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Migraine is a common clinical neurological disorder that adversely affects humans and society. The relationship between copper intake and migraine has been less studied and controversial. The purpose of this study was to determine the relationship between copper intake and migraine and to guide dietary interventions. The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2004, involving a total of 12,724 participants. The relationship between copper intake and migraine was examined using weighted multivariate logistic regression models, and smooth-fit curves were plotted to explore the relationship. After non-linear relationships were found, recursive algorithms and two-stage linear regression models were used to calculate inflection points. Stratified analyses were also performed to explore population differences. In the model corrected for all covariates, the OR (95% CI) of copper intake with migraine was 1.19 (0.97, 1.46), which was not statistically significant. However, the results of the linear trend test suggested that their relationship might be non-linear. Smooth-fit curves confirmed the non-linear relationship between copper intake and migraine, and an inflection point (0.98 mg/day) was identified. There was no statistical significance before the inflection point, but after the inflection point, copper intake was positively associated with migraine attacks. Stratified analyses showed that this non-linear relationship persisted in females, people under 45 years old, and people with BMI less than 30. In this large cross-sectional study, we found a non-linear correlation between copper intake and migraine. [ABSTRACT FROM AUTHOR]

Background: The impact of gestational diabetes mellitus (GDM) on incident dementia is unknown. Our aim was to evaluate the relationship between GDM and all‐cause dementia and the mediating effects of chronic diseases on this relationship. Methods: This prospective cohort study included women from the UK Biobank who were grouped based on GDM history. Multivariate Cox proportional hazard models were used to explore the associations between GDM and dementia. We further analysed the mediating effects of chronic diseases on this relationship and the interactions of covariates. Results: A total of 1292 women with and 204,171 women without a history of GDM were included. During a median follow‐up period of 45 years after first birth, 2921 women were diagnosed with dementia. Women with a GDM history had a 67% increased risk of incident dementia (hazard ratio 1.67, 95% confidence interval: 1.03–2.69) compared with those without a GDM history. According to mediation analyses, type 2 diabetes, coronary heart disease, chronic kidney disease and comorbidities (diagnosed with any two of the three diseases) explained 34.5%, 8.4%, 5.2% and 18.8% of the mediating effect on the relationship. Subgroup analyses revealed that physical activity modified the association between GDM history and dementia (p for interaction = 0.030). Among physically inactive women, GDM was significantly associated with incident dementia; however, this association was not observed among physically active women. Conclusions: A history of GDM was associated with a greater risk of incident dementia. Type 2 diabetes partially mediated this relationship. Strategies for dementia prevention might be considered for women with a history of GDM. [ABSTRACT FROM AUTHOR]

Background: Galangin, a flavonoid compound, is derived from Alpinia officinarum Hance. Previous studies have shown that galangin can inhibit the proliferation of hepatocellular carcinoma (HCC), but its mechanism is still unclear. This study aims to investigate the potential targets and molecular mechanisms of galangin on HCC through network pharmacology, bioinformatics, molecular docking, and experimental in vitro validation. Methods: In this study, network pharmacology was used to investigate the targets and mechanisms of galangin in the treatment of HCC. AutoDockTools software was used to simulate and calculate the binding of galangin to its core targets. GO and KEGG enrichment analyses were conducted in the DAVID database to explore the main biological functions and signaling pathways impacted by galangin intervention. In addition, bioinformatics was applied to examine the correlation between the differential expressions of the anti-HCC core targets of galangin and the survival of patients with HCC. Finally, the findings obtained from network pharmacology and bioinformatics were verified in cell experiments. Results: A total of 67 overlapping target genes of galangin and HCC were identified. Through the analysis of the protein-protein interaction (PPI) network, 10 hub genes with the highest degree of freedom were identified, including SRC, ESR1, MMP9, CDK4, CCNB1, MMP2, CDK2, CDK1, CHK1, and PLK1. These genes were found to be closely related to the degradation of the extracellular matrix, signal transduction, and the cell cycle. GO and KEGG enrichment analyses revealed that galangin exerts an anti-HCC role by affecting various signaling pathways, including the cell cycle, pathways in cancer, and the PI3K-Akt signaling pathway. The results of molecular docking indicated a significant interaction between galangin and CCNB1, CDK4, CDK1, and PLK1. Bioinformatics analysis revealed that CCNB1, CDK4, CDK1, and PLK1 were upregulated in the liver of patients with HCC at both the mRNA and protein levels. Flow cytometry analysis showed that galangin induced G0/G1 phase arrest and cell apoptosis in HepG2 and Huh7 cells. Additionally, galangin suppressed the expression of key proteins and mRNAs involved in the cell cycle pathway. Conclusions: These results suggest that galangin inhibits the growth of HCC cells by arresting the cell cycle at the G0/G1 phase. [ABSTRACT FROM AUTHOR]

Objective: To establish the quality standard for the compatibility solution of Alpinia officinarum Pogostemon cablin. Methods: Thin layer chromatography was used for qualitative identification for the two indicator components of galangin and pogostone in the compatibility solution of Alpinia officinarum Pogostemon cablin: the mixture of anpetroleum ether ethyl acetate (5:3), (5:1)as the developing solvent system on silica gel G thin layer plate, high efficiency silica gel G thin layer plate; High performance liquid chromatography was used to determine the content of galangin and pogostone: C18 chromatographic column (4.6 mmx250 mm, 5 μm)was used, and the mobile phase was methanol (A) 0.2% phosphoric acid (B), with a detection wavelength of 310 nm and gradient elution. Results:For the two indicator components of galangin and pogostone in the compatibility solution of Alpinia officinarum Pogostemon cablin, the fluorescent spots were clear, without interference from negative controls; Mass concentration was between 10.00-1 000.00 μg/mL and 10.00-640.00 μg/mL, and the linear relationship coefficients with peak area within the range of were R²= 0.999 0, R²= 0.999 9, respectively; The precision RSD was 0.63% and 0.56%, the stability RSD was 1.82% and 0.24%, and the repeatability RSD was 1.30% and 0.89%; The average recovery rates (n=9) were 103.19% (RSD=0.93%) and 100.87% (RSD=0.4%), respectively; The content of these two indicator components should not be less than 233.71 μg/mL and 61.48 μg/mL. Conclusion: A research method has been established for the quality standard of Alpinia officinarum Pogostemon cablin compatibility solution. The precision, accuracy, stability, and repeatability of this method meet the requirements. [ABSTRACT FROM AUTHOR]

AHP-3a, a triple-helix acidic polysaccharide isolated from Alpinia officinarum Hance, was evaluated for its anticancer and antioxidant activities. The physicochemical properties and structure of AHP-3a were investigated through gel permeation chromatography, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. The weight-average molecular weight of AHP-3a was 484 kDa, with the molar percentages of GalA, Gal, Ara, Xyl, Rha, Glc, GlcA, and Fuc being 35.4%, 21.4%, 16.9%, 11.8%, 8.9%, 3.1%, 2.0%, and 0.5%, respectively. Based on the results of the monosaccharide composition analysis, methylation analysis, and NMR spectroscopy, the main chain of AHP-3a was presumed to consist of (1→4)-α-D-GalpA and (1→2)-α-L-Rhap residues, which is a pectic polysaccharide with homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) structural domains containing side chains. In addition, the results of the antioxidant activity assay revealed that the ability of AHP-3a to scavenge DPPH, ABTS, and OH free radicals increased with an increase in its concentration. Moreover, according to the results from the EdU, wound healing, and Transwell assays, AHP-3a can control the proliferation, migration, and invasion of HepG2 and Huh7 hepatocellular carcinoma cells without causing any damage to healthy cells. Thus, AHP-3a may be a natural antioxidant and anticancer component. [ABSTRACT FROM AUTHOR]

Peptide toxins found in sea anemones venom have diverse properties that make them important research subjects in the fields of pharmacology, neuroscience and biotechnology. This study used high-throughput sequencing technology to systematically analyze the venom components of the tentacles, column, and mesenterial filaments of sea anemone Heteractis crispa, revealing the diversity and complexity of sea anemone toxins in different tissues. A total of 1049 transcripts were identified and categorized into 60 families, of which 91.0% were proteins and 9.0% were peptides. Of those 1049 transcripts, 416, 291, and 307 putative proteins and peptide precursors were identified from tentacles, column, and mesenterial filaments respectively, while 428 were identified when the datasets were combined. Of these putative toxin sequences, 42 were detected in all three tissues, including 33 proteins and 9 peptides, with the majority of peptides being ShKT domain, β-defensin, and Kunitz-type. In addition, this study applied bioinformatics approaches to predict the family classification, 3D structures, and functional annotation of these representative peptides, as well as the evolutionary relationships between peptides, laying the foundation for the next step of peptide pharmacological activity research. [ABSTRACT FROM AUTHOR]

Sea anemone venom, abundant in protein and peptide toxins, serves primarily for predatory defense and competition. This study delves into the insulin-like peptides (ILPs) present in sea anemones, particularly focusing on their role in potentially inducing hypoglycemic shock in prey. We identified five distinct ILPs in Exaiptasia diaphana, exhibiting varied sequences. Among these, ILP-Ap04 was successfully synthesized using solid phase peptide synthesis (SPPS) to evaluate its hypoglycemic activity. When tested in zebrafish, ILP-Ap04 significantly reduced blood glucose levels in a model of diabetes induced by streptozotocin (STZ) and glucose, concurrently affecting the normal locomotor behavior of zebrafish larvae. Furthermore, molecular docking studies revealed ILP-Ap04's unique interaction with the human insulin receptor, characterized by a detailed hydrogen-bonding network, which supports a unique mechanism for its hypoglycemic effects. Our findings suggest that sea anemones have evolved sophisticated strategies to activate insulin receptors in vertebrates, providing innovative insights into the design of novel drugs for the treatment of diabetes. [ABSTRACT FROM AUTHOR]

Bacterial biofilm infection is a serious obstacle to clinical therapeutics. Photodynamic therapy (PDT) plays a dynamic role in combating biofilm infection by utilizing reactive oxygen species (ROS)-induced bacterial oxidation injury, showing advantages of mild side effects, spatiotemporal controllability and little drug resistance. However, superfluous glutathione (GSH) present in biofilm and bacteria corporately reduces ROS levels and seriously affects PDT efficiency. Herein, we have constructed a Cu2+-infused porphyrin metal–organic framework (MOF@Cu2+) for the enhanced photodynamic combating of biofilm infection by the maximum depletion of GSH. Our results show that the released Cu2+ from porphyrin MOF@Cu2+ could not only oxidize GSH in biofilm but also consume GSH leaked from ROS-destroyed bacteria, thus greatly weakening the antioxidant system in biofilm and bacteria and dramatically improving the ROS levels. As expected, our dual-enhanced PDT nanoplatform exhibits a strong biofilm eradication ability both in vitro and in an in vivo biofilm-infected mouse model. In addition, Cu2+ can promote biofilm-infected wound closing by provoking cell immigration, collagen sediment and angiogenesis. Besides, no apparent toxicity was detected after treatment with MOF@Cu2+. Overall, our design offers a new paradigm for photodynamic combating biofilm infection. [ABSTRACT FROM AUTHOR]

In recent years, remote sensing analysis has gained significant attention in visual analysis applications, particularly in segmenting and recognizing remote sensing images. However, the existing research has predominantly focused on single-period RGB image analysis, thus overlooking the complexities of remote sensing image capture, especially in highly vegetated land parcels. In this paper, we provide a large-scale vegetation remote sensing (VRS) dataset and introduce the VRS-Seg task for multi-modal and multi-temporal vegetation segmentation. The VRS dataset incorporates diverse modalities and temporal variations, and its annotations are organized using the Vegetation Knowledge Graph (VKG), thereby providing detailed object attribute information. To address the VRS-Seg task, we introduce VRSFormer, a critical pipeline that integrates multi-temporal and multi-modal data fusion, geometric contour refinement, and category-level classification inference. The experimental results demonstrate the effectiveness and generalization capability of our approach. The availability of VRS and the VRS-Seg task paves the way for further research in multi-modal and multi-temporal vegetation segmentation in remote sensing imagery. [ABSTRACT FROM AUTHOR]

There is an urgent need for a mass population screening tool for diabetes. Skin tissue contains a large number of endogenous fluorophores and physiological parameter markers related to diabetes. We built an excitation‐emission spectrum measurement system with the excited light sources of 365, 395, 415, 430, and 455 nm to extract skin characteristics. The modeling experiment was carried out to design and verify the accuracy of the recovery of tissue intrinsic discrete three‐dimensional fluorescence spectrum. Blood oxygen modeling experiment results indicated the accuracy of the physiological parameter extraction algorithm based on the diffuse reflectance spectrum. A community population cohort study was carried out. The tissue‐reduced scattering coefficient and scattering power of the diabetes were significantly higher than normal control groups. The Gaussian multi‐peak fitting was performed on each excitation‐emission spectrum of the subject. A total of 63 fluorescence features containing information such as Gaussian spectral curve intensity, central wavelength position, and variance were obtained from each person. Logistic regression was used to construct the diabetes screening model. The results showed that the area under the receiver operating characteristic curve of the model for predicting diabetes was 0.816, indicating a high diagnostic value. As a rapid and non‐invasive detection method, it is expected to have high clinical value. [ABSTRACT FROM AUTHOR]

The pathological mechanism of autism spectrum disorder (ASD) remains unclear. Nowadays, surface-based morphometry (SBM) based on structural magnetic resonance imaging (sMRI) techniques have reported cortical thickness (CT) variations in ASD. However, the findings were inconsistent and heterogeneous. This current meta-analysis conducted a whole-brain vertex-wise coordinate‐based meta‐analysis (CBMA) on CT studies to explore the most noticeable and robust CT changes in ASD individuals by applying the seed-based d mapping (SDM) program. A total of 26 investigations comprised 27 datasets were included, containing 1,635 subjects with ASD and 1470 HC, along with 94 coordinates. Individuals with ASD exhibited significantly altered CT in several regions compared to HC, including four clusters with thicker CT in the right superior temporal gyrus (STG.R), the left middle temporal gyrus (MTG.L), the left anterior cingulate/paracingulate gyri, the right superior frontal gyrus (SFG.R, medial orbital parts), as well as three clusters with cortical thinning including the left parahippocampal gyrus (PHG.L), the right precentral gyrus (PCG.R) and the left middle frontal gyrus (MFG.L). Adults with ASD only demonstrated CT thinning in the right parahippocampal gyrus (PHG.R), revealed by subgroup meta-analyses. Meta-regression analyses found that CT in STG.R was positively correlated with age. Meanwhile, CT in MFG.L and PHG.L had negative correlations with the age of ASD individuals. These results suggested a complicated and atypical cortical development trajectory in ASD, and would provide a deeper understanding of the neural mechanism underlying the cortical morphology in ASD. [ABSTRACT FROM AUTHOR]

Obesity is a complex disorder, and the incidence of obesity continues to rise at an alarming rate worldwide. In particular, the growing incidence of overweight and obesity in children is a major health concern. However, the underlying mechanisms of obesity remain unclear and the efficacy of several approaches for weight loss is limited. As an important calcium‐permeable temperature‐sensitive cation channel, transient receptor potential vanilloid (TRPV) ion channels directly participate in thermo‐, mechano‐, and chemosensory responses. Modulation of TRPV ion channel activity can alter the physiological function of the ion channel, leading to neurodegenerative diseases, chronic pain, cancer, and skin disorders. In recent years, increasing studies have demonstrated that TRPV ion channels are abundantly expressed in metabolic organs, including the liver, adipose tissue, skeletal muscle, pancreas, and central nervous system, which has been implicated in various metabolic diseases, including obesity and diabetes mellitus. In addition, as an important process for the pathophysiology of adipocyte metabolism, adipocyte differentiation plays a critical role in obesity. In this review, we focus on the role of TRPV ion channels in adipocyte differentiation to broaden the ideas for prevention and control strategies for obesity. Significance statement: As an important calcium‐permeable temperature‐sensitive cation channel, transient receptor potential vanilloid (TRPV) ion channels directly have been implicated in various metabolic diseases. TRPV ion channels are involved in the maturation, differentiation, and thermogenesis of adipocytes. In this review, we provided an overview of the different effects of TRPV ion channels on adipocyte differentiation and central adiposity, which maybe potential therapeutic targets for managing obesity and related metabolic disorders. [ABSTRACT FROM AUTHOR]

Introduction. DN is a common complication of diabetes. However, diabetes combined with renal injury may involve DN or NDKD, with different treatment schemes. The purpose of our study was to determine the independent risk factors of DN and establish a risk score model to help differentiate DN and NDKD, providing a reference for clinical treatment. Methods. A total of 678 T2D patients who had undergone renal biopsy in four affiliated hospitals of Peking University were consecutively enrolled. Patients were assigned to the DN group and NDKD group according to histopathological results. Seventy percent of patients from PKUFH were randomly assigned to the training group, and the remaining 30% were assigned to the internal validation group. Patients from the other three centers were assigned to the external validation group. We used univariate and multivariate logistic regression analyses to identify independent risk factors of DN in the training group and conducted multivariate logistic regression analysis with these independent risk factors in the training group to find regression coefficients " β " to establish a risk score model. Finally, we conducted internal and external validation of the model with ROC curves. Results. Diabetic retinopathy, diabetes duration ≥ 5 years, eGFR < 30 ml / min / 1.73 m 2 , 24 h UTP ≥ 3 g , and no hematuria were independent risk factors (P < 0.05), and each factor scored 2, 1, 1, 1, and 1. We assigned the patients to a low-risk group (0-1 points), a medium-risk group (2-3 points), and a high-risk group (4-6 points), representing unlikely DN, possibly DN, and a high probability of DN, respectively. The AUCs were 0.860, 0.924, and 0.855 for the training, internal validation, and external validation groups, respectively. Conclusion. The risk score model could help differentiate DN and NDKD in a noninvasive manner, reduce the number of renal biopsies, and provide a reference for clinical treatment. [ABSTRACT FROM AUTHOR]

Objective To investigate the glucose metabolic status in patients with previous gestational diabetes mellitus (GDM) in the 5-6 years after delivery, and to explore the changes in insulin resistance and islet β cell function from postpartum short-term (6-12 weeks) to the long-term (5-6 years) after delivery, as well as the relationship with glucose metabolic status. Methods A total of 72 patients with a history of GDM who delivered in Peking University First Hospital and had complete short-and long-term postpartum follow-up data were included. They were divided into normal glucose metabolism (NGT) and abnormal glucose metabolism (AGT) groups according to their glucose metabolism status in 5-6 years after delivery. Pre-pregnancy, pregnancy, perinatal, short-and long-term postpartum clinical data were collected and compared between the two groups, including demographic indicators, glucose and lipid metabolism indicators [oral glucose tolerance test (OGTT) fasting blood glucose (FPG), 1-hour blood glucose (1hPG), 2-hour blood glucose (2hPG), 3-hour blood glucose (3hPG), total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol], insulin use ratio, fasting insulin (FINS), OGTT 2-hour insulin (2hINS), insulin sensitivity index (ISI), homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of β cell function index (HOMA-β) were calculated. The comparison between the two groups was conducted using independent sample t-test, rank sum test χ² test or Fisher's exact probability test. Multivariate logistic regression analysis was used to analyze the influence factors of abnormal glucose metabolism. Results There were 38 (52.78%) cases in NGT group and 34 (47.22%) cases in AGT group. Compared with the NGT group, there are differences in related metabolic indicators in AGT group from pregnancy to long-term postpartum period: During pregnancy, 3hPG in 75 g OGTT and the proportion of insulin users were higher in AGT group. As for 6-12 weeks postpartum, OGTT 2hPG and the incidence of blood glucose abnormalities and the proportion of hypertriglyceridemia were higher (all P<0.05). However, there was no statistically significant difference in HOMA-IR and HOMA-β between the two groups(P>0.05). At 5-6 years postpartum, FPG, OGTT 2hPG, and FINS were all higher, with a higher degree of insulin resistance and lower insulin sensitivity (ISI) in AGT group (all P<0.05). Compared with short-term postpartum period (6-12 weeks), FPG, FINS, HOMA-IR, HOMA-β were all significantly increased regardless of glucose metabolic status at 5-6 years postpartum, while OGTT 2hPG and 2hINS increased further in the AGT group (all P<0.05). OGTT 2hPG and insulin use during pregnancy were risk factors for abnormal glucose metabolism 5-6 years postpartum according to multivariate logistic regression analysis, with OR values (95%CI) of 1.646 (1.015-2.671) and 3.570 (1.009-12.624), respectively. Conclusions The incidence of AGT was still high in patients with previous GDM 5-6 years after delivery. Insulin resistance progressed gradually after delivery regardless of glucose metabolism, especially in patients with abnormal glucose metabolism. OGTT 2hPG and insulin use in pregnancy were risk factors for abnormal glucose metabolism in postpartum 5-6 years, suggesting that there is continuity in time and similarity in pathogenesis between GDM and T2DM. [ABSTRACT FROM AUTHOR]

Bacterial biofilm-associated infectious diseases remain serious menaces to human health. Recently, photodynamic therapy (PDT) has become a prospective strategy for combating biofilm infection. However, anaerobic conditions in a biofilm greatly inhibit its therapeutic efficacy. Here, a nanozyme-reinforced injectable hydrogel is prepared using Ca2+-crosslinked sodium alginate incorporated with photosensitizer-loaded MnO2 nanosheets and CaO2 nanoparticles for O2 self-sufficient PDT to eradicate biofilm infection. In our design, CaO2 reacts with water to produce locally concentrated H2O2, which could be catalyzed by MnO2 nanosheets (catalase-mimic nanozymes) to generate O2 and greatly relieve the hypoxic conditions in the biofilm, thus significantly strengthening PDT efficacy. In vitro assays confirmed that the hybrid hydrogel not only exhibits high-performance bactericidal activity in combating both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli but also shows great efficacy in eliminating biofilm infection. Moreover, benefiting from its good syringeability, the hybrid hydrogel is prone to fit irregular wounds and exhibits high efficiency in promoting wound healing in a biofilm-infected mice model. Besides, no obvious toxicity is detected in the hybrid hydrogel. Overall, we envision that our designed hydrogel could provide a prospective solution for combating biofilm-associated infections. [ABSTRACT FROM AUTHOR]

Aqueous zinc batteries are promising candidates for energy storage and conversion devices in the "post‐lithium" era due to their high energy density, high safety, and low cost. The electrolyte plays an important role in zinc batteries by conducting and separating the positive and negative electrodes. However, the issues of zinc dendrites growth, corrosion, by‐product formation, hydrogen evolution and leakage, and evaporation of the aqueous electrolytes affect the commercialization of the batteries. Moreover, the widely used aqueous electrolytes result in large battery sizes, which are not conducive to the emerging smart devices. The intrinsic properties of gel polymer electrolytes (GPEs) can solve the above problems. In order to promote the wider application of GPEs‐based zinc batteries, in this review, the working principle and the current problems of zinc batteries are first introduced, andthe merits of GPEs compared to aqueous electrolytes are then summarized. Subsequently, a series of challenges and corresponding strategies faced by GPE is discussed, and an outlook for its future development is finally proposed. [ABSTRACT FROM AUTHOR]

Lodging is one of the most important factors affecting the high and stable yield of wheat worldwide. Solid-stemmed wheat has higher stem strength and lodging resistance than hollow-stemmed wheat does. There are many solid-stemmed varieties, landraces, and old varieties of durum wheat. However, the transfer of solid stem genes from durum wheat is suppressed by a suppressor gene located on chromosome 3D in common wheat, and only hollow-stemmed lines have been created. However, synthetic hexaploid wheat can serve as a bridge for transferring solid stem genes from tetraploid wheat to common wheat. In this study, the F1, F2, and F2:3 generations of a cross between solid-stemmed Syn-SAU-119 and semisolid-stemmed Syn-SAU-117 were developed. A single dominant gene, which was tentatively designated Su-TdDof and suppresses stem solidity, was identified in synthetic hexaploid wheat Syn-SAU-117 by using genetic analysis. By using bulked segregant RNA-seq (BSR-seq) analysis, Su-TdDof was mapped to chromosome 7DS and flanked by markers KASP-669 and KASP-1055 within a 4.53 cM genetic interval corresponding to 3.86 Mb and 2.29 Mb physical regions in the Chinese Spring (IWGSC RefSeq v1.1) and Ae. tauschii (AL8/78 v4.0) genomes, respectively, in which three genes related to solid stem development were annotated. Su-TdDof differed from a previously reported solid stem suppressor gene based on its origin and position. Su-TdDof would provide a valuable example for research on the suppression phenomenon. The flanking markers developed in this study might be useful for screening Ae. tauschii accessions with no suppressor gene (Su-TdDof) to develop more synthetic hexaploid wheat lines for the breeding of lodging resistance in wheat and further cloning the suppressor gene Su-TdDof. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of iGlarLixi in the Asian Pacific (AP) population with type 2 diabetes (T2D) using derived time‐in‐ranges calculated from seven‐point self‐measured blood glucose. Methods: Two phase III trials were analysed. LixiLan‐O‐AP was performed in insulin‐naive T2D patients (n = 878) randomized to iGlarLixi, glargine 100 units/mL (iGlar) or lixisenatide (Lixi). LixiLan‐L‐CN was performed in insulin‐treated T2D patients (n = 426) randomized to iGlarLixi or iGlar. Changes in derived time‐in‐ranges from baseline to end‐of‐treatment (EOT) and estimated treatment differences (ETDs) were analysed. The proportions of patients achieving 70% or higher derived time‐in‐range (dTIR), 5% or higher dTIR improvement, and the composite triple target (≥ 70% dTIR, < 4% derived time‐below‐the‐range [dTBR] and < 25% derived time‐above‐the‐range [dTAR]) were calculated. Results: The changes from baseline to EOT in dTIR with iGlarLixi were greater versus iGlar (ETD1: 11.45% [95% CI, 7.66% to 15.24%]) or Lixi (ETD2: 20.54% [95% CI, 15.74% to 25.33%]) in LixiLan‐O‐AP, and versus iGlar (ETD: 16.59% [95% CI, 12.09% to 21.08%]) in LixiLan‐L‐CN. In LixiLan‐O‐AP, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT with iGlarLixi were 77.5% and 77.8%, respectively, higher than with iGlar (61.1% and 75.3%) or Lixi (47.0% and 53.0%). In LixiLan‐L‐CN, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT were 71.4% and 59.8% with iGlarLixi, greater than with iGlar (45.4% and 39.5%). More patients achieved the triple target with iGlarLixi compared with iGlar or Lixi. Conclusion: iGlarLixi achieved greater improvements in dTIR parameters versus iGlar or Lixi in insulin‐naïve and insulin‐experienced AP people with T2D. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to evaluate the stability and accuracy of glucose measurements determined using the metabolic heat conformation (MHC)-based non-invasive glucometer in a multicentre, self-controlled clinical trial. This device is the first to obtain a medical device registration certificate awarded by the National Medical Products Administration of China (NMPA). Methods: The multicentre clinical study was conducted at three sites and enrolled 200 subjects whose glucose was measured with a non-invasive glucometer (the Contour Plus blood glucose monitoring system) and by venous plasma glucose (VPG) measurements, in a fasted state and at 2 and 4 h after meals. Results: Based on both the non-invasive and VPG measurements, 93.9% (95% confidence interval 91.7–95.6%) of the blood glucose (BG) values fell within consensus error grid (CEG) zones A + B. The measurements obtained in a fasted state and at 2 h after meals were more accurate, with 99.0% and 97.0% of the BG values, respectively, falling within zones A + B. Compared to those subjects who received insulin, the proportion of values in zones A + B and the correlation coefficients were 3.1% and 0.0596 higher, respectively. The accuracy of the non-invasive glucometer was influenced by the level of insulin resistance calculated by the homeostatic model assessment method, which had a correlation coefficient with the mean absolute relative difference of − 0.1588 (P = 0.0001). Conclusion: The MHC-based non-invasive glucometer assessed in the present study demonstrates generally high stability and accuracy in the glucose monitoring of people with diabetes. The calculation model needs to be further explored and optimised for patients with different diabetes subtypes, levels of insulin resistance and insulin secretion capacity. Clinical trial registry number: ChiCTR1900020523. [ABSTRACT FROM AUTHOR]

A unique photosensitizer (PS), ERPS, with intrinsic endoplasmic reticulum (ER)-targeting ability and low oxygen-depletion type-I photosensitivity, is developed and used as a scaffold to construct an activatable theranostic agent for precise photodynamic therapy (PDT). The ER-targeted feature coupled with type-I photosensitivity endows ERPS with high phototoxicity toward tumor cells under both normoxic and hypoxic conditions. In addition, caging the phenol group of ERPS with a nitroreductase-sensitive triggering group provided a hypoxia-activatable PS (ERPSIm) that is encapsulated within a polymeric micelle to obtain a water-stable Im@NP nanoparticle for in vivo applications. After intravenous administration to 4T1 tumor-bearing BALB/c mice, Im@NP demonstrated highly efficient imaging-guided PDT ablation of implanted tumors. This is because the delivered ERPSIm cargos of Im@NP are specifically activated in the hypoxic microenvironment of solid tumor, and the activated ERPS molecules have efficient ER-targeted type-I photosensitivity. [ABSTRACT FROM AUTHOR]

Background: With advances in massive parallel sequencing (MPS) technology, whole-genome sequencing (WGS) has gradually evolved into the first-tier diagnostic test for genetic disorders. However, deployment practice and pipeline testing for clinical WGS are lacking. Methods: In this study, we introduced a whole WGS pipeline for genetic disorders, which included the entire process from obtaining a sample to clinical reporting. All samples that underwent WGS were constructed using polymerase chain reaction (PCR)-free library preparation protocols and sequenced on the MGISEQ-2000 platform. Bioinformatics pipelines were developed for the simultaneous detection of various types of variants, including single nucleotide variants (SNVs), insertions and deletions (indels), copy number variants (CNVs) and balanced rearrangements, mitochondrial (MT) variants, and other complex variants such as repeat expansion, pseudogenes and absence of heterozygosity (AOH). A semiautomatic pipeline was developed for the interpretation of potential SNVs and CNVs. Forty-five samples (including 14 positive commercially available samples, 23 laboratory-held positive cell lines and 8 clinical cases) with known variants were used to validate the whole pipeline. Results: In this study, a whole WGS pipeline for genetic disorders was developed and optimized. Forty-five samples with known variants (6 with SNVs and Indels, 3 with MT variants, 5 with aneuploidies, 1 with triploidy, 23 with CNVs, 5 with balanced rearrangements, 2 with repeat expansions, 1 with AOHs, and 1 with exon 7–8 deletion of SMN1 gene) validated the effectiveness of our pipeline. Conclusions: This study has been piloted in test development, optimization, and validation of the WGS pipeline for genetic disorders. A set of best practices were recommended using our pipeline, along with a dataset of positive samples for benchmarking. [ABSTRACT FROM AUTHOR]

The ascendant danger of bacterial infections has resulted in an urgent requirement for developing new antibacterial approaches. Recently, nitric oxide (NO) has shown a broad-spectrum antimicrobial activity while avoiding resistance. However, achieving effective NO-based antibacterial therapies remains challenging, mired by the safety concerns of NO donor, residual toxicity by the ingredients, or complicated procedures. Herein, a self-activated NO-releasing hydrogel depot is fabricated by Ca2+-crosslinked sodium alginate doped with CaO2 nanoparticles, L-arginine, and oxidized mesoporous carbon nanoparticles (OMCN) for photothermal enhanced bacteria killing. The locally concentrated H2O2, generated from the reaction of CaO2 nanoparticles and water, could oxidize L-arginine to release NO. Meanwhile, benefiting from the remarkable photothermal effect of OMCN, the hybrid hydrogel possesses a synergistic sterilization behavior in combating both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria in vitro. Moreover, the dual therapeutic hydrogel displays high efficiency in treatment of bacteria-infected mice with back wound model while showing no distinct toxicity. In addition, the restricted environment of hydrogel makes it easy to remove all the components from the infected wound, alleviating possible side effects from exogenous H2O2. As such, the designed NO-synergistic photothermal hydrogel provides a promising strategy for treating bacterial infections. [ABSTRACT FROM AUTHOR]

The most appropriate surgical procedure for tertiary hyperparathyroidism is still controversial. Medical management may be considered in those patients with failed previous surgical intervention. There are limited medical options for tertiary hyperparathyroidism with renal dysfunction. The monoclonal antibody denosumab has been used in patients with osteoporosis and hypercalcemia of malignancy. We report a case of medically refractory hypercalcemia caused by tertiary hyperparathyroidism treated with denosumab. A 46‐year‐old female was on hemodialysis for 10 years. She was diagnosed with tertiary hyperparathyroidism due to hypercalcemia with a high level of intact parathyroid hormone (iPTH, 1411 pg/ml). After right parathyroidectomy 6 weeks, her serum calcium remained persistently elevated (Ca, 3.17 mmoL/L). Denosumab (60 mg) was administered subcutaneously, and her serum calcium quickly decreased (from 3.43 to 2.04 mmoL/L within 8 days) and was slightly elevated (Ca, 2.8 mmoL/L) 3 months later. We conclude that denosumab has a significant effect on the reduction of serum calcium for tertiary hyperparathyroidism patients. The long‐term treatment effect and safety warrant more studies in the future. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a common neurodegenerative disorder associated with microglia-mediated neuroinflammation in pathogenesis. Regulatory T cells (Treg cells) are involved in the regulation of microglia activation and neuroinflammation. However, it is yet to be established whether exosomes derived from Treg cells (Treg-Exos) possess protective effect against MPP+-induced inflammation and oxidative stress in microglia. Objective: In our study, we examined the function of Treg cells in the in vitro PD model. MTT assay was used to assess the viability of BV2 cells. ROS, MDA, and SOD activity were detected, and ELISA was performed to estimate the inflammatory response and oxidative stress of BV-2 cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were applied to detect the level changes of genes involved in the TLR4/NF-κB signaling pathway. Results: The results showed that Treg-Exos improved the cell viability of MPP+-treated BV2 cells. MPP+-induced increase in ROS and MDA production, as well as decrease in SOD activity in BV2 cells were attenuated by Treg-Exos. The increased levels of inflammatory cytokines IL-β, IL-6, and TNF-α in MPP+-induced BV2 cells were also prevented by the treatment of Treg-Exos. Treg-Exos inhibited MPP+-induced activation of the TLR4/NF-κB signaling, indicated by decreased protein level of TLR4 and p-p65/p65 ratio in BV2 cells. Further, we also found that upregulation of TLR4 blocks the protective effect of Treg-Exos on MPP+-treated BV2 cells. Conclusions: Collectively, Treg-Exos attenuated MPP+-induced oxidative stress and inflammatory injury in BV-2 cells by inhibiting the TLR4/NF-κB signaling. [ABSTRACT FROM AUTHOR]

Introduction: This analysis investigated the efficacy and safety of add-on lixisenatide by disease duration in Asian people with type 2 diabetes inadequately controlled with basal insulin ± oral antidiabetic drugs. Methods: Data for Asian participants in the GetGoal-Duo 1, GetGoal-L, and GetGoal-L-C studies were pooled and categorized by diabetes duration: < 10 years (group 1), 10 to < 15 years (group 2), and ≥ 15 years (group 3). Efficacy and safety of lixisenatide versus placebo were evaluated by subgroup. The potential influence of diabetes duration on efficacy was examined using multivariable regression analyses. Results: A total of 555 participants were included (mean age 53.9 years, 52.4% male). No significant differences in treatment effect between the duration subgroups were observed for the changes from baseline to 24 weeks in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial glucose (PPG), PPG excursion, body weight or body mass index, or the proportion of participants with HbA1c < 7% at 24 weeks (all P values for interaction > 0.1). Change in insulin dosage (U/day) was significantly different between subgroups (P = 0.038). Multivariable regression analysis showed participants in group 1 had a smaller change in body weight and basal insulin dose over the 24-week treatment period than participants in group 3 (P = 0.014 and 0.030, respectively) and were less likely to achieve an HbA1c < 7% than participants in group 2 (P = 0.047). No severe hypoglycemia was reported. A higher proportion of participants in group 3 versus the other groups had symptomatic hypoglycemia, for both lixisenatide and placebo, and T2D duration had a significant effect on hypoglycemia risk (P = 0.001). Conclusions: Lixisenatide improved glycemic control in Asian individuals regardless of diabetes duration, without increasing the risk of hypoglycemia. Individuals with longer disease duration had a greater risk of symptomatic hypoglycemia than individuals with shorter disease duration regardless of treatment. No additional safety concerns were observed. Clinical Trial Registration: GetGoal-Duo 1, ClinicalTrials.gov record NCT00975286; GetGoal-L, ClinicalTrials.gov record NCT00715624; GetGoal-L-C, ClinicalTrials.gov record NCT01632163. [ABSTRACT FROM AUTHOR]

Atmospheric CH 4 is the second-largest anthropogenic contributor to global warming. However, its emissions, components, spatial–temporal variations and projected changes still remain largely uncertain from city to national scales. CH 4 emissions from waste treatment (including solid waste landfills, solid waste incineration and sewage) account for >50 % of total anthropogenic CH 4 emissions at the city scale, and considering the high temperature sensitivity of CH 4 emission factors (EFs) to biological-process-based sources such as waste treatment, large differences will occur when estimating future CH 4 emissions under different global warming scenarios. Furthermore, the relationships between temperature and waste treatment CH 4 emissions have only been studied in a few site-specific studies and lack representativity for whole cities, which contain various biophysical conditions and show heterogeneous distribution. The above factors cause uncertainty in the evaluation of city-scale CH 4 emissions (especially from waste treatments), and projected changes still remain unexplored. Here we conduct the first tower-based CH 4 observation network with three sites in Hangzhou, which is located in the developed Yangtze River Delta (YRD) area and ranks as one of the largest megacities in China. We found the a priori total annual anthropogenic CH 4 emissions and those from waste treatment were overestimated by 36.0 % and 47.1 % in Hangzhou, respectively. In contrast, the total emissions in the larger region, i.e., Zhejiang Province or the YRD area, were slightly underestimated by 7.0 %. Emissions from waste treatment showed obvious seasonal patterns following air temperature. By using the linear relationship constructed between monthly waste treatment CH 4 emissions and air temperature, we find the waste treatment EFs increase by 38 %–50 % with temperature increases of 10 ∘ C. Together with projected temperature changes from four climate change scenarios, the global-warming-induced EFs in Hangzhou will increase at the rates of 2.2 %, 1.2 %, 0.7 % and 0.5 % per decade for IPCC AR5 (Intergovernmental Panel on Climate Change, the Fifth Assessment Report) RCP (Representative Concentration Pathway) 8.5, RCP6.0, RCP4.5 and RCP2.6 scenarios, respectively. And the EFs will finally increase by 17.6 %, 9.6 %, 5.6 % and 4.0 % at the end of this century. Additionally, the derived relative changes in China also show high heterogeneity and indicate large uncertainty in projecting future national total CH 4 emissions. Hence, we strongly suggest temperature-dependent EFs and the positive feedback between global warming and CH 4 emissions should be considered in future CH 4 emission projections and climate change models. [ABSTRACT FROM AUTHOR]

Objective. We used network pharmacology, molecular docking, and cellular analysis to explore the pharmacodynamic components and action mechanism of Alpinia officinarum Hance (A. officinarum) in improving type 2 diabetes mellitus (T2DM). Methods. The protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the potential targets and mechanism of A. officinarum toward improving T2DM. The first 9 core targets and potential active compounds were docked using Discovery Studio 2019. Finally, IR-HepG2 cells and qPCR were applied to determine the mRNA expression of the top 6 core targets of the PPI network. Results. A total of 29 active ingredients and 607 targets of A. officinarum were obtained. T2DM-related targets overlapped with 176 targets. The core targets of the PPI network were identified as AKT serine/threonine kinase 1 (AKT1), an activator of transcription 3 (STAT3), tumor necrosis factor (TNF), tumor protein p53 (TP53), SRC proto-oncogene, nonreceptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), albumin (ALB), mitogen-activated protein kinase 1 (MAPK1), and peroxisome proliferator-activated receptor gamma (PPARG). A. officinarum performs an antidiabetic role via the AGE-RAGE signaling pathway, the HIF-1 signaling pathway, the PI3K-AKT signaling pathway, and others, according to GO and KEGG enrichment analyses. Molecular docking revealed that the binding ability of diarylheptanoid active components in A. officinarum to core target protein was higher than that of flavonoids. The cell experiments confirmed that the A. officinarum extracts improved the glucose uptake of IR-HepG2 cells and AKT expression while inhibiting the STAT3, TNF, TP53, SRC, and EGFR mRNA expression. Conclusion. A. officinarum Hance improves T2DM by acting on numerous components, multiple targets, and several pathways. Our results lay the groundwork for the subsequent research and broaden the clinical application of A. officinarum Hance. [ABSTRACT FROM AUTHOR]

Although cities only account for 3% of the global land area, they have disproportionately contributed 70% of total anthropogenic CO2 emissions; the main issue in estimating urban anthropogenic CO2 emissions is their large uncertainty. Tower-based atmospheric CO2 observations and simulations in urban areas have been frequently used as an independent approach to constrain and evaluate greenhouse gas emissions from city to regional scales, where only daytime CO2 observations and simulations are used considering the consensus that the large bias in simulating nighttime planetary boundary layer heights (PBLH) and atmospheric CO2 concentration will cause overestimation/underestimation in CO2 emission inversions. The above strategy of only using daytime observations makes the numbers of available concentration observations largely decrease even with the fact that tower-based atmospheric CO2 observations are sparsely distributed and conducted. Here, to solve the issue of large bias in nighttime CO2 simulations, we conducted four months of atmospheric CO2 observations from January to April in 2019, and raised an approach by coupling emission heights with dynamic PBLH variations in a WRF-STILT model. We found (1) the overestimation of simulated nighttime CO2 concentration decreased by 5–10 ppm, especially between 0:00 and 7:00. (2) The statistics for nighttime simulations were largely improved by using a revised model and posteriori emissions. The regression slopes of daily averages were 0.93 and 0.81 for the default model using a priori emissions and the revised model using the same a priori emissions, and the slope largely improved to 0.97 for the revised model using posteriori emissions. Moreover, the correlation coefficient also increased from 0.29 and 0.37 to 0.53; these results indicate our revised model obviously calibrated the bias in both nighttime and daily CO2 concentration simulations. In general, it is strongly recommended to use the revised WRF-STILT model in future inversion studies, which can effectively reduce the overestimation of nighttime spikes and make full use of nighttime observations. [ABSTRACT FROM AUTHOR]

A method based on capacitively coupled contactless conductivity detection (C4D), which has been proven effective for the rapid detection of available soil potassium content, was firstly proposed to apply to soil nutrient detection. By combining a detection signal spectrum analysis, geographic information system (GIS) data, and a cluster analysis, a soil nutrient management system to match the detection device was developed. This system included six modules: soil sample information management, electrophoresis analysis, quantitative calculation, nutrient result viewing, cluster analysis, and nutrient distribution map generation. The soil samples, which were collected from an experimental field in Xuchang City of Henan Province, were analyzed using the C4D and flame photometer methods. The results showed that the detection results for the soil samples obtained via the two methods were in good agreement. C4D technology was feasible for the detection of the soil available nutrients and had the advantages of a high timeliness, low sample volume, and low pollution. The soil nutrient management system adopted the hierarchical clustering method to classify the grid cells of the experimental field according to the nutrient detection results. A soil nutrient distribution map displayed the spatial difference in nutrients. This paper provides a systematic solution for soil nutrient zone management that includes nutrient detection, signal analysis, data management for the nutrient zone, and field nutrient distribution map generation to support decision making in variable fertilization. [ABSTRACT FROM AUTHOR]

Infections caused by bacteria are one of the biggest challenges humans face around the world. Photothermal therapy (PTT) has been regarded as a promising strategy in combating pathogenic infection, however the high temperatures (55–65 °C) required during a single PTT process can induce injury to healthy tissues nearby. Combination therapy could overcome this problem by reducing the photothermal temperature. Here, we developed a self-healing and injectable hydrogel to realize low-temperature PTT (LT-PTT, ≤45 °C) for antisepsis with high-efficiency. The hybrid hydrogel is prepared by incorporating borax into a mixture of 3-aminophenylboronic acid grafted sodium alginate and nano-silver decorated polydopamine nanoparticles. Our results showed that the SABA/Borax/PDA@AgNPs hydrogel possesses satisfactory mechanical properties and self-healing capacity, and as a result, it can repair itself after being damaged mechanically, retaining its integrality and recovering its initial functionalities. Furthermore, through utilizing the photothermal property of polydopamine nanoparticles and broad-spectrum antibacterial activity of nano-silver, the hybrid hydrogel achieves excellent LT-PTT for sterilization both in vitro as well as in an in vivo mice skin wound model with no distinct injury to normal tissues. Overall, our prepared hydrogel is expected to be an excellent candidate for treating bacterial infections. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to investigate the attitudes of people with diabetes mellitus (DM) on COVID-19 vaccination and its influence on the glycemic control. Methods: Data were collected from a consecutive series of adults (age > 18 years) with type 2 diabetes under regular follow-ups in the Integrated Care Diabetes Outpatient Clinic of Peking University First Hospital from December 1st to December 31st 2021. An online interview questionnaire was conducted, and demographic data including age, sex category, history of drug allergy, history of hypertension, the duration of diabetes, reasons for vaccine hesitancy (VH) and adverse reactions after each injection of vaccines was collected. Glucose levels were collected from medical records. Results: Thirty-nine (22.9%) subjects experienced VH and 131 (77.1%) people living with diabetes received inactivated vaccine against COVID-19. Hesitant individuals had a higher proportion of female gender (vaccinated group vs. VH group, 62/131 vs. 26/39, p = 0.044), higher baseline glycosylated hemoglobin A1c (HbA1c) (vaccinated group vs. VH group, 6.56 ± 0.95% vs. 7.54 ± 2.01%, p < 0.001) and elevated baseline postprandial blood glucose (PBG) (vaccinated group vs. VH group, 8.32 ± 1.97 mmol/L vs. 9.44 ± 2.94 mmol/L, p = 0.015). Subjects of male gender (p = 0.025) and history of hypertension (p = 0.021) were likely to get vaccinated, while higher HbA1c was negatively associated with an elevated propensity to receive anti-COVID-19 vaccine (p = 0.003). Most common reasons for hesitating to receive COVID-19 vaccination were worrying about the possibility of leading to other diseases (30.8%), followed by fearing of glucose variation (17.9%). Systemic adverse reactions were reported in 30.5% individuals after the first injection of inactivated vaccines, and resolved within 3 days in medium. Fasting blood glucose (FBG) decreased significantly after the third injection compared with FBG after the second dose (second vs. third, 6.78 ± 1.24 mmol/L vs. 6.41 ± 1.30 mmol/L, p = 0.027). HbA1c reduced significantly from 6.56% before vaccination to 6.35% after the second injection (p = 0.012). Conclusions: Our study demonstrated that vaccine hesitancy was lower among male subjects and people with hypertension, while vaccine confidence was reduced in people with poor glycemic control. HbA1c level was lower along with vaccination. [ABSTRACT FROM AUTHOR]

Background: Clinical guidelines indicate that chronic highland exposure could induce pulmonary hypertension; chronic hepatic disease may affect cardiac structure and functions. However, the simultaneous impact of hepatic echinococcosis (HE) and chronic highland exposure on cardiac structure and function in Tibetan residents are under‐investigated. Methods: One hundred and twenty patients with HE, 23 healthy high‐altitude migrants with a mean residence time of 7.15 ± 1.12 years, and 46 healthy Tibetan permanent residents were enrolled in this study. All participants received comprehensive transthoracic echocardiography. Results: High‐altitude migrants have a relatively lower pulmonary artery flow velocity (PV) and a slightly higher pulmonary artery mean pressure (PAMP) than the Tibetan permanent residents. Patients with HE presented relatively smaller dimensions of the main pulmonary artery and branches and a bigger right atrium and right ventricular cavity size than the two control groups. PV, PAMP and numbers of detectable tricuspid regurgitation jet velocity (TRJV), right ventricular fractional area change (RV_FAC), tricuspid annular plane systolic excursion (TAPSE), the ratio of tricuspid inflow velocities at early diastole to tricuspid annular early diastolic excursion velocity (RV_E/e′) and right ventricular myocardial performance index (RV_MPI) were increased in patients with HE compared to the two control groups. Similarly, decreased LVEF and Impaired left ventricular diastolic function were identified in patients with HE compared to the two control groups. Conclusions: Patients with HE presented with impaired biventricular contractile performance and diastolic dysfunction. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the efficacy and safety of iGlarLixi compared with iGlar in Chinese adults with type 2 diabetes advancing therapy from basal insulin ± oral antihyperglycaemic drugs. Materials and methods: LixiLan‐L‐CN (NCT03798080) was a 30‐week randomized, active‐controlled, open‐label, parallel‐group, multicentre study. Participants were randomized 1:1 to iGlarLixi or iGlar. The primary objective was to show the superiority of iGlarLixi over iGlar in glycated haemoglobin (HbA1c) change from baseline to Week 30. Results: In total, 426 participants were randomized to iGlarLixi (n = 212) or iGlar (n = 214). Mean age was 58 years, 67% had a body mass index ≥24 kg/m2, corresponding to overweight/obesity, and the mean diabetes duration was 12.3 years. From mean baseline HbA1c of 8.1% in both groups, greater decreases were seen with iGlarLixi versus iGlar [least squares mean difference: −0.7 (95% confidence interval: −0.9, −0.6)%; p <.0001] to final HbA1c of 6.7% and 7.4%, respectively. HbA1c <7.0% achievement was greater with iGlarLixi (63.3%) versus iGlar (29.9%; p <.0001). Mean body weight decreased with iGlarLixi and increased with iGlar [least squares mean difference: −0.9 (95% confidence interval: −1.4, −0.5) kg; p =.0001]. Hypoglycaemia incidence was similar between groups. Few gastrointestinal adverse events occurred (rated mild/moderate) with a slightly higher incidence with iGlarLixi than iGlar. Conclusions: iGlarLixi provided better glycaemic control and facilitated more participants to reach glycaemic targets alongside beneficial effects on body weight, no additional risk of hypoglycaemia, and few gastrointestinal AEs, supporting iGlarLixi use as an efficacious and well tolerated therapy option in Chinese people with long‐standing T2D advancing therapy from basal insulin. [ABSTRACT FROM AUTHOR]

Autoimmune thyroid diseases (AITDs), which include Hashimoto's thyroiditis (HT) and Graves' disease (GD), have a higher prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the literature. The effects of AITD-associated cytokines on SARS-CoV-2 infection-mediating molecule levels might be involved in the pathogenesis of susceptibility. We speculated that hydrogen sulfide (H2S) might attenuate this process since H2S has antiviral effects. Using immunohistochemistry, we found that angiotensin-converting enzyme-II (ACE2) expression was higher in the HT group and neuropilin 1 (NRP1) expression was higher in HT and GD groups than in the normal group, while transmembrane protease serine type 2 (TMPRSS2) expression was lower in HT and GD groups. When culturing primary thyrocytes with cytokines or sodium hydrosulfide (NaHS) plus cytokines, we found that ACE2 and NRP1 mRNA levels were upregulated while TMPRSS2 levels were downregulated by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). After pretreatment with NaHS in thyrocytes, ACE2 and NRP1 expression were downregulated compared to IFN-γ or TNF-α treatment, and NaHS had no effect on TMPRSS2 expression. Our findings suggested that IFN-γ and TNF-α, which are elevated in AITDs, promoted ACE2 and NRP1 expression and inhibited TMPRSS2 expression. H2S might protect against SARS-CoV-2 infection by downregulating ACE2 and NRP1 levels. [ABSTRACT FROM AUTHOR]

This study aimed to apply transcriptomics to determine how Molor-Dabos-4 (MD-4) protects healthy rats against indomethacin (IND)-induced gastric ulcers and to identify the mechanism behind this protective effect. Rats were pretreated with MD-4 (0.3, 1.5, or 3 g/kg per day) for 21 days before inducing gastric ulcers by oral administration with indomethacin (30 mg/kg). Unulcerated and untreated healthy rats were used as controls. Effects of the treatment were assessed based on the ulcer index, histological and pathological examinations, and indicators of inflammation, which were determined by enzyme-linked immunosorbent assay. Transcriptomic analysis was performed for identifying potential pharmacological mechanisms. Eventually, after identifying potential target genes, the latter were validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). After pretreatment with MD-4, gastric ulcers, along with other histopathological features, were reduced. MD-4 significantly (p < 0.05) increased the superoxide dismutase (SOD) levels in ulcers and reduced pepsin, TNF-α, and IL-6 levels. RNA-seq analysis identified a number of target genes on which MD-4 could potentially act. Many of these genes were involved in pathways that were linked to anti-inflammatory and antioxidant responses, and other protective mechanisms for the gastric mucosa. qRT-PCR showed that altered expression of the selected genes, such as Srm, Ryr-1, Eno3, Prkag3, and Eef1a2, was consistent with the transcriptome results. MD-4 exerts protective effects against IND-induced gastric ulcers by reducing inflammatory cytokines and pepsin and increasing the expression of SOD levels. Downregulation of Srm, Ryr-1, Eno3, Prkag3, and Eef1a2 genes involved in regulating arginine and proline metabolism, calcium signaling pathway, HIF-1 signaling pathway, oxytocin signaling pathway, and legionellosis are possibly involved in MD-4-mediated protection against gastric ulcers. [ABSTRACT FROM AUTHOR]

Introduction. Autoimmune thyroid diseases (AITDs) and antiphospholipid syndrome (APS) are commonly seen in childbearing-age women and can lead to recurrent miscarriages. Studies with a relatively small sample size were conducted and concluded inconsistent results on the relationship between AITDs and APS or the presence of antiphospholipid (aPL) antibodies. This meta-analysis aimed to provide evidence on the possible association between AITDs and APL using primary data from all relevant studies. Methods. Literature databases including PubMed, Embase, and Cochrane were searched from the time when the databases were established to March 2022. A total of 7 studies that met all inclusion criteria were selected in this meta-analysis, with 475 AITD patients and 764 healthy controls. After data extraction, the pooled odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. Results. The risk of positive APL in AITD patients was approximately 3 folds higher in AITD patients compared with those in healthy controls (OR 3.41, 95% CI 2.29–5.08, p < 0.001). There was no significant association between the risk of Graves' disease (GD) and positive APL (OR 9.3, 95% CI 0.10–824.73, p = 0.33). The risk of positive APL in patients with Hashimoto's thyroiditis (HT) increased over 2 folds compared with healthy controls (OR 3.35, 95% CI 1.55–7.23, p = 0.002). Conclusions. The result of this meta-analysis proved that the presence of APL was significantly increased in patients with AITD compared with healthy individuals, especially in patients with Hashimoto's thyroiditis. [ABSTRACT FROM AUTHOR]

Radio frequency fingerprint identification (RFFI) is a promising device authentication technique based on transmitter hardware impairments. The device-specific hardware features can be extracted at the receiver by analyzing the received signal and used for authentication. In this paper, we propose a scalable and channel-robust RFFI framework achieved by deep learning powered radio frequency fingerprint (RFF) extractor and channel independent features. Specifically, we leverage deep metric learning to train an RFF extractor, which has excellent generalization ability and can extract RFFs from previously unseen devices. Any devices can be enrolled via the pre-trained RFF extractor and the RFF database can be maintained efficiently for allowing devices to join and leave. Wireless channel impacts the RFF extraction and is tackled by exploiting channel independent features and data augmentation. We carried out extensive experimental evaluation involving 60 commercial off-the-shelf LoRa devices and a USRP N210 software defined radio platform. The results have successfully demonstrated that our framework can achieve excellent generalization abilities for rogue device detection and device classification as well as effective channel mitigation. [ABSTRACT FROM AUTHOR]

Diabetic peripheral neuropathy (DPN), peripheral artery disease (PAD), and foot deformity are the most common causes of diabetic foot, which can considerably worsen the patient's quality of life. In this study, we aimed to investigate the prevalence and risk factors associated with DPN, PAD, and foot deformity among patients with diabetes living in Beijing, China. In total, 3,898 diabetes patients from 11 hospitals in Beijing were evaluated using questionnaires and physical examinations, and 3,758 patients were included in the analysis. We compared the demographic, clinical, biological characteristics, and comorbidities of patients with and without DPN, PAD, or foot deformity, and used binary logistic regression analysis to identify potential factors associated with these outcomes. Overall, 882 patients (23.5%) had DPN, 437 patients (11.6%) had PAD, and 1,117 patients (29.7%) had foot deformities, including callus. The risk factors for DPN included: age ≥40 years, a ≥10+year duration of diabetes, a body mass index of <18.5 kg/m2 or ≥24 kg/m2, a systolic blood pressure (SBP) of ≥140 mm Hg, a hemoglobin A1c (HbA1c) level of ≥7%, chronic kidney disease, and cerebrovascular disease. The risk factors for PAD included: a 15+ year diabetes duration, a body mass index of <18.5 kg/m2, a SBP of ≥140 mm Hg, a HbA1c level of ≥7%, chronic kidney disease, coronary heart disease, and cerebrovascular disease. The risk factors for skeletal foot deformities included: women, age ≥40 years, a SBP ≥140 mm Hg, and hyperlipidemia. The risk factors for callus formation included: women, a SBP ≥140 mm Hg, and hyperlipidemia. In conclusion, the prevalence of foot deformities was higher than DPN and PAD in patients with diabetes. Managing the risk factors for DPN, PAD, and foot deformity is important for reducing the risk of diabetic foot. [ABSTRACT FROM AUTHOR]

Ixeris chinensis (Thunb.) Nakai (IC) is a folk medicinal herb used in Mongolian medical clinics for the treatment of hepatitis and fatty liver diseases even though its pharmacological mechanism has not been well characterized. This study investigated the hepatoprotective mechanism of IC on mice with nonalcoholic fatty liver disease (NAFLD) by integrating gut microbiota and metabolomic analysis. A high-fat diet (HFD) was used to develop nonalcoholic fatty liver disease, after which the mice were treated with oral IC (0.5, 1.5 and 3.0 g/kg) for 10 weeks. HFD induced NAFLD and the therapeutic effects were characterized by pathological and histological evaluations, and the serum indicators were analyzed by ELISA. The gut microbial and metabolite profiles were studied by 16S rRNA sequencing and untargeted metabolomic analysis, respectively. The results showed that the administration of IC resulted in significant decreases in body weight; liver index; serum biomarkers such as ALT, TG, and LDL-C; and the liver inflammatory factors IL-1β, IL-6, and TNF-α. The 16S rRNA sequencing results showed that administration of IC extract altered both the composition and abundance of the gut microbiota. Untargeted metabolomic analysis of liver samples detected a total of 212 metabolites, of which 128 were differentially expressed between the HFD and IC group. IC was found to significantly alter the levels of metabolites such as L-glutamic acid, pyridoxal, ornithine, L-aspartic acid, D-proline, and N4-acetylaminobutanal, which are involved in the regulation of glutamine and glutamate, Vitamin B6 metabolism, and arginine and proline metabolic pathways. Correlation analysis indicated that the effects of the IC extract on metabolites were associated with alterations in the abundance of Akkermansiaceae, Lachnospiraceae, and Muribaculaceae. Our study revealed that IC has a potential hepatoprotective effect in NAFLD and that its function might be linked to improvements in the composition of gut microbiota and their metabolites. [ABSTRACT FROM AUTHOR]

Purpose: COVID-19 pandemic is a significant threat toward the public health. However, the discussion of the mechanism of media literacy's effect in fighting against pandemic is limited. Thus, this study aims to explore the mechanism with a sociocognitive perspective. Methods: A survey was administrated to 420 college students in China. PROCESS macro of SPSS was applied to analyze the data and test the moderated mediation effect. Results: The moderated mediation model of media literacy, proxy efficacy, self-efficacy, and official media use was tested and supported. Official media use was a negative moderator on the association between media literacy and proxy efficacy. Conclusion: The study explored the media literacy's role as a determinant of proxy efficacy and self-efficacy, which contributed to the sociocognitive theory. [ABSTRACT FROM AUTHOR]

As LoRaWAN is one of the most popular long-range wireless protocols among low-power IoT applications, more and more focus is shifting towards security. In particular, physical layer topics become relevant to improve the security of LoRaWAN nodes, which are often limited in terms of computational power and communication resources. To this end, e.g., detection methods for wireless attacks improve the integrity and robustness of LoRaWAN access. Further, wireless physical layer techniques have potential to enhance key refreshment and device authentication. In this work, we aim to provide a comprehensive review of various vulnerabilities, countermeasures and security enhancing features concerning the LoRaWAN physical layer. Afterwards, we discuss the impact of the reviewed topics on LoRaWAN security and, subsequently, we identify research gaps as well as promising future research directions. [ABSTRACT FROM AUTHOR]

Background: Hearing loss affects approximately two out of every 1,000 newborns. Genetic factors and congenital cytomegalovirus (CMV) infections account for around 90% of the etiology. The purpose of this study was to develop and test a whole genome sequencing (WGS) approach to detect deafness-related genetic variants and CMV infections simultaneously in newborns. Method: Deafness-related genes causing congenital or childhood hearing loss were curated and selected for newborn screening. Nine dried blood spots from newborns with known genetic variants (n = 6) or CMV infections (n = 3) were employed to develop and validate the WGS testing and analytic pipeline. We then pilot tested the WGS analysis on 51 de-identified clinical samples. Results: 92 gene-disease pairs were selected for screening hearing loss in newborns. In the validation test, WGS accurately detected all types of genetic variants, including single nucleotide variations, insertions/deletions, and copy number variations in the nuclear or mitochondrial genome. Sequence reads mapping to the CMV reference genome were discovered in CMV infected samples. In the pilot test, WGS identified nine out of 51 (18%) newborns carrying pathogenic variants associated with deafness. Conclusion: WGS can simultaneously detect genetic variants and CMV infections in dried blood spot specimens from newborns. Our study provides proof of principle that genome sequencing can be a promising alternative for newborn screening of hearing loss. [ABSTRACT FROM AUTHOR]

Aims. To explore the associations between polymorphisms in SIRT1 and coronary heart disease (CHD) risk in Chinese Han patients with type 2 diabetes (T2D). Methods. This case-controlled study enrolled 492 patients with T2D: 297 with CHD and 195 without CHD. Five SIRT1 haplotype-tagging single-nucleotide polymorphisms (rs3818291, rs12242965, rs3818292, rs4746720, and rs16924934) were selected from Chinese Han data in the GRCh37.p13 phase 3 database and genotyped by polymerase chain reaction-restriction fraction length polymorphism or sequencing. Results. The rs16924934 G allele was associated with a higher risk of CHD than the A allele (odds ratio OR = 1.429 ; 95% confidence interval CI = 1.003 – 2.037 ; P = 0.048). Using an additive inheritance model, the rs3818291 G/A genotype was associated with a higher CHD risk than the G/G genotype ( OR ' = 1.683 ; 95 % CI = 1.033 – 2.743 ; P ' = 0.037 after adjustment for CHD risk factors). Smokers carrying G/A or A/A rs3818291 genotypes had a 3-fold higher CHD risk than those carrying GG (adjusted OR ' = 3.035 ; P ' = 0.011) and a 2.6-fold higher CHD risk than nonsmokers carrying GG (adjusted OR ' = 2.604 ; P ' = 0.033). Conclusions. Genetic polymorphisms of SIRT1 are associated with the risk of CHD in a Chinese Han population with T2D. [ABSTRACT FROM AUTHOR]

Graves' disease (GD) is a common autoimmune disorder with an elevation in pathogenic autoantibodies, specifically anti-thyrotropin receptor antibodies (TRAbs), which are secreted by autoreactive B cells. To date, there has been little research on self-reactive B cells in GD. In the current study, we reported that a unique B-cell subset, CD11c+ B cells, was expanded in the peripheral blood (PB) of GD patients, as detected by flow cytometry. The frequency of CD11c+ B cells was positively correlated with serum TRAb levels. The flow cytometry data showed that CD11c expression was higher in a variety of B-cell subsets and that CD11c+ B cells presented a distinct immunophenotype compared to paired CD11c- B cells. Immunohistochemical and immunofluorescence staining indicated the presence of CD11c+CD19+ B cells in lymphocyte infiltration areas of the GD thyroid. Flow cytometric analysis of PB and fine-needle aspiration (FNA) samples showed that compared to PB CD11c+ B cells, CD11c+ B cells in the thyroid accumulated and further differentiated. We found that CD11c+ B cells from the PB of GD patients were induced to differentiate into autoreactive antibody-secreting cells (ASCs) capable of secreting TRAbs in vitro. Luminex liquid suspension chip detection data showed that CD11c+ B cells also secreted a variety of cytokines, including proinflammatory cytokines, anti-inflammatory cytokines, and chemokines, which might play roles in regulating the local inflammatory response and infiltration of lymphocytes in the thyroid. In addition, we performed a chemotaxis assay in a Transwell chamber to verify that CD11c+ B cells were recruited by thyroid follicular cells (TFCs) via the CXCR3-CXCL10 axis. In conclusion, our study determined that CD11c+ B cells were involved in the pathogenesis of GD in multiple ways and might represent a promising immunotherapeutic target in the future. [ABSTRACT FROM AUTHOR]