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The deposition of lignin and carbohydrates in different cells and morphologically distinct cell wall layers during the development of Calamus simplicifolius was investigated by combined microscopic techniques. Lignin autofluorescence images showed that protoxylem vessels were the first to differentiate among vascular elements. At the subcellular level, high spatial resolution Raman images revealed that the deposition of carbohydrates in fibers preceded that of lignin. Additionally, the lignin and carbohydrates concentration in the secondary wall (SW) varied among different cell types. The carbohydrates concentration in SW of fibers presented the highest level, which was much higher than that in vessels and parenchyma. High concentrations of lignin were most visible in the SW of vessels, followed by fibers, with the lowest amount visible in parenchyma. Within the morphologically distinct cell wall layers, the carbohydrates and lignin in fibers SW and cell corners deposited rapidly at the early stage from the 7th to the 10th internode, while the deposition rate decreased from the 10th to the 50th internode. The findings have substantial theoretical significance to understand the biosynthesis of rattan cell walls.

Neutrophil-related chronic inflammation (NRCI) may contribute to the pathogenesis of diabetic kidney disease (DKD). We evaluated whether blocking NRCI with low-dose colchicine prevents DKD.A double-blind, randomized, placebo-controlled study was conducted. A total of 160 patients with type 2 diabetes (T2D) and microalbuminuria (urinary albumin creatinine ratio [UACR] 30 to 300 mg/g Cr) who received angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) for at least 3 months were included. Subjects were 1:1 randomized to a placebo or colchicine group (0.5 mg/day).The primary end point was the incidence of overt nephropathy (UACR 300 mg/g Cr). During the 36 months, 38 patients (51.4%) in colchicine group and 39 (54.1%) in the control group developed overt nephropathy (hazard ratio, 1.066; 95% confidence interval, 0.679-1.673; P = .78). Compared with placebo, colchicine modestly lowered levels of NRCI parameters (P values.05 for high-sensitivity C-reactive protein, white blood cell counts, neutrophil counts, and neutrophil-to-lymphocyte ratio), whereas the changes of UACR and estimated glomerular filtration rate (eGFR) were similar between the two groups. There were no significant differences between the two groups in drug-related adverse events, including infection, gastrointestinal symptoms, and limb numbness.In patients with T2D with microalbuminuria, low-dose colchicine effectively and safely lowered NRCI but did not prevent the incidence of overt nephropathy.背景: 中性粒细胞相关性慢性炎症(NRCI)可能与糖尿病肾病(DKD)的发生有关。我们用低剂量秋水仙碱抑制NRCI并评估其是否能延缓DKD的发生。 方法: 本研究为一项双盲、随机、安慰剂对照临床试验。研究共纳入2型糖尿病合并微量白蛋白尿(肌酐比 [UACR] 30-300mg/g Cr)的患者共160名, 所有患者均接受血管紧张素转换酶抑制剂(ACEi)或血管紧张素受体拮抗剂(ARBs)类药物至少3个月。患者按1:1随机分为安慰剂组或秋水仙碱组(接受秋水仙碱0.5mg/d)。 结果: 本研究的主要终点为显著肾病(UACR300mg/g Cr)的发生率。在随访的36个月中, 秋水仙碱组的38名患者(51.4%)以及安慰剂组的39名患者(54.1%)发展成为了显著肾病(危险比1.066; 95%置信区间 0.679-1.673; p=0.78)。秋水仙碱组与安慰剂组相比, NRCI水平有所下降(高灵敏C-反应蛋白、白细胞总数、中性粒细胞总数、中性粒细胞-淋巴细胞比值等指标, 两组有显著性差异, p0.05), 但两组的UACR变化率、估算肾小球滤过率变化率无显著差异。两组的药物相关不良反应, 包括感染、胃肠道症状、肢体麻木等症状无显著差异。 结论: 在2型糖尿病合并微量白蛋白尿的患者中, 低剂量秋水仙碱能有效且安全地降低NRCI, 但是不能延缓DKD的发生。.

Natural bamboo is rapidly replacing wood, but it is highly hygroscopic and has poor dimensional stability. Herein, Moso bamboo was subjected to hygrothermal treatment at different temperatures. The hydrophobicity and dimensional stability of bamboo increased, as indicated by the 16.5% decrease in volumetric swelling and three-fold increase in the contact angle at 220 °C. The fibers and parenchyma cells delaminated, and pores appeared after treatment at 200 °C. These changes were attributed to the significant degradation of hemicelluloses. The acetyl groups of hemicelluloses decomposed into acetic acid. The apparent crystallinity of cellulose increased mainly due to the reduced hemicellulose content. Furthermore, a breakage of xylan and β-O-4 bonds was observed, and S units were condensed after treatment at 220 °C. In addition, the syringyl/guaiacyl ratio showed more than a five-fold increase, while associated ferulic acid decreased after hygrothermal treatment, indicating that the dense structure of the cell walls was broken. These data were used to propose a mechanism for changes in the bamboo cell walls during hygrothermal treatment. This simple and environmentally-friendly approach holds great potential for use in high-humidity environments.

The permanent fixation is essential for the full industrialization of sandwich-compressed wood. In this study, sandwich-compressed wood was modified with superheated steam for compression fixation. Effects of superheated steam pressure on set-recovery were investigated. Changes in microstructure, chemical structure and cellulose crystalline structure of the compressed wood were analyzed, to clarify the reason and mechanism for sandwich compression fixation under superheated steam treatment. It was found that set-recovery of central-compressed wood was higher than that of surface-compressed wood. Effects of superheated steam treatment on set-recovery were statistically significant (P

Objective: To investigate whether serum bisphenol A (BPA) concentration is related to the occurrence of dyslipidemia. Methods: A total of 574 adults were enrolled at baseline and followed up for 5 years. Concentrations of serum BPA, triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured. Dyslipidemia was defined as the existence of one or more of the following conditions: high-LDL-cholesterolemia (LDL ≥140 mg/dL), hypertriglyceridemia (TGs ≥150 mg/dL), or low-HDL-cholesterolemia (HDL

Background A total of 44.7% adults in China have hypertension, but the prevalence of primary aldosteronism (PA) in Chinese hypertensive patients is unknown. Objectives This study prospectively investigated the prevalence, characteristics, and outcomes of PA in newly diagnosed hypertensive patients. Methods In a large community health center, consecutive hypertensive patients with an aldosterone-renin ratio >20 ng/mIU and plasma aldosterone concentration >10 ng/dl underwent captopril challenge test and/or saline infusion test for confirmation of PA. Adrenal computed tomography scan and adrenal vein sampling were used for subtyping. PA patients treated with surgery or medication were followed up for 1 year, and outcomes after treatment were evaluated. Results In total, 1,020 newly diagnosed hypertensive patients were screened over 16 months, of whom 40 were diagnosed with PA, 948 with non-PA, 32 with probable PA, resulting in a prevalence of more than 4.0%. Compared with non-PA, PA patients more frequently displayed microalbuminuria (p = 0.031), but the incidence of cardiovascular events was not different (p = 0.927). For surgically treated patients (n = 7), a complete biochemical success rate was 100% and a complete clinical success rate was 85.7%. For medically treated patients (n = 29), the proportion with optimal blood pressure control was 79%, and among them, 91% (21 of 23) only needed 1 antihypertensive drug: the mineralocorticoid receptor antagonist. Conclusions The prevalence of PA in patients with newly diagnosed hypertension in China was at least 4%. PA screening in newly diagnosed hypertensive patients leads to good clinical outcomes. (Primary Aldosteronism In Hypertensive Patients in China [PA-China]; NCT03155139)

N6-methyladenine (N6-mA) of DNA is an emerging epigenetic mark in mammalian genome. Levels of N6-mA undergo drastic fluctuation during early embryogenesis, indicative of active regulation. Here we show that the 2-oxoglutarate-dependent oxygenase ALKBH1 functions as a nuclear eraser of N6-mA in unpairing regions (e.g., SIDD, Stress-Induced DNA Double Helix Destabilization regions) of mammalian genomes. Enzymatic profiling studies revealed that ALKBH1 prefers bubbled or bulged DNAs as substrate, instead of single-stranded (ss-) or double-stranded (ds-) DNAs. Structural studies of ALKBH1 revealed an unexpected “stretch-out” conformation of its “Flip1” motif, a conserved element that usually bends over catalytic center to facilitate substrate base flipping in other DNA demethylases. Thus, lack of a bending “Flip1” explains the observed preference of ALKBH1 for unpairing substrates, in which the flipped N6-mA is primed for catalysis. Co-crystal structural studies of ALKBH1 bound to a 21-mer bulged DNA explained the need of both flanking duplexes and a flipped base for recognition and catalysis. Key elements (e.g., an ALKBH1-specific α1 helix) as well as residues contributing to structural integrity and catalytic activity were validated by structure-based mutagenesis studies. Furthermore, ssDNA-seq and DIP-seq analyses revealed significant co-occurrence of base unpairing regions with N6-mA in mouse genome. Collectively, our biochemical, structural and genomic studies suggest that ALKBH1 is an important DNA demethylase that regulates genome N6-mA turnover of unpairing regions associated with dynamic chromosome regulation.

Context The saline infusion test (SIT) is a common confirmatory test for primary aldosteronism (PA). According to the guideline, a postinfusion plasma aldosterone concentration (PAC) of 5-10 ng/dL is considered indeterminate, and recommendations for diagnostic strategies are currently limited in this situation. Objective To explore whether an addition of the captopril challenge test (CCT) could improve the diagnostic accuracy in patients with indeterminate SIT. Methods A total of 280 hypertensive patients with high risk of PA completed this study. Subjects were defined as SIT indeterminate based on their PAC post-SIT. These patients then underwent the CCT where PACs post-CCT >11 ng/dL were considered positive. Using fludrocortisone suppression test (FST) as the reference standard, diagnostic parameters including area under the receiver-operator characteristic curves (AUC), sensitivity and specificity were calculated. Results There were 65 subjects (23.2%) diagnosed as PA indeterminate after SIT. With the addition of CCT, true-positive numbers increased from 134 to 147, and false-negative numbers decreased from 27 to 14. Compared to SIT alone, a combination of SIT and CCT showed a higher AUC (0.91 [0.87,0.94] vs 0.87 [0.83,0.91], P = .041) and an increased sensitivity for the diagnosis of PA (0.91 [0.86,0.95] vs 0.83 [0.76,0.89], P = .028), while the specificity remained similar. In the subgroup with indeterminate SIT results, using PAC post-CCT resulted in a 36% higher AUC than using PAC post-SIT alone for the diagnosis of PA. Conclusion For patients under investigation for possible PA who have indeterminate SIT results, an addition of CCT improves the diagnostic accuracy.

SummaryOverlapping coding regions balance selective forces between multiple genes. One possible division of nucleotide sequence is that the predominant selective force on a particular nucleotide can be attributed to just one gene. While this arrangement has been observed in regions in which one gene is structured and the other is disordered, we sought to explore how overlapping genes balance constraints when both protein products are structured over the same sequence. We use a combination of sequence analysis, functional assays and selection experiments to examine an overlapped region in HIV-1 that encodes helical regions in both Env and Rev. We find that functional segregation occurs even in this overlap, with each protein spacing its functional residues in a manner that allows a mutable non-binding face of one helix to encode important functional residues on a charged face in the other helix. Additionally, our experiments reveal novel and critical functional residues in Env and have implications for the therapeutic targeting of HIV-1.

Electro-biological particle electrode (EBPE) prepared by lithium slag was used to remove salicylic acid in a three-dimensional electrocatalytic biological coupling reactor (3D-EBCR). The physical and chemical properties of the EBPE, the removal performance of salicylic acid and the degradation mechanism were studied. Results revealed as follows: (1) the EBPE prepared by lithium slag contained effective catalytic components including Fe2O3, SnO2, ZnO, MnO, Rb2O and TiO2, with stable structure and good adsorption performance; (2) the 3D-EBCR with EBPE had strong adaptability to the current intensity in the range of 0.25-0.40 A, and the removal rates of COD and salicylic acid were maintained above 87.1% and 85.2% respectively; (3) salicylic acid was removed through the synergistic action of adsorption, electrochemical oxidation and biological action.

The combination of surface densification and superheated steam treatment is an effective method to improve the mechanical properties and dimensional stability of low-density wood. The objective of the current work is to evaluate the effects of superheated steam treatment on the micromechanical behavior of surface densified wood. The microstructure, chemical composition, cellulose crystalline structure, and micromechanical behavior of surface densified wood under different superheated steam pressures were investigated. Results indicated that both 0.1 MPa and 0.3 MPa superheated steam treatments increased the elastic modulus and hardness of fiber cell walls in surface densified wood. However, the average creep ratio and maximum creep compliance J(50) of surface densified wood under 0.3 MPa decreased by 41.59% and 6.76%, respectively, compared with untreated wood. The improvement of elastic modulus, hardness and creep resistance of surface densified wood treated with superheated steam was associated with the increase of relative crystallinity (CrI) and crystalline size. In addition, 0.3 MPa superheated steam treatment displayed a better effect on the enhancement of the elastic modulus, hardness, and creep resistance of the fiber cell wall than 0.1 MPa superheated steam treatment.

Lignin is the major components limiting enzymatic hydrolysis and normally removed by acidified sodium chlorite in laboratory. However, the information on delignification kinetics and selectivity at cellular level as the reaction proceeds is limited. In this work, the dynamic removal of lignin and its monolignol in different cell types of poplar were visualized in real time by confocal Raman microscopy. At the initial stage, substantial reduction in lignin concentration was observed especially in cell corner and compound middle lamella of fiber, but the removal rate slowed down in the following process. Delignification was highly cell-selective that the vessel was the most resistant to delignification followed by ray and then by fiber. Besides, the removal behavior of lignin monomers in ray varied significantly with vessel and fiber. In the whole process, the syringyl units was more prone to being removed than guaiacyl units. This information could lead to a better understanding of the delignification process of lignocellulosic biomass by chlorite treatment.

The goal of this research was to develop a new process for simultaneously removing organics and heavy metals of electroplating wastewater by in-situ ion exchange electrocatalysis biological coupling (i-IEEBC). The study evaluated the removal efficiency of coexisting refractory organics and heavy metal ions, and investigated the effects of current density (CD) on the removal performance of the i-IEEBC method. The results indicated the i-IEEBC reactor exhibited higher average removal rates of COD, TOC, Cr and Cu ions, i.e. 87.23%, 80.42%, 91.25%, and 95.97% in that order, which represented an increase by 32.59%, 40.10%, 31.86%, and 33.82%, respectively, compared with BAF. The optimum CD for simultaneously removing organics and heavy metals of electroplating wastewater in i-IEEBC was 0.40 mA/(cm)2. The change of biodegradability and the presence of short chain organic compounds also indirectly confirmed the excellent removal organic pollutants performance of i-IEEBC at the optimum CD. In addition, the composition and construction of CER before and after the application, under the optimum CD, SEM, EDS and FT-IR spectroscopy also showed that the cation exchange properties of CER improved the catalytic lifetime of the particle electrodes. This research provides a highly efficient new alternative to electroplating wastewater treatment technology.

Wavelength-sized microdisk resonators were fabricated on a single crystalline 4H-silicon-carbide-oninsulator platform (4H-SiCOI). By carrying out microphotoluminescence measurements at room temperature, we show that the microdisk resonators support whispering-gallery modes (WGMs) with quality factors up to $5.25 \times 10^3$ and mode volumes down to $2.69 \times(\lambda /n)^3$ at the visible and near-infrared wavelengths. Moreover, the demonstrated wavelength-sized microdisk resonators exhibit WGMs whose resonant wavelengths compatible with the zero-phonon lines of spin defects in 4H-SiCOI, making them a promising candidate for applications in cavity quantum electrodynamics and integrated quantum photonic circuits., Comment: 5 pages, 4 figures

Objective. It has been increasingly appreciated that G protein-coupled estrogen receptor 1 (GPER1) mediates both proinflammatory and anti-inflammatory response of estrogen. It is also involved in some rapid vascular effects of aldosterone in a mineralocorticoid receptor (MR) independent manner. However, whether GPER1 mediates aldosterone-induced inflammation response in endothelial cells and its relationship with MR are yet undetermined and therefore require further explanation. Method. Based on the hypothesis that GPER1 plays a role in the aldosterone-related vascular inflammation, the present study utilized a model of human umbilical vein endothelial cells transfected with MR siRNA and induced for inflammatory response with increasing concentration of aldosterone. Results. It was discovered that induction of aldosterone had no effect on the expression of GPER1 but promoted the expression of MR. Suppression of MR did not influence GPER1 expression, and GPER1 was capable of mediating part of aldosterone-induced endothelial inflammatory response. This effect may involve phosphoinositide 3-kinases (PI3K) pathway signaling. Conclusion. These findings not only demonstrated the role of GPER1 in aldosterone-induced vascular inflammation but also suggested an alternative for pharmaceutical treatment of hyperaldosteronism considering the unsatisfying effect on cardiovascular risks with MR antagonists.

Metasurface silicon-based optical devices are highly integrated and high-performance, meeting the requirements of photonics integrated circuits. We present a design method for metasurface silicon-based gradient index (GRIN) optical lens. With easy calculation, this method supports large-area GRIN elements design. The Luneburg lens and integrated coupler are shown as examples. Such devices show good performances in simulations. The simulations show that the Luneburg lens can focus light from all directions equally well. The optical 1-dB bandwidth of the integrated coupler is about 100 nm. Our method provides a convenient and feasible approach for designing silicon-based GRIN lenses.

Aldosterone-producing adenoma (APA) is a main cause of primary aldosteronism (PA). Given that a large benign-appearing unilateral masse (>1 cm in diameter) may represent an aldosterone and cortisol-co-secreting adenoma, dexamethasone suppression testing is required in such patients to exclude or confirm the diagnosis of hypercortisolism. Tuberculosis is highly prevalent in China, and rifamycins are often used in these patients. Rifapentine belongs to the rifamycin family, and we herein for the first time report a case of misdiagnosis of hypercortisolism due to rifapentine use in a patient with APA. Thus, in patients treated with rifapentine, diagnosis of hypercortisolism based on dexamethasone suppression tests can be very misleading.

Objective: This study aimed to investigate the effect of anti-osteoporosis therapy on plasma aldosterone concentration (PAC), plasma renin concentration (PRC) and the aldosterone/renin ratio (ARR) in patients with postmenopausal osteoporosis. Methods: In 60 patients with postmenopausal osteoporosis, bone mineral density (BMD), PAC and PRC were measured before and after treatment with alendronate (70 mg/week, n=22) or recombinant human parathyroid hormone (20 μg/day, n=35) for 48 weeks. Results: PAC was negatively correlated with the T-score of lumbar spine BMD and femoral neck BMD (lumbar r=−0.386, p37 pg/μIU, and the proportion decreased to 8% (5/57) after treatment. Conclusion: Treatment with alendronate or parathyroid hormone causes decreased PAC and increased PRC, resulting in a decreased ARR in postmenopausal women with osteoporosis.

IntroductionAldosterone is a mediator of progressive renal disease, but the mechanisms for aldosterone-mediated renal impairment in mice with diabetes are not fully defined.MethodsAldosterone and/or mineralocorticoid receptor antagonist eplerenone were used to treat the db/db mice with diabetes. Proximal tubule epithelial cells (PTECs) and fibroblasts were cultured. Blood and kidney samples from patients with diabetes with or without diabetic kidney disease (DKD) were used to verify the findings from animals and cultured cells.ResultsWe found that aldosterone promoted proteinuria and tubulointerstitial extracellular matrix (ECM) accumulation in db/db mice with diabetes while eplerenone mitigated the adverse effect of aldosterone. However, coculture of PTECs and fibroblasts found that when PTECs-derived extracellular vesicles (EVs) were taken up by fibroblasts, ECM production increased remarkably. Moreover, C57BL/6 mice injected with EVs from renal cortex of aldosterone-treated db/db mice showed increased ECM accumulation. Function of the ingredients of PTECs-derived EVs were analyzed, and RNAs were identified to be responsible for the EVs-induced fibroblast dysfunction. Furthermore, microRNA (miRNA) array analysis revealed that miR-196b-5p was the most remarkably increased miRNA in PTECs-derived EVs with aldosterone stimulation. Overexpression of miR-196b-5p in fibroblasts increased ECM production, accompanied by inhibition of the SOCS2 expression and enhanced STAT3 phosphorylation. In addition, plasma levels of miR-196b-5p was higher in patients with DKD as compared with patients without DKD and miR-196b-5p levels positively correlated with the albuminuria concentration. In kidney specimens from patients with diabetes, expression of miR-196b-5p, located mainly in PTECs, increased in patients with DKD as compared with the non-DKD.ConclusionThis study demonstrates the involvement of miR-196b-5p-EVs pathway as a novel mechanism in aldosterone-induced renal fibrosis in diabetes. EVs rich in miR-196b-5p mediate the crosstalk between PTECs and fibroblast during the development of renal fibrosis, which might be associated with STAT3/SOCO2 signaling pathway.

Background The prevalence of primary aldosteronism concurrent with subclinical Cushing’s syndrome was higher than previously thought. Through analyzing a rare clinical case, we summarized the diagnosis and management of primary aldosteronism with subclinical Cushing’s syndrome. Case presentation A 54-year-old Chinese man of Han nationality was diagnosed as having primary aldosteronism with subclinical Cushing’s syndrome. An abdominal computed tomography scan revealed a mass in his left adrenal gland and a mass in his right adrenal gland. After finishing sequential adrenal venous sampling without adrenocorticotropic hormone, the result reminded us that the left and right nodules were responsible for hypercortisolism and aldosterone hypersecretion, respectively. Right and left adrenalectomy were performed successively. The pathological diagnosis was adrenocortical adenoma for both. Histological findings revealed that the right one had positive immunostaining for CYP11B2 and the left one had positive immunostaining for CYP11B1. The immunohistochemistry result helped us to confirm the diagnosis. Somatic KCNJ5 mutation (Leu168Arg) was found in the right tumor; there was no KCNJ5 mutation in the left adrenal tumor. Conclusions We suggest that patients with primary aldosteronism should have a low-dose overnight dexamethasone suppression test to screen for hypercortisolism. It can help avoid misdiagnoses and contribute to proper understanding of the adrenal vein sampling result. Making sure of the nidus of aldosterone and cortisol secretion is crucial for the therapy of patients with primary aldosteronism and subclinical Cushing’s syndrome.

Low refractive index magnesium fluoride (MgF2) dielectric layers with anti-reflection function were inserted between metal Al gratings and Al2O3 substrates in the form of continuous thin film and grating to construct type-I and type-II sub-wavelength wire-grid polarizers, respectively. The two types of wire-grid polarizers (type-1 and type-11) were designed to operate in the wavelength range of 3.0 similar to 5.0 Am. The structures of type-1 and type-II polarizers were optimized in terms of the substrate material, refractive index and thickness of dielectric layer using the finite-difference time-domain method. The results show that surface plasmon modes at the interface between Al gratings and Al2O3 substrate are weakened owing to the introduction of MgF2 dielectric layer, and a cavity mode in Al grating grooves begins to play a major role. In addition, equivalent refractive index of MgF2 dielectric grating is lower and MgF2 dielectric film is larger than the refractive index of ideal anti-reflection layer. Thus, MgF 2 dielectric grating has better antireflection function and higher transmittance towards the transverse magnetic polarization light. The distribution of electric field intensity indicates the existence of a cavity mode and stronger electric field intensity in the metal grating grooves of type-II. Higher TM transmittance and extinction ratio are achieved for type-11, which are obtained to be 99% and 30 dB at the wavelength of 4.0 mu m, respectively.

Arctigenin (ATG) is a major component of Fructus Arctii, a traditional herbal remedy that reduced proteinuria in diabetic patients. However, whether ATG specifically provides renoprotection in DKD is not known. Here we report that ATG administration is sufficient to attenuate proteinuria and podocyte injury in mouse models of diabetes. Transcriptomic analysis of diabetic mouse glomeruli showed that cell adhesion and inflammation are two key pathways affected by ATG treatment, and mass spectrometry analysis identified protein phosphatase 2 A (PP2A) as one of the top ATG-interacting proteins in renal cells. Enhanced PP2A activity by ATG reduces p65 NF-κB-mediated inflammatory response and high glucose-induced migration in cultured podocytes via interaction with Drebrin-1. Importantly, podocyte-specific Pp2a deletion in mice exacerbates DKD injury and abrogates the ATG-mediated renoprotection. Collectively, our results demonstrate a renoprotective mechanism of ATG via PP2A activation and establish PP2A as a potential target for DKD progression., Arctigenin (ATG) is the major active component of a Chinese herbal remedy known to reduce proteinuria in patients with diabetic kidney disease (DKD). Here, Zhong et al. identify PP2A as a pharmacological target of ATG in podocytes, and find that PP2A is responsible for some of the beneficial effects of ATG in mouse models of DKD.

Plasma aldosterone/renin ratio (ARR) is a useful method for primary aldosteronism (PA) screening. However some confounders, such as medications and dietary, affect plasma renin and aldosterone levels, resulting in false-negative or -positive plasma ARR. This study investigated the association between postmenopausal osteoporosis (PMO) and plasma ARR. Bone mineral density (BMD) was measured by dual-energy X-ray-absorptiometry (DXA) in 324 normotensive postmenopausal women. Based on clinical characteristics and BMD, 186 and 96 subjects were diagnosed as PMO and osteopenia respectively, and the remaining 42 subjects were grouped as normal BMD. Plasma aldosterone concentration (PAC), plasma renin concentration (PRC), parathyroid hormone (PTH), bone alkaline phosphatase (BALP) and 25-Hydroxyvitamin D(25-(OH)D) were determined. Subjects with PMO showed significantly higher levels of PAC (121.0 ± 78.8 vs. 81.8 ± 71.5 pg/ml, p

Acidified sodium chlorite (NaClO2) and sodium hydroxide (NaOH) solutions were successfully used to eliminate lignin and hemicellulose, respectively, from isolated bamboo fibers to investigate their microstructures, composition and micro-tensile properties in individual cellulose fibers. The results demonstrated that isolated fibers and chemically treated fibers clearly displayed different wrinkles, pores and microfibril aggregations on the cell wall surface. Field emission environmental scanning electron microscope images together with confocal scanning laser microscope measurements revealed that chemical treatments have a reduction effect on micro-tensile strength and modulus. Two methods of freeze-drying and air-drying produced varying interfaces and pores in microfibril aggregations and resulted in different tensile behavior. Notably, the reductions of Young’s modulus and tensile strength in freeze-drying (52.99 and 13.32%) fibers are larger than that (18.21 and 10.93%) in air-drying samples. These results suggest that most fractures occur in the weak interspaces or pores that are caused by the loss of matrix materials during chemical treatments.

Background/Aims: Whether angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) could benefit patients with diabetes and albuminuria remains controversial. A systematic review and meta-analysis were conducted to answer this question by comparing ACE inhibitors or ARB with placebo among these patients. Methods: In this meta-analysis, electronic data sources (Medline, the Cochrane Collaboration, and EMBASE) were searched. Randomized controlled trials (RCTs) comparing ACE inhibitors or ARB with placebo in subjects with diabetes and albuminuria (defined as urinary albumin-to-creatinine ratio, UACR≥30mg/g Cr) were included. Outcomes parameters were all-cause mortality, end stage renal disease (ESRD), doubling of serum creatinine levels, and cardiovascular events (CV). Results: Twenty-six RCTs (including 20 for ACE inhibitors and 6 for ARB) were included, comprising 10378 participants with diabetes and albuminuria. Compared to placebo, treatment with ACE inhibitors or ARBs did not reduce all-cause mortality or CV. For renal outcomes, ARBs significantly reduced the risk of ESRD by 23% (odds ratio 0.77, 95%CI 0.65-0.92), while ACE inhibitors were not associated with a decreased risk of ESRD (0.69, 0.43-1.10). Both ACE inhibitors and ARBs reduced the risk of doubling of the serum creatinine level (0.60, 0.39-0.91 for ACE inhibitors; 0.75, 0.64-0.88 for ARBs), and subgroup analyses for patients with macroalbuminuria or microalbuminuria showed similar results. Conclusion: In patients with diabetes and albuminuria, ARBs reduced risks of ESRD and doubling of the serum creatinine level. ACE inhibitors and ARBs failed to reduce all-cause mortality and CV. Based on the renoprotective effects, ARBs may be preferred for diabetic patients with albuminuria.

Novel particle electrodes, i.e. flotation tailings particle electrode (FPE), were prepared using flotation tailings, garden soil, and soluble starch with a mass ratio of 16:3:1, and then used in tetracycline wastewater treatment. The physicochemical properties of FPE were systematically characterized using SEM, XRD, FT-IR and XRF. Tetracycline adsorption and its adsorption mechanism onto FPE was explored for the first time. Parameters affecting FPE's degradation efficiency and energy consumption such as current density, electrolysis time, initial concentration, initial pH and aeration rate were examined. The electrocatalytic degradation of tetracycline shows that the degradation of tetracycline meets the pseudo-first-order kinetics. Moreover, the numbers of •OH produced on the surfaces of the cathode, anode and particle electrode were compared. Results showed that the adsorption-saturated FPE can be regenerated by electrochemical action to induce further absorption and form in-situ electrocatalysis. In order to find out the transformation products in water and degradation pathways of Tetracycline, UHPLC method was used to obtain the degradation pathways for Tetracycline. So, this work could provide a fabrication of high-efficiency and low-cost electrocatalytic for removal of pharmaceuticals pollutants from waste water as well as deeper insight into electrocatalytic mechanism, transformation products, and degradation pathways of Tetracycline in water.

Presently, porous materials have become essential to many technological applications. In this account, 3-dimensional skeleton composite materials consisting of a core-shell amorphous porous carbon/multilayer graphene are synthesized by chemical vapor deposition on Ni foam using a facile one-step growth method. The data suggest that these composites have not only outstanding electrical and mechanical properties of the multilayer graphene but also the mesoporous characteristics of the amorphous carbon. Moreover, the composited carbon materials perfectly inherit the macroporous structure of Ni foam, and the amorphous carbon core in the skeleton serves as a cushion to buffer the volume variation after the removal of Ni. The carbon composites reveal ultralow density (4.45 mg cm-3) and high conductivity (45 S cm-1), essentially issued from the perfectly preserved structural integrity of graphene. The novel carbon composites can be used as anodes for lithium ion batteries. After these carbon composites are incorporated with NaBiO3, superior electrochemical activities above 2 V can be achieved with a discharge capacity of ∼300 mAh g-1.

Bisphenol A (BPA), one of the most common environmental endocrine disruptors, is considered to promote hepatic lipid deposition. However, the mechanism has not been fully elucidated. The polarization of Kupffer cells (KCs) plays an important role in hepatic inflammation by promoting pro-inflammatory M1 phenotype (M1KCs), which contributes to dysregulated lipid metabolism. The purpose of this study is to investigate the role of KC polarization in BPA-induced hepatosteatosis in male mice. In this study, we examined hepatic lipid contents and quantified M1KC in BPA-treated CD1 mice, and further explored the interaction between KCs and hepatocytes using conditional HepG2 cell culture. BPA treatment significantly increased hepatic fat contents in CD1 mice, accompanied by increased number of pro-inflammatory M1KCs and enhanced secretion of inflammatory cytokines. Increased lipid contents were also observed in HepG2 cells treated with BPA. Interestingly, higher TG contents were observed in HepaG2 cells treated with conditional media from BPA-treated KCs, compared with those treated with BPA directly. Incubation of KCs with BPA promoted the polarization of KCs to pro-inflammatory M1 dominant subtypes, which was blocked by estrogen antagonist ICI182780. Taken together, our results revealed that M1KCs polarization is involved in BPA-induced hepatic fat deposition, which is possibly associated with the estrogen receptor signaling pathway.

Rattan-based silicon carbide (R-SiC) ceramics, R-SiCSiO2 and R-SiCSi, were successfully prepared from silica (SiO2) sol and silicon (Si) powder, respectively. The rattan powder was impregnated, respectively, with SiO2 sol at ambient temperature and liquid melt-Si at high temperature. This was followed by one-step direct pyrolysis at 1500 °C under an argon (Ar) atmosphere. The final SiC samples were analyzed using mass analysis, X-ray diffraction (XRD), X-ray fluorescence (XRF), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), energy dispersive X-ray analysis (EDAX), and nitrogen (N2) physisorption techniques. Experimental results showed that the mass residual of R-SiCSi (42.56 wt%) was almost equal to R-SiCSiO2 (42.45 wt%). However, R-SiCSiO2 had a higher yield of SiC, a higher specific surface area and a more intact porous morphology preserved from the rattan biomass. In addition, some rod-like SiC whiskers and tablet-like SiC particles were found in R-SiCSiO2. By comparison, R-SiCSi had a large amount of unreacted Si, as well as certain amount of SiC and unreacted C. Thus, it can be concluded that SiO2 sols are more appropriate for use in preparation of SiC from rattan, whatever the porous microstructure, yield, and purity of SiC.

The effects of chemical treatments (H2O2 + CH3COOH, acidified NaClO2, and NaOH) and freeze-drying on bamboo fibers were studied at a submicron level, to characterize chemical and mechanical changes to the secondary cell wall. Specifically, a field emission environmental scanning electron microscope (FE-ESEM) and imaging fourier transform infrared spectroscopy (FTIR) were used to demonstrate degradation in morphology and molecular structure, and nanoindentation was used to track changes in micromechanical properties. The results showed that cellular structures after chemical treatments clearly displayed wrinkles, pores, and microfibrils. The decreased bands at 1508 cm-1 and 1426 cm−1 showed that lignin was degraded on treatment of H2O2 + CH3COOH and acidified NaClO2, which directly resulted in a decrease in hardness (H) in the secondary cell wall for treated fibers. In addition, a diminishing peak at 1733 cm−1 caused by NaOH solution indicated that hemicellulose was seriously degraded. It resulted in a decreased modulus (E r) by 13.71 % in bamboo fibers, while no obvious reduction was observed in the first two steps.

The association between primary aldosteronism (PA) and obstructive sleep apnea (OSA) has been a matter of debate. 2016 Endocrine Society guideline recommends screening for PA all hypertensive patients with OSA. We designed a multicenter, multiethnic, cross-sectional study to evaluate the prevalence of PA in patients with OSA and the prevalence of OSA in unselected patients with PA. Two hundred and three patients with OSA (102 whites and 101 Chinese) were screened for PA, and 207 patients with PA (104 whites, 100 Chinese, and 3 of African descent) were screened for OSA by cardiorespiratory polygraphy. Eighteen patients with OSA (8.9%) had PA (11.8% of white and 5.9% of Chinese ethnicity). In patients without other indications for PA screening, the prevalence of PA dropped to 1.5%. The prevalence of OSA in patients with PA was 67.6%, consistent in both white and Chinese patients. A correlation between aldosterone levels and apnea/hypopnea index was observed in white patients with PA ( R 2 =0.225, P =0.016) but not in Chinese patients. Multinomial logistic regression confirmed a significant and independent association between plasma aldosterone levels and moderate to severe OSA diagnosis in white patients (odds ratio, 1.002; P =0.002). In conclusion, aldosterone levels may contribute to the severity of OSA in white patients with hyperaldosteronism, but patients with OSA are not at high risk of PA. Results of the present study challenge the current recommendation of the Endocrine Society guideline that all patients with OSA should be screened for PA, irrespective of the grade of hypertension.

Chemical modifications on histones constitute a key mechanism for gene regulation in chromatin context. Recently, histone lysine β-hydroxybutyrylation (Kbhb) was identified as a new form of histone acylation that connects starvation-responsive metabolism to epigenetic regulation. Sirtuins are a family of NAD+-dependent deacetylases. Through systematic profiling studies, we show that human SIRT3 displays class-selective histone de-β-hydroxybutyrylase activities with preference for H3 K4, K9, K18, K23, K27, and H4K16, but not for H4 K5, K8, K12, which distinguishes it from the Zn-dependent HDACs. Structural studies revealed a hydrogen bond-lined hydrophobic pocket favored for the S-form Kbhb recognition and catalysis. β-backbone but not side chain-mediated interactions around Kbhb dominate sequence motif recognition, explaining the broad site-specificity of SIRT3. The observed class-selectivity of SIRT3 is due to an entropically unfavorable barrier associated with the glycine-flanking motif that the histone Kbhb resides in. Collectively, we reveal the molecular basis for class-selective histone de-β-hydroxybutyrylation by SIRT3, shedding lights on the function of sirtuins in Kbhb biology through hierarchical deacylation.

Electro-biological particle electrode (EPE) made from steel converter slag (SCS) was used as a particle electrode in an enlarged anode electric biological (EAEB) reactor for Rhodamine B (RhB) wastewater treatment, and its purification performance and microbial community were examined. The results revealed that (1) the EAEB reactor showed much higher average removal rates of RhB, COD and NH4+-N, i.e. 91.68%, 87.63%, and 90.54%, which meant an increase by 59.86%, 20.48%, and 14.22%, respectively, compared with BAF; (2) The optimum current intensity (CI) for simultaneously removing RhB, COD and NH4+-N in the EAEB reactor was at 1.00 A; and (3)Methylophilus, Aeromonas, Pseudomonas, Pelomonas and Zoogloea accounted for the main bacterial community in EAEB. Therefore, the EAEB reactor with EPE produced from steel converter slag (SCS) was suitable to simultaneously remove RhB, COD and NH4+-N.

We propose a composite photonic crystal based on phase change material to realize the photonic bandgap dependent all-optical switch in the mid-near infrared band. The demonstrated photonic crystal all-optical switch is built on the surface of integrated silicon waveguide on standard SOI and matched with standard CMOS lithography process. The communication light in the silicon waveguide is modulated by VO2 with Mott metal-insulator transition at near room temperature which results in the shifting of optical bandgap. The simulations based on the finite difference time domain method show that the photonic crystal device possess a modulation depth of 0.95 and an insertion loss of 1.27 dB for fundamental TM mode propagating at 1550 nm. We also discuss the influence of device length and thickness of photonic crystal on the switching performance. Moreover, the compound logic gate derived from proposed switch is also designed to provide NOT and NOR operations simultaneously for the next-generation all-optical chips. Due to the reversible phase transition process of VO2 photonic crystal, the proposed device can realize the fast state switching of light and is expected to provide some help for the research of silicon-based optical chips.

Polarization beam splitters are indispensable components in on-chip polarization-division-multiplexing systems. We propose a compact integrated polarization beam splitter based on a metasurface structure with a 300 nm periodic silicon column array with a variable duty cycle on a silicon-on-insulator substrate. Simulation results indicate a low insertion loss, high extinction ratio, and a 6×12 μm2 footprint within the C+L band. The robustness of our device with respect to manufacturing tolerance and nonideal input light has also been confirmed. The proposed polarization beam splitter can be fabricated in a single lithography step with input/output waveguides, which will be advantageous for device fabrication.

It has been previously demonstrated that miR-1934 was specially regulated by adiponectin, an anti-inflammatory adipokine, in adipose tissue (AT) in vivo. Herein we investigated the role of miR1934 in the regulation of inflammatory response. Compared with chow-diet fed mice, miR1934 expression was down-regulated in epididymal AT of high-fat diet-induced obese mice. miR1934 expression was down-regulated as well in omental AT of obese subjects in comparison with lean subjects. The circulating miR-1934 was also lower in obese subjects and its levels were correlated negatively with body mass index (BMI), waist circumference (WC), low-density lipoprotein cholesterol (LDL-c), insulin resistance and high-sensitivity C-reactive protein (hs-CRP). The down-regulation of miR1934 in obesity was mimicked by TNF-α treatment of 3T3-L1 adipocytes. Moreover, overexpression of miR1934 suppressed the TNF-α-induced gene expression of interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in 3T3-L1 adipocytes. De novo formed AT in nude mice transplanted with 3T3-L1 preadipocytes overexpressing miR1934 displayed a reduction in IL-6, TNF-α, IL-1β and an enhancement in IL-10 gene expression when compared with transplant with 3T3-L1 preadipocytes overexpressing miR1934 scrambled control sequence. These results suggest that miR1934 is an important anti-inflammatory factor and may represent a novel mechanism for controlling AT inflammation.

This study aims to evaluate the mechanical properties of rattan/polymer composites prepared by polymerization with methyl methacrylate (MMA). The P. kerrana rattan samples were impregnated in a vacuum system and polymerized in an oven at 60 °C for 8 h, using 0.5 wt.% of azobisisobutyronitrile as a catalyst. The macro-mechanical properties of the treated and untreated samples were analyzed. The bending modulus and strength of the treated rattan increased by 206% and 215%, respectively. Additionally, the compressive modulus and strength increased by 109% and 107%, compared to untreated rattan. Scanning electron microscopy (SEM) images showed that MMA penetrated the cell lumen. Furthermore, Fourier transform infrared spectroscopy (FTIR) analysis revealed that MMA diffused into the parenchyma and vessels, but it was not found in the fiber wall. Thus, it can be inferred that the improvement in the mechanical properties of treated rattan was mainly caused by the strengthened parenchyma and vessels. Modification with MMA was shown to be an effective way to enhance the macro-mechanical properties of P. kerrana.

The Enlarged Anode Electric Biological (EAEB) Reactor was proposed, as an alternative to the common BAF. The goal of this research was to develop a new process for simultaneously removing, NH4+-N and Rhodamine B (RhB) from dyeing wastewater. The performance of EAEB was evaluated based on COD, NH4+-N and RhB removal efficiency in the effluent. The study found that the removal rate of RhB, which is a characteristic of the inoculation and start period, reaches 80% in EAEB and 30% in common BAF. A current intensity of 0.5 A, HRT of 3.5 h, and electrode area of 0.13 m2 were identified as operating parameters that could guarantee excellent RhB removal efficiency. It is worth noting that the removal of RhB in the two reactors was mainly concentrated in the 80 cm–140 cm area (measuring upwards at the top of the support layer). The removal rate of EAEB in this area was 97.7%, and the common BAF was 84.3%. Besides, in each segment of EAEB, the removal effect of RhB was better than in common BAF. This study elucidated the synergistic effects of electricity and biofilm on contaminant removal and identified important roles of improvements to the anode electro-biodegradation process. As compared to conventional technologies, the proposed process provides a highly efficient new alternative to dyeing wastewater treatment technology.

The relationship between monocyte count and mortality seemed to be varied in different diseases, and it remains unclear in type 2 diabetes (T2D). We conducted a prospective study to investigate whether monocyte count predict all-cause mortality in patients with T2D. In this prospective study, a total of 1073 patients with T2D were enrolled at baseline and 880 patients completed the follow up. The median follow-up time was 47 months. At baseline, clinical characteristics including height, weight, waist circumference, blood pressure were recorded. Biochemical parameters including counts of white blood cells (WBCC), neutrophil (NC) and monocyte (MC), lipid profiles, glycated hemoglobin (HbA1c), serum creatinine were measured. Charlson comorbidity index (CCI) was calculated based on age and comorbidities. Participants were stratified into low, median, and high tertiles according to the baseline MC. Regression models were used to analyze the associations of peripheral MC and the all-cause mortality. Compared to the survived subjects, the baseline MC was significantly higher in patients who deceased during the follow-up (0.45 ± 0.16 vs 0.37 ± 0.15 × 109/L, P = .003). In the multivariate Cox hazard models, subjects in higher MC tertile showed higher risks of all-cause mortality (low tertile as the reference, hazard ratio [HR] 95%CI 2.65 [0.84,8.31] and 3.73 [1.14,12.24] for middle and high MC tertile, respectively) after adjusted for gender, body mass index, CCI, duration of T2D, history of hypertension and metabolic syndrome, drugs, levels of high-sensitivity C-reactive protein, systolic blood pressure, HbA1c, WBCC, and NC. In T2D patients with macro-vascular complications at baseline, 1-SD increment of MC resulted in 1.92-fold higher risk of all-cause mortality. However, the relationship disappeared in subjects without macro-vascular complications at baseline (1.13 [0.72, 1.78], P = .591). Peripheral monocyte count is an independent predictor of all-cause mortality in T2D, especially for subjects with macro-vascular complications.

The HIV-1 protein Rev is an essential viral regulatory protein that facilitates the nuclear export of intron-containing viral mRNAs. Its sequence is organized into short, structured, functionally well-characterized motifs joined by less understood linker regions. We recently carried out a competitive deep mutational scanning study, which determined the relative fitness of every amino acid at every position of Rev in replicating viruses. This study confirmed many known constraints in Rev’s established interaction motifs, but also identified positions of mutational plasticity within these regions as well as in surrounding linker regions. Here, we probe the mutational limits of these linkers by designing and testing the activities of multiple truncation and mass substitution mutations. We find that these regions possess previously unknown structural, functional or regulatory roles, not apparent from systematic point mutational approaches. Specifically, the N- and C-termini of Rev contribute to protein stability; mutations in a turn that connects the two main helices of Rev have different effects in nuclear export assays and viral replication assays; and a linker region which connects the second helix of Rev to its nuclear export sequence has structural requirements for function. Thus, we find that Rev function extends beyond its characterized motifs, and is in fact further tuned by determinants within seemingly plastic portions of its sequence. At the same time, Rev’s ability to tolerate many of these massive truncations and substitutions illustrates the overall mutational and functional robustness inherent in this viral protein.Author Summary (non-technical summary)HIV-1 Rev is an essential viral protein that controls a critical step in the HIV life cycle. It is responsible for transporting viral mRNA messages from the nucleus to the cytoplasm where they can contribute to the formation new virus particles. In order to understand how different regions of the Rev protein sequence are involved in its function, we introduced truncations and mass substitution mutations in the protein sequence and tested their effect on protein function. Through this study, we not only confirmed previous work highlighting known functionally important regions in Rev, but also found that a large portion of Rev, with little known functional roles influence Rev function and stability. We also show that although protein sequence is critical to its function, Rev can tolerate large variations to its sequence without disrupting its function significantly.

Ferroelectric poly(vinylidene fluoride) (PVDF) has been proposed in the past decades as an electroactive material for various applications in microelectronic devices due to its ferro/piezo/pyroelectric properties. However, fabrication of smooth PVDF thin films with a high content of β-phase and controlled chain orientation is a long-standing problem. Here we report on the control over polymorphs of PVDF thin films by exploring the interfacial ion-dipolar interactions. The ion-dipolar interactions are provided by CF2 bonds of PVDF and imidazolium type ionic liquid immobilized onto substrates via biomimetic catecholic attachment chemistry. By simply melt crystallization of spin-coated PVDF thin films at elevated temperatures, the ferroelectric polar β-phase with a lying-down chain orientation is formed. The thin films exhibit excellent ferro/piezoelectric properties when applying electric field due to the immobilization of ionic liquids. The results may boost the applications of PVDF in microelectronic devices.

Objective This study aims to evaluate whether serum Bisphenol A (BPA) is a risk factor for hyperuricemia. Methods In this prospective study, a total of 482 participants without hyperuricemia were enrolled at baseline and followed up for 6 years. Clinical characteristics were recorded, and serum levels of uric acid and BPA were measured. Participants were stratified into tertiles according to low, median, and high baseline serum BPA levels. Regression models were used to analyze associations of serum BPA with the change in uric acid and the risk of developing hyperuricemia. Results At baseline, serum concentrations of BPA was 0.51 (0.24–2.37) ng/mL. After 6 years of follow-up, the change in serum uric acid concentration from baseline to the 6-year mark was significantly higher in subjects with higher baseline BPA concentration (0.03 ± 0.19, 0.07 ± 0.21, and 0.11 ± 0.25 mg/dL for low, median, and high tertiles, respectively, P = 0.006). When adjusted for potential confounders, such as age, renal function, and history of diabetes and hypertension, multivariable logistic analyses showed that subjects in the median or high baseline BPA tertiles exhibited a twofold higher risk of 6-year hyperuricemia incidence compared to subjects in the low baseline BPA tertile [odds ratio (OR) = 2.28 (95% CI: 1.05–4.95) for the median tertile; 2.42 (1.07–5.48) for the high tertile, Pfor Trend = 0.043]. Conclusion In conclusion, serum BPA is an independent risk factor for hyperuricemia.

Chemical modifications on histones constitute a key mechanism for gene regulation in chromatin context. Recently, histone lysine β-hydroxybutyrylation (Kbhb) was identified as a new form of histone acylation that connects starvation-responsive metabolism to epigenetic regulation. Sirtuins are a family of NAD+-dependent deacetylases. Through systematic profiling studies, we show that human SIRT3 displays unique class-selective histone de-β-hydroxybutyrylase activities with preferences for H3 K4, K9, K18, K23, K27 and H4K16, but not H4 K5, K8, K12. Structural studies revealed a hydrogen bond-lined hydrophobic pocket favored for the S-form Kbhb recognition and catalysis. β-backbone but not side chain-mediated interactions around Kbhb dominate sequence motif recognition, explaining the broad site-specificity of SIRT3. The observed class-selectivity against sites like H4K8 is due to the intrinsic flexibility of the glycine-flanking motif they reside in. Collectively, we revealed the molecular basis for class-selective histone de-β-hydroxybutyrylation by SIRT3, shedding new lights on the function of sirtuins in Kbhb biology through hierarchical deacylation.

Deep eutectic solvents are considered as new and green solvents that can be widely used in analytical chemistry such as microextraction. In the present work, a new dl-menthol-based hydrophobic deep eutectic solvent was synthesized and used as extraction solvents in an air-assisted dispersive liquid-liquid microextraction method for preconcentration and extraction of benzophenone-type UV filters from aqueous samples followed by high-performance liquid chromatography with diode array detection. In an experiment, the deep eutectic solvent formed by dl-menthol and decanoic acid was added to an aqueous solution containing the UV filters, and then the mixture was sucked up and injected five times by using a glass syringe, and a cloudy state was achieved. After extraction, the solution was centrifuged and the upper phase was subjected to high-performance liquid chromatography for analysis. Various parameters such as the type and volume of the deep eutectic solvent, number of pulling, and pushing cycles, solution pH and salt concentration were investigated and optimized. Under the optimum conditions, the developed method exhibited low limits of detection and limits of quantitation, good linearity, and precision. Finally, the proposed method was successfully applied to determine the benzophenone-type filters in environmental water samples with relative recoveries of 88.8-105.9%.

The prevalence of hyperuricemia has increased rapidly over the past decades. Bisphenol A (BPA) is an environmental endocrine disruptor. We investigated the effects of BPA on uric acid metabolism and its potential mechanisms. Experiments were performed in different animal models, cell cultures, and humans. In 3 different animal models, BPA exposure increased serum and hepatic uric acid with enhanced activity of xanthine oxidase (XO) in liver, whereas the excretion of uric acid was unchanged. Both in vivo and in vitro, BPA-induced uric acid production was decreased after treatment with allopurinol, which is a XO inhibitor. XO led to the accumulation of uric acid after xanthine was added, with the enzyme-catalyzed reaction, which was enhanced by BPA. Altered secondary structures of XO were found by circular dichroism analysis in the conditions of different BPA concentrations. Molecular docking portrayed Asp360 and Lys422 of XO to be the preferred binding sites for BPA. Mutation of both sites significantly blocked the effect of BPA on XO activity. In humans, patients with hyperuricemia exhibited higher levels of serum BPA than subjects without hyperuricemia. These findings demonstrate BPA promotes hyperuricemia by increasing hepatic uric acid synthesis via the activation of XO, probably through direct binding.-Ma, L., Hu, J., Li, J., Yang, Y., Zhang, L., Zou, L., Gao, R., Peng, C., Wang, Y., Luo, T., Xiang, X., Qing, H., Xiao, X., Wu, C., Wang, Z., He, J. C., Li, Q., Yang, S. Bisphenol A promotes hyperuricemia via activating xanthine oxidase.

Background The aim of the present study was to investigate the combined effects of sex hormone-binding globulin (SHBG) and sex hormones on the risk of type 2 diabetes (T2D). Methods A nested case-control study of Chinese participants in the Environment, Inflammation and Metabolic Diseases Study (2008–13) was performed. Of the 3510 subjects free of diabetes, 145 men and 87 women developed diabetes over the 5-year follow-up. One age- and sex-matched control subject was selected for each case. Baseline concentrations of SHBG, estradiol, testosterone, and dehydroepiandrosterone sulfate (DHEA-S) were divided into tertiles and subjects were classified as having low, intermediate and high levels accordingly. Results After multivariate adjustment, men with low SHBG levels had a fourfold greater risk of T2D than men with high SHBG levels. Conversely, men with high estradiol levels had a fourfold greater risk of T2D than men with low estradiol levels. Men with low SHBG + high estradiol had a 20-fold greater risk of T2D than men with high SHBG + low estradiol (odds ratio [OR] 20.23; 95% confidence interval [CI] 4.62–51.33). These risk associations in men were not observed for testosterone or DHEA-S, alone or in combination with SHBG. Compared with low SHBG, the risk of T2D decreased with increasing SHBG tertile (OR 0.92 [95% CI 0.21–4.53], 0.14 [95% CI 0.10–0.74]; Ptrend = 0.043) after multivariate adjustment in women. Estradiol, testosterone, and DHEA-S levels showed no association with T2D in women. Conclusion Low SHBG in conjunction with high estradiol has an additive detrimental effect on the risk of T2D in men.

Aim It is well known that lipid accumulation and inflammation are two important steps in pathogenesis and progress of nonalcoholic fatty liver disease (NAFLD). However, fewer studies have explored the direct relationship between lipid accumulation and inflammation in early NAFLD. Tumor necrosis factor alpha (TNF-α) is one of the classical inflammatory cytokines. AMP-activated protein kinase (AMPK) is known as a critical regulator of energy homeostasis in metabolic processes. This study aims to investigate the role of TNF-α on lipid deposition of HepG2 cells and examine the modification of AMPK pathway. Main methods TNF-α was added in HepG2 cells and lipid accumulation was analyzed by Oil Red O staining and quantitative test of triglyceride (TG). The expressions of phosphorylated AMPK and its pathway (including mTOR and SREBP-1) were determined. Furthermore, an AMPK agonist (metformin or AICAR) or antagonist (compound C) was co-administrated with TNF-α in HepG2 cells to investigate its effect on TNF-α induced lipid deposition. Key findings A significant increment of TG content in HepG2 cells was observed after TNF-α treatment. Meanwhile, substantially suppressed AMPK and ACC phosphorylation, enhanced mTOR and p70S6K phosphorylation, and increased protein expression of FAS and SREBP-1 were found. Co-treatment with metformin or AICAR decreased the TNF-α-induced intracellular TG, accompanied by significantly enhanced AMPK and ACC phosphorylation, suppressed mTOR and p70S6K phosphorylation, and reduced SREBP-1 and FAS expressions. On the contrary, while co-incubated with compound C, AMPK and ACC phosphorylation were suppressed and the inhibitory effect of metformin on HepG2 cell lipid deposition was also attenuated. Significance Our results suggest that TNF-α directly induces lipid accumulation in HepG2 cells, at least in part, through the inhibition of AMPK/mTOR/SREBP-1 pathway.

The synthesis of magnetic biochar composites is a major new research area in advanced materials sciences. A series of magnetic bamboo charcoal composites (MBC800, MBC1000 and MBC1200) with high saturation magnetization (Ms) was fabricated in this work by mixing bamboo charcoal powder with an aqueous ferric chloride solution and subsequently pyrolyzing under different temperatures (800, 1000 and 1200 °C) in a tube furnace. All the products were characterized using X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectrometer (EDAX), high-resolution transmission electron microscopy (HRTEM), Raman spectroscopy and a superconducting quantum interference device (SQUID). The results show that the pyrolytic temperature plays a significant role in determining the final structures and magnetic properties of the products. The magnetite (Fe3O4) and a certain amount of amorphous hematite (α-Fe2O3) coexist in MBC800. However, zerovalent iron (ZVI) is the only detectable magnetic phase in both MBC1000 and MBC1200. The Ms values of MBC1000 and MBC1200 are 118.1 and 122.7 emu g−1, respectively. Excellent magnetic properties of the two ZVI/bamboo charcoal composites not only facilitate the separation of solid phase, but also indicate that these materials could have high potential for other applications, such as in the biomedical or ferrofluid fields.

Viral regulatory complexes perform critical functions during virus replication and are important targets for therapeutic intervention. In HIV, the Tat and Rev proteins form complexes with multiple viral and cellular factors to direct transcription and export of the viral RNA. These complexes are composed of many proteins and are dynamic, making them difficult to fully recapitulate in vitro . Therefore, we developed a cell-based reporter assay to monitor the assembly of viral complexes for inhibitor screening. We screened a small-molecule library and identified multiple hits that inhibit the activity of the viral complexes. A subsequent chemistry effort was focused on a thieno[2,3-b]pyridine scaffold, examples of which inhibited HIV replication and the emergence from viral latency. Notable aspects of the effort to determine the structure-activity relationship (SAR) include migration to the regioisomeric thieno[2,3-c]pyridine ring system and the identification of analogs with single-digit nanomolar activity in both reporter and HIV infectivity assays, an improvement of >100-fold in potency over the original hits. These results validate the screening strategy employed and reveal a promising lead series for the development of a new class of HIV therapeutics.

Transcription complexes that assemble at the HIV-1 promoter efficiently initiate transcription but generate paused RNA polymerase II downstream from the start site. The virally encoded Tat protein hijacks positive transcription elongation factor b (P-TEFb) to phosphorylate and activate this paused polymerase. In addition, Tat undergoes a series of reversible post-translational modifications that regulate distinct steps of the transcription cycle. To identify additional functionally important Tat cofactors, we performed RNAi knockdowns of sixteen previously identified Tat interactors and found that a novel E3 ligase, PJA2, ubiquitinates Tat in a non-degradative manner and specifically regulates the step of HIV transcription elongation. Interestingly, several different lysine residues in Tat can function as ubiquitin acceptor sites, and variable combinations of these lysines support both full transcriptional activity and viral replication. Further, the polyubiquitin chain conjugated to Tat by PJA2 can itself be assembled through variable ubiquitin lysine linkages. Importantly, proper ubiquitin chain assembly by PJA2 requires that Tat first binds its P-TEFb cofactor. These results highlight that both the Tat substrate and ubiquitin modification have plastic site usage, and this plasticity is likely another way in which the virus exploits the host molecular machinery to expand its limited genetic repertoire.