The Initial COVID-19 Reliable Interactive DNA Methylation Markers and Biological Implications.

Earlier research has established the existence of reliable interactive genomic biomarkers. However, reliable DNA methylation biomarkers, not to mention interactivity, have yet to be identified at the epigenetic level. This study, drawing from 865,859 methylation sites, discovered two miniature sets of Infinium MethylationEPIC sites, each having eight CpG sites (genes) to interact with each other and disease subtypes. They led to the nearly perfect (96.87-100% accuracy) prediction of COVID-19 patients from patients with other diseases or healthy controls. These CpG sites can jointly explain some post-COVID-19-related conditions. These CpG sites and the optimally performing genomic biomarkers reported in the literature become potential druggable targets. Among these CpG sites, cg16785077 (gene MX1), cg25932713 (gene PARP9), and cg22930808 (gene PARP9) at DNA methylation levels indicate that the initial SARS-CoV-2 virus may be better treated as a transcribed viral DNA into RNA virus, i.e., not as an RNA virus that has concerned scientists in the field. Such a discovery can significantly change the scientific thinking and knowledge of viruses.

Development of a selective electrochemical microsensor based on molecularly imprinted polydopamine/ZIF-67/laser-induced graphene for point-of-care determination of 3-nitrotyrosine.

3-nitrotyrosine (3-NT) is a biomarker closely associated with the early diagnosis of oxidative stress-related disorders. The development of an accurate, cost-effective, point-of-care 3-NT sensor holds significant importance for self-monitoring and clinical treatment. In this study, a selective, sensitive, and portable molecularly imprinted electrochemical sensor was developed. ZIF-67 with strong adsorption capacity was facilely modified on an electrochemically active laser-induced graphene (LIG) substrate (formed ZIF-67/LIG). Subsequently, biocompatible dopamine was chosen as the functional monomer, and interference-free ʟ-tyrosine was used as the dummy template to create molecularly imprinted polydopamine (MIPDA) on the ZIF-67/LIG, endowing the sensor with selectivity. The morphologies, electrochemical properties, and detection performance of the sensor were comprehensively investigated using scanning electron microscopy, cyclic voltammetry, electrochemical impedance spectroscopy, and differential pulse voltammetry. To achieve the best performance, several parameters were optimized, including the number of polymerization cycles (15), elution time (60 min), incubation time (7 min), and pH of the buffer solution (6). The turnaround time for this sensor is 10 min. Benefiting from the alliance of MIPDA, ZIF-67, and LIG, the sensor exhibited excellent sensitivity with a detection limit of 6.71 nM, and distinguished selectivity against 11 interfering substances. To enable convenient clinical diagnosis, a customized electrochemical microsensor with MIPDA/ZIF-67/LIG was designed, showcasing excellent reliability and convenience in detecting biological samples without pretreatment. The proposed microsensor will not only facilitate clinical diagnosis and improve patient care, but also provide inspiration for the development of other portable and accurate electrochemical biosensors.

Establishment of the molecular subtypes and a risk model for stomach adenocarcinoma based on genes related to reactive oxygen species.

Background: Oxidative stress promotes the development of stomach adenocarcinoma (STAD) and resistance of STAD patients to chemotherapy. This study developed a risk classification and prognostic model for STAD based on genes related to oxidative stress. Methods: Univariate Cox regression and least absolute shrinkage and selection operator (Lasso) regression analysis were performed using transcriptome data of STAD from The Cancer Genome Atlas (TCGA) and reactive oxygen species (ROS)-related genes from Gene Set Enrichment Analysis (GSEA) website to develop a risk model. Genetic landscape, pathway characteristics and immune characteristics between the two risk groups were assessed to evaluate patients' response to anti-tumor therapy. Further, a nomogram was created to evaluate the clinical outcomes of STAD patients. The mRNA levels of genes were detected by reverse transcription quantitative PCR (RT-qPCR). Results: Two ROS-related molecular subtypes (subtype C1 and C2) were classified, with subtype C2 having unfavorable prognosis, higher immune score, and greater infiltration of macrophages, myeloid-derived suppressor cells (MDSCs), mast cells, regulatory T cells, and C-C chemokine receptor (CCR). Five ROS-related genes (ASCL2, COMP, NOX1, PEG10, and VPREB3) were screened to develop a prognostic model, the robustness of which was validated in TCGA and external cohorts. RT-qPCR analysis showed that ASCL2, COMP, NOX1, and PEG10 were upregulated, while the mRNA level of VPREB3 was downregulated in gastric cancer cells. The risk score showed a negative relation to tumor mutation burden (TMB). Low-risk patients exhibited higher mutation frequencies of TTN, SYNE1, and ARID1A, higher response rate to immunotherapy and were more sensitive to 32 traditional chemotherapeutic drugs, while high-risk patients were sensitive to 13 drugs. Calibration curve and DCA confirmed the accuracy and reliability of the nomogram. Conclusion: These findings provided novel understanding on the mechanism of ROS in STAD. The current study developed a ROS-related signature to help predict the prognosis of patients suffering from STAD and to guide personalized treatment.

Towards precision oncology discovery: four less known genes and their unknown interactions as highest-performed biomarkers for colorectal cancer.

The goal of this study was to use a new interpretable machine-learning framework based on max-logistic competing risk factor models to identify a parsimonious set of differentially expressed genes (DEGs) that play a pivotal role in the development of colorectal cancer (CRC). Transcriptome data from nine public datasets were analyzed, and a new Chinese cohort was collected to validate the findings. The study discovered a set of four critical DEGs - CXCL8, PSMC2, APP, and SLC20A1 - that exhibit the highest accuracy in detecting CRC in diverse populations and ethnicities. Notably, PSMC2 and CXCL8 appear to play a central role in CRC, and CXCL8 alone could potentially serve as an early-stage marker for CRC. This work represents a pioneering effort in applying the max-logistic competing risk factor model to identify critical genes for human malignancies, and the interpretability and reproducibility of the results across diverse populations suggests that the four DEGs identified can provide a comprehensive description of the transcriptomic features of CRC. The practical implications of this research include the potential for personalized risk assessment and precision diagnosis and tailored treatment plans for patients.

Association Between Family Context and Sleep Trajectory in Middle-Aged and Elderly Chinese Adults.

Objective: The study aims to reveal the association between family context and sleep trajectories in middle-aged and elderly Chinese adults. Methods: Subjects (n=7777) aged between 40 and 65 years were selected from the China Family Panel Studies (CFPS). Latent class analysis and the multi-trajectory method were used to identify the family context and sleep trajectories from 2010 to 2018. Multinomial (polytomous) logistic regression was performed to explore the relationship between family context and sleep trajectories. Results: Five family context classes were identified according to family demographic characteristics. Simultaneously, four sleep trajectories were determined based on three sleep-related indexes. Subjects from family that had only sons or multiple-child are liable to shorten or prolong sleep duration and increase midday nap ratios compare with subjects who from family that had one or more daughters, and in future public health prevention and control, more attention could be paid to such families. Conclusion: The study found that family context is associated with sleep trajectories among middle and old Chinese adults. Subjects from families with only girls seemed to have more stable sleep trajectories, while those with one or more boys' families had unstable sleep trajectories. Further interventions would be carried out for sleep disorders, it is necessary to pay more attention to the family context, especially the number and gender of children.

Reconstruction of the Near-Field Electric Field by SNOM Measurement.

Scanning near-field optical microscope (SNOM) with nanoscale spatial resolution has been a powerful tool in studying the plasmonic properties of nano materials/structures. However, the quantification of the SNOM measurement remains a major challenge in the field due to the lack of reliable methodologies. We employed the point-dipole model to describe the tip-surface interaction upon laser illumination and theoretically derived the quantitative relationship between the measured results and the actual near-field electric field strength. Thus, we can experimentally reconstruct the near-field electric field through this theoretically calculated relationship. We also developed an experimental technique together with FEM simulation to get the above relationship experimentally and reconstruct the near-field electric field from the measurement by SNOM.

Incorporation of Th4+ and Sr2+ into Rhabdophane/Monazite by Wet Chemistry: Structure and Phase Stability.

Rhabdophane is an important permeable reactive barrier to enrich radionuclides from groundwater and has been envisaged to host radionuclides in the backend of the nuclear fuel cycle. However, understanding of how An4+ and Sr2+ precipitate into rhabdophane by wet chemistry has not been resolved. In this work, Th4+ and Sr2+ incorporation in the rhabdophane/monazite structure as La1-2xSrxThxPO4·nH2O solid solutions is successfully achieved in the acid solution at 90 °C. Some specific issues such as lattice occupation of Th4+ and Sr2+, precipitation reaction kinetics, and crystal growth affected by starting stoichiometry are discussed in detail, along with investigating the chemical stability of La1-2xSrxThxPO4·nH2O precipitations and associated La1-2xSrxThxPO4 monazite. The results reveal that the excess of Sr2+ appears to be a prevailing factor with a suggested initial Sr: Th ≥ 2 to obtain the stability domain of La1-2xSrxThxPO4·nH2O (x = 0∼ 0.1). A rapid ion removal associated with a nucleation process has been observed within 8 h, and Th4+ can be removed more than 98% after 24 h in 0.01 mol/L solutions. From structural energetics based on density functional theory, the lattice occupation of Th4+ and Sr2+ is energetically favorable in nonhydrated lattice sites of [LaO8], although two-thirds of lattice sites are associated with [LaO8·H2O] hydrated sites. Intriguingly, the crystal transformation from rhabdophane to monazite associated with the transformation from [SrO8] to [SrO9] polyhedra can greatly improve the leaching stability of Sr2+.

Five Critical Gene-Based Biomarkers With Optimal Performance for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most fatal cancers in the world. There is an urgent need to understand the molecular background of HCC to facilitate the identification of biomarkers and discover effective therapeutic targets. Published transcriptomic studies have reported a large number of genes that are individually significant for HCC. However, reliable biomarkers remain to be determined. In this study, built on max-linear competing risk factor models, we developed a machine learning analytical framework to analyze transcriptomic data to identify the most miniature set of differentially expressed genes (DEGs). By analyzing 9 public whole-transcriptome datasets (containing 1184 HCC samples and 672 nontumor controls), we identified 5 critical differentially expressed genes (DEGs) (ie, CCDC107, CXCL12, GIGYF1, GMNN, and IFFO1) between HCC and control samples. The classifiers built on these 5 DEGs reached nearly perfect performance in identification of HCC. The performance of the 5 DEGs was further validated in a US Caucasian cohort that we collected (containing 17 HCC with paired nontumor tissue). The conceptual advance of our work lies in modeling gene-gene interactions and correcting batch effect in the analytic framework. The classifiers built on the 5 DEGs demonstrated clear signature patterns for HCC. The results are interpretable, robust, and reproducible across diverse cohorts/populations with various disease etiologies, indicating the 5 DEGs are intrinsic variables that can describe the overall features of HCC at the genomic level. The analytical framework applied in this study may pave a new way for improving transcriptome profiling analysis of human cancers.

Highly Sensitive Detection of Formaldehyde by Laser-Induced Graphene-Coated Silver Nanoparticles Electrochemical Sensing Electrodes.

Formaldehyde (HCHO) poses a grave threat to human health because of its toxicity, but its accurate, sensitive, and rapid detection in aqueous solutions remains a major challenge. This study proposes a novel electrochemical sensor composed of a graphene-based electrode that is prepared via laser induction technology. The precursor material, polyimide, is modified via the metal ion exchange method, and the detective electrode is coated with graphene and silver nanoparticles. And the special structure of graphene-coated Ag was demonstrated using scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD), Fourier transform infrared (FT-IR), and X-ray photoelectron spectroscopy (XPS) results show that graphene provides more sites for Ag NRs to be exposed and increases the surface area of contact between the solution and the detection object. In addition, differential pulse voltammetry (DPV) analysis exhibits high linearity over the HCHO concentration range from 0.05 to 5 µg/mL, with a detection limit of 0.011 µg/mL (S/N = 3). The Ag NPs in the electrochemical reaction will adsorb the intermediate •CO and •OH, catalyze their combination, and finally convert to CO2 and H2O, respectively. A microdetection device, specially designed for use with commercial micro-workstations, is employed to fully demonstrate the practical application of the electrode, which paves a way for developing formaldehyde electrochemical sensors.

Design of a versatile and selective electrochemical sensor based on dummy molecularly imprinted PEDOT/laser-induced graphene for nitroaromatic explosives detection.

Considering the formidable explosive power and human carcinogenicity of nitroaromatic explosives, the implementation of an accurate and sensitive detection technology is imperative for ensuring public safety and monitoring post-blast environmental contamination. In the present work, a versatile and selective electrochemical sensor based on dummy molecularly imprinted poly (3,4-ethylenedioxythiophene)/laser-induced graphene (MIPEDOT/LIG) was successfully developed and the specific detection of multiple nitroaromatic explosives was realized in the single sensor. The accessible and nontoxic trimesic acid (TMA) and superior 3, 4-ethylenedioxythiophene (EDOT) were selected as the dummy-template and the functional monomer, respectively. The interaction between the functional monomer and the template, and the morphology, electrochemical properties and detection performance of the sensor were comprehensively investigated by ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, scanning electron microscopy, cyclic voltammetry, and differential pulse voltammetry. Benefiting from the alliance of TMA and EDOT, the MIPEDOT/LIG sensor manifested outstanding selectivity and sensitivity for 2,4,6-trinitrotolueen (TNT), 2,4,6-trinitrophenol (TNP), 2,4-dinitrotoluene (DNT), 1,3,5-trinitrobenzene (TNB), 2,4-dinitrophenol (DNP), and 1,3-dinitrobenzene (DNB) (representative nitroaromatic explosives) with limits of determination of 1.95 ppb, 3.06 ppb, 2.49 ppb, 1.67 ppb, 1.94 ppb, and 4.56 ppb, respectively. The sensor also exhibited extraordinary reliability and convenience for environmental sample detection. Therefore, a perfect combination of versatility and selectivity in the MIPEDOT/LIG sensor was achieved. The findings of this work provide a new direction for the development of multi-target electrochemical sensors using a versatile dummy template for explosives detection.

METTL14 promotes the development of diabetic kidney disease by regulating m6A modification of TUG1.

BACKGROUND: Diabetic kidney disease (DKD) is one of the most common diabetic complications. Endoplasmic reticulum stress (ERS) is an important step for renal tubular epithelial cell apoptosis during DKD progression. Herein, the role and regulatory mechanism of METTL14 in ERS during DKD progression were investigated. METHODS: DKD animal and cell models were established by streptozotocin (STZ) and high glucose (HG), respectively. HE and Masson staining were performed to analyze renal lesions in DKD mouse. Cell viability and proliferation were determined by MTT and EdU staining, respectively. HK2 cell apoptosis was analyzed by flow cytometry. TUG1 m6A level was determined by Me-RIP. The interaction between TUG1, LIN28B and MAPK1 was analyzed by RIP and RNA pull-down assays. RESULTS: HG stimulation promoted apoptosis and increased ERS marker proteins (GRP78, CHOP and caspase12) expression in HK2 cells, while these changes were reversed by METTL14 knockdown. METTL14 inhibited TUG1 stability and expression level in an m6A-dependent manner. As expected, TUG1 knockdown abrogated METTL14 knockdown's inhibition on HG-induced HK2 cell apoptosis and ERS. In addition, TUG1 inactivated MAPK1/ERK signaling by binding with LIN28B. And TUG1 overexpression's repression on HG-induced HK2 cell apoptosis and ERS was abrogated by MAPK1 signaling activation. Meanwhile, METTL14 knockdown or TUG1 overexpression protected against STZ-induced renal lesions and renal fibrosis in DKD mouse. CONCLUSION: METTL14 promoted renal tubular epithelial cell apoptosis and ERS by activating MAPK/ERK pathway through m6A modification of TUG1, thereby accelerating DKD progression.

Observation of the Systolic Function of Isolated Right Atria from Guinea Pigs.

Common chronic heart failure (CHF) is characterized by impaired ventricular filling and/or ejection function, which leads to insatiable cardiac output and increased incidence. The decline in cardiac systolic function is a key factor in the pathogenesis of CHF. Systolic function is simply the filling of oxygenated blood in the left ventricle, followed by the blood being pumped throughout the body during a heartbeat. A weak heart and the inability of the left ventricle to contract appropriately as the heart beats indicate poor systolic function. Many traditional herbs have been suggested to strengthen the systolic function of the heart in patients. However, stable and efficient experimental methods for screening compounds that enhance myocardial contractility are still lacking in the process of ethnic medicine research. Here, taking digoxin as an example, a systematic and standardized protocol is provided for screening compounds that enhance myocardial contractility by using isolated right atria from guinea pigs. The results showed that digoxin could markedly enhance the contractility of the right atrium. This systematic and standardized protocol is intended to serve as a methodological reference for screening the active ingredients of ethnic medicines in the treatment of CHF.

A Case of Complete Remission in Proficient Mismatch Repair (pMMR) Advanced Colon Cancer Treated with Sintilimab and XELOX.

Introduction: Colorectal cancer (CRC) is the 3rd most common malignant tumors after breast cancer and lung cancer, accounting for 9.4% of patients. Some patients had distant metastasis at the time of diagnosis without surgery opportunity. It is particularly important to prolong patient survival and improve quality of life. Patient Concerns: A 73-year-old female was admitted with discomfort over 2 months. Enlarged lymph nodes in the left supraclavicular fossa were observed in chest computed tomography (CT). Enhanced abdominal CT showed thickening of the right colon wall with multiple metastatic lymph nodes in the abdomen. Colonoscopy showed ileocecal mass and pathology showed moderately and poorly differentiated adenocarcinoma. Physical examination showed a 2*2 cm lymph node could be touched in the left supraclavicular fossa. The patient was diagnosed advanced colon cancer by the histopathological examination and imaging findings. Actually, it is hardly to resect radically. Intervention: Sintilimab combined with XELOX was initiated. Two period of treatment after initial therapy, laparoscopic radical resection of right colon cancer was performed successfully. Outcomes: After conversion treatment, the enlarged lymph nodes and primary tumor were significantly reduced. The patient was discharged successfully three weeks after surgery. Both specimen and 14 lymph nodes dissected showed no malignancy in pathology. Tumor regression grading (TRG) is 0, which indicate complete regression with no residual tumor cells including lymph nodes. The patient obtained a pathological complete response (pCR). Lessons: The patient achieved a great therapeutic benefit with the above-mentioned chemotherapy in this case. The case provides a potential reference for pMMR CRC patients treating with immune checkpoint inhibitors (ICIs).

Impact of heat on all-cause and cause-specific mortality: A multi-city study in Texas.

BACKGROUND: Studies on the health effects of heat are particularly limited in Texas, a U.S. state in the top 10 highest number of annual heat-related deaths per capita from 2018 to 2020. This study assessed the effects of heat on all-cause and cause-specific mortality in 12 metropolitan statistical areas (MSAs) across Texas from 1990 to 2011. METHODS: First, we determined the heat thresholds for each MSA above which the relation between temperature and mortality is linear. We then conducted a distributed lag non-linear model for each MSA, followed by a random effects meta-analysis to estimate the pooled effects for all MSAs. We repeated this process for each mortality cause and age group to achieve the effect estimates. RESULTS: We found a 1 °C temperature increase above the heat threshold is associated with an increase in the relative risk of all-cause mortality of 0.60% (95%CI [0.39%, 0.82%]) and 1.10% (95%CI [0.65%, 1.56%]) for adults older than 75. For each MSA, the relative risk of mortality for a 1 °C temperature increase above the heat threshold ranges from 0.10% (95%CI [0.09%, 0.10%]) to 1.29% (95%CI [1.26%, 1.32%]). Moreover, elevated temperatures showed a slight decrease in cardiovascular mortality (0.37%, 95%CI [-0.35%, 1.09%]) and respiratory disease (1.97%, 95%CI [-0.11%, 4.08%]), however this effect was not considered statistically significant.. CONCLUSION: Our study found that high temperatures can significantly impact all-cause mortality in Texas, and effect estimates differ by MSA, age group, and cause of death. Our findings generate critical information on the impact of heat on mortality in Texas, providing insights for policymakers on resource allocation and strategic intervention to reduce heat-related health effects.

Genetic Variants of SIRT1 Gene Promoter in Type 2 Diabetes.

Type 2 diabetes (T2D) is a highly heterogeneous and polygenic disease. To date, genetic causes and underlying mechanisms for T2D remain unclear. SIRT1, one member of highly conserved NAD-dependent class III deacetylases, has been implicated in many human diseases. Accumulating evidence indicates that SIRT1 is involved in insulin resistance and impaired pancreatic ß-cell function, the two hallmarks of T2D. Thus, we speculated that altered SIRT1 levels, resulting from the genetic variants within its regulatory region of SIRT1 gene, may contribute to the T2D development. In this study, the SIRT1 gene promoter was genetically analyzed in T2D patients (n = 218) and healthy controls (n = 358). A total of 20 genetic variants, including 7 single-nucleotide polymorphisms (SNPs), were identified. Five heterozygous genetic variants (g.4114-15InsA, g.4801G > A, g.4816G > C, g.4934G > T, and g.4963_64Ins17bp) and one SNP (g.4198A > C (rs35706870)) were identified in T2D patients, but in none of the controls. The frequencies of two SNPs (g.4540A > G (rs3740051) (OR: 1.75, 95% CI: 1.24-2.47, P < 0.001 in dominant genetic model) and g.4821G > T (rs35995735)) (OR: 3.58, 95% CI: 1.94-6.60, P < 0.001 in dominant genetic model) were significantly higher in T2D patients. Further association and haplotype analyses confirmed that these two SNPs were strongly linked, contributing to the T2D (OR: 1.442, 95% CI: 1.080-1.927, P < 0.05). Moreover, most of the genetic variants identified in T2D were disease-specific. Taken together, the genetic variants within SIRT1 gene promoter might contribute to the T2D development by altering SIRT1 levels. Underlying molecular mechanism needs to be further explored.

The Relationship Between Social Capital and Hypertension Among Type 2 Diabetes Mellitus Patients: The Moderating Effect of Depressive Symptoms.

Purpose: This study aimed to evaluate the relationship between social capital (SC) and hypertension among type 2 diabetes mellitus (T2DM) patients, considering the moderation effects of depressive symptoms. Patients and Methods: A total of 1761 Chinese T2DM patients completed measure scales of social capital and epidemiological survey depression scale (CES-D). The Bootstrap methods PROCESS program is employed to test the moderation model. Results: The prevalence of hypertension among T2DM patients was 39.3%. The SC was negatively correlated with the CES-D score (r=-0.18, P<0.01); the SC was also negatively correlated with diastolic blood pressure (r=-0.05, P<0.05); and the CES-D score was positively correlated with systolic blood pressure (r=0.05, P<0.05). Both logistic regression analysis and the Bootstrap method showed that depressive symptoms weakened the protective effect of SC on hypertension, there existed a moderating effect of depressive symptoms on the relationship between SC and hypertension among T2DM patients. Conclusion: Depressive symptoms may be one crucial moderator of the relationship between SC and hypertension in a representative sample of Chinese diabetes patients. The findings indicate that improving SC and mental health may help manage hypertension among T2DM patients.

Long non-coding RNA SNHG15 regulates cardiomyocyte apoptosis after hypoxia/reperfusion injury via modulating miR-188-5p/PTEN axis.

Nowadays the most effective way to cure myocardial infarction (MI) is reperfusion, which inevitably leads to cardiomyocyte apoptosis. In this study, we discussed the functions of SNHG15 in regulating cardiomyocyte apoptosis through the modulation of miR-188-5p/PTEN axis. We examined the links between SNHG15 and miR-188-5p/PTEN in mice with MI. Extensive experiments, measurements and comparisons were performed, including RT-PCR, western blotting, luciferase reporter assay, flow cytometry analysis etc. Through a series of comparisons and analysis, we discovered that SNHG15 could interact with the miR-188-5p/PTEN axis and impact the cellular physiology of cardiomyocyte apoptosis. PTEN was upregulated in hypoxia cells, but this effect was attenuated by miR-188-5p. MiR-188-5p could combine with SNHG15 and PTEN, and form a SNHG15-miR-188-5p-PTEN axis, which regulated the apoptosis of MCs. These results suggest that LncRNA SNHG15 regulates cardiomyocyte apoptosis induced by hypoxia or reperfusion injury through modulating of miR-188-5p/PTEN axis.

A Novel Scoring System in Predicting Prognosis After Adjuvant FOLFOX Chemotherapy in Gastric Cancer.

Purpose: To evaluate the impact of neutrophil-to-lymphocyte ratio (NLR) and preoperative prognostic nutritional index (PNI) on prognosis of gastric cancer (GC) after adjuvant FOLFOX chemotherapy. Materials and Methods: Data on 749 GC patients who received operation after by adjuvant FOLFOX chemotherapy between January 2013 and December 2015 were enrolled in this study, retrospectively. Receiver-operating characteristic curve analysis was employed to assess optimal cutoff thresholds for PNI and NLR. The GC subjects having a low PNI (<52.8) and high NLR (>1.79) received a score of 2. Any variable that met these standards was scored as 1. If none of the two variables met these standards of the patient was assigned a score of 0. Correlation between PNI-NLR score and GC stage was also evaluated. Results: The mean overall survival (OS) and 5-year OS rate for subjects with PNI-NLR = 2 was lower than those of subjects with PNI-NLR = 1, or 0 (40.9% vs. 52.1%, 76.4% [46.0 vs. 61.0], 68.0 months, p ≤ 0.001). In multivariate analyses, the PNI-NLR score (p ≤ 0.001) and WHO grade (p ≤ 0.001) showed potential to independently influence OS. Conclusions: High PNI-NLR scores can independently affect worse prognosis of GC. Thus, it can be utilized to differentiate low risk from high risk subjects.

Genomic Transcriptome Benefits and Potential Harms of COVID-19 Vaccines Indicated from Optimized Genomic Biomarkers.

COVID-19 vaccines can be the tugboats for preventing SARS-CoV-2 infections when they are practical and, more importantly, without adverse effects. However, the reality is that they may result in short-term or long-term impacts on COVID-19-related diseases and even trigger the formation of new variants of SARS-CoV-2. Using published data, we use a set of optimized-performance COVID-19 genomic biomarkers (MND1, CDC6, ZNF282) to study the benefits and adverse effects of the BNT162b2 vaccine. We found that the vaccine lowered the expression values of genes MND1 and CDC6 while heightening the expression values of ZNF282 in individuals who are SARS-CoV-2 naïve, which is expected and satisfies the biological equivalence between the COVID-19 disease and the genomic signature patterns established in the literature. However, we also found that COVID-19-convalescent octogenarians responded reversely. The vaccine heightened the expression values of MND1 and CDC6. In addition, it lowered the expression values of ZNF282. Such adverse effects raise outstanding concerns about whether or not COVID-19-convalescent individuals should take the current vaccine or when they can take it. These findings are new at the genomic level and can provide insights into developing next-generation vaccines, antiviral drugs, and pandemic management guidance.