Protective effects of oyster polypeptide from oyster (Crassostrea ariakensis) on cyclophosphamide induced immunosuppression rats based on 1H NMR metabolomics and 16S rRNA gene sequencing.

BACKGROUND: Oyster polypeptide (OP) is a mixture of oligopeptides extracted from oysters through enzyme lysis, separation and purification. OP is associated with immunomodulatory effects, but the underlying mechanisms are not known. Therefore, this study combined 1H-NMR urinary metabolomics and 16S rRNA gene sequencing of the gut microbiome to determine the immunoprotective mechanisms of OP in rats subjected to cyclophosphamide-induced immunosuppression. RESULTS: OP can restored the body weight and the structure of spleen and thymus in cyclophosphamide-induced immunosuppression rats. OP upregulated the levels of white blood cells (WBCs), hemoglobin (HGB), platelets (PLT), red blood cells (RBCs), immunoglobulin G (IgG), immunoglobulin M (IgM), cytokines such as IL-6 and TNF-α, and the numbers of CD3+ and CD4+ T cells in the immunosuppression rats. The 1H-NMR metabolomics results showed that OP significantly reversed the levels of ten metabolites in urinary, including 2-oxoglutarate, citrate, dimethylamine, taurine, N-phenylacetylglycine, alanine, betaine, creatinine, uracil, and benzoate. The 16S rRNA gene sequencing results showed that OP restored the gut microbiome homeostasis by increasing the abundance of beneficial bacteria and reducing the abundance of pathogenic bacteria. Finally combining metabolomics and microbiomics found that taurine an hypotaurine metabolism, also alanine, aspartate and glutamate metabolish were disturbed, but these metabolic pathways were restored by OP. CONCLUSION: This study demonstrated that OP had immunoprotective effects in cyclophosphamide-induced immunosuppression rats by restoring key metabolic pathways and the gut microbiome homeostasis. Our findings provides a framework for further research into the immunoregulatory mechanisms of OP and its potential use in drugs and nutritional supplements. This article is protected by copyright. All rights reserved.

Microsatellite instability evaluation by a novel PCR-based 8-loci test kit in colorectal cancer.

Microsatellite instability (MSI) assessment is strongly recommended for colorectal cancer patients, as MSI status is crucial in determining optimal treatment and predicting prognosis. This study evaluated the reliability and accuracy of a novel polymerase chain reaction (PCR)-based 8-loci MSI test kit, a rapid test kit designed to detect MSI, by comparing its performance with immunohistochemistry (IHC) and the National Cancer Institute (NCI) 2B3D Panel. MSI status was determined in 186 formalin-fixed paraffin-embedded (FFPE) colorectal cancer tissue samples with known mismatch repair (MMR) status by IHC using the novel PCR-based 8-loci MSI test kit. Additionally, the consistency between the NCI 2B3D Panel and the novel PCR-based 8-loci panel was compared using 69 FFPE tumor tissues paired with adjacent non-cancerous tissue. The novel PCR-based 8-loci MSI test kit and IHC demonstrated high concordance (overall agreement: 97.8%). However, four samples displayed discordant results, exhibiting MMR deficiency using IHC and microsatellite stability using the novel PCR-based 8-loci MSI test kit. Of the 69 samples reanalyzed using the NCI 2B3D Panel, high concordance with the novel PCR-based 8-loci MSI test kit was observed in 67 of 69 cases (overall agreement: 97.1%). The novel PCR-based 8-loci MSI test kit is a rapid and reliable tool for accurately detecting MSI status in colorectal cancer.

Physiological Mechanisms of Citrus Fruit Cracking: Study on Cell Wall Components, Osmoregulatory Substances, and Antioxidant Enzyme Activities.

Fruit cracking affects both the yield and economic efficiency of citrus; however, the underlying mechanism remains unclear. Therefore, this study focused on resistant and susceptible cultivars to identify the mechanisms underlying fruit cracking. The results showed that in 'Mingrijian', pectin morphological transformation and hemicellulose and lignin degradation in the pericarp were important contributing factors. During the critical fruit-cracking period (115-150 days after flowering), the water-soluble pectin, protopectin, and lignin contents in the pericarp of 'Daya' presented inverse changes relative to those in 'Mingrijian', thus enhancing the mechanical properties and resistance of pericarp. From 115 to 150 days after flowering, the soluble sugar content in the pulp of 'Mingrijian' increased rapidly by 97.35%, aiding in pulp water absorption and expansion. Moreover, the soluble protein content in the pericarp of 'Mingrijian' exhibited a declining trend and was lower than that of 'Daya', thus affecting the overall metabolism. The superoxide dismutase (SOD) activity in the pericarp of 'Mingrijian' gradually decreased from 115 to 180 days after flowering, while the peroxidase (POD) activity remained at a low level, resulting in weaker antioxidant capacity and lower environmental resistance. This study provides valuable insights into the mechanisms of citrus fruit cracking, laying the foundation for preventive and control strategies.

Dysfunction of DMT1 and miR-135b in the gut-testis axis in high-fat diet male mice.

BACKGROUND: Obese patients have been found to be susceptible to iron deficiency, and malabsorption of dietary iron is the cause of obesity-related iron deficiency (ORID). Divalent metal transporter 1 (DMT1) and ferroportin (FPN), are two transmembrane transporter proteins expressed in the duodenum that are closely associated with iron absorption. However, there have been few studies on the association between these two proteins and the increased susceptibility to iron deficiency in obese patients. Chronic inflammation is also thought to be a cause of obesity-related iron deficiency, and both conditions can have an impact on spermatogenesis and impair male reproductive function. Based on previous studies, transgenerational epigenetic inheritance through gametes was observed in obesity. RESULTS: Our results  showed that obese mice had decreased blood iron levels (p < 0.01), lower protein and mRNA expression for duodenal DMT1 (p < 0.05), but no statistically significant variation in mRNA expression for duodenal FPN (p > 0.05); there was an increase in sperm miR-135b expression (p < 0.05). Bioinformatics revealed ninety overlapping genes and further analysis showed that they were primarily responsible for epithelial cilium movement, fatty acid beta-oxidation, protein dephosphorylation, fertilization, and glutamine transport, which are closely related to spermatogenesis, sperm development, and sperm viability in mice. CONCLUSIONS: In obese mice, we observed downregulation of DMT1 in the duodenum and upregulation of miR-135b in the spermatozoa.

Novel portable photoelectrochemical sensor based on CdS/Au/TiO2 nanotube arrays for sensitive, non-invasive, and instantaneous uric acid detection in saliva.

Uric acid (UA) monitoring is the most effective method for diagnosis and treatment of gout, hyperuricemia, hypertension, and other diseases. However, challenges remain regarding detection efficiency and rapid on-site detection. Here, we first synthesized a CdS/Au/TiO2-NTAs Z-scheme heterojunction material using a titanium dioxide nanotube array (TiO2-NTAs) as the substrate and modified with gold nanoparticles (Au) and cadmium sulfide particles (CdS). This material achieves bandgap alignment to generate a large number of electron-hole pairs under illumination. Then, using CdS/Au/TiO2-NTAs as the working electrode and molecularly imprinted polymers (MIP) as the recognition unit, we constructed a portable photoelectrochemical (PEC) sensor for non-invasive instant detection of UA concentration in human saliva, which has unique advantages in the field of high-sensitivity PEC instant detection. The portable MIP-PEC sensor achieves a linear range of 0.01-50 µM and a detection limit as low as 5.07 nM (S/N = 3). At the same time, the portable MIP-PEC sensor exhibits excellent sensitivity, specificity as well as stability, and shows no statistically significant difference compared to traditional high-performance liquid chromatography (HPLC) in practical sample detection. Compared to traditional PEC modes, this work demonstrates a novel and universal method for high-sensitivity instant detection in the field of PEC.

A comprehensive "quality-quantity-activity" approach based on portable near-infrared spectrometer and membership function analysis to systematically evaluate spice quality: Cinnamomum cassia as an example.

Spices have long been popular worldwide. Besides serving as aromatic and flavorful food and cooking ingredients, many spices exhibit notable bioactivity. Quality evaluation methods are essential for ensuring the quality and flavor of spices. However, existing methods typically focus on the content of particular components or certain aspects of bioactivity. For a systematic evaluation of spice quality, we herein propose a comprehensive "quality-quantity-activity" approach based on portable near-infrared spectrometer and membership function analysis. Cinnamomum cassia was used as a representative example to illustrate this approach. Near-infrared spectroscopy and chemometric methods were combined to predict the geographical origin, cinnamaldehyde content, ash content, antioxidant activity, and integrated membership function value. All the optimal prediction models displayed good predictive ability (correlation coefficient of prediction > 0.9, residual predictive deviation > 2.1). The proposed approach can provide a valuable reference for the rapid and comprehensive quality evaluation of spices.

Effect of Natural Variation and Rootstock on Fruit Quality and Volatile Organic Compounds of 'Kiyomi tangor' (Citrus reticulata Blanco) Citrus.

In this study, we compared the fruit quality and color of 'Kiyomi' (WT) and its mutant (MT) grafted on Ziyang xiangcheng (Cj) (WT/Cj, MT/Cj), and the MT grafted on Trifoliate orange (Pt) (MT/Pt). The differences in sugar, organic acid, flavonoids, phenols, and volatile substances of the three materials were also analyzed by high performance liquid chromatography (HPLC) and headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). The results showed significant differences in the appearance of WT/Cj, MT/Cj, and MT/Pt. MT/Pt, compared to WT/Cj, MT/Cj, had lower sugar, acid, phenol and flavonoid contents in the pulp. However, MT/Pt pulp was higher in vitamin C (VC), and the peel had significantly higher total phenol and flavonoid contents. In terms of pulp, WT/Cj had the greatest diversity of volatile organic compounds (VOCs). 4-methyl-1-pentanol was significantly higher in MT/Cj pulp, while MT/Pt pulp had a unique octanoic acid, methyl ester. VOCs were more diverse in the peels of the three materials. ß-Myrcene and valencen were significantly higher in MT/Cj peels. In contrast, 16 unique VOCs were detected in MT/Pt, and D-limonene content was significantly higher than in WT/Cj and MT/Cj. The results suggest Trifoliate orange is a suitable rootstock for MT.

Correction of a transcranial acoustic field using a transient ultrasound field visualization technique.

Ultrasound, due to its noninvasive nature, has the potential to enhance or suppress neural activity, making it highly promising for regulating intractable brain disorders. Precise ultrasound stimulation is crucial for improving the efficiency of neural modulation and studying its mechanisms. However, the presence of the skull can cause distortion in the ultrasound field, thereby affecting the accuracy of stimulation. Existing correction methods primarily rely on magnetic resonance guidance and numerical simulation. Due to the large size and high cost, the MR-guided transcranial ultrasound is difficult to be widely applied in small animals. The numerical simulation usually requires further validation and optimization before application, and the most effective method is to visualize the excited ultrasound field. However, the ultrasound field correction methods based on acoustic field visualization are still lacking. Therefore, a shadowgraph-based transient ultrasonic field visualization system is developed, and an ex vivo transcranial ultrasound field correction is performed. By visualizing the ultrasound field with or without a rat skull and then calculating the time difference of each element's ultrasound wavefront, the parameters for ultrasound field correction can be achieved. The experimental results show that this method can improve both the shape and the size of the focal spot, as well as enhance the acoustic pressure at the focus. Overall, the results demonstrate that the ultrasonic field visualization technology can effectively improve the transcranial ultrasound focusing effect and provide a new tool for achieving precise ultrasonic neural modulation.

Association between levels of IgG antibodies from vaccines and Omicron symptomatic infection among children and adolescents in China.

Background: Measurements of IgG antibodies to wild-type SARS-CoV-2 antigens can assess vaccine efficacy, but the absolute risk of Omicron symptomatic infection at different IgG levels for children and adolescents remains uncertain, as well as the minimum effective antibody level. We sought to determine the relationship between the tertiles of IgG antibodies to wild-type SARS-CoV-2 antigens and children with symptomatic infection of the pandemic and duration to negative conversion in China for the first time. Methods: A retrospective study was conducted, including 168 participants under 18 years old from the No.2 People's Hospital of Lanzhou, China, diagnosed with Omicron variant BA.2.38 between July 8, 2022, and August 2, 2022. We calculated odds ratios (OR) in univariate and multivariate regression to assess the association of symptomatic infection with the tertiles of IgG, respectively. Kaplan-Meier curves and Cox proportional hazards regression were used to evaluate the relationship between IgG level and negative conversion time. Results: The average age of the 168 children included in this study was 7.2 (4.7) years old, 133 (79.2%) were symptomatic patients, and the average negative conversion time was 12.2 (3.5) days. The participants with high IgG levels were less likely to become symptomatic, had a shorter turnaround time, and had higher values of IgM and nucleic acid CT. Compared to those with the lowest tertile of IgG, patients with the highest tertile had a 91% lower risk of developing a symptomatic infection after fully adjusting for confounders (OR = 0.09, 95% CI, 0.02-0.36, p = 0.001). There's no robust relationship between IgG level and negative conversion time in multivariate Cox regression. Conclusion: The risk of developing a symptomatic infection can be predicted independently by tertiles of IgG antibodies to wild-type SARS-CoV-2 antigens. High IgG levels can inhibit viral replication, vastly reduce the risk of symptomatic infections and promote a virus-negative conversion, especially when IgG quantitative detection was ≥3.44 S/CO, a potential threshold for protection and booster strategy in the future. More data and research are needed in the future to validate the predictive models.

Quality control for a traditional Chinese medicine, Millettia speciosa Champ, using ultra-high-performance liquid chromatography fingerprint, serum pharmacochemistry and network pharmacology.

Millettia speciosa (M. speciosa) Champ (MSC) is a healthy food type with medicinal and edible homology, which is now considered a clinically significant anti-rheumatoid arthritis medicine. However, there is currently no standardized or generally accepted research strategy by which we can assess M. speciosa. Thus, it is essential to develop novel theories, strategies and evaluation methods for the scientific quality control of M. speciosa. Herein, our use ultra-high-performance liquid chromatography (UPLC)-MS/MS analysis identified 12 common bioactive components absorbed into MSC serum. Next, network pharmacology analysis exhibited that 5 MSC components may be those active components in treating rheumatoid arthritis and may be considered potential quality markers. These 5 components were then quantified using a fast UPLC approach, based on the quality marker of measurability, showing that lenticin can be regarded as the MSC quality marker. The cumulative study findings, based on systematic assessment of chemical composition both in vivo and in vitro, and the potential efficacy of M. speciosa, provide a novel approach for M. speciosa quality control.

A genetically encodable and fluorogenic photo-crosslinker via photo-induced defluorination acyl fluoride exchange.

We report a genetically encodable m-trifluoromethylaniline modified L-lysine (m-TFMAK) which defluorinates upon light activation and covalently conjugates to native residues via acyl fluoride exchange. The encoded m-TFMAK photo-crosslinks with temporal controllability, residue selectivity, and fluorogenic tracking features, making it suitable for identifying protein interactions in living systems.

A Case of Coma Bullae Associated with Brachioradial Artery.

We present the first case of coma bullae observed in a 67-year-old woman due to pressure and ischemia associated with brachioradial artery. A skin biopsy taken from the ulcer border revealed extensive loss of the epidermis, fibrosis of dermis, mild infiltration by lymphocytes and neutrophils, and necrosis of the focal eccrine ducts. CT angiography of the right upper limb showed a high origin of the radial artery, meanwhile both high originating radial artery and the anastomoses were tortuous and were of relatively small caliber. The diagnosis of coma bullae was made. After tissue debridement, the skin lesions gradually recovered, leaving atrophic scars.

Cardiovascular involvement in Epstein-Barr virus infection.

Cardiovascular involvement is an uncommon but severe complication of Epstein-Barr virus (EBV) infection caused by direct damage and immune injury. Recently, it has drawn increasing attention due to its dismal prognosis. It can manifest in various ways, including coronary artery dilation (CAD), coronary artery aneurysm (CAA), myocarditis, arrhythmias, and heart failure, among others. If not treated promptly, cardiovascular damage can progress over time and even lead to death, which poses a challenge to clinicians. Early diagnosis and treatment can improve the prognosis and reduce mortality. However, there is a lack of reliable large-scale data and evidence-based guidance for the management of cardiovascular damage. Consequently, in this review, we attempt to synthesize the present knowledge of cardiovascular damage associated with EBV and to provide an overview of the pathogenesis, classification, treatment, and prognosis, which may enhance the recognition of cardiovascular complications related to EBV and may be valuable to their clinical management.

miR-146a-5p Modulates Adult Hippocampal Neurogenesis Deficits Through Klf4/p-Stat3 Signaling in APP/PS1 Mice.

Alzheimer's disease (AD) is the most common neurodegenerative disease, and currently, no effective treatment strategies exist for this condition. MicroRNAs (miRNAs) have emerged as promising therapeutic targets of AD. Previous studies have highlighted the significant role of miR-146a-5p in regulating adult hippocampal neurogenesis (AHN). Here, we aimed to investigate whether miR-146a-5p plays a role in the mechanisms of AD. We employed quantitative real-time PCR (qRT-PCR) to assess the expression of miR-146a-5p. Additionally, we examined the expression of Krüppel-like factor 4 (Klf4), Signal transducer and activator of transcription 3 (Stat3), and phosphorylated Stat3 (p-Stat3) using western blot analysis. Furthermore, we validated the interaction between miR-146a-5p and Klf4 using a dual-luciferase reporter assay. Immunofluorescence staining was employed to evaluate AHN. And Contextual fear conditioning discrimination learning (CFC-DL) experiment was used to detect pattern separation. Our findings in the hippocampus of APP/PS1 mice revealed upregulated levels of miR-146a-5p and p-Stat3, while Klf4 levels were downregulated. Interestingly, both miR-146a-5p antagomir and p-Stat3 inhibitor obviously rescued neurogenesis and pattern separation in APP/PS1 mice. Moreover, application of miR-146a-5p agomir reversed the protective effects of Klf4 upregulation. These findings open new avenues for protection against AD through the modulation of neurogenesis and cognitive decline via the miR-146a-5p/Klf4/p-Stat3 pathway.

Natural Variation Confers 'Aiyuan 38' Citrus Mutant a New Color and Unique Flavor.

Citrus exhibits unique nutritional values. Most citrus cultivars are derived from mutations. However, the effect of these mutations on fruit quality is unclear. We have previously found a yellowish bud mutant in the citrus cultivar 'Aiyuan 38'. Therefore, this study aimed to determine the effect of the mutation on fruit quality. 'Aiyuan 38' (WT) and a bud mutant variant (MT) were used to analyze variations in fruit color variation and flavor substances using colorimetric instruments, high-performance liquid chromatography (HPLC), headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS), and odor activity values (OAVs). The mutation in MT conferred yellowish characteristics to its peel. Although the differences in total sugar and acid content of the pulp were not statistically significant between WT and MT, the MT glucose content was significantly lower and the malic acid level was significantly higher. HS-SPME-GC-MS analysis revealed that the MT pulp released more types and contents of volatile organic compounds (VOCs) than the WT, whereas the opposite trend was observed for the peel. Analysis of the OAV revealed that the MT pulp contains 6 unique VOCs, whereas the peel contains only 1. This study provides a useful reference for the study of flavor substances associated with citrus bud mutations.

Integrating metabonomics and metagenomics sequencing to study the anti-liver fibrosis effects of palmatine in Corydalis saxicola Bunting.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis saxicola Bunting (CS), a traditional Chinese folk medicine, has been effectively used for treating liver disease in Zhuang nationality in South China. However, the main anti-liver fibrosis ingredients in CS are incompletely understood. AIM OF THE STUDY: To elucidate the main anti-liver fibrosis ingredients in CS and its underlying mechanism. MATERIAL AND METHODS: Firstly, spectrum-effect relationship (SER) strategy was applied to identify the major ingredients against liver fibrosis in CS. Subsequently, 1H NMR metabonomics and metagenomics sequencing techniques were used to clarify the intervention of palmatine (PAL) on liver fibrosis. Furthermore, the expression of tight junction proteins and the levels of liver inflammation factors were examined, the effect of PAL on microbiota was verified by FMT. RESULTS: The SER model revealed that PAL was the most important active ingredient in CS. 1H NMR fecal metabonomics showed that PAL could reserve the abnormal levels of gut microbial-mediated metabolites of liver fibrosis, such as isoleucine, taurine, butyrate, propionate, lactate, glucose, which mainly involved in amino acid metabolism, intestinal flora metabolism and energy metabolism. Metagenomics sequencing found that PAL could callback the abundance of s__Lactobacillus_murinus, s__Lactobacillus_reuteri, s__Lactobacillus_johnsonii, s__Lactobacillus_acidophilus and s__Faecalibaculum_rodentium to varying degree. Furthermore, the intestinal barrier function and the levels of hepatic inflammation factors were significantly ameliorated by PAL. FMT demonstrated that the therapeutic efficiency of PAL was closely associated with gut microbiota. CONCLUSION: The effects of CS on liver fibrosis were attributed in part to PAL by alleviating metabolic disorders and rebalancing gut microbiota. The SER strategy may be a useful method for the discovery of active constituents in natural plants.

Multi-disturbance identification from mine wind-velocity data based on MSSW and WPT-GBDT.

To overcome the false alarm problem that arises for mine wind-velocity sensors due to air-door and mine-car operation, a wind-velocity disturbance identification method based on the wavelet packet transform and gradient lifting decision tree is proposed. In this method, a multi-scale sliding window discretizes continuous wind-velocity monitoring data, the wavelet packet transform extracts the hidden features of discrete data, and a gradient lifting decision tree multi-disturbance classification model is established. Based on the overlap degree rule, the disturbance identification results are merged, modified, combined, and optimized. In accordance with a least absolute shrinkage and selection operator regression, the air-door operation information is further extracted. A similarity experiment is performed to verify the method performance. For the disturbance identification task, the recognition accuracy, accuracy, and recall of the proposed method are 94.58%, 95.70% and 92.99%, respectively, and for the task involving further extraction of disturbance information related to air-door operation, those values are 72.36%, 73.08%, and 71.02%, respectively. This algorithm gives a new recognition method for abnormal time series data.

Photo-induced defluorination acyl fluoride exchange as a fluorogenic photo-click reaction for photo-affinity labeling.

Photo-click chemistry has emerged as a powerful tool for revolutionizing bioconjugation technologies in pharmacological and various biomimetic applications. However, enriching the photo-click reactions to expand the bioconjugation toolkit remains challenging, especially when focusing on spatiotemporal control endowed by light activation. Herein, we describe a photo-induced defluorination acyl fluoride exchange (photo-DAFEx) as a novel type of photo-click reaction that is mediated through acyl fluorides produced by the photo-defluorination of m-trifluoromethylaniline to covalently conjugate with primary/secondary amines and thiols in an aqueous environment. (TD)-DFT calculations, together with experimental discovery, indicate that the m-NH2PhF2C(sp3)-F bond in the excited triplet state is cleaved by water molecules, which is key to inducing defluorination. Intriguingly, the benzoyl amide linkages built by this photo-click reaction exhibited a satisfactory fluorogenic performance, which allowed visualization of its formation in situ. Accordingly, this photo-controlled covalent strategy was exploited not only for the decoration of small molecules, peptide cyclization and functionalization of proteins in vitro, but also for designing photo-affinity probes targeting endogenous carbonic anhydrase II (hCA-II) in living cells.

Discovery of pterostilbene analogs as novel NLRP3 inflammasome inhibitors for potential treatment of DSS-induced colitis in mice.

The pterostilbene skeleton is a promising chemical scaffold that exerts anti-inflammatory, anti-depressant, and anti-tumor effects. In this study, we aim to reduce in vivo and in vitro toxicity of compound 32 (preliminary work) and maintain its biological activity. A series of novel pterostilbene derivatives (D1-D43) were designed and synthesized, and their anti-inflammatory activities were screened. All compounds were screened to evaluate their inhibitory effect on LPS/Nigericin-induced IL-1ß production and pyroptosis. The structure-activity relationships was deduced, and finally 1-((E)-4-(2-ethoxyethoxy)styryl)-3,5-dimethoxy-2-((E)-2-nitrovinyl)benzene (D22) was found to be a low-toxic compound with most potent inhibitory efficacy (against IL-1ß: IC50 = 2.41 µM). Preliminary mechanism studies showed that compound D22 may affect the assembly of NLRP3 inflammasome by targeting NLRP3 protein, thereby inhibiting the activation of NLRP3 inflammasome. The in vivo anti-inflammatory activity indicated that compound D22 had significant therapeutic effects on DSS-induced mouse acute colitis models.

Improved detection of homologous recombination deficiency in Chinese patients with ovarian cancer: a novel non-exonic single-nucleotide polymorphism-based next-generation sequencing panel.

As homologous recombination deficiency (HRD) is a biomarker to predict the efficiency of PARP inhibitor treatment, this study developed a non-exonic single-nucleotide polymorphism (SNP)-based targeted next-generation sequencing panel and comprehensively examined it both on standard and clinical ovarian cancer tissues. The HRD scores calculated by the panel and whole-genome sequencing were consistent, with the analysis by sequenza being the most reliable. The results on clinical samples revealed that the panel performed better in HRD analysis compared with the SNP microarray. There are several distinctions between this newly developed kit and reported HRD detection panels. First, the panel covers only 52 592 SNPs, which makes it capable of detecting genomic instability. Secondly, all the SNPs are non-exonic; as a result, the panel can be used cooperatively with any exon panel. Thirdly, all the SNPs selected have a high minor allele frequency in Chinese people, making it a better choice for HRD detection in Chinese patients. In summary, this panel shows promise as a clinical application to guide PARP inhibitors or platinum drugs used in the treatment of ovarian and other cancers.