The association of cardiometabolic multimorbidity and fear of falling among older adults: Data from the national health and aging trends study.

OBJECTIVES: Cardiometabolic diseases (CMDs) have been individually associated with fall-related outcomes, but their combined effect on fear of falling (FOF) has not been investigated. This study aims to examine the association between cardiometabolic multimorbidity and FOF in older adults. METHODS: Data from the National Health and Aging Trends Study, 4,295 community-dwelling older adults ≥ 65 years were analyzed in this longitudinal study. CMDs were assessed at baseline, including heart disease, diabetes, stroke, and hypertension. FOF was evaluated by asking participants if they worried about falling in the past month. Data were analyzed using multi-adjusted logistic regression. RESULTS: Cardiometabolic multimorbidity was associated with a higher risk of FOF. The combination of heart disease and diabetes showed the highest risk of FOF (OR = 3.47, 95 % CI: 1.63-7.40). CONCLUSIONS: These findings underscore the need for targeted interventions to mitigate the combined impact of cardiometabolic multimorbidity on FOF in older adults.

Synergy of lytic phage pB23 and meropenem combination against carbapenem-resistant Acinetobacter baumannii.

Phage-antibiotic combination treatment is a novel noteworthy drug delivery method in anti-infection. In the current study, we have isolated a new phage, pB23, against carbapenem-resistant Acinetobacter baumannii 2023. Synergistic antibacterial effect between phage pB23 and meropenem combination could be more stable, using moderate doses of phage (multiplicity of infection ranging from 0.1 to 1,000) based on results of in vitro antibacterial activity. Phage pB23 and meropenem combination could effectively clear mature biofilms and prevent biofilm formation of carbapenem-resistant Acinetobacter baumannii in vitro. Phage pB23 and meropenem combination also has good synergistic antibacterial effects against carbapenem-resistant Acinetobacter baumannii in different growth phases under static culture conditions. The pig skin explant model shows that phage pB23 and meropenem combination has a synergistic effect to remove bacteria from wounds ex vivo. Phage pB23 and meropenem combination also exhibited a synergistic antibacterial effect in vivo using a zebrafish infection mode. The potential promotion of phage proliferation by meropenem and the sensitivity recovery of phage-resistant bacteria to meropenem might elucidate the mechanism of the synergistic antimicrobial activity. In summary, our study illustrates that phage pB23 and meropenem combination could produce synergistic antibacterial effects against carbapenem-resistant Acinetobacter baumannii under static growth conditions. This study also demonstrates that phage-antibiotic combination will become an effective strategy to enhance antibacterial activity of individual drug and provide a new idea of the drug development for the treatment of infections due to carbapenem-resistant Acinetobacter baumannii and other multidrug-resistant bacteria.

Exploring the role of mindfulness on obligatory exercise among young athletes: mediating roles of obsessive passion and cognitive state anxiety.

Introduction: In the current trend toward youthfulness and age reduction in competitive sports, the issue of obligatory exercise among young athletes is becoming more severe. This not only affects their physical and mental health but also hampers their future prospects in the sports world. While delving into the impact of mindfulness on the issue of obligatory exercise among young athletes, it reveals the mediating role of obsessive passion and cognitive state anxiety. Methods: This study is a cross-sectional research that employs convenience and snowball sampling methods. We selected 403 young athletes from several universities and high-level sports teams in the central-southern region of China as valid samples and used AMOS v.23 to construct a structural equation model to validate the hypotheses. Results: The research findings indicate a significant positive correlation between obsessive passion, cognitive state anxiety, and obligatory exercise. Furthermore, obsessive passion and cognitive state anxiety mediate the relationship between mindfulness and obligatory exercise. This implies that young athletes can better regulate their emotional state during training, manage training loads sensibly, and avoid issues with obligatory exercise through mindfulness training. Discussion: In conclusion, to enhance the cognitive levels of young athletes and reduce their obligatory exercise behaviors, national sports authorities and coaching teams should develop reasonable mindfulness training programs for athletes and encourage their participation in mindfulness training.

Integrating rapid pathogen identification and antimicrobial susceptibility testing through multiplex TaqMan qPCR assay.

Timely bacterial identification (ID) and antimicrobial susceptibility testing (AST) are of significance for therapy of bacteria-infected patients. In the present study, we developed a multiplex TaqMan qPCR assay for rapid and accurate ID and AST of three common hospital acquired pneumonia species, namely Acinetobacter baumannii, Klebsiella pneumoniae and Staphylococcus aureus. In this assay, DNA extraction and bacterial co-incubation with antibiotics are accomplished based on a common PCR instrument. ID of three bacteria is based on specific conserved DNA sequence fragment (gltA for A. baumannii, phoE for K. pneumoniae and nuc for S. aureus) detection through multiplex TaqMan qPCR assay within 80 min. AST of three bacteria could be acquired within 200 min based on genomic DNA fold change detection after 2 h of antibiotic exposure. Testing of 23 bronchoalveolar lavage fluid samples spiked by different A. baumannii isolates, 20 bronchoalveolar lavage fluid samples spiked by different K. pneumoniae isolates, and 14 bronchoalveolar lavage fluid samples spiked by different S. aureus isolates showed that the multiplex TaqMan qPCR assay had 100% (95% CI: 85.69-100), 100% (95% CI: 83.89-100) and 100% (95% CI:78.47-100) identification agreement with the initial spiked bacteria. Subsequent AST results compared with the standard broth microdilution method showed an overall agreement of 91.30% (95% CI: 73.20 to 97.58) for A. baumannii, 90% (95% CI: 69.90 to 97.21) for K. pneumoniae and 92.86% (95% CI: 68.53 to 98.73) for S. aureus based on the current multiplex TaqMan assay. Due to the high rapidity, good agreement, simplicity, and high throughput, this multiplex TaqMan assay could be helpful for ID and broad-spectrum AST in A. baumannii, K. pneumoniae and S. aureus, as well as potentially applicable for other clinical bacteria by changing the primers and probes.

The impact of liver fibrosis on the progression of hepatocellular carcinoma via a hypoxia-immune-integrated prognostic model.

The impact of liver fibrosis on the deterioration of hepatocellular carcinoma (HCC) remains controversial. We hope to explore this issue through establishing a fibrosis-hypoxia-glycolysis-immune related prognostic model. Liver fibrosis-related genes from Molecular Signatures Database were used to evaluate the degree of fibrosis in HCC patients from the TCGA database. The patients were divided into two groups using the fibrosis-related expression matrix based on the algorithm uniform manifold approximation and projection (UMAP) and evaluated for fibrosis by UMAP cluster and gene enrichment analysis. Prognostic model was constructed by differential analysis, LASSO, and multivariate regression analysis. Immune-infiltration analysis was performed by CIBERSORT. Quantitative PCR and immunohistochemistry were performed to measure the gene expression levels in HCC patients from our hospital. In 365 HCC patients from the TCGA database, 111 HCC patients with high fibrosis score have a worse prognosis than those with low fibrosis based on 129 genes related to liver fibrosis, which may be caused by the interaction between fibrosis, angiogenesis, hypoxia, glycolysis, inflammatory response, and high immune infiltration. We constructed a Fibrosis-Hypoxia-Glycolysis-Immune Prognostic Model (FHGISig), which could significantly predict disease progression in HCC patients. Furthermore, we revealed a close correlation between FHGISig and immune cell infiltration level as well as immune checkpoints. Finally, PCR results found TFF3 mRNA was significantly lower in cirrhotic HCC patients compared with non-cirrhotic ones. Liver fibrosis is a poor-prognostic factor for HCC, and our FHGISig could significantly predict disease progression, which could also be a potential predictive marker for immunotherapy in HCC patients.

Synergistic Antibacterial Effect of Phage pB3074 in Combination with Antibiotics Targeting Cell Wall against Multidrug-Resistant Acinetobacter baumannii In Vitro and Ex Vivo.

Synergistic effects of phages in combination with antibiotics have received increasing attention. In this present study, we isolated a new phage pB3074 against clinically isolated multidrug-resistant Acinetobacter baumannii. Phage pB3074 combined with cell wall-targeting antibiotics could produce synergistic antibacterial effect in vitro bactericidal activities. Further research indicates that the bacteriophage dose is critical to synergistic antimicrobial effect of phage and antibiotic combination. Cefotaxime and meropenem were selected as the representative cell wall-targeting antibiotics for further synergistic antibacterial study. Results illustrated that phage pB3074 and cefotaxime or meropenem combination was very effective for the removal of mature biofilm and inhibition of biofilm formation. In a pig skin explant model, results also showed that phage pB3074 and cefotaxime or meropenem combination was very effective for the treatment of wound infection ex vivo. Subsequent studies showed that some extent recovery of drug sensitivity to cell wall-targeting antibiotics might be vital mechanism of synergistic antibacterial effect between bacteriophage pB3074 and these antibiotics. The existence of antibiotics could promote phage adsorption and proliferation, which might also be potential mechanism for synergistic antibacterial activities and have been observed in cefotaxime and meropenem application. In summary, results in the current study demonstrated that phage pB3074 has the potential to be developed as an antibacterial agent and combined application of phages and antibiotics might be a new choice for the treatment of current multidrug-resistant bacterial infections. IMPORTANCE Combined application of phages and antibiotics cannot only effectively inhibit the appearance of phage-resistant bacteria, but also reduce the effective use concentration of antibiotics, and even make some bacteria regain sensitivity to some resistant antibiotics. Therefore, phage-antibiotic combination (PAC) could improve the antibacterial activity of individual drug, providing a new choice for clinical treatment of multidrug-resistant bacterial infections.

The advanced lung cancer inflammation index predicts chemotherapy response and infection risk in multiple myeloma patients receiving induction chemotherapy.

Objective: This study aims to determine the clinical significance of the advanced lung cancer inflammation index (ALI) in predicting prognosis, chemotherapy response, and infection risk in newly diagnosed multiple myeloma (MM) patients receiving induction therapy. Methods: A retrospective analysis of the clinical characteristics and laboratory data of 111 newly diagnosed MM patients from the Haematology Department of the Third Xiangya Hospital of Central South University from January 2014 to March 2020 was performed. We first determined the relationship between ALI and overall survival (OS), as well as clinical and laboratory parameters. Second, predictive factors for chemotherapy response were analysed by univariate and multivariate regression analyses. Third, univariate regression analysis of risk factors was performed using infection as the evaluable outcome. Results: Of the 111 evaluable patients, the low ALI group (<32.7) exhibited significantly poorer survival than the high ALI group (51 months versus 77 months). Multivariable analysis showed that advanced age, chemotherapy response and serum calcium level were independent prognostic factors for OS. Better chemotherapy efficacy in the high ALI group (89.3%) than in the low ALI group (42.2%) (p < 0.001) was noted. Multivariate analysis suggested that only ALI [HR: 0.110, 95% CI (0.035-0.350), p = 0.000] is an independent predictive factor in evaluating the efficiency of induction chemotherapy. Forty patients (36.04%) presented with infection after induction chemotherapy. Univariate analysis suggested that low ALI and abnormal renal function increase risk of infection in newly diagnosed MM patients. Conclusion: Our study confirmed that ALI is not only a prognostic biomarker for newly diagnosed patients, but also predicts chemotherapy efficacy in newly diagnosed MM patients receiving induction therapy.

Identification and validation of an immunological microenvironment signature and prediction model for epstein-barr virus positive lymphoma: Implications for immunotherapy.

Background: Epstein-Barr virus (EBV) is considered a carcinogenic virus, which is associated with high risk for poor prognosis in lymphoma patients, and there has been especially no satisfying and effective treatment for EBV+ lymphoma. We aimed to identify the immunological microenvironment molecular signatures which lead to the poor prognosis of EBV+ lymphoma patients. Methods: Differential genes were screened with microarray data from the GEO database (GSE38885, GSE34143 and GSE13996). The data of lymphoid neoplasm diffuse large B-cell lymphoma (DLBC) from the TCGA database and GSE4475 were used to identify the prognostic genes. The data of GSE38885, GSE34143, GSE132929, GSE58445 and GSE13996 were used to eluate the immune cell infiltration. Formalin-fixed, paraffin-embedded tissue was collected for Real Time Quantitative PCR from 30 clinical samples, including 15 EBV+ and 15 EBV- lymphoma patients. Results: Four differential genes between EBV+ and EBV- lymphoma patients were screened out with the significance of the survival and prognosis of lymphoma, including CHIT1, SIGLEC15, PLA2G2D and TMEM163. Using CIBERSORT to evaluate immune cell infiltration, we found the infiltration level of macrophages was significantly different between EBV+ and EBV- groups and was closely related to different genes. Preliminary clinical specimen verification identified that the expression levels of CHIT1 and TMEM163 were different between EBV+ and EBV- groups. Conclusions: Our data suggest that differences in expression levels of CHIT1 and TMEM163 and macrophage infiltration levels may be important drivers of poor prognosis of EBV+ lymphoma patients. These hub genes may provide new insights into the prognosis and therapeutic target for EBV+ lymphoma.

Clinical Diagnostic and Prognostic Potential of NDRG1 and NDRG2 in Hepatocellular Carcinoma Patients.

Background: Primary liver cancer is still the most common lethal malignancy. The N-myc downstream-regulated gene family (NDRG1-4) is a group of multifunctional proteins associated with carcinogenesis. However, systematic evaluation of the diagnostic and prognostic values of NDRG1 or NDRG2 expression in liver cancer is poorly investigated. Method: The gene expression matrix of liver hepatocellular carcinoma (LIHC) was comprehensively analyzed by the "limma" and "Dseq2" R packages. The Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) were used to identify the biological functional differences. A single-sample GSEA (ssGSEA) was conducted to quantify the extent of immune cell infiltration. Finally, the clinical and prognostic information of LIHC patients was systematically investigated using Kaplan-Meier analysis and logistic and Cox regression analysis. Results: Compared with normal tissues, NDRG1 expression was higher, whereas NDRG2 expression was lower in tumor tissues (P <0.001). The area under the receiver operator characteristic curve (AUROC) of NDRG1 and NDRG2 for LIHC was 0.715 and 0.799, respectively. Kaplan-Meier analysis revealed that NDRG1 and NDRG2 were independent clinical prognostic biomarkers for the overall survival (OS, P = 0.001 and 2.9e-06), progression-free interval (PFI, P = 0.028 and 0.005) and disease-specific survival (DSS, P = 0.027 and P <0.001). The C-indexes and calibration plots of the nomogram suggest that NDRG1 and NDRG2 have an effective predictive performance for OS (C-index: 0.676), DSS (C-index: 0.741) and PFI (C-index: 0.630) of liver cancer patients. The mutation rate of NDRG1 in liver cancer reached up to 14%, and DNA methylation levels of NDRG1 and NDRG2 promoters correlated significantly with clinical prognosis. Conclusions: The mRNA expression and DNA methylation of NDRG superfamily members have the potential for LIHC diagnosis and prognosis via integrative analysis from multiple cohorts.

Evaluation of a direct phage DNA detection-based Taqman qPCR methodology for quantification of phage and its application in rapid ultrasensitive identification of Acinetobacter baumannii.

BACKGROUND: Rapid phage enumeration/quantitation and viable bacteria determination is critical for phage application and treatment of infectious patients caused by the pathogenic bacteria. METHODS: In the current study, a direct phage DNA detection-based Taqman qPCR methodology for quantification of phage P53 and rapid ultrasensitive identification of Acinetobacter baumannii (A. baumannii) was evaluated. RESULTS: The assay was capable of quantifying P53 phage DNA without DNA extraction and the detection limit of the assay was 550 PFU/mL. The agreement bias between the quantitative results of three different phage concentrations in this assay and double agar overlay plaque assay were under 3.38%. Through the built detection system, down to 1 log CFU/mL of viable A. baumannii can be detected within 4 h in A. baumannii spiked swab and bronchoalveolar lavage fluid samples. Compared with the Taqman qPCR that targets the conserved sequence of A. baumannii, the sensitivity of the assay built in this study could increase four orders of magnitude. CONCLUSIONS: The methodology offers a valid alternative for enumeration of freshly prepared phage solution and diagnosis of bacterial infection caused by A. baumannii or other bacterial infection in complicated samples through switching to phages against other bacteria. Furthermore, the assay could offer drug adjustment strategy timely owing to the detection of bacteria vitality.

Bactericidal Synergism between Phage YC#06 and Antibiotics: a Combination Strategy to Target Multidrug-Resistant Acinetobacter baumannii In Vitro and In Vivo.

Phage-antibiotic combination (PAC) therapy is a potential new alternative to treat infections caused by pathogenic bacteria, particularly those caused by antibiotic-resistant bacteria. In the present study, phage YC#06 against highly multidrug-resistant Acinetobacter baumannii 4015 was isolated, identified, and characterized. Compared with antibiotics alone, the time-kill experiments in vitro showed that YC#06 and antibiotic mixtures that include the chloramphenicol, imipenem, and cefotaxime combination could produce phage-antibiotic synergy (PAS), which reduced the ultimate effective concentration of antibiotics. No phage-resistant bacteria have been isolated during the whole time-kill experiments in vitro. Of note, PAS was dose dependent, requiring a moderate phage dose to achieve maximum PAS effect. In addition, PAS could effectively inhibit biofilm formation and remove mature biofilms in vitro. Furthermore, PAS between the combination of YC#06 and antibiotic mixtures in vivo was validated using a zebrafish infection model. Overall, the results of this study demonstrate that PAC could be a viable strategy to treat infection caused by high-level multidrug-resistant Acinetobacter baumannii or other drug-resistant bacteria through switching to other types of phage and antibiotic mixtures. IMPORTANCE The treatment of multidrug-resistant bacterial infection is an urgent clinical problem. The combination of bacteriophages and antibiotics could produce synergistic bactericidal effects, which could reduce the emergence of antibiotic resistance and antibiotic consumption in antibiotic-sensitive bacteria, restore efficacy to antibiotics in antibiotic-resistant bacteria, and prevent the occurrence of phage-resistant bacteria. Phage-antibiotic combination (PAC) might be a potential new alternative for clinical treatment of multidrug-resistant bacterial infections.

Realization of Ultra-Scaled MoS2 Vertical Diodes via Double-Side Electrodes Lamination.

Schottky diode is the fundamental building blocks for modern electronics and optoelectronics. Reducing the semiconductor layer thickness could shrink the vertical size of a Schottky diode, improving its speed and integration density. Here, we demonstrate a new approach to fabricate a Schottky diode with ultrashort physical length approaching atomic limit. By mechanically laminating prefabricated metal electrodes on both-sides of two-dimensional MoS2, the intrinsic metal-semiconductor interfaces can be well retained. As a result, we demonstrate the thinnest Schottky diode with a length of 2.6 nm and decent rectification behavior. Furthermore, with a diode length smaller than the semiconductor depletion length, the carrier transport mechanisms are investigated and explained by thickness-dependent and temperature-dependent electrical measurements. Our study not only pushes the scaling limit of a Schottky diode but also provides a general double-sided electrodes integration approach for other ultrathin vertical devices.

Colchicine prevents ventricular arrhythmias vulnerability in diet-induced obesity rats.

AIMS: This study aimed to assess the role of colchicine in ventricular arrhythmias (VAs) induced by high fat diet (HFD)-fed rats. METHODS AND RESULTS: Male rats were divided into four groups: CTL, normal diet plus saline; CTC, normal diet plus colchicine; HFD, HFD plus saline; HFC: HFD plus colchicine. Metabolic parameters, ECG parameters, ventricular electrophysiological parameters, ventricular histology, Western blot and RT-qPCR were measured. Compared with the HFD group, colchicine treatment significantly improved metabolic parameters, reduced ventricular fibrosis, increased the expression of Cav1.2, Kv4.2, Nav1.5, and Cx43, reduced CaMKII, p-CaMKII, p-RyR2 (S2808), and p-RyR2 (S2814) expression in LV. Furthermore, colchicine inhibited the inflammatory responses, prolonged ventricular effective refractory period (ERP), reduced corrected QT interval (QTc) and Tpeak-Tend interval, so as to reduce the susceptibility to VAs in obesity rats. CONCLUSIONS: Colchicine could mitigate ventricular fibrosis, ventricular electrical remodeling, as well as the expression of ion channels, and inhibit obesity-induced inflammatory responses, which provides a new idea for colchicine to prevent VAs in obese individuals.

Strain-Plasmonic Coupled Broadband Photodetector Based on Monolayer MoS2.

2D Semiconductors are promising in the development of next-generation photodetectors. However, the performances of 2D photodetectors are largely limited by their poor light absorption (due to ultrathin thickness) and small detection range (due to large bandgap). To overcome the limitations, a strain-plasmonic coupled 2D photodetector is designed by mechanically integrating monolayer MoS2 on top of prefabricated Au nanoparticle arrays. Within this structure, the large biaxial tensile strain can greatly reduce the MoS2 bandgap for broadband photodetection, and at the same time, the nanoparticles can significantly enhance the light intensity around MoS2 with much improved light absorption. Together, the strain-plasmonic coupled photodetector can broaden the detection range by 60 nm and increase the signal-to-noise ratio by 650%, representing the ultimate optimization of detection range and detection intensity at the same time. The strain-plasmonic coupling effect is further systematically characterized and confirmed by using Raman and photoluminescence spectrophotometry. Furthermore, the existence of built-in potential and photo-switching behavior is demonstrated between the strained and unstrained region, constructing a self-powered homojunction photodetector. This approach provides a simple strategy to couple strain effect and plasmonic effect, which can provide a new strategy for designing high-performance and broadband 2D optoelectronic devices.

Dry Exfoliation of Large-Area 2D Monolayer and Heterostructure Arrays.

Two-dimensional (2D) semiconductors have attracted considerable attention in recent years. However, to date, there is still no effective approach to produce large-scale monolayers while retaining their intrinsic properties. Here, we report a simple mechanical exfoliation method to produce large-scale and high-quality 2D semiconductors, by designing an atomically flat Au-mesh film as the peeling tape. Using our prefabricated mesh tape, the limited contact region (between the 2D crystal and Au) could provide enough adhesion to mechanically exfoliate uniform 2D monolayers, and the noncontact region (between the mesh holes and monolayers) ensures weak interaction to mechanically release the 2D monolayers on desired substrates. Together, we demonstrate a scalable method to dry exfoliate various 2D monolayer arrays onto different substrates without involving any solutions or contaminations, representing the optimization between material yield, scalability, and quality. Furthermore, detailed optical and electrical characterizations are conducted to confirm their intrinsic quality. With the ability to mechanically exfoliate various 2D arrays and further restacking them, we have demonstrated large-scale van der Waals heterostructure arrays through layer-to-layer assembling. Our study offers a simple and scalable method for dry exfoliating 2D monolayer and heterostructure arrays with intrinsic material quality, which could be crucial to accelerate fundamental investigations as well as practical applications of proof-of-concepts devices.

Dynamic changes and prevalence of SARS-CoV-2 IgG/IgM antibodies: Analysis of multiple factors.

OBJECTIVE: To investigate the dynamic characteristics of serological antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is of much current significance. METHODS: The dynamic changes and prevalence of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against SARS-CoV-2 were assessed from the time of symptom onset up to 210 days. Antibodies were detected using a chemiluminescence immunoassay. RESULTS: The average titers and IgG/IgM positivity rates reached a peak within 30 days of symptom onset and then began to decline continuously. Between 180 and 210 days following symptom onset, the titers of IgG and IgM were 43.1 ± 27.0 AU/mL and 4.4 ± 5.2 AU/mL, respectively, while the respective positivity rates were 84.3% and 12.0%. Further statistical analyses revealed that the dynamic changes and prevalence of the SARS-CoV-2 IgG/IgM antibodies were related to age and disease severity, but not to sex. The dynamic changes and the prevalence were similar for both the IgM and the IgG antibodies. Even so, there was a more rapid rate of decline for the IgM antibodies. It was found that an IgG level of 16.33 ± 3.15 AU/mL may represent a threshold value that should act as an alert, as it may indicate that the IgG level will become undetectable within the next 30-60 days. CONCLUSION: The results provide important information concerning COVID-19 and may be of relevance for diagnosis, treatment, and vaccine development.

Reconfigurable electronics by disassembling and reassembling van der Waals heterostructures.

Van der Waals heterostructures (vdWHs) have attracted tremendous interest owing to the ability to assemble diverse building blocks without the constraints of lattice matching and processing compatibility. However, once assembled, the fabricated vdWHs can hardly be separated into individual building blocks for further manipulation, mainly due to technical difficulties in the disassembling process. Here, we show a method to disassemble the as-fabricated vdWHs into individual building blocks, which can be further reassembled into new vdWHs with different device functionalities. With this technique, we demonstrate reconfigurable transistors from n-type to p-type and back-gate to dual-gate structures through re-stacking. Furthermore, reconfigurable device behaviors from floating gate memory to Schottky diode and reconfigurable anisotropic Raman behaviors have been obtained through layer re-sequencing and re-twisting, respectively. Our results could lead to a reverse engineering concept of disassembled vdWHs electronics in parallel with state-of-the-art vdWHs electronics, offering a general method for multi-functional pluggable electronics and optoelectronics with limited material building blocks.

Value of swab types and collection time on SARS-COV-2 detection using RT-PCR assay.

OBJECTIVE: Low viral load from patients infected with SARS-CoV-2 during infection late stage easily lead to false negative nucleic acid testing results, thus having great challenges to the prevention and control of the current pandemic. In present study, we mainly aimed to evaluate specimen types and specimen collection timepoint on the positive detection of 2019 novel coronavirus from patients at infection late stage based on RT-PCR testing. METHODS: Paired nasopharyngeal swabs, nasal swabs, oropharyngeal swabs and anal swabs were collected from patients infected with SARS-CoV-2 during infection late stage before washing in the morning and afternoon on the same day. Then virus RNA was extracted and tested for 2019-nCoV identification by RT-PCR within 24 h. RESULTS: Viral load was low at late infection stage. Specimens collected before washing in the morning would increase the detection ratio of 2019-nCoV. Detection ratio of nasopharyngeal swab [65 (95 % CI: 49.51-77.87) vs 42.5(95 % CI: 28.51-57.8)] or nasal swab [57.5 (95 % CI: 42.2-71.49) vs 35 (95 % CI: 22.13-50.49)] is higher not only than oropharyngeal swab[22.5 (95 % CI: 12.32-37.5) vs 7.5 (95 % CI: 2.58-19.86)], but also anal swab[2.5 (95 % CI: 0.44-12.88) vs 5 (95 % CI: 1.38-16.5)]. CONCLUSIONS: In summary, our research discovers that nasopharyngeal or nasal swab collected before washing in the morning might be more suitable for detecting of large-scale specimens from patients infected with low SARS-CoV-2 load during infection late stage. Those results could facilitate other laboratories in collecting appropriate specimens for improving detection of SARS-CoV-2 from patients during infection late stage as well as initially screening.

Up-regulation of FAT4 enhances the chemosensitivity of colorectal cancer cells treated by 5-FU.

BACKGROUND: Colorectal cancer (CRC) has high mortality, and 5-fluorouracil (5-FU) is a common clinical chemotherapeutic drug. The current study aimed to investigate the role of FAT4 in chemosensitivity of CRC cells treated by 5-FU. METHODS: The immunohistochemistry and qRT-PCR was conducted to measure the FAT4 expression in CRC and adjacent tissues. The FAT4 expression was determined by qRT-PCR and Western blot, comparison of FAT expression between normal and several CRC cell lines was then made, so as to identify cell lines with the highest (LS174T) and the lowest (SW-620) expressions of FAT4. The effects of 5-FU stimulation at various doses on cell viability were determined by CCK-8, and the level of FAT4 was also measured. After FAT4 knockdown in LS174T or FAT4 overexpression in SW-620 with or without pretreatment of 5-FU (30 µg/mL), cell growth, colony formation, cell migration and invasion, angiogenesis were determined by flow cytometry, wound-healing, transwell assay and tube formation assay, respectively. The expression levels of epithelial-mesenchymal transition (EMT) markers were detected by qRT-PCR and Western blot. RESULTS: FAT4 was down-regulated in CRC tissues and cells, cell viability of CRC cells was decreased. The level of FAT4 was increased with the increase of 5-FU concentrations. Moreover, 5-FU stimulation increased FAT4 expression, and reduced cell proliferation, migration, invasion, angiogenesis and cell EMT process, furthermore, such effects of 5-FU stimulation could be enhanced by FAT4 overexpression but reversed by FAT4 knockdown. CONCLUSIONS: Upregulation of FAT4 could increase the sensitivity of CRC cells to 5-FU.