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Background: Breast cancer (BRCA) is the most common malignant tumor and the leading cause of cancer death worldwide. Adenylosuccinate synthetase (ADSS) is highly expressed in BRCA and its subtypes malignant tumors and is associated with poor prognosis. Methods: By applying ROC curve, survival analysis, WGCNA, enrichment analysis, Cox regression model and other methods, this study explores the role of ADSS in BRCA and constructs a scoring model. Results: In this study, the ADSS demonstrated good diagnostic efficacy and high expression in breast cancer tissues. Further exploration of the role of ADSS in BRCA revealed that its significantly related coexpressed genes are clearly involved in biological functions and signaling pathways associated with cell proliferation and differentiation. Additionally, the ADSS-related scoring model showed a significant prognostic impact on clinical characteristics, such as metastasis to lymph nodes, and it was discovered that the ADSS score and related scoring genes may affect the immune microenvironment of BRCA patients, potentially participating in the occurrence of this disease. Conclusion: In summary, our gene expression analysis of ADSS in BRCA generated a clinical scoring model based on the ADSS that may be used to assess prognostic risk and provide potential clinical applications and rational therapeutic targets., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Diabetes mellitus (DM) has been related to a higher risk of intervertebral disc degeneration (IVDD). However, the previous studies showed inconsistent results. We performed a systematic review and meta-analysis to comprehensively investigate the association between DM and IVDD in adult population., Methods: Observational studies relevant to the aim of the meta-analysis were retrieved by search of electronic databases including PubMed, Web of Science, and Embase. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity., Results: Eleven observational studies involving 2,881,170 adults were included. Among them, 1,211,880 had DM. Compared to those with normoglycemia, patients with DM were associated with a higher odds ratio of IVDD (OR: 1.68, 95% confidence interval: 1.24 to 2.29, P<0.001; I 2 =98%). Further sensitivity analysis excluding database studies with IVDD diagnosed via International Classification of Diseases codes showed consistent results (odds ratio: 1.47, 95% confidence interval: 1.06 to 2.02, P=0.02) with no statistical heterogeneity (I 2 =0%). Subgroup analyses showed a stronger association between DM and IVDD in cohort studies than that in cross-sectional studies, in studies evaluating overall IVDD than that evaluating lumbar disc degeneration, and in studies that adjusted age and body mass index than that did not (P for subgroup differences all <0.05). Subgroup analyses according to study country and quality score did not significantly affect the association., Conclusions: DM may be associated with IVDD in adult population, which seems to be independent of age and body mass index., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The interfacial properties between carbon fiber (CF) and thermoplastic resin are relatively weak, which can be problematic for composites in structural applications. Improving the surface roughness of CF is regarded as an effective way to enhance the interface of composites. However, most CF modifying methods are complex and time-consuming, which cannot meet the demand for industrial production. Therefore, it is of great significance to research a fast technique of CF surface modification to strengthen the interface of composites. Herein, a one-pot reaction based on the aryl diazonium salt modification was applied to enhance the interface between CF and poly ether ether ketone (PEEK) resin. Carbon nanotubes (CNTs) were linked to CF by p-phenylenediamine (PPD) via cyclic voltammetry (CV). The surface morphology, chemical characteristics and surface energy of modified CF illustrated the effectiveness of this method, and the interfacial properties of as-prepared modified CF/PEEK demonstrated the increased tendency. All the CF was treated within 5 min and the interfacial shear strength (IFSS) of CF/PEEK was increased to the maximum of 99.62 MPa by aryl diazonium salt modification. This work may shed some light on the industrialized application of CF reinforced high-performance engineering thermoplastic composites.

Carbon-fiber-reinforced polyimide (PI) resin composites have gained significant attention in the field of continuous-fiber-reinforced polymers, in which the interfacial bonding between carbon fiber and matrix resin has been an important research direction. This study designed and prepared a water-soluble thermoplastic polyamide acid sizing agent to improve the wettability of carbon fiber, enhance the van der Waals forces between carbon fiber and resin and strengthen the chemical bonding between the sizing agent and the alkyne-capped polyimide resin by introducing alkyne-containing functional groups into the sizing agent. This study found that the addition of a sizing layer effectively bridged the large modulus difference between the fiber and resin regions, resulting in the formation of an interfacial layer approximately 85 nm thick. This layer facilitated the transfer of stress from the matrix to the reinforced carbon fiber, leading to a significant improvement in the interfacial properties of the composites. Adjusting the concentration of the sizing agent showed that composites treated with 3% had the best interfacial properties. The interfacial shear strength increased from 82.08 MPa to 108.62 MPa (32.33%) compared to unsized carbon fiber. This research is significant for developing sizing agents suitable for carbon-fiber-reinforced polyimide composites.

The toughening modification of epoxy resin has received widespread attention. The addition of the second-phase resin has a good toughening effect on epoxy resin. In order to investigate the effect of the second-phase resin on the interphase of composites, in this work the interfacial properties of carbon fiber (CF)/epoxy resin with the second-phase resin structure were investigated. Methodologies including surface structure observation, chemical characteristics, surface energy of the CF, and micro-phase structure characterization of resin were tested, followed by the micro-interfacial performance of CF/epoxy composites before and after hygrothermal treatment. The results revealed that the sizing process has the positive effect of increasing the interfacial bonding properties of CF/epoxy. From the interfacial shear strength (IFSS) test, the introduction of the second phase in the resin reduced the interfacial bonding performance between the CF and epoxy. After the hygrothermal treatment, water molecules diffused along the interfacial paths between the two resins, which in turn created defects and consequently brought about a reduction in the IFSS.

Aims: Chronic hyperglycemia-induced inflammation of the hippocampus is an important cause of cognitive deficits in diabetic patients. The receptor for advanced glycation end products (RAGE), which is widely expressed in the hippocampus, is a crucial factor in this inflammation and the associated cognitive deficits. We aimed to reveal the underlying mechanism by which RAGE regulates neuroinflammation in the pathogenesis of diabetes-induced cognitive impairment., Methods: We used db/db mice as a model for type 2 diabetes to investigate whether receptor-interacting serine/threonine protein kinase 1 (RIPK1), which is expressed in microglia in the hippocampal region, is a key protein partner for RAGE. GST pull-down assays and AutoDock Vina simulations were performed to identify the key structural domain in RAGE that binds to RIPK1. Western blotting, co-immunoprecipitation (Co-IP), and immunofluorescence (IF) were used to detect the levels of key proteins or interaction between RAGE and RIPK1. Cognitive deficits in the mice were assessed with the Morris water maze (MWM) and new object recognition (NOR) and fear-conditioning tests., Results: RAGE binds directly to RIPK1 via the amino acid sequence (AAs) 362-367, thereby upregulating phosphorylation of RIPK1, which results in activation of the NLRP3 inflammasome in microglia and ultimately leads to cognitive impairments in db/db mice. We mutated RAGE AAs 362-367 to reverse neuroinflammation in the hippocampus and improve cognitive function, suggesting that RAGE AAs 362-367 is a key structural domain that binds directly to RIPK1. These results also indicate that hyperglycemia-induced inflammation in the hippocampus is dependent on direct binding of RAGE and RIPK1., Conclusion: Direct interaction of RAGE and RIPK1 via AAs 362-367 is an important mechanism for enhanced neuroinflammation in the hyperglycemic environment and is a key node in the development of cognitive deficits in diabetes., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

The receptor for advanced glycation end products (RAGE) contributes to diabetes-associated cognitive dysfunction (DACD) through the interaction of its C-terminal AAs 2-5 with mitogen-activated protein kinase kinase 3 (MKK3). However, the associated MKK3 binding site is unknown. Here, db/db mice were used as a model for type 2 diabetes. GST pull-down assays and AutoDock Vina simulations were conducted to identify the key RAGE binding site in MKK3. This binding site was mutated to investigate its effects on DACD and to elucidate the underlying mechanisms. The interaction of MKK3 and RAGE, the levels of inflammatory factors, and the activation of microglia and astrocytes were tested. Synaptic morphology and plasticity in hippocampal neurons were assessed via electrophysiological recordings and Golgi staining. Behavioral tests were used to assess cognitive function. In this study, MKK3 bound directly to RAGE via its lysine 329 (K329), leading to the activation of the nuclear factor-κB (NF-κB) signaling pathway, which in turn triggered neuroinflammation and synaptic dysfunction, and ultimately contributed to DACD. MKK3 mutation at K329 reversed synaptic dysfunction and cognitive deficits by downregulating the NF-κB signaling pathway and inhibiting neuroinflammation. These results confirm that neuroinflammation and synaptic dysfunction in the hippocampus rely on the direct binding of MKK3 and RAGE. We conclude that MKK3 K329 binding to C-terminal RAGE (ct-RAGE) is a key mechanism by which neuroinflammation and synaptic dysfunction are induced in the hippocampus. This study presents a novel mechanism for DACD and proposes a novel therapeutic avenue for neuroprotection in DACD.

Eucalyptus cinerea is an evergreen tree in the Myrtaceae. It is native to southern and eastern New South Wales and northern and eastern Victoria, Australia. It was introduced into China in the 1980s (Silva et al. 2011). Because of its unique shape, flexible stems, and rapid growth characteristics, it is widely used in the pulp industry and in decorative materials such as flower bouquets. In July 2022, 5- to 10-year-old E. cinerea showing symptoms of dehydration, withering and yellowing leaves, were found in forests and nurseries in Kunming and Songming, China. More than 37% of the trees showed these symptoms at each location, and disease severity was about 30%. Sixty symptomatic plants were collected from five tree nurseries. Diseased roots with 2-cm-long lesions were soaked in 75% ethanol for 15 s, 0.1% mercuric chloride for 2 min, rinsed with sterilized water, and placed on potato dextrose agar (PDA) at 25℃ for 3 days. Thirty samples were plated, and 21 isolates (YJLGF01 to YJLGF21) obtained, 11 strains with similar colony morphology (including representative strains YJLGF03 to YJLGF05). Three isolates (YJLGF03 to YJLGF05) were obtained by single-spore purification. On PDA, the colonies were circular with fluffy white to light yellow mycelium; the underside was yellowish brown. Conidiophores were bifurcated, with macroconidia borne terminally. The macroconidia were cylindrical with rounded, blunt ends, yellow to transparent, 1 to 3 septate (22.5 to 47.6 × 4.5 to 7.1 µm); microconidia were 0 to 1 septate (12.5 to 19.6 × 4.7 to 6.4 µm). Chlamydospores were spherical, rosary-like, and light yellow. Morphological characteristics were consistent with published descriptions of Dactylonectria pauciseptata (Piperkova et al. 2017). For molecular identification, the internal transcribed spacer (ITS), translation elongation factor 1- alpha (ef1-α) gene, and the beta-tubulin 2 (β-tub2) gene were amplified and sequenced (ITS accessions OR735053, OR735054, OR735055; β-tub2 accessios OR757447, OR757448, OR757449; ef1-α accessions OR757450, OR757451, OR757451) using published primers (White et al. 1990; Carbone et al. 1999). A phylogenetic tree was developed by Maximum Parsimony (MP) and Maximum Likelihood (ML) methods. These three isolates fell into the D. pauciseptata clade and were distinguished clearly from other species. Pathogenicity tests were performed using the same three isolates. Each isolate was cultured on PDA, and then subcultured in V8 juice broth on an orbital shaker at 180 RPM for 5 days. Conidia were collected by centrifugation at 6,000 RPM for 5 min, and then resuspended in sterilized distilled water (1×106 conidia/ml). Injured roots of one-year-old E. cinerea were soaked in the spore suspension for 1 h before being transplanted in sterile vermiculite. The plants were incubated at 25℃ with a 12 h photoperiod and 90% humidity. Five plants were inoculated as a group for each treatment and the entire experiment was completed three times. Among the inoculated plants, the incidence of disease development was 100%. A small sot appeared after 4 days, with a water-soaked lesion appearing and gradually expanding during days 5 to 7. After 10 days symptoms of root necrosis were similar to the those observed in the nursery, and aboveground plant parts had yellow, withering leaves and defoliation after 10 to 15 days. Control plants treated with sterile water showed no disease symptoms. The three strains were successfully reisolated from inoculated seedlings and confirmed them using DNA sequencing. No isolates were obtained from the control plants, thus fulfilling Koch's postulates. Dactylonectria pauciseptata was first reported from necrotic tissue of infected grape roots (Schroers et al. 2008). So far, it has been reported in Turkey, Canada, Brazil, Italy, and other countries (Erper et al. 2013; Úrbez-Torres et al. 2014; Santos et al. 2014). Based on our results, E. cinerea is a new host plant of D. pauciseptata in China. This disease is a threat to the nursery production of E. cinerea, potentially leading to a reduction in yields and economic losses.

Transition metal single atom electrocatalysts (SACs) with metal-nitrogen-carbon (M-N-C) configuration show great potential in oxygen evolution reaction (OER), whereby the spin-dependent electrons must be allowed to transfer along reactants (OH - /H 2 O, singlet spin state) and products (O 2 , triplet spin state). Therefore, it is imperative to modulate the spin configuration in M-N-C to enhance the spin-sensitive OER energetics, which however remains a significant challenge. Herein, we report a local field distortion induced intermediate to low spin transition by introducing a main-group element (Mg) into the Fe-N-C architecture, and decode the underlying origin of the enhanced OER activity. We unveil that, the large ionic radii mismatch between Mg 2+ and Fe 2+ can cause a FeN 4 in-plane square local field deformation, which triggers a favorable spin transition of Fe 2+ from intermediate (d xy 2 d xz 2 d yz 1 d z2 1 , 2.96 μ B ) to low spin (d xy 2 d xz 2 d yz 2 , 0.95 μ B ), and consequently regulate the thermodyna-mics of the elementary step with desired Gibbs free energies. The as-obtained Mg/Fe dual-site catalyst demonstrates a superior OER activity with an overpotential of 224 mV at 10 mA cm -2 and an electrolysis voltage of only 1.542 V at 10 mA cm -2 in the overall water splitting, which outperforms those of the state-of-the-art transition metal SACs., (© 2023 Wiley-VCH GmbH.)

Both environmental and genetic factors contribute to the etiology of autoimmune thyroid disease (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT). However, the exact pathogenesis and interactions that occur between environmental factors and genes remain unclear, and therapeutic targets require further investigation due to limited therapeutic options. To solve such problems, this study utilized single-cell transcriptome, whole transcriptome, full-length transcriptome (Oxford nanopore technology), and metabolome sequencing to examine thyroid lesion tissues from 2 HT patients and 2 GD patients as well as healthy thyroid tissue from 1 control subject. HT patients had increased ATF4-positive thyroid follicular epithelial (ThyFoEp) cells, which significantly increased endoplasmic reticulum stress. The enhanced sustained stress resulted in cell death mainly including apoptosis and necroptosis. The ATF4-based global gene regulatory network and experimental validation revealed that N 6 -methyladenosine (m 6 A) reader hnRNPC promoted the transcriptional activity, synthesis, and translation of ATF4 through mediating m 6 A modification of ATF4. Increased ATF4 expression initiated endoplasmic reticulum stress signaling, which when sustained, caused apoptosis and necroptosis in ThyFoEp cells, and mediated HT development. Targeting hnRNPC and ATF4 notably decreased ThyFoEp cell death, thus ameliorating disease progression. Collectively, this study reveals the mechanisms by which microenvironmental cells in HT and GD patients trigger and amplify the thyroid autoimmune cascade response. Furthermore, we identify new therapeutic targets for the treatment of autoimmune thyroid disease, hoping to provide a potential way for targeted therapy., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023. Published by Elsevier Ltd.)

Autism Spectrum Disorders (ASD) and schizophrenia are distinct neurodevelopmental disorders that share certain symptoms and genetic components. Both disorders show abnormalities in dendritic spines, which are the main sites of excitatory synaptic inputs. Recent studies have identified the synaptic scaffolding protein Shank3 as a leading candidate gene for both disorders. Mutations in the SHANK3 gene have been linked to both ASD and schizophrenia; however, how patient-derived mutations affect the structural plasticity of dendritic spines during brain development is unknown. Here we use live two photon in vivo imaging to examine dendritic spine structural plasticity in mice with SHANK3 mutations associated with ASD and schizophrenia. We identified shared and distinct phenotypes in dendritic spine morphogenesis and plasticity in the ASD-associated InsG3680 mutant mice and the schizophrenia-associated R1117X mutant mice. No significant changes in dendritic arborization were observed in either mutant, raising the possibility that synaptic dysregulation may be a key contributor to the behavioral defects previously reported in these mice. These findings shed light on how patient-linked mutations in SHANK3 affect dendritic spine dynamics in the developing brain, which provides insight into the synaptic basis for the distinct phenotypes observed in ASD and schizophrenia., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Lung adenocarcinoma (LUAD) is a common type of lung cancer with a high risk of metastasis, but the exact molecular mechanisms of metastasis are not yet understood., Methods: This study acquired single-cell transcriptomics profiling of 11 distal normal lung tissues, 11 primary LUAD tissues, and 4 metastatic LUAD tissues from the GSE131907 dataset. The lung multicellular ecosystems were characterized at a single-cell resolution, and the potential mechanisms underlying angiogenesis and metastasis of LUAD were explored., Results: We constructed a global single-cell landscape of 93,610 cells from primary and metastatic LUAD and found that IGF2BP2 was specifically expressed both in a LUAD cell subpopulation (termed as LUAD&#95;IGF2BP2), and an endothelial cell subpopulation (termed as En&#95;IGF2BP2). The LUAD&#95;IGF2BP2 subpopulation progressively formed and dominated the ecology of metastatic LUAD during metastatic evolution. IGF2BP2 was preferentially secreted by exosomes in the LUAD&#95;IGF2BP2 subpopulation, which was absorbed by the En&#95;IGF2BP2 subpopulation in the tumor microenvironment. Subsequently, IGF2BP2 improved the RNA stability of FLT4 through m 6 A modification, thereby activating the PI3K-Akt signaling pathway, and eventually promoting angiogenesis and metastasis. Analysis of clinical data showed that IGF2BP2 was linked with poor overall survival and relapse-free survival for LUAD patients., Conclusions: Overall, these findings provide a novel insight into the multicellular ecosystems of primary and metastatic LUAD, and demonstrate that a specific LUAD&#95;IGF2BP2 subpopulation is a key orchestrator promoting angiogenesis and metastasis, with implications for the gene regulatory mechanisms of LUAD metastatic evolution, representing themselves as potential antiangiogenic targets., (© 2023. The Author(s).)

Aim: The purpose of this study was to elucidate the potential mechanisms of Alzheimer's disease (AD) induced by Type 2 diabetes mellitus (T2DM) through bioinformatics analysis, to provide new treatment targets for this disease. Methods: We used weighted gene coexpression network analysis and differentially expressed genes analysis to identify significantly differentially expressed genes shared by T2DM and AD. Molecular docking was used to predict possible protein targets for T2DM-induced AD. Results: The direct interaction of CD44 and STAT3 may play a significant role in the development of T2DM-induced AD. Conclusion: A new approach to treating T2DM-associated AD may be provided by these hub genes and their predicted molecular targets.

Design of non-noble metal electrocatalysts with high catalytic activity and stability to replace commercial Pt/C is crucial in the commercialization development of Zn-air batteries (ZABs). In this work, Co catalyst nanoparticles coupled with nitrogen-doped hollow carbon nanoboxes were well designed through zeolite-imidazole framework (ZIF-67) carbonization. As a result, the 3D hollow nanoboxes reduced the charge transport resistance, and the Co nanoparticles loaded on nitrogen-doped carbon supports exhibited excellent electrocatalytic performance for oxygen reduction reaction (ORR, E 1/2 =0.823 V vs. RHE), similar to that of commercial Pt/C. Moreover, the designed catalysts showed an excellent peak density of 142 mW cm -2 when applied on ZABs. This work provides a promising strategy for the rational design of non-noble electrocatalysts with high performance for ZABs and fuel cells., (© 2023 Wiley-VCH GmbH.)

The prevalence and mortality of hepatocellular carcinoma (HCC) are still increasing. This study aimed to identify potential therapeutic targets related to patient prognosis. Data were downloaded from TCGA, GSE25097, GSE36376, and GSE76427 datasets. Differential analysis and enrichment analysis were performed in HCC. Cell deaths were evaluated, and least absolute shrinkage and selection operator regression (LASSO) regression was analyzed to screen candidate genes. Additionally, immune cell infiltration in HCC was assessed. We identified 4088 common DEGs with the same direction of differential expression in all four datasets, they were mainly enriched in immunoinflammation and cell cycle pathways. Apoptosis was significantly suppressed in HCC in GSEA and GSVA. After LASSO regression analysis, we screened CD69, CDC25B, MGMT, TOP2A, and TXNIP as candidate genes. Among them, CD69 significantly influenced the overall survival of HCC patients in both TCGA and GSE76427. CD69 may be a protective factor for outcome of HCC patients. In addition, CD69 was positive correlation with T cells and CD3E. CD69, CDC25B, MGMT, TOP2A, and TXNIP were potential diagnostic and prognostic target for HCC, especially CD69., (© 2023. The Author(s).)

Background: Fibromyalgia (FM) is a common and intractable chronic musculoskeletal pain syndrome, but its exact underlying mechanisms are unknown. This study sought to identify biomarkers of FM and the underlying molecular mechanisms of the disease., Methods: FM-related gene expression profiles (GSE67311) and methylation profiles (GSE85506) were obtained from the Gene Expression Omnibus database, and a differential expression analysis was performed to identify the methylation factors. Subsequently, an enrichment analysis and gene set enrichment analysis (GSEA) were conducted to examine the methylation factors. In addition, the transcriptional regulators of the methylation factors were predicted, and key methylation factors were identified by a receiver operating characteristic curve analysis and nomogram models. Finally, the relationship between FM and cell death (pyroptosis, necroptosis, and cuproptosis) was assessed by a GSEA and gene set variation analysis., Results: A total of 455 methylation factors were identified. The enrichment analysis and GSEA results showed that methylation factors were clearly involved in the biological functions and signaling pathways related to neural, immune inflammation, and pain responses. The transcriptional regulator specificity protein 1 (SP1) may have a broad regulatory role. Finally, seven key methylation factors were identified, of which amino beta (A4) precursor protein binding family B member 2 (APBB2), A-kinase anchor protein 12 (AKAP12), and cluster of differentiation 38 (CD38) had strong clinical diagnostic power. In addition, AKAP12 and CD38 were significantly and negatively associated with sepsis, necrotizing sepsis, and cupular sepsis., Conclusions: Our study suggests that FM is associated with deoxyribonucleic acid methylation. The methylation factors APBB2, AKAP12, and CD38 may be potential biomarkers and should be further examined to provide a new biological framework of the possible disease mechanisms underlying FM., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-6631/coif). The authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Patients with diabetes mellitus (DM) have an increased risk of diabetic encephalopathy symptoms such as depressive-like behaviour and cognitive impairment. Exercise is an effective strategy for preventing and treating DM and diabetic complications. The aim of this study is to investigate the effects and potential mechanisms of treadmill exercise training on diabetes-induced depressive-like behavior and cognitive impairment in db/db mice. In this study, the mice were divided into three groups (n = 10 per group) as follows: healthy-sedentary (db/m), diabetes-sedentary (db/db), and diabetes-treadmill exercise training (db/db-TET). The db/db-TET mice were performed five days per week at a speed of 8 m/min for 60 min/day for 8 weeks, following which body weight, fasting blood glucose, insulin resistance, behavioral, synaptic ultrastructure, oxidative stress, apoptotic signaling, and inflammatory responses were evaluated. As a result, treadmill exercise training significantly decreased body weight and fasting blood glucose levels, increased insulin sensitivity, protected synaptic ultrastructure, reduced depression-like behavior, and improved learning and memory deficits in db/db mice. In addition, treadmill exercise training significantly suppressed NOX2-mediated oxidative stress, resulting in a decrease in NOX2-dependent ROS generation in the db/db mouse hippocampus CA1 region. Reduced ROS generation prevented the apoptotic signaling pathway and NLRP3 inflammasome activation, thereby ameliorating hippocampus neuronal damage. In summary, the results indicated that treadmill exercise training significantly ameliorates hippocampus injury by suppressing oxidative stress-induced apoptosis and NLRP3 inflammasome activation, consequently ameliorating diabetes-induced depressive-like behavior and cognitive impairment in db/db mice., 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 © 2022 Elsevier Inc. All rights reserved.)

Ionizing radiation (IR) has been widely used in the diagnosis and treatment of clinical diseases, with radiation therapy (RT) being particularly rapid, but it can induce "bystander effects" that lead to biological responses in non-target cells after their neighboring cells have been irradiated. To help clarify how radiotherapy induces these effects, To help clarify how radiotherapy induces these effects, we analyzed single-cell RNA sequencing data from irradiated intestinal tissues on day 1 (T1 state), day 3 (T3 state), day 7 (T7 state), and day 14 (T14 state) after irradiation, as well as from healthy intestinal tissues (T0 state), to reveal the cellular level, molecular level, and involvement of different time irradiated mouse intestinal tissues in biological signaling pathways. In addition, changes in immune cell subpopulations and myeloid cell subpopulations after different radiation times were further explored, and gene regulatory networks (GRNs) of these cell subpopulations were constructed. Cellular communication between radiation-specific immune cells was explored by cell-to-cell communication events. The results suggest that radiotherapy trigger changes in immune cell subsets, which then reprogram the immune ecosystem and mediate systemic bystander effects. These radiation-specific immune cells participate in a wide range of cell-to-cell communication events. In particular, radiation-specific CD8+T cells appear to be at the core of communication and appear to persist in the body after recovery from radiotherapy, with enrichment analysis showing that radiation-specific CD8+ T cells are associated with ferroptosis. Thus, radiation-specific CD8+ T cells may be involved in cellular ferroptosis-mediated adverse effects caused by RT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Han, Chen, Zhang, Huang, He, Li, Wei, Song, Mo and Lv.)

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating diseases affecting the swine industry worldwide. To investigate the role of miRNAs in the infection and susceptibility of PRRS virus (PRRSV), twenty-four miRNA libraries were constructed and sequenced from PRRSV-infected and mock-infected Porcine alveolar macrophages (PAMs) of Meishan, Landrace, Pietrain and Qingping pigs at 9 hours post infection (hpi), 36 hpi, and 60 hpi. The let-7 family miRNAs were significantly differentially expressed between PRRSV-infected and mock-infected PAMs from 4 pig breeds. The let-7 family miRNAs could significantly inhibit PRRSV-2 replication by directly targeting the 3'UTR of the PRRSV-2 genome and porcine IL6, which plays an important role in PRRSV replication and lung injury. NEAT1 acts as a competing endogenous lncRNA (ceRNA) to upregulate IL6 by attaching let-7 in PAMs. EMSA and ChIP results confirmed that ARID3A could bind to the promoter region of pri-let-7a/let-7f/let-7d gene cluster and inhibit the expression of the let-7 family. Moreover, the NF-κB signaling pathway inhibits the expression of the let-7 family by affecting the nuclear import of ARID3A. The pEGFP-N1-let-7 significantly reduced viral infections and pathological changes in PRRSV-infected piglets. Taken together, NEAT1/ARID3A/let-7/IL6 play significant roles in PRRSV-2 infection and may be promising therapeutic targets for PRRS., Competing Interests: The authors have declared that no competing interests exist.

Flaps are common technical choices in aesthetic and reconstructive surgeries. However, the poor flap survival rate remains to be a difficult issue that troubles plastic surgeon. Recent research evidence supports that the use of Botulinum toxin type A (BTXA) can increase the flap survival rate. For verification, the present study was carried out to evaluate the effect of BTXA on flap surgery. Eight databases (PubMed, Cochrane Library, Ovid, Web of Science, Embase, Scopus, CBM, CNKI and WANFANG database) were searched for related published literature up to September 2020. A meta-analysis was then conducted to compare the effect of using BTXA with that of using saline or no treatment in flap surgery. Seventeen studies with a total of 565 animals were finally included in this review after strict exclusion and inclusion. Compared with saline/no treatment + flap group, BTXA + flap group showed a significantly higher flap tissue survival rate (mean difference [MD] 15.55, p  < 0.00001), blood flow (standardized mean difference [SMD] 1.97, p  < 0.00001) and vascular endothelial growth factor (VEGF) expression (at mRNA level: SMD 6.01, p  = 0.02; at protein level: SMD 3.35, p  < 0.00001). BTXA combined with flap surgery may have a positive effect on improving the flap tissue survival rate, blood flow of flaps and VEGF expression. Besides, the timing of BTXA injection may be an important factor for exerting its effect on flap surgery.

Abundant immune cells reside in barrier tissues. Understanding the regulation of these cells can yield insights on their roles in tissue homeostasis and inflammation. Here, we report that the chemokine CCL27 is critical for establishment of resident lymphocytes and immune homeostasis in barrier tissues. CCL27 expression is associated with normal skin and hair follicle development independent of commensal bacterial stimulation, indicative of a homeostatic role for the chemokine. Accordingly, in the skin of CCL27-knockout mice, there is a reduced presence and dysregulated localization of T cells that express CCR10, the cognate receptor to CCL27. Besides, CCL27-knockout mice have overreactive skin inflammatory responses in an imiquimod-induced model of psoriasis. Beyond the skin, CCL27-knockout mice have increased infiltration of CCR10 + T cells into lungs and reproductive tracts, the latter of which also exhibit spontaneous inflammation. Our findings demonstrate that CCL27 is critical for immune homeostasis across barrier tissues., Competing Interests: Na Xiong has an US patent (# 10,588,941) that is related to this work. All the other authors declare no competing interests., (© 2022 The Author(s).)

Background: Diabetic retinopathy (DR) is a common microvascular complication of diabetes and one of the most common causes of visual impairment and blindness. However, it is not yet known how abnormal retinal cell subpopulations contribute to disease progression., Methods: In this study, we used the Gene Expression Omnibus database to construct a single-cell atlas of DR and healthy samples to explore changes in the abundance of different cell subpopulations, and identify the molecular pathways potentially involved in DR., Results: Our results showed that DR was associated with significantly reduced numbers of bipolar cells, Müller glia, retinal pigment epithelial cells, and cone photoreceptors, but was also associated with significantly greater numbers of pericytes, rod photoreceptors, anaplastic cells, and microglia. Our results suggest that subpopulations of Müller glia, microglia, endothelial cells, and bipolar cells in DR tissues may be involved in various oxidative stress- and inflammation-related pathways., Conclusions: In summary, we showed that Müller glia, endothelial cells, microglia, and bipolar cells in DR tissues are involved in oxidative stress- and inflammation-related pathways, which may contribute to the progression of the disease and ultimately lead to visual impairment and blindness. This study will provide a theoretical basis for further exploring the specific mechanism of DR., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-1546/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Ulcerative colitis is a chronic, non-specific inflammatory disease that affects mainly the colonic mucosa and submucosa. The pathogenesis of ulcerative colitis is unclear, which limits the development of effective treatments. In this study, single-cell sequencing data from 18 ulcerative colitis samples and 12 healthy controls were downloaded from the Single Cell Portal database, cell types were defined through cluster analysis, and genes in each cluster that were differentially expressed in ulcerative colitis were identified. These genes were enriched in functional pathways related to apoptosis, immunity and inflammation. Analysis using iTALK software suggested extensive communication among immune cells. Single-cell sequencing data from adipose-derived mesenchymal stem cells from three healthy female donors were obtained from the Sequence Read Archive database. The SingleR package was used to identify different cell types, for each of which a stemness score was calculated. Pseudotime analysis was performed to infer the trajectory of cells. SCENIC software was used to identify the gene regulatory network in adipose-derived mesenchymal stem cells, and iTALK software was performed to explore the relationship among macrophages, adipose-derived mesenchymal stem cells and enterocytes. Molecular docking confirmed the possibility of cell-cell interactions via binding between surface receptors and their ligands. The bulk data were downloaded and analyzed to validate the expression of genes. Our bioinformatics analyses suggest that ulcerative colitis involves communication between macrophages and enterocytes via ligand-receptor pairs. Our results further suggest that adipose-derived mesenchymal stem cells may alleviate ulcerative colitis by communicating with macrophages to block inflammation.

Background and Objectives: An adequate iodine status during pregnancy is very important for maternal and infant health. The aim of this study was to characterize the iodine nutritional status of healthy pregnant women in Chengdu by measuring urinary iodine (UI) and analyzing dietary iodine intake., Methods and Study Design: Pregnant women who underwent regular antenatal examinations were invited to participate in this study. Each woman underwent UI determination and urinary creatinine (Cr) measurement and recorded the details of her diet and salt intake at the beginning and end of one week., Results: In total, 139 healthy pregnant women underwent UI determination in this study; among them, 116 participants completed the diet survey. The median urine iodine/ creatinine (UI/Cr) of the 139 patients was 216 μg/g, and the median dietary iodine level of 104 patients who completed the 7-day dietary record was 230 μg/d. The dietary iodine sources of the pregnant women were mainly seafood (11%), iodized salt (51%), iodized multivitamins (17%) and daily food (21%)., Conclusions: We concluded that healthy pregnant women in Chengdu showed appropriate iodine nutritional status. The 7-day dietary record can be a nice way to evaluate dietary iodine nutritional status, and there is a strong correlation between dietary iodine intake and UI concentration.

Melanoma has gradually entered the public view because of its high morbidity and rising prevalence rate, which is a serious threat to human life and health. Recently, N6-methyladenine (m6A) modification has been increasingly confirmed as a potential role in the development of tumogenesis. The purpose of this study is to explore the role and function of m6a-related regulators in the development of melanoma disease at the molecular, cellular and clinical levels through bioinformatics and traditional experiments. We screened and validated differential expression genes (DEGs) in m6A regulators via the GEO, GTEx, TCGA database. The biological processes and signaling pathway involved by DEGs were improved by constructing bioinformational methods such as PPI, GO enrichment, KEGG enrichment, GSEA enrichment, and immune infiltration analysis. And then, we explored the biological function of the key gene, SPRR1B, through cell invasion, migration, infiltration, and tissue chips. The gene IGF2BP3 which was differentially expressed in m6A regulatory factor gene was screened. The results of the enrichment analysis are significantly enriched in the biological processes and pathways of the skin barrier, epidermal differentiation, cytoskeleton, lymphocyte migration and other pathways, pointing to the direction of tumor immunity and tumor metastasis. Tumor immune-related genes YTHDC1, YTHDC2 and ALKBH5 were found. Knock SPRR1B reduction group had a significantly lower invasive ability, the ability to migrate. Nomogram prediction model shows that SPRR1B increased, expressing a worse prognosis. For this purpose, the relationship between m6A regulatory factor and melanoma progression was explored. At the same time, it was found that the abnormal up-regulated expression of SPRR1B before metastasis would lead to poor prognosis of melanoma. SPRR1B promotes the proliferation, invasion and migration of human melanoma cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shi, Fan, Liu, Huang and Zhou.)

Background and Aim: This single-arm, open-label, multicenter, phase 3 trial evaluated the efficacy and safety of seraprevir, an hepatitis C virus (HCV) nonstructural protein 3/4A (NS3/4A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic HCV infection without cirrhosis., Methods: Treatment-naive or interferon-experienced adult patients without cirrhosis were treated with a universal, combinational regimen of seraprevir 100 mg, twice daily and sofosbuvir 400 mg, once daily, for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response at week 12 after treatment (SVR12)., Results: Overall, 205 patients with genotype 1 HCV infection without cirrhosis were enrolled from 23 sites, 202 of whom completed the full treatment and post-treatment course and 3 discontinued follow-up. In total, 27 patients (13.2%) were interferon experienced. SVR12 was achieved by 201 out of 205 (98.0% [95% CI, 95.1%, 99.5%]) patients, 100.0% of patients with genotype 1a, and 98.0% of genotype 1b. In the other exploratory study, SVR 12 was achieved by 100% patients with genotype 2 (n = 21), genotype 3 (n = 7), and genotype 6 (n = 8). The majority of adverse events were mild to moderate and transient and did not require a specific medical intervention., Conclusions: The all-oral, ribavirin-free regimen of seraprevir and sofosbuvir is an effective and well-tolerated treatment option for Chinese patients mono-infected with HCV, including those with a history of interferon treatment., (© 2021 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The brain-gut-microbiome axis has emerged as an important pathway through which perturbations in the gut and/or microbial microenvironment can impact neurological function. Such alterations have been implicated in a variety of neuropsychiatric disorders, including depression, anxiety, and Alzheimer's Disease (AD) and the use of probiotics as therapy for these diseases remains promising. However, the mechanisms underlying the gut microenvironment's influence on disease pathogenesis and therapy remain unclear., Objective: The objective of this study is to investigate the effect of a novel probiotic formula, BIOCG, on cognitive function and pathobiological mechanisms, including amyloid processing and dendritic spine dynamics, in a mouse model of AD., Methods: BIOCG was administered for 3 months to 3xTg or 3xTg; Thy1-YFP AD mice and functional outcomes were assessed via behavioral testing and electrophysiology. Mechanisms relevant to AD pathogenesis including dendritic spine morphology and turnover, Amyloid Precursor Protein (APP) processing and microglial phenotype were also evaluated. Finally, we sequenced fecal samples following probiotic treatment to assess the impact on gut microbial composition and correlate the changes with the above described measures., Results: Mice treated with BIOCG demonstrated preserved cognitive abilities and stronger Long- Term Potentiation (LTP), spontaneous Excitatory Postsynaptic Currents (sEPSC), and glutamate-induced LTPs, indicative of functional and electrophysiological effects. Moreover, we observed attenuated AD pathogenesis, including reduced Amyloid Beta (Aβ) burden, as well as more mature dendritic spines in the BIOCG-treated. Our finding of changes in microglial number and phenotype in the treatment group suggests that this formulation may mediate its effects via attenuation of neuroinflammation. Sequencing data confirmed that the gut microbiome in treated mice was more varied and harbored a greater proportion of "beneficial" bacteria., Conclusion: Overall, our results indicate that treatment with BIOCG enhances microbial diversity and, through gut-brain axis interactions, attenuates neuroinflammation to produce histologic and functional improvement in AD pathogenesis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Porcine reproductive and respiratory syndrome (PRRS) caused by a single-stranded RNA virus (PRRSV) is a highly infectious respiratory disease and leads to huge economic losses to the swine industry worldwide. To investigate the role of miRNAs in the infection and lung injury induced by PRRSV, the differentially expressed miRNAs (DE-miRs) were isolated from PRRSV-2 infected/mock-infected PAMs of Meishan, Landrace, Pietrain, and Qingping pigs at 9, 36, and 60 hpi. Mir-331-3p was the only common DE-miR in each set of miRNA expression profile at 36 hpi. Mir-210 was one of 7 common DE-miRs between PRRSV infected and mock-infected PAMs of Meishan, Pietrain, and Qingping pigs at 60 hpi. Mir-331-3p/mir-210 could target PRRSV-2 ORF1b, bind and downregulate porcine TNF- α/ STAT1 expression, and inhibit PRRSV-2 replication, respectively. Furthermore, STAT1 and TNF- α could mediate the transcriptional activation of MCP-1, VCAM-1 , and ICAM-1 . STAT1 could also upregulate the expression of TNF- α by binding to its promoter region. In vivo , pEGFP-N1-mir-331-3p could significantly reduce viral replication and pathological changes in PRRSV-2 infected piglets. Taken together, Mir-331-3p/mir-210 have significant roles in the infection and lung injury caused by PRRSV-2, and they may be promising therapeutic targets for PRRS and lung injury/inflammation., (Copyright © 2020 You, Qu, Zhang, Huang, Gao, Huang, Luo, Liu, Liu and Xu.)

Polypyrrole/Attapulgite-supported nanoscale zero-valent iron (PPy/APT-nZVI) composites employed to extract Naphthol Green B (NGB) from aqueous solution, were successfully fabricated by chemical oxidative polymerization and liquid-phase reduction method. Comparison experiment of different materials showed that 99.59% of NGB was removed using PPy/APT-nZVI (1:0.5) after 25 min, much higher than APT, PPy, PPy/APT and nZVI. The morphology and structure of PPy/APT-nZVI (1:0.5) composites were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), which confirmed the high disperse and activity of nZVI after supported by PPy/APT. Furthermore, dynamic studies revealed that removal process was highly consistent with not only the pseudo-second-order model for adsorption but also pseudo-first-order model for degradation process, which proved the removal was controlled by chemical surface-limiting step. A possible removal mechanism, containing prompt adsorption of NGB onto the PPy/APT-nZVI (1:0.5) surface and being degraded by nZVI, was put forward. Additionally, the stability study verified the activity of nZVI can retain longer time than that of single nZVI due to such powerfully protective layers of PPy/APT., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The convergence between amyloid precursor protein (APP) and its β-secretase β-site APP cleaving enzyme 1 (BACE1) is a prerequisite for the generation of β-amyloid peptide, a key pathogenic agent for Alzheimer's disease. Yet the underlying molecular mechanisms regulating their convergence remain unclear. Here, we show that the polarity protein partitioning-defective 3 (Par3) regulates the polarized convergence between APP and BACE1 in hippocampal neurons. Par3 forms a complex with BACE1 through its first PDZ domain, which is important for regulating BACE1 endosome-to-TGN trafficking. In the absence of Par3, there is an increase in the convergence between internalized APP and BACE1. In hippocampal neurons, loss of Par3 leads to increased APP and BACE1 convergence in axons but not in dendrites. This polarized convergence mainly occurs in retrograde or stalled axonal late endocytic organelles and is likely due to compartment-specific regulation of APP trafficking by Par3. Together, our data show a novel function for Par3 in regulating polarized convergence between APP and BACE1 in hippocampal neurons., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Successful pregnancy requires normal placentation, which largely depends on the tight regulation of proliferation, invasion, and migration of trophoblast cells. Abnormal functioning of trophoblast cells may cause failure of uterine spiral artery remodeling, which may be related to pregnancy-related disorders, such as preeclampsia. Here, we reported that an actin-binding protein, α-actinin (ACTN)4, was dysregulated in placentas from early onset preeclampsia. Moreover, knockdown of ACTN4 markedly inhibited trophoblast cell proliferation by reducing AKT membrane translocation. Furthermore, E-cadherin regulated ACTN4 and β-catenin colocalization on trophoblast cell podosomes, and ACTN4 down-regulation suppressed the E-cadherin-induced cell invasion increase via depolymerizing actin filaments. Moreover, loss of ACTN4 recapitulated a number of the features of human preeclampsia. Therefore, our data indicate that ACNT4 plays a role in trophoblast function and is required for normal placental development.-Peng, W., Tong, C., Li, L., Huang, C., Ran, Y., Chen, X., Bai, Y., Liu, Y., Zhao, J., Tan, B., Luo, X., Wang, H., Wen, L., Zhang, C., Zhang, H., Ding, Y., Qi, H., Baker, P. N. Trophoblastic proliferation and invasion regulated by ACTN4 is impaired in early onset preeclampsia.

Recent studies have demonstrated that antibiotics/or probiotics administration in early life play key roles on modulating intestinal microbiota and the alterations might cause long-lasting consequences both physiologically and immunologically. We investigated the effects of early life ceftriaxone, vancomycin and Bifidobacterium bifidum TMC3115 (TMC3115) treatment on intestinal microbiota and immunity both in neonates and adults even after termination of antibiotics exposure. We found that ceftriaxone and vancomycin, but not TMC3115, significantly altered the intestinal microbiota, serum total IgE level, and the morphology and function of the intestinal epithelium in the neonatal mice. In the adult stages, the diversity and composition of the intestinal microbiota were significantly different in the antibiotic-treated mice, and ceftriaxone-treated mice exhibited significantly higher serum total IgE and OVA-specific IgE levels. TMC3115 significantly mitigated the alteration of intestinal microbiota caused by ceftriaxone not vancomycin. Antibiotics and TMC3115 can differently modulate intestinal microbiota and SCFAs metabolism, affecting the development and function of the immunity and intestinal epithelium to different degrees in neonatal mice. Neonatal ceftriaxone-induced abnormal intestinal microbiota, immunity and epithelium could last to adulthood partly, which might be associated with the enhancement of host susceptibility to IgE-mediated allergies and related immune responses, TMC3115 may protect against the side effects of antibiotic treatment, at least partly.

Background: Anxiety and depression continue to be significant comorbidities for people with HIV infection. We investigated the prevalence of and factors associated with anxiety and depression among adult HIV-infected patients across China. Methods: In this cross-sectional study, we described clinical and psychosocial variables related to depression and anxiety in 4103 HIV-infected persons. Doctors assessed anxiety and depression by asking patients whether they had experienced anxiety or depression in the prior month. Patients also self-administered the Hospital Anxiety and Depression (HAD) scale; those with score ≥8 on HAD-A/D were considered to be at high risk of anxiety or depression. Results: Associations between socio-demographic, psychosocial, and ART-related clinical factors and risk of depression or anxiety were investigated using multivariable logistic regression. Among patients assessed between 9/2014 and 11/2015, 27.4% had symptoms of anxiety, 32.9% had symptoms of depression, and 19.0% had both. Recentness of HIV diagnoses ( P = 0.046) was associated with elevated odds of anxiety. Older age ( P = 0.004), higher educational attainment ( P < 0.001), employment ( P = 0.001), support from family / friends ( P < 0.001), and sleep disturbance ( P < 0.001), and number of ART regimen switches ( P = 0.046) were associated with risk of depression, while neither sex nor transmission route showed any associations. There were no significant associations with HIV-specific clinical factors including current CD4 + T cell count and current viral load. Conclusions: Prevalence of symptoms of anxiety and depression is high in this cohort of treatment-experienced HIV patients. Psychological and social-demographic factors, rather than HIV disease status, were associated with risk of depression and anxiety. This finding highlights the need to deliver interventions to address the mental health issues affecting HIV-infected persons with fully successful immune restoration across China.

Purpose: To evaluate whether yogurt supplemented with a probiotic strain could protect middle-aged and elderly people from acute upper respiratory tract infections (URTI) using a randomized, blank-controlled, parallel-group design., Patients and Methods: Two hundred and five volunteers aged ≥45 years were randomly divided into two groups. The subjects in the intervention group were orally administered 300 mL/d of yogurt supplemented with a probiotic strain, Lactobacillus paracasei N1115 (N1115), 3.6×10 7 CFU/mL for 12 weeks, while those in the control group retained their normal diet without any probiotic supplementation. The primary outcome was the incidence of URTI, and changes in serum protein, immunoglobulins, and the profiles of the T-lymphocyte subsets (total T-cells [CD3 + ], T-helper cells [CD4 + ], and T-cytotoxic-suppressor cells [CD8 + ]) during the intervention were the secondary outcomes., Results: Compared to the control group, the number of persons diagnosed with an acute URTI and the number of URTI events significantly decreased in the intervention group ( P =0.038, P =0.030, respectively). The risk of URTI in the intervention group was evaluated as 55% of that in the control group (relative risk =0.55, 95% CI: 0.307-0.969). The change in the percentage of CD3 + cells in the intervention group was significantly higher than in the control group ( P =0.038). However, no significant differences were observed in the total protein, albumin, globulin, and prealbumin levels in both groups ( P >0.05)., Conclusion: The study suggested that yogurt with selected probiotic strains such as N1115 may reduce the risk of acute upper tract infections in the elderly. The enhancement of the T-cell-mediated natural immune defense might be one of the important underlying mechanisms for probiotics to express their anti-infective effects., Competing Interests: Disclosure This work was supported by Shijiazhuang Junlebao Dairy Co. Ltd. The authors report no other conflicts of interest in this work.

This study evaluated the prevalence and factors associated with sleep disturbance in a large cohort of HIV-infected patients across China. A cross-sectional study was conducted among HIV-infected patients on antiretroviral therapy at 20 AIDS clinics. The Pittsburgh Sleep Quality Index was self-administered by subjects. Socio-demographic characteristics, medical history and HIV-related clinical data were collected. 4103 patients had complete data for analysis. Sleep disturbances were observed in 43.1% of patients. Associated factors in multivariable analysis included psychological factors: anxiety (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.44-4.00; P < 0.001), depression (OR, 2.09; 95% CI, 1.70-2.57; P < 0.001), and both anxiety and depression (OR, 5.90; 95% CI, 4.86-7.16; P < 0.001); sociodemographic factors: MSM (OR, 1.26; 95% CI, 1.04-1.52; P = 0.018), being single (OR, 1.45; 95%CI 1.21-1.74; P < 0.001), higher education (OR, 1.25; 95% CI, 1.03-1.53; P = 0.025); and clinical factors: suboptimal adherence (OR,1.51; 95% CI,1.23-1.85; P < 0.001), regimen-switching (OR, 1.94; 95% CI, 1.12-3.35; P = 0.018), and antidepressant use (OR, 1.98; 95% CI, 1.47-2.67; P = 0.044). Prevalence of sleep disturbance is high in this large Chinese cohort. Associated factors appear related to psychological and social-demographic factors. Health workers may consider routinely assessing sleep disturbances among HIV-infected patients, especially in the first three months after HIV diagnosis, and referring for mental health services, which may positively impact adherence to treatment.

Most mechanobiological investigations focused on in situ mechanical regulation of cells on stiffness-controlled substrates with few downstream applications, as it is still challenging to harvest and expand mechanically primed cells by enzymatic digestion (e.g., trypsin) without interrupting cellular mechanical memory between passages. This study develops thermoresponsive hydrogels with controllable stiffness to generate mechanically primed cells with intact mechanical memory for augmented wound healing. No significant cellular property alteration of the fibroblasts primed on thermoresponsive hydrogels with varied stiffness has been observed through thermoresponsive harvesting. When reseeding the harvested cells for further evaluation, softer hydrogels are proven to better sustain the mechanical priming effects compared to rigid tissue culture plate, which indicates that both the stiffness-controlled substrate and thermoresponsive harvesting are required to sustain cellular mechanical memory between passages. Moreover, epigenetics analysis reveals that thermoresponsive harvesting could reduce the rearrangement and loss of chromatin proteins compared to that of trypsinization. In vivo wound healing using mechanically primed fibroblasts shows featured epithelium and sebaceous glands, which indicates augmented skin recovery compared with trypsinized fibroblasts. Thus, the thermoresponsive hydrogel-based cell harvesting system offers a powerful tool to investigate mechanobiology between cell passages and produces abundant cells with tailored mechanical priming properties for cell-based applications., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: An intervention study was performed to determine if supplement containing folic acid, vitamin B 6 , and vitamin B 12 could improve cognitive function and lower homocysteine in middle-aged and elderly patients with hyperhomocysteinemia., Methods: One hundred and four participants with hyperhomocysteinemia were recruited in Tianjin, China, aged 55-94 years old. Fifty-seven individuals with hyperhomocysteinemia were included in the intervention group (vitamin B group, which received 800 µg/day of folate, with 10 mg of vitamin B 6 and 25 µg of vitamin B 12 ) and 47 patients in the placebo group. The endpoint was the improvement in cognitive function as evaluated by Basic Cognitive Aptitude Tests (BCATs). All parameters were measured before and after the treatment period of 14 weeks., Results: The BCAT total score and four sub-tests scores (digit copy, Chinese character rotation, digital working memory, and recognition of meaningless figure) of BCAT at 14 weeks significantly increased only for the vitamin B group. Serum total homocysteine (tHcy) levels significantly decreased in the intervention group, while serum concentrations of folate, vitamin B 6 , and vitamin B 12 significantly increased in the intervention group., Conclusion: The results demonstrated that supplement containing folate, vitamin B 6 , and vitamin B 12 in middle-aged and elderly patients with hyperhomocysteinemia could improve their cognitive function partly and reduce serum tHcy levels.

Objective: To systematically evaluate the clinical effect of cultured milk products as adjunctive therapy in the anti- Helicobacter pylori (H. pylori) treatment.
, Methods: The randomized controlled trials (RCT) and Quasi-randomized controlled clinical trials (Quasi-RCT), which were used to evaluate the efficacy and safety of eradicating H. pylori by fermented milk-based routine treatment, were searched and collected in Pubmed, Embase, CNKI (China National Knowledge Infrastructure), CBM (Chinese BioMedical Literature Database), Wangfang Database, VIP (VIP Citation Database) from establishment of these database to February 2015. The combined relative risk (RR) of H. pylori eradication rate and the rate of side effects were analyzed. Sub-group and sensitivity analysis was performed, and the publication bias was also tested. 
, Results: A total of 9 studies including 1 644 cases were identified. The H. pylori eradication rate was 79.5% in fermented milk products combined with routine therapy, and 67.0% in routine therapy. The combined RR of H. pylori eradication rate was 1.186 (95% CI 1.118-1.257), and the combined RR of total side effects was 0.706 (95% CI 0.373-1.340).
, Conclusion: Cultured milk products as adjunctive therapy is effective in improving the eradication rate during eradication therapy for H. pylori. However, it could not effectively decrease the risk of side effects.

Etiology of esophageal cancer has not yet been clearly documented, especially in high-risk regions. To evaluate the association between salted meat intake and esophageal squamous-cell carcinoma (ESCC) and to explore its joint effects with alcohol drinking and smoking, a population-based case-control study was conducted in a high ESCC risk area in China, including 942 incident ESCC cases and 942 age- and sex-matching controls. A validated food frequency questionnaire was used to collect information on dietary factors, alcohol drinking and tobacco smoking. Conditional logistic regressions were applied to estimate the association between salted meat intake and ESCC and its interactions with alcohol drinking and smoking, with adjustment for other confounders, including total energy intake. Salted meat intake was associated with an increased risk of ESCC, showing an exposure-response relationship (p for trend <0.001). Consumption of 50 g salted meat per week was related to an increased risk by 18% (odds ratio = 1.18, 95% confidence interval: 1.13-1.23). Salted meat in combination with either alcohol drinking or smoking had a greater risk than salted meat alone, which was more than additive. The strongest association was seen in the combination of all the three factors, particularly at the highest level of salted meat intake (odds ratio = 29.27, 95% confidence interval: 13.21-64.89). Salted meat intake is strongly associated with ESCC and its interactions with alcohol drinking and/or smoking highlights the significance of reducing salted meat intake among smokers and drinkers with respect to ESCC prevention., (© 2014 UICC.)

Our goal is to establish criteria for evaluating satisfaction of medical staff and patients of Chinese hospitals and propose measures for improvement. A survey was conducted among medical staff and patients of infectious disease hospitals in three locations, i.e., Shanghai, Chongqing, and Nanning. The analyses included item analysis, factor analysis, reliability analysis, Pearson correlation and one-way analysis of variance. For the patient group, Kaiser-Meyer-Olkin (KMO) = 0.973, Cronbach's α = 0.962 and the Pearson correlation coefficients among the five dimensions of satisfaction ranged from 0.583 to 0.795. For the medical staff group, KMO = 0.972, Cronbach's α = 0.970, and the Pearson correlation coefficients among the five dimensions of satisfaction ranged from 0.603 to 0.854. The means on the five dimensions of satisfaction for the patient group were 0.74 to 1.34, 0.81 to 1.17, 0.78 to 1.07, 0.89 to 1.34, and 0.71 to 1.10. The means on the five dimensions of satisfaction for the medical staff group were 0.17 to 1.03, ‒ 0.16 to 0.60, ‒ 0.18 to 0.74, 0.23 to 0.72, and ‒ 0.39 to 0.37. The clinicians were less satisfied with the hospitals than the patients. Medical staff and patients in Shanghai were relatively more satisfied. Improving the evaluation criteria and survey methods with respect to medical staff and patient satisfaction with Chinese hospitals may increase clinician and patient satisfaction and improve the health care environment in China.

To find a credible nutritional screening tool for evaluating relationship between nutritional status and diseases in Chengdu female residents, the reliability and validity of a revised semi-quantitative food frequency questionnaire (SQFFQ) were tested. The validity was assessed by comparing the SQFFQ with the 'standard' method of 3 days' dietary recall, and the reliability was assessed by comparing the first SQFFQ with the second SQFFQ at 4 weeks interval. Correlation analysis showed that, for reliability, the average correlation coefficient (CC) of 22 kinds of nutrients was 0.66 and reduced to 0.60 after adjusting for energy; the average of intra-class correlation coefficients (ICC) was 0.65. For validity, the average CC was 0.35 and remained stable after adjusting for CC of energy or nutrients. Validity of 17 nutrients in SQFFQ survey had correlation with result of 3 days' dietary recall. The results showed that the revised SQFFQ can be used for investigating the role of nutrients in development of disease in Chengdu female residents.

Objective: To develop a new model of desirable dietary pattern (N-DDP) score for Chinese diets and to validate it against the nutrient-rich foods (NRF) index., Design: The N-DDP score model followed the principles of the traditional DDP (T-DDP) score model (DDP-China for 2000) proposed in 1991 and of food grouping in the dietary pagoda for Chinese residents in 2007, and made detailed ratings by expressing the food weight coefficient, reasonable maximum limit of the score and an algorithm of the deserved score for each group of foods after considering current nutritional problems of Chinese residents. The N-DDP score model was validated against the NRF9·3 index with linear regression analysis and compared with the T-DDP score model. Settings One set of dietary data was extracted from the diet recommended by the dietary pagoda for Chinese residents in 2007 and the literature on dietary surveys in China. The other two sets of dietary data were from a dietary survey in 2011. DDP scores for all three dietary data sets were calculated with the N-DDP score model and the T-DDP score model., Subjects: All items of dietary records in the three dietary data sets were included in the present study., Results: All DDP scores obtained with the N-DDP score model were positively correlated (P = 0·000) with the NRF9·3 index. DDP scores obtained with the N-DDP score model had higher R 2 with the NRF9·3 index than those of the T-DDP score model, as well as higher β values., Conclusions: It can be considered that the N-DDP score is a more accurate and convenient tool to evaluate current individual and group diet for Chinese residents.

Zinc supplementation can help maintain learning and memory function in rodents. In this study, we hypothesized that zinc supplementation could antagonize the neurotoxicity induced by aluminum in rats. Animals were fed a diet containing different doses of zinc (50, 100, 200 mg/kg) for 9 weeks, and orally administered aluminum chloride (300 mg/kg daily) from the third week for 7 consecutive weeks. Open-field behavioral test results showed that the number of rearings in the group given the 100 mg/kg zinc supplement was significantly increased compared with the group given the 50 mg/kg zinc supplement. Malondialdehyde content in the cerebrum was significantly decreased, while dopamine and 5-hydroxytryptamine levels were increased in the groups given the diet supplemented with 100 and 200 mg/kg zinc, compared with the group given the diet supplemented with 50 mg/kg zinc. The acetylcholinesterase activity in the cerebrum was significantly decreased in the group given the 100 mg/kg zinc supplement. Hematoxylin-eosin staining revealed evident pathological damage in the hippocampus of rats in the group given the diet supplemented with 50 mg/kg zinc, but the damage was attenuated in the groups given the diet supplemented with 100 and 200 mg/kg zinc. Our findings suggest that zinc is a potential neuroprotective agent against aluminum-induced neurotoxicity in rats, and the optimal dosages are 100 and 200 mg/kg.

The present study investigated the potential health-promoting effects of heat-inactivated Lactobacillus gasseri TMC0356 (TMC0356) on the metabolic syndrome (MS) and the probable mechanisms underlying these effects using an MS rat model. For the purpose of the study, sixty Sprague-Dawley rats were randomly divided into five groups: a control group fed a conventional diet, an MS model group fed a high-fat and high-salt (HFS) diet and three TMC0356 test groups (low-, medium- and high-dose groups) fed an HFS diet supplemented with TMC0356 at 41.8, 83.5 and 167.0 mg/kg body weight (BW) per d, respectively. Food intake and BW were measured weekly. Fasting blood glucose (FBG), lipid profiles and blood pressure (BP) were measured at 0, 5, 10 and 15 weeks. Organ coefficients, immune cell counts and serum insulin, adiponectin, C-reactive protein (CRP), IL-6, TNF-α, IgG and secretory IgA levels were measured at the 15th week after diet intervention. The HFS diet increased the BW, liver or fat:BW ratio, FBG, homeostatic model assessment of insulin resistance, adiponectin, serum LDL-cholesterol and total cholesterol levels and BP (P< 0.01). Average food and energy intakes in the three TMC0356 groups were significantly lower than those of the MS model group. All the metabolic indices, except BP, were markedly improved (P< 0.05) by oral administration of low and medium doses of TMC0356. The thymus index in the medium-dose group and lymphocyte, CRP, IL-6, TNF-α and IgG levels in all the three TMC0356 groups were significantly increased (P< 0.05 or P< 0.01) compared with those in the MS model group. These results suggest that TMC0356 can improve the metabolic characteristics of MS rats by suppressing appetite. Additionally, the enhancement of inflammatory immune response may be, at least in part, the mechanism underlying the health-promoting effects of TMC0356 on the MS.

This study was conducted to investigate the association between consumption of processed foods and esophageal cancer risk. A population-based case-control study was designed. For the present study, 254 patients with esophageal squamous cell carcinoma with pathological diagnoses were selected from Yanting during 2008 and 2010 and 254 community-based controls were selected from the same area, individually matched with cases by age and sex. Data on demographic, lifestyle and dietary factors were collected using food frequency questionnaires. A conditional logistic regression model was used to estimate the odds ratio (OR) with adjustments for potential confounders. Compared to the frequency of <1 time/week, the intake frequency of >3 times/week of preserved vegetables had a significant association with esophageal cancer (OR = 5.01, 95% confidence interval [CI] 2.07, 12.17). In stratified analyses, the OR of increasing intake of preserved vegetables for esophageal cancer were 2.02 in men (95% CI 1.18, 3.48), 3.15 in women (95% CI 1.28, 7.75), 2.41 (95% CI 1.45 4.01) in the persons <65 years old and 1.28 (95% CI 0.35, 4.65) in persons ≥65 years old. Consumption of pickled vegetables was not associated significantly with esophageal cancer risk. Intake of salted meat with a frequency of ≥1 time/week meant that the OR increased to 2.57 (95%CI 1.02, 6.43), but no significant trend or association in subgroup analysis was observed. Preserved vegetable consumption was associated with increased risk of esophageal cancer, while no association was found with pickled vegetables., (© 2012 Japanese Cancer Association.)

The objective of this study was to develop a new Tween-80 microbiological assay (Tween-80 MBA) to determine human or animal serum folate levels and to verify its reliability. The effects of the Lactobacillius casei subspecies rhamnosus (L. casei, ATCC No. 7469) inoculum concentration, incubation time, and Tween-80 on L. casei growth were studied, and the serum folate levels were investigated. Serum samples were collected from patients with esophageal cancer (EC) and healthy control subjects in Yanting, healthy adult subjects in Chengdu, Sichuan, and in male Sprague-Dawley rats. Optimal conditions for the new MBA were as follows: 1.28 x 10(7) CFU/mL working inoculum, vitamin folic acid assay broth with 0.24% (w/w) Tween-80, and anaerobic incubation with L. casei at 37 degrees C for 22 h. Under the optimal conditions, the working curve was in simple linear rather than logarithmic equation; the linear working curve of the folic acid standard working solution concentration versus the turbidity (adsorption value) of medium with L. casei ranged from 0.05 to 1.00 microg/L; the linear correlation coefficient was 0.9989 (SD 0.0007); the recovery rate of folate was 105.4-112.7%; and the minimum concentration for detecting folate was 0.03 microg/L. The RSD within-day and between-day precisions were 5.6 and 3.3%, respectively. The serum folate level of 100 EC patients was 6.4 (SEM 0.4) microg/L which was significantly lower than that of healthy control subjects [8.0 (SEM 0.6) microg/L, n = 100, P=0.020]. The new Tween-80 MBA is considered to be a reliable method for measuring serum folate level.

Objective: The effect of serum from rats supplemented with selenium and zinc on the proliferation of human esophageal cancer cell line Eca109 was observed by serophysiology., Methods: Rats were randomly divided into seven groups. Eight rats in each group were fed with basic feeds (deprived of both selenium and zinc). The experimental rat groups were supplemented with selenium or zinc at low or high dosage intragastrically for 30 days Serum selenium and zinc content of rats was measured by Graphite Furnace Atomic Absorption Spectrometry (GFAAS) and Flame Atomic Absorption Spectrophotometry (FAAS). MTT assay,3H-TDR incorporation and flow cytometry were used to explore the effect of serum from different rat groups on the growth and proliferation of cancer cell line Ecal09 cells., Results: (1) The content of serum zinc in the high zinc group was the highest and the content of serum zinc was the lowest in basic diet group. The content of serum selenium in high selenium and high zinc group was the highest and the content of serum selenium was the lowest in the basic diet group. (2) In comparing the growth of control cancer cell group cultured with calf serum, the growth of cancer cells cultured with the serum from high selenium and high zinc rats was inhibited in culturing for 72 h, but the growth of normal liver cells were also inhibited. The growth of cancer cells were promoted by serum from other groups. (3) Both MTT assay and 3H-TDR incorporation test showed that the DNA synthesis in cancer cells was inhibited by the serum from high selenium and high zinc group, but the DNA synthesis of normal liver cells was also inhibited by this type of serum. The result of DNA synthesis in other cell groups was closed to the control group., Conclusions: Low serum selenium and zinc might promote the growth of EC cell. Elevating the content of serum selenium and zinc by increasing selenium and zinc intake might inhibit EC cell proliferation.

Objective: To measure the energy expenditure of healthy adults engaged in light activities in southern China, and to provide reference database for revising Chinese RNI., Methods: Thirty four healthy adults eligible for the energy metabolic experiment were selected. A 3-day recycled dietary prescription was designed. The food intake of all foods per person per meal were weighed and recorded, and the energy intake from diets was determined by chemical analysis. The energy expenditure was calculated by combining the change of body weight and dietary consumption., Results: The average energy intake was (8424 +/- 1616) kJ/d [(2013 +/- 386) kcal/d], which was (9990 +/- 798) kJ/d [(2388 +/- 191) kcal/d] for men and (7032 +/- 384)kJ/d [(1681 +/- 92) kcal/d] for women. The average change of body weight of all subjects in 16 days was reduced 0.02 kg, the men increased 0.15 kg, and the women decreased 0.17 kg. According to the energy balance principle, the ultimate energy expenditure of healthy adults in southern China was (8468 +/- 1762) kJ/d [(2024 +/- 421) kcal/d], the men was (9680 +/- 1759) kJ/d [(2314 +/- 420) kcal/d], and the women was (7391 +/- 827) kJ/d [(1767 +/- 198) kcal/d]., Conclusions: The energy expenditure of healthy adult male engaged in light activities in southern China was 9680 +/- 1759 kJ/d [(2314 +/- 420 kcal/d)], and that of female was 7391 +/- 827 kJ/d [(1767 +/- 198 kcal/d)]. The energy expenditure of men and women measured in this study were 86kcal and 333kcal lower than the Chinese energy RNI (2400kcal and 2100 kcal) established in 2000.

Objective: To investigate relations between milk consumption and lactose intolerance (LI) in adults and to explore the effect of milk consumption on lactase activity., Methods: Total of 182 subjects aged 20-70 years were recruited and interviewed by questionnaires, and their accumulative cow's milk intake (AMI) was calculated. LI was evaluated by hydrogen breath test (HBT)., Results: A negative correlation was found between AMI and severity of observed LI symptom (r=-0.2884; P<0.05). Binary logistic regression analysis showed a negative correlation between LI and duration and frequency of milk consumption (OR, 0.317 and 0.465, respectively; both P<0.05) and a positive correlation between LI and amount of milk consumed per sitting (OR, 6.337; P<0.05)., Conclusion: LI is related to various milk consumption behaviors. Most Chinese adults with LI may tolerate moderate milk consumption <160 mL., (Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.)

Objective: Using an energy zero balance method to investigate and analyze the level of dietary energy intake of healthy adults in southern China, in order to provide basic data for revising Chinese energy DRIs., Methods: A total of 32 healthy adults engaged in light physical activities were recruited randomly. The food intake of each subject including meals and snacks was weighed and made records at same days intervals in a period of 2 month (covering Monday to Sunday of a week). The energy intake was calculated and adjusted with the change of body weight according to the energy balance principle., Results: The average total energy intake of subjects in energy zero balance was (8.895 +/- 1.535) MJ/d, (10.070 +/- 1.150) MJ/d for male and (7.719 +/- 0.765) MJ/d for female., Conclusion: The energy intake of healthy adults at zero balance could be measured at same days intervals within a 2 month period. The method was convenient, economical, available and practicable.