Unraveling the influence of CRISPR/Cas13a reaction components on enhancing trans-cleavage activity for ultrasensitive on-chip RNA detection.

The CRISPR/Cas13 nucleases have been widely documented for nucleic acid detection. Understanding the intricacies of CRISPR/Cas13's reaction components is pivotal for harnessing its full potential for biosensing applications. Herein, we report on the influence of CRISPR/Cas13a reaction components on its trans-cleavage activity and the development of an on-chip total internal reflection fluorescence microscopy (TIRFM)-powered RNA sensing system. We used SARS-CoV-2 synthetic RNA and pseudovirus as a model system. Our results show that optimizing Mg2+ concentration, reporter length, and crRNA combination significantly improves the detection sensitivity. Under optimized conditions, we detected 100 fM unamplified SARS-CoV-2 synthetic RNA using a microtiter plate reader. To further improve sensitivity and provide a new amplification-free RNA sensing toolbox, we developed a TIRFM-based amplification-free RNA sensing system. We were able to detect RNA down to 100 aM. Furthermore, the TIRM-based detection system developed in this study is 1000-fold more sensitive than the off-coverslip assay. The possible clinical applicability of the system was demonstrated by detecting SARS-CoV-2 pseudovirus RNA. Our proposed sensing system has the potential to detect any target RNA with slight modifications to the existing setup, providing a universal RNA detection platform.

Sugar intake and risk of hypertension: a systematic review and dose-response meta-analysis of cohort and cross-sectional studies.

Several epidemiological studies have investigated the association between sugar intake, the levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the risk of hypertension, but findings have been inconsistent. We carried out a systematic review and meta-analysis of observational studies to examine the associations between sugar intake, hypertension risk, and BP levels. Articles published up to February 2, 2021 were sourced through PubMed, EMBASE and Web of Science. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a fixed- or random-effects model. Restricted cubic splines were used to evaluate dose-response associations. Overall, 35 studies were included in the present meta-analysis (23 for hypertension and 12 for BP). Sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) were positively associated with hypertension risk: 1.26 (95% CI, 1.15-1.37) and 1.10 (1.07-1.13) per 250-g/day increment, respectively. For SBP, only SSBs were significant with a pooled ß value of 0.24 mmHg (95% CI, 0.12-0.36) per 250 g increase. Fructose, sucrose, and added sugar, however, were shown to be associated with elevated DBP with 0.83 mmHg (0.07-1.59), 1.10 mmHg (0.12-2.08), and 5.15 mmHg (0.09-10.21), respectively. Current evidence supports the harmful effects of sugar intake for hypertension and BP level, especially SSBs, ASBs, and total sugar intake.

Biomedical association analysis between G2/M checkpoint genes and susceptibility to HIV-1 infection and AIDS progression from a northern chinese MSM population.

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.

[Characterization of genetic variants in children with refractory epilepsy].

OBJECTIVE: To analyze the characteristics of genetic variants among children with refractory epilepsy (RE). METHODS: One hundred and seventeen children with RE who had presented at the Affiliated Jinhua Hospital of Zhejiang University School of Medicine from January 1, 2018 to November 21, 2019 were selected as the study subjects. The children were divided into four groups according to their ages of onset: < 1 year old, 1 ~ 3 years old, 3 ~ 12 years old, and >= 12 years old. Clinical data and results of trio-whole exome sequencing were retrospectively analyzed. RESULTS: In total 67 males and 50 females were included. The age of onset had ranged from 4 days to 14 years old. Among the 117 patients, 33 (28.21%) had carried pathogenic or likely pathogenic variants. The detection rates for the < 1 year old, 1 ~ 3 years old and >= 3 years old groups were 53.85% (21/39), 12.00% (3/25) and 16.98% (9/53), respectively, with a significant difference among the groups (χ2 = 19.202, P < 0.001). The detection rates for patients with and without comorbidities were 33.33% (12/36) and 25.93% (21/81), respectively (χ2 = 0.359, P = 0.549). Among the 33 patients carrying genetic variants, 27 were single nucleotide polymorphisms (SNPs) or insertion/deletions (InDels), and 6 were copy number variations (CNVs). The most common mutant genes were PRRT2 (15.15%, 5/33) and SCN1A (12.12%, 4/33). Among children carrying genetic variants, 72.73% (8/11) had attained clinical remission after adjusting the medication according to the references. CONCLUSION: 28.21% of RE patients have harbored pathogenic or likely pathogenic variants or CNVs. The detection rate is higher in those with younger age of onset. PRRT2 and SCN1A genes are more commonly involved. Adjusting medication based on the types of affected genes may facilitate improvement of the remission rate.

The effect of SNPs in lncRNA as ceRNA on the risk and prognosis of hepatocellular carcinoma.

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.

The rs9953490 polymorphism of DAL-1 gene is associated with gastric cancer risk in the Han population in Northeast China.

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.

BMI and risk of all-cause mortality in normotensive and hypertensive adults: the rural Chinese cohort study.

OBJECTIVE: The impact of baseline hypertension status on the BMI-mortality association is still unclear. We aimed to examine the moderation effect of hypertension on the BMI-mortality association using a rural Chinese cohort. DESIGN: In this cohort study, we investigated the incident of mortality according to different BMI categories by hypertension status. SETTING: Longitudinal population-based cohort. PARTICIPANTS: 17 262 adults ≥18 years were recruited from July to August of 2013 and July to August of 2014 from a rural area in China. RESULTS: During a median 6-year follow-up, we recorded 1109 deaths (610 with and 499 without hypertension). In adjusted models, as compared with BMI 22-24 kg/m2, with BMI ≤ 18, 18-20, 20-22, 24-26, 26-28, 28-30 and >30 kg/m2, the hazard ratios for mortality in normotensive participants were 1·92 (95% CI 1·23, 3·00), 1·44 (95% CI 1·01, 2·05), 1·14 (95% CI 0·82, 1·58), 0·96 (95% CI 0·70, 1·31), 0·96 (95% CI 0·65, 1·43), 1·32 (95% CI 0·81, 2·14) and 1·32 (95% CI 0·74, 2·35), respectively, and in hypertensive participants were 1·85 (95% CI 1·08, 3·17), 1·67 (95% CI 1·17, 2·39), 1·29 (95% CI 0·95, 1·75), 1·20 (95% CI 0·91, 1·58), 1·10 (95% CI 0·83, 1·46), 1·10 (95% CI 0·80, 1·52) and 0·61 (95% CI 0·40, 0·94), respectively. The risk of mortality was lower in individuals with hypertension with overweight or obesity v. normal weight, especially in older hypertensives (≥60 years old). Sensitivity analyses gave consistent results for both normotensive and hypertensive participants. CONCLUSIONS: Low BMI was significantly associated with increased risk of all-cause mortality regardless of hypertension status in rural Chinese adults, but high BMI decreased the mortality risk among individuals with hypertension, especially in older hypertensives.

Preparation and luminescence properties of Tb3+ -doped garnet Y2 Mg2 Al2 Si2 O12 luminescent materials.

We prepared Y2 Mg2 Al2 Si2 O12 :xTb3+ (x = 0.02, 0.04, 0.06, 0.08, 0.10, 0.12, 0.14 and 0.16) luminescent materials using a nodulizing procedure. The phase and luminescence properties of these materials were investigated. X-ray diffraction results demonstrated that Tb3+ ions doped into Y2 Mg2 Al2 Si2 O12 hosts successfully and the Y2 Mg2 Al2 Si2 O12 :xTb3+ materials showed a pure cubic phase. Y2 Mg2 Al2 Si2 O12 :xTb3+ materials had the characteristic Tb3+ emission bands derived from 5 D4 →7 F6 , 7 F5 , 7 F4 , and 7 F3 transitions when excited at 365 nm. The green emission band that derived from the 5 D4 →7 F5 transition was highest due to the high possibility of both electric-dipole and magnetic-dipole transitions. Emission spectra indicated that the critical concentration of Tb3+ in the Y2 Mg2 Al2 Si2 O12 host was 0.14. The concentration quenching of Y2 Mg2 Al2 Si2 O12 :Tb3+ was derived from a dipole-dipole interaction.

Association Between Nonsyndromic Cleft Lip and Palate and 2 Polymorphic Loci: A Meta-Analysis.

OBJECTIVES: The relationship between Noggin (NOG) and methylenetetrahydrofolate reductase and nonsyndromic cleft lip and palate (NSCLP) has been reported participate in craniofacial development but need further evidence. To indicate the susceptibility between the 2 genes and NSCLP, rs227731 and rs1801131 polymorphisms were included in the present research. This research may provide some genetic clues for disease detection and surveillance. DESIGN: Seventeen studies including 4023 cases and 5691 controls were provided for meta-analysis, and odds ratio (OR) with 95% CI were obtained to estimate NSCLP risk. RESULTS: Our analysis suggested potential association of rs227731C on increasing the risk of NSCLP in the Caucasian group and total group but not Asian group under all models: allele (OR = 1.45, 95% CI = 1.21-1.75, P < .0001), homozygote (OR = 2.03, 95% CI = 1.42-2.90, P < .0001), heterozygote (OR = 1.44, 95% CI = 1.19-1.73, P = .0001), dominant (OR = 1.61, 95% CI = 1.27-2.04, P < .0001), and recessive models (OR = 1.63, 95% CI = 1.25-2.12, P = .0003). Besides, increased risk is related to rs1801131 in Asian group under 3 models: allele (OR = 1.24, 95% CI = 1.06-1.44, P = .006), heterozygote (OR = 1.24, 95% CI = 1.02-1.52, P = .03), and dominant models (OR = 1.29, 95% CI = 1.06-1.56, P = .009). CONCLUSIONS: Our analysis indicates polymorphisms rs227731 and rs1801131 are associated with NSCLP, with predominance of different ethnic group and deepen understanding of NSCLP.

Association between polymorphisms in MRE11 and HIV-1 susceptibility and AIDS progression in a northern Chinese MSM population.

BACKGROUND: Previous studies reported that DNA damage repair (DDR) genes may play an important role in HIV-1 infection. The MRE11 gene, a member of the MRN complex, plays an essential part in the homologous recombination pathway, which is one of the classical DDR pathways. Previous reports have demonstrated that MRE11 has an effect on HIV-1 replication. However, the role of SNPs in the MRE11 gene and their impact on HIV-1 infection and AIDS progression remain unknown. METHODS: In this study, 434 MSM HIV-1-infected patients in northern China and 431 age-matched healthy controls were enrolled. Five SNPs (rs2155209, rs10831234, rs13447720, rs601341 and rs11020803) at the MRE11 gene were genotyped. Another series of cases (409 MSM HIV-1-infected patients) and controls (403 age-matched healthy males) were recruited as the validation set. RESULTS: In our study, rs10831234 showed differences in allele frequencies between cases and controls (P = 0.005). Additionally, there was an association between rs10831234 and HIV-1 infection susceptibility in dominant and additive models (P = 0.005 and P = 0.006, respectively). All significant associations were replicated in the validation set, and the associations were still significant after Bonferroni correction for multiple testing when the two data sets were combined. Furthermore, in haplotype association analyses between the case and control groups, the frequencies of the haplotypes Crs11020803Crs10831234 and Trs11020803Trs10831234 showed significant differences (P = 0.0181 and P = 0.0068, respectively). CONCLUSIONS: We demonstrated that the MRE11 rs10831234-T allele may confer increased risk of HIV-1 infection.

Effect of a Roughness Element on the Hypersonic Boundary Layer Receptivity Due to Different Types of Free-Stream Disturbance with a Single Frequency.

The hypersonic flow field around a blunt cone was simulated using a high-order finite difference method. Fast acoustic waves, slow acoustic waves, entropy waves, and vortical waves were introduced into the free-stream to determine the influence of a free-stream with disturbances on the hypersonic flow field and boundary layer. The effect of disturbance type on the evolution of perturbations in the hypersonic boundary layer was analyzed. Fast Fourier Transform was adopted to analyze the effect of the disturbance type on the evolution of different modes in the boundary layer. A roughness element was introduced into the flow field to reveal the impact of the roughness element on hypersonic boundary layer receptivity. The results showed that a free-stream with disturbances affected the hypersonic flow field and boundary layer; acoustic waves had the greatest influence. The impact of slow acoustic waves on the flow field was mainly concentrated in the region between the shock and the boundary layer, whereas the influence of fast acoustic waves was mainly concentrated in the boundary layer. Multi-mode perturbations formed in the boundary layer were caused by the free-stream with disturbances, wherein the fundamental mode was the dominant mode of the perturbations in the boundary layer caused by fast acoustic waves, entropy waves, and vortical waves. The dominant modes of the perturbations in the boundary layer caused by slow acoustic waves were both the fundamental mode and the second harmonic mode. The roughness element changed the propagation process of different modes of perturbations in the boundary layer. In the downstream region of the roughness element, perturbations in the boundary layer caused by the slow acoustic waves had the greatest influence. The second harmonic mode in the boundary layer was significantly suppressed, and the fundamental mode became the dominant mode. The effects of fast acoustic waves and entropy waves on the boundary layer receptivity were similar, except the amplitude of the perturbations in the boundary layer caused by the fast acoustic waves was larger.

The distribution of three candidate cold-resistant SNPs in six minorities in North China.

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.

Effect of a Roughness Element on the Receptivity of a Hypersonic Boundary Layer over a Blunt Cone Due to Pulse Entropy Disturbance with a Single Frequency.

A high-order finite difference method was used to simulate the hypersonic flow field over a blunt cone with different height roughness elements. The unsteady flow field induced by pulse disturbances was analyzed and compared with that under continuous disturbances. The temporal and spatial evolution characteristics of disturbances in the boundary layer were investigated and the propagation of different disturbance modes in the boundary layer was researched through the fast Fourier transform (FFT) method. The effect of the roughness element on the receptivity characteristic of the hypersonic boundary layer under pulse entropy disturbances was explored. The results showed that the different mode disturbances near roughness in the boundary layer were enlarged in the upstream half of the roughness element and suppressed in the downstream half. However, the effect of roughness weakened gradually as the disturbance frequency increased in the boundary layer. A phenomenon of mode competition in the downstream region of the roughness element exited. As the disturbances propagated downstream, the fundamental mode gradually became the dominant mode. A certain promotion effect on the mode competition was induced by the roughness element and the effect was enhanced with the increase in the roughness element height.

Association of single nucleotide polymorphisms of APOBEC3G with susceptibility to HIV-1 infection and disease progression among men engaging in homosexual activity in northern China.

Men who have sex with men (MSM) are at high risk of HIV infection. The APOBEC3G (apolipoprotein B mRNA editing catalytic polypeptide 3G) protein is a component of innate antiviral immunity that inhibits HIV-1 replication. In the present study, a total of 483 HIV-1 seropositive men and 493 HIV-1 seronegative men were selected to investigate the association between single nucleotide polymorphisms (SNPs) of the APOBEC3G gene and susceptibility to HIV-1 infection and AIDS progression among MSM residing in northern China. Genotyping of four SNPs (rs5757465, rs3736685, rs8177832, and rs2899313) of the APOBEC3G was performed using the SNPscan™ Kit, while the rs2294367 polymorphism was genotyped using the SNaPshot multiplex system. Our results disclosed no association between the SNPs of APOBEC3G and susceptibility to HIV-1, or effects of these polymorphisms on the CD4+ T cell count or clinical phase of disease. A meta-analysis of 1624 men with HIV-1 infection and 1523 controls suggested that the association between rs8177832 and susceptibility was not significant. However, we observed a trend towards association with HIV-1 infection for haplotype TTACA (p = 0.082). The potential role of variants of APOBEC3G in HIV-1/AIDS warrants further investigation.

Fluorescence Imaging of Intracellular Telomerase Activity Using Enzyme-Free Signal Amplification.

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.

A direct assay of carboxyl-containing small molecules by SALDI-MS on a AgNP/rGO-based nanoporous hybrid film.

Silver nanoparticles (AgNPs) and reduced graphene oxide (rGO) hybrid nanoporous structures fabricated by the layer-by-layer (LBL) electrostatic self-assembly have been applied as a simple platform for the rapid analysis of carboxyl-containing small molecules by surface-assisted laser desorption/ionization (D/I) mass spectrometry (SALDI-MS). By the simple one-step deposition of analytes onto the (AgNP/rGO)9 multilayer film, the MS measurements of various carboxyl-containing small molecules (including amino acids, fatty acids and organic dicarboxylic acids) can be done. In contrast to other energy transfer materials relative to AgNPs, the signal interferences of a Ag cluster (Agn(+) or Agn(-)) and a C cluster (Cn(+) or Cn(-)) have been effectively reduced or eliminated. The effects of various factors, such as the pore structure and composition of the substrates, on the efficiency of D/I have been investigated by comparing with the (AgNP)9 LBL nanoporous structure, (AgNP/rGO)9/(SiO2NP)6 LBL multilayer film and AgNP/prGO nanocomposites.

The Utilization of Shape Memory Alloy as a Reinforcing Material in Building Structures: A Review.

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.

Repression of the SUMO-conjugating enzyme UBC9 is associated with lowered double minutes and reduced tumor progression.

Double 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.

Combinational analysis of linkage and exome sequencing identifies the causative mutation in a Chinese family with congenital cataract.

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.