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.

Predicting malignant potential of solitary pulmonary nodules in patients with COVID-19 infection: a comprehensive analysis of CT imaging and tumor markers.

OBJECTIVE: To analyze the value of combining computed tomography (CT) with serum tumor markers in the differential diagnosis of benign and malignant solitary pulmonary nodules (SPNs). METHODS: The case data of 267 patients diagnosed with SPNs in the First Affiliated Hospital of Zhengzhou University from March 2020 to January 2023 were retrospectively analyzed. All individuals diagnosed with coronavirus disease 2019 (COVID-19) were confirmed via respiratory specimen viral nucleic acid testing. The included cases underwent CT, serum tumor marker testing and pathological examination. The diagnostic efficacy and clinical significance of CT, serum tumor marker testing and a combined test in identifying benign and malignant SPNs were analyzed using pathological histological findings as the gold standard. Finally, a nomogram mathematical model was established to predict the malignant probability of SPNs. RESULTS: Of the 267 patients with SPNs, 91 patients were not afflicted with COVID-19, 36 exhibited malignant characteristics, whereas 55 demonstrated benign features. Conversely, within the cohort of 176 COVID-19 patients presenting with SPNs, 62 were identified as having malignant SPNs, and the remaining 114 were diagnosed with benign SPNs. CT scans revealed statistically significant differences between the benign and malignant SPNs groups in terms of CT values (P<0.001), maximum nodule diameter (P<0.001), vascular convergence sign (P<0.001), vacuole sign (P = 0.0007), air bronchogram sign (P = 0.0005), and lobulation sign (P = 0.0005). Malignant SPNs were associated with significantly higher levels of carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) compared to benign SPNs (P < 0.05), while no significant difference was found in carbohydrate antigen 125 (CA125) levels (P = 0.054 for non-COVID-19; P = 0.072 for COVID-19). The sensitivity (95.83%), specificity (95.32%), and accuracy (95.51%) of the comprehensive diagnosis combining serum tumor markers and CT were significantly higher than those of CT alone (70.45%, 79.89%, 76.78%) or serum tumor marker testing alone (56.52%, 73.71%, 67.79%) (P < 0.05). A visual nomogram predictive model for malignant pulmonary nodules was constructed. CONCLUSION: Combining CT with testing for CEA, CA125, and NSE levels offers high diagnostic accuracy and sensitivity, enables precise differentiation between benign and malignant nodules, particularly in the context of COVID-19, thereby reducing the risk of unnecessary surgical interventions.

USP13 Deficiency Impairs Autophagy and Facilitates Age-related Lung Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an age-related disease. Failure of the proteostasis network with age, including insufficient autophagy, contributes to the pathology of IPF. Mechanisms underlying autophagy disruption in IPF are unclear and may involve regulation of USP (ubiquitin-specific protease) by post-translational modifications. To expand our previous observation of low USP13 expression in IPF, this study evaluated the role of USP13 in age-related lung fibrosis. Here, we demonstrated that Usp13-deficient aged mice exhibited impaired autophagic activity and increased vulnerability to bleomycin-induced fibrosis. Mechanistically, USP13 interacted with and deubiquitinated Beclin 1, and Beclin 1 overexpression abolished the effects of USP13 disruption. In addition, Beclin 1 inhibition resulted in insufficient autophagy and more severe lung fibrosis after bleomycin injury, consistent with the phenotype of aged Usp13-deficient mice. Collectively, we show a protective role of USP13 in age-related pulmonary fibrosis. Aging-mediated USP13 loss impairs autophagic activity and facilitates lung fibrosis through Beclin 1 deubiquitination. Our findings support the notion that age-dependent dysregulation of autophagic regulators enhances vulnerability to lung fibrosis.

IL-17A promotes lung fibrosis through impairing mitochondrial homeostasis in type II alveolar epithelial cells.

The dysfunction of type II alveolar epithelial cells (AECIIs), mainly manifested by apoptosis, has emerged as a major component of idiopathic pulmonary fibrosis (IPF) pathophysiology. A pivotal mechanism leading to AECIIs apoptosis is mitochondrial dysfunction. Recently, interleukin (IL)-17A has been demonstrated to have a pro-fibrotic role in IPF, though the mechanism is unclear. In this study, we report enhanced expression of IL-17 receptor A (IL-17RA) in AECIIs in lung samples of IPF patients, which may be related to the accumulation of mitochondria in AECIIs of IPF. Next, we investigated this relationship in bleomycin (BLM)-induced PF murine model. We found that IL-17A knockout (IL-17A-/- ) mice exhibited decreased apoptosis levels of AECIIs. This was possibly a result of the recovery of mitochondrial morphology from the improved mitochondrial dynamics of AECIIs, which eventually contributed to alleviating lung fibrosis. Analysis of in vitro data indicates that IL-17A impairs mitochondrial function and mitochondrial dynamics of mouse primary AECIIs, further promoting apoptosis. PTEN-induced putative kinase 1 (PINK1)/Parkin signal-mediated mitophagy is an important aspect of mitochondria homeostasis maintenance. Our data demonstrate that IL-17A inhibits mitophagy and promotes apoptosis of AECIIs by decreasing the expression levels of PINK1. We conclude that IL-17A exerts its pro-fibrotic effects by inducing mitochondrial dysfunction in AECIIs by disturbing mitochondrial dynamics and inhibiting PINK1-mediated mitophagy, thereby leading to apoptosis of AECIIs.

Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis.

BACKGROUND & AIMS: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. METHODS: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. RESULTS: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. CONCLUSIONS: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. LAY SUMMARY: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

Global and regional burden of interstitial lung disease and pulmonary sarcoidosis from 1990 to 2019: results from the Global Burden of Disease study 2019.

BACKGROUND: Interstitial lung disease (ILD) and pulmonary sarcoidosis are common respiratory diseases with a heterogeneous distribution worldwide. The global burden and temporal trends of ILD and sarcoidosis are rarely explored. METHODS: Using the classification 'ILD and pulmonary sarcoidosis' from the Global Burden of Disease 2019 dataset, we described the age-standardised rates of incidence, mortality, disability-adjusted life-years (DALYs), and their average annual percentage change from 1990 to 2019 by sex, Sociodemographic Index (SDI) and region. RESULTS: In 2019, the global incidence and mortality of ILD and pulmonary sarcoidosis were 24.2 million and 169 833 cases, respectively. From 1990 to 2019, the global incidence, deaths and DALYs due to ILD and pulmonary sarcoidosis increased by 118.6%, 166.63% and 122.87% respectively. The global incidence of ILD and pulmonary sarcoidosis was higher in men and was mainly concentrated among persons aged 70‒79 of both sexes. Significant regional differences could be seen in the disease burden of ILD and pulmonary sarcoidosis: since 2006, high-SDI regions had higher age-standardised incidence rates but lower age-standardised death rates compared with the low-SDI regions. CONCLUSIONS: Our study suggests the incidence, mortality and DALYs from ILD and pulmonary sarcoidosis are increasing globally. To reduce the ongoing burden of this condition, early diagnosis and treatment are vital, and more targeted and specific strategies should be established in high-burden regions. Differences in incidence and mortality across regions may reflect the influence of genetic, environmental, diagnostic, pharmacotherapeutic, and health system factors.

Prosthodontic Rehabilitation of a Patient with Hypophosphatasia Using Dental Implants: A Case Report with Seven Years Follow-Up.

Hypophosphatasia is a rare metabolic inherited dento-osseous disorder. Although there is some available literature on various dental characteristics of hypophosphatasia patients, few reports focus on the effects of hypophosphatasia on the permanent dentition and prosthodontic rehabilitation, particularly in relation to the use of dental implants. This paper reports a case with hypophosphatasia and prosthodontic rehabilitation using dental implants with 7-year follow-up.

Comparisons of CO2 emission performance between secondary and service industries in Yangtze River Delta cities.

To put the brakes on global climate change, China, the world's top emitter, has established ambitious CO2 emissions reduction targets. Industry-level emissions analysis can help policymakers determine better ways to achieve mitigation targets. This study is the first to target the total-factor carbon emission performance (TCPI) of secondary and service industries. We first compile industry-level CO2 emission inventories of 25 Yangtze River Delta cities during 2007-2016. The TCPI of secondary and service industries is then estimated by the non-radial directional distance function. We then compare the TCPI of the two industries across levels, dynamics, and inequalities using a global metafrontier approach. The results show the TCPI of the service industry (0.563 in 2016) was significantly higher than that of secondary industry (0.256 in 2016), suggesting that the service industry was more carbon-friendly. The TCPI gap between the secondary and service industries narrowed over the study period. The TCPI of secondary industry showed a promising increase during 2007-2016 with an annual growth rate of 2.30%, reflecting the positive effects of the government's reforms and environmental regulations. By contrast, the service industry saw a downward trend in TCPI, decreasing by 1.68% annually, primarily because it is a newcomer to low-carbon development. TCPI inequality in secondary industry was much larger than in the service industry, suggesting that significant heterogeneity exists in secondary industry. Therefore, policymakers should implement targeted mitigation policies for secondary industry, and place decarbonising the service industry on the agenda to reverse its decreasing TCPI.

Radiologic and Clinicopathologic Findings of Inflammatory Myofibroblastic Tumor.

PURPOSE: The aim of the study was to describe the clinical, radiographic, and pathologic features of inflammatory myofibroblastic tumor (IMT) to enhance the recognition of this rare disease. MATERIALS AND METHODS: The clinical, imaging, and pathologic findings were retrospectively reviewed in 54 patients with IMT lesions, which were conformed by biopsy or surgical pathology. Of 54 patients, 51 had preoperative computed tomography (CT) examination and 13 had preoperative magnetic resonance imaging records. RESULTS: The clinical appearances of these 54 patients had some relationship with the locations of lesions. Of 54 IMT patients, 87.0% cases (47/54) had solitary lesion. The mean long diameter of the lesions located at the sites of chest, abdomen, and pelvic regions was bigger than that of other locations (F = 3.025, P = 0.038). On plain CT images, soft tissue mass was found in all IMT lesions, except for 3 lesions that arose in the intestine tract, appearing as focal or diffuse thickening in the bowel wall. After contrast administration, all lesions were persistently enhanced; 72.7% cases (24/33) demonstrated heterogeneous enhancement with various cystic regions. Comparing the CT features with different anatomic lesions, ill-defined margin on the plain CT images and calcification were seen more frequently in the lesions of the head and neck (P = 0.010 and 0.035); however, the other radiological findings had no significant differences (all P > 0.05). Twelve of 51 IMT patients showed invasion into adjacent structures. On magnetic resonance imaging, 92.3% lesions (12/13) showed soft tissue masses demonstrating isointense to hypointense contrast compared with skeletal muscle on T1-weighted images and heterogeneously high signals on T2-weighted images; 85.7%(6/7) of lesions were heterogeneously enhanced with cystic changes. Immunohistochemistry showed that the percentage of positive staining for SMA, vimentin, anaplastic lymphoma kinase, CD68, CD34, CD99, B-cell lymphoma/leukemia-2, cytokeratin, Desmin, and S-100 protein were 88.9%, 87.0%, 44.4%, 59.3%, 53.7%, 29.6%, 42.6%, 28.5%, 13.0%, and 24.1%, respectively. CONCLUSIONS: Inflammatory myofibroblastic tumor can involve any part of the body, and the clinical and radiological appearances are various owing to different anatomic sites. An ill-defined soft tissue mass heterogeneous enhancement with or without invasion into adjacent structures on computed tomographic or magnetic resonance images and positive staining for SMA and vimentin on immunohistochemical examination could suggest the diagnosis.

A pilot study using low-dose Spectral CT and ASIR (Adaptive Statistical Iterative Reconstruction) algorithm to diagnose solitary pulmonary nodules.

BACKGROUND: Lung cancer is the most common cancer which has the highest mortality rate. With the development of computed tomography (CT) techniques, the case detection rates of solitary pulmonary nodules (SPN) has constantly increased and the diagnosis accuracy of SPN has remained a hot topic in clinical and imaging diagnosis. The aim of this study was to evaluate the combination of low-dose spectral CT and ASIR (Adaptive Statistical Iterative Reconstruction) algorithm in the diagnosis of solitary pulmonary nodules (SPN). METHODS: 62 patients with SPN (42 cases of benign SPN and 20 cases of malignant SPN, pathology confirmed) were scanned by spectral CT with a dual-phase contrast-enhanced method. The iodine and water concentration (IC and WC) of the lesion and the artery in the image that had the same density were measured by the GSI (Gemstone Spectral Imaging) software. The normalized iodine and water concentration (NIC and NWC) of the lesion and the normalized iodine and water concentration difference (ICD and WCD) between the arterial and venous phases (AP and VP) were also calculated. The spectral HU (Hounsfield Unit ) curve was divided into 3 sections based on the energy (40-70, 70-100 and 100-140 keV) and the slopes (λHU) in both phases were calculated. The ICAP, ICVP, WCAP and WCVP, NIC and NWC, and the λHU in benign and malignant SPN were compared by independent sample t-test. RESULTS: The iodine related parameters (ICAP, ICVP, NICAP, NICVP, and the ICD) of malignant SPN were significantly higher than that of benign SPN (t = 3.310, 1.330, 2.388, 1.669 and 3.251, respectively, P <0.05). The 3 λHU values of venous phase in malignant SPN were higher than that of benign SPN (t = 3.803, 2.846 and 3.205, P <0.05). The difference of water related parameters (WCAP, WCVP, NWCAP, NWCVP and WCD) between malignant and benign SPN were not significant (t = 0.666, 0.257, 0.104, 0.550 and 0.585, P > 0.05). CONCLUSIONS: The iodine related parameters and the slope of spectral curve are useful markers to distinguish the benign from the malignant lung diseases, and its application is extremely feasible in clinical applications.