A case of IgG4-related interstitial nephritis with ureteral obstruction: case report and literature review.

BACKGROUND: IgG4-related disease (IgG4-RD) is a newly discovered systemic disease that can affect any organ or tissue in the body. IgG4-related kidney disease (IgG4-RKD) is relatively rare but essential to IgG4-RD. However, there are few reports of IgG4-RD mimicking malignant ureteral tumors leading to hydronephrosis. We report here a rare case of IgG4-RD involving the ureter. CASE PRESENTATION: An 87-year-old man presented to our nephrology department with anorexia, nausea, and acute kidney injury in November 2020. Urinary computed tomography (CT) examination revealed a right lower ureter mass with right renal and ureter hydronephrosis. The serum level of IgG4 was 1890 mg/dL, and the concurrently renal biopsy revealed extensive infiltration of IgG4-positive plasma cells in renal interstitium, which was diagnosed as IgG4-associated tubule-interstitial nephritis(IgG4-TIN). The renal function improved significantly after double-J tube implantation of the right ureter and moderate-dose hormone therapy. The serum IgG4 decreased to the normal range, and the right lower ureter mass almost disappeared after one year of low-dose hormone maintenance therapy. CONCLUSION: IgG4-RD can present as a mass in the renal pelvis and (or) ureter, leading to hydronephrosis. Therefore, early recognition of this disease is significant. Most patients respond well to hormonal therapy to avoid surgical treatment due to misdiagnosis as malignant tumors, causing secondary harm to patients.

New 3D Porous Silver Nanopolycluster as a Highly Effective Supercapacitor Electrode: Synthesis and Study of the Optical and Electrochemical Properties.

A high-nucleus silver nanopolycluster as a new type of silver-based polymer supercapacitor (SSc) by a simple and single-step synthesis process was designed and synthesized. The structural, optical, and electrochemical properties of SSc-2 were determined. This highly stable conductive 3D nanopolycluster shows great cycling stability, large capacity, and high energy density without any modification or doping process and so acts as an excellent SSc (412 F g-1 at 1.5 A g-1). In addition, there was a stable cycling performance (94% capacitance) following 7000 cycles at 3 A g-1 current density. The presence of fluorinated groups, 3D expansion of high-nucleus metallic clusters, and porosity are the advantages of SSc-2 that lead to stability, conductivity, and high capacity, respectively. These results lead to the development of a novel kind of SSc by overcoming the low conductivity and limited capacity challenges without any modification.

New HIV diagnoses in patients with COVID-19: two case reports and a brief literature review.

BACKGROUND: COVID-19 is novel infectious disease with an evolving understanding of its epidemiology and clinical manifestations. Severe cases developed life-threatening complications, such as respiratory failure, shock, and multiple organs dysfunction. Immunocompromised patients often present atypical presentations of viral infected diseases. CASE PRESENTATION: We report newly diagnosed HIV infections in two patients with COVID-19 in China. In our two cases, both patients with elevated IL-6 received Tocilizumab treatment, but did not present obvious therapeutic effect. CONCLUSIONS: These cases highlight possible co-detection of known immunocompromised diseases such as HIV. The two cases we reported stressed the risk of misdiagnosis, especially during the pandemic of an infectious disease and the importance of extended testing even if in immune-compromised condition the immune state may be ignored.

High-throughput screening campaign identifies a small molecule agonist of the relaxin family peptide receptor 4.

Relaxin/insulin-like family peptide receptor 4 (RXFP4) is a class A G protein-coupled receptor (GPCR), and insulin-like peptide 5 (INSL5) is its endogenous ligand. Although the precise physiological role of INSL5/RXFP4 remains elusive, a number of studies have suggested it to be a potential therapeutic target for obesity and other metabolic disorders. Since selective agonists of RXFP4 are scarcely available and peptidic analogs of INSL5 are hard to make, we conducted a high-throughput screening campaign against 52,000 synthetic and natural compounds targeting RXFP4. Of the 109 initial hits discovered, only 3 compounds were confirmed in secondary screening, with JK0621-D008 displaying the best agonism at human RXFP4. Its S-configuration stereoisomer (JK1) was subsequently isolated and validated by a series of bioassays, demonstrating a consistent agonistic effect in cells overexpressing RXFP4. This scaffold may provide a valuable tool to further explore the biological functions of RXFP4.

W2476 ameliorates ß-cell dysfunction and exerts therapeutic effects in mouse models of diabetes via modulation of the thioredoxin-interacting protein signaling pathway.

Recent evidence shows that high glucose levels recruit carbohydrate response element-binding protein, which binds the promoter of thioredoxin-interacting protein (txnip), thereby regulating its expression in ß-cells. Overexpression of txnip not only induces ß-cell apoptosis but also reduces insulin production. Thus, the discovery of compounds that either inhibit TXNIP activity or suppress its expression was the focus of the present study. INS-1E cells stably transfected with either a txnip proximal glucose response element connected to a luciferase reporter plasmid (BG73) or full-length txnip promoter connected to a luciferase reporter plasmid (CL108) were used in primary and secondary high-throughput screening campaigns, respectively. From 256 000 synthetic compounds, a small molecule compound, W2476 [9-((1-(4-acetyl-phenyloxy)-ethyl)-2-)adenine], was identified as a modulator of the TXNIP-regulated signaling pathway following the screening and characterized using a battery of bioassays. The preventive and therapeutic properties of W2476 were further examined in streptozotocin-induced diabetic and diet-induced obese mice. Treatment with W2476 (1, 5, and 15 µmol/L) dose-dependently inhibited high glucose-induced TXNIP expression at the mRNA and protein levels in INS-1E cells and rat pancreatic islets. Furthermore, W2476 treatment prevented INS-1E cells from apoptosis induced by chronic exposure of high glucose and enhanced insulin production in vitro. Oral administration of W2476 (200 mg·kg-1·d-1) rescued streptozotocin-induced diabetic mice by promoting ß-cell survival and enhancing insulin secretion. This therapeutic property of W2476 was further demonstrated by its ability to improve glucose homeostasis and insulin sensitivity in diet-induced obese mice. Thus, chemical intervention of the TXNIP-regulated signaling pathway might present a viable approach to manage diabetes.

Stability of tryptophan-containing LOs in flaxseed oil and their response towards γ-tocopherol.

Linusorbs (LOs), significantly influence oil quality and sensory properties of flaxseed oil. Trp-containing LOs exhibit distinct oxidative behavior when γ-tocopherol (γ-T) is present. Polar fractions of crude flaxseed oil were stripped via silica absorption, and reintroduced (LO and γ-T) separately into the oil matrix to investigate their interaction during storage. Compared with crude oil, LOs account for 18.49% reduction of p-anisidine value, while LOs with γ-T contributed to most of the endogenous antioxidant effect in crude oil. γ-T was found to suppress oxidation of Trp-containing LO at early stage (Met form), while facilitate oxidation while at their mid-stage (MetO form, Methionine sulfoxide). In vitro oxidation shows that CLD more likely cleaved into peptide fragments, while few products retain intact ring structures. LC-MS/MS analysis and silicon simulation revealed proximity between MetO and Trp residues, facilitating inter- or intra-molecular reactions and ring structure rupture. Remarkably, the presence of γ-T facilitate these phenomena.

Relationship of inflammation and endothelial dysfunction with risks to cardiovascular disease among people in Inner Mongolia of China.

OBJECTIVE: To explore the relationship of inflammation and endothelial dysfunction with risks to cardiovascular disease (CVD). METHODS: Blood pressure, body weight, body height, waist circumference and lifestyle risk factors were measured and studied among 2589 participants in Inner Mongolia of China, and biomarkers of inflammation and endothelial dysfunction including high-sensitivity C-reactive protein (hsCRP), soluble inter-cellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin), and angiotensin II were investigated. RESULTS: Subjects with metabolic risk factors for CVD had higher levels of hsCRP, sE-selectin and sICAM-1 than those without such risk factors (all P<0.05). Levels of all biomarkers positively and significantly increased with aggregation of the metabolic risk factors among the subjects (all P for trend <0.001). Data from the multivariate analysis showed that participants with high levels of hsCRP [odds ratio (OR): 1.96, 95% confidence interval (CI): 1.52-2.53], sE-selectin (OR: 1.35, 95% CI: 1.05-1.72), and angiotensin II (OR: 1.81, 95% CI: 1.40-2.33) were more likely to develop hypertension; participants with high levels of hsCRP (OR: 2.33, 95% CI: 1.85-2.94), sE-selectin (OR: 1.24, 95% CI: 1.00-1.54), and sICAM-1 (OR: 1.70, 95% CI: 1.30-2.22) were more likely to develop dyslipidemia, and those with high levels of hsCRP (OR: 2.95, 95% CI: 2.27-3.83) and sICAM-1(OR: 2.80, 95% CI: 2.06-3.80) were more likely to develop hyperglycemia. CONCLUSION: Biomarkers of inflammation and endothelial dysfunction were separately associated with relevant metabolic risk factors for CVD. And appropriate measures should be taken to control inflammation and improve endothelial function among individuals with different metabolic risk factors for CVD.

Identification of catalytic and non-catalytic activity inhibitors against PRC2-EZH2 complex through multiple high-throughput screening campaigns.

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) along with embryonic ectoderm development (EED) and suppressor of zeste 12 (SUZ12), which implements transcriptional repression mainly by depositing trimethylation marks at lysine 27 of histone H3 (H3K27me3). Its catalytic activity is closely correlated with the stability of PRC2, and somatic activating mutation of EZH2 Y641F within the catalytic SET domain drives tumor aggressiveness, drug resistance, and poor prognosis. Here, we report two high-throughput screening (HTS) campaigns targeting EZH2 Y641F and EZH2-EED interaction, respectively. For the EZH2 Y641F mutant, the HTS campaign involved a library of 250,000 compounds using a homogenous time-resolved fluorescence (HTRF) assay and identified 162 hits, while 60,160 compounds were screened against EZH2-EED interaction with a fluorescence polarization (FP) assay resulting in 97 hits. Among the 162 EZH2 Y641F inhibitors, 38 also suppressed EZH2-EED interaction and 80 showed inhibitory effects on the wide-type (WT) EZH2. Meanwhile, 10 of the 97 EZH2-EED interaction inhibitors were active against WT EZH2. These hit compounds provide useful tools for the development of novel PRC2-EZH2 inhibitors targeting its catalytic and non-catalytic activities.

Subclinical hypothyroidism is associated with lipid-rich plaques in patients with coronary artery disease as assessed by optical coherence tomography.

BACKGROUND: Subclinical hypothyroidism (SCH) has recently been acknowledged as an unconventional risk factor for coronary artery disease (CAD) and characterized by poor prognosis, which may be due to atherosclerotic plaque characteristics. We conducted this study to observe coronary plaque characteristics in coronary artery disease patients with concomitant SCH. METHODS: Patients with coronary artery disease were enrolled in the study and divided into an SCH group (patients, n = 26; plaques, n = 35) and a non-SCH group (patients, n = 52; plaques, n = 66). They were divided 1: 2 according to propensity-matched analysis including age, diabetes mellitus, gender, CAD severity and culprit vessel. Optical coherence tomography (OCT) imaging was performed on all patients, and images were analyzed by two independent investigators. Lipid-rich plaques (LRP), the precursor of vulnerable plaques, were defined as having more than one quadrant occupied with lipid pool. Maximum lipid arcs were simultaneously recorded. Fibrotic plaques and calcific plaques were also identified. The presence of coronary dissection, plaque erosion, thrombus, macrophage, calcific nodule, thin-cap fibroatheroma and micro channel were all noted. RESULTS: The ratio of LRP in SCH group was significantly higher than that in non-SCH group (54% vs. 30.3%, P = 0.037). That was the case as well for the maximum lipid arcs value (181.5° ± 61.6° vs. 142.1° ± 35.9°, P = 0.046). While thin-cap fibroatheroma (TCFA) was detected, no difference was identified between the two groups in either TCFA ratio (20% vs. 16.7%, P = 0.579) or fibrous cap thickness (57.5 ± 14.0 vs. 63.5 ± 10.7 µm, P = 0.319). Other OCT characteristics such as dissection, plaque erosion, thrombus, macrophage shadow and calcific nodule were also similar. CONCLUSION: Higher ratio of LRP with greater lipid arc in SCH patients may be related to the plaque instability and poor prognosis in CAD patients with SCH.

The hydrogen-bonded complex bis(tert-butylammonium) 2,6-dichlorophenolate 2,4-dichlorophenol-2,4-dichlorophenolate tetrahydrofuran disolvate containing a chiral R53(10) hydrogen-bonded ring as a supramolecular synthon.

A fixed hydrogen-bonding motif with a high probability of occurring when appropriate functional groups are involved is described as a `supramolecular hydrogen-bonding synthon'. The identification of these synthons may enable the prediction of accurate crystal structures. The rare chiral hydrogen-bonding motif R53(10) was observed previously in a cocrystal of 2,4,6-trichlorophenol, 2,4-dichlorophenol and dicyclohexylamine. In the title solvated salt, 2C4H12N+·C6H3Cl2O-·(C6H3Cl2O-·C6H4Cl2O)·2C4H8O, five components, namely two tert-butylammonium cations, one 2,4-dichlorophenol molecule, one 2,4-dichlorophenolate anion and one 2,6-dichlorophenolate anion, are bound by N-H...O and O-H...O hydrogen bonds to form a hydrogen-bonded ring, with the graph-set motif R53(10), which is further associated with two pendant tetrahydrofuran molecules by N-H...O hydrogen bonds. The hydrogen-bonded ring has internal symmetry, with a twofold axis running through the centre of the 2,6-dichlorophenolate anion, and is isostructural with a previous and related structure formed from 2,4-dichlorophenol, dicyclohexylamine and 2,4,6-trichlorophenol. In the title crystal, helical columns are built by the alignment and twisting of the chiral hydrogen-bonded rings, along and across the c axis, and successive pairs of rings are associated with each other through C-H...π interactions. Neighbouring helical columns are inversely related and, therefore, no chirality is sustained, in contrast to the previous case.

A hydrogen-bonded three-component complex: bis(dicyclohexylammonium) 2,4-dichlorophenolate 2,4,6-trichlorophenolate 2,4-dichlorophenol.

The title complex, 2C12H24N(+)·C6H3Cl2O(-)·C6H2Cl3O(-)·C6H4Cl2O, consists of three different achiral components, dicyclohexylammonium cations, 2,4,6-trichlorophenolate anions and H-atom-bridged 2,4-dichlorophenolate/2,4-dichlorophenol units, held together by O-H···N and O-H···O hydrogen bonds to form a chiral hydrogen-bonded ring. A helical cylinder is established by the packing of these rings along a crystallographic 41 screw axes. Helical cylinders may be generated from each other by translation, resulting in the formation of the chiral crystal. Neighbouring parallel helical cylinders are associated by van der Waals interactions only.

[Epidemiological study on hyperuricemia and gout in Foshan areas, Guangdong province].

OBJECTIVE: To determine the prevalence rates and risk factors of hyperuricemia (HUA) and gout among residents aged over 20 years in Foshan areas. METHODS: A randomly stratified cluster sampling was conducted, and 7403 inhabitants were investigated on their prevalence rates of HUA and gout. RESULTS: (1) The prevalence of HUA was 15.09%, and the standardized rate was 15.27%, in which the prevalence in males was 19.90% and females was 10.54%. The prevalence of gout was 1.04% and the standardized rate was 1.08%, in which the prevalence in males was 1.73% and females was 0.39%. The prevalence of gout in patients with HUA was 6.89%. (2) Average serum uric acid was (336.4 ± 81.5) µmol/L, with (347.1 ± 88.6) µmol/L in males and (289.7 ± 78.6) µmol/L in females. The serum uric acid levels in male patients with HUA was higher than those in women. (3) Age, body mass index, systolic blood pressure, diastolic blood pressure, serum uric acid, blood sugar, triglyceride (TG), total cholesterol were significantly higher in patients with HUA and gout than in the normal group (P < 0.05 - 0.01). The incidence rates of patients with hyperuricemia and gout in the following indices as:overweight and obesity, high blood pressure, high blood sugar were significantly higher than those in the normal group (P < 0.05). Patients having gout in the following indices as age, TG, serum uric acid levels were significantly higher than the HUA group (P < 0.05). (4) Data from non-conditional logistic regression analysis showed that age, overweight, hypertension, diabetes, hyperlipidemia, use of diuretics, family history, alcohol uptake, eating seafood and drinking meat broth, post-menopausal women, and other factors were similar to those factors as patients with hyperuricemia. Tea, fresh vegetables, fruits seemed to be the protective factors. CONCLUSION: Both the prevalence rates of HUA and gout had significantly increased in Foshan areas in recent years. Restricting the intake of food with rich purine, alcohol intake as well as controlling obesity and blood pressure, improving the status of lipid metabolic disorder together with programs as hypertension control etc. were important measures in the strategies on prevention and treatment on hyperuricemia and gout.

Comparative study of pathological lesions induced by multiwalled carbon nanotubes in lungs of mice by intratracheal instillation and inhalation.

The pathological lesions induced by multiwalled carbon nanotubes (MWCNTs) in bronchi and alveoli of mice were studied by intratracheal instillation and inhalation. In instillation groups, the dose was 0.05 mg MWCNTs/mouse. Similar size clumps of MWCNTs were distributed in bronchi and alveoli. The clumps led to inflammation to the lining wall of bronchi and severe destruction to alveolar netted structure around them. In the inhalation groups, the mice were exposed to aerosolized MWCNTs with mean concentration of 32.61 mg/m(3), the intralung deposition dose were roughly 0.07, 0.14, and 0.21 mg in the 8-day group, 16-day group, and 24-day group, respectively. Most of aggregations of MWCNTs in the alveoli were smaller than that in bronchi. The aggregations induced proliferation and thickening of alveolar walls. With the exception of these moderate pathological lesions, the general alveolar structure was still remained. The preliminary study demonstrated a difference in lung pathological lesions induced by instilled MWCNTs and inhaled ones, which may be due to the different size and distribution of aggregations of MWCNTs in lung.

catena-Poly[[(2,2'-biimidazole-kappa2N,N')chlorocopper(II)]-mu-chloro].

In the polymeric title compound, [CuCl2(C6H6N4)]n, each CuII ion is five-coordinated by four basal atoms (two N atoms from a 2,2'-biimidazole molecule and two Cl- anions) and one axial Cl- anion, in a distorted square-pyramidal coordination geometry. Cl- anions bridge the {Cu(C6H6N4)Cl} units into one-dimensional linear chains, which are reinforced by pi-pi interactions. Adjacent linear chains are linked by N-H...Cl hydrogen bonds, resulting in a grid layer. The hydrogen-bonding pattern can be described in graph-set notation as C(2)2(9)R(2)2(9)R(2)2(14). This study extends our knowledge of the multifunctional properties of the 2,2'-biimidazole ligand and of the coordination stereochemistry of copper(II).