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The flatwise compression and mechanical response of gradient-tandem Nomex honeycomb sandwich panels were investigated by quasi-static compression tests. Finite element models of the gradient-tandem Nomex honeycomb sandwich panels were established to evaluate the effects of layer sequences, separator materials, and layer heights on the mechanical properties through parametric studies. The different assembly of honeycomb sequence and separator material affected the deformation sequence and peak stress of the sandwich panels. Under quasi-static compression, the response curves are smoother when the appropriate separator material and assembly sequence are chosen. Meanwhile, the peak stresses are effectively reduced. The research results can guide the individualized design of tandem Nomex honeycomb sandwich panels. [ABSTRACT FROM AUTHOR]

Sandwich panels are often subjected to unpredictable impacts and crashes in applications. The core type and impactor shape affect their impact response. This paper investigates the responses of five tandem Nomex honeycomb sandwich panels with different core-types under low-velocity-impact conditions with flat and hemispherical impactors. From the force response and impact displacement, gradient-tandem and foam-filled structures can improve the impact resistance of sandwich panels. Compared with the single-layer sandwich panel, the first peak of contact force of the foam-gradient-filled tandem honeycomb sandwich panels increased by 34.84%, and maximum impact displacement reduced by 50.98%. The resistance of gradient-tandem Nomex honeycomb sandwich panels under low-velocity impact outperformed uniform-tandem structures. Foam-filled structures change the impact responses of the tandem sandwich panels. Impact damage with a flat impactor was more severe than the hemispherical impactor. The experimental results are helpful in the design of tandem Nomex honeycomb sandwich panels. [ABSTRACT FROM AUTHOR]

X-chromosome inactivation (XCI) is the form of dosage compensation in mammalian female cells to balance X-linked gene expression levels of the two sexes. Many diseases are related to XCI due to inactivation escape and skewing, and the symptoms and severity of these diseases also largely depend on the status of XCI. They can be divided into 3 types: X-linked diseases, diseases that are affected by XCI escape, and X-chromosome aneuploidy. Here, we review representative diseases in terms of their definition, symptoms, and XCI's role in the pathogenesis of these diseases. [ABSTRACT FROM AUTHOR]

The linker of nucleoskeleton and cytoskeleton (LINC) complex is a protein complex across the nuclear envelope and has maintained its general assembly mode throughout evolution. SUN and KASH proteins, which are the major components of LINC complex, interact with each other in the nuclear lumen to transmit forces across the nuclear envelope and have diverse functions. However, research of LINC complex in budding yeast has been limited due to the lack of identification of a canonical KASH protein and a cytoskeleton factor. Here, we review recent findings that addressed these puzzles in budding yeast. We highlight the distinct assembly model of the telomere-associated LINC complex in budding yeast, which could be beneficial for identifying LINC variants in other eukaryotes. [ABSTRACT FROM AUTHOR]

As an intriguing topological defect, global monopole's influence on behaviors of black holes has always been anticipated but still remains obscure. Analyzing the thermodynamics of charged Anti-de Sitter (AdS) black hole incorporating a global monopole manifests that the black hole undergoes a Van der Waals-like first-order phase transition near the critical point. This paper concentrates on further investigating the transition, aiming at clarifying how the global monopole affects the criticality and microstructure of the charged AdS black holes. As a highlight, this research is implemented by employing new state parameters other than (T, P, V) description and contributes to deeper understanding the rich critical phenomena and phase structure of black holes. [ABSTRACT FROM AUTHOR]

During X chromosome inactivation, many chromatin changes occur on the future inactive X chromosome, including acquisition of a variety of repressive covalent histone modifications, heterochromatin protein associations, and DNA methylation of promoters. Here, we summarize trans-acting factors and cis elements that have been shown to be involved in the human inactive X chromosome organization and compaction. [ABSTRACT FROM AUTHOR]

The curvaton scenario received much attention recently. It provides an alternative way to generate scale-invariant perturbations for the observed universe, besides the standard inflation paradigm. This paper studies the preheating in the nonminimal derivative coupling curvaton model with a nonstandard kinetic matter term, as a consequence of the large scale power spectrums of curvature perturbation. It is found that the nonstandard kinetic matter term is able to modify the behavior of the preheating, compared to the nonminimal derivative coupling curvaton model with standard kinetic matter term. Our result may provide an insight to the preheating process for bouncing cosmology or brane-inspired cosmology. [ABSTRACT FROM AUTHOR]

Abstract The emergence of circulating miRNAs as potential biomarkers for cancer necessitates reliable approaches to detect miRNAs with high sensitivity and specificity. We disclose a highly sensitive method for rapid and direct quantification of circulating miRNA in serum by combining dynamic DNA circuit and single-molecule fluorescence detection. The product of DNA circuits based amplification is detected by total internal reflection fluorescence microscopy (TIRFM). The single-molecule counting allows the quantification of miRNA targets. Owing to the high sensitivity for fluorophore labeled nucleic acids of TIRFM, the products generated by 15 min amplification are sufficient for quantification. Meanwhile, the fast detection also addresses the problem of leakage because non-target triggered DNA circuits is relatively slow. There miRNA biomarkers miR-141, miR-21, miR-16 were detected with remarkable sensitivity as detection limits of 0.017, 0.012, 0.006 fM, respectively. This approach was applied for the direct quantification of the circulating miRNAs in human serum. The results of 29 health samples, 18 prostate cancer samples, 23 breast cancer samples imply that miR-141 and miR-21 are up-regulated in the prostate cancer samples and the breast cancer samples, respectively, and as reference miR-16 shows no difference in health and patient samples. Graphical abstract Image 1 Highlights • Single-molecule fluorescence was combined with catalytic hairpin assembly for ultrasensitive detection of miRNA. • The sensitivity of the single-molecule detection effectively addresses the leakage of DNA circuits. • Excellent LOD was achieved for three miRNA biomarkers. • Circulating miRNA in human serum was detected which is in good agreement with RT-qPCR. [ABSTRACT FROM AUTHOR]

Thermodynamical properties of charged AdS black holes with a global monopole still remain obscure. In this paper, we investigate the thermodynamics and phase transition of the black holes in the extended phase space. It is shown that thermodynamical quantities of the black holes exhibit an interesting dependence on the internal global monopole, and they perfectly satisfy both the first law of thermodynamics and Smarr relation. Furthermore, analysis of the local and the global thermodynamical stability manifests that the charged AdS black hole undergoes an elegant phase transition at critical point. Of special interest, critical behaviors of the black holes resemble a Van der Waals liquid-gas system. Our results not only reveal the effect of a global monopole on thermodynamics of AdS black holes, but also further support that Van der Waals-like behavior of the black holes is a universal phenomenon. [ABSTRACT FROM AUTHOR]

T-cell large granular lymphocyte (T-LGL) leukemia is a rare lymphoproliferative disorder characterized by infiltration of blood and bone marrow with large granular lymphocytes, splenomegaly, and cytopenias. Most patients with T-LGL leukemia follow an indolent course, with a median survival of over 10 years. However, a subset of T-LGL leukemia cases exhibits more aggressive clinical behavior. Recent identification of recurrent activating STAT3 gene mutations in T-LGL leukemia suggests that sequence alterations play a role in the persistence of clonal T-cell expansions. However, cytogenetic alterations have rarely been reported in T-LGL leukemia. Here we present the chromosomal microarray analysis (CMA) of twenty T-LGL leukemia cases, which represents the largest cohort to date. All cases were analyzed by the CytoScan HD chromosomal microarray. Detected alterations were classified based on the published ACMG/CGC guidelines. Copy number abnormalities and copy neutral loss of heterozygosity were detected in seven T-LGL leukemia cases (7/20, 35%), with few recurrent CNAs identified, indicating extensive genetic heterogeneity. The most common copy-number abnormality was a gain of 1p36, and the most common copy-neutral abnormality was a loss of heterozygosity of 17q12q25. Data from this pilot study demonstrates that a subset of T-LGL leukemia cases carry recurrent cytogenetic alterations. Follow-up CMA testing of additional cases is currently underway to clarify the contribution of recurrent cytogenetic alterations to the pathogenesis of T-LGL leukemia. Additionally, correlation of the cytogenetic alterations profile with the clinical course may provide prognostic insight into the existence of aggressive or transformed variants of T-LGL leukemia. [ABSTRACT FROM AUTHOR]

Objective Familial aggregation of fibromyalgia has been increasingly recognized. The goal of this study was to conduct a genome-wide linkage scan to identify susceptibility loci for fibromyalgia. Methods We genotyped members of 116 families from the Fibromyalgia Family Study and performed a model-free genome-wide linkage analysis of fibromyalgia with 341 microsatellite markers, using the Haseman-Elston regression approach. Results The estimated sibling recurrence risk ratio (λs) for fibromyalgia was 13.6 (95% confidence interval 10.0-18.5), based on a reported population prevalence of 2%. Genome-wide suggestive evidence of linkage was observed at markers D17S2196 (empirical P [ Pe] = 0.00030) and D17S1294 ( Pe = 0.00035) on chromosome 17p11.2-q11.2. Conclusion The estimated sibling recurrence risk ratio (λs) observed in this study suggests a strong genetic component of fibromyalgia. This is the first report of genome-wide suggestive linkage of fibromyalgia to the chromosome 17p11.2-q11.2 region. Further investigation of these multicase families from the Fibromyalgia Family Study is warranted to identify potential causal risk variants for fibromyalgia. [ABSTRACT FROM AUTHOR]

Squalene is a medically valuable bioactive compound that can be used as a raw material for fuels. Microbial fermentation is the preferred method for the squalene production. In this study, we employed several metabolic engineering strategies to increase squalene yield in Rhodopseudomonas palustris. A 57% increase in squalene titer was achieved by blocking the carotenoid pathway, thus directing more FPP into the squalene biosynthetic pathway. In order to cut down the conversion of squalene to haponoids, a recombinant strain R. palustris [Δshc, ΔcrtB] in which both carotenoid and haponoid pathways were blocked was then constructed, resulting in a 50‐fold increase in squalene titer. Based on the expression of rate‐limiting enzymes involved in the squalene pathway, the final squalene content reached 23.3 mg/g DCW, which was 178‐times higher than that of the wild‐type strain. In this study, several methods effective in improving squalene yield have been described and the potential of R. palustris for producing squalene has been demonstrated. [ABSTRACT FROM AUTHOR]

Oxygen vacancy engineering is a promising strategy to enhance the electrocatalytic activities in conventional metal oxide electrocatalysts. However, the utilization of oxygen vacancies in high‐entropy oxides remains unknown, primarily due to the challenges associated with facile introduction of the oxygen vacancies and explanation of their roles in complex high‐entropy systems. Herein, the facile introduction of oxygen vacancies into high‐entropy oxides is realized and the unique high entropy‐driven role of oxygen vacancies for oxygen evolution reaction (OER) process is revealed. A low‐temperature surface carbonization–decarbonization approach is developed to introduce and regulate the oxygen vacancies in high‐entropy spinel oxides (HEOs). The oxygen vacancies in HEOs can both facilitate pre‐oxidation process for faster OH− adsorption and induce the unique bridge site pathway for easier deprotonation, distinctive in conventional oxides where oxygen vacancies favor *OH adsorption yet hinder the deprotonation. Consequently, the as‐prepared high‐entropy spinel oxides with oxygen vacancies (HEOs‐Ov) exhibit superior OER activities, outperforming the HEOs and most reported oxide‐based electrocatalysts. Besides, this universal method can be extended to other spinel oxides with different configuration entropies and can be scaled up. The work paves the way for the exploration of oxygen vacancies in high‐entropy oxides toward electrocatalysis fields. [ABSTRACT FROM AUTHOR]

PZT matrix ferroelectric composite is an important research topic in material science because of its many practical, industrial, and scientific applications. Materials with high dielectric permittivity are used to manufacture electronic devices, particularly capacitors and dynamic random access memory (DRAM). Therefore, the development of reliable and efficient micro models to be utilized in analyzing electrical properties can be of great value in accelerating research in this field. In this paper, a 3D microstructure model for PZT matrix ferroelectric composites has been developed and adopted the finite element method (FEM) to calculate the dielectric constant. The microscopy parameters of developed microstructure model are acquired based on the real composites from X-ray (micro-) diffraction and stereological method. The dielectric constant of different volume ratios of PZT matrix ferroelectric composites can be calculated by accurately controlling the volume of Ferrite particles. At the point of validation, the proposed approach makes visual and numeric comparisons between the morphology of the real microstructure and the model generated by the proposed technique. The simulation results by our method was essentially in agreement with experimental results in other literature. Simulation Experimental results also demonstrate that the dielectric constant of PZT matrix ferroelectric composites is significantly changed while the volume ratio of high dielectric phase particles was below 20%. PZT matrix ferroelectric composites Consequently, this method can be easily extended to composites preparation. [ABSTRACT FROM AUTHOR]

Elucidating the aerosol dynamics in the pulmonary acinar region is imperative for both health risk assessment and inhalation therapy, especially nowadays with the occurrence of the global COVID-19 pandemic. During respiration, the chest's outward elastic recoil and the lungs' inward elastic recoil lead to a change of transmural pressure, which drives the lungs to expand and contract to inhale and expel airflow and aerosol. In contrast to research using predefined wall motion, we developed a four-generation acinar model and applied an oscillatory pressure on the model outface to generate structure deformation and airflow. With such tools at hand, we performed a computational simulation that addressed both the airflow characteristic, structural mechanics, and aerosol dynamics in the human pulmonary acinar region. Our results showed that there is no recirculating flow in the sac. The structural displacement and stress were found to be positively related to the change of model volume and peaked at the end of inspiration. It was noteworthy that the stress distribution on the acinar wall was significantly heterogeneous, and obvious concentrations of stress were found at the junction of the alveoli and the ducts or the junction of the alveoli and alveoli in the sac. Our result demonstrated the effect of breathing cycles and aerosol diameter on deposition fraction and location of aerosols in the size range of 0.1–5 μm. Multiple respiratory cycles were found necessary for adequate deposition or escape of submicron particles while having a negligible influence on the transport of large particles, which were dominated by gravity. Our study can provide new insights into the further investigation of airflow, structural mechanics, and aerosol dynamics in the acinar depth. • Oscillatory pressure is applied on the model outface to generate tissue deformation. • Airflow, structure and aerosol dynamics are analyzed in a four-generation FSI model. • Structural displacement & stress are positively linked to the change of model volume. • The stress distribution on the acinar wall is significantly heterogeneous. • Multi breathing cycles are necessary for adequate deposition of submicron particles. [ABSTRACT FROM AUTHOR]

Globally, dental caries is one of the most common non-communicable diseases for patients of all ages; Streptococcus mutans (S. mutans) is its principal pathogen. Lactobacillus paracasei (L. paracasei) shows excellent anti-pathogens and immune-regulation functions in the host. The aim of this study is to evaluate the effects of L. paracasei ET-22 on the formation of S. mutans biofilms. The living bacteria, heat-killed bacteria, and secretions of L. paracasei ET-22 were prepared using the same number of bacteria. In vitro, they were added into artificial-saliva medium, and used to coculture with the S. mutans. Results showed that the living bacteria and secretions of L. paracasei ET-22 inhibited biofilm-growth, the synthesis of water-soluble polysaccharide and water-insoluble polysaccharide, and virulence-gene-expression levels related to the formation of S. mutans biofilms. Surprisingly, the heat-killed L. paracasei ET-22, which is a postbiotic, also showed a similar regulation function. Non-targeted metabonomics technology was used to identify multiple potential active-substances in the postbiotics of L. paracasei ET-22 that inhibit the formation of S. mutans biofilms, including phenyllactic acid, zidovudine monophosphate, and citrulline. In conclusion, live bacteria and its postbiotics of L. paracasei ET-22 all have inhibitory effects on the formation of S. mutans biofilm. The postbiotics of L. paracasei ET-22 may be a promising biological anticariogenic-agent. [ABSTRACT FROM AUTHOR]

Virus-like particles (VLPs) are viral structural protein that are noninfectious as they do not contain viral genetic materials. They are safe and effective immune stimulators and play important roles in vaccine development because of their intrinsic immunogenicity to induce cellular and humoral immune responses. In the design of antiviral vaccine, VLPs based vaccines are appealing multifunctional candidates with the advantages such as self-assembling nanoscaled structures, repetitive surface epitopes, ease of genetic and chemical modifications, versatility as antigen presenting platforms, intrinsic immunogenicity, higher safety profile in comparison with live-attenuated vaccines and inactivated vaccines. In this review, we discuss the mechanism of VLPs vaccine inducing cellular and humoral immune responses. We outline the impact of size, shape, surface charge, antigen presentation, genetic and chemical modification, and expression systems when constructing effective VLPs based vaccines. Recent applications of antiviral VLPs vaccines and their clinical trials are summarized. [ABSTRACT FROM AUTHOR]

It is critical to accurately estimate the deposition of inhaled particles in the pulmonary acinus to reduce the damage of ambient aerosols or maximize drug particles' efficacy. However, interparticle interactions were always neglected in the simulation of aerosol deposition in human acinus. A four-generation human acinar model with varying sizes of each generation was developed. Two boundary conditions, rigid wall and moving wall were investigated to simulate the effect of wall motion on the flow field and aerosol deposition for the size range of 0.1–5 μm. Results show that wall motion has a net effect on particles' location and deposition, especially for submicron particles. Moreover, interparticle collisions were employed to gain richer aerosol particle dynamics. Results demonstrate that the minimum concentration of particles for coalescence is 8.5 × 104 particles/cm3 in the acinar region. The coalescence of particles is influenced by particle concentration and diameter, and wall motion and has a non-negligible effect on particle deposition. Furthermore, it should be noted that the influence of collision would be more significant during more respiratory cycles. Our findings demonstrate that wall motion and interparticle collisions play a non-negligible role in the aerosol deposition. • Rigid and moving walls are investigated to simulate the effect of wall motion. • Interparticle collisions and coalescence are employed to gain richer aerosol particle dynamics. • Wall motion and interparticle collisions are proved to affect particle sites and deposition. • The minimum concentration of particles for coalescence is 8.5 × 104 particles/cm3 in the acinar region. • The coalescence of particles is influenced by particle concentration and diameter, and wall motion. [ABSTRACT FROM AUTHOR]

Objective To investigate the differential expression of DNA methyltransferase (DNMT) in hepatocellular carcinoma (HCC). Methods DNMT mRNA expression was measured by fluorescence quantitative - PCR in specimens of cancerous tissues (n -44) and case - matched ciirhotic ( n - 35 ) and non - cancerous, non - cirrhotic ( normal ; n - 44 ) liver tissues from 44 HCC patients with diferent tumor stages. Results The mean mRNA levels of the four DNMT types tested (1,2, 3A, 3B) were higher in cancerous and ciirhotic tissues than in adjacent normal tissues. The DNMT1 elevated expression reached statistical significance ( vs. adjacent normal tissues, ? <0. 01 for cancerous tissue and ? -0. 02 for ciihotic tissue), unlike the DNMT elevated expression which did not reach statistical significance (vs. addacent normal tissues, ? - 0. 12 for cancerous and ? - 0. 35 for cirrhotic tissues) . Both DNMT3 isoforms, A and B, were significantly higher than the levels detected in the addacent healthy tissues ( DNMT3A : ? < 0. 01 for cancerous and ? - 0. 01 for ciihotic tissue ; DNMT3B : ? -0. 03 for cancerous and ? <0. 05 for ciirhotic tissue). Stratification analysis of the four DNMTs mRNA expression levels according to patient sex, tumor staging, and tumor diferentiation revealed no correlations ( DNMT1 : ?-0.23; DNMT: ?-0.45; DNMTA: ?-0.32; DN-MTB: ? -0.36). However, trends were found for increased DNMTs mRNA expression levels and male sex, poor tumor diferentiation, and high tumor stage. Conclusion The mRNA expressions of DNMT1, DNMT3A, and DNMTB are higher in cancerous and ciihotic tissues from HCC patients than in their addacent non - cancerous, non - ciirhotic liver tissues. Expression of DNMTs may be associated with pathogenesis of HCC or HCC associated with ciirhosis. [ABSTRACT FROM AUTHOR]

Objectives: Although germline mutations of mismatch repair (MMR) genes (Lynch syndrome) are not typically associated with cholangiocarcinomas, the US Food and Drug Administration recently approved the use of pembrolizumab in patients with advanced solid tumors at all sites that show MMR deficiency or associated high microsatellite instability.Methods: We analyzed 96 cases of intra- and extrahepatic cholangiocarcinomas for morphology using H&E and for MMR status using immunohistochemical staining. We submitted any results with MMR loss for microsatellite instability testing.Results: We found that 6% of samples showed MMR deficiency. The best predictive factor was a nontypical infiltrating pattern of invasion (P < .0001). No patients with MMR deficiency had a history of a cancer typically associated with Lynch syndrome.Conclusions: Solid, mucinous, or signet-ring appearance of a cholangiocarcinoma should prompt MMR testing for immunotherapy options but should not necessarily raise concern about Lynch syndrome. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study is to examine the association between Intraoperative cell salvage (ICS), allogeneic blood transfusion (ABT) and coagulation function in obstetrics.Methods: A total of 486 pregnant women undergoing cesarean delivery, of whom 157 were enrolled in this retrospective study. Patients were divided into ICS group (n = 101, ICS used during operation) and control group (n = 56, ICS not used during operation). Clinical data, including plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and thrombin time (TT) levels, were collected from all patients preoperatively (within 12-24 h) and postoperatively (within 6-12 h) and analyzed by t test, two-way repeated-measures ANOVA and Spearman's correlation.Results: The use of ICS is associated with lower requirement rate for ABT (P < .001), while the blood loss was similar between the two groups (P = .990). Mean volume of ICS transfusion was 432.65 mL. Compared to preoperative values, the postoperative PT and APTT levels were significantly increased, while Fib was decreased in the two groups (all P < .01). No significant difference in coagulation function was observed between groups in preoperative and postoperative phase (P > .05). Furthermore, PT, APTT and TT after surgery were not correlated with the transfused volume of salvaged blood (P > .05) while the levels of Fib were negatively correlated with the volume (P < .01). In addition, there were no transfusion reactions in both two groups.Conclusions: Intraoperative cell salvage is correlated with reduced allogeneic blood requirements but did not impair blood coagulation significantly in patients undergoing cesarean delivery. [ABSTRACT FROM AUTHOR]

The AAA + ATPase R2TP complex facilitates assembly of a number of ribonucleoprotein particles (RNPs). Although the architecture of R2TP is known, its molecular basis for acting upon multiple RNPs remains unknown. In yeast, the core subunit of the box C/D small nucleolar RNPs, Nop58p, is the target for R2TP function. In the recently observed U3 box C/D snoRNP as part of the 90 S small subunit processome, the unfolded regions of Nop58p are observed to form extensive interactions, suggesting a possible role of R2TP in stabilizing the unfolded region of Nop58p prior to its assembly. Here, we analyze the interaction between R2TP and a Maltose Binding Protein (MBP)-fused Nop58p by biophysical and yeast genetics methods. We present evidence that R2TP interacts largely with the unfolded termini of Nop58p. Our results suggest a general mechanism for R2TP to impart specificity by recognizing unfolded regions in its clients. [ABSTRACT FROM AUTHOR]

[Display omitted] Since December 2019, coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a great challenge to the world's public health system. Nosocomial infections have occurred frequently in medical institutions worldwide during this pandemic. Thus, there is an urgent need to construct an effective surveillance and early warning system for pathogen exposure and infection to prevent nosocomial infections in negative-pressure wards. In this study, visualization and construction of an infection risk assessment of SARS-CoV-2 through aerosol and surface transmission in a negative-pressure ward were performed to describe the distribution regularity and infection risk of SARS-CoV-2, the critical factors of infection, the air changes per hour (ACHs) and the viral variation that affect infection risk. The SARS-CoV-2 distribution data from this model were verified by field test data from the Wuhan Huoshenshan Hospital ICU ward. ACHs have a great impact on the infection risk from airborne exposure, while they have little effect on the infection risk from surface exposure. The variant strains demonstrated significantly increased viral loads and risks of infection. The level of protection for nurses and surgeons should be increased when treating patients infected with variant strains, and new disinfection methods, electrostatic adsorption and other air purification methods should be used in all human environments. The results of this study may provide a theoretical reference and technical support for reducing the occurrence of nosocomial infections. [ABSTRACT FROM AUTHOR]

Abstract: Background: Although genetic variants may play a key role in development of treatment-resistant depression (TRD), relevant research is scarce. Methods: To examine whether the polymorphisms of BDNF (rs6265) and NTRK2 (rs1387923, rs2769605 and rs1565445) genes confer risk for TRD in major depressive disorder (MDD), a total of 948 MDD patients were recruited in a 12-week, multicenter, prospective longitudinal study. Results: Our study showed a significant allelic association between rs1565445 and TRD with an excess of the T allele in the TRD group, compared to non-TRD group (OR = 1.43, 95%CI: 1.16–1.76, p = 0.0008); while patients with genotype C/C and T/C in rs1565445 were less likely to develop TRD than those carrying T/T (OR = 0.52, 95%CI: 0.33–0.82; OR = 0.72, 95%CI: 0.54–0.97, respectively; p = 0.005). Haplotype T–T (rs1565445 and rs1387923) had 1.41-fold increased risk of TRD (p = 0.0014). Furthermore, significant four-locus (rs1387923-rs1565445-rs2769605-rs6265) gene–gene interactions were detected by the Multifactor-dimensionality reduction (MDR) method. Discussion: These results suggest that the interactions of BDNF (rs6265) with NTRK2 (rs1387923, rs2769605 and rs1565445) gene polymorphisms likely play an essential role in the development of TRD in Han Chinese MDD patients. [Copyright &y& Elsevier]

Strong evidence indicates that central serotoninergic system dysfunction is associated with suicidal behavior. The relationship between the serotonin transporter protein (5-HTT) gene of psychotic patients in Han Chinese with suicidal behavior was studied since the 5-HTT plays an important role in serotoninergic transmission. Two hundred and seventy-two psychotic inpatients with suicidal behavior (suicide group) and 275 psychotic inpatients without suicidal behavior (patient control group) were recruited from six mental health facilities in Shanghai, China. Another 628 healthy adults (healthy control group) without suicidal behavior and mental disorder history were enrolled from Shanghai, China. All subjects were Han Chinese. The genotypes and the alleles of 5-HTT genes of the three groups were examined by PCR amplification. Neither the intron 2 variable number tandem repeat (VNTR) polymorphism and 5-HTTLPR (5-HTT gene-linked polymorphic region), nor the haplotype frequencies of this gene have significant differences between the suicide group and the two control groups. However, there was a significant difference in 5-HTTLPR polymorphism between inpatients with a first episode of suicidal behavior and those with recurrent suicidal behavior. Except for the possible heterogeneity between inpatients with a first episode of suicidal behavior and those with more than one, the 5-HTT gene was unlikely to be associated with suicidal behavior of psychotic patient in Han Chinese. [Copyright &y& Elsevier]

Background: Breast cancer is the leading cause of oncological mortality among women. Efficient detection of cancer cells in an early stage and potent therapeutic agents targeting metastatic tumors are highly needed to improve survival rates. Emerging evidence indicates that lncRNAs (long noncoding RNAs) are critical regulators of fundamental cellular processes in a variety of tumors including breast cancer. The functional details of these regulatory elements, however, remain largely unexplored. Methods: In this study, lncRNA ROR (linc-ROR) was examined by real-time PCR in different breast cancer cell lines and breast tumor tissues/non-tumor tissues were collected from both breast cancer patients and healthy controls. Linc-ROR was knockdown in breast cancer cell lines and the effects on cell proliferation, migration and invasion were tested both in vitro and in vivo tumor model. Effects of linc-ROR knockdown on TGF-β signaling pathway were investigated by Western blot. Results: Our studies have suggested that linc-ROR, a critical factor for embryonic stem cell maintenance, probably acts as an oncogenic factor in breast cancer cells, causing poor prognostic outcomes. Overexpression of linc-ROR seems to be responsible for promoting proliferation and invasion of cancer cells as well as tumor growth in nude mice. The regulatory action of linc-ROR can affect the activity of the TGF-β signaling pathway, which has been proven critical for mammary development and breast cancer. Conclusions: The results have highlighted the potential importance of linc-ROR in the progression of advanced breast cancer, and thus will stimulate efforts in the development of novel diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]