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.

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.

Radiologic and clinicopathologic findings of peripheral primitive neuroectodermal tumors.

BACKGROUND: Primitive neuroectodermal tumors (PNETs) constitute a rare type of malignant neuroectodermal tumors that have chromosomal translocations identical to Ewing's sarcoma (ES), and the characteristics of this disease remain unclear. PURPOSE: To describe the clinical, radiological, and pathological features of peripheral PNETs (pPNETs) to enhance their recognition. MATERIAL AND METHODS: The clinical, imaging, and pathologic findings of 35 patients with pPNETs were retrospectively reviewed, all being confirmed by biopsy or surgical pathology. All 35 patients had preoperative computed tomography (CT) examinations; 10 patients had preoperative magnetic resonance imaging (MRI) studies. RESULTS: Of 35 pPNET patients, 54.3% had a primary tumor in soft tissue, the others in bone. On plain CT images, 33 lesions demonstrated heterogeneous hypodense masses with multiple lamellar lower density, and with osteolytic destruction if the tumor originated in bone. Calcification was only found in five lesions arising in soft tissue. All lesions enhanced heterogeneously with varying areas of cystic changes, and all lesions in bone and 52.6% of lesions in soft tissue showed ill-defined margins after contrast administration. On MRI, these tumors appeared in conjunction with osteolytic bone destruction and irregular soft tissue masses iso- to hypointense to skeletal muscle on T1-weighted images and showed heterogeneously high intensity on T2-weighted images. All lesions enhanced heterogeneously with cystic changes. Homer-Wright rosettes were observed in 15 lesions, and 97.1% lesions were positive for CD99 in histopathological results. CONCLUSION: pPNETs can involve any part of the body, and a large, ill-defined, aggressive soft tissue mass and heterogeneous enhancement with or without osteolytic bone destruction on CT or MR images could suggest the diagnosis.

[The best noise index combined with ASIR weighting selection in low-dose chest scanning].

OBJECTIVE: To discuss the best noise index combined with ASIR weighting selection in low-dose chest scanning based on BMI. METHODS: 200 patients collected from May to December 2014 underwent non-contrast chest CT examinations, they were randomly assigned into standard dose group (Group A, NI15 combined with 30% ASIR) and low-dose groups (Group B, NI25 combined with 40% ASIR, Group C, NI30 combined with 50% ASIR, Group D, NI35 combined with 60% ASIR), 50 cases in each group; the patients were assigned into three groups based on BMI (kg/m2): BMI<18.5; 18.5≤BMI≤25; BMI>25. Signal-to-nosie ratio (SNR), contrast-to noise ratio (CNR), CT dose index volume (CTDIvol), dose-length product (DLP), effective dose (ED) and subjective scoring between the standard and low-dose groups were compared and analyzed statistically. Differences of SNR, CNR, CTDIvol, DLP and ED among groups were determined with ANOVA analysis and the consistency of diagnosis with Kappa test. RESULTS: SNR, CTDIvol, DLP and ED reduced with the increase of nosie index, the differences among the groups were statistically significant (P<0.05). Kappa value of the two reviewers were 0.888. Subjective scoring of four groups were all above 3 points in BMI<18.5 kg/m2 group; subjective scoring of ABC groups were all above 3 points in 18.5 kg/m2≤BMI≤25 kg/m2 group and subjective scoring of AB groups were all above 3 points in BMI>25 kg/m2 group. CONCLUSIONS: NI35 combined with 60% ASIR in BMI<18.5 kg/m2 group; NI30 combined with 50% ASIR in 18.5 kg/m2≤BMI≤25 kg/m2 group; NI25 combined with 40% ASIR in 18.5 kg/m2≤BMI≤25 kg/m2 group were the best parameters combination which both can significantly reduce the radiation dose and ensure the image quality.

Low-carbon development pathways for resource-based cities in China under the carbon peaking and carbon neutrality goals.

Resource-based cities are important strategic bases for securing resources in China and have made great contributions to the country's economic development. Long-term extensive resource development has made resource-based cities an important region constraining China from achieving comprehensive low-carbon development. Therefore, it is of great significance to explore the low-carbon transition path of resource-based cities for their energy greening, industrial transformation, and high-quality economic development. This study compiled the CO2 emission inventory of resource-based cities in China from 2005 to 2017, explored the contribution to CO2 emissions from three perspectives (driver, industry, and city), and predicted the peak of CO2 emissions in resource-based cities. The results show that resource-based cities contribute 18.4% of the country's GDP and emit 44.4% of the country's CO2 and that economic growth and CO2 emissions have not yet been decoupled. The per capita CO2 emissions and emission intensity of resource-based cities are 1.8 times and 2.4 times higher than the national average, respectively. Economic growth and energy intensity are the biggest drivers and main inhibitors of CO2 emissions growth. Industrial restructuring has become the biggest inhibitor of CO2 emissions growth. Based on the different resource endowments, industrial structures, and socio-economic development levels of resource-based cities, we propose differentiated low-carbon transition pathways. This study can provide references for cities to develop differentiated low-carbon development paths under the "double carbon" target.

Global transboundary synergies and trade-offs among Sustainable Development Goals from an integrated sustainability perspective.

Domestic attempts to advance the Sustainable Development Goals (SDGs) in a country can have synergistic and/or trade-off effects on the advancement of SDGs in other countries. Transboundary SDG interactions can be delivered through various transmission channels (e.g., trade, river flow, ocean currents, and air flow). This study quantified the transboundary interactions through these channels between 768 pairs of SDG indicators. The results showed that although high income countries only comprised 14.18% of the global population, they contributed considerably to total SDG interactions worldwide (60.60%). Transboundary synergistic effects via international trade were 14.94% more pronounced with trade partners outside their immediate geographic vicinity than with neighbouring ones. Conversely, nature-caused flows (including river flow, ocean currents, and air flow) resulted in 39.29% stronger transboundary synergistic effects among neighboring countries compared to non-neighboring ones. To facilitate the achievement of SDGs worldwide, it is essential to enhance collaboration among countries and leverage transboundary synergies.

Mechanosynthesis of Pyrrole-2-carboxylic Acids via Copper-Catalyzed Spiroannulation/Ring-Opening Aromatization of 4-Arylidene Isoxazol-5-ones with Enamino Esters.

An efficient and practical tandem reaction of 4-arylidene isoxazol-5-ones with enamino esters catalyzed by an inexpensive copper salt has been established in a ball mill. This innovative approach yields a diverse array of structurally novel pyrrole-2-carboxylic acids, showing excellent tolerance toward different functional groups. By integrating spiroannulation and ring-opening aromatization processes, this protocol introduces a facile and cost-effective strategy for synthesizing highly functionalized pyrrole derivatives.

Microscopic insights to spin transport-driven ultrafast magnetization dynamics in a Gd/Fe bilayer.

Laser-induced spin transport is a key ingredient in ultrafast spin dynamics. However, it remains debated to what extent ultrafast magnetization dynamics generates spin currents and vice versa. We use time- and spin-resolved photoemission spectroscopy to study an antiferromagnetically coupled Gd/Fe bilayer, a prototype system for all-optical switching. Spin transport leads to an ultrafast drop of the spin polarization at the Gd surface, demonstrating angular-momentum transfer over several nanometers. Thereby, Fe acts as spin filter, absorbing spin majority but reflecting spin minority electrons. Spin transport from Gd to Fe was corroborated by an ultrafast increase of the Fe spin polarization in a reversed Fe/Gd bilayer. In contrast, for a pure Gd film, spin transport into the tungsten substrate can be neglected, as spin polarization stays constant. Our results suggest that ultrafast spin transport drives the magnetization dynamics in Gd/Fe and reveal microscopic insights into ultrafast spin dynamics.

Interleukin-17A plays a key role in pulmonary fibrosis following Propionibacterium acnes-induced sarcoidosis-like inflammation.

Sarcoidosis is a granulomatous disease of unknown etiology, with limited therapeutic options. Chronic sarcoidosis can result in pulmonary fibrosis and can be lethal. Enhanced expression of pro-inflammatory cytokines, such as interleukin-17A (IL-17A), has been observed in sarcoid granulomas in humans. However, the role of IL-17A in the pathogenesis of chronic sarcoidosis or sarcoidosis-related pulmonary fibrosis and its potential therapeutic effects remain unclear. This study investigated whether IL-17A is critical in granulomatosis and its role in chronic inflammation in a profibrotic manner. Wild-type and IL-17A-knockout C57BL/6 mice were repeatedly challenged with heat-killed Propionibacterium acnes (PA) to induce sarcoidosis-like granulomata and sarcoidosis-related pulmonary fibrosis. Wild-type mice with granulomatosis were treated with anti-IL-17A antibody. Administration of PA enhanced the expression of IL-17A, granulomatosis, and fibrosis in mouse lungs after boost stimulation. Neither granulomata nor fibrosis were observed in IL-17A-knockout mice, even in the presence of interferon-γ enhancement. Neutralizing IL-17A antibody reduced inflammatory cells in bronchoalveolar lavage fluid and ameliorated both granulomatosis and fibrosis in sarcoidosis mice. In conclusion, our data demonstrate that IL-17A plays a critical role in PA-induced sarcoidosis-like inflammation in both granulomatosis inflammation and disease progression to pulmonary fibrosis, thus providing novel insights into the treatment of chronic sarcoidosis or sarcoidosis-related pulmonary fibrosis.

Cyprinus carpio Decoction Improves Nutrition and Immunity and Reduces Proteinuria through Nephrin and CD2AP Expressions in Rats with Adriamycin-Induced Nephropathy.

Cyprinus carpio decoction (CCD) is a well-known Chinese food medicine formula, accepted widely as a useful therapy in preventing edema and proteinuria caused by renal disease. However, the mechanism underlying this effect remains unclear. The current study investigated the potential mechanism of CCD in alleviating nephropathy induced by adriamycin (ADR) in rats. 70 eight-week-old Wistar rats were randomly divided into normal, model, fosinopril, YD, YG groups. All rats except for the normal group received 6.5 mg/kg·bw of ADR injection into the vena caudalis once. Different doses of CCD (11.3 and 22.5 g kg(-1)) were lavaged to rats in YD and YG groups, respectively. Then the serum biochemical values of the total protein (TP), albumin (ALB), blood urea nitrogen (BUN), creatinine (Cr), electrolyte levels, and the urinary protein (UP) content in 12 hr urine were measured. Interleukin-4 (IL-4) and interferon (INF-γ) were measured by enzyme-like immunosorbent assay (ELISA). The pathomorphological analysis was observed using light and electron microscopy, and the expressions of nephrin and CD2-associated protein (CD2AP) in renal tissues were determined by immunohistochemical assay. The results indicated that CCD can relieve ADR-induced nephropathy (ADN) by improving the nutrition status, regulating the immunity, and inhibiting proteinuria by increasing nephrin and CD2AP expressions.

[Effects of selenium and zinc on the proliferation of human esophageal cancer cell line studied by serophysiology].

OBJECTIVE: The effect of serum from rats supplemented with selenium and zinc on the proliferation of human esophageal cancer cell line Eca109 was observed by serophysiology. METHODS: Rats were randomly divided into seven groups. Eight rats in each group were fed with basic feeds (deprived of both selenium and zinc). The experimental rat groups were supplemented with selenium or zinc at low or high dosage intragastrically for 30 days Serum selenium and zinc content of rats was measured by Graphite Furnace Atomic Absorption Spectrometry (GFAAS) and Flame Atomic Absorption Spectrophotometry (FAAS). MTT assay,3H-TDR incorporation and flow cytometry were used to explore the effect of serum from different rat groups on the growth and proliferation of cancer cell line Ecal09 cells. RESULTS: (1) The content of serum zinc in the high zinc group was the highest and the content of serum zinc was the lowest in basic diet group. The content of serum selenium in high selenium and high zinc group was the highest and the content of serum selenium was the lowest in the basic diet group. (2) In comparing the growth of control cancer cell group cultured with calf serum, the growth of cancer cells cultured with the serum from high selenium and high zinc rats was inhibited in culturing for 72 h, but the growth of normal liver cells were also inhibited. The growth of cancer cells were promoted by serum from other groups. (3) Both MTT assay and 3H-TDR incorporation test showed that the DNA synthesis in cancer cells was inhibited by the serum from high selenium and high zinc group, but the DNA synthesis of normal liver cells was also inhibited by this type of serum. The result of DNA synthesis in other cell groups was closed to the control group. CONCLUSIONS: Low serum selenium and zinc might promote the growth of EC cell. Elevating the content of serum selenium and zinc by increasing selenium and zinc intake might inhibit EC cell proliferation.

Krebs von den Lungen-6 levels in untreated idiopathic pulmonary fibrosis.

BACKGROUND: Serum Krebs von den Lungen-6 (KL-6) has been reported to be elevated in patients with idiopathic pulmonary fibrosis (IPF). OBJECTIVE: The aim of this study was to evaluate the diagnostic value of KL-6 and whether the expression value of KL-6 could indicate the severity of the disease in IPF patients. To address this question, it is necessary to see whether the patients' physical characteristics and other clinical conditions could affect the baseline KL-6 level. DESIGN: We conducted a study of 100 patients who were diagnosed with IPF. Lung function, computed tomography (CT), and serological lab tests data were analyzed. RESULTS: The tests showed that there is a significant elevation of KL-6 in IPF patients compared with other interstitial lung disease (ILD) and healthy controls. It was noted that serum KL-6 is a stable biomarker not affected by lung infection and smoking, though IPF patients with antinuclear antibody (ANA) showed higher KL-6 levels. KL-6, in conjunction with poor pulmonary function and higher radiological fibrosis scores, indicates the severity of the disease but not poor survival. CONCLUSIONS: It is identified that serum KL-6 is a useful noninvasive biomarker to help improve the certainty of IPF diagnosis from other interstitial lung disease and assist evaluation of disease severity and prognosis.

A Novel N-Arylpyridone Compound Alleviates the Inflammatory and Fibrotic Reaction of Silicosis by Inhibiting the ASK1-p38 Pathway and Regulating Macrophage Polarization.

Silicosis is one of the potentially fatal occupational diseases characterized by respiratory dysfunction, chronic interstitial inflammation, and fibrosis, for which treatment options are limited. Previous studies showed that a novel N-arylpyridone compound named AKEX0011 exhibited anti-inflammatory and anti-fibrotic effects in bleomycin-induced pulmonary fibrosis; however, it is unknown whether it could also be effective against silicosis. Therefore, we sought to investigate the preventive and therapeutic roles of AKEX0011 in a silicosis rodent model and in a silica-stimulated macrophage cell line. In vivo, our results showed that AKEX0011 ameliorated silica-induced imaging lung damages, respiratory dysfunction, reduced the secretion of inflammatory and fibrotic factors (TNF-α, IL-1ß, IL-6, TGF-ß, IL-4, and IL-10), and the deposition of fibrosis-related proteins (collagen I, fibronectin, and α-SMA), regardless of early or advanced therapy. Specifically, we found that AKEX0011 attenuated silicosis by inhibiting apoptosis, blocking the ASK1-p38 MAPK signaling pathway, and regulating polarization of macrophages. In vitro, AKEX0011 inhibited macrophages from secreting inflammatory cytokines and inhibited apoptosis of macrophages in pre-treated and post-treated models, concurrent with blocking the ASK1-p38 pathway and inhibiting M1 polarization. Collectively, AKEX0011, as a novel N-arylpyridone compound, exerted protective effects for silica-induced pulmonary inflammation and fibrosis both in vivo and in vitro, and hence, it could be a strong drug candidate for the treatment of silicosis.