Screening and Analysis of SARS-CoV-2 Antibody Among Unvaccinated Blood Donors in Chongqing, China.

OBJECTIVE: To investigate the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody among unvaccinated voluntary blood donors in Chongqing, and to provide evidence for epidemic surveillance. METHODS: A total of 10,208 voluntary blood donors from January 5 to January 20, 2021, in the Chongqing area were collected, and the SARS-CoV-2 immunoglobulin (Ig) G and IgM antibodies were detected by chemiluminescence, and the differences of antibody-positive rate in different gender, age, ABO blood group, and different risk areas were analyzed. RESULTS: Among 10208 blood donors, 10 were found to be positive for SARS-COV-2 IgG antibody, giving a positivity rate of SARS-COV-2 IgG at 0.10%, and 29 were positive for SARS-CoV-2 IgM antibody, with a positivity rate of SARS-CoV-2 IgM at 0.28%. There was no statistical difference in the positive rate of antibody among different genders, ages, and ABO blood types, but it was related to the number of confirmed coronavirus disease 2019 (COVID-19) cases in each city. CONCLUSIONS: The SARS-CoV-2 seroprevalence rate in Chongqing was low and correlated with the number of confirmed COVID-19 cases.

Tenovin 3 induces apoptosis and ferroptosis in EGFR 19del non small cell lung cancer cells.

Epidermal growth factor receptor (EGFR) exon 19 deletion is a major driver for the drug resistance of non-small cell lung cancer (NSCLC). Identification small inhibitor capable of selectively inhibiting EGFR-19del NSCLC is a desirable strategy to overcome drug resistance in NSCLC. This study aims to screen an inhibitor for EGFR exon 19 deletion cells and explore its underlying mechanism. High through-put screen was conducted to identify an inhibitor for EGFR-19del NSCLC cells. And tenovin-3 was identified as a selective inhibitor of PC9 cells, an EGFR-19del NSCLC cells. Tenovin-3 showed particular inhibition effect on PC9 cells proliferation through inducing apoptosis and ferroptosis. Mechanistically, tenovin-3 might induce the apoptosis and ferroptosis of PC9 cells through mitochondrial pathway, as indicated by the change of VDAC1 and cytochrome c (cyt c). And bioinformatics analyses showed that the expression levels of SLC7A11 and CPX4 were correlated with NSCLC patient's survival. Our findings provide evidences for tenovin-3 to be developed into a novel candidate agent for NSCLC with EGFR exon 19 deletion. Our study also suggests that inducing ferroptosis may be a therapeutic strategy for NSCLC with EGFR exon 19 deletion.

Joint toxicity of cadmium (II) and microplastic leachates on wheat seed germination and seedling growth.

Cadmium (Cd) pollution ranks first in soils (7.0%) and microplastics usually have a significant adsorption capacity for it, which could pose potential threats to agricultural production and human health. However, the joint toxicity of Cd and microplastics on crop growth remains largely unknown. In this study, the toxic effects of Cd2+ and two kinds of microplastic leachates, polyvinyl chloride (PVC) and low-density polyethylene (LDPE), on wheat seed germination and seedlings' growth were explored under single and combined conditions. The results showed that Cd2+ solution and two kinds of microplastic leachates stimulated the wheat seed germination process but inhibited the germination rate by 0-8.6%. The combined treatments promoted wheat seed germination but inhibited the seedlings' growth to different degrees. Specifically, the combination of 2.0 mg L-1 Cd2+ and 1.0 mgC L-1 PVC promoted both seed germination and seedlings' growth, but they synergistically increased the antioxidant enzyme activity of seedlings. The toxicity of the PVC leachate to wheat seedlings was stronger than LDPE leachate. The addition of Cd2+ could alleviate the toxicity of PVC leachate on seedlings, and reduce the toxicity of LDPE leachate on seedlings under the same concentration class combinations but aggravated stress under different concentration classes, consistent with the effect on seedlings' growth. Overall, Cd2+, PVC, and LDPE leachates have toxic effects on wheat growth, whether treated under single or combined treatments. This study has important implications for the joint toxicity of Cd2+ solution and microplastic leachates in agriculture.

Effect of lesion dimension on survival in patients with T1a renal cell carcinoma who underwent deferred surgery.

BACKGROUND: Small renal masses (SRMs) have been shown to have low malignant potential. Active surveillance (AS), typically characterized by regular follow-up and delayed nephrectomy if necessary, is recommended as an option for frail patients with SRMs. Nevertheless, the impact of tumor size on survival in T1a RCC patients undergoing delayed nephrectomy for SRMs remains unclear. METHODS: Patients diagnosed with non-metastatic T1a RCC who underwent nephrectomy were identified from the Surveillance, Epidemiology, and End Results (SEER) database and divided into immediate (< 6 months) and delayed nephrectomy (≥ 6 months) groups based on the duration from diagnosis to nephrectomy. After propensity score matching (PSM), overall survival (OS) and cancer-specific survival (CSS) were estimated by K-M curves and compared with log-rank test. RESULTS: A total of 27,502 patients were enrolled, of whom 26,915 (97.9%) received immediate nephrectomy and 587 (2.1%) received delayed nephrectomy. After PSM, 1174 patients who underwent immediate nephrectomy and 587 patients who underwent delayed nephrectomy were included. With a median delay of 7 months, delayed nephrectomy resulted in non-inferior OS for RCC tumors sized 0.1-2.0 cm (HR = 1.12, p = 0.636). However, for RCC tumors sized 2.1-3.0 cm (HR = 1.60, p = 0.008) and 3.1-4.0 cm (HR = 1.89, p < 0.001), delayed nephrectomy showed inferior OS compared to immediate nephrectomy. Delayed nephrectomy did not result in significantly worse CSS than immediate nephrectomy in all tumor size subgroups (all p > 0.05), however this may be due to sample size limiting statistical power. CONCLUSION: Based on the SEER database, we found that with a median delay of 7 months, 2 cm may be an appropriate cut-off point of delayed nephrectomy for patients diagnosed with non-metastatic T1a RCC.

Gli1-mediated tumor cell-derived bFGF promotes tumor angiogenesis and pericyte coverage in non-small cell lung cancer.

BACKGROUND: Tumor angiogenesis inhibitors have been applied for non-small cell lung cancer (NSCLC) therapy. However, the drug resistance hinders their further development. Intercellular crosstalk between lung cancer cells and vascular cells was crucial for anti-angiogenenic resistance (AAD). However, the understanding of this crosstalk is still rudimentary. Our previous study showed that Glioma-associated oncogene 1 (Gli1) is a driver of NSCLC metastasis, but its role in lung cancer cell-vascular cell crosstalk remains unclear. METHODS: Conditioned medium (CM) from Gli1-overexpressing or Gli1-knockdown NSCLC cells was used to educate endothelia cells and pericytes, and the effects of these media on angiogenesis and the maturation of new blood vessels were evaluated via wound healing assays, Transwell migration and invasion assays, tube formation assays and 3D coculture assays. The xenograft model was conducted to establish the effect of Gli1 on tumor angiogenesis and growth. Angiogenic antibody microarray analysis, ELISA, luciferase reporte, chromatin immunoprecipitation (ChIP), bFGF protein stability and ubiquitination assay were performed to explore how Gli1 regulate bFGF expression. RESULTS: Gli1 overexpression in NSCLC cells enhanced the endothelial cell and pericyte motility required for angiogenesis required for angiogenesis. However, Gli1 knockout in NSCLC cells had opposite effect on this process. bFGF was critical for the enhancement effect on tumor angiogenesis. bFGF treatment reversed the Gli1 knockdown-mediated inhibition of angiogenesis. Mechanistically, Gli1 increased the bFGF protein level by promoting bFGF transcriptional activity and protein stability. Importantly, suppressing Gli1 with GANT-61 obviously inhibited angiogenesis. CONCLUSION: The Gli1-bFGF axis is crucial for the crosstalk between lung cancer cells and vascular cells. Targeting Gli1 is a potential therapeutic approach for NSCLC angiogenesis.

MRPS9-Mediated Regulation of the PI3K/Akt/mTOR Pathway Inhibits Neuron Apoptosis and Protects Ischemic Stroke.

Neuronal apoptosis is crucial in the pathophysiology of ischemic stroke (IS), albeit its underly24ing mechanism remaining elusive. Investigating the mechanism of neuronal apoptosis in the context of IS holds substantial clinical value for enhancing the prognosis of IS patients. Notably, the MRPS9 gene plays a pivotal role in regulating mitochondrial function and maintaining structural integrity. Utilizing bioinformatic tactics and the extant gene expression data related to IS, we conducted differential analysis and weighted correlation network analysis (WGCNA) to select important modules. Subsequent gene interaction analysis via the STRING website facilitated the identification of the key gene-mitochondrial ribosomal protein S9 (MRPS9)-that affects the progression of IS. Moreover, possible downstream signaling pathways, namely PI3K/Akt/mTOR, were elucidated via Kyoto Encyclopedia of Gene and Genomes (KEGG) and Gene Ontology (GO) pathway analysis. Experimental models were established utilizing oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro and middle cerebral artery occlusion/reperfusion (MCAO/R) in mice. Changes in gene and protein expression, as well as cell proliferation and apoptosis, were monitored through qPCR, WB, CCK8, and flow cytometry. An OGD/R cell model was further employed to investigate the role of MRPS9 in IS post transfusion of MRPS9 overexpression plasmids into cells. Further studies were conducted by transfecting overexpressed cells with PI3K/Akt/mTOR signaling pathway inhibitor LY294002 to unveil the mechanism of MRPS9 in IS. Bioinformatic analysis revealed a significant underexpression of MRPS9 in ischemic stroke patients. Correspondingly, in vitro experiments with HN cells subjected to OGD/R treatment demonstrated a marked reduction in MRPS9 expression, accompanied by a decline in cell viability, and an increase cell apoptosis. Notably, the overexpression of MRPS9 mitigated the OGD/R-induced decrease in cell viability and augmentation of apoptosis. In animal models, MRPS9 expression was significantly lower in the MCAO/R group compared to the sham surgery group. Further, the KEGG pathway analysis associated MRPS9 expression with the PI3K/Akt/mTOR signaling pathway. In cells treated with the specific PI3K/Akt/mTOR inhibitor LY294002, phosphorylation levels of Akt and mTOR were decreased, cell viability decreased, and apoptosis increased compared to the MRPS9 overexpression group. These findings collectively indicate that MRPS9 overexpression inhibits PI3K/Akt/mTOR pathway activation, thereby protecting neurons from apoptosis and impeding IS progression. However, the PI3K/Akt/mTOR inhibitor LY294002 is capable of counteracting the protective effect of MRPS9 overexpression on neuronal apoptosis and IS. Our observations underscore the potential protective role of MRPS9 in modulating neuronal apoptosis and in attenuating the pathophysiological developments associated with IS. This is achieved through the regulation of the PI3K/Akt/mTOR pathway. These insights forge new perspectives and propose novel targets for the strategic diagnosis and treatment of IS.

The effect of miR-223-3p on endothelial cells in coronary artery disease.

Endothelial cell damage and dysfunction are crucial factors in the development and early stages of coronary artery disease (CAD) and apoptosis plays a significant role in this process. In this study, We aimed to simulate the CAD vascular microenvironment by treating endothelial cells with tumor necrosis factor alpha (TNF-α) to construct an endothelial cell apoptosis model. Our findings revealed that the TNF-α model resulted in increased micro-RNA 223-3p (miR-223-3p) mRNA and Bax protein expression, decreased kruppel-like factor 15 (KLF15) and Bcl-2 protein expression, and decreased cell viability. More importantly, in the TNF-α-induced endothelial cell apoptosis model, transfection with the miR-223-3p inhibitor reversed the effects of TNF-α on Bcl-2, Bax expression. We transfected miRNA-223-3p mimics or inhibitors into endothelial cells and assessed miR-223-3p levels using RT-PCR. Cell viability was detected using CCK8. Western blot technology was used to detect the expression of Bcl-2, Bax, and KLF15. In summary, this study demonstrates the role and possible mechanism of miR-223-3p in endothelial cells during CAD, suggesting that miR-223-3p may serve as a promising therapeutic target in CAD by regulating KLF15.

JAM-C Is Important for Lens Epithelial Cell Proliferation and Lens Fiber Maturation in Murine Lens Development.

Purpose: The underlying mechanism of congenital cataracts caused by deficiency or mutation of junctional adhesion molecule C (JAM-C) gene remains unclear. Our study aims to elucidate the abnormal developmental process in Jamc-/- lenses and reveal the genes related to lens development that JAM-C may regulate. Methods: Jamc knockout (Jamc-/-) mouse embryos and pups were generated for in vivo studies. Four key developmental stages from embryonic day (E) 12.5 to postnatal day (P) 0.5 were selected for the following experiments. Hematoxylin and eosin staining was used for histological analysis. The 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and TUNEL staining were performed to label lens epithelial cell (LEC) proliferation and apoptosis, respectively. Immunofluorescence and Western blot were used to analyze the markers of lens epithelium, cell cycle exit, and lens fiber differentiation. Results: JAM-C was expressed throughout the process of lens development. Deletion of Jamc resulted in decreased lens size and disorganized lens fibers, which arose from E16.5 and aggravated gradually. The LECs of Jamc-/- lenses showed decreased quantity and proliferation, accompanied with reduction of key transcription factor, FOXE3. The fibers in Jamc-/- lenses were disorganized. Moreover, Jamc-deficient lens fibers showed significantly altered distribution patterns of Cx46 and Cx50. The marker of fiber homeostasis, γ-crystallin, was also decreased in the inner cortex and core fibers of Jamc-/- lenses. Conclusions: Deletion of JAM-C exhibits malfunction of LEC proliferation and fiber maturation during murine lens development, which may be related to the downregulation of FOXE3 expression and abnormal localization patterns of Cx46 and Cx50.

VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway.

Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.

A First-Class Degrader Candidate Targeting Both KRAS G12D and G12V Mediated by CANDDY Technology Independent of Ubiquitination.

"Undruggable" targets such as KRAS are particularly challenging in the development of drugs. We devised a novel chemical knockdown strategy, CANDDY (Chemical knockdown with Affinity aNd Degradation DYnamics) technology, which promotes protein degradation using small molecules (CANDDY molecules) that are conjugated to a degradation tag (CANDDY tag) modified from proteasome inhibitors. We demonstrated that CANDDY tags allowed for direct proteasomal target degradation independent of ubiquitination. We synthesized a KRAS-degrading CANDDY molecule, TUS-007, which induced degradation in KRAS mutants (G12D and G12V) and wild-type KRAS. We confirmed the tumor suppression effect of TUS-007 in subcutaneous xenograft models of human colon cells (KRAS G12V) with intraperitoneal administrations and in orthotopic xenograft models of human pancreatic cells (KRAS G12D) with oral administrations. Thus, CANDDY technology has the potential to therapeutically target previously undruggable proteins, providing a simpler and more practical drug targeting approach and avoiding the difficulties in matchmaking between the E3 enzyme and the target.

Alterations of large-scale functional network connectivity in patients with infantile esotropia before and after surgery.

BACKGROUND: Growing evidences have indicated neurodevelopmental disorders in infantile esotropia (IE). However, few studies have analyzed the characteristics of large-scale functional networks of IE patients or their postoperative network-level alterations. METHODS: Here, individuals with IE (n = 32) and healthy subjects (n = 30) accomplished the baseline clinical examinations and resting-state MRI scans. A total of 17 IE patients also underwent corrective surgeries and completed the longitudinal clinical assessments and resting-state MRI scans. Linear mixed effects models were applied for cross-sectional and longitudinal network-level analyses. Correlation analysis was performed to assess the relationship between longitudinal functional connectivity (FC) alterations and baseline clinical variables. RESULTS: In cross-sectional analyses, network-level FC were apparently aberrant in IE patients compared to controls. In longitudinal analyses, intra- and internetwork connectivity were observed with significant alterations in postoperative IE patients compared to the preoperative counterparts. Longitudinal FC changes are negatively correlated to the age at surgery in IE. CONCLUSIONS: Obviously, altered network-level FC benefiting from the corrective surgery serves as the neurobiological substrate of the observed improvement of stereovision, visuomotor coordination, and emotional management in postoperative IE patients. Corrective surgery should be performed as early as possible to obtain more benefits for IE in brain function recovery.

Transcriptomic analysis reveals the potential biological mechanism of AIS and lung adenocarcinoma.

Introduction: Acute ischemic stroke (AIS) and lung adenocarcinoma (LUAD) are associated with some of the highest morbidity and mortality rates worldwide. Despite reports on their strong correlation, the causal relationship is not fully understood. The study aimed to identify and annotate the biological functions of hub genes with clinical diagnostic efficacy in AIS and LUAD. Methods: Transcriptome and single-cell datasets were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We identified the differentially expressed genes (DEGs) upregulated in AIS and LUAD and found 372 genes intersecting both datasets. Hub genes were identified using protein-protein interaction (PPI) networks, and the diagnostic and prognostic utility of these hub genes was then investigated using receiver operating characteristic (ROC) curves, survival analysis, and univariable Cox proportional hazard regression. Single-cell analysis was used to detect whether the hub genes were expressed in tumor epithelial cells. The immune microenvironment of AIS and LUAD was assessed using the CIBERSORT algorithm. The protein expression of these hub genes was tracked using the Human Protein Atlas (HPA). We calculated the number of positive cells using the digital pathology software QuPath. Finally, we performed molecular docking after using the Enrichr database to predict possible medicines. Results: We identified the molecular mechanisms underlying hub genes in AIS and LUAD and found that CCNA2, CCNB1, CDKN2A, and CDK1 were highly expressed in AIS and LUAD tissue samples compared to controls. The hub genes were mainly involved in the following pathways: the cell cycle, cellular senescence, and the HIF-1 signaling pathway. Using immunohistochemical slices from the HPA database, we confirmed that these hub genes have a high diagnostic capability for AIS and LUAD. Further, their high expression is associated with poor prognosis. Finally, curcumin was tested as a potential medication using molecular docking modeling. Discussion: Our findings suggest that the hub genes we found in this study contribute to the development and progression of AIS and LUAD by altering the cellular senescence pathway. Thus, they may be promising markers for diagnosis and prognosis.

Silencing of LAMC2 Reverses Epithelial Mesenchymal Transition and Inhibits Progression in Pancreatic Ductal Adenocarcinoma via Inactivation of the NF-κB Signaling Pathway.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult to treat of all malignancies. Multimodality regimens provide only short-term symptomatic improvement with minor impact on survival, underscoring the urgent need for novel therapeutics and treatment strategies for PDAC. We screened out the highly expressed gene LAMC2 in PDAC tissues through the GEO online database, and further demonstrated that it is related to the poor prognosis of PDAC patients. Next, we investigated the effect of LAMC2 in the development and metastasis of PDAC by silencing LAMC2 expression in PDAC cells. The results showed that silencing of LAMC2 inhibited the proliferation, invasion and metastasis, and promoted apoptosis of PDAC cells, silencing of LAMC2 also reversed the epithelial mesenchymal transition (EMT) and suppressed the activation of NF-κB signaling pathway. Our results identify LAMC2 as a pivotal regulator of PDAC malignant progression, and its overexpression is sufficient to confer the characteristically aggressive clinical features of this disease.

Risk assessment based on dose-responsive and time-responsive genes to build PLS-DA models for exogenously induced lung injury.

Xenobiotics can easily harm human lungs owing to the openness of the respiratory system. Identifying pulmonary toxicity remains challenging owing to several reasons: 1) no biomarkers for pulmonary toxicity are available that might help to detect lung injury; 2) traditional animal experiments are time-consuming; 3) traditional detection methods solely focus on poisoning accidents; 4) analytical chemistry methods hardly achieve universal detection. An in vitro testing system able to identify the pulmonary toxicity of contaminants from food, the environment, and drugs is urgently needed. Compounds are virtually infinite, whereas toxicological mechanisms are countable. Therefore, universal methods to identify and predict the risks of contaminants can be designed based on these well-known toxicity mechanisms. In this study, we established a dataset based on transcriptome sequencing of A549 cells upon treatment with different compounds. The representativeness of our dataset was analyzed using bioinformatics methods. Artificial intelligence methods, namely partial least squares discriminant analysis (PLS-DA) models, were employed for toxicity prediction and toxicant identification. The developed model predicted the pulmonary toxicity of compounds with a 92 % accuracy. These models were submitted to an external validation using highly heterogeneous compounds, which supported the accuracy and robustness of our developed methodology. This assay exhibits universal potential applications for water quality monitoring, crop pollution detection, food and drug safety evaluation, as well as chemical warfare agent detection.

Effect of serum progesterone on human chorionic gonadotropin trigger day / metaphase II oocyte ratio on pregnancy and neonatal outcomes in women undergoing ICSI cycle.

BACKGROUND: The serum progesterone on human chorionic gonadotropin trigger day / metaphase II oocyte (P/MII) ratio might be a more predictable indicator of pregnancy and neonatal outcomes as compare to P/estradiol (E2) or P alone. Hence, we conducted a larger population study to compare the pregnancy and neonatal outcomes in the low and high P/MII ratio. METHODS: A retrospective, single-center, larger population cohort study between January 2015 and August 2021. Calculate the threshold effect of P/MII ratio on clinical pregnancy rate according to the construct smooth curve fitting. Divide data into two groups by threshold for comparison. RESULTS: 3566 fresh ICSI-ET cycles were included, in which 929 singleton delivery and 676 twin deliveries. Compare to P/MII ≤ 0.367 group, it indicated that the P/MII > 0.367 group had a lower clinical pregnancy rate and live birth rate, furthermore, a significantly higher rate of LBW and SGA were observed in the singleton and twin deliveries. No deleterious impact of high P/MII ratio on embryo quality and undesirable pregnancy outcomes was shown. CONCLUSIONS: When P/MII is higher than 0.367, may have adverse impacts on pregnancy and neonatal outcomes for ICSI cycle.

Identification of the MMP family as therapeutic targets and prognostic biomarkers in the microenvironment of head and neck squamous cell carcinoma.

BACKGROUND: Head and Neck Squamous Cell Carcinoma is a malignant tumor with high morbidity and mortality. The MMP family plays an important role in tumor invasion and metastasis. However, the mechanistic value of the MMP family as a therapeutic target and prognostic biomarker in HNSC has not been fully elucidated. METHODS: Oncomine, UALCAN, GEPIA, cBioportal, GeneMANIA, STRING, DAVID6.8, TRRUST, TIMER and Linkedomics were used for analysis. RESULTS: The mRNA expression levels of MMP1, MMP3, ILF3, MMP7, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16 were higher in HNSC than those in normal tissues, while the mRNA expression level of MMP15 was reduced. The relative expression levels of MMP1 and MMP14 were the highest in HNSC tissues. A significant correlation was found between the expression of MMP3, MMP11, MMP25 and the pathological stage of HNSC patients. There was no significant associations between all the MMP family members expression levels and DFS. Increased mRNA levels of MMP1, MMP8 and MMP25 were significantly associated with OS. In addition, we investigated the genetic changes of the MMP family in HNSC and found that all the MMP family members had genetic changes, most of which were amplification and depth loss. In the analysis of neighbor gene network and protein interaction, we found that the MMP family interacted with 25 neighboring genes, except for ILF3, MMP19, MMP20, MMP21, MMP23B, MMP27 and MMP28, other MMP proteins interacted with each other. Functional enrichment analysis showed that the MMP family could be present in the extracellular matrix, regulate peptidase activity, and participate in the catabolism of collagen. Meanwhile, we identified the transcription factor targets and kinase targets of the MMP family and found that ATM and ATR were the two most common kinase targets in the MMP family. We also found a significant correlation between the MMP family expression and immune cell infiltration. Cox proportional risk model analysis showed that macrophages, MMP14, MMP16, and MMP19 were significantly associated with clinical outcomes in HNSC patients. CONCLUSION: The MMP family might serve as therapeutic target and prognostic biomarker in HNSC.

The Antiangiogenic and Antitumor Effects of Scoparasin B in Non-Small-Cell Lung Cancer.

Angiogenesis and vasculogenic mimicry (VM) are crucial for the growth and metastasis of non-small-cell lung cancer (NSCLC). Most tumor angiogenesis inhibitors mainly target endothelial cell-mediated angiogenesis, ignoring tumor-cell-mediated VM and frequently leading to tumor recurrence and metastasis. Thus, development of bioactive molecules interfering with both tumor angiogenesis and VM is necessary. Identifying novel angiogenesis inhibitors from natural products is a promising strategy. Scoparasin B, a pimarane diterpene extracted from a marine-derived fungus, Eutypella sp. F0219, has an antibacterial effect. However, its effect on angiogenesis and VM remains unexplored. In this study, we first certified that scoparasin B showed a strong inhibition effect on angiogenesis and the VM process in vitro and ex vivo. Moreover, scoparasin B prominently impeded tumor growth, angiogenesis, and VM in an NCI-H1299 xenograft model. Further study revealed that scoparasin B restrained tumor angiogenesis and VM by reducing the VEGF-A level and suppressing the VEGF-A/VEGFR2 signaling pathway. This study first demonstrated scoparasin B inhibited tumor angiogenesis, VM, and tumor growth of NSCLC and revealed its underlying mechanism. These new findings further support the potential of scoparasin B as a novel angiogenesis inhibitor and give a hint for further exploring potential angiogenesis inhibitors from natural products.

Maternal Factors for Intrauterine Growth Retardation: Systematic Review and Meta-Analysis of Observational Studies.

Intrauterine growth retardation (IUGR) is a major complication of pregnancy and is the second leading cause of perinatal morbidity and mortality. The etiology of IUGR is multifactorial and the maternal factors are easily identifiable and modifiable. The present study aimed to perform a meta-analysis to identify the association between various maternal factors and IUGR. Eight electronic databases (PubMed, Cochrane, Embase, CIHNAL Plus, CNKI, VIP database, CBM, and WanFang database) were searched from their inception until July 2020. Eligibility screening, data extraction, and quality assessment of the retrieved articles were conducted independently by two reviewers. The Newcastle-Ottawa Quality Assessment Form and the Joanna Briggs Institute critical appraisal tool were used to evaluate the quality of included studies. The outcomes of study were calculated by OR with 95%CI. The study protocol was registered with PROSPERO (No. CRD42020210615). A total of 15 studies were included, with a sample size range from 152 to 9372. The quality of included studies ranged from moderate to high. The pooled results identified seven factors: smoking (OR = 1.62, 95%CI 1.38-1.90), primiparity (OR = 1.64, 95%CI 1.20-2.24), and prepregnancy.BMI < 18.5 (OR = 1.98, 95%CI 1.29-3.03), anemia (OR = 2.01, 95%CI 1.44-2.82), hypoproteinemia (OR = 2.91, 95%CI 1.94-4.36), pregnancy-induced hypertension (OR = 3.45, 95%CI 1.80-6.58), and maternal gestational weight gain (OR = 2.51, 95%CI 1.88-3.35). The present study identified several maternal factors for IUGR: smoking, primiparity, prepregnancy BMI < 18.5, poor gestational weight gain, PIH, anemia, and hypoproteinemia. The result could serve to generate risk factors prediction models, improve the management and education for child-bearing or early pregnant women.

CTHRC1 Is Associated With Immune Escape and Poor Prognosis in Gastric Cancer.

BACKGROUND/AIM: Collagen triple helix repeat containing-1 (CTHRC1) promotes tumor progression by regulating the immunosuppression of the tumor microenvironment. However, the function of CTHRC1 in gastric cancer (GC) and its relationship with tumor-infiltrating immune cells remains unclear. PATIENTS AND METHODS: Data were downloaded from The Cancer Genome Atlas (TCGA) database. The difference in expression of CTHRC1 in GC and adjacent non-tumor tissues was analyzed by R software and verified by the online database Oncomine. A Kaplan-Meier survival analysis was selected for evaluating the impact of CTHRC1 expression on the survival of GC and verified by the Kaplan-Meier plotter. The relationship between CTHRC1 expression and clinicopathological parameters was assessed by univariate and multivariate Cox regression. The correlation with tumor-infiltrating immune cells was analyzed by Tumor Immune Estimation Resource (TIMER). A gene set enrichment analysis (GSEA) was used to screen the signaling pathways between low and high CTHRC1 expression datasets. RESULTS: The expression of CTHRC1 in GC tissue was higher than that in adjacent non-tumor tissues. The Kaplan-Meier curve showed that patients with higher CTHRC1 expression had a worse prognosis. The univariate and multivariate Cox analyses showed that high expression of CTHRC1 was an important independent predictor of poor overall survival in GC. The TIMER database analysis revealed that CTHRC1 was associated with five tumor immunosuppressive cells in GC. The GSEA indicated that 10 signaling pathways were enriched in samples with a high CTHRC1 expression phenotype. CONCLUSION: CTHRC1 might be a new prognostic biomarker for CG and might be a potential target for treatment of GC.