Miracle-dz/UniFAR-FTUs huggingface dataset:
Adhesion-GPCR Gpr116 (ADGRF5) expression inhibits renal acid secretion

Significance Gpr116 is an adhesion G protein-coupled receptor (aGPCR) that is highly expressed in the kidney. Here, we report that Gpr116 localizes to A-intercalated cells in the murine collecting duct, where it functions as a significant and critical regulator of renal acid secretion by regulating the surface expression of V-ATPase proton pumps. Kidney-specific Gpr116 knockout mice develop a unique acid-base disorder, “renal tubular alkalosis,” characterized by acidic urine and alkaline blood. These findings have significant implications for other tissues with Gpr116 expression, as well as other acid-secreting epithelia. Furthermore, we propose that Gpr116 may more generally regulate endocytosis, a function that would have wide-ranging implications for both Gpr116 function and for our understanding of aGPCRs. The diversity and near universal expression of G protein-coupled receptors (GPCR) reflects their involvement in most physiological processes. The GPCR superfamily is the largest in the human genome, and GPCRs are common pharmaceutical targets. Therefore, uncovering the function of understudied GPCRs provides a wealth of untapped therapeutic potential. We previously identified an adhesion-class GPCR, Gpr116, as one of the most abundant GPCRs in the kidney. Here, we show that Gpr116 is highly expressed in specialized acid-secreting A-intercalated cells (A-ICs) in the kidney using both imaging and functional studies, and we demonstrate in situ receptor activation using a synthetic agonist peptide unique to Gpr116. Kidney-specific knockout (KO) of Gpr116 caused a significant reduction in urine pH (i.e., acidification) accompanied by an increase in blood pH and a decrease in pCO2 compared to WT littermates. Additionally, immunogold electron microscopy shows a greater accumulation of V-ATPase proton pumps at the apical surface of A-ICs in KO mice compared to controls. Furthermore, pretreatment of split-open collecting ducts with the synthetic agonist peptide significantly inhibits proton flux in ICs. These data suggest a tonic inhibitory role for Gpr116 in the regulation of V-ATPase trafficking and urinary acidification. Thus, the absence of Gpr116 results in a primary excretion of acid in KO mouse urine, leading to mild metabolic alkalosis (“renal tubular alkalosis”). In conclusion, we have uncovered a significant role for Gpr116 in kidney physiology, which may further inform studies in other organ systems that express this GPCR, such as the lung, testes, and small intestine.
T-cell agonists in cancer immunotherapy

Cancer cells can evade immune surveillance in the body. However, immune checkpoint inhibitors can interrupt this evasion and enhance the antitumor activity of T cells. Other mechanisms for promoting antitumor T-cell function are the targeting of costimulatory molecules expressed on the surface of T cells, such as 4-1BB, OX40, inducible T-cell costimulator and glucocorticoid-induced tumor necrosis factor receptor. In addition, CD40 targets the modulation of the activation of antigen-presenting cells, which ultimately leads to T-cell activation. Agonists of these costimulatory molecules have demonstrated promising results in preclinical and early-phase trials and are now being tested in ongoing clinical trials. In addition, researchers are conducting trials of combinations of such immune modulators with checkpoint blockade, radiotherapy and cytotoxic chemotherapeutic drugs in patients with advanced tumors. This review gives a comprehensive picture of the current knowledge of T-cell agonists based on their use in recent and ongoing clinical trials.
Effect of large dosage of Fuling on urinary protein of diabetic nephropathy

Abstract Introduction: Diabetic nephropathy (DN) is one of the most common and serious microvascular complications in patients with diabetes, which seriously affects their life quality and survival time. large dose herb Fuling or compound prescription contain large dose Fuling for treatment of DN has already been confirmed. However, due to the lack of evidence, there is no specific method or suggestion, so it is necessary to carry out systematic evaluation on Fuling and provide effective evidence for further research. Methods and analysis: The following databases will be searched from their inception to June 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, Nature, Science online, Chinese Biomedical Database WangFang, VIP medicine information, and China National Knowledge Infrastructure (CNKI). Primary outcomes:24-hurinary-albumin, Urinary albumin-to-creatinine ratio. Additional outcomes: Serum creatinine, Blood urea nitrogen, Glomerular filtration rate, Endogenous creatinine clearance rate. Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5. 3. and Stata V.12. 0. Results: The results of this study will systematically evaluate the effectiveness and safety of large dose Fuling intervention for people with DN. Conclusion: The systematic review of this study will summarize the current published evidence of large dose Fuling for the treatment of DN, which can further guide the promotion and application of it. Ethics and dissemination: This study is a systematic review, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations. Open Science Framework (OSF) registration number: August 24, 2020. osf.io/ym2c6. (https://osf.io/ym2c6).
An Infant Presenting With Fever, Abdominal Distension, Diarrhea and Vomiting.

1134 | www.pidj. com The Pediatric Infectious Disease Journal • Volume 39, Number 12, December 2020 Accepted for publication August 24, 2020. From the *Infectious Diseases Unit, The Royal Children’s Hospital Melbourne, Victoria, Australia; †Department of Paediatrics, The Royal Children’s Hospital Melbourne, Victoria, Australia; ‡Paediatric Intensive Care Unit, The Royal Children’s Hospital Melbourne, Victoria, Australia; §Department of Pediatric and Neonatal Intensive Care, Rigshospitalet, Copenhagen, Denmark; ¶Department of Cardiology, The Royal Children’s Hospital Melbourne, Victoria, Australia; ∥Department of Paediatric and Neonatal Surgery, The Royal Children’s Hospital, Victoria, Australia; **Department of Haematology, The Royal Children’s Hospital Melbourne, Victoria, Australia; ††Department of Paediatrics, The University of Melbourne, Victoria, Australia; ‡‡Department of Paediatrics, Monash University, Melbourne, Victoria, Australia; §§Infection and Immunity, Murdoch Children’s Research Institute, Victoria, Australia; and ¶¶Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia The authors have no conflicts of interest to disclose. Address for correspondence: Yara-Natalie Abo, MBBS, BMedSc, Infectious Diseases Unit, Royal Children’s Hospital Melbourne, 50 Flemington Road, Parkville, Victoria, Australia. E-mail: yaranatalie.abo@rch.org. au Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. Your Diagnosis, Please
Spore exudates and other factors affecting germination type of Cronartium quercuum f. sp. fusiforme basidiospores

Basidiospores of Cronartium quercuum f. sp. fusiforme were germinated under different conditions of agar concentration, pH, washing times, and spore exudate concentrations. At agar concentrations of 0.05-3% the percentage of washed spores that germinated directly, i.e., produced germ tubes, was significantly different from the percentage of unwashed spores that germinated directly. Ninety-nine percent of the washed spores germinated directly at all agar concentrations, while only 4-11% of unwashed (directly cast) basidiospores germinated directly. On pH 3 agar, germination of directly cast basidiospores was only 2%, but 98% of germinating spores germinated directly (produced germ tubes). On pH 4-11 agar, spore germination varied from 70-90% and was predominantly indirect (forming secondary basidiospores). When spores were washed in water at pH 2.2 or pH 5.5 for 2 or 5 min, percent direct germination was 10 times greater than those spores not washed with water. More than 95% of spores germinated directly after 30-min washing with water at either pH 2.2 or 5.5. Both spore exudates washed from the spores and those produced during germination were collected and reapplied to the spores. These applications increased the percentage of direct germination in directly cast spores but did not alter germination type in washed spores. The exudates inhibited germ tube length in both directly cast and washed basidiospores.
Synthesis, Characterization, and Electrochemistry of Diferrocenyl β-Diketones, -Diketonates, and Pyrazoles †

The synthesis of FcC(O)CH(R)C(O)Fc (Fc = Fe(η5-C5H4)(η5-C5H5); R = H, 5; nBu, 7; CH2CH2(OCH2CH2)2OMe, 9), [M(κ2O,O′-FcC(O)CHC(O)Fc)n] (M = Ti, n = 3, 10; M = Fe, n = 3, 11; M = BF2, n = 1, 12), and 1-R′-3,5-Fc2-cC3HN2 (R′ = H, 13; Me, 14; Ph, 15) is discussed. The solid-state structures of 5, 7, 9, 12, 13, 15, and 16 ([TiCl2(κ2O,O′-PhC(O)CHC(O)Ph)2]) show that 7 and 9 exist in their β-diketo form. Compound 13 crystallizes as a tetramer based on a hydrogen bond pattern, including one central water molecule. The electrochemical behavior of 5–7 and 9–16 was studied by cyclic and square-wave voltammetry, showing that the ferrocenyls can separately be oxidized reversibly between −50 and 750 mV (5–7, 9, 12–15: two Fc-related events; 10, 11: six events, being partially superimposed). For complex 10, Ti-centered reversible redox processes appear at −985 (TiII/TiIII) and −520 mV (TiIII/TiIV). Spectro-electrochemical UV-Vis/NIR measurements were carried out on 5, 6, and 12, whereby only 12 showed an IVCT (intervalence charge-transfer) band of considerable strength (νmax = 6250 cm−1, Δν½ = 4725 cm−1, εmax = 240 L·mol−1·cm−1), due to the rigid C3O2B cycle, enlarging the coupling strength between the Fc groups.
Methylarginine metabolites are associated with attenuated muscle protein synthesis in cancer-associated muscle wasting.

Cancer cachexia is characterized by reductions in peripheral lean muscle mass. Prior studies have primarily focused on increased protein breakdown as the driver of cancer-associated muscle wasting. Therapeutic interventions targeting catabolic pathways have, however, largely failed to preserve muscle mass in cachexia, suggesting that other mechanisms might be involved. In pursuit of novel pathways, we used untargeted metabolomics to search for metabolite signatures that may be linked with muscle atrophy. We injected seven-week old C57/BL6 mice with LLC1 tumor cells or vehicle. After 21 days, tumor-bearing mice exhibited reduced body and muscle mass and impaired grip strength compared to controls, which was accompanied by lower synthesis rates of mixed muscle protein and the myofibrillar and sarcoplasmic muscle fractions. Reductions in protein synthesis were accompanied by mitochondrial enlargement and reduced coupling efficiency in tumor-bearing mice. To generate mechanistic insights into impaired protein synthesis, we performed untargeted metabolomic analyses of plasma and muscle and found increased concentrations of two methylarginines, asymmetric dimethylarginine (ADMA) and NG-monomethyl-L-arginine, in tumor-bearing mice compared to control mice. Compared to healthy controls, human cancer patients were also found to have higher levels of ADMA in the skeletal muscle. Treatment of C2C12 myotubes with ADMA impaired protein synthesis and reduced mitochondrial protein quality. These results suggest that increased levels of ADMA and mitochondrial changes may contribute to impaired muscle protein synthesis in cancer cachexia and could point to novel therapeutic targets by which to mitigate cancer cachexia.
Value of Electroconvulsive Therapy in the General Public: A Willingness to Pay Study in Germany.

OBJECTIVE The aims of this study were to estimate the value a population-representative sample places on electroconvulsive therapy (ECT) through willingness to pay (WTP) and to assess the effects of individual characteristics on WTP for ECT. METHODS A German population-representative sample of 518 was presented with a hypothetical health loss scenario of depression and was asked to indicate WTP for ECT. Probit and quantile regression were used to estimate the effects of individual characteristics on the probability of stating a positive WTP and on the amount of money respondents were willing to pay. RESULTS Two thirds of respondents stated that they had no knowledge about ECT. Most (56.5%) respondents indicated zero WTP for health gains through ECT treatment. Mean WTP was &OV0556;5201 ($5612); median WTP was &OV0556;1000 ($1079). Respondents' monthly household income had a significant effect on the probability of stating a positive WTP. Assessing WTP above zero, income showed a significant positive effect, whereas a higher score of depressive complaints showed a significant negative effect on the amount respondents were willing to pay. CONCLUSION Knowledge about ECT treatment is particularly low in the German public.
Hydrothermal synthesis of a CoIn2S4/g-C3N4 heterojunctional photocatalyst with enhanced photocatalytic H2 evolution activity under visible light illumination

CoIn2S4, a black semiconducting material, possesses an outstanding visible light response and is employed to modify g-C3N4. A series of CoIn2S4/g-C3N4 heterojunctional photocatalysts are synthesized via a hydrothermal method, whereby cubic CoIn2S4 nanosheets are in situ immobilized on the surfaces of porous g-C3N4 nanosheets. Compared with the pristine g-C3N4 and CoIn2S4, under visible light (λ > 420 nm) irradiation, the CoIn2S4/g-C3N4 composite samples show markedly enhanced photocatalytic activity in hydrogen evolution. Among all of the samples, the 30% CoIn2S4/g-C3N4 sample shows the maximum H2 evolution rates, 5.2 and 23.9 times higher than those of g-C3N4 and CoIn2S4, respectively. The efficient photocatalytic activity of CoIn2S4/g-C3N4 composite photocatalysts is attributed to the formation of an intimate heterostructure, which not only significantly facilitates charge migration, but also enhances visible light absorption. Moreover, a plausible photocatalytic mechanism for the composite photocatalyst has been elucidated. This research provides a novel hint for fabricating visible-light-responsive heterojunction photocatalysts with high performance for energy production.
Longitudinal course of depressive, anxiety and post-traumatic stress disorder symptoms after heart surgery: a meta-analysis of 94 studies.

OBJECTIVE To analyze the longitudinal course of depression, anxiety and post-traumatic stress disorder (PTSD) symptoms in cardiac patients following heart surgery (HS). METHODS We conducted a systematic review and random-effects meta-analysis of cohort studies on patients undergoing HS, measuring anxiety, depressive, and PTSD symptoms before and at least 30 days after. Subgroup and meta-regression analyses, investigation of publication bias, and quality assessment were undertaken. RESULTS We included 94 studies relating to 15,561 patients. HS included coronary artery bypass graft surgery, valve replacement, implantable cardioverter defibrillator placement, left ventricular assist device placement, heart transplantation, and other types of HS. Across studies, symptoms of depression (g=0.32; 95%CI=0.25,0.39; p<0.001) and anxiety improved after HS (g=0.52; 95%CI=0.43,0.62; p<0.001), while PTSD symptoms worsened (g=-0.42; 95%CI=-0.80,-0.04; p=0.032). The reduction of depression and anxiety levels was more pronounced for patients with underlying coronary artery disease and heart failure, and persisted over one year after HS, whereas the increase in PTSD symptoms returned to baseline after 6 months. Depression improvement was inversely associated with older age, diabetes, hypertension and dyslipidemia, and positively with baseline heart failure. No additional clinical or demographic variables were associated with the course of anxiety symptoms. Quality of included studies was low overall. Publication bias was non-significant. CONCLUSIONS Depressive and anxiety symptoms improve over one-year after HS, while PTSD symptoms might worsen. Older patients, those with metabolic comorbidities, valve disease or ventricular arrhythmias are at higher risk for continued depressive and anxiety symptoms and should be monitored closely.
Nitrite Reductase 1 Is a Target of Nitric Oxide-Mediated Post-Translational Modifications and Controls Nitrogen Flux and Growth in Arabidopsis

Plant growth is the result of the coordinated photosynthesis-mediated assimilation of oxidized forms of C, N and S. Nitrate is the predominant N source in soils and its reductive assimilation requires the successive activities of soluble cytosolic NADH-nitrate reductases (NR) and plastid stroma ferredoxin-nitrite reductases (NiR) allowing the conversion of nitrate to nitrite and then to ammonium. However, nitrite, instead of being reduced to ammonium in plastids, can be reduced to nitric oxide (NO) in mitochondria, through a process that is relevant under hypoxic conditions, or in the cytoplasm, through a side-reaction catalyzed by NRs. We use a loss-of-function approach, based on CRISPR/Cas9-mediated genetic edition, and gain-of-function, using transgenic overexpressing HA-tagged Arabidopsis NiR1 to characterize the role of this enzyme in controlling plant growth, and to propose that the NO-related post-translational modifications, by S-nitrosylation of key C residues, might inactivate NiR1 under stress conditions. NiR1 seems to be a key target in regulating nitrogen assimilation and NO homeostasis, being relevant to the control of both plant growth and performance under stress conditions. Because most higher plants including crops have a single NiR, the modulation of its function might represent a relevant target for agrobiotechnological purposes.
Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

BACKGROUND Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking. OBJECTIVES The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition). METHODS A nested case-control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis. RESULTS Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC. CONCLUSIONS Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk.
Acute Poisoning with Rhabdomyolysis in the Intensive Care Unit: Risk Factors for Acute Kidney Injury and Renal Replacement Therapy Requirement

Acute kidney injury (AKI) is the major complication of rhabdomyolysis. We aimed to identify the predictive factors for AKI and renal replacement therapy (RRT) requirement in poisoning-associated rhabdomyolysis. We conducted a cohort study including 273 successive poisoned patients (median age, 41 years) who developed rhabdomyolysis defined as creatine kinase (CK) >1000 IU/L. Factors associated with AKI and RRT requirement were identified using multivariate analyses. Poisonings mainly involved psychotropic drugs. AKI occurred in 88 patients (37%) including 43 patients (49%) who required RRT. Peak serum creatinine and CK were weakly correlated (R2 = 0.17, p < 0.001). Death (13%) was more frequent after AKI onset (32% vs. 2%, p < 0.001). On admission, lithium overdose (OR, 44.4 (5.3–371.5)), serum calcium ≤2.1 mmol/L (OR, 14.3 (2.04–112.4)), female gender (OR, 5.5 (1.8–16.9)), serum phosphate ≥1.5 mmol/L (OR, 2.0 (1.0–4.2)), lactate ≥ 3.3 mmol/L (OR, 1.2 (1.1–1.4)), serum creatinine ≥ 125 µmol/L (OR, 1.05 (1.03–1.06)) and age (OR, 1.04 (1.01–1.07)) independently predicted AKI onset. Calcium-channel blocker overdose (OR, 14.2 (3.8–53.6)), serum phosphate ≥ 2.3 mmol/L (OR, 1.6 (1.1–2.6)), Glasgow score ≤ 5 (OR, 1.12; (1.02–1.25)), prothrombin index ≤ 71% (OR, 1.03; (1.01–1.05)) and serum creatinine ≥ 125 µmol/L (OR, 1.01; (1.00–1.01)) independently predicted RRT requirement. We identified the predictive factors for AKI and RRT requirement on admission to improve management in poisoned patients presenting rhabdomyolysis.
Biomineralized Bacterial Outer Membrane Vesicles Potentiate Safe and Efficient Tumor Microenvironment Reprogramming for Anticancer Therapy

The highly immunosuppressive tumor microenvironment (TME) in solid tumors often dampens the efficacy of immunotherapy. In this study, bacterial outer membrane vesicles (OMVs) are demonstrated as powerful immunostimulants for TME reprogramming. To overcome the obstacles of antibody‐dependent clearance and high toxicity induced by OMVs upon intravenous injection (a classic clinically relevant delivery mode), calcium phosphate (CaP) shells are employed to cover the surface of OMVs, which enables potent OMV‐based TME reprograming without side effects. Meanwhile, the pH‐sensitive CaP shells facilitate the neutralization of acidic TME, leading to highly beneficial M2‐to‐M1 polarization of macrophages for improved antitumor effect. Moreover, the outer shells can be integrated with functional components like folic acid or photosensitizer agents, which facilitates the use of the OMV‐based platform in combination therapies for a synergic therapeutic effect.