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Background: A disintegrin and metalloprotease 33 (ADAM33) has recently been suspected to be associated with psoriasis. Objective:To study the association between ADAM33 and psoriasis in the northeastern Chinese Han population. Methods: We genotyped six common single nucleotide polymorphisms from ADAM33 in 400 psoriasis cases and 398 controls using the Multiplex SNaPSHOT method. Results: We observed an increased risk of psoriasis to be associated with the rs2787094CC CG, rs528557CC CG genotypes (p < 0.05) and 3 haplotypes (H1, H3, and H5; p < 0.05). We also found that the rs512625AA rs612709AA GA genotypes and haplotype H8 may be protective against psoriasis (p < 0.05). Among these genotypes, rs2787094CC exhibited the strongest association with psoriasis (OR = 2.537,being the highest OR, p = 0.0014). Conclusions: ADAM33 polymorphisms are associated with psoriasis in the northeastern Chinese Han population. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective. It has been reported that some single-nucleotide polymorphisms ( -13910C/T, -22018G/A, -13907C/G, -13915T/G, and -14010G/C) within the lactase gene are associated with lactase persistence. In our previous study, we found that -13910C/T is not a good predictor of lactase persistence in Chinese populations. To obtain a better understanding of the mechanism of lactase persistence, we examined the frequencies in Northern China of the four other alleles that are associated with lactase persistence. Material and methods. We evaluated the allele frequencies of -22018G/A, -13907C/G, -13915T/G, and -14010G/C in six northern Chinese populations (Manchu, Mongol, Hezhen, Oroqen, Kazak, and northern Han) using the methods of polymerase chain reaction–restriction fragment length polymorphism and resequencing. Results. By genotyping 1092 chromosomes, we found that the frequency of the -22018A allele was highest in the Kazak population and extremely low in the northern Han population. Although there are little available data about the frequency of lactase persistence in northern Chinese populations, we compared the allele frequencies with the phenotype frequencies that have been published previously. We found that the frequency of the -22018A allele was basically consistent with the reported frequencies of lactase persistence in Northern China. With respect to the -13907C/G, -13915T/G, and -14010G/C polymorphisms, we found no individuals with the derived allele. Conclusions. The frequency of the -22018A allele differed significantly among the six populations and the frequency reflected the frequency of lactase persistence. Taking into consideration the results of previous studies, we believe that the origins of lactase persistence-associated alleles are different in different pastoral populations. [ABSTRACT FROM AUTHOR]

This study strategically fabricates a nucleic acid functionalized gold nanoparticle and graphene oxide composite probe (AuNP/GO probe) to achieve both the recognition and in situ monitoring of cytoplasmic target precursor microRNAs (pre-miRNAs) and mature microRNAs (miRNAs) in living cells. The pre-miRNA-21 detection with AuNP probes has a good linear range of 0–300 nM and a limit of detection (LOD) of 4.5 nM, whereas the GO probe has a linear relationship with mature miRNA-21 from 0.1 to 10 nM with a LOD of 1.74 nM. This assay was utilized to directly visualize the relative expression levels of pre- and mature forms of miRNA-21 and let-7a. The results suggested that the expression levels of precursor miRNAs remain constant in cancer cells and normal cells. However, the expression levels of mature miRNAs vary widely, demonstrating the “up-regulation” of miRNA-21 and “down-regulation” of let-7a in cancer cells in contrast to that in normal cells. The practicality of this strategy was verified by in situ monitoring changes in cytoplasmic pre-miRNA-21 and mature miRNA-21 in response to small-molecule inhibitors of miRNA-21. [ABSTRACT FROM AUTHOR]

Abstract 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 β 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. [ABSTRACT FROM AUTHOR]

The generation and expansion of cracks in concrete materials have always been a problem that needs to be solved, and an increasing number of scholars are beginning to hope that structures will have bionic functions of self-diagnosis and self-repairing of damage. In this study, shape memory alloy (SMA) concrete beams are prepared. The flexural and self-repairing properties of SMA concrete beams were investigated by a four-point bending test. The effects of various factors on the bearing capacity, ductility, and crack width before and after repair were analyzed. The experimental results indicate that the increase of SMA fiber content and the complexity of the SMA bar end shape can significantly enhance the flexural bearing capacity and repair performance of the beam. The increase in the bond length of SMA bars can enhance the bending resistance of the beam, but it will reduce its self-repairing performance. The repair rate of SMA on concrete cracks is 45.7 %-76.5 %, and the load recovery rate is between 49.4 % and 80.6 %. The flexural load capacity calculation formula is proposed, and the calculation results closely match the test values, providing a reference for the application of SMA. • The mechanism of SMA fiber on the flexural and repair function was explored. • The effects of the end shape on flexural and self-repairing properties were studied. • The results are analyzed by using grey correlation degree and response surface. • The calculation formula of flexural bearing capacity is proposed. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

In this paper, the central pull-out tests were carried out on shape memory alloy fiber-reinforced concrete (SMA-FRC) under monotonic load. The failure modes and failure mechanisms of the specimens were observed and analyzed, and the bond strength and slip distance were measured. The effects of different influencing factors on the mechanical behavior of bond-slip were investigated, and the bond-slip constitutive model of shape memory alloy (SMA) bar and SMA-FRC was proposed. The test results indicated that the ultimate bond strength between SMA bars and SMA-FRC gradually increased with the addition of SMA fiber, the reduction of SMA bar diameter, the decrease of anchorage length, and the lowering of temperature within a certain range. In this paper, based on the theoretical analysis of the test data, a reasonable bond-slip constitutive model was established, which can better predict the test results. • The effect of various factors on the bonding properties is analyzed and the best combination of factors is obtained. • The influencing factors were analyzed by response surface method, and the optimal solution of bond strength was obtained. • A new bond-slip constitutive model is proposed, which has wide applicability and accuracy. [ABSTRACT FROM AUTHOR]

Across the five sensory modalities we examine an unexplored difference in imagery: psychological distance. In particular, we propose that imagined senses can be psychologically more proximal or distal based on the maximum physical distance typically required for a stimulus to be sensed. Specifically, we propose that imagined senses that require close proximity to the body in order to be sensed (i.e., taste, touch) will feel more psychologically proximal than senses that do not require such close proximity (i.e., hearing, sight). We obtain support for our theoretical framework across a pilot study, four lab studies, and one field study by examining how images evoked using different sensory modalities differentially influence variables shown in past research to vary along psychological distance: (1) the imagined distance between the consumer and the stimulus, (2) product perceptions on other dimensions of psychological distance, and (3) persuasion when matched with other dimensions of psychological distance. [ABSTRACT FROM AUTHOR]

Chemotherapeutic resistance is a major obstacle to the effectiveness of cisplatin-based chemotherapy for gastric cancer (GC), leading to treatment failure and poor survival rates. However, the underlying mechanisms are not fully understood. Our study demonstrated that the transcription factor myocyte enhancer factor 2A (MEF2A) plays a role in chemotherapeutic drug resistance by regulating the transcription of PGC1α and KEAP1, promoting mitochondrial biogenesis. It was found that increased MEF2A expression is linked with poor prognosis, cisplatin insensitivity, and mitochondrial function in GC. MEF2A overexpression significantly decreases GC cell sensitivity in vitro and in vivo, while MEF2A knockdown enhances the sensitivity to cisplatin. Mechanistically, MEF2A activates the transcription of PGC1α, leading to increased mitochondrial biogenesis. In addition, MEF2A inhibits KEAP1 transcription, reduces NRF2 ubiquitination degradation, and activates the KEAP1/NRF2 signaling pathway, which modulates the reactive oxygen species level. The present study identifies MEF2A as a new critical oncogene involved in GC chemoresistance, suggesting a novel therapeutic target for GC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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 β 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.

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.

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 Mg 2+ 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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective To explore the regulatory mechanism of interleukin-33 (IL-33) on the inflammatory response in asthmatic mice. Methods Using 10 μg/mL of lipopolysaccharide (LPS) to establish a cellular inflammation model of mouse bone marrow mesenchymal stem cells (BMMSCs), the cells were divided into three groups: small interfering RNA of IL-33(si-IL-33) group, IL-33 overexpression (IL-33-OE) group, and model group, based on the transfection status of si-IL-33 plasmid and IL-33-OE plasmid. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect mRNA expression of IL-33, nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), IL-1β and IL-6. Fluo-3 AM was used to measure calcium ion content, and JC-1 mitochondrial membrane potential detection kit was performed to detect mitochondrial membrane potential changes. An asthma mouse model was established by intraperitoneal injection of sensitizers and activators. According to different treatment plans, the asthmatic mice were divided into si-IL-33 group, IL-33-OE group and model group, with 5 mice in each group. ELISA was used to detect the levels of IL-1β, IL-6 and NLRP3 in mouse serum, while HE staining and Masson staining were performed to assess lung tissue lesions. Results Compared with the model group, the mRNA expression levels of IL-33, NLRP3, IL-1β and IL-6 in the si-IL-33 group were all reduced, while those in the IL-33-OE group were increased. The calcium ion fluorescence was decreased in BMMSCs, while it was increased in the IL-33-OE group. In the si-IL-33 group, JC-1 existed in a polymer form in mitochondria, showing bright red fluorescence and weak green fluorescence, indicating stable mitochondria and normal mitochondrial function. After treating with IL-33-OE plasmid to reduce the mitochondrial membrane potentia, JC-1 cannot exist in polymer form within the mitochondrial matrix. At this point, the red fluorescence intensity inside the mitochondria decreases significantly, while the green fluorescence in the cytoplasm increases significantly. The levels of IL-1β, IL-6, and NLRP3 in the serum of mice in the si-IL-33 group were significantly lower, while those in the IL-33-OE group were significantly higher. In the si-IL-33 group, almost no inflammatory cell infiltration was observed, indicating a relief of inflammation and normal epithelial cell morphology. Additionally, the fibrotic portion of the lung tissue in the si-IL-33 group tended to be normal. The total wall area of bronchus (WAt)/basement membrane perimeter (Pbm) and wall area of bronchial smooth muscle (WAm)/Pbm were reduced in the si-IL-33 group compared with the model group, while they were increased in the IL-33-OE group. Conclusion Knockdown of IL-33 inhibits the inflammatory response in asthmatic mice by downregulating the expression of NLRP3, IL-1β and IL-6.

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.

Oculocutaneous albinism (OCA) is a genetically heterogeneous disease and is most inherited in an autosomal recessive manner. The characteristic manifestation of OCA is due to disfunction of melanin synthesis. OCA1 is the most severe subtype of OCA and is caused by homozygous or compound heterozygous variants in tyrosinase (TYR) gene, which is the key gene for melanin synthesis. This study aimed to identify the genetic variants of a northern Chinese family with OCA1. Clinical information and peripheral blood samples were collected. PCR amplification and Sanger sequencing were used to detect the entire exons and adjacent flanking sequences of TYR gene. Functional prediction of variants was performed by various bioinformatic analyses, while the pathogenicity classification of variants was evaluated according to ACMG standards and guidelines. A missense variant NM&#95;000372.5:c.107G > C;NP&#95;000363.1:p.C36S was discovered in TYR gene which converted cysteine to serine. Another variant in intron, NM&#95;000372.5:c.1037-7 T > A, also affected the function of TYR gene. We verified the pathogenicity of the intron variant with a pCAS2 mini-gene based splicing assay and found that c.1037-7 T > A led to an insertion of 5 bp upstream from the common acceptor site of exon 3, which caused a frameshift TYR:c.1037-7 T > A:p.G346Efs*11. The results showed that the compound heterozygous variants c.107G > C:p.C36S and c.1037-7 T > A:p.G346Efs*11 of TYR gene were the pathogenic variants for this OCA1 family., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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 (χ 2 = 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 (χ 2 = 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.

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., (© 2023. The Author(s).)