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Abstract Ultrasmall copper nanoclusters have recently emerged as promising photocatalysts for organic synthesis, owing to their exceptional light absorption ability and large surface areas for efficient interactions with substrates. Despite significant advances in cluster-based visible-light photocatalysis, the types of organic transformations that copper nanoclusters can catalyze remain limited to date. Herein, we report a structurally well-defined anionic Cu40 nanocluster that emits in the second near-infrared region (NIR-II, 1000−1700 nm) after photoexcitation and can conduct single-electron transfer with fluoroalkyl iodides without the need for external ligand activation. This photoredox-active copper nanocluster efficiently catalyzes the three-component radical couplings of alkenes, fluoroalkyl iodides, and trimethylsilyl cyanide under blue-LED irradiation at room temperature. A variety of fluorine-containing electrophiles and a cyanide nucleophile can be added onto an array of alkenes, including styrenes and aliphatic olefins. Our current work demonstrates the viability of using readily accessible metal nanoclusters to establish photocatalytic systems with a high degree of practicality and reaction complexity.

Abstract Despite promising preclinical and earlier clinical data, a recent phase III trial on the anti-β7 integrin antibody etrolizumab in Crohn’s disease (CD) did not reach its primary endpoint. The mechanisms leading to this outcome are not well understood. Here we characterize the β7+ T cell compartment from patients with CD in comparison to cells from individuals without inflammatory bowel disease. By flow cytometric, transcriptomic and functional profiling of circulating T cells, we find that triple-integrin-expressing (α4+β7+β1hi) T cells have the potential to home to the gut despite α4β7 blockade and have a specific cytotoxic signature. A subset of triple-integrin-expressing cells readily acquires αE expression and could be co-stimulated via E-Cadherin-αEβ7 interactions in vitro. Etrolizumab-s fails to block such αEβ7 signalling at high levels of T cell stimulation. Consistently, in CD patients treated with etrolizumab, T cell activation correlates with cytotoxic signatures. Collectively, our findings might add one important piece to the puzzle to explain phase III trial results with etrolizumab, while they also highlight that αEβ7 remains an interesting target for future therapeutic approaches in inflammatory bowel disease.

BackgroundYishen-Tongbi Decoction (YSTB), a traditional Chinese prescription, has been used to improve syndromes of rheumatoid arthritis (RA) for many years. Previous research has shown that YSTB has anti-inflammatory and analgesic properties. However, the underlying molecular mechanism of the anti-RA effects of YSTB remains unclear.Purpose and study designThe purpose of this research was to investigate how YSTB affected mice with collagen-induced arthritis (CIA) and RAW264.7 cells induced with lipopolysaccharide (LPS).ResultsThe findings show that YSTB could significantly improve the clinical arthritic symptoms of CIA mice (mitigate paw swelling, arthritis score, thymus and spleen indices, augment body weight), downregulated expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-17, while upregulated the level of anti-inflammatory like IL-10 and transforming growth factor-β (TGF-β). Meanwhile, YSTB inhibits bone erosion and reduces inflammatory cell infiltration, synovial proliferation, and joint destruction in CIA mice. In addition, we found that YSTB was able to suppress the LPS-induced inflammation of RAW264.7 cells, which was ascribed to the suppression of nitric oxide (NO) production and reactive oxygen species formation (ROS). YSTB also inhibited the production of inducible nitric oxide synthase and reduced the releases of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in LPS-induced RAW264.7 cells. Furthermore, the phosphorylation expression of JAK2, JAK3, STAT3, p38, ERK and p65 protein could be suppressed by YSTB, while the expression of SOCS3 could be activated.ConclusionTaken together, YSTB possesses anti-inflammatory and prevention bone destruction effects in RA disease by regulating the JAK/STAT3/SOCS3 signaling pathway.

Energy output and heating effects are essential for vapor-liquid fuel/air cloud detonation in the fuel-air explosive (FAE) applications or explosion accidents. The purpose of this study is to examine the dynamic large-size flame behavior, shock wave propagation law, and instantaneous thermal field generated by unconfined vapor-liquid propylene oxide (PO)/air cloud detonation. Based on computational fluid dynamics (CFD) and combustion theory, a numerical simulation is used to study the detonation process of a PO/air cloud produced by a double-event fuel-air explosive (DEFAE) of 2.16 kg. The large-scale flame behavior is characterized. The flame initially spreads radially and laterally in a wing shape. Subsequently, the developed flame increases with a larger aspect ratio. Moreover, the propagation laws of shock waves at different heights are discussed. The peak pressure of 1.3 m height level with a stepwise decline is obviously different from that of the ground with an amplitude of reversed 'N' shape. In the vast majority of the first 6.9 m, the destructive effect of the shock wave near the ground is greater than that of the shock wave at 1.3 m height. Furthermore, the dynamic instantaneous isothermal field is demonstrated. The scaling relationship of various isotherms in the instantaneous thermal field with the flame and initial cloud is summarized. The comprehensive numerical model used in this study can be applied to determine the overpressure and temperature distribution in the entire fuel/air cloud detonation field, providing guidance for assessing the extent of damage caused by DEFAE detonation.

The selective removal of targeted pollutants from complex wastewater is challenging. Herein, a novel persulfate (PS)-based advanced oxidation system equipped with a series of two-dimensional (2D) bimetallic oxide nanosheets (NSs) catalysts is developed to selectively degrade bisphenol A (BPA) within mixed pollutants via initiating nonradical-induced polymerization. Results indicate that the Ni0.60Co0.40Ox NSs demonstrate the highest catalytic efficiency among all Ni-Co NSs catalysts. Specifically, BPA degradation rate is 47.34, 27.26, and 9.72 times higher than that of 4-chlorophenol, phenol, and 2,4-dichlorophenol in the mixed solution, respectively. The lower oxidative potential of BPA in relation to the other pollutants renders it the primary target for oxidation within the PDS activation system. PDS molecules combine on the surface of Ni0.60Co0.40Ox NSs to form the surface-activated complex, triggering the generation of BPA monomer radicals through H-abstraction or electron transfer. These radicals subsequently polymerize on the surface of the catalyst through coupling reactions. Importantly, this polymerization process can occur under typical aquatic environmental conditions and demonstrates resistance to background matrices like Cl− and humic acid due to its inherent nonradical attributes. This study offers valuable insights into the targeted conversion of organic pollutants in wastewater into value-added polymers, contributing to carbon recycle and circular economy.

A high-energy pulsed vacuum ultraviolet (VUV) solid-state laser at 177 nm with high peak power by the sixth harmonic of a neodymium-doped yttrium aluminum garnet (Nd:YAG) amplifier in a KBe2BO3F2 prism-coupled device was demonstrated. The ultraviolet (UV) pump laser is a 352 ps pulsed, spatial top-hat super-Gaussian beam at 355 nm. A high energy of a 7.12 mJ VUV laser at 177 nm is obtained with a pulse width of 255 ps, indicating a peak power of 28 MW, and the conversion efficiency is 9.42% from 355 to 177 nm. The measured results fitted well with the theoretical prediction. It is the highest pulse energy and highest peak power ever reported in the VUV range for any solid-state lasers. The high-energy, high-peak-power, and high-spatial-uniformity VUV laser is of great interest for ultra-fine machining and particle-size measurements using UV in-line Fraunhofer holography diagnostics.

Abstract The advances in determining the total structure of atomically precise metal nanoclusters have prompted extensive exploration into the origins of chirality in nanoscale systems. While chirality is generally transferrable from the surface layer to the metal–ligand interface and kernel, we present here an alternative type of gold nanoclusters (138 gold core atoms with 48 2,4-dimethylbenzenethiolate surface ligands) whose inner structures are not asymmetrically induced by chiral patterns of the outermost aromatic substituents. This phenomenon can be explained by the highly dynamic behaviors of aromatic rings in the thiolates assembled via π − π stacking and C − H···π interactions. In addition to being a thiolate-protected nanocluster with uncoordinated surface gold atoms, the reported Au138 motif expands the size range of gold nanoclusters having both molecular and metallic properties. Our current work introduces an important class of nanoclusters with intrinsic chirality from surface layers rather than inner structures and will aid in elucidating the transition of gold nanoclusters from their molecular to metallic states.

LKB1 mutations have been associated with primary resistance to immune checkpoint inhibitors in patients with lung cancer. Here the authors show that Lkb1-deficient lung tumors are characterized by defective trafficking and adhesion of T cells and that, by upregulating ICAM1 expression, CDK4/6 inhibitors sensitize LKB1 mutant lung cancer to anti-PD1 blockade.

Abstract Background Culex pipiens pallens (Diptera: Culicidae) can survive at low temperature for long periods. Understanding the effects of low-temperature stress on the gut microflora and gene expression levels in Cx. pipiens pallens, as well as their correlation, will contribute to the study of the overwintering mechanism of Cx. pipiens pallens. Methods The gut bacteria were removed by antibiotic treatment, and the survival of Cx. pipiens pallens under low-temperature stress was observed and compared with the control group. Then, full-length 16S rRNA sequencing and the Illumina HiSeq X Ten sequencing platform were used to evaluate the gut microflora and gene expression levels in Cx. pipiens pallens under low-temperature stress. Results Under the low-temperature stress of 7 °C, the median survival time of Cx. pipiens pallens in the antibiotic treatment group was significantly shortened by approximately 70% compared to that in the control group. The species diversity index (Shannon, Simpson, Ace, Chao1) of Cx. pipiens pallens decreased under low-temperature stress (7 °C). Non-metric multidimensional scaling (NMDS) analysis divided all the gut samples into two groups: control group and treatment group. Pseudomonas was the dominant taxon identified in the control group, followed by Elizabethkingia and Dyadobacter; in the treatment group, Pseudomonas was the dominant taxon, followed by Aeromonas and Comamonas. Of the 2417 differentially expressed genes (DEGs), 1316 were upregulated, and 1101 were downregulated. Functional GO terms were enriched in 23 biological processes, 20 cellular components and 21 molecular functions. KEGG annotation results showed that most of these genes were related to energy metabolism-related pathways. The results of Pearson’s correlation analysis showed a significant correlation between the gut microcommunity at the genus level and several DEGs. Conclusions These results suggest that the mechanism of adaptation of Cx. pipiens pallens to low-temperature stress may be the result of interactions between the gut bacterial community and transcriptome. Graphical Abstract

Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is the most significant microvascular complication of diabetes and poses a severe public health concern due to a lack of effective clinical treatments. Autophagy is a lysosomal process that degrades damaged proteins and organelles to preserve cellular homeostasis. Emerging studies have shown that disorder in autophagy results in the accumulation of damaged proteins and organelles in diabetic renal cells and promotes the development of DN. Autophagy is regulated by nutrient-sensing pathways including AMPK, mTOR, and Sirt1, and several intracellular stress signaling pathways such as oxidative stress and endoplasmic reticulum stress. An abnormal nutritional status and excess cellular stresses caused by diabetes-related metabolic disorders disturb the autophagic flux, leading to cellular dysfunction and DN. Here, we summarized the role of autophagy in DN focusing on signaling pathways to modulate autophagy and therapeutic interferences of autophagy in DN.

BackgroundThe increased risk of cardiovascular events in patients prescribed macrolides has been subject to debate for decades.MethodsMedline, EMBASE databases and ClinicalTrials.gov were searched from inception until August 31, 2022 for studies investigating the link between macrolides and cardiovascular risk. A meta-analysis was performed using a random-effects model.ResultsA total of 80 studies involving 39,374,874 patients were included. No association was found between macrolides and all-cause death. However, compared with the non-macrolide group, macrolides were associated with a significantly increased risk of ventricular arrhythmia or sudden cardiac death (VA or SCD) (azithromycin, relative ratio [RR]: 1.53; 95% confidence interval [CI]: 1.19 to 1.97; clarithromycin, RR: 1.52; 95% CI: 1.07 to 2.16). Besides, administration of macrolides was associated with a higher risk of cardiovascular disease (CVD) death (azithromycin, RR: 1.63; 95% CI: 1.17 to 2.27) and a slightly increased risk of myocardial infarction (MI) (azithromycin, RR: 1.08; 95% CI: 1.02 to 1.15). Interestingly, no association was observed between roxithromycin and adverse cardiac outcomes. Increased risk of VA or SCD was observed for recent or current use of macrolides, MI for former use, and CVD death for current use.ConclusionAdministration of macrolide antibiotics and timing of macrolide use are associated with increased risk for SCD or VTA and cardiovascular death, but not all-cause death.

AIM: To observe the early visual quality of the tri-focal and the mono-focal intraocular lens(IOLs)implantation in patients with age-related cataract, under comparison and analysis.METHODS: A retrospective research design. Totally 168 eyes of 119 age-related cataract patients who underwent cataract phacoemulsification combined with tri-focal and mono-focal IOLs implantation surgery in the cataract department from June 2018 to January 2021 were enrolled. In tri-focal and mono-focal group, 61 eyes of 44 cases and 107 eyes of 75 cases. One month after phacoemulsification combined with IOLs implantation, visual acuity, visual quality and contrast sensitivity were inspected. All data were under statistical analysis.RESULTS: On LogMAR uncorrected distance visual acuity(UDVA),uncorrected intermediate visual acuity(UIVA), uncorrected near visual acuity(UNVA), best corrected distance visual acuity(BDVA), distance corrected intermediate visual acuity(DIVA), distance corrected near visual acuity(DNVA), tri-focal group were extremely better than mono-focal group(all P0.05).CONCLUSION: Tri-focal IOLs can provide a full range of relatively better vision and visual quality in patients after age-related cataract phacoemulsification combined with IOLs implantation, and perform well under different conditions.

Abstract Background Hepatic cavernous hemangioma is the most common type of benign liver tumor. Although ruptures and hemorrhages of hepatic hemangioma are rare complications, they are associated with high mortality. Most practitioners only pay more attention to abdominal hemorrhages caused by the rupture of hepatic hemangiomas. However, spontaneous intracapsular hemorrhages can often be neglected and poorly understood. Case presentation A 65-year-old man was referred to our institution with right upper quadrant pain, which had occurred suddenly and without a history of recent trauma. The blood test results were normal. Magnetic resonance imaging (MRI) of the abdomen showed a cystic mass in the right liver lobe. Considering the possibility of hepatic cystadenoma with hemorrhage, the patient underwent a right hepatic lobectomy. The pathological findings unexpectedly revealed intratumoral hemorrhage of hepatic hemangioma. The patient recovered well and was discharged eight days after surgery. Conclusions Intracapsular hemorrhage of hepatic cavernous hemangioma is challenging to diagnose and has a high potential risk of rupture. MRI is beneficial for diagnosing subacute internal hemorrhage cases, and it is recommended to undergo surgery for patients with a definitive diagnosis.

BackgroundThe clinical features of urticaria have not been fully illustrated.ObjectivesTo demonstrate clinical features of urticaria in different areas of southern and northern China.MethodsIn this hospital-based multicenter study, outpatients with urticaria filled in a questionnaire during the initial visit and follow-up (once per week, lasting for a month).ResultsOverall, 1,715 outpatients with urticaria with a mean age of 37.86 ± 16.08 years (range = 0.5–87 years) were recruited. The median disease duration was 1.94 ± 4.31 years (range = 0–58 years). More itching was observed in the northern areas higher than that in the southern areas (99.5 vs 94.1%, P < 0.001). The incidence of pain, arthralgia, and family history in southern areas was higher than that in northern areas (5.1 vs 1.1%, 9.6 vs 0, 10.6% vs 3.2%, P < 0.001). The leading subtypes of specified urticaria were chronic spontaneous urticaria (81.4%) and symptomatic dermographism (35.9%). The incidence of symptomatic dermographism and cold urticaria in the southern areas was lower than that in the northern areas (31.8 vs. 50.3%, 4 vs. 8.5%, P < 0.001). Allergic diseases were the most common concomitant disorders of urticaria. More than half of the patients had to avoid certain food, such as fish-prawn-crab (30.7%) and alcohol (20%). Ebastine (41.1%) was the most commonly prescribed drug. The disease duration negatively correlated with the severity of itching and number of wheals (>50/24H) (Spearman’s rank correlation test, p < 0.001).ConclusionThis study provides a profile of clinical characteristics of urticaria in China and filled the gap in the field of regional comparative studies on urticaria.

Background The prognostic value of early repolarization pattern (ERP) remains controversial. We aim to test the hypothesis that temporal changes in ERP are associated with increased risks for sudden cardiac death (SCD) and cardiovascular death. Methods and Results A total of 14 679 middle‐aged participants from the prospective, population‐based cohort were included in this analysis, with ERP status recorded at baseline and during 3 follow‐up visits in the ARIC (Atherosclerosis Risk in Communities) study. We related baseline ERP, time‐varying ERP, and temporal changes in ERP to cardiovascular outcomes. Cox models were used to estimate the hazard ratios (HRs) adjusted for possible confounding factors. With a median follow‐up of 22.5 years, there were 5033 deaths, 1239 cardiovascular deaths, and 571 SCDs. Time‐varying ERP was associated with increased risks of SCD (HR, 1.59 [95% CI, 1.25–2.02]), cardiovascular death (HR, 1.70 [95% CI, 1.44–2.00]), and death from any cause (HR, 1.16 [95% CI, 1.05–1.27]). Baseline ERP was also associated with 3 outcomes. Compared with those with consistently normal ECG findings, subjects with new‐onset ERP or consistent ERP experienced increased risks of developing SCD and cardiovascular death. The time‐varying ERP in women, White subjects, and anterior leads and J‐wave amplitudes ≥0.2 mV appeared to indicate poorer cardiovascular outcomes. Conclusions Our findings suggest that baseline ERP, time‐varying ERP, new‐onset ERP, and consistent ERP were independent predictors of SCD and cardiovascular death in the middle‐aged biracial population. Repeated measurements of the ERP might improve its use as a risk indicator for SCD.

In this work, we have investigated the process Ds+→K+K−π+, taking into account the contributions from the S-wave pseudoscalar-pseudoscalar interaction within the chiral unitary approach, and also the intermediate ϕ resonance. By analyzing the BESIII and BABAR measurements, we conclude that the f0(980) state, dynamically generated from the S-wave pseudoscalar-pseudoscalar interaction, gives the dominant contribution close to the K+K− threshold in the K+K− invariant mass distribution of the decay Ds+→K+K−π+ in S-wave. On the other hand, our results imply that the lineshape adopted by BESIII and BABAR for the resonances a0(980) and f0(980) is not advisable in the fit to the data close to the K+K− threshold.

In this paper, the problems of finite-time stability and stabilization for switched positive linear time-delay systems under mode-dependent average dwell time (MDADT) are investigated. By proposing a novel multiple piecewise copositive Lyapunov-Krasovskii functional, new results on the sufficient conditions of finite-time stability are obtained. In order to solve the limitation of the multiple piecewise copositive Lyapunov-Krasovskii functional on designing controllers, a novel linear combinatorial copositive Lyapunov-Krasovskii functional is constructed, this provides a possibility for the numerical construction of the controller. Then by using state feedback controller, the finite-time stabilization is achieved. Finally, some simulation results are given to show the advantages of our methods.

In epithelial cells Zeb1 is involved in the epithelial to mesenchymal transition. In this study, the authors show in a mouse model of breast cancer, that Zeb1 expression in stromal cells is required for tumour formation and metastasis.

In the present study, we surveyed the ascomycetes from bamboo of Phyllostachys across Sichuan Province, China. A biphasic approach based on morphological characteristics and multigene phylogeny confirmed seven species, including one new genus, two new species, and five new host record species. A novel genus Paralloneottiosporina is introduced to accommodate Pa. sichuanensis that was collected from leaves of Phyllostachys violascens. Moreover, the newly introduced species Bifusisporella sichuanensis was isolated from leaves of P. edulis, and five species were newly recorded on bamboos, four species belonging to Apiospora, viz. Ap. yunnana, Ap. neosubglobosa, Ap. jiangxiensis, and Ap. hydei, and the last species, Seriascoma yunnanense, isolated from dead culms of P. heterocycla. Morphologically similar and phylogenetically related taxa were compared. Comprehensive descriptions, color photo plates of micromorphology are provided.

Deficiency of the DNA damage repair (DDR) signaling pathways is potentially responsible for genetic instability and oncogenesis in tumors, including colorectal cancer. However, the correlations of mutated DDR signaling pathways to the prognosis of colorectal cancer liver metastasis (CRLM) after resection and other clinical applications have not been fully investigated. Here, to test the potential correlation of mutated DDR pathways with survival and pre-operative chemotherapy responses, tumor tissues from 146 patients with CRLM were collected for next-generation sequencing with a 620-gene panel, including 68 genes in 7 DDR pathways, and clinical data were collected accordingly. The analyses revealed that 137 of 146 (93.8%) patients had at least one mutation in the DDR pathways. Mutations in BER, FA, HRR and MMR pathways were significantly correlated with worse overall survival than the wild-types (P < 0.05), and co-mutated DDR pathways showed even more significant correlations (P < 0.01). The number of mutated DDR pathways was also proved an independent stratifying factor of overall survival by Cox multivariable analysis with other clinical factors and biomarkers (hazard ratio = 9.14; 95% confidence interval, 1.21–68.9; P = 0.032). Additionally, mutated FA and MMR pathways were positively and negatively correlated with the response of oxaliplatin-based pre-operative chemotherapy (P = 0.0095 and 0.048, respectively). Mutated DDR signaling pathways can predict pre-operative chemotherapy response and post-operative survival in CRLM patients.

Abstract Background The transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) signaling pathways are both constitutively activated in triple-negative breast cancer (TNBC). We are interested in isolating the naturally-derived small-molecule inhibitor that could simultaneously targeting TGFβ/BMP pathways and further studying its anti-proliferative/−metastatic effects as well as the underlying mechanisms in multiple tumor models. Methods Multiple in vitro cell-based assays are used to examine the compound’s inhibitory efficacy on TNBC cell growth, stemness, epithelial-mesenchymal transition (EMT), invasion and migration by targeting TGFβ/BMP signaling pathways. Transgenic breast cancer mouse model (MMTV-PyMT), subcutaneous xenograft and bone metastasis models are used to examine ZL170’s effects on TNBC growth and metastasis potentials in vivo. Results ZL170 dose-dependently inhibits cell proliferation, EMT, stemness, invasion and migration in vitro via specifically targeting canonical TGFβ/BMP-SMADs pathways in TNBC cells. The compound significantly hinders osteolytic bone metastasis and xenograft tumor growth without inflicting toxicity on vital organs of tumor-bearing nude mice. ZL170 strongly inhibits primary tumor growth and lung metastases in MMTV-PyMT transgenic mice. ZL170-treated tumors exhibit impaired TGFβ/BMP signaling pathways in both epithelial and stromal compartments, thereby creating a suppressive tumor microenvironment characterized by reduced extracellular matrix deposition and decreased infiltration of stromal cells. Conclusions ZL170 inhibits tumor EMT, stemness and metastasis and could be further developed as a potent anti-metastatic agent used in combination with cytotoxic drugs for treatment of TNBC and other advanced metastatic cancers.

Neostagonosporella sichuanensis sp. nov. was found on Phyllostachys heteroclada collected from Sichuan Province in China and is introduced in a new genus Neostagonosporella gen. nov. in this paper. Evidence for the placement of the new taxon in the family Phaeosphaeriaceae is supported by morphology and phylogenetic analysis of a combined LSU, SSU, ITS and TEF 1-α DNA sequence dataset. Maximum-likelihood, maximum-parsimony and Bayesian inference phylogenetic analyses support Neostagonosporella as a distinct genus within this family. The new genus is compared with related genera of Phaeosphaeriaceae and full descriptions and illustrations are provided. Neostagonosporella is characterised by its unique suite of characters, such as multiloculate ascostromata and cylindrical to fusiform, transversely multiseptate, straight or curved ascospores, which are widest at the central cells. Conidiostromata are multiloculate, fusiform to long fusiform or rhomboid, with two types conidia; macroconidia vermiform or subcylindrical to cylindrical, transversely multiseptate, sometimes curved, almost equidistant between septa and microconidia oval, ellipsoidal or long ellipsoidal, aseptate, rounded at both ends. An updated phylogeny of the Phaeosphaeriaceae based on multigene analysis is provided.

Background/Aims: Early repolarization syndrome (ERS) has been recently recognized as early repolarization pattern with idiopathic ventricular fibrillation. However, the genetic background of ERS has not been fully understood. Methods: A Chinese family with sudden cardiac death associated with ERS was investigated. Direct sequencing of ERS susceptibility genes was performed on the proband and family members. Whole-cell patch-clamp methods were used to characterize the mutant channel expressed in HEK 293 cells. Results: One missense mutation (p. K801T) was found in the hERG (KCNH2 gene) by the direct sequencing of candidate genes. Whole cell voltage clamp studies of the K801T mutation in HEK 293 cells demonstrated a 1.5-fold increase in maximum steady state current (37.2±7.3 vs 20.3±4.4 pA/pF) that occurred at a 20 mV more positive potential compared to the wild type channels. The voltage dependence of inactivation was significantly shifted in the positive voltage direction (WT -59.5±1.4 vs K801T -44.3±1.2 mV). Kinetic analysis revealed slower inactivation rates of K801T, but faster rates of activation and deactivation. The hERG channel blockers tested inhibited K801T-hERG channel in concentration response, and the potencies of these drugs can be rank-ordered as follows: quinidine> disopyramide> sotalol> flecainide. Conclusion: Our study indicated that the K801T mutation caused the gain of function of hERG channels that may account for the clinical phenotype of ERS. Quinidine and disopyramide could improve the function of K801T-hERG mutant channel, and may be therapeutic options for patients with the K801T hERG mutation.

Background: Recent studies show that microRNA-145 (miRNA-145) might be an attractive tumor biomarker of considerable prognostic value, but little is known about their relationship with acute myocardial infarction (AMI). This study investigated the correlation between the level of miR-145 and AMI. Methods: One-hundred patients were divided into three groups: no coronary artery disease (CAD) group, non-ST segment elevation myocardial infarction group, and ST segment elevation myocardial infarction group. The plasma levels of miR-145 were quantified using real-time quantitative polymerase chain reaction. Logarithmic transformation of miRNA-145 levels (Ln_miRNA-145) was used for statistical analysis due to the skewed data distribution. Results: Plasma levels of miR-145 were significantly lower in patients with AMI compared to patients in the non-CAD group (−6.38 ± 0.11 vs. −4.47 ± 0.17, P< 0.0001). Compared to those without heart failure, the levels of miR-145 were significantly lower in patients with heart failure (−6.91 ± 0.20 vs. −5.35 ± 0.13, P< 0.0001). We also found that the lower plasma levels of miRNA-145 significantly correlated with increased serum levels of B-type natriuretic peptide (Spearman ρ= −0.60, P< 0.0001), troponin T (Spearman ρ= −0.62, P< 0.0001), and decreased ejection fraction (Spearman ρ= 0.65, P< 0.0001). In a multivariable linear regression analysis, AMI and heart failure were independently associated with lower Ln_miRNA-145 (estimate −0.99, standard error [SE] 0.28; P= 0.001 and estimate −0.62, SE 0.21; P= 0.004). Conclusions: Our results suggest that decreased plasma levels of miR-145 are associated with AMI. Circulating miR-145 may be useful in prognosticating cardiac function and the risk of developing heart failure.

Plant WRKY transcription factors are involved in various physiological processes, including biotic and abiotic stress responses, as well as developmental processes. In this study, the expression patterns of the WRKY68 protein during interactions between rice 4021 containing the bacterial blight resistance gene Xa21 and Xanthomonas oryzae pv. oryzae (Xoo) were investigated. A possible modified form of the WRKY68 protein appeared in the Xa21-mediated disease resistance response, and its expression levels were similar in compatible and incompatible responses, but differed significantly from that of the mock control treatment, suggesting that WRKY68 may be involved in the bacterial blight response in rice. To further understand WRKY68’s roles in the resistance signaling pathway, WRKY68 recombinant protein was expressed in Escherichia coli and a microscale thermophoresis analysis was performed to investigate the interactions between WRKY68 and cis-elements in crucial pathogenesis-related (PR) genes. The results showed that the WRKY68 protein binds to W-boxes in the PR1b promoter region, with an apparent dissociation constant of 25 nmol L−1, while the binding between WRKY68 and PR10a was W-box independent. The results suggested that a possible modified form of the WRKY68 protein was induced during the interaction between rice and Xoo, which then regulated the activity of the downstream PR genes by binding with the W-boxes in the PR1b gene’s promoter region. Moreover, the constitutive transcription of the WRKY68 gene in dozens of rice tissues and the expression of the WRKY68 protein in leaves during all growth stages suggests that WRKY68 plays important roles in rice during normal growth processes.

Phosphomannose isomerase (PMI) encoding gene manA is a desirable selective marker in transgenic research. Understanding of its expression patterns in transgenic plant and establishing highly sensitive detection method based on immunoassay have great impacts on the application of PMI. In this study, PMI-specific monoclonal antibodies were generated using recombinant protein as immunogen, and could be used in Western blot to detect as little as 0.5 ng His-tagged PMI protein or rice expressed PMI protein in sample accounted for 0.4% of single rice grain (about 0.08 mg). PMI protein driven by CaMV-35S promoter was detected in dozens of tested tissues, including root, stem, leaf, panicle, and seed at all developmental stages during rice growing, and PMI protein accounted for about 0.036% of total protein in the leaves at seedling stage. The established method potentially can be used to monitor PMI protein in rice grains.

AIM: To comparatively analyze the application of laser confocal microscopy and corneal smear in the diagnosis of fungal keratitis. METHODS: Totally 77 patients(77 eyes)diagnosed as fungal keratitis were selected. Laser confocal microscopy and corneal smear examination were performed to observe the characteristics of the images, and the detection rate of fungus were compared between the two methods. RESULTS: Of the 77 patients, 66 eyes(86%)were positive and 11 eyes were negative detected by laser confocal microscopy; 51 eyes(66%)were positive and 26 eyes were negative detected by corneal smear examination, the difference was statistically significant compared between two group(PCONCLUSION: Laser corneal confocal microscopy is relatively safe and sensitive. If combined the application of laser corneal confocal microscopy and corneal smear examination in clinical, the diagnosis rate of fungal keratitis may be improved.

Background: This study aimed to evaluate the characteristics of faculty and research activities of basic stem cell research groups in China. Methods: A questionnaire was administered to persons who knew the information among 46 basic stem cell research groups in China. Multiple linear regression models and repeated-measures analyses of variance were used. Repeated-measures analyses of variance were used. Results: Of the 46 groups, 39.1% did not have any faculty recruited from abroad from 2009 to 2013, 37.0% did not have any faculty with junior-level title, 34.8% had ≤25.0% faculty with either M.D. or Ph.D. degree. Papers published in SCI journals per faculty and having faculty recruited from abroad were positively associated with research funding per faculty. The groups with faculty recruited from abroad had significantly higher research funding per faculty over time compared with the group without faculty recruited from abroad. Repeated-measures analyses of variance showed the group with faculty recruited from abroad had significantly higher research funding per faculty over time compared with the group without faculty recruited from abroad. Conclusion: To increase the development of basic stem cell research, some characteristics of human resources should be improved, and the groups should recruit more faculty with overseas experience.

BackgroundRadiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of heart disease is uncertain. We performed a meta‐analysis to investigate the link between radiotherapy and long‐term cardiovascular morbidity and mortality in patients with breast cancer. Methods and ResultsWe performed a literature search using MEDLINE (January 1966 to January 2015) and EMBASE (January 1980 to January 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95%CIs for the associations of interest were included. Pooled effect estimates were obtained by using random‐effects meta‐analysis. Thirty‐nine studies involving 1 191 371 participants were identified. Patients who received left‐sided radiotherapy, as compared with those receiving right‐sided radiotherapy, experienced increased risks of developing coronary heart disease (RR 1.29, 95%CI 1.13‐1.48), cardiac death (RR 1.22, 95%CI 1.08‐1.37) and death from any cause (RR 1.05, 95%CI 1.01‐1.10). In a comparison of patients with radiotherapy and without radiotherapy, the RRs were 1.30 (95%CI 1.13‐1.49) for coronary heart disease and 1.38 (95%CI 1.18‐1.62) for cardiac mortality. Radiotherapy for breast cancer was associated with an absolute risk increase of 76.4 (95%CI 36.8‐130.5) cases of coronary heart disease and 125.5 (95%CI 98.8‐157.9) cases of cardiac death per 100 000 person‐years. The risk started to increase within the first decade for coronary heart disease and from the second decade for cardiac mortality. ConclusionsExposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent risk of coronary heart disease and cardiac mortality.

Background: As the number of empty-nest elderly rises in the city of Shanghai, ensuring their timely use of health care is a public health concern. The purpose of the study was to examine the home health care needs among the empty-nest elderly living in Shanghai. Methods: A questionnaire was administered to 504 empty-nest elderly and 424 non-empty-nest elderly in Shanghai, China. Logistic regression analysis was used to examine the predictors of home health care needs. Linear regression analysis was applied to examine the predictors of willingness to pay for home health care. Results: The empty-nest elderly had higher income, less social support, higher prevalence of chronic diseases, were more likely to have worries or concerns about their health and availability of daily care at home or assistance with travel to the doctor's office than the non-empty-nest elderly. They also had higher home health care needs and were willing to pay more money for home health care. Age, education level, social support, and chronic diseases were correlated with home health care needs. Income, social support, and age were associated with willingness to pay for onsite medical services, and income, social support, age, and education level were associated with willingness to pay for social services. Conclusion: The empty-nest elderly had more home health care needs due to their having less social support and higher prevalence of chronic diseases, and they were willing to pay more money for the home health care because of the higher income and less social support.

Background An early repolarization pattern (ERP) has been hypothesized to be arrhythmogenic in experimental studies, but the prognostic significance of the ERP in the general population is controversial. We performed a meta‐analysis to examine the link between ERP and the risk of sudden cardiac arrest (SCA), cardiac death, and death from any cause. Methods and Results We performed a literature search using MEDLINE (January 1, 1966 to July 31, 2015) and EMBASE (January 1, 1980 to July 31, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Sixteen studies involving 334 524 subjects were identified. Compared with those without ERP, subjects with ERP experienced significantly increased risk for developing SCA (RR 2.18; 95% CI 1.29–3.68), cardiac death (RR 1.48; 95% CI 1.06–2.07), and death from any cause (RR 1.21; 95% CI 1.02–1.42), respectively. The increased risk was present predominantly in Asians and whites but not in African Americans. ERP with J‐point elevation in inferior leads, notching configuration, and horizontal or descending ST segment connote higher risk. ERP was associated with an absolute risk increase of 139.6 (95% CI 130.3–149.3) additional SCAs per 100 000 person‐years and responsible for 7.3% (95% CI 1.9–15.2) of SCA in the general population. Conclusions ERP is associated with significant increased risk for SCA, cardiac death, and death from any cause. Future studies should focus on understanding the exact mechanisms for the arrhythmia risk and developing reliable tools for risk stratification.

To study the role of the Rho/ROCK pathway in Ang II and TGF-β1-induced atrial remodeling.A canine atrial fibrillation (AF) model was established by rapid atrial pacing (RAP) of the left atrium. The roles of TGF-β1, the RhoA/ROCK signaling pathway and connective tissue growth factor (CTGF) in atrial remodeling were studied via both in vitro and in vivo experiments. Each of the dogs that received RAP developed persistent AF within 4 weeks. The mRNA expression levels of TGF-β1 (1.32±0.38), Collagen-I(1.33±0.91), CTGF(5.83±3.71), RhoA(1.23±0.57) and ROCK-1 (1.02±0.27) in the left atrium were significantly increased following 4 weeks of RAP. Angiotensin II (Ang II) induced the proliferation of atrial fibroblasts and up-regulated the expression of both CTGF and ROCK-1 in a dose-dependent manner. Simvastatin and Y27632 reversed Ang II-induced CFs proliferation, as well as ROCK-1(0.89±0.05 and 1.27±0.03, respectively) and CTGF (0.87±0.04 and 0.91±0.02, respectively) expression. The expression mRNA of ROCK-1(1.74±0.13) and CTGF (2.28±0.11) can upregulated by TGF-β1, and down-regulated by Simvastatin (1.22±0.03 vs 2.27±0.11), Y27632 (1.01±0.04 vs 1.64±0.03), Los (1.04±0.11 vs 1.26±0.05), respectively. Losartan and Simvastatin attenuated the effects of TGF-β1, inhibited RhoA activity as opposed to RhoA protein expression. Y27632 had no effect on either the expression or the activity of RhoA.The increased expression of profibrotic factors (CTGF, ROCK1 and Smad2/3) played an important role in our RAP-induced AF model. Increased atrial profibrotic factors involve the activation of either the TGF-β1/RhoA/ROCK-1 or the TGF-β1/Smad2/3 signaling pathway.

Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system. There is no consensus regarding reported associations between human leukocyte antigen DQB1 (HLA-DQB1) polymorphisms and the risk for developing GBS. Here, we evaluated possible associations between HLA-DQB1 polymorphisms and the risk for GBS using a meta-analysis. We searched PubMed for case-control genetic association studies for HLA-DQB1 polymorphisms (*020x, *030x, *040x, *050x, and *060x) and the risk for GBS. Fixed-effect meta-analytical methods were used for the outcome measure and subgroup analyses. Estimated odds ratios (ORs) and 95% confidence intervals (CIs) were used to investigate the associations between HLA-DQB1 polymorphisms and the risk for GBS. Nine case-control studies involving 780 cases of GBS and 1353 controls were identified in the current study. The meta-analysis demonstrated no significant associations between HLA-DQB1 polymorphisms and the risk for GBS in Asian and Caucasian populations. There were two associations that approached significance: HLA-DQB1*030x in Asian patients (P = 0.07; OR: 0.76, 95% CI: 0.57-1.03) and HLA-DQB1*060x in all patients (P = 0.08; OR: 1.48, 95% CI: 0.96-2.29). Additional studies with larger sample sizes are required to establish a definitive assessment of the contribution of HLA-DQB1 polymorphisms to GBS risk.

In this study, we applied structure-based virtual screening techniques to identify natural product or natural product-like inhibitors of iNOS. The iNOS inhibitory activity of the hit compounds was characterized using cellular assays and an in vivo zebrafish larvae model. The natural product-like compound 1 inhibited NO production in LPS-stimulated Raw264.7 macrophages, without exerting cytotoxic effects on the cells. Significantly, compound 1 was able to reverse MPTP-induced locomotion deficiency and neurotoxicity in an in vivo zebrafish larval model. Hence, compound 1 could be considered as a scaffold for the further development of iNOS inhibitors for potential anti-inflammatory or anti-neurodegenerative applications.

BACKGROUND: The prognostic importance of B-type natriuretic peptide (BNP) or N-terminal pro BNP (NT-proBNP) in patients with end-stage renal disease (ESRD) remains controversial. METHODOLOGY/PRINCIPAL FINDINGS: We conducted an unrestricted search from the MEDLINE and EMBASE in all languages that were published between 1966 and Augest2013. Twenty-seven long-term prospective studies met our inclusion criterias. From the pooled analysis, elevated BNP/NT-proBNP was significantly associated with increased all cause mortality [odds ratio (OR), 3.85; 95% CI, 3.11 to 4.75], cardiovascular mortality (OR, 4.05; 95% CI, 2.53 to 6.84), and cardiovascular events (OR, 7.02; 95% CI, 2.21 to 22.33). The funnel plot showed no evidence of publication bias. The corresponding pooled positive and negative likelihood ratio for prediction of all cause mortality were 1.86 (95% CI, 1.66 to 2.08) and 0.48 (95% CI, 0.42 to 0.55), respectively. CONCLUSIONS/SIGNIFICANCE: BNP/NT-proBNP is a promising prognostic tool to risk-stratify the patients with ESRD. Further investigations are warranted to elucidate the specific pathogenic mechanisms and the impact of other potential prognostic factors.

We report herein a novel luminescent iridium(III) complex with two hydrophobic carbon chains as a non-reaction based chemosensor for the detection of Hg(2+) ions in aqueous solution (

OBJECTIVES: To evaluate the relationship between Patient Assessment of Chronic Illness Care in community health centers and self-management behaviors and glycemic control and to examine the relationship between Patient Assessment of Chronic Illness Care in community health centers and the utilization of community health centers for monitoring and treating diabetes among the patients with type 2 diabetes. METHODS: A questionnaire including self-management behaviors, glycemic control, Patient Assessment of Chronic Illness Care in community health centers and the most often utilized medical institutions for monitoring and treating diabetes (community health centers vs. hospitals) was administered to 960 patients with type 2 diabetes in Shanghai, China. The relationships between Patient Assessment of Chronic Illness Care and self-management behaviors, self-management behaviors and glycemic control, Patient Assessment of Chronic Illness Care and glycemic control, Patient Assessment of Chronic Illness Care and the most often utilized medical institutions for monitoring and treating diabetes were examined. RESULTS: Wilcoxon rank sum tests showed that the high scores of total Patient Assessment of Chronic Illness Care and five subscales in community health centers were positively related to almost all the proper self-management behaviors and good glycemic control (p

Coxsackieviruses A10 (CV-A10) and A6 (CV-A6) have been associated with increasingly occurred sporadic hand-foot-mouth disease (HFMD) cases and outbreak events globally. However, our understanding of epidemiological and genetic characteristics of these new agents remains far from complete. This study was to explore the circulation of CV-A10 and CV-A6 in HFMD and their genetic characteristics in China. A hospital based surveillance was performed in three heavily inflicted regions with HFMD from March 2009 to August 2011. Feces samples were collected from children with clinical diagnosis of HFMD. The detection and genotyping of enteroviruses was performed by real-time PCR and sequencing of 5'UTR/VP1 regions. Phylogenetic analysis and selection pressure were performed based on the VP1 sequences. Logistic regression model was used to identify the effect of predominant enterovirus serotypes in causing severe HFMD. The results showed 92.0% of 1748 feces samples were detected positive for enterovirus, with the most frequently presented serotypes as EV-71 (944, 54.0%) and CV-A16 (451, 25.8%). CV-A10 and CV-A6 were detected as a sole pathogen in 82 (4.7%) and 44 (2.5%) cases, respectively. Infection with CV-A10 and EV-71 were independently associated with high risk of severe HFMD (OR = 2.66, 95% CI: 1.40-5.06; OR = 4.81, 95% CI: 3.07-7.53), when adjusted for age and sex. Phylogenetic analysis revealed that distinct geographic and temporal origins correlated with the gene clusters based on VP1 sequences. An overall ω value of the VP1 was 0.046 for CV-A10 and 0.047 for CV-A6, and no positively selected site was detected in VP1 of both CV-A10 and CV-A6, indicating that purifying selection shaped the evolution of CV-A10 and CV-A6. Our study demonstrates variety of enterovirus genotypes as viral pathogens in causing HFMD in China. CV-A10 and CV-A6 were co-circulating together with EV-71 and CV-A16 in recent years. CV-A10 infection might also be independently associated with severe HFMD.

In the title compound, C20H34NO2P, the P atom has an irregular tetrahedral environment and exhibits Sp chirality. In the crystal, weak intermolecular N—H...O and C—H...O hydrogen bonds link the molecules into chains extending in [010].

The title compound, C19H31O2P, features a distorted tetrahedral P atom that bonds to the phenyl ring, isopropyl and 2-isopropyl-5-methylcyclohexyl groups, and is determined as having an Rp configuration. A chair conformation is observed for the cyclohexyl ring. In the crystal, molecules are linked into chains running along the a axis by weak intermolecular C—H...O hodrogen bonds.

In the title molecule, C22H35O2P, the two cyclohexyl rings exhibit chair conformations. In the crystal, molecules related by translation along the b axis are linked by the weak intermolecular C—H...O hydrogen bonds.

The title compound, C22H36NO2P, features a P atom bonded to a phenyl ring, a cyclohexylamine unit and the O atom of a menthyl group. In the crystal structure, intermolecular N—H...O hydrogen bonds connect molecules into a one-dimensional chain in the b direction.