Detection of monkeypox virus using helicase dependent amplification and recombinase polymerase amplification combined with lateral flow test.

The monkeypox virus (MPXV) is a zoonotic DNA virus that belongs to the poxvirus family. Conventional laboratory methods for detecting MPXV are complex and expensive, making them unsuitable for detecting the virus in regions with limited resources. In this study, we using the Helicase dependent amplification (HDA) method and the Recombinase polymerase amplification (RPA) technique in combination with the lateral flow test (LFT), together with a self-designed qPCR technique for the detection of the MPXV specific conserved fragment F3L, to compare the sensitivity and specificity of the three assays. By analyzing the sensitivity detection results using Probit, it can be seen that the limit of detection (LOD) of the HDA-LFT detection target is 9.86 copies/µL (95% confidence interval, CI 7.52 copies/µL lower bound), the RPA-LFT detection target is 6.97 copies/µL (95% CI 3.90 copies/µL lower bound), and the qPCR detection target is 479.24 copies/mL (95% CI 273.81 copies/mL lower bound). The specificity test results showed that the specificity of the three methods mentioned above was higher than 90% in detecting pseudoviruses of the same genus of MPXV. The simple, highly sensitive, and specific MPXV assay developed in this study is anticipated to provide a solid foundation for future applications in the early screening, diagnosis, and evaluation of the efficacy of MPXV. This is the first time the HDA-LFT assay has been utilized to detect MPXV infection.

Rapid and portable bunyavirus SFTSV RNA testing utilizing catalytic hairpin assembly coupled with lateral flow immunoassay.

Severe fever with thrombocytopenia syndrome (SFTS) is a prevalent, life-threatening, emergent infectious disease. Currently, reverse transcription-polymerase chain reaction is the gold standard for diagnosing SFTS virus (SFTSV) infection, which requires sophisticated equipment and professional personnel that are frequently unavailable in most SFTS endemic rural areas. Here, we reported a simple, rapid nucleic acid amplification system that combined the catalytic hairpin assembly (CHA) with a lateral flow immunoassay (LFIA) strip-based detection method for SFTSV detection. The detection of SFTSV RNA could be realized by generation of H1-H2 hybrid duplexes labeled with biotin and digoxin, which subsequently added to the LFIA test strips containing streptavidin conjugated with Alexa Fluor 647 as well as anti-digoxin antibodies. Our CHA-based LFIA assay offered high amplification efficiency and specificity with a detection limit of 1 aM. Crucially, this method enabled stable detection of 500 copies/mL of SFTSV within 30 min using clinical serum samples. Therefore, our CHA-based LFIA approach provided a potential useful tool to facilitate early and precise diagnosis of SFTS patients in poorly resourced SFTS endemic areas.IMPORTANCESevere fever with thrombocytopenia syndrome (SFTS) is an emerging and potentially fatal infectious disease prevalent in China. Here we report a simple, rapid nucleic acid amplification system, the catalytic hairpin assembly (CHA) in conjunction with a lateral flow immunoassay (LFIA) strip-based detection method for SFTS virus detection, which demonstrated high amplification efficiency and specificity with limit of detection of 1 aM. Most importantly, we also validate our CHA-based LFIA assay using the clinical serum samples, which was fully compatible with reverse transcription-PCR results. Therefore, our strategy provides a potential useful tool to facilitate early and precise diagnosis of SFTS patients especially in poorly resourced SFTS endemic areas.

Prognostic Prediction Value and Biological Functions of Non-Apoptotic Regulated Cell Death Genes in Lung Adenocarcinoma.

Objective To explore the potential biological functions and prognostic prediction values of non-apoptotic regulated cell death genes (NARCDs) in lung adenocarcinoma.Methods Transcriptome data of lung adenocarcinoma were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. We identified differentially expressed NARCDs between lung adenocarcinoma tissues and normal tissues with R software. NARCDs signature was constructed with univariate Cox regression analysis and the least absolute shrinkage and selection operator Cox regression. The prognostic predictive capacity of NARCDs signature was assessed by Kaplan-Meier survival curve, receiver operating characteristic curve, and univariate and multivariate Cox regression analyses. Functional enrichment of NARCDs signature was analyzed with gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. In addition, differences in tumor mutational burden, tumor microenvironment, tumor immune dysfunction and exclusion score, and chemotherapeutic drug sensitivity were analyzed between the high and low NARCDs score groups. Finally, a protein-protein interaction network of NARCDs and immune-related genes was constructed by STRING and Cytoscape software. Results We identified 34 differentially expressed NARCDs associated with the prognosis, of which 16 genes (ATIC, AURKA, CA9, ITGB4, DDIT4, CDK5R1, CAV1, RRM2, GAPDH, SRXN1, NLRC4, GLS2, ADRB2, CX3CL1, GDF15, and ADRA1A) were selected to construct a NARCDs signature. NARCDs signature was identified as an independent prognostic factor (P < 0.001). Functional analysis showed that there were significant differences in mismatch repair, p53 signaling pathway, and cell cycle between the high NARCDs score group and low NARCDs score group (all P < 0.05). The NARCDs low score group had lower tumor mutational burden, higher immune score, higher tumor immune dysfunction and exclusion score, and lower drug sensitivity (all P < 0.05). In addition, the 10 hub genes (CXCL5, TLR4, JUN, IL6, CCL2, CXCL2, ILA, IFNG, IL33, and GAPDH) in protein-protein interaction network of NARCDs and immune-related genes were all immune-related genes. Conclusion The NARCDs prognostic signature based on the above 16 genes is an independent prognostic factor, which can effectively predict the clinical prognosis of patients of lung adenocarcinoma and provide help for clinical treatment.

A colloidal gold test strip based on catalytic hairpin assembly for the clinical detection of influenza a virus nucleic acid.

Influenza A epidemics, which occur annually in varying degrees worldwide, is a global challenge to healthcare facilities owing to several limitations of the current detection methods. Therefore, the development of a rapid, convenient, and economical method for the early diagnosis of influenza A will aid clinical treatment and epidemic control. Currently, most of the commonly used clinical rapid tests utilize colloidal gold test strips that detect specific influenza virus antigens but are limited by low sensitivity. Therefore, this study combined catalytic hairpin assembly (CHA) with colloidal gold immunochromatographic assay (GICA) to develop a highly sensitive and visual CHA-GICA test strip. Clinical sample analysis revealed that the sensitivity of the assay was 81.8% and 74% under optimal (35 °C) and room temperature (25 °C) conditions, respectively. In conclusion, this study developed a rapid nucleic acid assay for detecting influenza A virus with high sensitivity and specificity, which can improve the clinical detection of influenza A.

Dual-targeted and dual-sensitive self-assembled protein nanocarrier delivering hVEGI-192 for triple-negative breast cancer.

Breast cancer is a highly prevalent malignancy worldwide among women with an increasing incidence in recent years. Triple-negative breast cancer (TNBC), a specific type of breast cancer, occurs primarily in young women and exhibits large tumor size, high clinical stage, and extremely poor prognosis with a high rate of lymph node, liver, and lung metastases. TNBC is insensitive to endocrine therapy and trastuzumab treatment, and there is an urgent need for effective therapeutics and treatment guidelines. However, investigations into antiangiogenic agents for the treatment of TNBC are ongoing. In this study, we successfully engineered a self-assembled protein nanocarrier TfRBP9-hVEGI-192-ELP fusion protein (TVEFP) to deliver the therapeutic protein, human vascular endothelial growth inhibitor (hVEGI-192). This was found to be effective in inhibiting tumor angiogenesis in vivo. The protein nanocarrier effectively inhibited the progression of TNBC in vivo and showed the behavior of self-assembly, thermoresponsiveness, enzyme stimulation-responsiveness, tumor-targeting, biocompatibility, and biodegradability. Near-infrared imaging studies showed that fluorescent dye-stained TVEFP effectively aggregated at the tumor site. The TVEFP nanocarrier significantly expands the application of the therapeutic protein hVEGI-192 and improves the imaging and biotherapeutic effects in TNBC, chiefly based on anti-angiogenesis effects.

Addition of dNTPs can improve the detection sensitivity of catalytic hairpin assembly.

Ever since the catalytic hairpin assembly (CHA) circuit has been highlighted as a powerful nucleic acid detection tool, nucleic acid detection methods based on CHA have been widely studied. However, the detection sensitivity of CHA-based methods is insufficient. The relatively high background signals resulting from the spontaneous reaction between the two hairpin probes is one of the major reasons for limiting the sensitivity of CHA. In this study, we established that the addition of deoxynucleotide triphosphates (dNTPs) to the reaction system can significantly reduce the background leakage of CHA. The dNTPs-CHA, coupled with a fluorescence lateral flow assay strip, is used for the rapid and highly sensitive detection of miRNA. It is capable of reliably detecting miRNA in serum samples down to a limit of 100 aM, which is an improvement in the lower detection limit by nearly five orders of magnitude compared to that of the pure CHA.

Isothermal nucleic acid amplification technology in HIV detection.

Nucleic acid testing for HIV plays an important role in the early diagnosis and monitoring of antiretroviral therapy outcomes in HIV patients and HIV-infected infants. Currently, the main molecular diagnostic methods employed are complex, time-consuming, and expensive to operate in resource-limited areas. Isothermal nucleic acid amplification technology overcomes some of the shortcomings of traditional assays and makes it possible to use point-of-care tests for molecular HIV detection. Here, we summarize and discuss the latest technological advances in isothermal nucleic acid amplification for HIV detection, with the intent of providing guidance for the development of subsequent HIV assays with high sensitivity and specificity.

A simple and programmable dual-mode aptasensor for the ultrasensitive detection of multidrug-resistant bacteria.

Accurately identifying multidrug-resistant (MDR) bacteria from clinical samples has long been a challenge. Herein, we report a simple and programmable dual-mode aptasensor called DAPT to reliably detect MDR bacteria. The DAPT method comprises two elements, namely the mode of dynamic light scattering (Mode-DLS) for ultrasensitive detection and the mode of fluorescence (Mode-Flu) for reliable quantification as a potent complement. Benefiting from the states of aptamer-modified gold nanoparticles (AptGNPs) sensitively changing from dispersion to aggregation, the proposed Mode-DLS achieved the rapid, specific, and ultrasensitive detection of methicillin-resistant Staphylococcus aureus (MRSA) at the limit of detection (LOD) of 4.63 CFU mL-1 in a proof-of-concept experiment. Simultaneously, the Mode-Flu ensured the accuracy of the detection, especially at a high concentration of bacteria. Moreover, the feasibility and universality of the DAPT platform was validated with four other superbugs by simply reprogramming the corresponding sequence. Overall, the proposed DAPT method based on a dual-mode aptasensor can provide a universal platform for the rapid and ultrasensitive detection of pathogenic bacteria due to its superior programmability.

Clinical application and detection techniques of liquid biopsy in gastric cancer.

Gastric cancer (GC) is one of the most common tumors worldwide and the leading cause of tumor-related mortality. Endoscopy and serological tumor marker testing are currently the main methods of GC screening, and treatment relies on surgical resection or chemotherapy. However, traditional examination and treatment methods are more harmful to patients and less sensitive and accurate. A minimally invasive method to respond to GC early screening, prognosis monitoring, treatment efficacy, and drug resistance situations is urgently needed. As a result, liquid biopsy techniques have received much attention in the clinical application of GC. The non-invasive liquid biopsy technique requires fewer samples, is reproducible, and can guide individualized patient treatment by monitoring patients' molecular-level changes in real-time. In this review, we introduced the clinical applications of circulating tumor cells, circulating free DNA, circulating tumor DNA, non-coding RNAs, exosomes, and proteins, which are the primary markers in liquid biopsy technology in GC. We also discuss the current limitations and future trends of liquid biopsy technology as applied to early clinical biopsy technology.

A Systematic Analysis of the Role of Unc-5 Netrin Receptor A (UNC5A) in Human Cancers.

Unc-5 netrin receptor A (UNC5A), a netrin family receptor, plays a key role in neuronal development and subsequent differentiation. Recently, studies have found that UNC5A plays an important role in multiple cancers, such as bladder cancer, non-small cell lung carcinoma, and colon cancer but its pan-cancer function is largely unknown. Herein, the R software and multiple databases or online websites (The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), The Tumor Immune Estimation Resource (TIMER), The Gene Set Cancer Analysis (GSCA), Gene Expression Profiling Interactive Analysis (GEPIA), and cBioPortal etc.) were utilized to examine the role of UNC5A in pan-cancer. UNC5A was found to be highly expressed across multiple human cancer tissues and cells, was linked to clinical outcomes of patients, and was a potential pan-cancer biomarker. The mutational landscape of UNC5A exhibited that patients with UNC5A mutations had poorer progress free survival (PFS) in head and neck squamous cell carcinoma (HNSC) and prostate adenocarcinoma (PRAD). Furthermore, UNC5A expression was associated with tumor mutation burden (TMB), neoantigen, tumor microenvironment (TME), tumor microsatellite instability (MSI), immunomodulators, immune infiltration, DNA methylation, immune checkpoint (ICP) genes, and drug responses. Our results suggest the potential of UNC5A as a pan-cancer biomarker and an efficient immunotherapy target, which may also guide drug selection for some specific cancer types in clinical practice.

Detection of Ureaplasma urealyticum by Catalytic Hairpin Assembly Combined with a Lateral Flow Immunoassay Strip.

Ureaplasma urealyticum is a common genital mycoplasma in men and women, which can cause reproductive tract infection and infertility, and is also related to adverse pregnancy outcomes and neonatal diseases. Pathogen culture and polymerase chain reaction (PCR) are the main methods for the diagnosis of U. urealyticum. However, pathogen culture takes too long, and PCR requires professional personnel and sophisticated instruments. Here, we report a simple, convenient, sensitive, and specific detection method, which combines catalytic hairpin assembly with a lateral flow immunoassay strip. Only a water bath and a fluorescence reader are needed to detect the results in 30 min. We can realize the point-of-care testing of U. urealyticum by this method. To verify this method, we selected 10 clinical samples for testing, and the test results were exactly the same as the clinical report.

Dexmedetomidine Attenuates Total Body Radiation-Induced Acute Liver Injury in Mice Through the Nrf2/HO-1 Pathway.

BACKGROUND: The purpose of this study was to investigate the protective effects of dexmedetomidine (DEX) on total body radiation-induced acute liver injury in mice and to explore the possible mechanisms. METHODS: A total of 40 mice were randomly divided into the Control group (Group C), Dexmedetomidine group (Group Dex), Radiation group (Group R), and Group R+Dex. Mice in Group Dex and Group R+Dex were intraperitoneally injected with 10 µg/mL Dex at 50 mg/kg. Both Group C and Group R received normal saline instead of Dex. Mice were treated via continuous administration for 10 days and injection once a day (pre-administration for 3 days and 7 days after radiation). One hour after administration on the third day, the mice in Group R and R+Dex received total body radiation with a total dose of 6 Gy at a rate of 2 Gy/min. Group C received sham radiation. Levels of aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and liver levels of tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA) were measured. HE staining was employed to evaluate the pathological changes in liver tissues, and the expressions of Nrf2 and HO-1 proteins in the liver were measured by western blot. RESULTS: Compared with group C, serum levels of AST and ALT, liver TNF-α, IL-1ß, MDA, and ROS levels increased, and SOD decreased in Group R. Group R mice had higher liver injury scores, and the protein expressions of Nrf2 and HO-1 proteins were lower (p ＜ 0.05). Compared with Group R, the levels of AST, ALT, TNF-α, IL-1ß, MDA, and ROS decreased, SOD increased, liver injury scores were lower, and the expressions of Nrf2 and HO-1 proteins were higher in the Group R+Dex group (all p ＜ 0.05). CONCLUSIONS: Dex exhibits a protective effect on reducing acute radiation-induced liver injury and oxidative stress, and the mechanism may be associated with the activation of Nrf2/HO-1 pathways.

Super-sensitive bifunctional nanoprobe: Self-assembly of peptide-driven nanoparticles demonstrating tumor fluorescence imaging and therapy.

The development of nanomedicine has recently achieved several breakthroughs in the field of cancer treatment; however, biocompatibility and targeted penetration of these nanomaterials remain as limitations, which lead to serious side effects and significantly narrow the scope of their application. The self-assembly of intermediate filaments with arginine-glycine-aspartate (RGD) peptide (RGD-IFP) was triggered by the hydrophobic cationic molecule 7-amino actinomycin D (7-AAD) to synthesize a bifunctional nanoparticle that could serve as a fluorescent imaging probe to visualize tumor treatment. The designed RGD-IFP peptide possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method. This fluorescent nanoprobe with RGD peptide could be targeted for delivery into tumor cells and released in acidic environments such as endosomes/lysosomes, ultimately inducing cytotoxicity by arresting tumor cell cycling with inserted DNA. It is noteworthy that the RGD-IFP/7-AAD nanoprobe tail-vein injection approach demonstrated not only high tumor-targeted imaging potential, but also potent antitumor therapeutic effects in vivo. The proposed strategy may be used in peptide-driven bifunctional nanoparticles for precise imaging and cancer therapy.

Facile, Rapid, and Low-Cost Detection for Influenza Viruses and Respiratory Syncytial Virus Based on a Catalytic DNA Assembly Circuit.

Influenza viruses and respiratory syncytial virus (RSV) have contributed to severe respiratory infections, causing huge economic and healthcare burdens. To achieve rapid and precise detection of influenza viruses and RSV, we proposed a catalytic hairpin assembly (CHA) combined with the lateral flow immunoassay (CHA-LFIA) detection method. The presence of the target RNA triggers the initiation of CHA circuits. H1/H2 complexes, the amplified signal products, which were labeled with digoxin and biotin, were detected with a highly sensitive lateral flow immunoassay system. The sensitivity of the CHA-LFIA system to influenza A and B viruses and RSV reached up to 1, 1, and 5 pM, respectively. In addition, this method exhibited excellent capability for differentiating between target RNA and base-mismatched RNA. The results demonstrated that an enzyme-free, rapid, highly sensitive, and specific method had been developed to detect influenza A and B viruses and RSV.

High expression of CLEC10A in head and neck squamous cell carcinoma indicates favorable prognosis and high-level immune infiltration status.

Immunotherapy has emerged as a promising treatment modality for HNSCC. However, only a small proportion of HNSCC patients experience clinical benefits from immunotherapy and identifying molecular markers that can serve as effective prognostic signatures and predictive indicators for immunotherapy response in patients with HNSCC is critical. CLEC10A has attracted attention because of its important role in improving the antitumor activity of immune cells. However, to our knowledge, no study has evaluated the role of CLEC10A in HNSCC prognosis, progression, and immune microenvironment. In the present study, we comprehensively analyzed expression profiles of CLEC10A and its association with tumor progression, HPV status, and survival of patients. Moreover, we explored the association between CLEC10A expression relative to immune infiltration and the response to immunotherapy. We explored the association between the timing of the receipt of palliative care relative to cancer diagnosis and survival. Our results revealed that CLEC10A has decreased expression in HNSCC compared with normal tissues, and that low expression of CLEC10A was associated with an advanced clinical stage and poor prognosis. Furthermore, a higher level of CLEC10A expression correlated with immune infiltration presence and response to immunotherapy in HNSCC. Thus, we demonstrated that CLEC10A could be a potential prognostic marker in patients with HNSCC, and a potential target for immunotherapy.

Comprehensive analysis of matrix metalloproteinases and their inhibitors in head and neck squamous cell carcinoma.

Objective: This study aimed to explore the association of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) with cancer progression and prognosis in head and neck squamous cell carcinoma (HNSCC).Methods: Differentially expressed genes (DEGs) were identified by LIMMA package using R software. The correlation between the expression levels of MMPs and TIMPs in HNSCC cancer samples and adjacent normal tissue samples was performed using Pearson correlation analysis. The Kruskal-Wallis test (H-test) was used to determine the association between the expression level of MMPs/TIMPs and HNSCC clinical stage. The survival result was expressed as a KM curve, and the log-rank test was used for statistical analysis. Lasso regression and multivariate Cox regression analyses were used to examine whether the gene signature based on MMPs and TIMPs was an independent prognostic factor in patients with HNSCC.Results: Among the top 10 most up-regulated genes in HNSCC cancer tissues when compared with normal tissues, six genes belonged to the MMPs. Spearman correlation analysis revealed that only MMP11 and MMP23B were positively correlated with tumor stage. Survival analysis showed that patients with a high expression of MMP14, MMP20, TIMP1, and TIMP4 had a worse prognosis than low expression patients. Additionally, a novel five-gene (MMP3, MMP17, MMP19, MMP24, and TIMP1) signature was constructed and significantly associated with prognosis as an independent prognostic signature.Conclusions: Our data show that the accuracy of a single gene of MMP or TIMP as predictors of progression and prognosis of HNSCC is limited, although some studies have proposed that MMPs act as driving factors for cancer progression. The prediction performance of the five-gene signature prediction model was much better than that of the gene signatures based on every single gene in prognosis prediction.

Sensitive detection of hepatitis C virus using a catalytic hairpin assembly coupled with a lateral flow immunoassay test strip.

Currently, PCR is the gold standard for the detection of hepatitis C virus (HCV). However, the PCR technique is complicated and time-consuming, which prevents its application and, clinical point-of-care testing (POCT). Herein, we report a POCT method with simplicity, high sensitivity and specificity, which consists of a catalytic hairpin assembly (CHA) signal amplification system coupled with a lateral flow immunochromatographic (LFIA) test strip for the detection of HCV. Two ingeniously designed hairpin probes were hybridized to form the H1-H2 duplex in the presence of the target DNA. The catalytic hairpin assembly which was characterized of isothermal and enzyme-free, was accomplished within 40 min and the reaction was then applied to a LFIA test strip. Only the H1-H2 duplex labeled with both digoxin and biotin could be captured by the test strip, and the fluorescence value was determined. In addition, we evaluated the application potential for the detection of clinical samples. The reported method demonstrated high sensitivity with a detectable minimum concentration at 1 fM and showed a good linear range from 10 nM to 10pM, and high specificity for various mismatched sequences. The results demonstrated that clinically positive samples could be successfully detected. In conclusion, the reported method is simple, rapid, and free of large-scale equipment. POCT is expected to be useful for HCV detection in clinic.

Rapid point-of-care testing for SARS-CoV-2 virus nucleic acid detection by an isothermal and nonenzymatic Signal amplification system coupled with a lateral flow immunoassay strip.

An outbreak of a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in December 2019. Accurate, rapid, convenient, and relatively inexpensive diagnostic methods for SARS-CoV-2 infection are important for public health and optimal clinical care. The current gold standard for diagnosing SARS-CoV-2 infection is reverse transcription-polymerase chain reaction (RT-PCR). However, RTPCR assays are designed for use in well-equipped laboratories with sophisticated laboratory infrastructure and highly trained technicians, and are unsuitable for use in under-equipped laboratories and in the field. In this study, we report the development of an accurate, rapid, and easy-to-implement isothermal and nonenzymatic signal amplification system (a catalytic hairpin assembly (CHA) reaction) coupled with a lateral flow immunoassay (LFIA) strip-based detection method that can detect SARSCoV-2 in oropharyngeal swab samples. Our method avoids RNA isolation, PCR amplification, and elaborate result analysis, which typically takes 6-8 h. The entire CHA-LFIA detection method, from nasopharyngeal sampling to obtaining test results, takes less than 90 min. Such methods are simple and require no expensive equipment, only a simple thermostatically controlled water bath and a fluorescence reader device. We validated our method using synthetic oligonucleotides and clinical samples from 15 patients with SARS-CoV-2 infection and 15 healthy individuals. Our detection method provides a fast, simple, and sensitive (with a limit of detection (LoD) of 2000 copies/mL) alternative to the SARS-CoV-2 RT-PCR assay, with 100 % positive and negative predictive agreements.

Nanocarrier-delivered small interfering RNA for chemoresistant ovarian cancer therapy.

Ovarian cancer is the fifth leading cause of cancer-related death in women in the United States. Because success in early screening is limited, and most patients with advanced disease develop resistance to multiple treatment modalities, the overall prognosis of ovarian cancer is poor. Despite the revolutionary role of surgery and chemotherapy in curing ovarian cancer, recurrence remains a major challenge in treatment. Thus, improving our understanding of the pathogenesis of ovarian cancer is essential for developing more effective treatments. In this review, we analyze the underlying molecular mechanisms leading to chemotherapy resistance. We discuss the clinical benefits and potential challenges of using nanocarrier-delivered small interfering RNA to treat chemotherapy-resistant ovarian cancer. We aim to elicit collaborative studies on nanocarrier-delivered small interfering RNA to improve the long-term survival rate and quality of life of patients with ovarian cancer. This article is categorized under: RNA Methods > RNA Nanotechnology Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action.

Metabolic Signatures of Genetically Elevated Vitamin D Among Chinese: Observational and Mendelian Randomization Study.

CONTEXT: Observational studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels are associated with favorable serum lipids and related metabolites. However, whether such observations reflect causality remains unclear. OBJECTIVE: We aimed to investigate the causal effect of elevated 25(OH)D with a detailed systemic metabolite profile in Chinese adults. METHODS: A total of 225 lipid and other metabolites were quantified in 4662 individuals in the China Kadoorie Biobank. Instrumental variable analyses were performed to test the causal associations of plasma 25(OH)D with lipids and metabolites. RESULTS: Higher plasma 25(OH)D was related to favorable lipid profiles in observational analyses. The genetic risk score was robustly correlated with observed 25(OH)D (beta[SE] = 3.54 [0.32]; P < 1 × 10-5, F-statistic = 122.3) and explained 8.4% of the variation in 25(OH)D in the Chinese population. For all individual metabolites, the causal estimates were not significant at the threshold P < 5 × 10-4 (multiple testing corrected). However, a Mendelian randomization (MR) estimate showed that per 1-SD increase in genetically determined 25(OH)D was suggestive of association with decreased levels of cholesterol, lipoprotein particles, and phospholipids within very small very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) (P ≤ 0.05, nominal significance). For amino acids, fatty acids, ketone bodies, glycoprotein acetyls, fatty acids, and other traits, we did not observe any significant causal association. CONCLUSIONS: The MR analysis of metabolic data based a population-based cohort suggested a potential causal association of plasma 25(OH)D with cholesterol, lipoprotein particle, phospholipid concentrations, and total lipids within very small VLDL and IDL. Our findings highlight a long-term effect of 25(OH)D levels in maintaining healthy lipid metabolism.