patients with total hip arthroplasty.

Non-coding RNAs and gastrointestinal cancers prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies.

Aim: Provide an overview and a systematic evaluation of the evidence quality on the association between non-coding RNAs (ncRNAs) and prognosis value for gastrointestinal cancers (GICs). Methods: We searched the literature from three electronic databases: Pubmed, Embase, and Web of science, then carefully screened and extracted the primary information and results from the included articles. We use A measurable systematic review and meta-analysis evaluation tool (AMSTAR2) to evaluate the quality of methodology and then use the Grading of Recommendations Assessment 2, Development and Evaluation guideline (GRADE) make sure the reliability of the meta-analysis. Results: Overall, 182 meta-analyses from 58 studies were included in this study. Most of these studies are of low or very low quality. Using the scoring tool, we found that only two meta-analyses were rated as high reliability, and 17 meta-analyses were rated as medium reliability. Conclusions: Although ncRNA has good prognostic value in some studies, only a tiny amount of evidence is highly credible at present. More research is needed in the future. PROSPERO registration number: CRD42022382296.