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Abstract Background MSM are at high risk of HIV infection. Previous studies have shown that the cell cycle regulation plays an important role in HIV-1 infection, especially at the G2/M checkpoint. ATR, Chk1, Cdc25C and CDK1 are key genes of G2/M checkpoint. However, the association between SNPs of these genes and susceptibility to HIV-1 infection and AIDS progression remains unknown. Methods In this study, 42 tSNPs from the above four G2/M checkpoint genes were genotyped in 529 MSM and 529 control subjects from northern China to analyze this association. Results The results showed that rs34660854 A and rs75368165 A in ATR gene and rs3756766 A in Cdc25C gene could increase the risk of HIV-1 infection (P = 0.049, OR = 1.234, 95% CI 1.001–1.521; P = 0.020, OR = 1.296, 95% CI 1.042–1.611; P = 0.011, OR = 1.392, 95% CI 1.080–1.794, respectively), while Chk1 rs10893405 (P = 0.029, OR = 1.629, 95% CI 1.051–2.523) were significantly associated with AIDS progression. Besides, rs34660854 (P = 0.019, OR = 1.364, 95% CI 1.052–1.769; P = 0.022, OR = 1.337, 95% CI 1.042–1.716, under Codominant model and Dominant model, respectively) and rs75368165 (P = 0.006, OR = 1.445, 95% CI = 1.114–1.899; P = 0.007, OR = 1.418, 95% CI 1.099–1.831, under Codominant model and Dominant model, respectively) in ATR gene, rs12576279 (P = 0.013, OR = 0.343, 95% CI 0.147-0.800; P = 0.048, OR = 0.437, 95% CI 0.192–0.991, under Codominant model and Dominant model, respectively) and rs540436 (P = 0.012, OR = 1.407, 95% CI 1.077–1.836; P = 0.021, OR = 1.359, 95% CI 1.048–1.762, under Codominant model and Dominant model, respectively) in Chk1 gene, rs3756766 (P = 0.013, OR = 1.455, 95% CI 1.083–1.954; P = 0.009, OR = 1.460, 95% CI 1.098–1.940, under Codominant model and Dominant model, respectively) in Cdc25C gene and rs139245206 (P = 0.022, OR = 5.011, 95% CI 1.267–19.816; P = 0.020, OR = 5.067, 95% CI 1.286–19.970, under Codominant model and Recessive model, respectively) in CDK1 gene were significantly associated with HIV-1 infection under different models. Conclusions We found that genetic variants of G2/M checkpoint genes had a molecular influence on the occurrence of HIV-1 infection and AIDS progression in a northern Chinese MSM population.

Shape memory alloy (SMA), a type of smart material, is widely used in the design of reinforcement and repair, isolation, and shock absorption of building structures because of its outstanding characteristics, such as the shape memory effect (SME), superelasticity (SE), and high damping. It not only improves the bearing capacity, ductility, and mechanical properties of the structural components of buildings but can also effectively slow down the strong response of engineering structures under the effect of an earthquake. It plays a key role in energy dissipation and shock absorption as well as sustainable development. To promote the application of SMA in building structures, this paper summarizes the research on the use of SMA as a reinforcing material in building structures, including work related to SMA material characteristics and types, SMA-reinforced structural components, and SMA isolation devices. In addition, the shortcomings of SMA applications in building structures are analyzed, and valuable suggestions for future research methods are put forward. SMA has been applied to engineering practice in the form of embedded and external reinforcement, which shows that it has broad application prospects in future buildings.

ABSTRACTDouble minutes (DMs), extrachromosomal gene fragments found within certain tumors, have been noted to carry onco- and drug resistance genes contributing to tumor pathogenesis and progression. After screening for SUMO-related molecule expression within various tumor sample and cell line databases, we found that SUMO-conjugating enzyme UBC9 has been associated with genome instability and tumor cell DM counts, which was confirmed both in vitro and in vivo. Karyotyping determined DM counts post-UBC9 knockdown or SUMOylation inhibitor 2-D08, while RT-qPCR and Western blot were used to measure DM-carried gene expression in vitro. In vivo, fluorescence in situ hybridization (FISH) identified micronucleus (MN) expulsion. Western blot and immunofluorescence staining were then used to determine DNA damage extent, and a reporter plasmid system was constructed to detect changes in homologous recombination (HR) and non-homologous end joining (NHEJ) pathways. Our research has shown that UBC9 inhibition is able to attenuate DM formation and lower DM-carried gene expression, in turn reducing tumor growth and malignant phenotype, via MN efflux of DMs and lowering NHEJ activity to increase DNA damage. These findings thus reveal a relationship between heightened UBC9 activity, increased DM counts, and tumor progression, providing a potential approach for targeted therapies, via UBC9 inhibition.

Abstract Background Most susceptible loci of hepatocellular carcinoma (HCC) identified by genome-wide association studies (GWAS) are located in non-coding regions, and the mechanism of action remains unclear. The objective of this study was to explore the association of single nucleotide polymorphisms (SNPs) on long non-coding RNAs (lncRNAs) that affect competing endogenous RNAs (ceRNA) regulation mechanism with the risk and prognosis of HCC. Methods Based on a set of bioinformatics strategies, eight lncRNA genes that affect HCC through the mechanism of lncRNA-mediated ceRNA were systematically screened, and 15 SNPs that affect microRNA (miRNA) binding in these lncRNA genes were annotated. Genotyping was performed in 800 HCC cases and 801 healthy controls to examine associations of these SNPs with HCC in a northeastern Chinese Han population. Results The GG, GC and GG + GC genotypes of HOTAIR rs7958904 were associated with a 0.65, 0.59 and 0.63-fold decreased HCC risk, respectively. In addition, HCC patients with PVT1 rs3931282 AA + GA genotypes were less prone to develop late-stage cancers in a stratified analysis of clinical characteristics. When stratified by clinical biochemical indexes, rs1134492 and rs10589312 in PVT1 and rs84557 in EGFR-AS1 showed significant associations with aspartate aminotransferase (AST), alanine aminotransferase (ALT) or AST/ALT ratio in HCC patients. Furthermore, we constructed potential ceRNA regulatory axes that might be affected by five positive SNPs to explain the causes of these genetic associations. Conclusions HOTAIR rs7958904, PVT1 rs3931282, rs1134492 and rs10589312, and EGFR-AS1 rs84557 might be predictors for HCC risk or prognosis. Our results provide new insights into how SNPs on lncRNA-mediated ceRNAs confer interindividual differences to occurrence and progression of HCC.

In order to trace the research history of diseases and pests in rubber tree and explore the potential for their natural control, a bibliometric analysis was conducted based on relevant documents retrieved from the Clarivate Analytics Web of Science (WoS) core collection SCI-E database. VOSviewer software was utilized to analyze the research distribution, scientific collaboration, knowledge structure, and research frontiers. The results show that annual publications on the diseases and pests of rubber tree have increased rapidly after 2005 after a long period of emergence and fluctuation. A total of 624 relevant publications from 51 countries/regions were identified. China was the most productive country with 152 documents, most of which were related to Colletotrichum leaf disease, powdery mildew, and other emerging diseases of rubber tree. France and Brazil produced rich research to tackle South American leaf blight, and have established a close collaborative relationship. Based on the analysis of themes and trend topics, pathogenicity mechanisms of fungal pathogens and plant defense mechanisms are currently hot topics. By further looking into the research, the defense-related genes of rubber tree and antagonistic mechanisms behind candidate biocontrol agents reveal great potential in developing natural control strategies. This study provides a useful reference about the progress and evolution of research into diseases and pests in rubber tree.

Abstract Background DAL-1 gene was reported to inhibit proliferation, migration, invasion, and epithelial to mesenchymal transition (EMT) of gastric cancer (GC) cells in our previous study. The association between the genomic variants in DAL-1 gene with risk of GC is still unclear. Methods In this study, 505 GC cases and 544 healthy controls (HCs) were collected to evaluate the association between six single nucleotide polymorphisms (SNPs) (rs7240736, rs73937194, rs3817466, rs8082898, rs73381527, rs9953490) of DAL-1 gene and GC risk in the Han population in Northeast China. Results The TA + AA genotypes of rs9953490 were significantly associated with an increased risk in N3 compared with N0 subgroup (adjusted OR = 4.56, 95% CI = 1.49–13.98, P = 0.008), and also showed evident association with an increased risk in TNM stage III compared with stage I-II (adjusted OR = 2.33, 95% CI = 1.16–4.67, P = 0.017). Conclusion The rs9953490 of DAL-1 gene may play an important role in the occurrence and development of GC in the Han population in Northeast China.

Abstract Background Polydactyly is a common congenital malformation characterized by the presence of supernumerary fingers or toes. In this case study, we sought to identify the causative pathogenic factor in a family from a northern region of China affected by non‐syndromic postaxial polydactyly (PAP). Methods After recruiting a three‐generation family with PAP, whole‐exome sequencing was performed to identify the causative variant. In silico analysis and Sanger sequencing were used to validate the variant. Results We identified a novel heterozygous frameshift variant (NM_000168.6:c.4540delG, p.Asp1514Thrfs*5) in the transcriptional activator (TA1) domain of the GLI3 gene. Conclusion The novel frameshift variant identified in this study further confirms the relationship between non‐syndromic PAP and GLI3 and extends the previously established mutational and phenotypic spectra of GLI3.

Background: Some studies have shown that the base excision repair (BER) pathway has an effect on HIV-1 replication. APEX1 and XRCC1 as key BER genes may affect DNA repair capacity. However, the roles of single nucleotide polymorphisms (SNPs) in APEX1 and XRCC1 and their impact on HIV-1 infection and AIDS progression remain unclear.Methods: A custom-designed 48-Plex SNPscan Kit was used for detection of single nucleotide polymorphisms. 601 HIV-1-infected men who have sex with men (MSM) and 624 age-matched healthy individuals were recruited in northern China. Four SNPs (rs1130409, rs1760944, rs2307486 and rs3136817) in APEX1 gene and three SNPs (rs1001581, rs25487 and rs25489) in XRCC1 gene were genotyped. The generalized multifactor dimension reduction (GMDR) method was used to identify the SNP-SNP interactions.Results: In this study, rs1130409 G allele, rs1001581 C allele and rs25487 C allele were associated with a higher risk of HIV-1 infection susceptibility (p = 0.020, p = 0.007 and p = 0.032, respectively). The frequencies of APEX1 haplotype TT and XRCC1 haplotype CT showed significant differences between cases and controls (p = 0.0372 and p = 0.0189, respectively). Interestingly, stratified analysis showed that the frequency of rs1001581 C allele was significantly higher in AIDS patients with the CD4+ T-lymphocyte count 200 cells/μl (p = 0.022). Moreover, significant gene-gene interactions among rs1130409, rs1001581 and rs25487 were identified by GMDR (p = 0.0107). Specially, individuals with five to six risk alleles have a higher susceptibility to HIV-1 infection than those with zero to two risk alleles (p < 0.001).Conclusion:APEX1 and XRCC1 gene polymorphisms were associated with the susceptibility to HIV-1 infection and AIDS progression in MSM populations in northern China.

The objective of this study was to construct a BeiDou navigation satellite system (BDS)/ global positioning system (GPS)-integrated positioning algorithm that meets the accuracy requirement of forest surveys and to analyze its accuracy to provide theoretical and technical support for accurate positioning and navigation in forests. The Quercus variabilis broad-leaved forest in Jiufeng National Forest Park and the Sabina Coniferous forest in Dongsheng Bajia forest farm were selected as the study area. A Sanding T-23 multi-frequency three-constellation receiver and a u-blox NEO-M8T multi-constellation receiving module were used for continuous observation under the forest canopy. Compared with T-23, the u-blox NEO-M8T is much lighter and more flexible in the forest. The BDS/GPS-integrated positioning algorithm for forests was constructed by temporally and spatially unifying the satellite systems and using a reasonable observed value weighting method. Additionally, the algorithm is also written into the RTKLIB software to calculate the three-dimensional (3D) coordinates of the forest observation point in the World Geodetic System 1984 (WGS-84) coordinate system. Finally, the results were compared with the positioning results obtained using GPS alone. The experimental results indicated that, compared with GPS positioning, there were 13–27 visible satellites available for the BDS/GPS-integrated positioning algorithm for forests, far more than the satellites available for the GPS positioning algorithm alone. The Position Dilution of Precision (PDOP) values for the BDS/GPS-integrated positioning ranged from 0.5 to 1.9, lower than those for GPS positioning. The signal noise ratio (SNR) of the BDS/GPS-integrated satellite signals and GPS satellite signals were both in the range of 10–50 dB-Hz. However, because there were more visible satellites for the BDS/GPS-integrated positioning, the signals from the BDS/GPS-integrated satellites were stronger and had a more stable SNR than those from the GPS satellites alone. The results obtained using the BDS/GPS-integrated positioning algorithm for forests had significantly higher theoretical and actual accuracies in the X, Y and Z directions than those obtained using the GPS positioning algorithm. This suggests that the BDS/GPS-integrated positioning algorithm can obtain more accurate positioning results for complex forest environments.

In this paper, experiments and finite element analysis methods were adopted to study the flexural performance of shape memory alloy hybrid composites (SMAHC). The effect of embedding content and position of shape memory alloy (SMA) wire on the flexural properties of composite laminates was analyzed, and the optimal content and position of SMA wire were obtained. The optimal number of SMA wires for SMAHC laminates (B-2) is four. Compared with GFRP laminates, the flexural modulus of B-2-4 laminates increases by 5.19%, while the strength decreases by 5.76% on average. The finite element model of the SMAHC laminate was established by using ABAQUS finite element analysis software, and the validity of the model was verified by the comparison between the simulation results and the experimental results. The microscopic morphology results show that the weak interface between the matrix and SMA has a certain influence on the flexural performance of SMAHC specimens.

This study analyzed the process of vegetation restoration in the eastern margin ecotone of Qinghai-Tibet Plateau (EMEQTP) from 2001 to 2019 under different restoration modes based on the vegetation net primary productivity (NPP) which was estimated by the Carnegie-Ames-Stanford approach (CASA) model. Then the potential NPP was calculated and the durations of NPP restoration were predicted based on the Autoregressive Integrated Moving Average (ARIMA) model. Finally, the relative importance of main parameters in the CASA model as well as global sensitivity and uncertainty were discussed. The results showed that the NPP under a natural restoration mode had the highest increase with 20.1%, and its spatial change showed an overall trend of restoration. The NPP under the comprehensive restoration mode achieved an increase of 11.5%, with the southwestern area experiencing an insignificant trend of degradation, whereas the northeastern area experiencing a significant restoration trend. As for the NPP under the artificial restoration mode, it experienced the lowest increase with 10.5%, and the northern part experiencing a significant restoration trend, whereas the southeastern part experiencing an insignificant degradation trend. In addition, the highest potential NPP of vegetation restoration would be appeared in the area under a comprehensive restoration mode. The area under an artificial restoration mode would have the lowest potential NPP of vegetation restoration, but the duration of restoration would be longest under this mode, reaching up to 64 years. Although the natural restoration mode achieved the best effect of vegetation restoration, considering the limited scope of the promotion of this mode, further attention should be placed on restoration measures and the effects of the artificial and comprehensive restoration modes. Finally, APAR, GST and PET were relatively important for the CASA model, and the parameters including Topt, GST, and PET were sensitive. Those results can offer scientific references for the management of ecological environment in the EMEQTP.

Abstract Background Polycystic kidney disease (PKD) is an inherited disease that is life‐threatening. Multiple cysts are present in the bilateral kidneys of PKD patients. The progressively enlarged cysts cause structural damage and loss of kidney function. Methods This study examined and analyzed 12 families with polycystic kidney disease. Whole exome sequencing (WES) or whole genome sequencing (WGS) of the probands was performed to detect the pathogenic genes. The candidate gene segments for lineal consanguinity in the family were amplified by the nest PCR followed by Sanger sequencing. The variants were assessed by pathogenic and conservational property prediction analysis and interpreted according to the American College of Medical Genetics and Genomics. Results Nine of the 12 pedigrees were identified the disease causing variants. Among them, four novel variants in PKD1, c.6930delG:p.C2311Vfs*3, c.1216T>C:p.C406R, c.8548T>C:p.S2850P, and c.3865G>A:p.V1289M (NM_001009944.2) were detected. After assessment, the four novel variants were considered to be pathogenic variants and cause autosomal dominant polycystic kidney disease in family. The detected variants were interpreted. Conclusion The four novel variants in PKD1, c.6930delG:p.C2311Vfs*3, c.1216T>C:p.C406R, c.8548T>C:p.S2850P, and c.3865G>A:p.V1289M (NM_001009944.2) are pathogenic variants and cause autosomal dominant polycystic kidney disease in family.

The aim of this study was to identify the potential key candidate genes of multiple sclerosis (MS) and uncover mechanisms in MS. We combined data from the microarray expression profile of three MS stages and performed bioinformatics analysis. Differentially expressed genes (DEGs) were identified among the distinct stages of MS and healthy controls, and a total of 349 shared DEGs were identified. Gene ontology (GO) and pathway enrichment analyses showed that the DEGs were significantly enriched in the biological processes (BPs) of purine-related metabolic processes and signaling, especially the common DEGs, which were enriched in some immunological processes. Most of the DEGs were enriched in signaling pathways associated with the immune system, some immune diseases and infectious disease pathways. Through a protein–protein interaction (PPI) network analysis and a gene expression regulatory network constructed with MS-related miRNAs, we confirmed FOS, TP53, VEGFA, JUN, HIF1A, RB1, PTGS2, CXCL8, OAS2, NFKBIA and OAS1 as candidate genes of MS. Furthermore , we explored the potential SNPs associated with MS by database mining. In conclusion, this study provides the identified genes, SNPs, biological processes, and cellular pathways associated with MS. The uncovered candidate genes may be potential biomarkers involved in the diagnosis and therapy of MS.

Abstract Background Heilongjiang Province located in northeast China is a multi-ethnic region with people who have lived in cold conditions for several generations. Fatty acids are important to people with cold resistance. CPT1A encodes a protein that imports long-chain fatty acids into the mitochondria for fatty-acid oxidation. FADS is an essential enzyme for the synthesis of long-chain polyunsaturated fatty acids. Results In the present study, we investigated the distributions of three cold resistance-related SNPs (rs80356779 G > A in CPT1A, rs7115739 T > G in FADS3 and rs174570 C > T in FADS2) from six populations that included 1093 individuals who have lived in Heilongjiang Province for at least three generations. The frequencies of rs174570 and rs7115739 were different in our six north minorities compared to the Chinese Dai in Xishuangbanna (CDX) in southern China. All the SNPs in Hezhen were significantly different from other five studied populations. In addition, the genetic distribution of rs174570 in Daur was significantly different from Manchu and Korea, and the frequency of rs7115739 in Ewenki was significantly different from the other populations. The results also showed that the frequencies of the three SNPs in the six minorities were different from those of Greenlandic Inuit and Siberian population. Conclusions Our results showed the distributions of the three cold resistance-related SNPs from six populations that included 1093 individuals in northern China. Distributions of the allele frequencies for the cold resistance-related SNPs in northern China were statistically different from those in southern China. These data help to establish the DNA genome database for the six populations and fully preserve existing minority genetic information.

The increasing scale of urbanization and human activities has resulted in the fragmentation of natural habitats, leading to the reduction of ecological landscape connectivity and biodiversity. Taking Nanping as the study area, the core areas with good connectivity were extracted as ecological sources using a morphological spatial pattern analysis (MSPA) and landscape connectivity index. Then the ecosystem service functions of the ecological sources were evaluated based on the InVEST model. Finally, we extracted the potential ecological corridor based on the land type, elevation and ecosystem service functions. The results showed that the ecological source with higher landscape connectivity is distributed in the north and there are clear landscape connectivity faults in the northern and southern regions. Moreover, the areas with high habitat quality, soil retention and water production are mainly distributed in the northern ecological source areas. The 15 potential ecological corridors extracted were distributed unevenly. Among them, the important ecological corridors formed a triangle network, while the general ecological corridors were concentrated in the northwest. Therefore, it is suggested that the important core patches in the north be protected, and the effective connection between the north and south be improved. These results can provide a scientific basis for ecological construction and hierarchical management of the ecological networks.

A hypersonic flow field over a blunt wedge with or without roughness is simulated by a direct numerical simulation method. The effect of isolated and distributed roughnesses on the steady and unsteady hypersonic flow field and boundary layer is analyzed. The shape of roughness is controlled by cubic polynomial. The evolution of disturbance waves caused by slow acoustic wave in the boundary layer is investigated by fast Fourier spectrum analysis. The results show that there is a great influence of roughness on the evolution of disturbance waves in the hypersonic boundary layer. The disturbance waves are promoted in the upstream-half region of roughness while suppressed in the downstream-half region of roughness. There is always a mode competition among different modes both in the temporal domain and in the frequency domain in the boundary layer, and mode competition is affected by roughness. The location of the dominant mode which is changed to a second-order harmonic mode from the fundamental mode moves upstream. The vortices caused by roughness also impact the evolution of disturbance waves in the boundary layer. The fundamental mode is suppressed in the vortex region while other harmonic modes are promoted.

Shape memory epoxy polymer (SMEP) composite specimens with different graphene oxide (GO) contents were manufactured to study the effects of GO mass fractions on epoxy polymer composites. While ensuring the shape memory effect of SMEP, the addition of GO also remarkably strengthened the mechanical performance of the polymers. Analyses of the epoxy polymer composites’ thermal, mechanical, and shape memory performance were conducted through carrying out dynamic mechanical analysis (DMA), thermogravimetric analysis (TGA), and static tensile, three-point bending, impact, and shape memory tests. Moreover, the tensile fracture, bending fracture, and impact fracture interfaces of epoxy resin composites were examined with scanning electron microscopy. The final test results indicated that when the GO content was 0.8 wt %, SMEP composites had good shape memory performance and optimum thermal and mechanical performance.

Through studying the effects of the Al⁻5Ti-x(Mg⁻30%Ce) refiner on the microstructure of the Al⁻7Si alloy, we investigated the hardness, tensile, and impact properties of the Al⁻Si alloy before and after refinement. The refinement results show that Mg⁻30%Ce can improve the refinement effect of Al⁻5Ti on Al⁻7Si, and also refine α-Al and eutectic Si in Al⁻7Si. When 2%Mg⁻30%Ce is added, the refining effect of the aluminum⁻silicon alloy is most obvious. After refinement, the hardness and tensile properties of the Al⁻7Si alloy improve. When 2%Mg⁻30%Ce is added to the refiner, the tensile properties of the Al⁻Si alloy are the best. Dynamic mechanical tests were conducted on refined Al⁻7Si alloy. The impact toughness of Al⁻7Si⁻(Al⁻5Ti-2(Mg⁻30%Ce) improved and the impact toughness reached 34.91 J/cm2, which is 78.7% higher than that of Al⁻7Si⁻(Al⁻5Ti) specimens. The separate Hopkinson pressure bar test results show that, under a high strain rate, the strain rate sensitivity of the prepared Al⁻Si alloy is significant. The specimens of Al⁻7Si⁻(Al⁻5Ti-2(Mg⁻30%Ce) demonstrated the best anti-impact performance at the same velocity.

Trans-l,4-polyisoprene (TPI) shape memory polymer composites with different chopped carbon fiber mass fractions were prepared to study the effects of different chopped carbon fiber mass fractions and temperatures on the TPI shape memory polymer composites in this paper. While guaranteeing the shape memory effect of TPI shape memory polymers, the carbon fiber fillers also significantly enhanced the mechanical properties of the polymers. The thermodynamic properties and shape memory properties of TPI shape memory polymers were studied by a differential scanning calorimeter (DSC) test, dynamic mechanical analysis (DMA) test, thermal conductivity test, static tensile test, mechanical cycle test, thermodynamic cycling test and shape memory test. Furthermore, the tensile fracture interface of TPI shape memory polymer composites was analyzed by scanning electron microscopy. The experimental results show that when the chopped carbon mass fraction fiber is 8%, TPI shape memory polymers have good shape memory properties and the best mechanical properties.

Hepatocyte nuclear factor 1β (HNF1β), a transcription factor encoded by the transcription factor 2 gene (TCF2), plays a critical role in pancreatic cell formation and glucose homeostasis. It has been suggested that single nucleotide polymorphisms (SNPs) of TCF2 are associated with susceptibility to type 2 diabetes (T2D). However, published results are inconsistent and inclusive. To further investigate the role of these common variants, we examined the association of TCF2 polymorphisms with the risk of T2D in a Han population in northeastern China. We genotyped five SNPs in 624 T2D patients and 630 healthy controls by using a SNaPshot method, and evaluated the T2D risk conferred by individual SNPs and haplotypes. In the single-locus analysis, we found that rs752010, rs4430796 and rs7501939 showed allelic differences between T2D patients and healthy controls, with an OR of 1.26 (95% CI 1.08-1.51, P = 0.003), an OR of 1.23 (95% CI 1.06-1.55, P = 0.001) and an OR of 1.28 (95% CI 1.10-1.61, P = 0.001), respectively. Genotype association analysis of each locus also revealed that the homozygous carriers of the at-risk allele had a significant increased T2D risk compared to homozygous carriers of the other allele (OR 1.78, 95% CI 1.20-2.64 for rs752010; OR 1.82, 95% CI 1.24-2.67 for rs4430796; OR 1.95, 95% CI 1.31-2.90 for rs7501939), even after Bonferroni correction for multiple comparisons. Besides, the haplotype-based analysis demonstrated that AGT in block rs752010-rs4430796-rs7501939 was associated with about 30% increase in T2D risk (OR 1.31, 95% CI 1.09-1.57, P = 0.01). Our findings suggested that TCF2 variants may be involved in T2D risk in a Han population of northeastern China. Larger studies with ethnically diverse populations are warranted to confirm the results reported in this investigation.

Objective: We performed a meta-analysis, including dose-response analysis, to quantitatively determine the association of fried-food consumption and risk of cardiovascular disease and all-cause mortality in the general adult population.Methods: We searched PubMed, EMBASE and Web of Science for all articles before 11 April 2020. Random-effects models were used to estimate the summary relative risks (RRs) and 95% CIs.Results: In comparing the highest with lowest fried-food intake, summary RRs (95% CIs) were 1.28 (1.15 to 1.43; n=17, I2=82.0%) for major cardiovascular events (prospective: 1.24 (1.12 to 1.38), n=13, I2=75.7%; case-control: 1.91 (1.15 to 3.17), n=4, I2=92.1%); 1.22 (1.07 to 1.40; n=11, I2=77.9%) for coronary heart disease (prospective: 1.16 (1.05 to 1.29), n=8, I2=44.6%; case-control: 1.91 (1.05 to 3.47), n=3, I2=93.9%); 1.37 (0.97 to 1.94; n=4, I2=80.7%) for stroke (cohort: 1.21 (0.87 to 1.69), n=3, I2=77.3%; case-control: 2.01 (1.27 to 3.19), n=1); 1.37 (1.07 to 1.75; n=4, I2=80.0%) for heart failure; 1.02 (0.93 to 1.14; n=3, I2=27.3%) for cardiovascular mortality; and 1.03 (95% CI 0.96 to 1.12; n=6, I2=38.0%) for all-cause mortality. The association was linear for major cardiovascular events, coronary heart disease and heart failure.Conclusions: Fried-food consumption may increase the risk of cardiovascular disease and presents a linear dose-response relation. However, the high heterogeneity and potential recall and misclassification biases for fried-food consumption from the original studies should be considered. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most developing cancer worldwide and Lynch syndrome (LS) accounts for 3-4% of CRC. Genetic alteration in any of DNA mismatch repair (MMR) gene is the major cause of LS that disrupt the normal upstream and downstream MMR events. Germline mutation of MLH1 in heterozygous state have an increased risk for CRC. Defective MMR pathway mostly results in microsatellite instability (MSI) that occurs in high percentage of CRC associated tumors. Here, we reported a patient with LS like metastatic CRC (mCRC) associated with other related cancers. Whole exome sequencing (WES) of the proband was performed to identify potential causative gene. Genetic screening validated by Sanger sequencing identified a heterozygous missense mutation in exon 12 of MLH1 (c.1151T>A, p.V384D). The clinical significance of identified variant was elucidated on the basis of clinicopathological data, computational predictions and various in vitro functional analysis. In silico predictions classified the variant to be deleterious and evolutionary conserved. In vitro functional studies revealed a significant decrease in protein expression because of stability defect leading to loss of MMR activity. Mutant residue found in MutL transducer domain of MLH1 that localized in the nucleus but translocation was not found to be significantly disturbed. In conclusion, our study give insight into reliability of combinatorial prediction approach of in silico and in vitro expression analysis. Hence, we highlighted the pathogenic correlation of MLH1 variant with LS associated CRC as well as help in earlier diagnosis and surveillance for improved management and genetic counselling. [ABSTRACT FROM AUTHOR]

Background: Prenatal intake of folic acid is important for prevention of NSCL/P (nonsyndromic cleft lip with or without cleft palate). Associated genes in folate pathway are major enzymes of folic acid metabolism that is crucial for preventing birth defects. The present meta-analysis aims to investigate the association between four SNPs in folate pathway genes and the risk of NSCL/P. Methods: Comprehensive bioinformatics analysis was used to predict the functional pathogenicity of genetic variation. The PubMed, Embase database and Google Scholar were searched by two researchers. Stata 11.0 software was used to analyze the results. Subgroup analysis was carried out to assess the influence of genetic background. Sensitivity analysis, regression analysis and publication analysis were also conducted to enhance the strength of our results. Results: It is estimated that the probability of two missense mutation rs1801133 in MTHFR and rs1801394 in MTRR are more likely to be damaging by bioinformatics analysis. A significant association between rs1801133 and risk of NSCL/P in two genetic models: TT genotype vs CC genotype (OR = 1.333 95%CI = 1.062-1.674, P = 0.013), and recessive model (OR = 1.325 95%CI = 1.075-1.634, P = 0.008). A significant protective association between rs1801394 GG genotype and NSCL/P in Asian (GG vs AA, OR = 0.520 95%CI = 0.321-0.841, P = 0.008) was observed. Meta-regression, sensitivity analysis, and publication bias analysis confirmed that the results of the present study were statistically significant. Conclusions: The present study identified that rs1801133 in MTHFR is associated with the risk of NSCL/P, and rs1801394 Gg genotype in MTRR play a protective role in Asian. Further, larger studies should be performed to confirm these findings. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-α (TNF-α) is involved in insulin resistance and has long been a candidate gene implicated in type 2 diabetes mellitus (T2DM), however the association between TNF-α polymorphisms -308G/A and -238G/A and T2DM remains controversial. The present study sought to verify associations between these polymorphisms and T2DM susceptibility using ameta-analysis approach. A total of 49 case-control studies were selected up to October 2018. Statistical analyses were performed by STATA 15.0 software. The odds ratios (ORs) and 95% confidence intervals were calculated to estimate associations. Meta-analyses revealed significant associations between TNF-α-308G/A and T2DM in the allele model (P=0.000); the dominant model (P=0.000); the recessive model (P=0.001); the overdominant model (P=0.008) and the codominant model (P=0.000). Subgroup analyses also showed associations in the allele model (P=0.006); the dominant model (P=0.004) and the overdominant model (P=0.005) in the Caucasian and in the allele model (P=0.007); the dominant model (P=0.014); the recessive model (P=0.000) and the codominant model (P=0.000) in the Asian. There were no associations between TNF-α-238G/A and T2DM in the overall and subgroup populations. Meta-regression, sensitivity analysis and publication bias analysis confirmed that results and data were statistically robust. Our meta-analysis suggests that TNF-α-308G/A is a risk factor for T2DM in Caucasian and Asian populations. It also indicates that TNF-α-238G/A may not be a risk factor for T2DM. More comprehensive studies will be required to confirm these associations. [ABSTRACT FROM AUTHOR]

A novel enzyme-free signal amplification-based assay for highly sensitive in situ fluorescence imaging and detection of intracellular telomerase activity was developed by using a gold nanoflare probe- triggered mimic-hybridization chain reaction (mimic-HCR) coupled with a graphene oxide (GO) surface-anchored fluorescence signal readout pathway. The nanoflare probe consists of gold nanoparticles (AuNPs) functionalized with a dense shell of nucleic acid sequences by Au-S bond formation. The nucleic acid sequence is composed of three segments: a long thiol- labeled sequence (HS-DNA) and two short sequences (a telomerase primer sequence, "Primer-DNA", and an FAM-terminated reporter sequence, "Flare-DNA"), both of which are complementary to HS-DNA. The mimic-HCR system is formed by two FAM-modified hairpin sequences that are adsorbed on GO. Upon endocytosis of the AuNP/GO combinatorial probe, the Primer-DNA can be extended by intracellular telomerase at its 3' end to produce the telomeric repeated sequence, which leads to inner chain substitution and not only releases the Flare-DNA to turn on the fluorescence of FAM but also initiates the subsequent signal amplification and enrichment for the mimic-HCR system anchored on GO. The proposed approach can sensitively detect telomerase activity in living cells, distinguish normal cells from cancer cells, and monitor the change in telomerase activity in response to a telomerase inhibitor. [ABSTRACT FROM AUTHOR]

Gene transcription analysis is important in cancer research, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) has been demonstrated to be an effective method to evaluate gene transcription in cancer. RT-qPCR requires an internal reference gene with a consistent level of mRNA transcription across various experimental conditions. However, it has been suggested that different treatments, including anticancer therapy, may influence the transcriptional stability of internal reference genes. Paclitaxel (PTX) and 10-hydroxycamptothecin (HCPT) are widely used to treat various types of cancer, and a suitable internal reference gene is required in order to analyze the transcription profiles of the cells following treatment. In the current study, the transcriptional stability of 30 candidate reference genes was investigated in cancer cells following treatment with PTX and HCPT. The two ovarian cancer cell lines, UACC-1598 and SKOV3, were treated with PTX and HCPT for 24 and 48 h, and the transcriptional levels of the candidate reference genes were subsequently evaluated by RT-qPCR analysis. The transcriptional stability of the selected genes was then analyzed using qbase+ and NormFinder software. A total of 9 genes were demonstrated to exhibit high transcriptional stability and one of these genes, ribosomal protein L13a (RPL13A), was identified to exhibit high transcriptional stability in every group. The current study identified various reference genes suitable under different circumstances, while RPL13A was indicated to be the most suitable reference gene for analyzing the transcription profile of ovarian cancer cells following treatment with PTX and HCPT. [ABSTRACT FROM AUTHOR]

Background Congenital cataract is a Mendelian disorder that frequently causes blindness in infants. To date, various cataract-associated loci have been mapped; more than 30 genes have been identified by linkage analysis. However, the pathogenic loci in some affected families are still unknown, and new research strategies are needed. In this study, we used linkage-exome combinational analysis to further investigate the pedigree of a four-generation Chinese family with autosomal dominant coralliform cataract. Methods We combined whole exome sequencing and linkage analysis to identify the causative mutation. The exome capture and next-generation sequencing were used to sequence the protein-coding regions in the genome of the proband to identify rare mutations, which were further screened for candidate mutations in linkage regions. Candidate mutations were independently verified for co-segregation in the whole pedigree using Sanger sequencing. Results We identified a C to A transversion at nucleotide position c.70 in exon 2 of CRYGD, a cataract-associated gene. This mutation resulted in a threonine substitution for proline at amino acid residue 24. Conclusions We identified a missense P24T mutation in CRYGD that was responsible for coralliform cataract in our studied family. Our findings suggest that the combination of exome sequencing and linkage analysis is a powerful tool for identifying Mendelian disease mutations that might be missed by the classic linkage analysis strategy. [ABSTRACT FROM AUTHOR]

The association between multiple sclerosis (MS) and tumor necrosis factor-alpha gene ( TNF-α) polymorphisms has been analyzed in several studies, but conflicting results have been reported. The main purpose of this study was to integrate previous findings and explore whether the three single nucleotide polymorphisms (SNPs; -238G/A, -308G/A, and -376G/A) of TNF-α are associated with susceptibility to MS. A total of 2,639 patients and 3,303 controls from 21 studies, which were identified by searching the ISI Web of Knowledge database and the PubMed database up to December 2009, were collected for this meta-analysis. The association between MS and TNF-α -238G/A, -308G/A, and -376G/A was previously analyzed in 4, 18, and 4 studies, respectively. Overall, no associations were identified for the TNF-α -238G/A polymorphism and MS in any of genetic model. Similarly, no associations were found for the TNF-α -308G/A polymorphism and MS or between the TNF-α -376G/A polymorphism and MS. Furthermore, no significant association between the three SNPs and MS was identified using subgroup analyses examining ethnicity and clinical manifestation. The results of the present study indicated that TNF-α -238G/A, -308G/A, or -376G/A may not be the main risk factor for MS, which should be interpret with caution for the limited study numbers. [ABSTRACT FROM AUTHOR]

It has been reported that single nucleotide polymorphisms (SNPs) in the promoter of the CCR5 gene are associated with the risk for HIV-1 infection and AIDS progression. Using resequencing, we performed a systematic survey of 78 HIV-1 seropositive individuals and 70 population-matched healthy control individuals from northern China to investigate SNPs of the CCR5 gene promoter and evaluated their effects on HIV-1 infection and the progression of AIDS. Linkage disequilibrium (LD) plots and haplotypes were generated using Haploview software. The association analyses were statistically compared using the Chi-square test with SPSS13.0 software for Windows. Seven SNPs (58755A>G, 58791C>T, 58934G>T, 59029A>G, 59353C>T, 59402A>G and 59653C>T) in the region of the CCR5 gene promoter were evaluated in this study. Among the seven SNPs, the minor allele frequencies of 58755G and 58791T were less than 2%. The differences in frequencies of the other five SNPs were not significant between case and control cohorts ( P > 0.05). In the case cohort, the association between these SNPs and clinical features (CD4 T-lymphocyte counts and clinical categories) was not significant ( P > 0.05); however, there was a significant association between the haplotype GGTAC and susceptibility to HIV-1 infection ( P < 0.05), which is not consistent with other reports studied in different populations. The results suggest that the haplotype GGTAC may have a role in the process of HIV-1 infection in the northern Chinese population. [ABSTRACT FROM AUTHOR]

• Twelve machine learning algorithms are compared to construct a retrieval model. • The TN concentration is retrieved using the UAV Hyper Spectral Remote Sensing data. • Spatial distribution of TN concentration is retrieved with high resolution. • Providing scientific references for water quality monitoring and management. Monitoring the water pollution level in real time is the most critical issue for protecting the water quality of water reservoirs. Due to the restrictions on flight areas of Unmanned Arial Vehicles (UAV), four sensitive regions with the area of 1–2 km2 were first selected in this study based on the spatial distribution of total nitrogen (TN) concentration changes estimated by the Landsat remote sensing data. And then twelve machine learning algorithms including Support Vector Machine (SVM), Artificial Neural Networks (ANN), Bayesian Ridge Regression (BRR), Lasso Regression (Lasso), Elastic Net (EN), Linear Regression (LR), Decision Tree Regression (DTR), K Neighbors Regression (KNR), Random Forest Regression (RFR), Extra Trees Regression (ETR), AdaBoost Regression (ABR) and Gradient Boosting Regression (GBR) were compared to construct a more accurate retrieval model by using the UAV hyper spectral remote sensing and ground monitoring data. And then the TN concentration was estimated after the process of dimensionality reduction and compressed sensing denoing. Finally, spatial heterogeneity of the TN concentration was analyzed in four sensitive areas of the Miyun reservoir. The results demonstrated that among the tested algorithms the Extra Trees Regression was best suitable for the construction of a TN concentration retrieval model on the basis of UAV hyper spectral data, and its absolute squared error was 0.000065. The spatial distribution of the TN showed that the concentration was highest within the water area of the Bulaotun village and the Houbajiazhuang village, while it was relatively low for the Chao river dam and Bai river dam. Additionally, no significant differences regarding the concentrations were shown in the single UAV flight area except the Houbajia village, which indicated that the water quality in Miyun reservoir was relatively stable and changed in a small interval. These conclusions can provide scientific references for water quality monitoring and management in the water reservoir. [ABSTRACT FROM AUTHOR]