[Source and Cause Analysis of High Concentration of Inorganic Aerosol During Two Typical Pollution Processes in Winter over Tianjin].

Inorganic aerosol is the main component of haze days in winter over Tianjin. In this study, two typical high concentrations of secondary inorganic aerosol (SIA) processes, defined as CASE1 and CASE2, were selected during polluted days in January 2020 over Tianjin, and the effects of meteorological factors, regional transport, and chemical processes were comprehensively investigated combined with observations and numerical models (WRF-NAQPMS). The average SIA concentrations in CASE1 and CASE2 were 76.8 µg·m-3 and 66.0 µg·m-3, respectively, and the nitrate concentration was higher than that of sulfate and ammonium, which were typical nitrate-dominated pollution processes. Meteorological conditions played a role in inorganic aerosol formation. The temperature of approximately -6-0℃ and 2-4℃ and the relative humidity of 50%-60% and 80%-100% would be suitable conditions for the high SIA concentration (>80 µg·m-3) in CASE1, whereas the temperature of approximately 2-4℃ and the relative humidity of 60%-70% would be suitable in CASE2. The average contribution rates of external sources to SIA in the CASE1 and CASE2 processes were 62.3% and 22.1%, which were regional transport-dominant processes and local emission-dominant processes, respectively. The contribution of the local emission of CASE1 to nitrate and sulfate was 16.2 µg·m-3 and 8.2 µg·m-3, respectively, higher than that of external sources (31.7 µg·m-3 and 8.8 µg·m-3). the local contribution of CASE2 to nitrate and sulfate was 29.3 µg·m-3 and 25.1 µg·m-3, respectively, whereas the contribution from external sources was 8.1 µg·m-3 and 9.4 µg·m-3, respectively. The quantitative result indicated that local formation and regional transport resulted in higher nitrate concentration than sulfate in CASE1, in contrast to only local sources in CASE2. The gas phase reaction was the main source of inorganic aerosol formation, contributing 48.9% and 57.8% in CASE1 and CASE2, respectively, whereas the heterogeneous reactions were also important processes, with contribution rates of 48.1% and 42.2% to SIA. The effect of aqueous phase reaction was negligible.

Crohn's disease as the intestinal manifestation of pan-lymphatic dysfunction: An exploratory proposal based on basic and clinical data.

Crohn's disease (CD) is caused by immune, environmental, and genetic factors. It can involve the entire gastrointestinal tract, and although its prevalence is rapidly increasing its etiology remains unclear. Emerging biological and small-molecule drugs have advanced the treatment of CD; however, a considerable proportion of patients are non-responsive to all known drugs. To achieve a breakthrough in this field, innovations that could guide the further development of effective therapies are of utmost urgency. In this review, we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases, and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data. The supporting evidence is fully summarized, including the existence of lymphatic system dysfunction, recognition of the inside-out model, disorders of immune cells, changes in cell plasticity, partial overlap of the underlying mechanisms, and common gut-derived fatty and bile acid metabolism. Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases, especially CD, as this model is good at presenting and mimicking lymphatic dysfunction. More importantly, the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.

Single-cell RNA sequencing reveals the immunoregulatory roles of PegIFN-α in patients with chronic hepatitis B.

BACKGROUND AND AIMS: Chronic hepatitis B (CHB) is caused by HBV infection and affects the lives of millions of people worldwide by causing liver inflammation, cirrhosis, and liver cancer. Interferon-alpha (IFN-α) therapy is a conventional immunotherapy that has been widely used in CHB treatment and achieved promising therapeutic outcomes by activating viral sensors and interferon-stimulated genes (ISGs) suppressed by HBV. However, the longitudinal landscape of immune cells of CHB patients and the effect of IFN-α on the immune system are not fully understood. APPROACH AND RESULTS: Here, we applied single-cell RNA sequencing (scRNA-seq) to delineate the transcriptomic landscape of peripheral immune cells in CHB patients before and after PegIFN-α therapy. Notably, we identified three CHB-specific cell subsets, pro-inflammatory (Pro-infla) CD14+ monocytes, Pro-infla CD16+ monocytes and IFNG+ CX3CR1- NK cells, which highly expressed proinflammatory genes and positively correlated with HBsAg. Furthermore, PegIFN-α treatment attenuated percentages of hyperactivated monocytes, increased ratios of long-lived naive/memory T cells and enhanced effector T cell cytotoxicity. Finally, PegIFN-α treatment switched the transcriptional profiles of entire immune cells from TNF-driven to IFN-α-driven pattern and enhanced innate antiviral response, including virus sensing and antigen presentation. CONCLUSIONS: Collectively, our study expands the understanding of the pathological characteristics of CHB and the immunoregulatory roles of PegIFN-α, which provides a new powerful reference for the clinical diagnosis and treatment of CHB.

Paeoniflorin alleviates hypoxia/reoxygenation injury in HK-2 cells by inhibiting apoptosis and repressing oxidative damage via Keap1/Nrf2/HO-1 pathway.

Acute kidney injury (AKI) is a serious disorder associated with significant morbidity and mortality. AKI and ischemia/reperfusion (hypoxia/reoxygenation, H/R) injury can be induced due to several reasons. Paeoniflorin (PF) is a traditional herbal medicine derived from Paeonia lactiflora Pall. It exerts diverse therapeutic effects, including anti-inflammatory, antioxidative, antiapoptotic, and immunomodulatory properties; thus, it is considered valuable for treating several diseases. However, the effects of PF on H/R injury-induced AKI remain unknown. In this study, we established an in vitro H/R model using COCL2 and investigated the functions and underlying mechanisms of PF on H/R injury in HK-2 cells. The cell vitality was evaluated using the cell count kit-8 assay. The DCFH-DA fluorescence probe was used to measure the levels of reactive oxygen species (ROS). Oxidative damage was detected using superoxide dismutase (SOD) and malondialdehyde (MDA) assay kits. Apoptotic relative protein and Keap1/Nrf2/HO-1 signaling were evaluated by Western blotting. Our results indicated that PF increased cell viability and SOD activity and decreased the ROS and MDA levels in HK-2 cells with H/R injury. PF inhibits apoptosis by increasing Bcl-2 and decreasing Bax. Furthermore, PF significantly upregulated the expression of HO-1 and Nrf2, but downregulated the expression of HIF-1α and Keap1. PF considerably increased Nrf2 nuclear translocation and unregulated the HO-1 expression. The Nrf2 inhibitor (ML385) could reverse the abovementioned protective effects of PF, suggesting that Nrf2 can be a critical target of PF. To conclude, we found that PF attenuates H/R injury-induced AKI by decreasing the oxidative damage via the Nrf2/HO-1 pathway and inhibiting apoptosis.

Acid-base transformative HADLA micelles alleviate colitis by restoring adaptive immunity and gut microbiome.

Inflammatory bowel disease (IBD) is a worldwide public health issue with an increasing number of patients annually. However, there is no curative drug for IBD, and the present medication for IBD generally focuses on suppressing hyperactive immune responses, which can only delay disease progression but inevitably induce off-target side effects, including infections and cancers. Herein, late-model orally administered nanotherapeutic micelles (HADLA) were developed based on a conjugate of hyaluronic acid (HA) and dehydrolithocholic acid (DLA), which was simple to achieve and obtained satisfactory therapeutic efficacy in a murine colitis model with a full safety profile. HADLA is capable of targeting inflammatory colon tissues, restoring intestinal barrier function and reducing intestinal epithelial cell death. Moreover, it modulates the adaptive immune system by inhibiting the activation of pathogenic T helper 17 (Th17) cells, and it exhibits more remarkable effects in preventing colitis than DLA alone. Finally, HADLA exhibits a remarkable ability to modulate dysregulated gut microbiomes by increasing beneficial probiotics and decreasing pathogenic bacteria, such as Turicibacter. Compared with the current systemic or subcutaneous administration of biologics, this study opens new avenues in the oral delivery of immune-modulating nanomedicine and introduces DLA as a new medication for IBD treatment.

Detection of N­glycoprotein associated with IgA nephropathy in urine as a potential diagnostic biomarker using glycosylated proteomic analysis.

The aim of the present study was to elucidate the potential diagnostic value of urinary N-glycoprotein in patients with IgA nephropathy (IgAN) using mass spectrometry (MS). All procedures were performed between June 2021 and June 2023 at Guangan People's Hospital (Guangan, China). Fresh mid-morning fasting midstream urine samples were collected from a total of 30 patients with IgAN and 30 sex- and age-matched healthy volunteers. Data acquired from 6 participants are available through ProteomeXchange with the identifier PXD041151. By comparison between the IgAN group (n=3) and healthy controls (n=3) and selection criteria of P<0.05 and |log fold-change|>2, a total of 11 upregulated and 22 downregulated glycoproteins in patients with IgAN were identified. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that glycoproteins are involved in various functions, such as the regulation of cell growth, cell adhesion, cellular component organization and protein binding, as well as multiple pathways, including p53, Notch and mTOR signaling pathways. The urine levels of afamin were further measured by ELISA in a validation cohort to assess the diagnostic performance of the single indicator model. In conclusion, MS-based proteomics of urinary glycoproteins may be an alternative option for diagnosing patients with IgAN. Biomarkers of IgAN may include, but are not limited to, CCL25, PD-L1, HLA-DRB1, IL7RD and WDR82. In addition, the levels of urinary AFM indicators are of diagnostic value for IgAN.

Fluorofenidone Attenuates Renal Interstitial Fibrosis by Enhancing Autophagy and Retaining Mitochondrial Function.

BACKGROUND: Fluorofenidone (AKF-PD) is a novel pyridone agent and has potent anti-NLRP3 inflammasome and anti-fibrotic activities. However, the mechanisms underlying its pharmacological actions are not fully understood. METHODS: A renal fibrosis rat model was established by the unilateral ureteral obstruction (UUO) procedure and the rats were randomized and treated with, or without, AKF-PD for 3 and 7 days. The levels of renal fibrosis, NLRP3 inflammasome activation, mitochondrial function, and autophagy were tested in rat kidney tissues. Macrophages following lipopolysaccharides (LPS) and adenosine 5'-triphosphate (ATP) stimulation were examined by Western blot, spectrophotometry, and TEM. RESULTS: Compared with the untreated UUO rats, AKF-PD treatment significantly mitigated the UUO procedure-induced renal fibrosis in rats. AKF-PD treatment decreased mitochondrial dysfunction and IL-Iß and caspase-1 expression in rat kidney tissues and reduced mitochondrial reactive oxygen species production in activated macrophages. Mechanistically, AKF-PD treatment significantly attenuated the PI3K/AKT/mTOR signaling, increased Beclin-1 and LC3 II expression and autophagosome formation, and ameliorated the mitochondrial damage in renal tissues and activated macrophages. CONCLUSION: The results indicated that AKF-PD treatment inhibited renal interstitial fibrosis by regulating the autophagy-mitochondria-NLRP3 inflammasome pathway.

Antagonizing adipose tissue-derived exosome miR-103-hepatocyte phosphatase and tensin homolog pathway alleviates autophagy in non-alcoholic steatohepatitis: A trans-cellular crosstalk.

BACKGROUND: Obesity plays a vital role in the occurrence and development of non-alcoholic steatohepatitis (NASH). However, the underlining mechanism is still unclear, where adipose tissue (AT) derived exosomes may actively participate. MicroRNAs (miRNAs) are commonly secreted from exosomes for cell communication. Though the regulation of miR-103 on insulin sensitivity has been reported, the specific role of AT-derived exosomes miR-103 in NASH is still vague and further investigation may provide novel therapeutic choices. AIM: To determine the specific role of AT-derived exosomes miR-103 in developing NASH through various methods. METHODS: The expression levels of miR-103 in the AT-derived exosomes and livers were detected and compared between NASH mice and control. The effect of miR-103 on NASH progression was also explored by antagonizing miR-103, including steatosis and inflammation degree changes. The interaction between miR-103 and the autophagy-related gene phosphatase and tensin homolog (PTEN) was confirmed by dual-luciferase reporter assay. The role of the interaction between miR-103 and PTEN on autophagy was verified in NASH-like cells. Finally, the effects of miR-103 from adipose-derived exosomes on NASH and autophagy were analyzed through animal experiments. RESULTS: The expression of miR-103 was increased in NASH mice, compared to the control, and inhibition of miR-103 could alleviate NASH. The results of the dual-luciferase reporter assay showed miR-103 could interact with PTEN. MiR-103-anta decreased p-AMPKa, p-mammalian target of rapamycin (mTOR), and p62 but increased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in NASH mice. Similar results were also observed in NASH-like cells, and further experiments showed PTEN silencing inhibited the effect of miR-103-anta. AT derived-exosome miR-103 aggravated NASH and increased the expressions of p-AMPKa, p-mTOR, and p62 but decreased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in mice. CONCLUSION: AT derived-exosome increased the levels of miR-103 in the liver, and miR-103 aggravated NASH. Mechanically, miR-103 could interact with PTEN and inhibit autophagy.

Esophageal anthracosis occurred after treatment of esophageal tuberculosis secondary to mediastinal tuberculous lymphadenitis: a rare case report.

BACKGROUND: Anthracosis is a disease generally considered to be in the lungs resulting from exposure to industrial dust in the workplace. Esophageal anthracosis is a fairly rare phenomenon and shows a strong correlation with tuberculosis. Moreover, esophageal involvement in tuberculosis is also rare. We here present an extremely rare case in which follow-up gastroesophageal endoscopy revealed a mass with a sunken, black area in the center and raised ring-like pattern in the surrounding mucosa resembling malignant melanoma. Uncovering the patient's tuberculosis history finally avoided a misdiagnosis or overtreatment. CASE PRESENTATION: A 67-year-old male patient was admitted to the hospital due to "repeated chest pain for 1 month". Endoscopic ultrasonography and contrast-enhanced CT scans revealed a mass adjacent to the esophageal wall with unclear boundaries. Aspiration biopsy confirmed that esophageal tuberculosis was caused by nearby mediastinal tuberculous lymphadenitis. After a standard anti-tuberculosis treatment regimen, the patient achieved a favorable prognosis. The follow-up gastroesophageal endoscopy showed a sunken black lesion with elevated peripheral mucosa replacing the original tuberculous mass, which was thought to be anthracosis, a disease that rarely occurs in the esophagus. CONCLUSION: The diagnosis of tuberculosis should be taken into consideration when a submucosal mass appears in the middle part of the esophagus. Endoscopic ultrasonography can effectively contribute to a definite diagnosis. Moreover, this is the first case of esophageal anthracosis observed only 1 year after the treatment of tuberculosis, indicating esophageal anthracosis can be a short-term disease. The traction of the reduction of tubercular mediastinal lymph nodes after anti-tuberculosis treatment may create a circumstance for pigmentation or dust deposition.

Impacts of meteorology and precursor emission change on O3 variation in Tianjin, China from 2015 to 2021.

Deterioration of surface ozone (O3) pollution in Northern China over the past few years received much attention. For many cities, it is still under debate whether the trend of surface O3 variation is driven by meteorology or the change in precursors emissions. In this work, a time series decomposition method (Seasonal-Trend decomposition procedure based on Loess (STL)) and random forest (RF) algorithm were utilized to quantify the meteorological impacts on the recorded O3 trend and identify the key meteorological factors affecting O3 pollution in Tianjin, the biggest coastal port city in Northern China. After "removing" the meteorological fluctuations from the observed O3 time series, we found that variation of O3 in Tianjin was largely driven by the changes in precursors emissions. The meteorology was unfavorable for O3 pollution in period of 2015-2016, and turned out to be favorable during 2017-2021. Specifically, meteorology contributed 9.3 µg/m3 O3 (13%) in 2019, together with the increase in precursors emissions, making 2019 to be the worst year of O3 pollution since 2015. Since then, the favorable effects of meteorology on O3 pollution tended to be weaker. Temperature was the most important factor affecting O3 level, followed by air humidity in O3 pollution season. In the midday of summer days, O3 pollution frequently exceeded the standard level (>160 µg/m3) at a combined condition with relative humidity in 40%-50% and temperature > 31°C. Both the temperature and the dryness of the atmosphere need to be subtly considered for summer O3 forecasting.

Land-sea difference of the planetary boundary layer structure and its influence on PM2.5 - Observation and numerical simulation.

A comprehensive set of observations were collected along a sea-coast-inland area. According to these observations, the planetary boundary layer heights (PBLH) during winter and summer for sampling locations in sea, coast, and inland areas were 737 m, 483 m and 372 m, and 450 m, 645 m and 646 m, respectively. Little seasonal difference was observed for the daily variation of sensible heat flux over the sea, with the maximum of 55 W/m2 at 12:00 in winter and 27 W/m2 at 13:00 in summer. The duration of sea breeze was ∼10 h in summer and only 3 h in winter, extended to inland area ∼ 50 km and upward 920 m vertically. PM2.5 at coastal area was about 5 µg/m3 higher than inland during summer afternoon. Over the sea, PM2.5 mainly concentrated below 200 m in winter, increased with height at night and decreased with height in the morning below 300 m in summer. A typical land-sea breeze episode was analyzed with observed and simulated result. According to the observed data, the sea breeze extended to inland ∼50 km and upward 300 m vertically. From the simulating result, there was a clear temperature gradient between sea and land from surface to 400 m, when influenced by the sea breeze, the wind and temperature profiles showed different characteristics, and forming a high concentration center of PM2.5 at 300 m. These results provide insights into the structure of land-sea planetary boundary layer, and provide support for the prediction of heavy pollution episode.

High-fat diet aggravates colitis via mesenteric adipose tissue derived exosome metastasis-associated lung adenocarcinoma transcript 1.

BACKGROUND: Obesity is associated with an increased risk of developing Crohn's disease (CD), higher disease activity, and comparatively worse clinical outcomes. AIM: To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals. METHODS: First, we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis. We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in mesenteric adipose tissue-derived exosomes and the colon. Next, we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6 (ATF6) axis. Finally, we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid (TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways. RESULTS: High-fat diet was found to aggravate TNBS-induced colitis in mice. The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased. The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway. This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p. CONCLUSION: Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice, which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.

Comparative methylomics and chromatin accessibility analysis in Osmanthus fragrans uncovers regulation of genic transcription and mechanisms of key floral scent production.

Linalool and ionone are two important aromatic components in sweet osmanthus petals, and the regulatory mechanisms that produce these two components remain unclear. In this study, we employed whole-genome methylation sequencing and ATAC-seq technology to analyze the genomic DNA methylation status and chromatin accessibility of the sweet osmanthus cultivars 'Zaohuang' and 'Chenghong Dangui'. Results showed that the promoter region of TPS2, a key gene in the linalool synthesis pathway, was less methylated in 'Chenghong Dangui' than in 'Zaohuang'. The chromatin was more accessible in 'Chenghong Dangui' than in 'Zaohuang', which resulted in a much stronger expression of this gene in 'Chenghong Dangui' than in 'Zaohuang'. This eventually led to a high quantity of linalool and its oxides in the petals of 'Chenghong Dangui', but there were lower levels present in the petals of 'Zaohuang'. These results suggest that DNA methylation and chromatin accessibility play major roles in linalool synthesis in sweet osmanthus. The methylation level of the promoter region of CCD4, a key gene for ionone synthesis, was higher in 'Zaohuang' than in 'Chenghong Dangui'. The chromatin accessibility was lower in 'Zaohuang' than in 'Chenghong Dangui', although the expression of this gene was significantly higher in 'Zaohuang' than in 'Chenghong Dangui'. ChIP-seq analysis and a series of experiments showed that the differential expression of CCD4 and CCD1 in the two cultivars may predominantly be the result of regulation by ERF2 and other transcription factors. However, a 183-bp deletion involving the CCD4 promoter region in 'Chenghong Dangui' may be the main reason for the low expression of this gene in its petals. This study provides an important theoretical basis for improving selective breeding of key floral fragrance components in sweet osmanthus.

Emulsifying properties of different soy hull pectin polysaccharides and application in mayonnaise.

Soy hull pectic polysaccharide (SHPP) is a kind of biological macromolecule prepared from soy hull, which has certain thickening and gel properties. In present study, SHPP was extracted with citric acid and sodium citrate from soybean hulls under the assistance of microwave, respectively. SHPPs were then compared with commercial pectin polysaccharide to test their emulsification ability. The emulsion prepared from SHPP extracted with sodium citrate has the best emulsifying effect, small particle size and uniform distribution. The rheological properties and particle size distribution of mayonnaise did not change significantly after the addition of different SHPPs and commercial pectin polysaccharides. However, microscopic observations revealed that the droplets were more uniformly distributed in the mayonnaise after the addition of SHPP extracted with sodium citrate under the assistance of microwave and commercial pectin APC141. SHPP extracted with sodium citrate may play an important role in maintaining emulsion stability in the future. Supplementary Information: The online version of this article (10.1007/s10068-022-01083-2) contains supplementary material, which is available to authorized users.

A method for in vivo treatment verification of IMRT and VMAT based on electronic portal imaging device.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) and volume-modulated arc therapy (VMAT) are rather complex treatment techniques and require patient-specific quality assurance procedures. Electronic portal imaging devices (EPID) are increasingly used in the verification of radiation therapy (RT). This work aims to develop a novel model to predict the EPID transmission image (TI) with fluence maps from the RT plan. The predicted TI is compared with the measured TI for in vivo treatment verification. METHODS: The fluence map was extracted from the RT plan and corrections of penumbra, response, global field output, attenuation, and scatter were applied before the TI was calculated. The parameters used in the model were calculated separately for central axis and off-axis points using a series of EPID measurement data. Our model was evaluated using a CIRS thorax phantom and 20 clinical plans (10 IMRT and 10 VMAT) optimized for head and neck, breast, and rectum treatments. RESULTS: Comparisons of the predicted and measured images were carried out using a global gamma analysis of 3%/2 mm (10% threshold) to validate the accuracy of the model. The gamma pass rates for IMRT and VMAT were greater than 97.2% and 94.5% at 3%/2 mm, respectively. CONCLUSION: We have developed an accurate and straightforward EPID-based quality assurance model that can potentially be used for in vivo treatment verification of the IMRT and VMAT delivery.

The sex steroid precursor dehydroepiandrosterone prevents nonalcoholic steatohepatitis by activating the AMPK pathway mediated by GPR30.

The prevalence of nonalcoholic steatohepatitis (NASH) caused by estrogen deficiency increased sharply in recent decades and has become a major threat to liver health in postmenopausal women. There is no effective strategy to control the incidence and development of NASH. Dehydroepiandrosterone (DHEA) is the most abundant circulating steroid with immune and metabolic regulatory properties, and its level markedly declines with increasing age in humans. Importantly, DHEA can convert into active sex hormones depending on the local needs of target tissues with little diffusion, which serves to avoid systemic side-effects from other tissues' exposure to estrogen. Here, we found that DHEA prevented the incidence and development of NASH, which is characterized by the reduction of hepatic steatosis, fibrosis, and inflammation in female mice fed with high-fat/high-cholesterol diets and effectively attenuated lipid accumulation, inflammatory response, and oxidative stress in palmitic acid-challenged hepatocytes. Mechanistically, in vitro and in vivo studies showed that the anti-NASH function of DHEA depended on its biotransformation into estrogen rather than androgen, and which up-regulates the expression of G protein-coupled estrogen receptor (GPR30), a non-classical estrogen receptor. The activation of GPR30-mediated AMP-activated protein kinase signaling is a necessary prerequisite for the alleviative effects of DHEA on NASH. Collectively, our data show the mechanisms of DHEA treatment and its effects on NASH that were previously overlooked; the data also show that GPR30 can be used as a target for treating lipid metabolism disorders and related diseases, such as NASH. Furthermore, these findings have the potential to help researchers develop new strategies for preventing NASH in postmenopausal women.

Prevalence of frailty and prediction of mortality in Chinese cancer patients using a frailty index-based clinical algorithm-A multicentre study.

PURPOSE: To investigate the frailty status in Chinese cancer patients through establishing a novel prediction algorithm. METHODS: The percentage of frailty in various age groups, locations, and tumor types in Chinese cancer patients was investigated. The prediction capacity of frailty on mortality of Chinese cancer patients was analysed by the frailty index composing of routine laboratory data (FI-LAB) accessible from a blood test and calculated as the ratio of abnormal factors to 22 total variables. The establishment of a novel algorithm, MCP (mortality of cancer patients), to predict the 5-year mortality in Chinese cancer patients was accomplished and the algorithm's prediction capacity was tested in the training and validation sets using receiver operating characteristic (ROC) analysis. RESULTS: We found that the risk of death in cancer patients can be successfully identified through FI-LAB. The univariable and multivariable Cox regression were used to evaluate the effect of frailty on death. In the 5-year follow-up, 20.6% of the 2959 participants (age = 55.8 ± 11.7 years; 43.5% female) died, while the mean FI-LAB score in baseline was 0.23 (standard deviation = 0.13; range = 0-0.73). Frailty (after adjusting for gender, age, and other confounders) directly correlated with an increased risk of death, hazard ratio of 12.67 (95% confidence interval [CI]: 7.19, 22.31), compared to those without frailty. In addition, the MCP algorithm (MCP) = 3.678 × FI-LAB + 1.575 × sex + 1.779 × first tumor node metastasis staging, presented an area under the ROC (AUC) of 0.691 (95% CI: 0.656-0.726) and 0.648 (95% CI: 0.613-0.684) in the training and validation sets, respectively. CONCLUSION: Frailty as defined by FI-LAB was common and indicated a significant death risk in cancer patients. Our novel developed algorithm MCP had a passable prediction capacity on 5-year MCP.

Dehydroepiandrosterone alleviates intestinal inflammatory damage via GPR30-mediated Nrf2 activation and NLRP3 inflammasome inhibition in colitis mice.

Dehydroepiandrosterone (DHEA) is a popular dietary supplement that has anti-inflammatory, anti-oxidant and immune-regulating role; meanwhile, it also can effective in the protection of inflammation diseases such as inflammatory bowel disease (IBD), but the underlying mechanisms remain elusive. Here, we demonstrated that DHEA inhibits excessive inflammation response and enhances gut barrier function via activating the G protein-coupled receptor 30 (GPR30). GPR30-induced the ERK phosphorylation and p62 accumulation led to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which subsequently inhibited the reactive oxygen species (ROS) overproduction and finally alleviated the intestinal barrier dysfunction. Furthermore, DHEA blocked the p38-induced NLRP3 inflammasome activation in both LPS-stimulated colon epithelial cells and macrophages. In addition, in vivo results showed that DHEA and GPR30 agonist G1 attenuated inflammatory responses and gut barrier dysfunction in colitis mice, while the GPR30 specific inhibitor G15 abrogated these beneficial effects of DHEA. Cumulatively, our study unveiled that DHEA is an effective anti-inflammatory agent and suggested that GPR30 could as a potential target for the treatment of IBD.

Nonlinear response of SIA to emission changes and chemical processes over eastern and central China during a heavy haze month.

This study used a chemical transport model to investigate the response of secondary inorganic aerosols (SIA) to chemical processes and its precursor emissions over northern and southern city-clusters of China in January 2014. Unexpectedly, SIA concentrations with low levels of precursor emissions were much higher over the southern regions than those over the northern region with high levels of precursor emissions, based on ground observations and high-precision simulations. The sensitivity analysis of chemical processes suggests that the gas-phase chemistry was a critical factor determining the SIA pattern, especially the higher efficiency of nitrogen conversion to nitrate in southern cities controlled by favorable meteorological elements than that in northern city. However, the heterogeneous process led to the decrease of SIA in southern regions by 3% to 36% and the increasing of SIA in NCP by 26.9%, mainly attributing to the impact on nitrate. The reason was that sulfate enhancement by the heterogeneous reactions can compete ammonia (NH3) and the excessive nitric acid converted into nitrogen oxide (NOx), leading to nitrate decrease in southern regions under NH3-deficient regimes. Moreover, through sensitivity experiments of precursor emission reduction by 20%, NH3 control was found to be the most effective for reducing SIA concentrations comparing to sulfur dioxide (SO2) and NOx reduction and a more remarkable decrease of SIA was in southern regions by 10% to 15% than that in northern region by 6.7%. The effect of the synergy control of precursors emission varied in different city-clusters, inferring that the control strategy aimed at improving air quality should be implemented based on specific characteristics of precursors emission in different regions of China.

Efficacy and Safety of Veverimer in the Treatment of Metabolic Acidosis Caused by Chronic Kidney Disease: A Meta-analysis.

Metabolic acidosis is a common complication of chronic kidney disease (CKD). Veverimer is an orally administrated, free amine polymer with high capacity and binding selectivity to hydrochloric acid from the gastrointestinal tract. This study pooled the current evidence of the efficacy and safety of veverimer for the treatment of metabolic acidosis associated with CKD. We conducted a systematic literature search on PubMed, Embase, and Cochrane Central for relevant randomized controlled trials (RCTs) in June 2020. In this study, three RCTs with 548 patients were included in our analysis. The analysis revealed that veverimer was associated with increased bicarbonate level of patients (weight mean difference [WMD] 3.08, 95% confidence interval [CI] [2.40, 3.77], p < 0.001) and improved physical function compared with placebo measured by Kidney Disease and Quality of Life Short Form 36, question 3 (physical functioning domain) (KDQoL-PFD) score (WMD 5.25, 95% CI [1.58, 8.92], p = 0.005). For safety outcomes, both groups exhibited similar risks for developing headache, diarrhea, flatulence, and hyperkalemia. In conclusion, current clinical evidence indicates that veverimer is efficacious and safe against metabolic acidosis related to CKD compared with placebo. Further research comparing long-term veverimer use with traditional alkali therapy is needed.