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1.
Nat Commun ; 14(1): 5601, 2023 09 12.
Article En | MEDLINE | ID: mdl-37699899

The immunomodulatory effects of ultraviolet B (UVB) radiation in human diseases have been described. Whether type 2 lung inflammation is directly affected by solar ultraviolet (UV) radiation is not fully understood. Here, we show a possible negative correlation between solar UVB radiation and asthmatic inflammation in humans and mice. UVB exposure to the eyes induces hypothalamus-pituitary activation and α-melanocyte-stimulating hormone (α-MSH) accumulation in the serum to suppress allergic airway inflammation by targeting group 2 innate lymphoid cells (ILC2) through the MC5R receptor in mice. The α-MSH/MC5R interaction limits ILC2 function through attenuation of JAK/STAT and NF-κB signaling. Consistently, we observe that the plasma α-MSH concentration is negatively correlated with the number and function of ILC2s in the peripheral blood mononuclear cells (PBMC) of patients with asthma. We provide insights into how solar UVB radiation-driven neuroendocrine α-MSH restricts ILC2-mediated lung inflammation and offer a possible strategy for controlling allergic diseases.


Asthma , alpha-MSH , Humans , Animals , Mice , Immunity, Innate , Leukocytes, Mononuclear , Lymphocytes , Inflammation , Lung
2.
Chemosphere ; 343: 140241, 2023 Dec.
Article En | MEDLINE | ID: mdl-37742768

In recent years, the biogeochemical behavior and environmental impact of Selenium (Se) on soil-plant systems have received widespread attention, and traditional statistical methods reveal generally positive correlations between rice Se and soil Se. However, that initial positive relationship may have been obscured by local external factors. Using local scale data from the geochemical evaluation of land quality project, this work employed geographically weighted regression (GWR) to examine the spatial variation of rice Se (as the dependent variable) and soil Se (as the independent variable) in Guangxi. Strong and weak correlation coefficients occur between rice Se and soil Se, thereby indicating that their relationships are spatially varying. Guangxi is characterized by significantly positive correlations in most areas, with weak correlations mostly found in the south-western and central-eastern regions. Areas with weak correlation can be divided into two patterns: high soil Se with low rice Se and high rice Se with low soil Se. The unique patterns are correlated with distinct natural factors, particularly the abundance of Fe-rich soils in the carbonate area; by contrast, sandstone areas in central Guangxi may have been affected by anthropogenic activities. To reveal the spatially varying relationships at the local scale, we employed GWR, an effective tool that allowed us to identify the association between environmental variables and influencing factors and explore spatially varying relationships between them. This study breaks through the existing understanding that soil Se is completely positively correlated with rice Se for the first time, and concludes that their correlation is spatially variable, providing an effective approach for the study of complex relationships.


Oryza , Selenium , Soil Pollutants , Selenium/analysis , Spatial Regression , Oryza/chemistry , Soil/chemistry , China , Soil Pollutants/analysis
3.
Cell Discov ; 9(1): 82, 2023 Aug 01.
Article En | MEDLINE | ID: mdl-37528081

The Mulibrey (Muscle-liver-brain-eye) nanism caused by loss-of-function variants in TRIM37 gene is an autosomal recessive disorder characterized by severe growth failure and constrictive pericarditis. These patients also suffer from severe respiratory infections, co-incident with an increased mortality rate. Here, we revealed that TRIM37 variants were associated with recurrent infection. Trim37 FINmajor (a representative variant of Mulibrey nanism patients) and Trim37 knockout mice were susceptible to influenza virus infection. These mice showed defects in follicular helper T (TFH) cell development and antibody production. The effects of Trim37 on TFH cell differentiation relied on its E3 ligase activity catalyzing the K27/29-linked polyubiquitination of Bcl6 and its MATH domain-mediated interactions with Bcl6, thereby protecting Bcl6 from proteasome-mediated degradation. Collectively, these findings highlight the importance of the Trim37-Bcl6 axis in controlling the development of TFH cells and the production of high-affinity antibodies, and further unveil the immunologic mechanism underlying recurrent respiratory infection in Mulibrey nanism.

4.
Chemosphere ; 340: 139846, 2023 Nov.
Article En | MEDLINE | ID: mdl-37598945

The selenium (Se)-deficient soil belt in China has gained widespread attention. During large-scale soil surveys in China, Se-rich soils within low-Se belts have been identified. However, the sources of Se in those soils and the controlling factors for their enrichment remain unclear. Here we summarize Se concentrations and spatial distributions in the Yuanzhou district of the Loess Plateau. We evaluated Se variations in soil profiles, Se migration into water bodies, and considered soil indicators, topographic characteristics and the influence of land-use types on soil Se concentrations. The average Se concentration in the topsoil of the Yuanzhou district was 0.164 µg/g. High-Se soils (>0.222 µg/g) were found in the western valley plain and the southern red bed hilly area, as well as sporadically in higher elevation forestland and grassland areas in the east. Enrichment of Se in the topsoil in the eastern and southern areas was primarily due to Se adsorption and accumulation by soil organic matter as well as enrichment in gypsum, berlinite, and clay minerals during soil formation. Widespread enrichment in the southern area was linked to high Se concentrations in red Tertiary sedimentary rocks. In the western area, enrichment of Se in topsoil was found on both sides of the Qingshui River at low elevations with gentle slopes, with river water being the primary carrier of Se enrichment. These findings provide valuable insights into the epigenetic geochemical behavior of soil Se in China's low-Se belt that accounts for development of Se-rich soils in the region.


Selenium , Soil , China , Forests , Water
5.
Sci Total Environ ; 898: 165482, 2023 Nov 10.
Article En | MEDLINE | ID: mdl-37467982

The Quaternary sediment-distributed regions of South China are suitable for rice cultivation, which is crucial for ensuring food security. Spatial correlations between soil cadmium (Cd) and rice Cd contents are generally poor, making the evaluation of rice quality and associated health risks challenging. In this study, we developed machine learning algorithms for predicting rice Cd contents using 654 data pairs of soil-rice samples collected in Guangxi province, China. After a comprehensive comparison, our results showed that the random forest (RF) had the better performance than artificial neural network (ANN) based on all the data (RMSEtesting 0.066 vs. 0.099 and R2testing 0.860 vs. 0.688). The feature importance analysis showed that soil CaO, Cd, elevation, and rainfall were the four most important features affecting the rice Cd contents in the study area. Using the established RF-predicated model, the rice Cd contents were predicted at the provincial level with an additional dataset of 1176 paddy soil samples. The prediction result revealed about 23 % of farmland cultivated rice with Cd content over 0.2 mg kg-1 in the study area. Therefore, it is recommended to implement strict measures by local agricultural departments to reduce rice Cd contents and ensure food safety in these areas. Our study provides valuable insights into the prediction of rice Cd contents, thus contributing to ensuring food safety and preventing Cd exposure-associated health risks.

6.
Brain Behav ; 13(7): e3054, 2023 07.
Article En | MEDLINE | ID: mdl-37165747

BACKGROUNDS: Previous studies have demonstrated that both serum lipid levels and sex are crucial factors associated with individual cognition. However, the impact of sex and serum lipid interaction effects on the brain and cognition remains largely unknown. This study aimed to explore the underlying neural mechanisms among sex, serum lipids, and cognition using large-scale brain networks. METHODS: Resting-state functional MRI data were collected from 157 young healthy adults. Independent component analysis was used to examine large-scale inter- and intra-network functional connectivity (FCs). Peripheral venous blood samples were collected to measure serum lipid levels. The three-back task was employed to assess cognition (i.e., working memory). General linear model, correlation, and mediation analyses were conducted to examine the interaction effects of sex and serum lipids on large-scale brain networks and their relationship with working memory. RESULTS: We found that inter-network connectivity with the executive control network at its core was more susceptible to sex and triglyceride interaction effects. The intra-network connectivity in the dorsal attention networks (DANs), lateral visual networks, and anterior default mode networks was influenced by the interaction effects of sex and total cholesterol (TC)/low-density lipoprotein cholesterol. Specifically, correlations between serum lipids and affected brain networks were found to be sex-specific. In addition, higher intra-network FC in the right inferior parietal (R-IPL) of the DAN correlated with a longer three-back reaction time in females. More importantly, the relationship between serum TC levels and three-back reaction time was mediated by intra-network connectivity in the R-IPL of the DAN. CONCLUSIONS: Our findings describe the impact of sex and serum lipid interaction effects on large-scale brain networks, as well as on cognitive function. Our data suggest that sex-specific usage of serum lipids or brain networks would be beneficial for monitoring and therapy in dyslipidemia-related cognition decline.


Brain Mapping , Memory, Short-Term , Male , Adult , Female , Humans , Neural Pathways , Brain/diagnostic imaging , Cognition , Cholesterol , Lipids , Magnetic Resonance Imaging , Nerve Net/diagnostic imaging
7.
Plants (Basel) ; 12(6)2023 Mar 20.
Article En | MEDLINE | ID: mdl-36987066

This study investigated the protective effects of exogenous ascorbic acid (AsA, 0.5 mmol·L-1) treatment on salt-induced photosystem inhibition in tomato seedlings under salt stress (NaCl, 100 mmol·L-1) conditions with and without the AsA inhibitor lycorine. Salt stress reduced the activities of photosystem II (PSII) and PSI. AsA treatment mitigated inhibition of the maximal photochemical efficiency of PSII (Fv/Fm), maximal P700 changes (Pm), the effective quantum yields of PSII and I [Y(II) and Y(I)], and non-photochemical quenching coefficient (NPQ) values under salt stress conditions both with and without lycorine. Moreover, AsA restored the balance of excitation energy between two photosystems (ß/α-1) after disruption by salt stress, with or without lycorine. Treatment of the leaves of salt-stressed plants with AsA with or without lycorine increased the proportion of electron flux for photosynthetic carbon reduction [Je(PCR)] while decreasing the O2-dependent alternative electron flux [Ja(O2-dependent)]. AsA with or without lycorine further resulted in increases in the quantum yield of cyclic electron flow (CEF) around PSI [Y(CEF)] while increasing the expression of antioxidant and AsA-GSH cycle-related genes and elevating the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG). Similarly, AsA treatment significantly decreased the levels of reactive oxygen species [superoxide anion (O2-) and hydrogen peroxide (H2O2)] in these plants. Together, these data indicate that AsA can alleviate salt-stress-induced inhibition of PSII and PSI in tomato seedlings by restoring the excitation energy balance between the photosystems, regulating the dissipation of excess light energy by CEF and NPQ, increasing photosynthetic electron flux, and enhancing the scavenging of reactive oxygen species, thereby enabling plants to better tolerate salt stress.

8.
Ecotoxicol Environ Saf ; 255: 114808, 2023 Apr 15.
Article En | MEDLINE | ID: mdl-36958262

Soils developed in karst regions have naturally high background values of molybdenum (Mo) due to geological factors. However, the enrichment mechanism of Mo in these soils are not fully understood, making it challenging to assess their ecological risk and utilize Mo-rich land resources. To shed light on this issue, this study collected and analyzed data from the 1:50,000 geochemical survey in Guangxi, including 536,503 sets of soil data and 3043 sets of rock data, as well as 40 sets of carbonate rock-soil from typical karst regions. The results showed that soil Mo enrichment is highly correlated with the distribution of carbonate rocks in karst regions. The carbonate rocks in these regions contain Mo ranging from 0.03 to 1.06 mg·kg-1 (with a mean of 0.22 mg·kg-1). In comparison, the soil Mo derived from carbonate rocks can reach up to 6.00 mg·kg-1 (with a mean of 2.75 mg·kg-1), representing an average enrichment of soil Mo that is 24 times higher compared to the carbonate parent rock. The enrichment of soil Mo in karst regions is primarily controlled by secondary enrichment during the weathering process of carbonate. During the insoluble residue accumulation process, the dissolution of carbonate leads to a dramatic reduction in bedrock volume, and the adsorption of clay minerals and Fe minerals in insoluble residues plays an essential role in Mo enrichment during these stages. During the soil-forming stage of the insoluble residue, most Mo leaches into the water body due to the mineral transformation of insoluble residue. Consequently, as Fe-Mn nodules in soils become more enriched with increasing weathering intensity, some Mo is absorbed and passivated by iron and manganese oxides (hydroxides). Accordingly, the contribution of Fe-Mn nodules and the degree of leaching were closely related to the enrichment of soil Mo in karst regions. This study provides insights into the enrichment mechanisms of Mo in soils developed in karst regions, which will help to evaluate their ecological risk in these environments.


Molybdenum , Soil , Soil/chemistry , China , Environmental Monitoring/methods , Minerals , Carbonates/analysis
9.
Cell Mol Immunol ; 20(4): 404-418, 2023 04.
Article En | MEDLINE | ID: mdl-36823235

Group 2 innate lymphoid cells (ILC2s) are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13, which mediate the type 2 immune response. However, specific drug targets on lung ILC2s have rarely been reported. Previous studies have shown that type 2 cytokines, such as IL-5 and IL-13, are related to depression. Here, we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression. Interestingly, serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation. Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs. Furthermore, an HTR2A selective agonist (DOI) impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro. Mice with ILC2-specific depletion of HTR2A (Il5cre/+·Htr2aflox/flox mice) abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation. In conclusion, serotonin and DOI could restrict the type 2 lung immune response, indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ ILC2s.


Immunity, Innate , Pneumonia , Humans , Animals , Mice , Papain , Interleukin-13 , Interleukin-5 , Serotonin , Lymphocytes , Pneumonia/chemically induced , Lung , Cytokines , Interleukin-33
10.
Front Neurol ; 13: 908151, 2022.
Article En | MEDLINE | ID: mdl-36247766

Objective: Assessing the risk of postoperative recurrence of chronic subdural hematoma (CSDH) is a clinical focus. To screen the main factors associated with the perioperative hematoma recurrence. The brain re-expansion is the core factor of recurrence. A clinical prognostic scoring system was also proposed. Methods: We included 295 patients with unilateral CSDH as the training group for modeling. Factors predicting postoperative recurrence requiring reoperation (RrR) were determined using univariate and multivariate regression analyses, and bivariate Pearson correlation coefficient analysis was used to exclude related factors. Receiver operating characteristic curve analysis evaluates the ability of main factors to predict RrR and determines the cut-off value of brain re-expansion rate. We developed a prognostic scoring system and conducted preliminary verification. A verification group including 119 patients with unilateral CSDH was used to verify the grading systems. Results: The key factors for predicting unilateral CSDH recurrence were cerebral re-expansion rate (≤ 40%) at postoperative days 7-9 (OR 25.91, p < 0.001) and the preoperative CT density classification (isodense or hyperdense, or separated or laminar types) (OR 8.19, p = 0.007). Cerebral atrophy played a key role in brain re-expansion (OR 2.36, p = 0.002). The CSDH prognostic grading system ranged from 0 to 3. An increased score was associated with a more accurate progressive increase in the RrR rate (AUC = 0.856). Conclusions: Our prognostic grading system could screen clinically high-risk RrR patients with unilateral CSDH. However, increased attention should be paid to brain re-expansion rate after surgery in patients with CSDH.

11.
Bull Environ Contam Toxicol ; 109(5): 910-919, 2022 Nov.
Article En | MEDLINE | ID: mdl-35915172

To determine whether the national soil heavy metal standards (GB 15618-2018) are applicable to some carbonate and non-carbonate zones in Southwest China, rice and rhizosphere soil samples were collected in Chongqing and analyzed for heavy metal contents, pH, and other chemical parameters. In addition, regression analysis was also used to predict the risk threshold of soil heavy metals. The Cd risk screening value in GB 15618-2018 was strict for alkaline soils (pH > 7.5) as compared to those revealed in carbonate and non-carbonate areas, while the calculated pollution threshold for Cd in acidic soils (pH ≤ 5.5) in the non-carbonate area was lower than that in GB 15618-2018. Therefore, to improve the applicability of the evaluation results, a soil-crop system evaluation is recommended.


Metals, Heavy , Soil Pollutants , Soil/chemistry , Soil Pollutants/analysis , Cadmium/analysis , Environmental Monitoring , Risk Assessment , Metals, Heavy/analysis , China
12.
Nat Immunol ; 23(7): 1021-1030, 2022 07.
Article En | MEDLINE | ID: mdl-35794369

Interleukin-33 (IL-33), an epithelial cell-derived cytokine that responds rapidly to environmental insult, has a critical role in initiating airway inflammatory diseases. However, the molecular mechanism underlying IL-33 secretion following allergen exposure is not clear. Here, we found that two cell events were fundamental for IL-33 secretion after exposure to allergens. First, stress granule assembly activated by allergens licensed the nuclear-cytoplasmic transport of IL-33, but not the secretion of IL-33. Second, a neo-form murine amino-terminal p40 fragment gasdermin D (Gsdmd), whose generation was independent of inflammatory caspase-1 and caspase-11, dominated cytosolic secretion of IL-33 by forming pores in the cell membrane. Either the blockade of stress granule assembly or the abolishment of p40 production through amino acid mutation of residues 309-313 (ELRQQ) could efficiently prevent the release of IL-33 in murine epithelial cells. Our findings indicated that targeting stress granule disassembly and Gsdmd fragmentation could reduce IL-33-dependent allergic airway inflammation.


Allergens , Interleukin-33 , Phosphate-Binding Proteins/metabolism , Pore Forming Cytotoxic Proteins/metabolism , Animals , Caspase 1/metabolism , Inflammation , Interleukin-1beta/metabolism , Interleukin-33/genetics , Interleukin-33/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Mice , Peptide Hydrolases/metabolism , Stress Granules
13.
ACS Chem Neurosci ; 13(3): 330-339, 2022 02 02.
Article En | MEDLINE | ID: mdl-35044760

Parkinson's disease (PD) is a devastating disease of the central nervous system that occurs mainly in the elderly age group, affecting their quality of life. The PD pathogenesis is not yet fully understood and lacks the disease-modifying treatment strategies. Sanghuangprous vaninii (S. vaninii) is a perennial fungus with a plethora of pharmacological activities including anti-cancer and antioxidant activity and so on. However, no study till date has reported its neuroprotective effect against symptoms that are similar to PD in pre-clinical investigation. In the current study, we investigated anti-PD-like effects of S. vaninii mycelium extracts (SvMEs) on MPTP-induced PD in zebrafish. We observed that the loss of dopaminergic neurons and neurovascular reduction were reversed by using SvMEs in the zebrafish brain in a concentration-independent manner. Moreover, it also relieved locomotor impairments in MPTP-induced PD zebrafish. In addition, SvMEs exerted significant antioxidant activity in vitro, which was also demonstrated in vivo on ktr4:NTR-hKikGR zebrafish. Upon investigating the underlying mechanism, we found that SvMEs may alleviate oxidant stress and accelerate α-synuclein degradation and then alleviate PD-like symptoms. Antioxidant-related genes (sod1, gss, gpx4a, gclm, and cat) implied that the SvMEs exhibited anti-PD activity due to the antioxidation mechanism. Finally, upon analysis of chemical composition of SvMEs by liquid chromatography-mass spectrometry, we identified 10 compounds that are plausibly responsible for the anti-PD-like effect of SvMEs. On the limiting part, the finding of the study would have been more robust had we investigated the protein expression of genes related to PD and oxidative stress and compared the effects of SvMEs with any standard anti-PD therapy. Despite this, our results indicated that SvMEs possess anti-PD effects, indicating SvMEs as a potential candidate that is worth exploring further in this avenue.


Basidiomycota , MPTP Poisoning , Neuroprotective Agents , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Animals , Disease Models, Animal , Dopaminergic Neurons/metabolism , MPTP Poisoning/pathology , Mice , Mice, Inbred C57BL , Neuroprotective Agents/pharmacology , Quality of Life , Zebrafish
14.
Allergy ; 77(7): 2104-2120, 2022 07.
Article En | MEDLINE | ID: mdl-34995358

BACKGROUND: Organisms have orchestrated coagulation and immune systems. Although a link between inflammation and haemostasis has been reported in asthma, the interaction mechanism has not been completely elucidated. Here, we investigated the direct link between the mammalian immune and coagulation systems. METHODS: Mice were administered protease or antigens intranasally to induce airway inflammation with or without thrombin inhibitors treatment. The effects of thrombin and its inhibitors on interleukin (IL)-33 were investigated both in vivo and in vitro. Peripheral blood mononuclear cells (PBMCs) and plasma from asthma patients are collected to verify the correlation between thrombin and group 2 innate lymphocytes (ILC2s). RESULTS: Low-molecular-weight heparin (LMWH, an indirect inhibitor of thrombin) restrained both papain- and fungus-induced type 2 immune responses in mice by inhibiting IL-33 cleavage. Upon examining the potential thrombin protease consensus sites, we found that IL-33 was directly cleaved by thrombin at specific amino acids (R48 and R106) to generate a mature form of IL-33 with potent biological activity. In addition, we found that bivalirudin TFA (a direct inhibitor of thrombin) inhibited a variety of type 2 inflammatory responses, such as those in house dust mite (HDM)- and ovalbumin (OVA)-mediated pulmonary inflammation models. We found that plasma thrombin-antithrombin complex (TATc) levels in asthma patients were positively associated with the number and function of IL-33-responder group 2 innate lymphocytes (ILC2s) among peripheral blood mononuclear cells (PBMCs) from asthma patients. CONCLUSION: The data suggested that thrombin inhibitors administration could be effective in treating lung inflammation by regulating ILC2s via IL-33 maturation, indicating that targeting thrombin is a potential way to treat allergic diseases.


Alveolitis, Extrinsic Allergic , Asthma , Pulmonary Eosinophilia , Animals , Cytokines/metabolism , Heparin, Low-Molecular-Weight/metabolism , Heparin, Low-Molecular-Weight/pharmacology , Immunity, Innate , Inflammation/metabolism , Interleukin-33/metabolism , Leukocytes, Mononuclear/metabolism , Lung , Lymphocytes , Mice , Thrombin/metabolism , Thrombin/pharmacology
15.
Front Oncol ; 11: 738534, 2021.
Article En | MEDLINE | ID: mdl-34692516

This investigation was conducted to elucidate whether atractylenolide-I (ATL-1), which is the main component of Atractylodes macrocephala Koidz, can sensitize triple-negative breast cancer (TNBC) cells to paclitaxel and investigate the possible mechanism involved. We discovered that ATL-1 could inhibit tumor cell migration and increase the sensitivity of tumor cells to paclitaxel. ATL-1 downregulated the expression and secretion of CTGF in TNBC cells. Apart from inhibiting TNBC cell migration via CTGF, ATL-1 downregulated the expression of CTGF in fibroblasts and decreased the ability of breast cancer cells to transform fibroblasts into cancer-associated fibroblasts (CAFs), which in turn increased the sensitivity of TNBC cells to paclitaxel. In a mouse model, we found that ATL-1 treatments could enhance the chemotherapeutic effect of paclitaxel on tumors and reduce tumor metastasis to the lungs and liver. Primary cultured fibroblasts derived from inoculated tumors in mice treated with ATL-1 combined with paclitaxel expressed relatively low levels of CAF markers. Collectively, our data indicate that ATL-1 can sensitize TNBC cells to paclitaxel by blocking CTGF expression and fibroblast activation and could be helpful in future research to determine the value of ATL-1 in the clinical setting.

16.
Clin Genet ; 100(3): 340-347, 2021 09.
Article En | MEDLINE | ID: mdl-34101167

PKD2 gene variants account for 4.5% to 20% of patients with autosomal dominant polycystic kidney disease (ADPKD). Little is known about the clinical characteristics of PKD2 variants in Chinese patients with ADPKD. Herein, we performed a comprehensive search for variants of PKD2 gene in 44 Chinese ADPKD pedigrees and a total of 37 variants were identified. Of these 37 variants, 18 were nonsense variants, 10 frameshift variants, 4 missense variants, and 5 splice site variants. 11/37 variants were detected for the first time. The median age at diagnosis was 30.5 years, and positive family history was detected in 77.27% patients, liver cysts in 68.18%, hypertension in 45.45%, nephrolithiasis in 31.82%, macro-hematuria in 22.73%, and proteinuria in 13.63%. The level of estimated glomerular filtration rate in 8/39 patients were blow 60 ml/min/1.73m2 . 11/17 patients were classified as rapid progression by Mayo Clinic classification. The end stage renal disease (ESRD) events were reported in 9/22 pedigrees, and the presence of nephrolithiasis and macro-hematuria were significantly associated with ESRD in the pedigrees with PKD2 variants. The identified variants and clinical features will facilitate the early diagnosis and prognosis prediction in Chinese ADPKD patients with PKD2 variants.


Polycystic Kidney, Autosomal Dominant/genetics , TRPP Cation Channels/genetics , Adolescent , Adult , Asian People/genetics , DNA Mutational Analysis , Female , Humans , Male , Middle Aged , Mutation , Pedigree , Polycystic Kidney, Autosomal Dominant/enzymology , Polycystic Kidney, Autosomal Dominant/physiopathology , Young Adult
17.
Org Biomol Chem ; 19(17): 3932-3939, 2021 05 05.
Article En | MEDLINE | ID: mdl-33949584

A new three-component reaction of 3-oxo-3-arylpropanenitriles with arylsulfonyl hydrazides has been established, and an expanded inventory of 3-aryl-4-(arylthio)-1H-pyrazol-5-amines is synthesized by sequential cyclization and sulfenylation reactions under the action of NIS. In addition to the attractive features of multicomponent reactions, the protocol presents broad substrate scope, good functional group tolerance and mild reaction conditions. The utility of this procedure is further established by gram-scale synthesis as well as the diversified transformations of the products to useful compounds.

18.
Cell Mol Immunol ; 18(2): 350-362, 2021 02.
Article En | MEDLINE | ID: mdl-32094504

Loss of the colonic inner mucus layer leads to spontaneously severe colitis and colorectal cancer. However, key host factors that may control the generation of the inner mucus layer are rarely reported. Here, we identify a novel function of TRIM34 in goblet cells (GCs) in controlling inner mucus layer generation. Upon DSS treatment, TRIM34 deficiency led to a reduction in Muc2 secretion by GCs and subsequent defects in the inner mucus layer. This outcome rendered TRIM34-deficient mice more susceptible to DSS-induced colitis and colitis-associated colorectal cancer. Mechanistic experiments demonstrated that TRIM34 controlled TLR signaling-induced Nox/Duox-dependent ROS synthesis, thereby promoting the compound exocytosis of Muc2 by colonic GCs that were exposed to bacterial TLR ligands. Clinical analysis revealed that TRIM34 levels in patient samples were correlated with the outcome of ulcerative colitis (UC) and the prognosis of rectal adenocarcinoma. This study indicates that TRIM34 expression in GCs plays an essential role in generating the inner mucus layer and preventing excessive colon inflammation and tumorigenesis.


Carrier Proteins/physiology , Colitis-Associated Neoplasms/prevention & control , Colitis/prevention & control , Colon/pathology , Goblet Cells/pathology , Mucus/physiology , Animals , Carcinogenesis , Carrier Proteins/genetics , Carrier Proteins/metabolism , Colitis/etiology , Colitis-Associated Neoplasms/etiology , Colitis-Associated Neoplasms/pathology , Colon/immunology , Colon/metabolism , Goblet Cells/immunology , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Mucin-2/metabolism
20.
Cell Mol Biol (Noisy-le-grand) ; 66(2): 153-156, 2020 May 15.
Article En | MEDLINE | ID: mdl-32415952

Atypical extraventricular neurocytoma (EVN) is a rare condition characterized by diffuse tumor cell hyperplasia, increased neovascularization, increased necrosis, and aggressive characteristics. A case of a 25-year old man who presented with atypical EVN in his left parietal - occipital flaps is reported. Magnetic resonance imaging (MRI) revealed a well-defined globular mass with heterogeneous signals in the left parietal lobe, and mild perilesional edema. After left parietal craniotomy and tumor excision, pathologic examination of the resected tissue revealed that the lesion was localized mainly in the white matter and imbued with tumor cells possessing round hyperchromatic nuclei with perinuclear halos and increased microvascular proliferation. The patient underwent radiotherapy at 21st postoperative day. Over the past 26 months, the patient has been regularly followed up, and so far no neurologic deficits have been observed. The latest MRI showed that the tumor bed was stable with slight peritumoral edema. The results of clinical, histopathological and immunohistochemical examinations indicate that atypical EVN is a rare neoplasm with unique radiographic and pathologic characteristics. It possesses more aggressive properties than typical EVN.


Brain Neoplasms/diagnosis , Neurocytoma/diagnosis , Adult , Brain/diagnostic imaging , Brain/pathology , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Brain Neoplasms/radiotherapy , Humans , Magnetic Resonance Imaging , Male , Nestin/metabolism , Neurocytoma/diagnostic imaging , Neurocytoma/pathology , Neurocytoma/radiotherapy , Synaptophysin/metabolism
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