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Detection of kilonova AT2017gfo proves that binary neutron star mergers can be the dominant contributor to the production of heavy elements in our Universe. Neutrinos from the radioactive decay of heavy elements would be the most direct messengers of merger ejecta. Based on r-process nucleosynthesis calculations, we study the neutrinos emitted from the β-decay of r-process elements and find that about half of the β-decay energy is carried away by neutrinos. The neutrino energy generation rate remains approximately constant at the early stage (t ≲ 1 s) and then decays as a power-law function with an index of −1.3. This powers a short-lived fast neutrino burst with a peak luminosity of ∼1049 erg s−1 in the early stage. Observation of neutrinos from neutron star mergers will be an important step towards understanding the properties of extremely neutron-rich nuclei and r-process nucleosynthesis, since the dominant contribution to the early time neutrino production is from nuclides near the r-process path. The typical neutrino energy is ≲8 MeV, which is within the energy ranges of the water-Cherenkov neutrino detectors such as Super-Kamiokande and future Hyper-Kamiokande, but the extremely low neutrino flux and event rate in our local Universe challenge the detection of the neutrino flashes.

Several breast cancer studies have reported the use of adjuvant opioids with the paravertebral block (PVB) to improve outcomes. However, there is no level-1 evidence justifying its use.To elucidate if the addition of opioids to PVB improves pain control in breast cancer surgery patients.We conducted an electronic literature search across PubMed, Embase, Scopus, and Google Scholar databases up to October 20, 2020. Only randomized controlled trials (RCTs) comparing the addition of opioids to PVB with placebo for breast cancer surgery patients were included.Six RCTs were included. Our meta-analysis indicated significantly reduced 24-h total analgesic consumption with the addition of opioids to PVB as compared to placebo [standardized mean difference (SMD) -1.57, 95% confidence interval (CI): -2.93, -0.21,Current evidence suggests a limited role of adjuvant opioids with PVB for breast cancer surgery patients. Further homogenous RCTs with a large sample size are needed to clarify the beneficial role of opioids with PVB.

The aim of this study was to investigate how peritoneal dialysis and other influencing factors affect patients' cognitive function.The 85 subjects in the study group were regular patients in our center. The control group included 88 age and gender matched healthy individuals who were with normal renal function. The study subjects' cognitive levels and related factors were analyzed using several screening instruments: the cognitive function was measured using the Montreal Cognitive Assessment Scale and statistical analysis was conducted based on the relevant data.The results showed that cognitive impairment was higher in peritoneal dialysis patients than in non-dialysis subjects. Age and educational background were single factors that affected cognitive function, which was more likely to be impaired at a higher age level and/or a lower educational level.Cognitive function can be impaired by peritoneal dialysis, and age and education levels are influencing factors.

Background: Restoration of blood flow during ischemic stroke leads to Cerebral Ischemia- Reperfusion Injury (CIRI) by activating neuroinflammatory cascades. Pomelo Peel Volatile Oil (PPVO) extracted from Citrus maxima (Burm.) from the genus Rutaceae, comprises some antiinflammatory ingredients, such as limonene and β-myrcene. Objective: The present study aimed to investigate the potential effect of PPVO on alleviating CIRI related to the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) pathway. Methods: Transient middle cerebral artery occlusion/reperfusion (tMCAO/R) was performed on 65 rats, which were then distributed into five groups (n = 13/group) depending on the intervention they received: Normal Saline (NS) group, normal Glycerin (GL) group, low-dose PPVO (LP, 10mg/kg) group, high-dose PPVO (HP, 30 mg/kg) group, and Sham-operated (SH) group. Neurological Deficit Scores (NDSs) and histological changes were evaluated. Infarct volumes were measured by 2,3,5- Triphenyltetrazolium Chloride (TTC) staining. The expression of TLR4 and neutrophil infiltration were detected by Immunofluorescence (IF) staining. Moreover, the downstream molecules of the TLR4/NF-κB signaling pathway, such as IL-6, IL-1β, TNF-α, p-IκB/IκB, and p-NF-κB p65/NF-κB p65 were analyzed by Western Blot (WB). Results & Discussion: The results showed that PPVO (30 mg/kg) significantly decreased infarct volumes, improved neurological deficits and pathologic changes, inhibited TLR4/NF-κB signaling pathway suppressed neutrophil infiltration, and suppressed pro-inflammatory cytokine release. Conclusion: It can be concluded that PPVO may alleviate neuroinflammation and protect against CIRI via inhibiting the TLR4/NF-κB signaling pathway.

Mining activities are well-known sources of potentially toxic elements (PTEs) pollution, which often jeopardize the biosphere, pedosphere, and hydrosphere. However, the soil and groundwater pollution caused by active private mining activities has long been neglected. This study investigated the occurrence of PTEs and cyanide (CN) in agricultural soils, mine tailings, and groundwater nearby the cyanide baths from a private gold mine in Hainan Province, southern China. Results indicated that concentrations of Pb, As, Cd, Hg, and CN in different soil depths and mine tailings were up to ten thousand mg/kg, and relatively higher content of As and Pb was detected in groundwater. The chemical forms of Cd, Pb, As, and Hg varied greatly in different soil depths; over 80% of Cd distributed in the water-soluble fraction, suggesting its higher mobility in soils, while approximately 60–90% of Pb, As, and Hg distributed in other chemical fractions, indicating relatively lower mobility in soils. The pollution indices also revealed the serious pollution and deterioration of site quality in this area. Human risk assessments also reflected a high non-carcinogenic/carcinogenic health risk in this area. The framework of integrated management strategies for private metal mines was proposed to mitigate PTEs pollution and reduce health risks.

This study aimed to investigate the efficiency, safety and cost-efficiency of blood purification (BP) in treating patients with severe-acute pancreatitis (SAP). A literature search was conducted using PubMed, OVID, International Clinical Trials Register (ICTRP), and Cochrane Central Register of Controlled Trials (CENTRAL). A total of 11 prospective studies and 6 retrospective studies, which reported the mortality of 1279 SAP patients, were included for analysis. Decreased short-term mortality and incidence rate of infection were observed in the high-volume hemofiltration (HVHF) group, but not in patients treated with other types of BP. There was no significant difference in the incidence of multiple-organ dysfunction (MODS), duration of hospital stay, or cost of hospitalization between the BP and non-BP groups. The starting time point, substitution fluid flow rate, filter membrane type, hemofilter change interval, anticoagulation, and sustaining times of BP varied across studies. In conclusion, HVHF may reduce the short-term mortality (

All over the world, non-steroidal anti-inflammatory drugs (NSAIDs) are taken annually by about three hundred million people and this figure is constantly increasing. At the same time, NSAIDs are also one of the most common causes of side effects of drug therapy. The development and implementation of new anti-inflammatory drugs, including those of plant origin, with minimal side effects is an urgent task of modern pharmaceutical science. Vaccinium corymbosum L. (family Ericaceae), which is gaining more and more popularity among berry crops and is successfully cultivated in Ukraine, is promising in this direction for research. The aim: phytochemical analysis of dry extracts from blueberry leaves to establish the possibility of creating new drugs with anti-inflammatory activity. Materials and methods.The objects of the study were dry extracts of northern highbush blueberry leaves. The content of amino acids and phenolic compounds was determined by HPLC and spectrophotometry. The prototypal activity was studied in vivo and in vitro. Research results.4 dry extracts were obtained from northern highbush blueberry leaves. In the extracts obtained by HPLC, 7 amino acids were identified, including 3 essential ones: arginine, histidine, and phenylalanine. As a result of the HPLC study, 7 phenolic compounds were identified in extracts from the leaves of northern highbush blueberry: 5 flavonoids - rutin, quercetin-3-O-glucoside, kaempferol-3-O-glucoside, quercetin and kaempferol and 2 hydroxycinnamic acids, chlorogenic and caffeic acid. For the first time, the anti-inflammatory effect of extracts from blueberry leaves was investigated. It was revealed that extract 1 at a dose of 50 mg/kg and extract 4 modified with arginine at a dose of 25 mg/kg have the highest anti-inflammatory activity. Conclusions.The results of the conducted studies indicate that extracts from the leaves of northern highbush blueberry in terms of the content of biologically active substances are promising sources for the creation of new drugs and dietary supplements with anti-inflammatory activity

Context Pomelo peel oil (PPO) [Citrus maxima (Burm.) Merr. (Rutaceae)] is reported to possess antioxidant and antimelanogenic activities. Objective To investigate the effect of PPO [Citrus maxima (Burm.) Merr. cv. Shatian Yu] on tumour necrosis factor-α (TNF-α)-induced necroptosis in cerebral ischaemia–reperfusion injury (CIRI) after cardiac arrest (CA). Materials and methods Male Sprague Dawley rats were randomly assigned to six groups: sham group, PP0-L (10 mg/kg), PPO-M (20 mg/kg), PPO-H (40 mg/kg) and two control groups (CA, 0.9% saline; Gly, 10% glycerol). All drugs were administered intravenously to the CA/CPR rats within 10 min after return of spontaneous circulation (ROSC). After 24 h, rats were assessed for neuronal injury via the neurological deficit score (NDS), cerebral cortex staining and transmission electron microscopy (TEM) and expression levels of TNF-α and necroptosis-related proteins by immunoreactivity staining and western blotting. Results Compared to those in the sham group (survival rate, 100% and NDS, 80), the survival rate and NDS were significantly reduced in the model groups (CA, 56.25%, 70; Gly, 62.5%, 71; PPO-L, 75%, 72; PPO-M, 87.5%, 75; PPO-H, 81.25%, 74). In the PPO-M group, Nissl bodies were significantly increased (43.67 ± 1.906 vs. 17 ± 1.732), the incidence of pathomorphological injury was lower and the necroptosis markers (TNF-α, RIPK1, RIPK3, p-MLKL/MLKL) expression was downregulated compared to those in the CA group (p

Background Mitochondria play a critical role as effectors and targets of brain injury in the post-resuscitation period. Although we found previously that the extracellular signal-regulated kinase (ERK)1/2 inhibitor PD98059 (PD) protects the brain against mitochondrial-mediated cell death at 24 h post-resuscitation in rats subjected to cardiac arrest/cardiopulmonary resuscitation (CA/CPR), it is not clear whether PD also exerts mitochondrial protective effect for a lasting time. Therefore, we examined the effect of PD on brain mitochondria at 48 h post-resuscitation to evaluate the time-effect of PD in the current study. Methods Experimental rats were divided randomly into 5 groups: Sham, CA, dimethylsulfoxide (DMSO), 0.15mg/kg PD and 0.3mg/kg PD. Rats except for sham group were subjected to CA for 6 min followed by CPR. We detected survival rates and neurologic deficit scores, cerebral cortex mitochondrial function by evaluating adenosine triphosphate (ATP) levels, mitochondrial permeability transition pore (MPTP) opening, and the expression of mitofusin2 (Mfn2) and observing the ultrastructure by electron microscopy at 48 h post-resuscitation in a 6-min CA rat model. Results PD improved survival rates and neurologic deficit scores, alleviated cerebral cortex mitochondrial damage by reducing MPTP opening and increasing Mfn2 production at 48 h post-resuscitation in a 6-min CA rat model. Conclusion A single dose of PD improved 48 h post-resuscitation outcome and mitochondrial function, indicating the potential of the use of ERK inhibitors for the treatment of brain injury resulting from CA in the future.

Background This study was conducted to explore whether the effect of edaravone (5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol3-one, EDR) can ameliorate renal warm ischemia-reperfusion injury (IRI) by modulating endoplasmic reticulum stress (ERS) and its downstream effector after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in a rat model. Methods The rats (n=10) experienced anaesthesia and intubation followed by no CA inducement were defined as the Sham group. Transoesophageal alternating current stimulation was employed to establish 8 min of CA followed by conventional CPR for a resuscitation model. The rats with successful restoration of spontaneous circulation (ROSC) randomly received EDR (3 mg/kg, EDR group, n=10) or equal volume normal saline solution (the NS group, n=10). At 24 hr after ROSC, serum creatinine (SCR), blood urea nitrogen (BUN) levels, and cystatin-C (Cys-C) levels were determined and the protein level of glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), extracellular signal-regulated kinase (ERK), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), Bax/Bcl-2, and caspase-3 were detected by Western blot method. Results At 24 hrs after ROSC, SCR, BUN and Cys-C were obviously increased and the proteins expression, including GRP78, CHOP and p-ERK1/2, cleaved-caspase 3 Bax/Bcl-2 ratio, were significantly upregulated in the NS group compared with the Sham group (p

AAssociation of GW170817/GRB170817A/AT2017gfo provides the first direct evidence for neutron star mergers as significant sources of $r$-process nucleosynthesis. A gamma-ray transient (GRT) would be powered by the radioactive decay of the freshly-synthesized $r$-process elements. By analyzing the composition and gamma-ray opacity of the kilonova ejecta in details, we calculate the lightcurve and spectrum of the GRT for a range of spherically symmetric merger ejecta models with mass $M_{\rm ej}=0.001 \sim 0.05M_{\odot}$ and expansion velocity $v_{\rm ej}= 0.1\sim 0.4c$. It is found that the peak of the GRT lightcurve depends on $M_{\rm ej}$ and $v_{\rm ej}$ as $t_{\rm pk} \approx 0.5~{\rm days} ~ (M_{\rm ej}/0.01M_{\odot})^{1/2}(v_{\rm ej}/0.1c)^{-1}$ and $L_{\rm pk} \approx 2.0\times10^{41} ~{\rm erg~s} ^{-1} (M_{\rm ej}/0.01M_{\odot})^{1/2}(v_{\rm ej}/0.1c)$. Most radiating photons are in the $100-3000$ keV band and the spectrum peaks at about 800~keV for different nuclear physics inputs. The line features are blurred out by the Doppler broadening effect. Adopting the ejecta parameters reported in literature, we examine the detection probability of the possible GRT associated with AT2017gfo. We show that the GRT cannot be convincingly detected neither with current nor with the proposed missions in the MeV band, such as ETCC and AMEGO. The low gamma-ray flux, together with the extremely low event rate at local universe, makes a discovery of GRTs a great challenge., Comment: 16 pages, 7 figures. Accepted for publication in the ApJ Letters

Rheumatoid Arthritis (RA) remains a major global public health challenge. Disease-modifying anti-rheumatic drugs (DMARDs) are standard therapeutic drugs for RA. Conventional DMARDs (c-DMARDs) are a subgroup of approved synthetic DMARDs. The c-DMARDs experienced lesser response with longer disease duration or drug exposure, and unwanted adverse events (AEs). The combination treatments (CTs) of c-DMARDs and Chinese Herbal Medicines (CHMs) were often used in RA clinical trials for increasing the therapeutic effectiveness and reducing the AEs. This systematic review aimed to evaluate the efficacy and safety of the CTs for RA. Databases were searched from inception to October 2020 for identification of randomized controlled trials (RCTs) that investigated the CTs in the management of RA. Twenty-three RCTs with 2,441 participants were included. The assessments and analyses found CTs improved American College of Rheumatology (ACR) 20 (RR: 1.33, 95% CI [1.21, 1.45], 10 studies, n=1,075) and alleviated AEs (RR: -0.40, 95% CI [-0.30, -0.53], 19 studies, n=2,011) in comparison with c-DMARDs. The CTs also significantly improved RA symptoms and patient-reported outcomes; reduced disease activity score (DAS) 28, serum acute-phase reactants and RA biomarkers. The five most commonly used herbs in included studies were

Background Various and opposite roles of epigallocatechin gallate (EGCG) have been reported in different studies. We aimed to investigate how EGCG affects the cerebral injury in a cardiac arrest/cardiopulmonary resuscitation (CA/CPR) model of rat. Methods The rats which were subjected to CA/CPR randomly received low dose of EGCG (3 mg/kg, Low-EGCG group, n=16), high dose of EGCG (9 mg/kg, High-EGCG group, n=16) and equal volume of 0.9% saline solution (NS group, n=16) at the first minute after return of spontaneous circulation (ROSC). The rats underwent anesthesia and intubation were defined as Sham group (n=16). Twenty-four hours after ROSC, neural defect score (NDS), ROS fluorescence intensity, degree of mitochondrial permeability transition pore (mPTP) opening, ATP contents and mitochondrial ATP synthase expression were evaluated in the four groups. The expression of extracellular signal-regulated kinase (ERK) activity and cleaved-caspase 3 were also detected by Western blot. Results CA/CPR induced severe ischemia-reperfusion injury (IRI), resulted in mitochondrial dysfunction and upregulated phosphorylation of ERK. EGCG dose-dependently alleviated the IRI after CA/CPR, inhibited ERK activity and restored mitochondrial function and, as indicated by improved NDS, reduced ROS level, decreased mPTP opening, elevated ATP content, increased ATPase expression and downregulated cleaved-caspase 3 level. Conclusion EGCG alleviated global cerebral IRI by restoring mitochondrial dysfunction and ERK modulation in a rat CA/CPR model, which might make it a potential candidate agent against IRI after CA/CPR in the future. Further study is needed to determine whether higher dosage of EGCG might aggravate cerebral IRI post-CA/CPR.

MicroRNA-499 (miR-499) rs3746444 polymorphism has been associated with the risk of coronary heart disease (CHD). However, results from several studies are inconsistent. This meta-analysis aimed to further investigate the possible association between miR-499 rs3746444 polymorphism and CHD risk. A total of 9 case-control studies included 5063 CHD cases and 4603 healthy subjects. The A allele at rs374644 was associated with significantly decreased CHD risk in the total population according to the allelic model (OR = 0.80, 95% CI = 0.68-0.93, P = 0.005), homozygous model (OR = 0.52, 95% CI = 0.39-0.71, P 0.001) and heterozygous model (OR = 0.57, 95% CI = 0.43-0.77, P 0.001). A similar trend was found specifically in Asian and Chinese populations. In contrast, the wild-type GG genotype at rs374644 was associated with significantly increased CHD risk in the total population, according to the dominant model (OR = 1.83, 95% CI = 1.39-2.42, P 0.001), and a similar trend was found in Asian and Chinese populations. These results indicate that in the total population, as well as in Asian and Chinese populations, the wild-type GG genotype at rs374644 may be related to increased susceptibility to CHD, while the A allele may be protective against CHD.

Background：Improving the diagnosis and treatment of acute kidney injury (AKI) in local hospitals is of great significance in developing countries. The aim of the present survey was to describe the characteristics of AKI in local hospitals at different economic levels and in different regions in mainland China. Methods：We used the database of a nation-wide survey on AKI in mainland China and extracted the data from 22 local hospitals. These hospitals were divided into three groups based on the local per capita gross domestic product (pcGDP) levels. We also divided the hospitals by geographic regions into Northwest China, North China, South China, and Southwest China. Using this data, we analyzed all characteristics associated with AKI. Results: 1,942 patients were diagnosed with AKI in the 22 local hospitals between January and July 2013, with a detection rate of 1.66%. There were significant differences in the detection rates and the classification of AKI across regions with different economic levels or geographic locations. The proportion of patients who had not been recognized with AKI on time, or with unclassifed AKI was higher in local hospitals from regions with lowest and moderate pcGDP levels than that in regions with the highest pcGDP levels. Renal hypoperfusion, drug factors and associated with other serious diseases were the most common causal factors of AKI in all regions. Northwest and Southwest regions had higher proportion of patients with potential nephrotoxic drugs use. The Southwest region had the most patients with environmental toxin-induced AKI compared to other regions. AKI caused by sepsis or surgical factors was more common in South China. The all-cause in-hospital mortality was 10.5%. Advanced age, male gender, staying in ICU, higher AKI stages, using nephrotoxic drugs, being with other critical illness, and delayed recognition were associated with increased in-hospital mortality, while in hospitals from South China or from regions with the highest pcGDP levels were associated with decreased in-hospital mortality.Conclusions: The detection rate of AKI in local hospitals in China is significantly lower than that in provincial hospitals. The etiology of AKI varies across different geographic regions and the level of economic development is closely related to the diagnosis of AKI in local hospitals.

Background The present meta-analysis of propensity score-matching studies aimed to compare the long-term survival outcomes and adverse events associated with coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients with chronic kidney disease (CKD). Methods Electronic databases were searched for studies comparing CABG and PCI in patients with CKD. The search period extended to 13 February 2021. The primary outcome was all-cause mortality, and the secondary endpoints included myocardial infarction, revascularization, and stroke. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were used to express the pooled effect. Study quality was assessed using the Newcastle–Ottawa scale. The analyses were performed using RevMan 5.3. Results Thirteen studies involving 18,005 patients were included in the meta-analysis. Long-term mortality risk was significantly lower in the CABG group than in the PCI group (HR: 0.76, 95% CI: 0.70–0.83, p .05). Subgroup analysis among patients on dialysis yielded similar results. Conclusions Our propensity score matching analysis revealed that, based on long-term follow-up outcomes, CABG remains superior to PCI in patients with CKD.

Orthotopic liver transplantation (OLT) in rats is a tried and proven animal model used for preoperative, intraoperative, and postoperative studies, including ischemia-reperfusion injury (IRI) of extrahepatic organs. This model requires numerous experiments and devices. The duration of anhepatic phase is closely related to the time to develop IRI after transplantation. In this experiment, we used hemodynamic changes to induce extrahepatic organ damage in rats and determined the maximum tolerance time. The time until the most severe organ injury varied for different organs. This method can easily be replicated and can also be used to study IRI of the extrahepatic organs after liver transplantation.

Aims Exercise-based cardiac rehabilitation has been recommended a treatment for patients with cardiovascular disease. Nevertheless, it remains controversial which exercise characteristics are most beneficial for post-myocardial infarction (MI) patients. We performed a systematic review and meta-analysis to investigate the effects of high-intensity interval training (HIIT) in these patients. Methods and results We searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang Dataset (from the earliest date available to February 2021) for randomized controlled trials and cohort studies that evaluated the effects of HIIT on post-MI patients. Studies were selected according to inclusion and exclusion criteria. Data synthesis was performed with R software version 4.0.1. Eight studies met the study criteria, including 387 patients. Compared to the control group [moderate-intensity continuous training (MICT) and/or routine physical activity], HIIT significantly improved peak oxygen uptake (peak VO2) [mean difference = 3.83 mL/kg/min, 95% confidence interval (CI) (3.25, 4.41), P Conclusion Compared with MICT and routine physical activity, HIIT could significantly improve exercise capacity in post-MI patients, and appears to be safe.

Light chain cast nephropathy is the most common form of renal lesion in multiple myeloma. Kidney impairment caused by light chain cast nephropathy can be reversed and survival can be improved if early diagnosis is available. It is thus of imperative importance to develop a non-invasive method to diagnose light chain cast nephropathy once the kidney biopsy is not always applicable. We consecutively screened newly diagnosed multiple myeloma patients with kidney biopsies from 4 centers in China. Kidney pathologies were reviewed and clinical presentations were recorded. Then a diagnostic model was established by logistic regression and the predictive values were assessed. Between 1 June 1999 and 30 June 2019, a kidney biopsy was performed in 94 patients with newly diagnosed multiple myeloma, and light chain cast nephropathy was the most common pattern, seen in 52% of biopsied patients. The diagnostic model was established by multivariate logistic regression analysis as P(z) = 1/(1 + e−z) and z = − 0.093 Hemoglobin (g/L) + 0.421 Serum albumin (g/L) + 3.463 Acute kidney injury (0/1) − 9.207 High-density lipoprotein (mmol/L). If P(z) ≥ 0.55, the diagnosis pointed to light chain cast nephropathy; if P(z)

BACKGROUND: Eighteen known susceptibility loci for IgAN account for only a small proportion of IgAN risk. METHODS: Genome-wide meta-analysis was performed in 2628 patients and 11,563 controls of Chinese ancestry, and a replication analysis was conducted in 6879 patients and 9019 controls of Chinese descent and 1039 patients and 1289 controls of European ancestry. The data were used to assess the association of susceptibility loci with clinical phenotypes for IgAN, and to investigate genetic heterogeneity of IgAN susceptibility between the two populations. Imputation-based analysis of the MHC/HLA region extended the scrutiny. RESULTS: Identification of three novel loci (rs6427389 on 1q23.1 [P=8.18×10(−9), OR=1.132], rs6942325 on 6p25.3 [P=1.62×10(−11), OR=1.165], and rs2240335 on 1p36.13 [P=5.10×10(−9), OR=1.114]), implicates FCRL3, DUSP22.IRF4, and PADI4 as susceptibility genes for IgAN. Rs2240335 is associated with the expression level of PADI4, and rs6427389 is in high linkage disequilibrium with rs11264799, which showed a strong expression quantitative trail loci effect on FCRL3. Of the 24 confirmed risk SNPs, six showed significant heterogeneity of genetic effects and DEFA showed clear evidence of allelic heterogeneity between the populations. Imputation-based analysis of the MHC region revealed significant associations at three HLA polymorphisms (HLA allele DPB1*02, AA_DRB1_140_32657458_T, and AA_DQA1_34_32717152) and two SNPs (rs9275464 and rs2295119). CONCLUSIONS: A meta-analysis of GWAS data revealed three novel genetic risk loci for IgAN, and three HLA polymorphisms and two SNPs within the MHC region, and demonstrated the genetic heterogeneity of seven loci out of 24 confirmed risk SNPs. These variants may explain susceptibility differences between Chinese and European populations.

Light chain cast nephropathy is the most common form of renal lesion in multiple myeloma. Kidney impairment caused by light chain cast nephropathy can be reversed and survival can be improved if early diagnosis is available. It is thus of imperative importance to develop a non-invasive method to diagnose light chain cast nephropathy once the kidney biopsy is not always applicable.We consecutively screened newly diagnosed multiple myeloma patients with kidney biopsies from 4 centers in China. Kidney pathologies were reviewed and clinical presentations were recorded. Then a diagnostic model was established by logistic regression and the predictive values were assessed.Between 1 June 1999 and 30 June 2019, a kidney biopsy was performed in 94 patients with newly diagnosed multiple myeloma, and light chain cast nephropathy was the most common pattern, seen in 52% of biopsied patients. The diagnostic model was established by multivariate logistic regression analysis as P(z) = 1/(1 + eWe built a novel, non-invasive diagnostic model through a multicenter study, which may be helpful in the diagnosis of light chain cast nephropathy in newly diagnosed multiple myeloma patients.

The NLR family pyrin domain-containing 3 (NLRP3) inflammasome, which is composed of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) and pro-caspase-1 protein complexes, is activated by the reactive oxygen species (ROS) that are associated with ischemia-reperfusion (I/R) and are involved in brain damage. Pomelo peel oil (PPO) exhibits antioxidant activity. However, it is unclear whether PPO is able to attenuate NLRP3 inflammasome-induced inflammation and pyroptosis. Healthy male Sprague-Dawley rats were subjected to 7 min of cardiac arrest via trans-esophageal electrical stimulation, followed by cardiopulmonary resuscitation (CPR). The rats were then treated with PPO prior to reperfusion for 24 h. Hematoxylin and eosin staining was used to evaluate brain tissue and cell damage. In the brain tissues, reactive oxygen species (ROS) were assayed, immunofluorescence was used to analyze the expression of NLRP3 and western blotting was performed to determine the expression levels of neuroenolase (NSE), NF-κB, interleukin-1β (IL-1β), gasdermin D (GSDMD) and the NLRP3 inflammasome. Treatment of the rats with PPO significantly decreased the pathological damage of the brain tissue and reduced the expression of NSE, production of ROS and secretion of NF-κB, NLRP3, IL-1β and GSDMD. In conclusion, these results demonstrate the ability of PPO to protect the brain against I/R injury in rats after CPR by a mechanism involving inhibition of the inflammation and pyroptosis mediated by NLRP3 inflammasome activation.

Mining activities are well-known sources of potentially toxic elements (PTEs) pollution, which often jeopardize the biosphere, pedosphere, and hydrosphere. However, the soil and groundwater pollution caused by active private mining activities has long been neglected. This study investigated the occurrence of PTEs and cyanide (CN) in agricultural soils, mine tailings, and groundwater nearby the cyanide baths from a private gold mine in Hainan Province, southern China. Results indicated that concentrations of Pb, As, Cd, Hg, and CN in different soil depths and mine tailings were up to ten thousand mg/kg, and relatively higher content of As and Pb was detected in groundwater. The chemical forms of Cd, Pb, As, and Hg varied greatly in different soil depths; over 80% of Cd distributed in the water-soluble fraction, suggesting its higher mobility in soils, while approximately 60-90% of Pb, As, and Hg distributed in other chemical fractions, indicating relatively lower mobility in soils. The pollution indices also revealed the serious pollution and deterioration of site quality in this area. Human risk assessments also reflected a high non-carcinogenic/carcinogenic health risk in this area. The framework of integrated management strategies for private metal mines was proposed to mitigate PTEs pollution and reduce health risks.

Kidney disease is a significant health concern worldwide. Ineffective treatment can lead to disastrous consequences, such as organ failure and death. Research has turned to cell-based therapy, but has yet to produce an effective and reliable treatment for kidney disease. To address this problem, we examined four datasets of gene expression profiles from diseased and healthy kidney tissue in humans, mice, and rats. Differentially expressed genes (DEGs) were screened and subjected to enrichment analyses. Up-regulated genes in diseased kidney tissue were significantly enriched in pathways associated with regulatory T cells (Tregs). Analysis with the xCell tool showed that Tregs were generally increased in diseased kidney tissue in all species. To validate these results in vivo, kidneys were removed from mice with Adriamycin-induced nephropathy, and histology confirmed increase of Tregs. Furthermore, Tregs were adoptively transferred from healthy mice into mice with kidney injury, restoring normal structure to the damaged kidneys. Treg cells that were co-cultured with M2c macrophages exhibited up-regulation of chemokine receptors CCR2, CCR5, CCR7, CD62L, and CX3CR1. This may be the mechanism by which M2c cells enhance the migration of Tregs to the site of inflammation. We propose that Tregs may be an effective, novel candidate for cell-based therapy in pre-clinical kidney injury models.

Background. Reducing cerebral ischemia-reperfusion injury is crucial for improving survival and neurologic outcomes after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The purpose of this study is to investigate the neuroprotective effects of green tea polyphenols (GTPs) concern with the modulation of endogenous antioxidation and endoplasmic reticulum stress. Methods. After subjecting to CA/CPR, rats were randomized into the saline group (NS, n = 40) and the GTPs group (GTPs, n = 40). Each group was blindly located into four subgroups according to four time points (12 h, 24 h, 48 h, and 72 h). Other rats without experiencing CA/CPR severed as the Sham group (Sham, n = 10). Brain tissue samples were harvested at relative time points. The expressions of superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), caspase-3, and C/EBP-homologous protein (CHOP) were detected by immunofluorescence, dead neurons were assayed by TUNEL staining, and the expressions of caspase-12 and glucose-regulated proteins 78 kDa (GRP78) were evaluated by western blotting, respectively. Results. Comparing with that in NS group, GTPs increased the expression of SOD1 and SOD2 at 12 h, 24 h, 48 h, 72 h, and the expression of GRP78 at 24 h and 48 h (p<0.05) butdecreased caspase-12, CHOP, caspase-3 level, and apoptotic number of neurons (p<0.05) after restoration of spontaneous circulation (ROSC). Conclusion. GTPs exert neuroprotective effects via mechanisms that may be related to the enhancement of endogenous antioxidant capacity and inhibition of endoplasmic reticulum stress in CA/CPR rat models.

The observation of a radioactively powered kilonova AT~2017gfo associated with the gravitational wave-event GW170817 from binary neutron star merger proves that these events are ideal sites for the production of heavy $r$-process elements. The gamma-ray photons produced by the radioactive decay of heavy elements are unique probes for the detailed nuclide compositions. Basing on the detailed $r$-process nucleosynthesis calculations and considering radiative transport calculations for the gamma-rays in different shells, we study the gamma-ray emission in a merger ejecta on a timescale of a few days. It is found that the total gamma-ray energy generation rate evolution is roughly depicted as $\dot{E}\propto t^{-1.3}$. For the dynamical ejecta with a low electron fraction ($Y_{\rm e}\lesssim0.20$), the dominant contributors of gamma-ray energy are the nuclides around the second $r$-process peak ($A\sim130$), and the decay chain of $^{132}$Te ($t_{1/2}=3.21$~days) $\rightarrow$ $^{132}$I ($t_{1/2}=0.10$~days) $\rightarrow$ $^{132}$Xe produces gamma-ray lines at $228$ keV, $668$ keV, and $773$ keV. For the case of a wind ejecta with $Y_{\rm e}\gtrsim0.30$, the dominant contributors of gamma-ray energy are the nuclides around the first $r$-process peak ($A\sim80$), and the decay chain of $^{72}$Zn ($t_{1/2}=1.93$~days) $\rightarrow$ $^{72}$Ga ($t_{1/2}=0.59$~days) $\rightarrow$ $^{72}$Ge produces gamma-ray lines at $145$ keV, $834$ keV, $2202$ keV, and $2508$ keV. The peak fluxes of these lines are $10^{-9}\sim 10^{-7}$~ph~cm$^{-2}$ s$^{-1}$, which are marginally detectable with the next-generation MeV gamma-ray detector \emph{ETCC} if the source is at a distance of $40$~Mpc., Comment: 24 pages, 7 figures, 2 tables, accepted for publication in ApJ

In recent years, kidney damage caused by ingestion of Chinese medicinal herbs containing Aristolochic acid (AA) has attracted extensive attention. However, whether the nephrotoxicity of AA is related to NLRP3 inflammasome has not been reported. Hirsutella sinensis (HS) has a certain therapeutic effect on aristolochic acid nephropathy (AAN) and is related to NLRP3 inflammasome. Therefore, this study explores whether HS plays a role in renal injury induced by AA through NLRP3 inflammasome pathway. AA-stimulated renal tubular epithelial cells showed that AA could promote the expression of NLRP3, ASC, and α-SMA, increase the secretion and expression of caspase-1, IL-1β, and IL-18, and inhibit the expression of E-cadherin in a dose- and time-dependent manner. When NLRP3 was down-regulated, the expression of α-SMA and E-cadherin did not change significantly, but significantly blocked the regulation of α-SMA and E-cadherin expression by AA. When AA and HS were added to renal tubular epithelial cells at the same time, the effects of AA on the expression of NLRP3, ASC, caspase-1, IL-1β, IL-18, and α-SMA gradually decreased to the level of control group with the increase of HS dosage. At the same time, HS can reduce the transdifferentiation of renal tubular epithelial cells by inhibiting the activation of NLRP3 inflammasome. These findings will provide important pharmacological references for the treatment of AAN and the clinical application of HS.

Objective: In the current study, we investigated the incidence of acute kidney injury (AKI) induced by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) and whether such an AKI can recover spontaneously in rats. Methods: We used transesophageal alternating current stimulation to establish 7 min of CA rat model followed by conventional CPR. The experimental rats were randomly divided into three groups (n = 20 per group) according to the different time points after restoration spontaneous circulation (ROSC): the ROSC 24 h, ROSC 48 h, and ROSC 72 h group. The diagnosis of rat AKI refers to the 2012 KDIGO adult AKI diagnostic criteria. The severity of AKI quantified by the serum creatinine (SCR), blood urea nitrogen (BUN) levels and histological features of renal tissue. Results: The incidence rates of AKI in ROSC 24 h, ROSC 48 h, and ROSC 72 h group were 65%, 45%, and 42.9%. Moreover, the values of SCR and BUN were highest at ROSC 24 h, and then gradually decreased with the time of ROSC. The histological changes of the renal tissues such as glomerular collapse, renal tubular cell swelling, and inflammatory cell infiltration had also observed. Conclusion: The incidence of AKI in rats was high after suffering from CA and CPR, but renal function improved with the prolongation of ROSC time, indicating the ability of the kidney to self-repair.

Aims Mitochondrial dysfunction has been regarded as one of the hallmarks of cerebral ischemia-reperfusion injury. In previous studies, we have provided evidence that the extracellular signaling pathway (ERK) 1/2 inhibitor PD98059 improved the neurological deficits by modulating antioxidant and anti-apoptotic activities in rats subjected to cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Since oxidative stress can activate mitochondria-dependent apoptosis and autophagy, we further explored the effects of PD98059 on mitochondria involved with apoptosis and autophagy in rat CA model. Materials and methods We disposed PD98059 in CA/CPR rats, tested the mitochondrial-mediated apoptosis pathway in brain tissues at 24 h post-resuscitation by mitochondrial permeability transition pores (MPTP), cytochrome c (CytC), BCL-2, BAX, caspase-3, as well as autophagy by LC3, Beclin-1, and p62. Furthermore, we explored the relationship of dynamin-related protein 1 (Drp1) with apoptosis and autophagy. Key findings Our study showed that PD98059 decreased the openings of MPTP, CytC release, caspase3 activation, apoptotic indices, LC3-II, Beclin-1and increased P62. PD98059 also inhibited mitochondria-dependent apoptosis and the activity of autophagy in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. The generation of phosphorylated Drp1-616 was down-regulated accompanied by a decrease of TUNEL-positive cells and LC3 in dual immunostaining after PD98059 inhibited activation of ERK signaling pathway in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. Significance PD98059 protects the brain against mitochondrial-mediated apoptosis and autophagy at 24 h post-resuscitation in rats subjected to CA/CPR, which is linked with the downregulation of Drp1 expression.

Background This study was conducted to explore whether the effect of edaravone (5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol3-one, EDR) can ameliorate renal warm ischemia-reperfusion injury (IRI) by modulating endoplasmic reticulum stress (ERS) and its downstream effector after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in a rat model. Methods The rats (n=10) experienced anaesthesia and intubation followed by no CA inducement were defined as the Sham group. Transoesophageal alternating current stimulation was employed to establish 8 min of CA followed by conventional CPR for a resuscitation model. The rats with successful restoration of spontaneous circulation (ROSC) randomly received EDR (3 mg/kg, EDR group, n=10) or equal volume normal saline solution (the NS group, n=10). At 24 hr after ROSC, serum creatinine (SCR), blood urea nitrogen (BUN) levels, and cystatin-C (Cys-C) levels were determined and the protein level of glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), extracellular signal-regulated kinase (ERK), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), Bax/Bcl-2, and caspase-3 were detected by Western blot method. Results At 24 hrs after ROSC, SCR, BUN and Cys-C were obviously increased and the proteins expression, including GRP78, CHOP and p-ERK1/2, cleaved-caspase 3 Bax/Bcl-2 ratio, were significantly upregulated in the NS group compared with the Sham group (p