Sensitivity-improved SERS detection of SARS-CoV-2 spike protein by Au NPs/COFs integrated with catalytic-hairpin-assembly amplification technology.

BACKGROUND: The COVID-19 pandemic, caused by the novel coronavirus, has had a profound impact on global health and economies worldwide. This unprecedented crisis has affected individuals, communities, and nations in diverse manners. Developing simple and accurate diagnostic methods is an imperative task for frequent testing to mitigate the spread of the virus. Among these methods, SARS-CoV-2 antigen tests in clinical specimens have emerged as a promising diagnostic method for COVID-19 due to their sensitive and accurate detection of spike (S) protein, which plays a crucial role in viral infection initiation. RESULTS: In this work, a dual-signal amplification surface enhanced Raman scattering (SERS)-based S protein biosensor was constructed based on Au NPs/COFs and enzyme-free catalytic hairpin assembly (CHA) amplification method. The approach relies on a released free DNA sequence (T), which is generated from the competition reaction between Aptamer/T and Aptamer/S protein, to trigger a CHA reaction. Due to the high binding affinity and selectivity between the S protein and its aptamer, CHA process was triggered with the maximum SERS tags (H2-conjugated Au@4-mercaptobenzonitrile@Ag) anchored onto Au NPs/COFs substrate surface. This SERS platform could detect the S protein at concentrations with high sensitivity (limit of detection = 3.0 × 10-16 g/mL), wide detection range (1 × 10-16 to 1 × 10-11 g/mL), acceptable reproducibility (relative standard deviation = 7.01 %) and excellent specificity. The biosensor was also employed to detect S protein in artificial human salivas. SIGNIFICANCE: Thus, this study not only developed a novel Au NPs/COFs substrate exhibiting strong SERS enhancement ability and high reproducibility, but also proposed a promising dual-signal amplification SERS-based diagnostic method for COVID-19, holding immense potential for the detection of a wide range of antigens and infectious diseases in future applications.

Transcription factor FoAce2 regulates virulence, vegetative growth, conidiation, and cell wall homeostasis in Fusarium oxysporum f. sp. cubense.

Fusarium wilt of banana, caused by the fungus Fusarium oxysporum f. sp. cubense (Foc), is a serious fungal disease that affects banana plants globally. To explore the virulence mechanisms of this pathogen, we created a null mutation of the transcription factor gene FoAce2 (encoding F. oxysporum angiotensin converting enzyme 2). Deletion of FoAce2 resulted in slower growth, decreased aerial mycelia and conidiation, and a significant decrease in fungal virulence against banana hosts relative to those of the wild-type (WT) fungus. Additionally, transmission electron microscopy showed that the cell wall was thicker in the FoAce2 deletion mutants. Consistent with this finding, the cell wall glucose level was decreased in the ΔFoAce2 mutants compared with that in the WT and complemented strain, ΔFoAce2-C1. Complementation with the WT FoAce2 gene fully reversed the mutant phenotypes. Analysis of the transcriptome of ΔFoAce2 and the WT strain showed alterations in the expression levels of many genes associated with virulence and growth. Thus, FoAce2 appears to be essential for Foc virulence, cell wall homeostasis, conidiation, and vegetative growth.

Association Between Gestational Weight Gain and Delayed Onset of Lactogenesis II: a Systematic Review and Meta-Analysis.

Background: Gestational weight gain (GWG) may be associated with delayed onset of lactogenesis II (DOL II), but it is still unclear and controversial. Object: The study aims to evaluate the relationship between GWG and DOL II. Methods: A comprehensive search was performed in 10 electronic databases from inception to May 21, 2023, for studies that reported outcomes in breastfeeding. Data were extracted by two independent reviewers. A meta-analysis was conducted to calculate the pooled estimates of association using random-effect models with Review Manager (RevMan) software version 5.4. The primary outcome was the rate of DOL II. Results: In this study, 248,515 women were included in 16 eligible articles. Women with excessive GWG have a higher risk of DOL II (odds ratio [OR] = 1.28; 95% confidence interval [CI]: 1.15-1.43). Specifically, prepregnancy overweight and obese women with GWG above recommendations (OR = 3.01, 95% CI: 1.38-6.57) and underweight women with excessive GWG before pregnancy have a higher risk of DOL II (OR = 3.32, 95% CI: 1.69-6.53). Nonetheless, there is no distinction between women with inadequate GWG and those with adequate GWG in DOL II(OR = 1.08, 95% CI: 0.88-1.33). In addition, the women whose GWG is above the recommendations also tend to stop exclusive breastfeeding 1 month postpartum (OR = 0.82, 95% CI: 0.80-0.85). Conclusion: Excessive GWG has a negative influence on the timing of the onset of lactogenesis and exclusive breastfeeding within 1 month postpartum.

The Effectiveness and Safety of Intrapartum or Postpartum Catheterization in the Prevention of Postpartum Urinary Retention: A Scoping Review.

INTRODUCTION AND HYPOTHESIS: Catheterization is a common treatment for postpartum urinary retention (PUR); however, its application before diagnosis of PUR remains unclear. The aim was to give an overview of the existing literature on the effectiveness and safety of intrapartum or postpartum catheterization in the prevention of PUR. METHODS: This scoping review followed a methodological framework. PubMed, the Cochrane Library, Embase, Web of Science, the China National Knowledge Infrastructure, WanFang, the China Science and Technology Journal Database, and the China Biomedical Literature Database were searched from the inception of each database to 21 May 2023. RESULTS: The search revealed 16 studies examining three different catheterization methodologies, including 12 intrapartum studies. Ten studies concluded that intrapartum or postpartum catheterization prevented PUR, two of which were only for overt or covert PUR. In 4 out of 13 experimental studies, no significant difference was found: one for intrapartum catheterization versus routine nursing, the other for intrapartum or postpartum intermittent versus indwelling catheterization. However, one found that postpartum disposable catheterization after ineffective targeted care reduced the incidence of PUR compared with indwelling catheterization. One out of the 3 case-control studies concluded that prenatal catheterization ≥2 times was a risk factor for PUR. CONCLUSIONS: Based on the findings in this scoping review, catheterization prior to the diagnosis of PUR appears to play a role in preventing PUR and is safe. Preliminary evidence is accumulating on the effectiveness of three types of catheterization methods in preventing PUR, but more comprehensive studies are needed to establish these findings.

Emerging innovations in portable chemical sensing devices: Advancements from microneedles to hydrogel, microfluidic, and paper-based platforms.

With the public heightened emphasis on mitigating the occurrence risks of health-related ailment and optimizing personal physical performance, portable chemical sensing devices emerged as an indispensable component of pervasive health monitoring. Chemical sensing enabled the immediate and on-site identification of biomarkers in biological fluids by integrating colorimetry, fluorescence, electrochemical, and other methods into portable sensor devices. These sensor devices incorporated microneedles, hydrogels, microfluidic modules, and papers, facilitating conformal human-device contact and providing several visual sensing options for disease prevention and healthcare management. This review systematically overviewed recent advancements in chemical sensors for marker detection, categorizing them based on monitoring device types. Furthermore, we also offered recommendations and opportunities for developing portable chemical sensing devices by summarizing sensor integration methods and tracking sites on the human body.

Chlamydia psittaci detected at a live poultry wholesale market in central China.

BACKGROUND: We investigated the presence of Chlamydia psittaci in poultry and the environment in live poultry wholesale markets in Changsha during 2021-2022 and conducted a phylogenetic analysis to understand its distribution in this market. METHODS: In total, 483 samples were analyzed using real-time polymerase chain reaction and 17 C. psittaci-positive samples using high-throughput sequencing, BLAST similarity, and phylogenetic analysis. RESULTS: Twenty-two out of 483 poultry and environmental samples were positive for C. psittaci (overall positivity rate: 4.55%) with no difference in positivity rates over 12 months. Chlamydia psittaci was detected at 11 sampling points (overall positivity rate: 27.5%), including chicken, duck, and pigeon/chicken/duck/goose shops, with pigeon shops having the highest positivity rate (46.67%). The highest positivity rates were found in sewage (12.5%), poultry fecal (7.43%), cage swab (6.59%), avian pharyngeal/cloacal swab (3.33%), and air (2.29%) samples. The ompA sequences were identified in two strains of C. psittaci, which were determined to bear genotype B using phylogenetic analysis. Thus, during monitoring, C. psittaci genotype B was detected in the poultry and environmental samples from the poultry wholesale market in Changsha. CONCLUSIONS: To address the potential zoonotic threat, C. psittaci monitoring programs in live poultry markets should be enhanced.

ITGAV Promotes the Progression of Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) refers to the malignancy of squamous cells in the head and neck region. Ranked as the seventh most common cancer worldwide, HNSCC has a very low survival rate, highlighting the importance of finding therapeutic targets for the disease. Integrins are cell surface receptors that play a crucial role in mediating cellular interactions with the extracellular matrix (ECM). Within this protein family, Integrin αV (ITGAV) has received attention for its important functional role in cancer progression. In this study, we first demonstrated the upregulation of ITGAV expression in HNSCC, with higher ITGAV expression levels correlating with significantly lower overall survival, based on TCGA (the Cancer Genome Atlas) and GEO datasets. Subsequent in vitro analyses revealed an overexpression of ITGAV in highly invasive HNSCC cell lines UM1 and UMSCC-5 in comparison to low invasive HNSCC cell lines UM2 and UMSCC-6. In addition, knockdown of ITGAV significantly inhibited the migration, invasion, viability, and colony formation of HNSCC cells. In addition, chromatin immunoprecipitation (ChIP) assays indicated that SOX11 bound to the promoter of ITGAV gene, and SOX11 knockdown resulted in decreased ITGAV expression in HNSCC cells. In conclusion, our studies suggest that ITGAV promotes the progression of HNSCC cells and may be regulated by SOX11 in HNSCC cells.

Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer.

The accumulation of unfolded or misfolded proteins within the endoplasmic reticulum (ER), due to genetic determinants and extrinsic environmental factors, leads to endoplasmic reticulum stress (ER stress). As ER stress ensues, the unfolded protein response (UPR), comprising three signaling pathways-inositol-requiring enzyme 1, protein kinase R-like endoplasmic reticulum kinase, and activating transcription factor 6 promptly activates to enhance the ER's protein-folding capacity and restore ER homeostasis. However, prolonged ER stress levels propels the UPR towards cellular demise and the subsequent inflammatory cascade, contributing to the development of human diseases, including cancer, neurodegenerative disorders, and diabetes. Notably, increased expression of all three UPR signaling pathways has been observed in these pathologies, and reduction in signaling molecule expression correlates with decreased proliferation of disease-associated target cells. Consequently, therapeutic strategies targeting ER stress-related interventions have attracted significant research interest. In this review, we elucidate the critical role of ER stress in cancer, metabolic, and neurodegenerative diseases, offering novel therapeutic approaches for these conditions.

Effects of first-line nucleot(s)ide analogues on lipid profiles in patients with chronic hepatitis B: a network meta-analysis.

INTRODUCTION: Recent studies have found that lipid levels in patients with chronic hepatitis B (CHB) may change during antiviral therapy. OBJECTIVE: To assess the effects of first-line nucleot(s)ide analogues (NAs) on lipid profiles in patients with CHB using network meta-analysis. METHODS: Seven electronic databases (PubMed, Embase, Cochrane Library, and four Chinese databases) were searched for cohort studies on the effect of NA on lipids in patients with CHB up to August 1, 2023. The changes of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were taken as outcomes. The mean difference (MD) of continuous variables and 95% confidence intervals (CI) were calculated using RevMan 5.4 and Stata 16.0 software, and network meta-analysis was based on a frequentist framework. RESULTS: A total of 4194 patients were included in the study, including patients with CHB treated with entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), as well as patients not receiving antiviral therapy [patients with inactive CHB who were not receiving antiviral therapy (referred as inactive CHB patients) and non-HBV-infected patients]. TDF reduced TC levels compared to the non-antiviral group (TDF vs. inactive CHB patients: MD = - 17.27, 95% CI (- 30.03, - 4.47); TDF vs. non-HBV-infected individuals: MD = - 17.10, 95% CI (- 20.13, - 14.07)). TC changes in the TAF and ETV groups were not statistically different from the non-antiviral group (TAF vs. inactive CHB patients: MD = - 2.69, 95% CI (- 14.42, 9.04); TAF vs. non-HBV-infected individuals: MD = - 2.52, 95% CI (- 8.47, 3.43); ETV vs. inactive CHB patients: MD = - 4.24, 95% CI (- 17.12, 8.64); ETV vs. non-HBV-infected individuals: MD = - 4.07, 95% CI (- 9.90, 1.75)). The ranking of the effects for lowering TC is as follows: CHB patients treated with nucleotide analogues [with varying efficacy: TDF (SUCRA = 99.9) > ETV (SUCRA = 59.3) > TAF (SUCRA = 43.6)] > inactive CHB patients (SUCRA = 27.3) > non-HBV-infected individuals (SUCRA = 19.9). As for secondary outcomes, among the three antiviral drugs, TDF had the most significant effect on lowering TG, LDL-C, and HDL-C, but none of the three drugs was statistically different from the non-antiviral group. Subgroup analysis showed that the lipid-lowering effect of TDF was more pronounced in the elderly (≥ 50 years). CONCLUSION: TDF was effective in lipid reduction, particularly pronounced in the older population. TAF and ETV had a neutral effect to TC, TG, LDL-C, and HDL-C. Despite a relative increase in lipids observed in patients transitioning from TDF to TAF or ETV, these changes remained within acceptable limits.

Probable targets and mechanism of ginsenoside Rg1 for non-alcoholic fatty liver disease: a study integrating network pharmacology, molecular docking, and molecular dynamics simulation.

Ginsenoside Rg1 (GRg1), a key bioactive component of medicinal herbs, has shown beneficial effects on non-alcoholic fatty liver disease (NAFLD) and numerous other conditions. Nevertheless, the specific targets that are actively involved and the potential mechanisms underlying NAFLD treatment remain unclear. This study aimed to elucidate the therapeutic effects and mechanism of GRg1 in alleviating NAFLD using a combined approach of network pharmacology and molecular biology validation. The analysis yielded 294 targets for GRg1 and 1293 associated with NAFLD, resulting in 89 overlapping targets. Through protein-protein interactions (PPI) network topology analysis, 10 key targets were identified. Upon evaluating the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis, GRg1 may exert therapeutic effects on NAFLD by negatively regulating the apoptotic process, insulin and endocrine resistance, the AGE-RAGE signaling pathway in diabetic complications, and the Estrogen, PI3K/Akt, and MAPK pathways. The three differential gene targets for Akt1, EGFR, and IGF1 were identified through the compound-target network in conjunction with the aforementioned methods. The molecular docking and molecular dynamics (MD) simulations showed that AKT1 and EGFR had a strong binding affinity with GRg1. Overall, our findings point to a novel therapeutic strategy involving NAFLD, with further in vivo and in vitro studies promising to deepen our comprehension and validate its potential advantages.Communicated by Ramaswamy H. Sarma.

RNA-seq analysis revealed genes associated with neuropathic pain induced by chronic compressive injury in interferon regulatory factors 4 knockout mice.

OBJECTIVE: To explore the differential expression of genes between wild-type chronic compressive injury (CCI) mice (WT-CCI) and interferon regulatory factors 4 (IRF4) knockout CCI mice (KO-CCI) by RNA-seq analysis of the mouse spinal cord. METHODS: RNA-seq analysis of the spinal cord tissue of the chronic sciatic nerve ligation mice and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used. RESULTS: A total of 104 genes were up-regulated and 116 genes were down-regulated in spinal cord of the mice in IRF4 knockout (KO-CCI) group compared with that in the wild-type CCI (WT-CCI) group. There were 1472 differentially expressed genes in the biological process group, 62 differentially expressed genes in the cellular component group, and 163 differentially expressed genes in the molecular function group in KO-CCI mice. A total of 14 genes related to inflammatory reactions were differentially expressed. Real-time PCR results confirmed that Pparg and Grpr mRNA expression was up-regulated and Arg 1 and Ccl11 mRNA expression was down-regulated in the KO-CCI group. CONCLUSION: IRF4 is involved in neuropathic pain in CCI mice, IRF4 may participate in neuropathic pain by regulating Grpr, Mas1, Galr3, Nos2, Arg1, Ccl11, Ptgs2, S100a8, Pparg, Cd40, Has2, Gpr151, Il123a, Capns2, Ankrd1, Ccnb1, and Nppb genes.

Routine Workflow of Spatial Proteomics on Micro-formalin-Fixed Paraffin-Embedded Tissues.

In the era of single-cell biology, spatial proteomics has emerged as an important frontier. However, it still faces several challenges in technology. Formalin-fixed paraffin-embedded (FFPE) tissues are an important material in spatial proteomics, in which fixed tissues are excised using laser capture microdissection (LCM), followed by protein identification with mass spectrometry. For a satisfied spatial proteomics upon FFPE tissues, the excision area is expected to be as small as possible, and the identified proteins are countered upon as much as possible. For a general laboratory for spatial proteomics, a routine workflow is required, not relying on any special device, and is easily operating. In view of these challenges in technology, we initiated a technology evaluation throughout the entire procedure of proteomic analysis with micro-FFPE tissues. In contrast to the protocols reported previously, several innovations in technology were proposed and conducted, such as removal of destaining, decross-linking with "hang-down", solution simplification for peptide generation and balancing to excision area, and capture rate of micro-FFPE tissues. After optimization of all the necessary steps, a routine workflow was established, in which the minimized area for protein identification was 0.002 mm2, while the excision area for a consistent proteomic analysis was 0.05 mm2. Using the developed workflow and collecting the micro-FFPE tissues continuously, for the first time, a spatial proteomic atlas of mouse brain was preliminarily constructed, which exhibited the typical characteristics of spatial-dependent protein abundance and functional enrichment.

Based on disulfidptosis-related glycolytic genes to construct a signature for predicting prognosis and immune infiltration analysis of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) comprises several distinct molecular subtypes with varying prognostic implications. However, a comprehensive analysis of a prognostic signature for HCC based on molecular subtypes related to disulfidptosis and glycolysis, as well as associated metabolomics and the immune microenvironment, is yet to be fully explored. Methods: Based on the differences in the expression of disulfide-related glycolytic genes (DRGGs), patients with HCC were divided into different subtypes by consensus clustering. Establish and verify a risk prognosis signature. Finally, the expression level of the key gene SLCO1B1 in the signature was evaluated using immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) in HCC. The association between this gene and immune cells was explored using multiplex immunofluorescence. The biological functions of the cell counting kit-8, wound healing, and colony formation assays were studied. Results: Different subtypes of patients have specific clinicopathological features, prognosis and immune microenvironment. We identified seven valuable genes and constructed a risk-prognosis signature. Analysis of the risk score revealed that compared to the high-risk group, the low-risk group had a better prognosis, higher immune scores, and more abundant immune-related pathways, consistent with the tumor subtypes. Furthermore, IHC and qRT-PCR analyses showed decreased expression of SLCO1B1 in HCC tissues. Functional experiments revealed that SLCO1B1 overexpression inhibited the proliferation, migration, and invasion of HCC cells. Conclusion: We developed a prognostic signature that can assist clinicians in predicting the overall survival of patients with HCC and provides a reference value for targeted therapy.

Single-Cell Analysis of circRNA Using ddPCR.

Droplet digital polymerase chain reaction (ddPCR) is a new quantitative PCR method based on water-oil emulsion droplet technology. ddPCR enables highly sensitive and accurate quantification of nucleic acid molecules, especially when their copy numbers are low. In ddPCR, a sample is fractionated into ~20,000 droplets, and every nanoliter-sized droplet undergoes PCR amplification of the target molecule. The fluorescence signals of droplets are then recorded by an automated droplet reader. Circular RNAs (circRNAs) are single-stranded, covalently closed RNA molecules that are ubiquitously expressed in animals and plants. CircRNAs are promising as biomarkers for cancer diagnosis and prognosis and as therapeutic targets or agents to inhibit oncogenic microRNAs or proteins (Kristensen LS, Jakobsen T, Hager H, Kjems J, Nat Rev Clin Oncol 19:188-206, 2022). In this chapter, the procedures for the quantitation of a circRNA in single pancreatic cancer cells using ddPCR are described.

Establishment of an animal model of sciatic nerve injury induced by local anesthetics.

Peripheral neurotoxicity injury caused by local anesthetics is a common complication of clinical anesthesia. The study of its mechanism is helpful to prevent and treat the neurotoxic injury of local anesthetics. Previous studies on peripheral neurotoxicity injury caused by local anesthetics have mainly focused on in vitro cell experiments. Due to the lack of an animal model of peripheral neurotoxicity damage caused by local anesthetics, there are few in vivo experimental studies regarding this topic. Herein, 1% ropivacaine hydrochloride was injected into the sciatic nerve by direct incision and exposure of the sciatic nerve to create a local anesthetic neurotoxic injury model. The results showed that 1% ropivacaine hydrochloride could reduce the lower limb motor score and mechanical paw withdrawal threshold in mice 48 hours after injection. Pathological sections showed that 48 hours after treatment with 1% ropivacaine hydrochloride, the sciatic nerve showed increased axonal edema and degeneration, edema between nerve fiber bundles, increased degeneration of axon and myelin sheath vacuoles, edema of nerve bundle membrane and local degeneration and necrosis, and a large number of inflammatory cells around the nerve adventitia were soaked. The above results show that under open vision, 1% ropivacaine hydrochloride can cause injury to the sciatic nerve after 48 h of treatment, which can simulate the neurotoxic damage of local anesthetics. This animal model provides a research tool for studying the mechanism of neurotoxic injury caused by local anesthetics.

Identification of distinct tumor cell patterns with single-cell RNA sequencing integrating primary lung adenocarcinoma and brain metastasis tumor.

Background: Lung adenocarcinoma (LUAD) is the most common form of lung cancer and is often accompanied by brain metastasis (BM). The heterogeneity of the tumor renders all current conventional treatments less effective. This study aims to dissect tumor cell heterogeneity and identify potential therapeutic targets. Methods: We conducted single-cell RNA-sequencing (scRNA-seq) in 8 patients with treatment-naïve LUAD BM and included scRNA-seq data of 10 primary LUAD samples and their matched adjacent normal tissue from GSE131907 to determine the tumor cell heterogeneity. Results: Our analyses revealed tumor cells derived from brain metastases were more heterogeneous. Tumor cells from BM harbored significantly more copy number variants (CNVs), and cells of magnoid subtype were the critical source of malignant cells both in BM and the primary lung tumor. Pseudo-time trajectory analysis revealed that malignant cells had upregulated genes enriched for cell cycle and cell division. Integrated analysis of tumor cells revealed 2 distinct malignant cell clusters (cluster 4 and cluster 6) and their marker genes. The signatures identified in the single-cell profile had prognostic value in the bulk tumor profiles. Moreover, the signature of cluster 4 had significant prognostic value in predicting patients surviving longer than 3.5 years, while the signature of cluster 6 showed better predictive ability within 1 year. Magnoid-type cells are most likely to develop into the riskiest cell type and potentially promote tumor progression. Conclusions: scRNA profiling that integrates LUAD BM and primary LUAD can provide information on those malignant cells with BM potential, offering additional prognostic information at cellular level, and may serve as a foundational resource for further tumor cell dissection and therapeutic target exploration.

High-sensitivity long-range surface plasmon resonance sensing assisted by gold nanoring cavity arrays and nanocavity coupling.

In many of the existing refractive index (RI) sensing works, only the shape and size of plasmonic structures are usually taken into account, while the parameters of spacer layers are ignored. In this publication, we explored the long-range surface plasmon resonance (LRSPR) and Fabry-Pérot resonance coupling effects of our proposed gold nanoring cavity array/spacer layer/Au mirror/glass substrate. Both the RI sensitivity and full width at half-maximum (FWHM) values were superior than those of conventional surface plasmon resonance substrates. We discussed the tunability of the RI sensitivity through changing the RI and thickness of the spacer layer. Then, under the optimized parameter conditions of the spacer layer, the geometry parameters (including size, gap and periodicity) of gold nanoring cavity arrays were tuned to optimize the best RI sensitivity. Finally, we broke the structural symmetry of a nanoring cavity to introduce Fano resonances into our system, and a high RI sensitivity and figure-of-merit (FOM) of 695 nm per RIU (refractive index unit) and 96.5, respectively, were achieved when the breaking angle θ was 30°. This study opens up many possibilities for boosting the FOM of RI sensing by taking into account the hybridization effects of localized surface plasmon resonance, LRSPR, and Fabry-Pérot and Fano resonances.

[Association Between Socioeconomic Status, Productive Aging, and Frailty Index in Urban Elderly Population in China].

Objective: To explore the impact of socioeconomic status and productive aging on the frailty index of urban elderly population in China, and to provide reference for improving their health level. Methods: We obtained data from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS) and included 1890 urban elderly people aged 60 and over in the study. Multiple linear regression model was used to analyze the influencing factors of the productive aging and the frailty index of the urban elderly population in China. A structural equation model was constructed to explore the relationship between socioeconomic status, productive aging, and frailty index. Results: Elderly people with high socioeconomic status ( ß=0.082, P<0.001) had higher level of productive aging. Elderly people with high socioeconomic status ( ß=－0.091, P<0.001) and high level of productive aging ( ß=－0.330, P<0.001) had lower frailty index. Productive aging played an intermediary role ( ß=－0.259, 95% CI: －0.380--0.181) between socioeconomic status and frailty index. Conclusion: The socioeconomic status and productive aging of the elderly people are important predictors of their frailty index. The government should exert its leadership functions to encourage the elderly, especially those with low education and income levels, to actively learn knowledge and skills, and to provide support for the elderly to participate in productive activities.

Ginsenoside Rg1 attenuates the NASH phenotype by regulating the miR-375-3p/ATG2B/PTEN-AKT axis to mediate autophagy and pyroptosis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is one of the most frequent liver diseases at present, and there is no radical treatment. The consequences of a variety of ginsenoside compounds on this situation have before been reported, however, the specific effect on the monomeric ginsenoside Rg1 (Rg1) and its associated underlying molecular mechanism stay unknown. MATERIAL AND METHODS: In vitro, the cell models were constructed by exposing free fatty acids (FFAs) to HepG2 cells. A methionine and choline deficiency (MCD)-induced NASH mouse model was also established over 5-6 weeks of treatment. Rg1 is a traditional Chinese medicine monomer. These NASH models were treated with Rg1 and analyzed by qRT-PCR, Western Blot, sequencing, Oil red O staining, immunofluorescence, enzyme activity, HE staining, ELISA, double luciferase reporter assay, and immunohistochemistry. RESULTS: Overexpression of ATG2B, an autophagy-related protein, attenuated lipid droplet accumulation and reduces ALT, AST, inflammatory cytokines, hydrogen peroxide, and pyroptosis in established mouse and cellular models of NASH and increased levels of ATP and autophagy. The binding sites of miR-375-3p and ATG2B were verified by bioinformatic prediction and a dual-luciferase reporter gene. Knockdown of miR-375-3p promoted autophagy and inhibited pyroptosis. ATG2B knockdown substantially attenuated the impact of miR-375-3p on NASH. Rg1 appears to regulate the occurrence and development of NASH inflammation through miR-375-3p and ATG2B in vitro and in vivo, and is regulated by PTEN-AKT pathway. CONCLUSIONS: This study showed that Rg1 participates in autophagy and pyroptosis through the miR-375-3p/ATG2B/PTEN-AKT pathway, thereby alleviating the occurrence and development of NASH, for that reason revealing Rg1 as a candidate drug for NASH.

A New Method for Inversion of Dam Foundation Hydraulic Conductivity Using an Improved Genetic Algorithm Coupled with an Unsaturated Equivalent Continuum Model and Its Application.

Seepage is a main cause of dam failure, and its stability analysis is the focus of a dam's design, construction, and management. Because a geological survey can only determine the range of a dam foundation's hydraulic conductivity, hydraulic conductivity inversion is crucial in engineering. However, current inversion methods of dam hydraulic conductivity are either not accurate enough or too complex to be directly used in engineering. Therefore, this paper proposes a new method for the inversion of hydraulic conductivity with high application value in hydraulic engineering using an improved genetic algorithm coupled with an unsaturated equivalent continuum model (IGA-UECM). This method is implemented by a new code that fully considers engineering applicability. In addition to overcoming the premature convergence shortcomings of traditional genetic algorithms, it converges faster than Bayesian optimization and tree-structured Parzen estimator inversion algorithms. This method is verified by comparing the water head from drilling exploration and inversion. The results of the inversion are used to study the influence of a cement grouting curtain layout scheme on the seepage field of the Hami concrete-face rockfill dam in China, which is used as an engineering application case of the IGA-UECM. The law of the seepage field is reasonable, which verifies the validity of the IGA-UECM. The new inversion method of hydraulic conductivity and the proposed cement grouting curtain layout in this study offer possible strategies for the design, construction, and management of concrete-face rockfill dams.