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Oxidative stress and inflammation significantly contribute to the pathogenesis of diabetic cardiomyopathy (DCM). Persistent inflammatory stimuli drive the progression of myocardial fibrosis and impaired cardiac function. Phloridzin (Phl), a natural compound, demonstrates both anti-inflammatory and antioxidant properties. Nevertheless, its therapeutic potential and underlying mechanisms in DCM remain unclear. This study aimed to elucidate the mechanisms through which Phl inhibited myocardial fibrosis and exerted its antioxidative effects. The impact of Phl on DCM was evaluated using a high-fat/high-sugar diet combined with streptozotocin to induce an animal model and an in vitro H9C2 cell model stimulated by high glucose (HG). Untargeted metabolomics identified potential mechanisms underlying myocardial fibrosis. Phl treatment significantly enhanced left ventricular ejection fraction (EF%) and shortening fraction (FS%), while reducing myocardial injury markers, such as lactate dehydrogenase and creatine phosphokinase-MB, and suppressing myocardial collagen fiber accumulation. Simultaneously, Phl attenuated myocardial inflammation via inhibition of MyD88/NF-κB signaling, modulated the Nrf2/GPX4 axis to counter oxidative stress, and mitigated ferroptosis. In vitro, Phl inhibited high glucose-induced myocardial hypertrophy and fibrosis in H9C2 cells, while also repressing NF-κB activation in cardiomyocytes. Metabolomic profiling revealed that Phl ameliorated DCM through modulation of glycerophospholipid metabolic pathways, linking these metabolic shifts to enhanced antioxidant capacity, thereby reflecting its ability to reduce oxidative stress in the myocardium. Collectively, Phl provides cardioprotective effects by alleviating inflammation and oxidative damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Biological ion channels usually conduct the high-flux transport of 10 7  ~ 10 8  ions·s - 1 ; however, the underlying mechanism is still lacking. Here, by applying the KcsA potassium channel as a typical example, and performing multitimescale molecular dynamics simulations, we demonstrate that there is coherence of the K + ions confined in biological channels, which determines transport. The coherent oscillation state of confined K + ions with a nanosecond-level lifetime in the channel dominates each transport event, serving as the physical basis for the high flux of ~10 8  ions∙s - 1 . The coherent transfer of confined K + ions only takes several picoseconds and has no perturbation effect on the ion coherence, acting as the directional key of transport. Such ion coherence is allowed by quantum mechanics. An increase in the coherence can significantly enhance the ion conductance. These findings provide a potential explanation from the perspective of coherence for the high-flux ion transport with ultralow energy consumption of biological channels., (© 2024. The Author(s).)

Background: The complex relationship between atrial fibrillation (AF) and type 2 diabetes mellitus (T2DM) suggests a potential role for epicardial adipose tissue (EAT) that requires further investigation. This study employs bioinformatics and experimental approaches to clarify EAT's role in linking T2DM and AF, aiming to unravel the biological mechanisms involved., Method: Bioinformatics analysis initially identified common differentially expressed genes (DEGs) in EAT from T2DM and AF datasets. Pathway enrichment and network analyses were then performed to determine the biological significance and network connections of these DEGs. Hub genes were identified through six CytoHubba algorithms and subsequently validated biologically, with further in-depth analyses confirming their roles and interactions. Experimentally, db/db mice were utilized to establish a T2DM model. AF induction was executed via programmed transesophageal electrical stimulation and burst pacing, focusing on comparing the incidence and duration of AF. Frozen sections and Hematoxylin and Eosin (H&E) staining illuminated the structures of the heart and EAT. Moreover, quantitative PCR (qPCR) measured the expression of hub genes., Results: The study identified 106 DEGs in EAT from T2DM and AF datasets, underscoring significant pathways in energy metabolism and immune regulation. Three hub genes, CEBPZ, PAK1IP1, and BCCIP, emerged as pivotal in this context. In db/db mice, a marked predisposition towards AF induction and extended duration was observed, with HE staining verifying the presence of EAT. Additionally, qPCR validated significant changes in hub genes expression in db/db mice EAT. In-depth analysis identified 299 miRNAs and 33 TFs as potential regulators, notably GRHL1 and MYC. GeneMANIA analysis highlighted the hub genes' critical roles in stress responses and leukocyte differentiation, while immune profile correlations highlighted their impact on mast cells and neutrophils, emphasizing the genes' significant influence on immune regulation within the context of T2DM and AF., Conclusion: This investigation reveals the molecular links between T2DM and AF with a focus on EAT. Targeting these pathways, especially EAT-related ones, may enable personalized treatments and improved outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The thymus, a site to culture the naïve T lymphocytes, is susceptible to atrophy or involution due to aging, inflammation, and oxidation. Epigallocatechin-3-gallate (EGCG) has been proven to possess anti-inflammatory, antioxidant, and antitumor activity. Here, we investigate the effects of EGCG on thymic involution induced by lipopolysaccharide (LPS), an endotoxin derived from Gram-negative bacteria. The methodology included an in vivo experiment on female Kunming mice exposed to LPS and EGCG. Morphological assessment of thymic involution, immunohistochemical detection, and thymocyte subsets analysis by flow cytometry were further carried out to evaluate the potential role of EGCG on the thymus. As a result, we found that EGCG alleviated LPS-induced thymic atrophy, increased mitochondrial membrane potential and superoxide dismutase levels, and decreased malondialdehyde and reactive oxygen species levels. In addition, EGCG pre-supplement restored the ratio of thymocyte subsets, the expression of autoimmune regulator, sex-determining region Y-box 2, and Nanog homebox, and reduced the number of senescent cells and collagen fiber deposition. Western blotting results indicated that EGCG treatment elevated LPS-induced decrease in pAMPK, Sirt1 protein expression. Collectively, EGCG relieved thymus architecture and function damaged by LPS via regulation of AMPK/Sirt1 signaling pathway. Our findings may provide a new strategy on protection of thymus from involution caused by LPS by using EGCG. And EGCG might be considered as a potential agent for the prevention and treatment of thymic involution., (© 2024 The Societies and John Wiley & Sons Australia, Ltd.)

Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy., (© 2024. The Author(s).)

We propose a robust and automatic method to construct manifold cages for 3D triangular meshes. The cage contains hundreds of triangles to tightly enclose the input mesh without self-intersections. To generate such cages, our algorithm consists of two phases: (1) construct manifold cages satisfying the tightness, enclosing, and intersection-free requirements and (2) reduce mesh complexities and approximation errors without violating the enclosing and intersection-free requirements. To theoretically make the first stage have those properties, we combine the conformal tetrahedral meshing and tetrahedral mesh subdivision. The second step is a constrained remeshing process using explicit checks to ensure that the enclosing and intersection-free constraints are always satisfied. Both phases use a hybrid coordinate representation, i.e., rational numbers and floating point numbers, combined with exact arithmetic and floating point filtering techniques to guarantee the robustness of geometric predicates with a favorable speed. We extensively test our method on a data set of over 8500 models, demonstrating robustness and performance. Compared to other state-of-the-art methods, our method possesses much stronger robustness.

Cryptophytes are ancestral photosynthetic organisms evolved from red algae through secondary endosymbiosis. They have developed alloxanthin-chlorophyll a/c2-binding proteins (ACPs) as light-harvesting complexes (LHCs). The distinctive properties of cryptophytes contribute to efficient oxygenic photosynthesis and underscore the evolutionary relationships of red-lineage plastids. Here we present the cryo-electron microscopy structure of the Photosystem II (PSII)-ACPII supercomplex from the cryptophyte Chroomonas placoidea. The structure includes a PSII dimer and twelve ACPII monomers forming four linear trimers. These trimers structurally resemble red algae LHCs and cryptophyte ACPI trimers that associate with Photosystem I (PSI), suggesting their close evolutionary links. We also determine a Chl a-binding subunit, Psb-γ, essential for stabilizing PSII-ACPII association. Furthermore, computational calculation provides insights into the excitation energy transfer pathways. Our study lays a solid structural foundation for understanding the light-energy capture and transfer in cryptophyte PSII-ACPII, evolutionary variations in PSII-LHCII, and the origin of red-lineage LHCIIs., (© 2024. The Author(s).)

Background: More than 2 billion women are experiencing the menopausal transition in China, and some of these women have hypertension. Limited studies has focused on perimenopausal syndrome and hypertension in a specific population, so we aimed to investigate the prevalence of perimenopausal syndrome and hypertension and to analyse their relationships and risk factors in perimenopausal women in South China., Methods: This cross-sectional study included 3553 women aged 40 to 60 years from South China. We collected medical report, lifestyle, blood sample, general condition questionnaire, and modified Kupperman index (mKMI) data. Multivariate logistic regression analysis was performed to identify risk factors for perimenopausal syndrome and hypertension during perimenopause., Results: The prevalence of hypertension in perimenopause patients was 16.58%, and the prevalence of perimenopausal syndrome was 9.9%. Compared with women without hypertension during perimenopause, women with HTN during perimenopause had an increased risk of perimenopausal syndrome (26.4% vs. 8.7%, P < 0.001). Lipid levels and urinary tract infections were risk factors for hypertension and perimenopausal syndrome, in addition to the presence of breast nodules, the intake of snacks at night, high-salt diets, red meat and sugar-sweetened beverages, and a history of smoking and drinking for perimenopausal syndrome and the presence of gestational hypertension and diabetes for hypertension., Conclusion: We concluded that perimenopausal syndrome and HTN are common in perimenopausal women in South China, and the associations between them are strong and positive. Perimenopausal syndrome shares some common risk factors with HTN during perimenopause, such as BMI and dyslipidaemia. Therefore, gynaecological endocrinologists in China should consider screening for perimenopausal syndrome in hypertensive perimenopausal women, and appropriate management of perimenopause is needed to alleviate these conditions., (© 2024. The Author(s).)

Symbiodinium are the photosynthetic endosymbionts for corals and play a vital role in supplying their coral hosts with photosynthetic products, forming the nutritional foundation for high-yield coral reef ecosystems. Here, we determine the cryo-electron microscopy structure of Symbiodinium photosystem I (PSI) supercomplex with a PSI core composed of 13 subunits including 2 previously unidentified subunits, PsaT and PsaU, as well as 13 peridinin-Chl a/c-binding light-harvesting antenna proteins (AcpPCIs). The PSI-AcpPCI supercomplex exhibits distinctive structural features compared to their red lineage counterparts, including extended termini of PsaD/E/I/J/L/M/R and AcpPCI-1/3/5/7/8/11 subunits, conformational changes in the surface loops of PsaA and PsaB subunits, facilitating the association between the PSI core and peripheral antennae. Structural analysis and computational calculation of excitation energy transfer rates unravel specific pigment networks in Symbiodinium PSI-AcpPCI for efficient excitation energy transfer. Overall, this study provides a structural basis for deciphering the mechanisms governing light harvesting and energy transfer in Symbiodinium PSI-AcpPCI supercomplexes adapted to their symbiotic ecosystem, as well as insights into the evolutionary diversity of PSI-LHCI among various photosynthetic organisms., (© 2024. The Author(s).)

Microplastics(MPs), as a new type of environmental pollutants, have gradually attracted widespread attention since they were introduced by British scientists in 2004. Soil is an important accumulation site for microplastics, which can expand the scope of contamination and accumulate with agricultural practices such as irrigation and tillage. Microplastics in soil cause a variety of toxicities to terrestrial plants. The small particle size, difficult degradation, and strong adsorption capacity bring a challenge to the microplastic pollution treatment of soil. In this study, the toxicity of microplastics to terrestrial plants was reviewed in terms of their direct or indirect toxicity and combined effects with other pollutants, mainly in terms of mechanical injury, induction of oxidative stress, and cytotoxicity and genotoxicity to plants, resulting in plant growth and plant tissue metabolism obstruction. In general, the toxicity of microplastics depended on the polymer type, size, and dose; plant tolerance; and exposure conditions. In addition, the production of secondary microplastics and endogenous contaminants during their degradation in soil enhanced the biotoxicity of microplastics. Further, the physical, chemical, and microbial degradation mechanisms of microplastics were introduced in this study based on the current research. At first, the physical and chemical degradation of microplastics mainly occurred by changing the particle size and surface properties of microplastics and producing intermediates. Then, smaller-sized microplastics and their intermediates could eventually be converted to water and carbon dioxide through physical, chemical, and biological functions. Finally, further prospects regarding soil microplastics were introduced, and we provided information for future improvement and pollution control of microplastics.

Objective: To analyze and compare the risk factors for hemorrhagic stroke and ischemic stroke and understand the exposure levels in population. Methods: A cohort study of risk factors of stroke was conducted in a rural community in Fengxian District of Shanghai in 2003, and the common risk factors of stroke were investigated at baseline survey, the cerebrovascular hemodynamics indexes were detected, the cerebrovascular function score was calculated according to the unified integral rule, and the incidence of stroke was observed in follow up. The risk factors for hemorrhagic stroke and ischemic stroke were analyzed by cohort study. The risk factors for two subtypes of stroke were compared. Result: A total of 10 565 participants were included in the study, with a mean follow-up period of (11.15±2.26) years, and 103 hemorrhagic stroke cases and 268 ischemic stroke cases were observed during follow-up period. The independent risk factors of hemorrhagic stroke included decreased cerebrovascular function score [hazard ratio ( HR )=1.56, 95% CI : 1.23-1.98], history of alcohol consumption ( HR =2.46, 95% CI : 1.39-4.34), hypertension ( HR =1.75, 95% CI : 1.00-3.07) and older age ( HR =1.07, 95% CI : 1.04-1.10). The independent risk factors of ischemic stroke included decreased cerebrovascular function score ( HR =1.43, 95% CI : 1.25-1.65), smoking history ( HR =1.52, 95% CI : 1.13-2.05), hypertension ( HR =1.51, 95% CI : 1.10-2.07), family history of stroke ( HR =1.89, 95% CI : 1.13-3.15), left ventricular hypertrophy ( HR =1.74, 95% CI : 1.07-2.81) and older age ( HR =1.07, 95% CI : 1.05-1.08). Conclusions: Decreased cerebrovascular function score, hypertension, and older age were common independent risk factors of both types of stroke, alcohol consumption history was an independent risk factor of hemorrhagic stroke, and smoking history, and family history of stroke and left ventricular hypertrophy were independent risk factors of ischemic stroke.

Purpose: The relationship between vitamin D levels and cancer incidence and mortality in individuals with metabolic syndrome (MetS) remains poorly explored. Herein, we aimed to determine the association between 25-hydroxyvitamin D [25(OH)D] concentrations and the risk of 16 cancer incidence types and cancer/all-cause mortality in patients with MetS., Methods: We enrolled 97,621 participants with MetS at recruitment from the UK Biobank cohort. The exposure factor was baseline serum 25(OH)D concentrations. The associations were examined using Cox proportional hazards models, which were displayed as hazard ratios (HRs) with 95% confidence intervals (CIs)., Results: Over a median follow-up period of 10.92 years for cancer incidence outcomes, 12,137 new cancer cases were recorded. We observed that 25(OH)D concentrations were inversely related to the risk of colon, lung, and kidney cancer, and HRs (95% CI) for 25(OH)D ≥ 75.0 vs. < 25.0 nmol/L were 0.67 (0.45-0.98), 0.64 (0.45-0.91), and 0.54 (0.31-0.95), respectively. The fully adjusted model revealed a null correlation between 25(OH)D and the incidence of stomach, rectum, liver, pancreas, breast, ovary, bladder, brain, multiple myeloma, leukemia, non-Hodgkin lymphoma, esophagus, and corpus uteri cancer. Over a median follow-up period of 12.72 years for mortality outcomes, 8286 fatalities (including 3210 cancer mortalities) were documented. An "L-shaped" nonlinear dose-response correlation was detected between 25(OH)D and cancer/all-cause mortality; the respective HRs (95% CI) were 0.75 (0.64-0.89) and 0.65 (0.58-0.72)., Conclusion: These findings emphasize the importance of 25(OH)D in cancer prevention and longevity promotion among patients with MetS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Improved markers for predicting recurrence are needed to stratify patients with localised (stage I-III) renal cell carcinoma after surgery for selection of adjuvant therapy. We developed a novel assay integrating three modalities-clinical, genomic, and histopathological-to improve the predictive accuracy for localised renal cell carcinoma recurrence., Methods: In this retrospective analysis and validation study, we developed a histopathological whole-slide image (WSI)-based score using deep learning allied to digital scanning of conventional haematoxylin and eosin-stained tumour tissue sections, to predict tumour recurrence in a development dataset of 651 patients with distinctly good or poor disease outcome. The six single nucleotide polymorphism-based score, which was detected in paraffin-embedded tumour tissue samples, and the Leibovich score, which was established using clinicopathological risk factors, were combined with the WSI-based score to construct a multimodal recurrence score in the training dataset of 1125 patients. The multimodal recurrence score was validated in 1625 patients from the independent validation dataset and 418 patients from The Cancer Genome Atlas set. The primary outcome measured was the recurrence-free interval (RFI)., Findings: The multimodal recurrence score had significantly higher predictive accuracy than the three single-modal scores and clinicopathological risk factors, and it precisely predicted the RFI of patients in the training and two validation datasets (areas under the curve at 5 years: 0·825-0·876 vs 0·608-0·793; p<0·05). The RFI of patients with low stage or grade is usually better than that of patients with high stage or grade; however, the RFI in the multimodal recurrence score-defined high-risk stage I and II group was shorter than in the low-risk stage III group (hazard ratio [HR] 4·57, 95% CI 2·49-8·40; p<0·0001), and the RFI of the high-risk grade 1 and 2 group was shorter than in the low-risk grade 3 and 4 group (HR 4·58, 3·19-6·59; p<0·0001)., Interpretation: Our multimodal recurrence score is a practical and reliable predictor that can add value to the current staging system for predicting localised renal cell carcinoma recurrence after surgery, and this combined approach more precisely informs treatment decisions about adjuvant therapy., Funding: National Natural Science Foundation of China, and National Key Research and Development Program of China., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Solar flares are one of the severest solar activities that have important effects on near-Earth space. Previous studies have shown that flight arrival delays increase as a result of solar flares, but the intrinsic mechanism behind this relationship is still unknown. In this study, we conducted a comprehensive analysis of flight departure delays during 57 solar X-ray events by using a huge amount of flight data (~ 5 × 10 6 records) gathered over a 5-year period. It is found that the average flight departure delay time during solar X-ray events increased by 20.68% (7.67 min) compared to quiet periods. Our analysis also revealed apparent time and latitude dependencies, with flight delays being more serious on the dayside than on the nightside and longer (shorter) delays tending to occur in lower (higher) latitude airports during solar X-ray events. Furthermore, our results suggest that the intensity of solar flares (soft X-ray flux) and the Solar Zenith Angle directly modulate flight departure delay time and delay rate. These results indicate that communication interferences caused by solar flares directly affect flight departure delays. This work expands our conventional understanding of the impacts of solar flares on human society and provides new insights for preventing or coping with flight delays., (© 2023. The Author(s).)

Although the sun is really far away from us, some solar activities could still influence the performance and reliability of space-borne and ground-based technological systems on Earth. Those time-varying conditions in space caused by the sun are also called solar storm or space weather. It is known that aviation activities can be affected during solar storms, but the exact effects of space weather on aviation are still unclear. Especially how the flight delays, the top topic concerned by most people, will be affected by space weather has never been thoroughly researched. By analyzing huge amount of flight data (~ 4 × 10 6 records), for the first time, we quantitatively investigate the flight delays during space weather events. It is found that compared to the quiet periods, the average arrival delay time and 30-min delay rate during space weather events are significantly increased by 81.34% and 21.45% respectively. The evident negative correlation between the yearly flight regularity rate and the yearly mean total sunspot number during 22 years also confirms such correlation. Further studies show that the flight delay time and delay rate will monotonically increase with the geomagnetic field fluctuations and ionospheric disturbances. These results indicate that the interferences in communication and navigation during space weather events may be the most probable reason accounting for the increased flight delays. The above analyses expand the traditional field of space weather research and could also provide us with brand new views for improving the flight delay predications., (© 2023. The Author(s).)

Objective: To explore the characteristics and clinical phenotypes of rheumatoid arthritis (RA) and provide the basis for further understanding, interventions and outcomes of this disease., Methods: RA patients attended at Peking University People's Hospital from 2018 to 2021 were enrolled in the study. Data collection included demographic data, the sites and numbers of joints involved, extra-articular manifestations (EAM), comorbidities and laboratory variables. Statistical and bioinformatical analysis was performed to establish clinical subtypes by clustering analysis based on the type of joint involved, EAM involvement and other autoimmune diseases overlapped. The characteristics of each subtype were analyzed., Results: A total of 411 patients with RA were enrolled. The mean age was (48.84±15.17) years, and 346 (84.2%) were females. The patients were classified into 4 subtypes: small joint subtype (74, 18.0%), total joint subtype (154, 37.5%), systemic subtype (100, 24.3%), and overlapping subtype (83, 20.2%). The small joint subtype had no medium or large joint involvement, and 35.1% had systemic involvement. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and platelet count (PLT) were lower than those in other subtypes, and the rates of positive rheumatoid factors (RF-IgA and RF-IgG) were significantly higher in the small joint subtype. The total joint subtype had both large and small joint involvement but no systemic involvement. The rate of morning stiffness and positive antinuclear antibodies (ANA) in this subtype were lower than those in other subtypes. In the systemic subtype, interstitial lung disease and secondary Sjögren syndrome were the most common systemic involvements, with prominent levels of disease activity score 28-joint count (DAS28-ESR and DAS28-CRP). The overlapping subtype was commonly combined with Hashimoto's thyroiditis or primary Sjögren syndrome. Female in the overlapping subtype was more common than in other subtypes. This subtype was characterized by hyperglobulinemia, hypocomplementemia and high rate of positive ANA, especially spotting type., Conclusion: Based on the clinical features, RA patients could be classified into 4 subtypes: small joint subtype, total joint subtype, systemic subtype, and overlapping subtype. Each subtype had its own clinical characteristics. They help for further understanding and a more individualized treatment strategy of RA.

Objective: To investigate the effects of Rosa roxburghii on insulin resistance in obese rats and the regulation of phosphatidylinositol 3-kinase (PI3K)/ protein kinase Bβ(PKB β /Akt2)/ glucose transporter 4(GLUT4) signaling pathway. Methods: Five-week-old male SD rats were randomly divided into normal control group (NC), model group (M), positive control group (PC), low-dose rosa roxburghii group (LD) and high-dose rosa roxburghii group (HD), with 10 rats in each group. The rats in the NC group were fed with normal diet, while those in the M, PC, LD and HD groups were fed with high-fat diet. From the 13th week, according to the dose standard of 6 ml/kg, rats in the LD group were intragastrically administered with 100 mg/kg Rosa roxburghii Tratt, the HD group were treated with 300 mg/kg Rosa roxburghii Tratt, the PC group were treated with 0.11 g/kg Chiglitazar sodium, and the NC and M groups were intragastrically administered with the same volume of normal saline. The body weight was measured every week until 20 weeks. The rats were sacrificed 24 h after the last experiment. Blood and skeletal muscle were collected. Serum total cholesterol (TC) and triglyceride (TG) contents were detected by colorimetric method, serum superoxide dismutase (SOD) activity was detected by xanthine oxidase method, serum malondialdehyde (MDA) content was detected by thiobarbituric acid method, blood glucose (FBG) value was detected by glucose oxidase method, insulin (FINS) content was detected by ELISA, and PI3K, Akt2, and GLUT4 protein and gene expressions were detected by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Results: Compared with the NC group, the body weight, serum MDA, TG, TC, FBG, FINS, HOMA-IR levels in the M group were significantly increased ( P ＜0.01), while SOD activity, PI3K、Akt2、GLUT4 protein and mRNA expression levels were significantly increased( P ＜ 0.01). Compared with group M, the body weight, serum MDA, TG, TC, FBG, FINS, and HOMA-IR were decreased significantly in LD group, HD group and PC group ( P ＜0.05 or P ＜0.01), while SOD activity, PI3K, Akt2, GLUT4 protein and mRNA expression levels were increased significantly ( P ＜0.05 or P ＜0.01). Conclusion: Rosa roxburghii can improve insulin resistance in obese rats by antioxidant stress and up-regulating the expressions of PI3K, Akt2, and GLUT4 proteins and genes, which may be related to the PI3K/Akt2/GLUT4 signaling pathway.

The importance of anti-HLA antibodies in transplantation settings, such as HLA-mismatched or haploidentical hematopoietic stem cell transplantation and platelet refractoriness, is widely recognized. In previous reports, it was mentioned that several cut-off values of donor-specific anti-HLA antibodies mean fluorescence intensity (MFI) were related to graft rejection in the environment of HLA mismatched stem cell transplantation and the aim of this study was to investigate the prevalence and risk factors of anti-HLA antibodies according to those cut-off values of MFI. A total of 3805 patients with hematologic disease were prospectively enrolled and analyzed. When using MFI of anti-HLA antibodies ≥500, ≥1000, ≥1500, ≥2000, ≥5000, and ≥ 10,000 as cut-off values for positivity, the prevalence of class I or II anti-HLA antibodies ranged from 4.6% to 20.2% in all cases. When the MFI cut-off value was ≥500 for positivity, multivariate analysis indicated that platelet transfusion, underlying disease, and pregnancy were the most important risk factors for the presence of anti-HLA antibodies for the total patients. Subgroup analysis according to age, gender, and underlying disease showed that pregnancy was the most important risk factor for the presence of anti-HLA antibodies. For all patients (n = 3805), when anti-HLA antibody positivity was defined according to different MFI cut-off values, including ≥1000, ≥1500, ≥2000, ≥5000, and ≥ 10,000, an association of platelet transfusion and pregnancy with anti-HLA antibodies was also demonstrated. Our results suggest that pregnancy and platelet transfusion are the main risk factors for the prevalence of anti-HLA antibodies in haploid allograft candidates, providing evidence for guiding the evaluation of anti-HLA antibodies and helping donor selection for HLA-mismatched transplant candidates., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To quantitatively evaluate the association between mild cognitive impairment and all-cause mortality. Methods: The research papers of the association between cognitive impairment and all-cause mortality in the elderly in the databases of PubMed, EMBASE, Wang Fang data and CNKI published as of August 1, 2021 were comprehensively retrieved. Software R 4.02 was used for Meta-analysis. Results: A total of 9 research papers were included, involving 48 709 patients. The quality of included papers was high. The results of Meta-analysis showed that the association between mild cognitive impairment and the increased risk of all-cause mortality was statistically significant. Compared with the normal cognitive population, the risk of mortality in the elderly with mild cognitive impairment increased by 39% ( HR =1.39, 95% CI : 1.18-1.63). Conclusions: The current research evidence showed that mild cognitive impairment assessed by MMSE screening scale can be used as an independent predictor of the increased risk of all-cause mortality in the elderly population in China. However, due to the limitation of the number of included studies and sample size, the conclusions need to be supported by more evidence studies.

Objective: Yang-deficiency constitution (YADC) is a common unbalanced constitution that predisposes individuals to certain diseases. However, not all people with YADC manifest develop diseases. This calls for delineation of the underlying molecular mechanisms. Previous studies suggested that the gut microbiota and gene differential expression should be considered., Methods: In the present study, we compared profiles of gut microbiota between four healthy YADC individuals and those of five healthy balanced constitution (BC) counterparts, based on 16S rRNA gene sequence analysis. Furthermore, YADC relevant genes identified by comparing 62 healthy YADC and 58 healthy BC individuals in total to perform intersection analysis, functional clustering and pathway enrichment analyses., Results: The levels of harmful gut microbiota (Prevotellaceae, LDA score > 4.0, P = 0.0141) and beneficial gut microbiota (Ruminococcaceae, LDA score > 4.0, P = 0.0025, Faecalibacterium, LDA score > 4.0, P = 0.0484) were both elevated in healthy YADC individuals. Also, we found that the specific metabolic pathway with 2, 6-Dichloro-p-hydroquinone 1, 2-Dioxygenase (PcpA) as the core in gut microbiota and the glutathione transferase activity has been enriched by YADC relevant genes in healthy YADC individuals were both responsible for the detoxification of halogenated aromatic hydrocarbon substances., Conclusions: Both beneficial and harmful factors had been detected in healthy YADC individuals, functionally, they may have triggered homeostasis to maintain the health of individuals with YADC. The homeostasis may be maintained by beneficial and harmful factors from gut flora and genes. Future studies are expected to focus on halogenated aromatic hydrocarbons and their detoxification processes.

Long noncoding RNAs (lncRNAs) have been reported to exert important roles in tumors, including clear cell renal cell carcinoma (ccRCC). PVT1 is an important oncogenic lncRNA which has critical effects on onset and development of various cancers, however, the underlying mechanism of PVT1 functioning in ccRCC remains largely unknown. VHL deficiency-induced HIF2α accumulation is one of the major factors for ccRCC. Here, we identified the potential molecular mechanism of PVT1 in promoting ccRCC development by stabilizing HIF2α. PVT1 was significantly upregulated in ccRCC tissues and high PVT1 expression was associated with poor prognosis of ccRCC patients. Both gain-of-function and loss-of function experiments revealed that PVT1 enhanced ccRCC cells proliferation, migration, and invasion and induced tumor angiogenesis in vitro and in vivo. Mechanistically, PVT1 interacted with HIF2α protein and enhanced its stability by protecting it from ubiquitination-dependent degradation, thereby exerting its biological significance. Meanwhile, HIF2α bound to the enhancer of PVT1 to transactivate its expression. Furthermore, HIF2α specific inhibitor could repress PVT1 expression and its oncogenic functions. Therefore, our study demonstrates that the PVT1/ HIF2α positive feedback loop involves in tumorigenesis and progression of ccRCC, which may be exploited for anticancer therapy., (© 2021. The Author(s).)

Objective: To fit and predict the trend of COVID-19 epidemics in the United States (USA) and the United Kingdom (UK), and analyze the effect of vaccination. Methods: Based on the SEIR dynamic model, considering the presymptomatic infections, isolation measures, vaccine vaccination coverage, etc ., we developed a SEIR with vaccine inoculation, Presymptomatic infectious, unconfirmed infectious, hospital isolation and domiciliary isolation dynamics model. The publicly released incidence data of COVID-19 from November 6, 2020 to January 31, 2021 in USA and from November 23, 2020 to January 31, 2021 in UK were used to fit the model and the publicly released incidence data of COVID-19 from February 1, 2021 to April 1 were used to evaluate the predicting power of the model by software R 4.0.3 and predict changes in the daily new cases in the context of different vaccination coverage. Results: According to the cumulative confirmed cases, the fitting bias and the predicting bias of the SVEPIUHDR model for USA and UK were less than 5%, respectively. From the model prediction results, the cumulative cases after COVID-19 vaccination in USA in early April reached 31 864 970. If there had not had such vaccination, the cumulative cases of COVID-19 would have reached to 35 317 082, with a gap of more than 3.4 million cases. In UK, the cumulative cases of COVID-19 after the vaccination was estimated to be 4 195 538 in early April, compared with 4 268 786 cases if no COVID-19 vaccination had been provided, there would have heen a gap of more than 70 000 cases. Conclusion: SVEPIUHDR model shows a good prediction effect on the epidemic of COVID-19 in both USA and UK.

Osteosarcoma (OS) is a malignant disease with high morbidity and mortality rates in children and adolescents. Evidence has indicated that long non‑coding RNAs (lncRNAs) may serve important roles in human cancer progression, including OS. In the present study, the role of lnc‑double homeobox A pseudogene 8 (DUXAP8) in the development of OS was identified. The expression of lncRNA‑DUXAP8 was determined by reverse transcription‑quantitative polymerase chain reaction in OS tissues. Cell proliferation was evaluated using Cell Counting kit‑8 and colony formation assays, and Transwell assays were conducted to measure cell invasion. Cell migration was evaluated using a wound healing assay. The binding site between lnc‑DUXAP8 and miR‑635 RNAs was investigated using a luciferase reporter assay. The expression of lnc‑DUXAP8 was significantly upregulated in OS samples and OS cell lines compared with normal tissues. High expression of lncRNA DUXAP8 was associated with shorter overall survival times. Knockdown of lncRNA DUXAP8 inhibited proliferation, migration and invasion in OS cells. Notably, mechanistic investigation revealed that lncRNA DUXAP8 predominantly acted as a competing endogenous RNA in OS by regulating the miR‑635/topoisomerase alpha 2 (TOP2A) axis. lncRNA DUXAP8 is upregulated in OS, and lncRNA DUXAP8‑knockdown serves a vital antitumor role in OS cell progression through the miR‑635/TOP2A axis. The results of the present study suggested that lncRNA DUXAP8 may be a novel, promising biomarker for the diagnosis and prognosis of OS.

TcpC is a multifunctional virulence factor of uropathogenic E. coli (UPEC). Neutrophil extracellular trap formation (NETosis) is a crucial anti-infection mechanism of neutrophils. Here we show the influence of TcpC on NETosis and related mechanisms. We show NETosis in the context of a pyelonephritis mouse model induced by TcpC-secreting wild-type E. coli CFT073 (CFT073 wt ) and LPS-induced in vitro NETosis with CFT073 wt or recombinant TcpC (rTcpC)-treated neutrophils are inhibited. rTcpC enters neutrophils through caveolin-mediated endocytosis and inhibits LPS-induced production of ROS, proinflammatory cytokines and protein but not mRNA levels of peptidylarginine deiminase 4 (PAD4). rTcpC treatment enhances PAD4 ubiquitination and accumulation in proteasomes. Moreover, in vitro ubiquitination kit analyses show that TcpC is a PAD4-targetd E3 ubiquitin-ligase. These data suggest that TcpC inhibits NETosis primarily by serving as an E3 ligase that promotes degradation of PAD4. Our findings provide a novel mechanism underlying TcpC-mediated innate immune evasion.

Objective: To compare epicardial electrograms between the left atrium (LA) and pulmonary veins (PVs) dynamically at development of persistent atrial fibrillation(AF) in goats PVs. Methods: Ten female goats were instrumented with electrodes at the LA and left side PV. Sustained AF (＞24 h) was induced in the goat by rapid intermittent left atrial pacing for(9.5±2.3)days at a pacing interval of 20 ms for 1 s with a maximum output of 6.0 V, followed by a 2-s period without pacing. Characteristics of PVs and LA epicardial electrograms were analyzed in the development of AF. Results: With prolonged stimulation, the duration of AF was prolonged, complex fractionated atrial electrograms(CFAEs) in LA and was increased gradually, PVs had more CFAEs than LA all the time. When induced AF lasted for more than 24 h, CFAEs in PVs became sustained approximately (2.7%±3.6% vs 92.6%±6.4%, at onset of AF vs AF lasted for more than 24 h, P ＜0.05), and the ratio of CFAEs in PVs was more than that in LA (92.6%±6.4% vs 72.8%±5.3%, P ＜0.05). Conclusion: The epicardial CFAEs are in specific area, which increase along with electrical remodeling. The epicardial CFAEs may play an important role in the maintenance of AF in this model.

TcpC is a virulence factor of uropathogenic E. coli (UPEC). It was found that TIR domain of TcpC impedes TLR signaling by direct association with MyD88. It has been a long-standing question whether bacterial pathogens have evolved a mechanism to manipulate MyD88 degradation by ubiquitin-proteasome pathway. Here, we show that TcpC is a MyD88-targeted E3 ubiquitin ligase. Kidney macrophages from mice with pyelonephritis induced by TcpC-secreting UPEC showed significantly decreased MyD88 protein levels. Recombinant TcpC (rTcpC) dose-dependently inhibited protein but not mRNA levels of MyD88 in macrophages. Moreover, rTcpC significantly promoted MyD88 ubiquitination and accumulation in proteasomes in macrophages. Cys12 and Trp106 in TcpC are crucial amino acids in maintaining its E3 activity. Therefore, TcpC blocks TLR signaling pathway by degradation of MyD88 through ubiquitin-proteasome system. Our findings provide not only a novel biochemical mechanism underlying TcpC-medicated immune evasion, but also the first example that bacterial pathogens inhibit MyD88-mediated signaling pathway by virulence factors that function as E3 ubiquitin ligase., Competing Interests: The authors have declared that no competing interests exist.

Background: Before effective vaccines become widely available, sufficient understanding of the impacts of climate, human movement and non-pharmaceutical interventions on the transmissibility of COVID-19 is needed but still lacking., Methods: We collected by crowdsourcing a database of 11 003 COVID-19 cases from 305 cities outside Hubei Province from December 31, 2019 to April 27, 2020. We estimated the daily effective reproduction numbers ( R t ) of COVID-19 in 41 cities where the crowdsourced case data are comparable to the official surveillance data. The impacts of meteorological variables, human movement indices and nonpharmaceutical emergency responses on R t were evaluated with generalized estimation equation models., Findings: The median R t was 0•46 (IQR: 0•37-0•87) in the northern cities, higher than 0•20 (IQR: 0•09-0•52) in the southern cities ( p =0•004). A higher local transmissibility of COVID-19 was associated with a low temperature, a relative humidity near 70-75%, and higher intracity and intercity human movement. An increase in temperature from 0℃ to 20℃ would reduce R t by 30% (95 CI 10-46%). A further increase to 30℃ would result in another 17% (95% CI 5-27%) reduction. An increase in relative humidity from 40% to 75% would raise the transmissibility by 47% (95% CI 9-97%), but a further increase to 90% would reduce the transmissibility by 12% (95% CI 4-19%). The decrease in intracity human movement as a part of the highest-level emergency response in China reduced the transmissibility by 36% (95% CI 27-44%), compared to 5% (95% CI 1-9%) for restricting intercity transport. Other nonpharmaceutical interventions further reduced R t by 39% (95% CI 31-47%)., Interpretation: Climate can affect the transmission of COVID-19 where effective interventions are implemented. Restrictions on intracity human movement may be needed in places where other nonpharmaceutical interventions are unable to mitigate local transmission., Funding: China Mega-Project on Infectious Disease Prevention; U.S. National Institutes of Health and National Science Foundation., Competing Interests: We declare no competing interests., (© 2020 The Author(s). Published by Elsevier Ltd.)

Aim: Exploring the mechanisms of the combination therapy using VEGFR-TKI and immune checkpoint inhibitors might be useful to control the development of osteosarcoma. Materials & methods: The expression of PD-L1 and STAT3 in osteosarcoma were determined with western blot. Proliferation, migration and invasion were determined with CCK-8 and Transwell assays. Lung metastases, tumor growth, survival and immune cell populations were performed in tumor-bearing mice. Results: Sunitinib reduced the expression of PD-L1 by inhibiting the activation of STAT3 and suppressed the migration and invasion in osteosarcoma cells. Combination therapy reduced lung metastases, tumor growth, improved survival and reverse tumor microenvironment in tumor-bearing mice. Conclusion: Sunitinib inhibits PD-L1 expression by targeting STAT3 and remodels the immune system in tumor-bearing mice.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

In this paper, the development of a simple dilute-and-shoot method for quantifying urinary creatinine by CE-ESI-MS was described. The creatinine analysis time was about 7 min/sample by conventional single injection (SI) method and can be significantly reduced to less than 2 min/sample with multi-segment injection (MSI). In addition, the standard addition analysis of 5-hydroxyindole-3-acetic acid (5-HIAA) and creatinine normalization was performed within one run by the MSI technique, and the total analysis time was 14-min faster compared to the SI method for analyzing the same set of samples. The uses of isotopic and non-isotopic internal standards (ISs) were compared. Creatinine-(methyl- 13 C) and 5-hydroxyindole-4,6,7-D 3 -3-acetic-D 2 acid (5-HIAA-D 5 ) used as isotopic ISs can provide both accurate and precise results. In contrast, 1,5,5-trimethylhydantoin (1,5,5-TH) used as the non-isotopic IS for creatinine may cause a bias of over 13% in SI method and even worse when the MSI technique was used. Another compound, 2-methyl-3-indoleacetic acid (2-MIAA), was determined not suitable for MSI analysis of 5-HIAA due to endogenous interferences despite its acceptable performance in conventional methods of analysis., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this work, the two-dimensional profile of the light transmission through a prism-like metallic film sample of Au was measured at a wavelength of 632.8 nm in the visible intraband transition region to verify that, beyond the possible mechanisms of overcoming the diffraction limit, a strongly nonuniform optical absorption path length of the light traveling in the metal could induce a lensing effect, thereby narrowing the image of an object. A set of prism-like Au samples with different angles was prepared and experimentally investigated. Due to the nonuniform paths of the light traveling in the Au samples, lens-effect-like phenomena were clearly observed that reduced the imaged size of the beam spot with decreasing light intensity. The experimental measurements presented in the work may provide new insight to better understand the light propagation behavior at a metal/dielectric interface.

The gray level run length matrix (GLRLM) whose entries are statistics recording distribution and relationship of images pixels is a widely used method for extracting statistical features for medical images, e.g., magnetic resonance (MR) images. Recently these features are usually employed in some artificial neural networks to identify and distinguish texture patterns. But GLRLM construction and features extraction are tedious and computationally intensive while the images are too big with high resolution, or there are too many small or intermediate Regions of Interest (ROI) to process in a single image, which makes the preprocess a time consuming stage. Hence, it is of great importance to accelerate the procedure which is nowadays possible with the rapid development of massively parallel Graphics Processing Unit, i.e. the GPU computing technology. In this article, we propose a new paradigm based on mature parallel primitives for generating GLRLMs and extracting multiple features for many ROIs simultaneously in a single image. Experiments show that such a paradigm is easy to implement and offers an acceleration over 5 fold increase in speed than an optimized serial counterpart.

Objective: To determine the associations between the family history of rheumatic diseases and clinical features in patients with rheumatoid arthritis (RA)., Methods: In total, eight hundred and ninety patients with RA were enrolled. The demographic and clinical data were collected, including gender, age, height, body weight, age of disease onset, history of smoking and drinking, family history of rheumatic diseases, clinical and laboratory features, pain and global visual analogue scale (VAS), and multi-dimensional health assessment questionnaire (MDHAQ). Finally, 803 patients were completed the dataset and were included in the study., Results: In this cohort, the male/female ratio was 1:3.5, and the age of onset was (45.09±14.50) years. A total of 123 (15.32%) patients were accompanied with family history of rheumatic diseases, including RA, spondyloarthritis, Sjögren's syndrome, systemic lupus erythematosus and systemic sclerosis. The percentages of first degree, second degree and both first and second degree relatives were 91 (73.98%), 22 (17.89%), and 10 (8.13%) respectively. The most common disease was RA (70.73%), followed by other rheumatic diseases (21.95%), and RA combined with other rheumatic diseases (7.32%). The clinical and laboratory characteristics were compared between the patients with and without family history. The onset-age of the subjects was significantly different between those with and without family history of rheumatic diseases (39.97 ±13.68 vs. 46.01±14.46; P<0.01), which meant that the onset-age in patients with family history was 6.04 years earlier than that in patients without family history. The patients with family history had higher positive rate of rheumatoid factor (RF) compared with those without family history (78.48% vs. 66.67%, P<0.05). By adjusting with gender, body mass index (BMI), smoking and alcohol drinking, anti-cyclic citrullinated peptide (CCP) antibody and RF level, the age at disease onset in the patients with family history was 4.54 years earlier than that in the patients without family history (β=-4.54; 95%CI:-8.70, -0.38; P<0.05). Further hierarchical regression analysis showed that, the age at onset of the RA patients with family history was 10.02 years earlier than that without family history among the smoking patients (β= -10.02; 95%CI:-17.60, -2.43; P=0.01), while the age at onset of the RA patients with family history was 3.27 years earlier than that without family history among the never smoking patients (β=-3.27; 95%CI:-8.37, 1.82; P=0.21)., Conclusion: The family history of rheumatic diseases is a risk factor for early onset of RA, and may interact with smoking.

Thermodynamic properties of alkali and alkaline earth metal amides are critical for their performance in hydrogen storage as well as catalytic ammonia synthesis. In this work, the ammonia equilibrium concentrations of LiNH 2 , KNH 2 and Ba(NH 2 ) 2 at ca.10 bar of hydrogen pressure and different temperatures were measured by using a high-pressure gas-solid reaction system equipped with a conductivity meter. Hydrogenation of KNH 2 gives the highest ammonia equilibrium concentration, followed by Ba(NH 2 ) 2 and LiNH 2 . Based on these data, the entropy and enthalpy changes of the reaction of ANH 2 +H 2 →AH+NH 3 (A=Li, K, and Ba) were obtained from the van't Hoff equation. These thermodynamic parameters provide important information on the understanding of metal amides in catalytic ammonia synthesis reaction., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Normal bone mass is maintained by balanced bone formation and resorption. Myosin X (Myo10), an unconventional "myosin tail homology 4-band 4.1, ezrin, radixin, moesin" (MyTH4-FERM) domain containing myosin, is implicated in regulating osteoclast (OC) adhesion, podosome positioning, and differentiation in vitro. However, evidence is lacking for Myo10 in vivo function. Here we show that mice with Myo10 loss of function, Myo10 m/m , exhibit osteoporotic deficits, which are likely due to the increased OC genesis and bone resorption because bone formation is unchanged. Similar deficits are detected in OC-selective Myo10 conditional knockout (cko) mice, indicating a cell autonomous function of Myo10. Further mechanistic studies suggest that Unc-5 Netrin receptor B (Unc5b) protein levels, in particular its cell surface level, are higher in the mutant OCs, but lower in RAW264.7 cells or HEK293 cells expressing Myo10. Suppressing Unc5b expression in bone marrow macrophages (BMMs) from Myo10 m/m mice by infection with lentivirus of Unc5b shRNA markedly impaired RANKL-induced OC genesis. Netrin-1, a ligand of Unc5b, increased RANKL-induced OC formation in BMMs from both wild-type and Myo10 m/m mice. Taken together, these results suggest that Myo10 plays a negative role in OC formation, likely by inhibiting Unc5b cell-surface targeting, and suppressing Netrin-1 promoted OC genesis. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Liver cancer, which is the second leading cause of tumor-associated mortality, is of great concern worldwide due to its resistance to chemotherapeutic drugs. Transcatheter arterial chemoembolization (TACE) has previously been used as a treatment for unresectable liver tumors in China; however, the response to TACE treatment differs between patients. It has been reported that hepatitis B virus (HBV)-as sociated tumors are less sensitive to TACE treatment compared with non-HBV-associated liver cancer. Previous studies have demonstrated that exosomes serve a crucial role in hepatic carcinoma chemoresistance. We therefore hypothesized that HBV may modulate chemosensitivity via exosomes. The aim of the present study was to investigate how exosomes affect chemoresistance by assessing their role in chaperone-mediated autophagy (CMA)-dependent chemoresistance in HBV-associated liver cancer. Iconography data from HBV-positive and HBV-negative patients with hepatic carcinoma receiving TACE treatment were assessed, and it was revealed that the tumor volume was decreased in the patients with non-HBV-associated liver cancer compared with that in the patients with HBV-associated tumors following TACE therapy. Furthermore, it was revealed that exosomes from HBV-infected liver cancer cells were able to downregulate cell apoptosis when treated with oxaliplatin compared with exosomes from normal HepG2 cells. Furthermore, the results demonstrated that HBV-associated exosomes modulate cell death via activating the CMA pathway, and its key molecule, lysosome-associated membrane protein (Lamp2a), was also upregulated. Lamp2a-knockdown was also found to reverse anti-apoptotic effects in liver cancer. Taken together, the results of the present study suggest that chemoresistance in patients with HBV-associated hepatic tumors may be mediated by exosomes, and thus may provide a basis for the development of novel treatment strategies for chemoresistant liver cancer.

To understand how would the maize production in northeast China adapt to climate change, we adopted two strategies, inclduing using stress resistant varieties and delayed sowing date, combined with the daily meteorological data of RCP4.5 scenario and RCP8.5 scenario from 2010 to 2099 simulated by regional climatic model, to analyze the changes of climatic potential productivity of maize under different climate change scenarios. The results showed that in 2010-2099, the spatial characteristics of climatic potential productivity of maize in northeast China decreased from southeast to northwest. The climatic potential productivity of maize under RCP4.5 scenario was higher than that under RCP8.5 scenario, while years with the lowest values under RCP8.5 scenario was more than that under RCP4.5 scenario. The climatic potential productivity for stress resistant varieties of maize was higher than the original varieties. Under RCP4.5 scenario, the heat resistant variety had higher productivity. Under RCP8.5 scenario, the drought resistant variety performed better. The variety with both heat and drought resistance characters achieved the highest productivity under both scenarios. Under RCP4.5 scenario, yield increased with postponed sowing, with 30-40 days delay achieving the highest yield. Under RCP8.5 scenario, yield reduction occurred in some areas. Such a result indicated that the appropriate delay in sowing is conducive to improve the maize productivity, with differences among regions.

Iguratimod (IGU) is a novel disease-modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA). Like other DMARDs, IGU exhibited significant differences in effectiveness and safety., Aim: The aim of this study was to identify genetic predictorsof efficacyand toxicity of IGU in patients with RA., Materials & Methods: Seven SNPs from IGU-metabolizing genes were genotyped in 272 IGU-treated patients with RA. Results: ABCG2 rs2231142 A allele conferred a higher response to IGU, while NAT2 rs1495742 G carriersconferred a lower response to IGU. CYP2C19*2 rs4244285 A carriers had higher risk for IGU-induced toxicity compared to the GG carriers., Conclusion: Our study suggests that the polymorphisms of ABCG2 (rs2231142), NAT2 (rs1495741)and CYP2C19*2 (rs4244285) may help to predict thetherapeutic effectiveness and toxicity of IGU in patients with RA.

Noninvasive and specific visualization of lysosomes by fluorescence technology is critical for studying lysosomal trafficking in health and disease and for evaluating new cancer therapeutics that target tumor cell lysosomes. To date, there are two basic types of lysosomal probes whose lysosomal localization correlates with lysosomal acidity and endocytosis pathway, respectively. However, the former may suffer from pH-sensitive lysosomal localization and alkalization-induced lysosomal enzyme inactivation, and the latter need long incubation time to penetrate cell membrane due to the energy-dependency of endocytosis process. In this work, a new class of two-photon fluorescent dyes, termed amino-Si-rhodamines (ASiRs), were developed, which possess the intrinsic lysosome-targeted ability that is independent of lysosomal acidity and endocytosis pathway. As a result, ASiRs show not only the stable lysosomal localization against lysosomal pH changes and negligible interference to lysosomal function, but also excellent cell-membrane-permeability due to the energy-independent passive diffusion pathway. These merits, coupled with their excellent two-photon photophysical properties, long-term retention ability in lysosomes, and negligible cytotoxicity, make ASiRs very suitable for real-time and long-term tracking of lysosomes in living cells or tissues without interference to normal cellular processes. Moreover, the easy functionalization via amino linker further allows the construction of various fluorescent probes for biological targets of interest based on ASiR skeleton, as indicated by the cancer-targeted fluorescent probe ASiR6 as well as a fluorescent peroxynitrite probe ASiR-P., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Recent evidence from genetic, cell biology, and animal model studies has suggested a pivotal role of autophagy in mediating systemic lupus erythematosus (SLE). However, the genetic basis has not yet been thoroughly examined. Therefore, the aim of the present study was to identify additional susceptibility variants in autophagy-related genes along with their functional significance., Methods: First, we performed a gene family-based genetic association analysis in SLE patients with the use of ImmunoChip arrays, and then we selected the most strongly associated polymorphisms for replication in additional cohorts. To identify regulatory clues, we analyzed publicly available blood expression quantitative trait locus data and Encyclopedia of DNA Elements data on transcription factor binding sites and cell type-specific differential expression. Functional effects were tested by luciferase reporter assays, electrophoretic mobility shift assays, and differential gene expression assays., Results: In 14,474 samples, we observed that the rare Chinese variant rs933717T was associated with susceptibility to SLE (0.11% in cases versus 0.87% in controls; P = 2.36 × 10 -10 , odds ratio 0.13). The rs933717 risk allele C correlated with increased MAP1LC3B expression; increased MAP1LC3B messenger RNA was observed in SLE patients and in lupus-prone mice. In reporter gene constructs, the risk allele increased luciferase activity up to 2.7-3.8-fold in both HEK 293T and Jurkat cell lines, and the binding of HEK 293T and Jurkat cell nuclear extracts to the risk allele was also increased., Conclusion: We observed a likely genetic association between light chain 3B, a widely used marker for autophagy, and susceptibility to SLE., (© 2017, American College of Rheumatology.)

Background: Interleukin (IL)-37, also called IL1F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the role of IL1F7 gene polymorphism in RA susceptibility in a large cohort of patients., Methods: Five selected single-nucleotide polymorphisms in IL1F7 genes (rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270) were genotyped by TaqMan Allelic Discrimination in Northern Chinese Han population. The allele and the genotype were compared between patients with RA and healthy controls. Association analyses were performed on the entire data set and on different RA subsets based on the status of the anti-cyclic citrullinated peptide antibody and the rheumatoid factor by logistic regression, adjusting for age and gender., Results: Trend associations were detected between rs2723186, rs4241122, rs4392270, and RA in Stage I (160 patients with RA; 252 healthy controls). Further validation in Stage II comprised 730 unrelated patients with RA (mean age: 54.9 ± 12.6 years; 81.6% females) and 778 unrelated healthy individuals (mean age: 53.5 ± 15.7 years; 79.5% females). No significant differences in the distributions of alleles and genotypes were observed between the case and control groups in both the entire set and the different RA subsets. Disease activity and age of RA onset were also not associated with genotype distributions., Conclusion: IL1F7 gene polymorphism does not significantly influence RA susceptibility in the Northern Chinese Han population.

Alzheimer's disease (AD) is characterized by deposits of amyloid-β protein (Aβ) in brain which become foci of inflammation. Neurons are destroyed by this inflammatory process, leading to the cognitive deficits which define AD clinical onset. Epidemiological studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) can ameliorate this destructive process if they are started well before clinical signs develop. Biomarker studies indicate that the disease process starts at least a decade before cognitive deficits appear. This pre-clinical onset explains the NSAID effect. It also opens a window of opportunity for preventive treatment that can be met with a simple diagnostic test. Salivary levels of Aβ42 may fulfill that need. They can be measured by a simple ELISA test we have developed using commercially available reagents. By this ELISA test, normal controls, who are not at risk for AD, have levels of Aβ42 close to 20 pg/ml. AD cases, as well as high level controls, secrete levels in the range of 40-85 pg/ml. Widespread application of this test to detect high level controls, followed by NSAID consumption, could substantially reduce the prevalence of AD.

Objectives: Many studies have suggested the effectiveness of single control measures in the containment and mitigation of pandemic influenza A (H1N1) 2009. The effects of combined interventions by multiple control measures in reducing the impact of an influenza A (H1N1) 2009 outbreak in a closed physical training camp in Beijing, China were evaluated., Methods: Oseltamivir was prescribed for the treatment of confirmed cases and possible cases and as prophylaxis for all other participants in this training camp. Public health control measures were applied simultaneously, including the isolation of patients and possible cases, personal protection and hygiene, and social distancing measures. Symptom surveillance of all participants was initiated, and the actual attack rate was calculated. For comparison, the theoretical attack rate for this outbreak was projected using the Newton-Raphson numerical method., Results: A total of 3256 persons were present at the physical training camp. During the outbreak, 405 (68.3%) possible cases and 26 (4.4%) confirmed cases were reported before the intervention and completed oseltamivir treatment; 162 (27.3%) possible cases were reported after the intervention and received part treatment and part prophylaxis. The other 2663 participants completed oseltamivir prophylaxis. Of the possible cases, 181 with fever ≥38.5°C were isolated. The actual attack rate for this outbreak of pandemic influenza A (H1N1) 2009 was 18.2%, which is much lower than the theoretical attack rate of 80% projected., Conclusions: Combined interventions of large-scale antiviral ring prophylaxis and treatment and public health control measures could be applied to reduce the magnitude of influenza A (H1N1) 2009 outbreaks in closed settings., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lysosomes have recently been regarded as the attractive pharmacological targets for selectively killing of cancer cells via lysosomal cell death (LCD) pathway that is closely associated with reactive oxygen species (ROS). However, the details on the ROS-induced LCD of cancer cells are still poorly understood, partially due to the absence of a lysosome-targetable, robust, and biocompatible imaging tool for ROS. In this work, we brought forward a Si-rhodamine-based fluorescent probe, named PSiR, which could selectively and sensitively image the pathologically more relavent highly reactive oxygen species (hROS: HClO, HO, and ONOO - ) in lysosomes of cancer cells. Compared with many of the existing hROS fluorescent probes, its superiorities are mainly embodied in the high stability against autoxidation and photoxidation, near-infrared exitation and emission, fast fluorescence off-on response, and specific lysosomal localization. Its practicality has been demonstrated by the real-time imaging of hROS generation in lysosomes of human non-small-cell lung cancer cells stimulated by anticancer drug β-lapachone. Moreover, the probe was sensitive enough for basal hROS in cancer cells, allowing its further imaging applications to discriminate not only cancer cells from normal cells, but also tumors from healthy tissues. Overall, our results strongly indicated that PSiR is a very promising imaging tool for the studies of ROS-related LCD of cancer cells, screening of new anticancer drugs, and early diagnosis of cancers., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To prospectively clarify the predictive value of high-sensitivity C-reactive protein (hsCRP) on the risk for recurrent atrial arrhythmia in paroxysmal atrial fibrillation (PAF) population who accepted radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF)., Methods: There were 57 consecutive patients (53.32±9.98 years; 42 males) with drug-refractory PAF who underwent RFCA were included. Plasma levels of hsCRP and high-sensitivity cardiac troponin T (hs-cTnT) were measured on admission and first five days after RFCA. Twenty-five patients (43.86%) had early recurrence of atrial fibrillation (ERAF)., Results: Compared to patients without ERAF (no-AF-recurrence group), baseline hsCRP levels had no significant difference in patients with ERAF (AF recurrence group). There were no significant differences in the peak hsCRP and hs-cTnT levels between no-AF-recurrence group and AF recurrence group. However, change of hsCRP level was significantly correlated with change in hs-cTnT level in patients undergoing RFCA ( r =0.268, P =0.044)., Conclusions: Among those AF patients undergoing ablation, change of hsCRP level could be for the myocardial injury related to RFCA procedure, which may not be a risk factor to predict ERAF. The variety of hsCRP level may be related to the degree of myocardial injury induced by RFCA.

Aim: To investigate the mechanism of chaperone-mediated autophagy (CMA)-induced resistance to irradiation-triggered apoptosis through regulation of the p53 protein in hepatocellular carcinoma (HCC)., Methods: Firstly, we detected expression of lysosome-associated membrane protein 2a (Lamp-2a), which is the key protein of CMA, by western blot in HepG2 and SMMC7721 cells after irradiation. We further used shRNA Lamp-2a HCC cells to verify the radioresistance induced by CMA. Next, we detected the HMGB1 and p53 expression after irradiation by western blot, and we further used RNA interference and ethyl pyruvate (EP), as a HMGB1 inhibitor, to observe changes of p53 expression. Finally, an immunoprecipitation assay was conducted to explore the interaction between Lamp-2a and HMGB1, and the data were analyzed., Results: We found the expression of Lamp-2a was increased on irradiation while apoptosis decreased in HepG2 and SMMC7721 cells. The apoptosis was increased markedly in the shRNA Lamp-2a HepG2 and SMMC7721 cells as detected by western blot and colony formation assay. Next, we found p53 expression was gradually reduced on irradiation but obviously increased in shRNA Lamp-2a cells. Furthermore, p53 increased the cell apoptosis on irradiation in Hep3B (p53-/-) cells. Finally, p53 levels were regulated by HMGB1 as measured through RNA interference and the EP treatment. HMGB1 was able to combine with Lamp-2a as seen by immunoprecipitation assay and was degraded via the CMA pathway. The decreased HMGB1 inhibited p53 expression induced by irradiation and further reduced the apoptosis in HCC cells., Conclusion: CMA pathway activation appears to down-regulate the susceptibility of HCC to irradiation by degrading HMGB1 with further impact on p53 expression. These findings have clinical relevance for radiotherapy of HCC., Competing Interests: Conflict-of-interest statement: All authors in this paper declared that there is no conflicts of interest to this work.