Deciphering two decades of cellular reprogramming in cancer: A bibliometric analysis of evolving trends and research frontiers.

Recent research has reevaluated the traditional view of cancer's linear progression and recurrence by introducing cellular reprogramming a process in which cancer cells can their state under certain conditions. This change is driven by a combination of genetic and epigenetic factors, with pivotal roles played by key genes, and pathways, notably Wnt and Notch. The complexity of cancer's behavior is further influenced by factors such as the epithelial-mesenchymal transition (EMT) and therapy-induced stress, both of which are significant contributors to cancer recurrence. In this context bibliometric analysis emerges as a crucial tool for evaluating the impacts and trends within scientific literature. Our study utilized bibliometrics to analysis the role of cellular reprogramming oncology over the past two decades, highlighting its potential to improve cancer treatment outcomes. In conducting this analysis, we searched for literature search on cellular reprogramming (CR) in the Web of Science database, covering the years 2002-2022. We employed visualization tools like Citespace, VOSviewer, and Bibliometrix to analyze the collected data resulting in a dataset of 3102 articles. The United States and China emerged as leading contributors to this field, with the University of Texas MD Anderson Cancer Center being the most prolific institution. Menendez was the most influential scholar in this research domain. Cancers was the journal with the most publications on this subject. The most local-cited document was the article titled "Hallmarks of Cancer: The Next Generation". A comprehensive analysis has been conducted based on keywords and cited references. In recent years, the research emphasis has shifted to "extracellular vesicles," "cancer therapy," and "cellular plasticity". Therefore, this analysis uses bibliometrics to chart cutting-edge progress in cancer's cellular reprogramming, aiding experts to quickly understand and innovate in this crucial area.

Toxic mechanisms of nanoplastics exposure at environmental concentrations on juvenile red swamp crayfish (Procambarus clarkii): From multiple perspectives.

Nanoplastics pollution has emerged as a global issue due to its widespread potential toxicity. This study delved in to toxic effects of nanoplastics on juvenile P. clarkii and molecular mechanisms from perspectives of growth, biochemical, histopathological analysis and transcriptome level for the first time. The findings of this study indicated that nanoplastics of different concentrations have varying influence mechanisms on juvenile P. clarkii. Nanoplastics have inhibitory effects on growth of juvenile P. clarkii, can induce oxidative stress. The biochemical analysis and transcriptome results indicated that 10 mg/L nanoplastics can activate the antioxidant defense system and non-specific immune system in juvenile P. clarkii, and affect energy metabolism and oxidative phosphorylation. While 20 mg/L and 40 mg/L have a destructive influence on the immune function in juvenile P. clarkii, leading to lipid peroxidation and oxidative damage, and induce apoptosis, can affect ion transport and osmotic pressure regulation. The findings of this study can offer foundational data for delving further into impacts of nanoplastics on crustaceans and toxicity mechanism.

Inhibition of METTL3 Alleviates NLRP3 Inflammasome Activation via Increasing Ubiquitination of NEK7.

N6-methyladenosine (m6A) modification, installed by METTL3-METTL14 complex, is abundant and critical in eukaryotic mRNA. However, its role in oral mucosal immunity remains ambiguous. Periodontitis is a special but prevalent infectious disease characterized as hyperinflammation of oral mucosa and bone resorption. Here, it is reported that genetic deletion of Mettl3 alleviates periodontal destruction via suppressing NLRP3 inflammasome activation. Mechanistically, the stability of TNFAIP3 (also known as A20) transcript is significantly attenuated upon m6A modification. When silencing METTL3, accumulated TNFAIP3 functioning as a ubiquitin-editing enzyme facilitates the ubiquitination of NEK7 [NIMA (never in mitosis gene a)-related kinase 7], and subsequently impairs NLRP3 inflammasome assembly. Furtherly, Coptisine chloride, a natural small-molecule, is discovered as a novel METTL3 inhibitor and performs therapeutic effect on periodontitis. The study unveils a previously unknown pathogenic mechanism of METTL3-mediated m6A modifications in periodontitis and indicates METTL3 as a potential therapeutic target.

Psychosocial adjustment changes and related factors in young and middle-aged patients with first-episode acute myocardial infarction: a longitudinal study.

AIMS: This study aimed to explore the change trend and group heterogeneity of psychosocial adjustment level and to determine its influencing factors among young and middle-aged patients with first-episode acute myocardial infarction (AMI). METHODS AND RESULTS: The Psychosocial Adjustment Scale of Illness was used to assess the psychosocial adjustment level of the patients at 1, 3, and 6 months after discharge, respectively. Data were analyzed using Pearson correlation analysis, generalized estimating equations, and growth mixed models. A total of 233 patients were included, and their psychosocial adjustment scores at the three-time points were 57.18 ± 15.50, 36.17 ± 15.02, and 24.22 ± 12.98, respectively. The trajectories of changes in patients' psychosocial adjustment levels were divided into three latent categories: moderate adjustment improvement group (72.5%), low adjustment improvement group (16.3%), and persistent maladjustment group (11.2%). Among them, predictors of the persistent maladjustment group included no spouse, low monthly family income per capita, normal body mass index, never smoking, never exercising, combined with hyperlipidemia, low social support, submission coping, and high perceived stress. CONCLUSIONS: The psychosocial adjustment level of young and middle-aged patients with first-episode AMI showed an upward trend within 6 months after discharge, and there was group heterogeneity in the change trajectory of psychosocial adjustment level. It is suggested that a multi-center, large-sample longitudinal study should be carried out in the future, and the time of follow-up investigation should be extended to further clarify the change trajectory and influencing factors of psychosocial adjustment of patients with different subtypes, to provide the theoretical basis for formulating targeted intervention programs.

Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study.

BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

Pro-CRISPR PcrIIC1-associated Cas9 system for enhanced bacterial immunity.

The CRISPR system is an adaptive immune system found in prokaryotes that defends host cells against the invasion of foreign DNA1. As part of the ongoing struggle between phages and the bacterial immune system, the CRISPR system has evolved into various types, each with distinct functionalities2. Type II Cas9 is the most extensively studied of these systems and has diverse subtypes. It remains uncertain whether members of this family can evolve additional mechanisms to counter viral invasions3,4. Here we identify 2,062 complete Cas9 loci, predict the structures of their associated proteins and reveal three structural growth trajectories for type II-C Cas9. We found that novel associated genes (NAGs) tended to be present within the loci of larger II-C Cas9s. Further investigation revealed that CbCas9 from Chryseobacterium species contains a novel ß-REC2 domain, and forms a heterotetrameric complex with an NAG-encoded CRISPR-Cas-system-promoting (pro-CRISPR) protein of II-C Cas9 (PcrIIC1). The CbCas9-PcrIIC1 complex exhibits enhanced DNA binding and cleavage activity, broader compatibility for protospacer adjacent motif sequences, increased tolerance for mismatches and improved anti-phage immunity, compared with stand-alone CbCas9. Overall, our work sheds light on the diversity and 'growth evolutionary' trajectories of II-C Cas9 proteins at the structural level, and identifies many NAGs-such as PcrIIC1, which serves as a pro-CRISPR factor to enhance CRISPR-mediated immunity.

Polymorphism rs2327430 in TCF21 predicts the risk and prognosis of gastric cancer by affecting the binding between TFAP2A and TCF21.

BACKGROUND: Single nuclear polymorphisms (SNPs) have been published to be correlated with multiple diseases. Transcription Factor 21 (TCF21) is a critical transcription factor involved in various types of cancers. However, the association of TCF21 genetic polymorphisms with gastric cancer (GC) susceptibility and prognosis remains unclear. METHODS: A case-control study comprising 890 patients diagnosed with GC and an equal number of cancer-free controls was conducted. After rigorous statistical analysis, molecular experiments were carried out to elucidate the functional significance of the SNPs in the context of GC. RESULTS: TCF21 rs2327430 (OR = 0.78, P = 0.026) provides protection against GC, while rs4896011 (OR = 1.39, P = 0.005) exhibit significant associations with GC risk. Furthermore, patients with the (TC + CC) genotype of rs2327430 demonstrate a relatively favorable prognosis (OR = 0.47, P = 0.012). Mechanistically, chromatin immunoprecipitation assay and luciferase reporter assay revealed that the C allele of rs2327430 disrupts the binding of Transcription Factor AP-2 Alpha (TFAP2A) to the promoter region of TCF21, resulting in increased expression of TCF21 and inhibition of malignant behaviors in GC cells. CONCLUSION: Our findings highlight the significant role of TCF21 SNPs in both the risk and prognosis of GC and provide valuable insights into the underlying molecular mechanisms. Specifically, the disruptive effect of rs2327430 on TCF21 expression and its ability to modulate malignant cell behaviors suggest that rs2327430 may serve as a potential predictive marker for GC risk and prognosis.

Electrophysiological evidence of lexical processing impacted by foreign language reading anxiety.

Extensive studies have been conducted on the impact of foreign language reading anxiety on reading, primarily focusing on pedagogy and behavior but lacking electrophysiological evidence. The current study aimed to investigate the influence of foreign language reading anxiety on reading and its underlying mechanisms. The results revealed a negative correlation between foreign language reading anxiety and foreign language reading performance, irrespective of the native language. Adults with low levels of foreign language reading anxiety (LFLRA) demonstrated a significant difference in early lexical component N170 amplitude between foreign and native languages. However, this effect was not observed in adults with high levels of foreign language reading anxiety (HFLRA). In terms of N170 latency, HFLRA showed a longer N170 for the foreign language compared to the native language. Furthermore, the N170 effects were predominantly localized over the left occipitotemporal electrodes. Regarding N400 latency, a significant difference was found in LFLRA individuals between foreign and native language processing, while HFLRA individuals did not exhibit this difference. These findings suggest that HFLRA individuals experience inefficient lexical processing (such as orthography or semantics) during reading in foreign language.

Association between red blood cell distribution width and the all-cause mortality of patients with aortic stenosis: A retrospective study.

BACKGROUND: It is essential to assess the risk stratification of patients with aortic stenosis (AS). OBJECTIVE: To clarify the predictive value of red blood cell distribution width (RDW) in AS patients using a large cohort from the MIMIC-IV database. METHODS: Restricted cubic spline, the Kaplan-Meier method, and logistic and Cox regression analyses were used to explore the association between RDW and all-cause mortality in AS patients. Multivariate adjustments, propensity score matching and weighting, and subgroup analysis were conducted to exclude confounding factors. Receiver operating characteristic (ROC) and decision curve analysis (DCA) curves were drawn to evaluate the predictive performance of RDW. RESULTS: 1,148 patients with AS were included. Their death risks gradually increased with the elevation of RDW. Multivariate-adjusted 90-day (OR: 2.12; HR: 1.90; p = 0.001) and 1-year (OR: 2.07; HR: 1.97; p < 0.001) all-cause mortalities were significantly higher in patients with RDW≥14.7 %, which remained robust after propensity score matching and subgroup analysis. For AS patients with high RDW, those < 75 years old had higher death risks than those ≥ 75 years old. The area under the ROC curve of RDW were 0.741 and 0.75 at 90-day and 1-year follow-ups, respectively, exhibiting comparable performance to acute physiology score III and outperforming other critical illness scores in predicting the prognosis of AS patients. DCA curves also illustrated that RDW had a wide range of net benefits. CONCLUSIONS: High RDW was independently associated with increased 90-day and 1-year all-cause mortalities of AS patients, with strong predictive capability of prognosis.

Bioinformatics and system biology approaches to determine the connection of SARS-CoV-2 infection and intrahepatic cholangiocarcinoma.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), has infected millions of individuals worldwide, which poses a severe threat to human health. COVID-19 is a systemic ailment affecting various tissues and organs, including the lungs and liver. Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver cancer, and cancer patients are particularly at high risk of SARS-CoV-2 infection. Nonetheless, few studies have investigated the impact of COVID-19 on ICC patients. METHODS: With the methods of systems biology and bioinformatics, this study explored the link between COVID-19 and ICC, and searched for potential therapeutic drugs. RESULTS: This study identified a total of 70 common differentially expressed genes (DEGs) shared by both diseases, shedding light on their shared functionalities. Enrichment analysis pinpointed metabolism and immunity as the primary areas influenced by these common genes. Subsequently, through protein-protein interaction (PPI) network analysis, we identified SCD, ACSL5, ACAT2, HSD17B4, ALDOA, ACSS1, ACADSB, CYP51A1, PSAT1, and HKDC1 as hub genes. Additionally, 44 transcription factors (TFs) and 112 microRNAs (miRNAs) were forecasted to regulate the hub genes. Most importantly, several drug candidates (Periodate-oxidized adenosine, Desipramine, Quercetin, Perfluoroheptanoic acid, Tetrandrine, Pentadecafluorooctanoic acid, Benzo[a]pyrene, SARIN, Dorzolamide, 8-Bromo-cAMP) may prove effective in treating ICC and COVID-19. CONCLUSION: This study is expected to provide valuable references and potential drugs for future research and treatment of COVID-19 and ICC.

Characterization of three novel stem rot pathogens and their antagonistic endophytic bacteria associated with Cistanche deserticola.

Cistanche deserticola is a precious Chinese medicinal material with extremely high health care and medicinal value. In recent years, the frequent occurrence of stem rot has led to reduced or even no harvests of C. deserticola. The unstandardized use of farm chemicals in the prevention and control processes has resulted in excessive chemical residues, threatening the fragile desert ecological environment. Therefore, it is urgent to explore safe and efficient prevention and control technologies. Biocontrol agents, with the advantages of safety and environment-friendliness, would be an important idea. The isolation, screening and identification of pathogens and antagonistic endophytic bacteria are always the primary basis. In this study, three novel pathogens causing C. deserticola stem rot were isolated, identified and pathogenicity tested, namely Fusarium solani CPF1, F. proliferatum CPF2, and F. oxysporum CPF3. For the first time, the endophytic bacteria in C. deserticola were isolated and identified, of which 37 strains were obtained. Through dual culture assay, evaluation experiment and tissue culture verification, a biocontrol candidate strain Bacillus atrophaeus CE6 with outstanding control effect on the stem rot was screened out. In the tissue culture system, CE6 showed excellent control effect against F. solani and F. oxysporum, with the control efficacies reaching 97.2% and 95.8%, respectively, indicating its great potential for application in the production. This study is of great significance for the biocontrol of plant stem rot and improvement of the yield and quality of C. deserticola.

Development and validation of a radiosensitivity model to evaluate radiotherapy benefits in pan-cancer.

Radiotherapy, one of the most fundamental cancer treatments, is confronted with the dilemma of treatment failure due to radioresistance. To predict the radiosensitivity and improve tumor treatment efficiency in pan-cancer, we developed a model called Radiation Intrinsic Sensitivity Evaluation (RISE). The RISE model was built using cell line-based mRNA sequencing data from five tumor types with varying radiation sensitivity. Through four cell-derived datasets, two public tissue-derived cohorts, and one local cohort of 42 nasopharyngeal carcinoma patients, we demonstrated that RISE could effectively predict the level of radiation sensitivity (area under the ROC curve [AUC] from 0.666 to 1 across different datasets). After the verification by the colony formation assay and flow cytometric analysis of apoptosis, our four well-established radioresistant cell models successfully proved higher RISE values in radioresistant cells by RT-qPCR experiments. We also explored the prognostic value of RISE in five independent TCGA cohorts consisting of 1137 patients who received radiation therapy and found that RISE was an independent adverse prognostic factor (pooled multivariate Cox regression hazard ratio [HR]: 1.84, 95% CI 1.39-2.42; p < 0.01). RISE showed a promising ability to evaluate the radiotherapy benefit while predicting the prognosis of cancer patients, enabling clinicians to make individualized radiotherapy strategies in the future and improve the success rate of radiotherapy.

Astrocyte-mediated regulation of BLAWFS1 neurons alleviates risk-assessment deficits in DISC1-N mice.

Assessing and responding to threats is vital in everyday life. Unfortunately, many mental illnesses involve impaired risk assessment, affecting patients, families, and society. The brain processes behind these behaviors are not well understood. We developed a transgenic mouse model (disrupted-in-schizophrenia 1 [DISC1]-N) with a disrupted avoidance response in risky settings. Our study utilized single-nucleus RNA sequencing and path-clamp coupling with real-time RT-PCR to uncover a previously undescribed group of glutamatergic neurons in the basolateral amygdala (BLA) marked by Wolfram syndrome 1 (WFS1) expression, whose activity is modulated by adjacent astrocytes. These neurons in DISC1-N mice exhibited diminished firing ability and impaired communication with the astrocytes. Remarkably, optogenetic activation of these astrocytes reinstated neuronal excitability via D-serine acting on BLAWFS1 neurons' NMDA receptors, leading to improved risk-assessment behavior in the DISC1-N mice. Our findings point to BLA astrocytes as a promising target for treating risk-assessment dysfunctions in mental disorders.

Production of iron-enriched yeast and it's application in the treatment of iron-deficiency anemia.

Iron deficiency anemia (IDA) is one of the most serious forms of malnutrition. Wild type strains of Saccharomyces cerevisiae have higher tolerance to inorganic iron and higher iron conversion and accumulation capacity. The aim of this study was to investigate the effect of S. cerevisiae enriched iron as a potential organic iron supplement on mice with iron deficiency anemia. 60 male Kunming mice (KM mice, with strong adaptability and high reproduction rate, it can be widely used in pharmacology, toxicology, microbiology and other research) were randomly divided into normal control group and iron deficiency diet model group to establish IDA model. After the model was established, IDA mice were randomly divided into 5 groups: normal control group, IDA group, organic iron group (ferrous glycinate), inorganic iron group (ferrous sulfate) and S. cerevisiae enriched iron group. Mice in the experimental group were given different kinds of iron by intragastric administration once a day for 4w. The results showed that S. cerevisiae enriched iron had an effective recovery function, and the body weight and hematological parameters of IDA mice returned to normal levels. The activities of superoxide dismutase, glutathione peroxidase and total antioxidant capacity in serum were increased. In addition, the strain no. F8, able to grow in an iron-rich environment, was more effective in alleviating IDA and improving organ indices with fewer side effects compared to ferrous glycinate and ferrous sulfate groups. This study suggests that the iron-rich strain no. F8 may play an important role in improving IDA mice and may be developed as a new iron supplement.

Epidemiological insights into seasonal, sex­specific and age­related distribution of bacterial pathogens in urinary tract infections.

Urinary tract infections (UTIs) are prevalent and recurrent bacterial infections that affect individuals worldwide, posing a significant burden on healthcare systems. The present study aimed to explore the epidemiology of UTIs, investigating the seasonal, gender-specific and age-related bacterial pathogen distribution to guide clinical diagnosis. Data were retrospectively collected from electronic medical records and laboratory reports of 926 UTIs diagnosed in Fuding Hospital (Fujian University of Traditional Chinese Medicine, Fuding, China). Bacterial isolates were identified using standard microbiological techniques. χ2 tests were performed to assess associations between pathogens and the seasons, sex and age groups. Significant associations were found between bacterial species and seasons. Enterococcus faecium exhibited a substantial prevalence in spring (χ2, 12.824; P=0.005), while Acinetobacter baumannii demonstrated increased prevalence in autumn (χ2, 16.404; P=0.001). Female patients showed a higher incidence of UTIs. Gram-positive bacteria were more prevalent in males, with Staphylococcus aureus showing significant male predominance (χ2, 14.607; P<0.001). E. faecium displayed an age-related increase in prevalence (χ2, 17.775; P<0.001), whereas Escherichia coli tended to be more prevalent in younger patients (χ2, 12.813; P=0.005). These findings highlight the complex nature of UTIs and offer insights for tailored diagnostic and preventive strategies, potentially enhancing healthcare outcomes.

Dynamics of Listeriamonocytogenes and Salmonella enterica on Cooked Vegetables During Storage.

Fresh vegetables have been linked to multiple foodborne outbreaks in the U.S., with Listeria monocytogenes and Salmonella enterica identified as leading causes. Beyond raw vegetables, cooked vegetables can also pose food safety concerns due to improper cooking temperature and time combinations or postcooking contamination. Cooked vegetables, having had their native microbiota reduced through heat inactivation, might provide an environment that favors the growth of pathogens due to diminished microbial competition. While the risks associated with raw vegetables are recognized, the survival and growth of pathogens on cooked vegetables remain inadequately studied. This study investigated the growth kinetics of both L. monocytogenes and S. enterica on various cooked vegetables (carrot, corn, onions, green bell pepper, and potato). Vegetables were cooked at 177°C until the internal temperature reached 90°C and then cooled to 5°C. Cooled vegetables were inoculated with a four-strain cocktail of either L. monocytogenes or S. enterica at 3 log CFU/g, then stored at different temperatures (5, 10, or 25°C) for up to 7 days. Both pathogens survived on all vegetables when stored at 5°C. At 10°C, both pathogens proliferated on all vegetables, with the exception of L. monocytogenes on pepper. At 25°C, the highest growth rates were observed by both pathogens on carrot (5.55 ± 0.22 and 6.42 ± 0.23 log CFU/g/d for L. monocytogenes and S. enterica, respectively). S. enterica displayed higher growth rates at 25°C compared to L. monocytogenes on all vegetables. Overall, these results bridge the knowledge gap concerning the growth kinetics of both S. enterica and L. monocytogenes on various cooked vegetables, offering insights to further enhance food safety.

Charge transport properties and mechanisms of bacterial cellulose (BC)-Zinc complexes.

Most current flexible electronic devices are based on petroleum materials that are difficult to degrade. The exploration of sustainable and eco-friendly materials has become a major focus in both the scientific and industrial communities. In this study, BC-Zn-BIM (bacterial cellulose-Zn-benzimidazole), a novel composite electrode material based on biodegradable BC was developed. Here, BC acted as a conductive medium involved in the conductive behavior of the composite material. We've explored the charge transport mechanisms of BC-Zn-BIM by density functional theory (DFT) calculations, and applied it in the electrochemical detection of Bisphenol A (BPA). The results indicated that the oxygen-containing groups in BC and the nitrogen-containing heterocycles in BIM have a tendency to lose electrons, whereas zinc ions actively acquire electrons from these groups. This process promoted charge transfer within BC-Zn-BIM and endowed it with semiconductor-like properties, enhancing the electrocatalytic reaction of BPA. The detection limit of the electrochemical biosensor was 12 nM, and the sample recovery was 95.1%105.6%. This study clarified the mechanism of the higher electrical properties achieved in Zn-BIM complex grown in-situ on dielectric BC. This will further promote the development of low-cost, environmentally friendly flexible electronic devices.

Intratumoral injection of interferon gamma promotes the efficacy of anti-PD1 treatment in colorectal cancer.

Immune checkpoint inhibitors (ICIs) offer new options for the treatment of patients with solid cancers worldwide. The majority of colorectal cancers (CRC) are proficient in mismatch-repair (pMMR) genes, harboring fewer tumor antigens and are insensitive to ICIs. These tumors are often found to be immune-deserted. We hypothesized that forcing immune cell infiltration into the tumor microenvironment followed by immune ignition by PD1 blockade may initiate a positive immune cycle that can boost antitumor immunity. Bioinformatics using a public database suggested that IFNγ was a key indicator of immune status and prognosis in CRC. Intratumoral administration of IFNγ increased immune cells infiltration into the tumor, but induced PD-L1 expression. A combined treatment strategy using IFNγ and anti-PD-1 antibody significantly increased T cell killing of tumor cells in vitro and showed synergistic inhibition of tumor growth in a mouse model of CRC. CyTOF found drastic changes in the immune microenvironment upon combined immunotherapy. Treatment with IFNγ and anti-PD1 antibody in CT26 tumors significantly increased infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). IFNγ had a more pronounced effect in decreasing intratumoral M2-like macrophages, while PD1 blockade increased the population of CD8+Ly6C + T cells in the tumor microenvironment, creating a more pro-inflammatory microenvironment. Additionally, PD1 induced increased expression of lymphocyte activating 3 (LAG3) in a significant fraction of CD8+ T cells and Treg cells, indicating potential drug resistance and feedback mechanisms. In conclusion, our work provides preclinical data for the Combined immunotherapy of CRC using intratumoral delivery of IFNγ and systemic anti-PD1 monoclonoal antibody.

Identification of MACC1 as a potential biomarker for pulmonary arterial hypertension based on bioinformatics and machine learning.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by abnormal early activation of pulmonary arterial smooth muscle cells (PASMCs), yet the underlying mechanisms remain to be elucidated. METHODS: Normal and PAH gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database and analyzed using gene set enrichment analysis (GSEA) to uncover the underlying mechanisms. Weighted gene co-expression network analysis (WGCNA) and machine learning methods were deployed to further filter hub genes. A number of immune infiltration analysis methods were applied to explore the immune landscape of PAH. Enzyme-linked immunosorbent assay (ELISA) was employed to compare MACC1 levels between PAH and normal subjects. The important role of MACC1 in the progression of PAH was verified through Western blot and real-time qPCR, among others. RESULTS: 39 up-regulated and 7 down-regulated genes were identified by 'limma' and 'RRA' packages. WGCNA and machine learning further narrowed down the list to 4 hub genes, with MACC1 showing strong diagnostic capacity. In vivo and in vitro experiments revealed that MACC1 was highsly associated with malignant features of PASMCs in PAH. CONCLUSIONS: These findings suggest that targeting MACC1 may offer a promising therapeutic strategy for treating PAH, and further clinical studies are warranted to evaluate its efficacy.

Access to colorectal cancer screening in populations in China, 2020: A coverage-focused synthesis analysis.

In populations in China, colorectal cancer (CRC) screening can be mainly accessed through organized screening, opportunistic screening, and physical examination. This screening intervention is found to be effective but the exact coverage rate is difficult to measure. Based on data from published articles, official websites, and available program reports, the screening coverage rate and related indicators were quantified. A rapid review was then conducted to estimate the overall and the breakdown coverage rates of the sub-type screening services, by leveraging the numbers of articles and the by-type median sample sizes. Up to 2020, two central government-funded and four provincial/municipal-level organized CRC screening programs have been initiated and included in this analysis. For populations aged 40-74, the estimated coverage rate of organized programs in China was 2.7% in 2020, and the 2-year cumulative coverage rate in 2019-2020 was 5.3% and the 3-year cumulative coverage rate in 2018-2020 was 7.7%. The corresponding coverage rates of 50-74-year-olds were estimated to be 3.4%, 7.1%, and 10.3%, respectively. Based on the rapid review approach, the overall screening coverage rate for 40-74 years, considering organized screening programs, opportunistic screening, and physical examinations, was then estimated to be 3.0% in China in 2020. However, comparing the findings of this study with the number of health check-ups reported in the local national health statistics yearbooks suggests that the number of CRC physical examinations may be underestimated in this study. The findings suggest that further efforts are needed to improve population access to CRC screening in China. Furthermore, evidence for access to opportunistic CRC screening and physical examination is limited, and more quantitative investigation is needed.