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Abstract Coal-series diatomite (CSD) is widely distributed in China and has poor functional and structural properties and exhibits limited utilization of high value-added materials, resulting in a serious waste of resources and tremendous pressure on the environment. Moreover, due to differences in the mineralogical characteristics of CSD, different particle size scales (PSSs) have different functional structures and exhibit different self-similarities. In this study, we took CSD as the research object and PSS as the entry point and carried out a self-similarity study based on gas adsorption and an image processing method to illustrate the microstructures and self-similarities of different PSSs. The results showed that the pore structure of the CSD was dominated by mesopores and macropores and basically lacked micropores. The fractal dimensions were calculated with the Frenkel-Haisey-Hill (FHH) model and Menger model, and the D F1 values for − 0.025 mm and − 2 mm were 2.51 and 2.48, respectively, and the D M1 values were 3.75 and 3.79, respectively, indicating that the mesopore structure of the fine PSS was complex, whereas macropores were present in the coarse PSS. MATLAB was programmed to obtain grayscale thresholds, binarized images, grayscale histograms, three-dimensional (3D) reconstruction images and box dimensions, which enabled us to observe the microstructures and self-similarities of the CSD. Self-similarity studies based on particle sizes are very important for functional application of CSD.Please note that article title mismatch between MS and JS we have followed MS, kindly check and cofirm.Yes, I have checked and confirmed.Kindly check and confirm corresponding author mail id are correctly identified.Yes, I have checked and confirmed.

Abstract The boom-type roadheader plays a crucial role in coal mining. However, conducting the real-time monitoring of the mechanical performance and comprehensive adaptive cutting in the dynamic cutting process are challenging. To address these issues, a digital twin system that integrates the elements of “shape, performance, and control” for roadheaders is presented in this paper. The system comprises three components: physical space, service space, and twin space. The service space forms the core of the entire system. Within this space, twin models and control models are created using numerical simulation, artificial intelligence and multi-source data fusion technology. These models serve the purpose of predicting the roadheader’s mechanical performance and controlling the swing speed of the cutting arm. The physical space is built using technologies such as robot kinematics, electrical systems, hydraulic transmission, and other relevant techniques. This approach facilitates the transmission of multi-sensor data to twin models. The control model then manages the roadheader’s function based on the output signals from the control model. The twin space is constructed utilizing physical rendering engines, databases, and 3D modelling tools. This space visualizes and stores the movement, performance, and control parameters of the roadheader. The results demonstrate that the average absolute error between the measured data from the test’s three position strain gauges and the predicted data from the twin system is 10.38 MPa. Furthermore, the twin system achieves an average update interval of 0.34 s, allowing real-time stress monitoring of the structural components of the roadheader and preventing damage caused by overload. The proposed control model enables adaptive adjustment of the swing speed of the cutting arm in approximately 0.3 s. This improvement significantly enhances the adaptive cutting capabilities of roadheaders when dealing with complex coal and rock formations.

Abstract Rock burst disaster affects underground mining safety. The energy-absorbing hydraulic support for preventing tunnel impact has been implemented in rock burst mines. In order to compare the impact resistance characteristics of conventional columns and energy-absorbing columns, based on the derivation of energy theory, the CEL fluid–solid coupling simulation algorithm is used to simulate the process of static load 1000 kN superimposed impact load 1500 kN on φ180 mm type conventional column and energy-absorbing column. Combined with the static-dynamic combined test of the 6500 kN impact testing machine on the column, the accuracy and reliability of the CEL simulation column impact response are verified. The results showed that compared with conventional columns, the reaction force of energy-absorbing columns is reduced by 32.55%. The stress and expansion of the cylinder are significantly reduced. The acceleration of the mass movement has been reduced by 59.46%. The addition of the energy-absorbing device enhances the system's energy absorption by 33.46%, thereby reducing the energy absorption of the column itself to 23.58%. Additionally, the deformation of the energy-absorbing device increases the effective displacement by 239.45%. This also prolongs the impact duration, ensuring sufficient time for the safety valve to open, safeguarding the support from damage, and enhancing the overall integrity of the tunnel.

To address the epidemic, such as COVID-19, the government may implement the home quarantine policy for the infected residents. The logistics company is required to control the risk of epidemic spreading while delivering goods to residents. In this case, the logistics company often uses vehicles and unmanned aerial vehicles (UAVs) for delivery. This paper studies the distribution issue of cold chain logistics by integrating UAV logistics with epidemic risk management innovatively. At first, a "vehicle-UAV" joint distribution mode including vehicles, small UAVs and large UAVs, is proposed. The green cost for vehicles and UAVs is calculated, respectively. The formula for infection risk due to large numbers of residents gathering at distribution centers to pick up goods is then derived. Furthermore, based on the control of infection risk, an optimization model is developed to minimize the total logistics cost. A modified ant colony algorithm is designed to solve the model. The numerical results show that the maximum acceptable risk and the crowd management level of distribution centers both have significant effects on the distribution network, logistics cost and number of new infections. Our study provides a new management method and technical idea for ensuring the needs of residents during the epidemic.

BackgroundThis study aims to study the possible action mechanism of T-cell immunoglobulin and mucin domain 3 (TIM3) on the migratory and invasive abilities of thyroid carcinoma (TC) cells.MethodsGSE104005 and GSE138198 datasets were downloaded from the GEO database for identifying differentially expressed genes (DEGs). Functional enrichment analysis and protein-protein interaction (PPI) analysis were performed on the common DEGs in GSE104005 and GSE138198 datasets. Subsequently, in order to understand the effect of a common DEG (TIM3) on TC cells, we performed in vitro experiments using FRO cells. The migratory and invasive abilities of FRO cells were detected by wound scratch assay and Transwell assay. Proteins expression levels of the phosphorylated (p)-extracellular signal-regulated kinase (ERK)1/2, matrix metalloproteinase-2 (MMP-2) and MMP-9 were determined via Western blotting after ERK1/2 inhibition in TIM3-NC group and TIM3-mimic group.Results316 common DEGs were identified in GSE104005 and GSE138198 datasets. These DEGs were involved in the biological process of ERK1 and ERK2 cascade. TIM3 was significantly up-regulated in TC. In vitro cell experiments showed that TIM3 could promote migration and invasion of TC cells. Moreover, TIM3 may affect the migration, invasive abilities of TC cells by activating the ERK1/2 pathway.ConclusionThe above results indicate that TIM3 may affect the migratory and invasive of TC cells by activating the ERK1/2 pathway.

This study aimed to understand the prevalence of hyperuricemia and MetS in the United States and evaluate the potential effect of gender and ethnicity on hyperuricemia and MetS. Data was obtained from National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018. Logistic regression analysis was utilized to investigate the association between hyperuricemia and MetS. A total of 7273 participants with an average age of 47.59 ± 16.92 years old were enrolled in our analysis. Of all the people, 1833 were diagnosed with MetS, with which 547 (29.8 %) were found with hyperuricemia. As for gender, 261 (28.3 %) females were with both Mets and hyperuricemia and this number came to 286 (31.4 %) for males.For population distribution, Non-Hispanic American white, and Hispanic American making up 61.2 % of the cohort. The logistic regression analysis showed that there was a significant association between MetS and hyperuricemia (OR = 2.608, 95 %CI: 2.281–2.982). And the relationship still existed between both males (OR = 2.172, 95 %CI: 1.829–2.579) and females (OR = 3.464, 95 %CI: 2.868–4.185); in addition, participant’s ethnicity was also found to play an important role. And the association was found either in Hispanic Americans Non-Hispanic Americans White and black or from other races. In conclusion, our study found a significant association between hyperuricemia and MetS. The higher the uric acid level, the greater risk of people getting MetS and this risk was not influenced by people’s gender and ethnicity.

Introduction To explore the epidemiological characteristics of ankylosing spondylitis (AS) in Guangxi Province of China through a large sample survey of more than 50 million aboriginal aboriginal population. Material and methods A systematic search was conducted using the International Classification of Diseases 10 (ICD-10) codes M45.x00(AS), M45.x03+(AS with iridocyclitis), and M40.101(AS with kyphosis) to search the database in the National Health Statistics Network Direct Reporting System (NHSNDRS). 14004 patients were eventually included in the study. The parameters analyzed included the number of patients, gender, marriage, blood type, occupation, age at diagnosis, and location of household registration data each year, and statistical analysis was performed. Results AS incidence rates increased from 1.30 (95% CI: 1.20–1.40) per 100,000 person-years in 2014 to 5.71 (95% CI: 5.50–5.92) in 2020 in Guangxi Province, and decreased slightly in 2021. Males have a higher incidence than females; the ratio was 5.61 : 1. The mean age of diagnosis in male patients was 45.4 (95% CI: 45.1–45.7) years, in females 47.6 (95% CI: 46.8–48.4) years. The most frequent blood type was O, and the most frequent occupation was farmer. The AS incidence rate was disparate in different cities. Liuzhou city had the highest eight-year average AS incidence rates from 2014 to 2021, and Chongzuo city had the lowest (p 0.05). Conclusions The AS person-years incidence rate was increasing in Guangxi province of China from 2014 to 2020, which had obvious gender and regional differences, showing the characteristics of local area aggregation.

Abstract The significance of N6-methyladenosine (m6A) RNA modifications in the progression of breast cancer (BC) has been recognised. However, their potential role and mechanism of action in the tumour microenvironment (TME) and immune response has not been demonstrated. Thus, the role of m6A regulators and their downstream target gene components in BC remain to be explored. In this study, we used a series of bioinformatics methods and experiments to conduct exploratory research on the possible role of m6A regulators in BC. First, two regulatory modes of immune activation and inactivation were determined by tumour classification. The TME, immune cell infiltration, and gene set variation analysis results confirmed the reliability of this pattern. The prognostic model of the m6A regulator was established by the least absolute shrinkage and selection operator and univariate and multivariate Cox analyses, with the two regulators most closely related to survival verified by real-time quantitative reverse transcription polymerase chain reaction. Next, the prognostic m6A regulator identified in the model was crossed with the differential copy number of variant genes in invasive BC (IBC), and it was determined that YTHDF1 was a hub regulator. Subsequently, single-cell analysis revealed the expression patterns of m6A regulators in different IBC cell populations and found that YTHDF1 had significantly higher expression in immune-related IBC cells. Therefore, we selected the intersection of the BC differential expression gene set and the differential expression gene set of a cell line with knocked-down YTHDF1 in literature to identify downstream target genes of YTHDF1, in which we found IFI6, EIR, and SPTBN1. A polymerase chain reaction was conducted to verify the results. Finally, we confirmed the role of YTHDF1 as a potential prognostic biomarker through pan-cancer analysis. Furthermore, our findings revealed that YTHDF1 can serve as a new molecular marker for BC immunotherapy.

Abstract Objective Tuberous sclerosis complex (TSC) is a rare autosomal dominant disease characterized by lesions throughout the body. Our previous study showed the abnormal up-regulation of miRNAs plays an important part in the pathogenesis of TSC-related renal angiomyolipoma (TSC-RAML). circRNAs were known as important regulators of miRNA, but little is known about the circRNAs in TSC-RAMLs. Methods Microarray chips and RNA sequencing were used to identify the circRNAs and mRNAs that were differently expressed between the TSC-RAML and normal kidney tissue. A competitive endogenous RNA (ceRNA) regulatory network was constructed to reveal the regulation of miRNAs and mRNAs by the circRNAs. The biological functions of circRNA and mRNA were analyzed by pathway analysis. Microenvironmental cell types were estimated with the MCP-counter package. Results We identified 491 differentially expressed circRNAs (DECs) and 212 differentially expressed genes (DEGs), and 6 DECs were further confirmed by q-PCR. A ceRNA regulatory network which included 6 DECs, 5 miRNAs, and 63 mRNAs was established. Lipid biosynthetic process was significantly up-regulated in TSC-RAML, and the humoral immune response and the leukocyte chemotaxis pathway were found to be down-regulated. Fibroblasts are enriched in TSC-RAML, and the up-regulation of circRNA_000799 and circRNA_025332 may be significantly correlated to the infiltration of the fibroblasts. Conclusion circRNAs may regulate the lipid metabolism of TSC-RAML by regulation of the miRNAs. Fibroblasts are enriched in TSC-RAMLs, and the population of fibroblast may be related to the alteration of circRNAs of TSC-RAML. Lipid metabolism in fibroblasts is a potential treatment target for TSC-RAML.

Abstract In the burgeoning microbiome field, powerful sequencing approaches and accompanied bioanalytical methods have made tremendous contributions to the discoveries of breakthroughs, which favor to unravel the intimate interplay between gut microbiota and human health. The proper preservation of samples before being processed is essential to guarantee the authenticity and reliability of microbiome studies. Hence, the development of preservation methods is extremely important to hold samples eligible for the consequent analysis, especially population cohort-based investigations or those spanning species or geography, which frequently facing difficulties in suppling freezing conditions. Although there are several commercial products available, the exploration of cost-efficient and ready-to-use preservation methods are still in a large demand. Here, we performed shotgun metagenomic sequencing and demonstrated that microbial consortia in human fecal samples were substantially preserved within a temporary storage of 4 h, independent of the storage temperature. We also verified a previous reported self-made preservation buffer (PB buffer) could not only preserve fecal microbiota at room temperature up to 4 weeks but also enable samples to endure a high temperature condition which mimics temperature variations in summer logistics. Moreover, PB buffer exhibited suitability for human saliva as well. Collectively, PB buffer may be a valuable choice to stabilize samples if neither freezing facilities nor liquid nitrogen is available.

Abstract The aim of this study was to retrospectively compare hematological parameters among normal, α-, and β-thalassemia fetuses between 17 and 38 weeks of gestation. Pregnant women at risk of having fetuses with thalassemia major and underwent cordocentesis for prenatal diagnosis were recruited. Fetal cord blood samples were collected from 249 fetuses for hematological and DNA analysis. Fetuses were divided into subgroups according to thalassemia DNA genotypes. The average and gestational age of subjects were 27.95 ± 5.78 years and 27.78 ± 3.57 weeks, respectively. The distribution of α-thalassemia, β-thalassemia, and normal cases was 67.87%, 19.68%, and 12.45%, respectively. Significant differences in almost all the hematological parameters (HbF, HbA, Hb, HCT, MCV, MCH, MCHC, RDW, and NBRCs) were observed in three groups (P

De novo and acquired resistance are major impediments to the efficacy of conventional and targeted cancer therapy. In unselected gastric cancer (GC) patients with advanced disease, trials combining chemotherapy and an anti-EGFR monoclonal antibody have been largely unsuccessful. In an effort to identify biomarkers of resistance so as to better select patients for such trials, we screened the secretome of chemotherapy-treated human GC cell lines. We found that levels of CGA, the α-subunit of glycoprotein hormones, were markedly increased in the conditioned media of chemoresistant GC cells, and CGA immunoreactivity was enhanced in GC tissues that progressed on chemotherapy. CGA levels in plasma increased in GC patients who received chemotherapy, and this increase was correlated with reduced responsiveness to chemotherapy and poor survival. Mechanistically, secreted CGA was found to bind to EGFR and activate EGFR signaling, thereby conferring a survival advantage to GC cells. N-glycosylation of CGA at Asn52 and Asn78 is required for its stability, secretion, and interaction with EGFR. GATA2 was found to activate CGA transcription, whose increase, in turn, induced the expression and phosphorylation of GATA2 in an EGFR-dependent manner, forming a positive feedback circuit that was initiated by GATA2 autoregulation upon sublethal exposure to chemotherapy. Based on this circuit, combination strategies involving anti-EGFR therapies or targeting CGA with microRNAs (miR-708-3p and miR-761) restored chemotherapy sensitivity. These findings identify a clinically actionable CGA/EGFR/GATA2 circuit and highlight CGA as a predictive biomarker and therapeutic target in chemoresistant GC.

Background: mRNA-based cancer vaccines have been considered a promising anticancer therapeutic approach against various cancers, yet their efficacy for malignant mesothelioma (MESO) is still not clear. The present study is designed to identify MESO antigens that have the potential for mRNA vaccine development, and to determine the immune subtypes for the selection of suitable patients. Methods: A total of 87 MESO datasets were used for the retrieval of RNA sequencing and clinical data from The Cancer Genome Atlas (TCGA) databases. The possible antigens were identified by a survival and a genome analysis. The samples were divided into two immune subtypes by the application of a consensus clustering algorithm. The functional annotation was also carried out by using the DAVID program. Furthermore, the characterization of each immune subtype related to the immune microenvironment was integrated by an immunogenomic analysis. A protein–protein interaction network was established to categorize the hub genes. Results: The five tumor antigens were identified in MESO. FAM134B, ALDH3A2, SAV1, and RORC were correlated with superior prognoses and the infiltration of antigen-presenting cells (APCs), while FN1 was associated with poor survival and the infiltration of APCs. Two immune subtypes were identified; TM2 exhibited significantly improved survival and was more likely to benefit from vaccination compared with TM1. TM1 was associated with a relatively quiet microenvironment, high tumor mutation burden, and enriched DNA damage repair pathways. The immune checkpoints and immunogenic cell death modulators were also differentially expressed between two subtypes. Finally, FN1 was identified to be the hub gene. Conclusions: FAM134B, ALDH3A2, SAV1, RORC, and FN1 are considered as possible and effective mRNA anti-MESO antigens for the development of an mRNA vaccine, and TM2 patients are the most suitable for vaccination.

Abstract We report on a method to experimentally generate ionic wind by coupling an external large electric field with an intense femtosecond laser induced air plasma channel. The measured ionic wind velocity could be as strong as >4 m/s. It could be optimized by increasing the strength of the applied electric field and the volume of the laser induced plasma channel. The experimental observation was qualitatively confirmed by a numerical simulation of spatial distribution of the electric field. The ionic wind can be generated outside a high-voltage geometry, even at remote distances.

Brain hemorrhage: Lactate aids in recovery After a blood vessel bursts in the brain, lactate, a metabolic intermediary, accumulates around the bleeding site to increase new blood vessels and neurons. A team led by Tao Tang and Yang Wang at Central South University in Changsha, China, experimentally induced brain hemorrhage in rats and examined the effects of lactate in the brain. They showed that this metabolic signaling molecule protected against cell death and increased expression of growth factors involved in blood vessel formation and neural regeneration. Inhibiting lactate blocked these effects, while infusing exogenous lactate into the rat brains enhanced them. The findings suggest that lactate promotes angiogenesis and neurogenesis in experimental intracerebral hemorrhage.

Abstract Background Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder characterized by the development of numerous benign tumors. Renal angiomyolipoma (RAML) occur in up to 80% of TSC patients, which is a leading cause of TSC-related death in adult patients. The aim of the study was to evaluate the efficacy and safety profiles of everolimus in Chinese patients of TSC associated with RAML(TSC-RAML). Methods In this 2-years, nonrandomized, open-label trial, 18 patients of TSC-RAML, with at least one RAML 3 cm or larger in its longest diameter, were enrolled to assess the efficacy and safety of everolimus therapy in Chinese patients. Everolimus was administered for the first 12 months only. The primary endpoint was a reduction of 50% or more relative in RAML volume to the baseline in the absence of new RAML ≥1 cm and no RAML-related bleeding of grade ≥ 2. The secondary endpoints included: safety, lung function and skin lesions response rate. Serial computed tomography of RAML, magnetic resonance imaging of brain lesions and pulmonary-function tests were performed. Adverse events were investigated using CTCAE v4.0. All analyses used a significance level of 0.05 and were generated in SPSS19.0 software. Results The proportion of patients who achieved ≥50% reduction from baseline in the sum of volumes of target lesions increased from 52.94% at 3 months, to 58.82% and 66.67% at months 6 and 12, respectively. During the period of everolimus therapy, among patients with lymphangioleiomyomatosis, the mean forced expiratory volume in 1 s (FEV1) increased by 276 ± 78 ml (P

Abstract We report herein a visible light sensitizer-catalyzed aerobic oxidation of thioethers, affording sulfoxides in good to excellent yields. The loading of the catalyst was as low as 0.1 mol%. The selectivity was excellent. Mechanism studies showed both singlet oxygen and superoxide radical anion were likely involved in this transformation.

Abstract In realistic social system, the role or influence of each individual varies and adaptively changes in time in the population. Inspired by this fact, we thus consider a new coevolution setup of game strategy and vertex weight on a square lattice. In detail, we model the structured population on a square lattice, on which the role or influence of each individual is depicted by vertex weight, and the prisoner’s dilemma game has been applied to describe the social dilemma of pairwise interactions of players. Through numerical simulation, we conclude that our coevolution setup can promote the evolution of cooperation effectively. Especially, there exists a moderate value of δ for each ε that can warrant an optimal resolution of social dilemma. For a further understanding of these results, we find that intermediate value of δ enables the strongest heterogeneous distribution of vertex weight. We hope our coevolution setup of vertex weight will provide new insight for the future research.

Abstract We report a facile method for preparing silver-loaded membranes for point-of-use disinfection and disaster relief applications. A bio-inspired material, polydopamine, was coated onto a highly porous nanofibrous polyacrylonitrile substrate. We then take advantage of the redox properties of polydopamine to form silver nanoparticles in situ. These nanoparticles were uniformly distributed on the surface of nanofibers with no apparent agglomeration at a silver loading up to 4.36 wt.% (cPAN-Ag1.5). The silver-incorporated membrane cPAN-Ag1.5 achieved a high pure water flux of 130 Lm−2 h−1 at 10-cm water head, demonstrating the feasibility of energy-efficient gravity-driven filtration and eliminating the need for electrical power. The strong anti-bacterial activity and high physical rejection of the membrane led to an excellent disinfection power, with no viable bacterial cells detected in its permeate water. The membrane exhibited >7 log reduction for E. coli and >6 log reduction for B. subtilis. The strategy reported here provides an efficient and green route to synthesize point-of-use membranes. Combining their excellent permeability and disinfection effectiveness, these membranes offer an ideal solution to water supply in disaster-affected areas.

Background Rheumatoid arthritis (RA) is a chronic and nonspecific autoimmune disease, which leads to joint destruction and deformity. To investigate the potential of human mesenchymal stem cells (MSCs) as a new therapeutic strategy for patients with RA, we compared the therapeutic effects of bone marrow derived MSCs (BMSCs), umbilical cord derived MSCs (UCs), and stem cells derived from human exfoliated deciduous teeth (SHED) on collagen-induced arthritis (CIA) in mice. Methods A total of 24 DBA/1 mice were infused with type II collagen to induce RA in the experimental model. MSC-treated mice were infused with UCs, BMSCs, and SHED, respectively. Bone erosion and joint destruction were measured by micro-computed tomographic (micro-CT) analysis and hematoxylin and eosin staining. The levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were measured by immunohistochemistry and Enzyme-Linked Immunosorbent Assay (ELISA). Results Systemic delivery of MSCs significantly improved the severity of the symptoms related to CIA to greater extent compared with the untreated control group. Micro-CT revealed reduced bone erosions in the metatarsophalangeal joints upon treatment with MSCs. Additionally, according to histologic evaluation, reduced synovitis and articular destruction were observed in MSC-treated groups. The levels of TNF-α and IL-1β in the serum and joints decreased with treatment by MSCs. Conclusion Our findings suggest that systemic infusion of UCs, BMSCs, and SHED may significantly alleviate the effects of RA. The therapeutic effect of BMSCs was greater than that of SHED, while the UCs were shown to have the best therapeutic effect on CIA mice. In conclusion, compared with BMSCs and SHED, UCs may be a more suitable source of MSCs for the treatment of patients with RA.

Ischemic stroke is among the leading causes of morbidity and mortality worldwide. Improving the tolerance of neurons to ischemia and reperfusion injury could be a feasible strategy against ischemia. Adiponectin (APN) is a major adipokine that regulates glucose and lipid metabolism and plays an important role in the protection of the cerebral nervous system. We aimed to investigate the effects of APN on oxygen and glucose deprivation (OGD)-induced neuronal injury in hippocampal neuronal HT22 cells. APN displayed neuroprotective effects against OGD, evidenced by increased cell viability and decreased lactate dehydrogenase release and apoptotic rate. Additionally, APN also maintained mitochondrial ultrastructure and transmembrane potential, attenuated reactive oxygen species and malondialdehyde, and increased superoxide dismutase and glutathione peroxidase activity. Moreover, APN promoted Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) phosphorylation, enhanced STAT3 nuclear translocation, increased the Bcl-2/Bax ratio, and decreased cleaved caspase-3. The aforementioned APN-induced effects were almost reversed by a JAK2 inhibitor, AG490. APN may attenuate OGD-induced hippocampal HT22 neuronal impairment by protecting cells against mitochondrial oxidative stress and apoptosis, mediated by JAK2/STAT3 signaling.

Tumor necrosis factor-α (TNF-α), an important factor in systematic inflammation, is reportedly involved in several cancer types. The TNF-α -308 G>A (rs1800629) polymorphism in the promoter region influences TNF-α production. The association between TNF-α -308 G>A polymorphism and colorectal cancer (CRC) is not fully understood, especially the connections between TNF-α -308 G>A polymorphism and clinical features of CRC. In this study, TNF-α -308 G>A polymorphism was genotyped in 1140 individuals with or without CRC from Southwestern China. In case-control studies, we found no association between TNF-α -308 G>A polymorphism and CRC risk. Analysis of the correlations between TNF-α -308 G>A polymorphism and clinical features of CRC revealed that TNF-α -308 A allele was associated with higher body mass index (BMI) larger tumor size, and distant tumor metastasis in all CRC patients. Notably, rectal cancer (a subtype of CRC) patients with TNF-α -308 A allele had a very high risk of distant tumor metastasis [odds ratio (OR) = 4.481; 95% confidence interval (CI): 2.072-9.693; P = 0.00025]. The association between TNF-α -308 A allele and distant tumor metastasis remained even significant after adjusting all clinical characteristics (OR = 7.099; 95% CI: 2.482-20.301; P = 0.000256) in rectal cancer patients. Our results suggested that TNF-α -308 A allele was significantly associated with distant tumor metastasis in rectal cancer patients.

Recent studies have shown that variants in FAT atypical cadherin 3 (FAT3), kinectin 1 (KTN1), discs large homolog2 (DLG2) and deleted in colorectal cancer (DCC) genes influence the structure of the human mesolimbic reward system. We conducted a systematic analysis of the potential functional single nucleotide polymorphisms (SNPs) in these genes associated with heroin addiction. We scanned the functional regions of these genes and identified 20 SNPs for genotyping by using the SNaPshot method. A total of 1080 samples, comprising 523 cases and 557 controls, were analyzed. We observed that DCC rs16956878, rs12607853, and rs2292043 were associated with heroin addiction. The T alleles of rs16956878 (p = 0.0004) and rs12607853 (p = 0.002) were significantly enriched in the case group compared with the controls. A lower incidence of the C allele of rs2292043 (p = 0.002) was observed in the case group. In block 2 of DCC (rs2292043-rs12607853-rs16956878), the frequency of the T-T-T haplotype was significantly higher in the case group than in the control group (p = 0.024), and fewer C-C-C haplotypes (p = 0.006) were detected in the case group. DCC may be an important candidate gene in heroin addiction, and rs16956878, rs12607853, and rs2292043 may be risk factors, thereby providing a basis for further genetic and biological research.

Diabetic mellitus (DM) patients are at an increased risk of developing peripheral arterial disease (PAD). Danhong injection (DHI) is a Chinese patent medicine widely used for several cardiovascular indications but the mechanism of action is not well-understood. We investigated the therapeutic potential of DHI on experimental PAD in mice with chemically induced as well as genetic (KKAy) type 2 DM and the overlapping signaling pathways regulating both therapeutic angiogenesis and glucose homeostasis. Compared with normal genetic background wild type (WT) mice, both DM mice showed impaired perfusion recovery in hind-limb ischemia (HLI) model. DHI treatment significantly accelerated perfusion recovery, lowered blood glucose and improved glucose tolerance in both DM models. Bioluminescent imaging demonstrated a continuous ischemia-induced vascular endothelial growth factor receptor 2 (VEGFR-2) gene expressions with a peak time coincident with the maximal DHI stimulation. Flow cytometry analysis showed a DHI-mediated increase in endothelial progenitor cell (EPC) mobilization from bone marrow to circulating peripheral blood. DHI administration upregulated the expression of vascular endothelial growth factor A (VEGF-A) and VEGF receptor-2 (VEGFR-2) in ischemic muscle. A cross talk between ischemia-induced angiogenesis and glucose tolerance pathways was analyzed by Ingenuity Pathway Analysis (IPA) which suggested an interaction of VEGF-A/VEGFR-2 and peroxisome proliferator-activated receptor δ (PPARδ)/peroxisome proliferator-activated receptor γ (PPARγ) genes. We confirmed that upregulation of VEGF-A/VEGFR-2 by DHI promoted PPARδ gene expression in both type 2 diabetic mice. Our findings demonstrated that a multi-component Chinese medicine DHI effectively increased blood flow recovery after tissue ischemia in diabetic mice by promoting angiogenesis and improving glucose tolerance through a concomitant activation of VEGF-A/VEGFR-2 and PPARδ signaling pathways.

ObjectiveTo reveal the familial prevalence and molecular variation of α- and β-globin gene mutations in Guangdong Province.MethodsA total of 40,808 blood samples from 14,332 families were obtained and analyzed for both hematological and molecular parameters.ResultsA high prevalence of α- and β-globin gene mutations was found. Overall, 17.70% of pregnant women, 15.94% of their husbands, 16.03% of neonates, and 16.83% of couples (pregnant women and their husbands) were heterozygous carriers of α- or β-thalassemia. The regions with the highest prevalence were the mountainous and western regions, followed by the Pearl River Delta; the region with the lowest prevalence was Chaoshan. The total familial carrier rate (both spouses were α- or β-thalassemia carriers) was 1.87%, and the individual carrier rates of α- and β-thalassemia were 1.68% and 0.20%, respectively. The total rate of moderate-to-severe fetal thalassemia was 12.78% among couples in which both parents were carriers.ConclusionsThere was a high prevalence of α- and β-thalassemia in Guangdong Province. This study will contribute to the development of thalassemia prevention and control strategies in Guangdong Province.

Vascular inflammation plays an important role in the development and progression of atherosclerosis. Recently, salusins (salusin-α and salusin-β) have been reported to be associated wtih atherosclerosis. However, its underlying mechanism remains incompletely known. In this study, we observed the effects of salusins on vascular inflammation in apoE-deficient (apoE-/-) mice.Six-week old male apoE-/- mice were infused with salusin-α, salusin-β or vehicle for 8 weeks via osmotic mini-pumps. Our results showed that apoE-/- mice receiving vehicle alone developed severe atherosclerotic lesions and dyslipidemia, with significantly up-regulated levels of IL-6, TNF-α, VCAM-1 and MCP-1. For apoE-/- mice receiving 8 weeks of salusin-β infusion, the atherosclerotic lesions were markedly aggravated, and the levels of IL-6, TNF-α, VCAM-1 and MCP-1 were substantially increased, despite a similar plasma lipid concentration with that of apoE-/- mice. However, after 8 week-infusion of salusin-α, apoE-/- mice presented significant amelioration in atherosclerotic lesions, along with remarkably up-regulated level of high-density lipoprotein-cholesterol (HDL-C) and down-regulated levels of IL-6 and TNF-α, but without any effect on the expressions of VCAM-1 and MCP-1. Furthermore, the activation of nuclear factor-κB (NF-κB), an important transcription factor essential for inflammatory molecules, and the degradation of I-κBα, an inhibitor of NF-κB, were markedly increased in apoE-/- mice receiving vehicle alone. Treatment with salusin-β not salusin-α could remarkably accelerate the process of NF-κB nuclear translocation and I-κBα degradation.Salusin-β, but not salusin-α, promotes vascular inflammation in apoE-deficient mice via the I-κBα/NF-κB pathway. These findings provide further insight into the mechanism of salusins in atherosclerosis and potential targets for the prevention and treatment of atherosclerosis.

In the last decades, the Masson pine (Pinus massoniana) forests in Chongqing, southwest China, have increasingly declined. Soil acidification was believed to be an important cause. Liming is widely used as a measure to alleviate soil acidification and its damage to trees, but little is known about long-term effects of liming on the health and growth of declining Masson pine forests. Soil chemical properties, health condition (defoliation and discoloration), and growth were evaluated following application of limestone powder (0 (unlimed control), 1, 2, 3, and 4 t ha(-1)) in an acidified and declining Masson pine stand at Tieshanping (TSP) of Chongqing. Eight years after liming, in the 0-20 cm and 20-40 cm mineral soil layers, soil pH values, exchangeable calcium (Ca) contents, and Ca/Al molar ratios increased, but exchangeable aluminum (Al) levels decreased, and as a result, length densities of living fine roots of Masson pine increased, with increasing dose. Mean crown defoliation of Masson pines (dominant, codominant and subdominant pines, according to Kraft classes 1-3) decreased with increasing dose, and it linearly decreased with length densities of living fine roots. However, Masson pines (Kraft classes 1-3) in all treatments showed no symptoms of discoloration. Mean current-year twig length, twig dry weight, needle number per twig, needle length per twig, and needle dry weight per twig increased with increasing dose. Over 8 years, mean height increment of Masson pines (Kraft classes 1-3) increased from 5.5 m in the control to 5.8, 6.9, 8.3, and 9.5 m in the 1, 2, 3, and 4 t ha(-1) lime treatments, and their mean DBH (diameter at breast height) increment increased from 3.1 to 3.2, 3.8, 4.9, and 6.2 cm, respectively. The values of all aboveground growth parameters linearly increased with length densities of living fine roots. Our results show that liming improved tree health and growth, and these effects increased with increasing dose.

Mobile phone virus is a rogue program written to propagate from one phone to another, which can take control of a mobile device by exploiting its vulnerabilities. In this paper the propagation model of mobile phone virus is tackled to understand how particular factors can affect its propagation and design effective containment strategies to suppress mobile phone virus. Two different propagation models of mobile phone viruses under the complex network are proposed in this paper. One is intended to describe the propagation of user-tricking virus, and the other is to describe the propagation of the vulnerability-exploiting virus. Based on the traditional epidemic models, the characteristics of mobile phone viruses and the network topology structure are incorporated into our models. A detailed analysis is conducted to analyze the propagation models. Through analysis, the stable infection-free equilibrium point and the stability condition are derived. Finally, considering the network topology, the numerical and simulation experiments are carried out. Results indicate that both models are correct and suitable for describing the spread of two different mobile phone viruses, respectively.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare inherited disorder of the peripheral nervous system resulting from mutations in neurotrophic tyrosine kinase receptor 1 gene (NTRK1), which encodes the high-affinity nerve growth factor receptor TRKA. Here, we investigated the oral and craniofacial manifestations of a Chinese patient affected by autosomal-recessive CIPA and identified compound heterozygosity in the NTRK1 gene. The affected boy has multisystemic disorder with lack of reaction to pain stimuli accompanied by self-mutilation behavior, the inability to sweat leading to defective thermoregulation, and mental retardation. Oral and craniofacial manifestations included a large number of missing teeth, nasal malformation, submucous cleft palate, severe soft tissue injuries, dental caries and malocclusion. Histopathological evaluation of the skin sample revealed severe peripheral nerve fiber loss as well as mild loss and absent innervation of sweat glands. Ultrastructural and morphometric studies of a shed tooth revealed dental abnormalities, including hypomineralization, dentin hypoplasia, cementogenesis defects and a dysplastic periodontal ligament. Genetic analysis revealed a compound heterozygosity--c.1561T>C and c.2057G>A in the NTRK1 gene. This report extends the spectrum of NTRK1 mutations observed in patients diagnosed with CIPA and provides additional insight for clinical and molecular diagnosis.

Facility location, inventory control, and vehicle routes scheduling are critical and highly related problems in the design of logistics system for e-business. Meanwhile, the return ratio in Internet sales was significantly higher than in the traditional business. Many of returned merchandise have no quality defects, which can reenter sales channels just after a simple repackaging process. Focusing on the existing problem in e-commerce logistics system, we formulate a location-inventory-routing problem model with no quality defects returns. To solve this NP-hard problem, an effective hybrid genetic simulated annealing algorithm (HGSAA) is proposed. Results of numerical examples show that HGSAA outperforms GA on computing time, optimal solution, and computing stability. The proposed model is very useful to help managers make the right decisions under e-supply chain environment.

Neuron loss, glial activation and vascular degeneration are common sequelae of ischemia-reperfusion (I/R) injury in ocular diseases. The present study was conducted to explore the ability of curcumin to inhibit retinal I/R injury, and to investigate underlying mechanisms of the drug effects.Different dosages of curcumin were administered. I/R injury was induced by elevating the intraocular pressure for 60 min followed by reperfusion. Cell bodies, brn3a stained cells and TUNEL positive apoptotic cells in the ganglion cell layer (GCL) were quantitated, and the number of degenerate capillaries was assessed. The activation of glial cells was measured by the expression level of GFAP. Signaling pathways including IKK-IκBα, JAK-STAT1/3, ERK/MAPK and the expression levels of β-tubulin III and MCP-1 were measured by western blot analysis. Pre-treatment using 0.01%-0.25% curcumin in diets significantly inhibited I/R-induced cell loss in GCL. 0.05% curcumin pre-treatment inhibited I/R-induced degeneration of retinal capillaries, TUNEL-positive apoptotic cell death in the GCL, brn3a stained cell loss, the I/R-induced up-regulation of MCP-1, IKKα, p-IκBα and p-STAT3 (Tyr), and down-regulation of β-tubulin III. This dose showed no effect on injury-induced GFAP overexpression. Moreover, 0.05% curcumin administered 2 days after the injury also showed a vaso-protective effect.Curcumin protects retinal neurons and microvessels against I/R injury. The beneficial effects of curcumin on neurovascular degeneration may occur through its inhibitory effects on injury-induced activation of NF-κB and STAT3, and on over-expression of MCP-1. Curcumin may therefore serve as a promising candidate for retinal ischemic diseases.