Comparative study on chloroplast genome of Tamarix species.

Tamaricaceae comprises about 120 species and has a long evolutionary history, Tamarix Linn accounts for approximately 75% of the total species in this family. It is the most widely distributed and diverse genus in the family. They have important ecological significance for transforming deserts and improving climate conditions. However, Tamarix is the most poorly classified genera among flowering plants owing to its large variability and high susceptibility to interspecific hybridization. In this study, the complete chloroplast genomes of three Tamarix species and one draft chloroplast genome were obtained in this study. Combined with eight chloroplast genomes deposited in GenBank, complete chloroplast sequences of 12 Tamarix species were used for further analysis. There are 176 non-SSR-related indels and 681 non-indel-related SSRs in the 12 Tamarix chloroplast genomes. The mononucleotide SSRs are the most prevalent among all types of SSRs. The mVISTA results indicate high sequence similarities across the chloroplast genome, suggesting that the chloroplast genomes are highly conserved, except for sample Tamarix androssowii (ENC850343). The IR regions and the coding regions are more conserved than the single-copy and noncoding regions. The trnF-ndhJ, ndhC-trnM-CAU, ycf1, and trnL-UAG-ndhF regions are the most variable and have higher variability than those of the universal DNA markers. Finally, the first phylogenetic tree of Tamaricaceae was constructed which confirmed the monophyly of Tamarix in Tamaricaceae. The first phylogenetic tree of Tamarix was based on the complete chloroplast genome to date, the changes in branch length and support rate can potentially help us clarify the phylogenetic relationships of Tamarix. All the obtained genetic resources will facilitate future studies in population genetics, species identification, and conservation biology of Tamarix.

The applications of CT with artificial intelligence in the prognostic model of idiopathic pulmonary fibrosis.

TAKE HOME MESSAGE: The review summarizes the applications of CT and AI algorithms for prognostic models in IPF and procedures of model construction. It reveals the current limitations and prospects of AI-aid models, and helps clinicians to recognize the AI algorithms and apply them to more clinical work.

Proton pump inhibitors may increase the risk of cisplatin-induced acute kidney injury in patients with nasopharyngeal carcinoma: a prospective cohort study.

Cisplatin is the most commonly used platinum-based treatment for nasopharyngeal carcinoma (NPC). However, its clinical application is limited owing to its nephrotoxicity and gastrointestinal reactions. Proton pump inhibitors (PPIs) have been reported to increase nephrotoxicity risk in previous studies. We aimed to evaluate whether PPIs increase cisplatin-induced nephrotoxicity in patients with NPC. In total, 295 patients were included in this prospective cohort study: 145 in the PPIs group and 150 in the non-PPIs group. All patients underwent cisplatin-based induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy. The PPIs group received 40 mg of intravenous esomeprazole sodium for 7 days in each chemotherapy cycle. Chi-squared test and logistic regression analyses with odds ratios and 95% confidence intervals were applied to assess the association between PPIs and the risk of acute kidney injury (AKI). AKI incidence in the PPIs group was significantly higher than that in the non-PPIs group (P = 0.005). After adjusting for various confounders including demographic features, clinical features, and renal function indices, PPIs use was significantly associated with a higher AKI risk (odds ratio: 2.775; 95% confidence interval 1.280-6.020; P = 0.010). The incidences of acute and chronic kidney diseases were similar between both groups (P > 0.05), whereas the incidence of nausea was lower in the PPIs group than in the non-PPIs group (P = 0.029). This study has shown that PPIs use may increase the risk of cisplatin-induced acute nephrotoxicity in patients with NPC.

miR-584-5p is a New Potential Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: MicroRNA-584-5p (miR-584-5p) plays an important role in certain types of cancer. However, its precise role in head and neck squamous cell carcinoma (HNSC) remains unknown. OBJECTIVE: Our aim was to investigate how miR-584-5p influences HNSC. METHODS: The Cancer Genome Atlas (TCGA) provided samples for the study. We use statistical methods to evaluate the diagnostic value, the prognostic value, and the correlation with the clinical features of miR-584-5p. We analyze the target genes and the regulatory network of miR- 584-5p. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed the expression of miR- 584-5p in HNSC cell lines. RESULTS: MiR-584-5p expression of miR-584-5p varied significantly among different types of cancer. A notable correlation was observed between elevated miR-584-5p expression and gender (p < 0.001) and histological grade (p < 0.001). Furthermore, high levels of miR-584-5p were found to be associated with a decrease in overall survival (HR: 1.44; 95% CI: 1.10-1.88; p = 0.007), progression-free survival (HR: 1.35; 95% CI: 1.02-1.79; p = 0.035) and disease-specific survival (HR: 1.54; 95% CI: 1.09-2.18; p = 0.016) in the context of HNSC. miR-584-5p demonstrated independent prognostic significance in HNSC and potentially contributes to disease progression through multiple pathways, such as dilated cardiomyopathy and hypertrophic cardiomyopathy. In particular, HNSC cell lines exhibited a substantial upregulation of miR-584-5p compared to normal epithelial cells. CONCLUSIONS: It is possible that miR-584-5p could serve as a promising patent for a therapeutic target and prognostic biomarker for people with HNSC.

Annulation of 2-Aroyl D-A Cyclopropanes via Selectively Ring-Opening Process with o-Benzenediamines to Access Quinoxaline Derivatives.

An annulation reaction of 2-aroyl D-A cyclopropanes with o-benzenediamines via selective cleavage of C-C bonds of cyclopropane in the presence of DBU/Sc(OTf)3 reaction systems was developed for the direct preparation of 2-aryl-3-benzylquinoxalines. This synthetic approach tolerated a wide range of readily available aroyl-substituted D-A cyclopropanes with diverse functional groups and had operationally simple and mild reaction conditions.

Synthesis of Fully Substituted Pyrazoles with a Dicyanomethyl Group via DBU/Lewis Acid-Mediated Annulation of D-A Cyclopropanes with Arylhydrazines.

The efficient synthesis of fully substituted pyrazoles with a dicyanomethyl group was developed via an annulation reaction of 2-aroyl D-A cyclopropanes with arylhydrazines in the presence of DBU/AlCl3 reaction systems. This synthetic approach featured a wide range of readily available aroyl-substituted D-A cyclopropanes with diverse functional groups and a diversity of substituents on pyrazole products and had operationally simple and mild reaction conditions.

Tislelizumab plus neoadjuvant chemotherapy and concurrent chemoradiotherapy versus neoadjuvant chemotherapy and concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma: A retrospective study.

BACKGROUND: The efficacy of immunotherapy plus neoadjuvant chemotherapy and concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal carcinoma (LA-NPC) has not been reported. This study retrospectively compared the efficacy of tislelizumab plus neoadjuvant chemotherapy and CCRT with neoadjuvant chemotherapy followed by CCRT. METHODS: Ninety patients with stages III-IVa NPC were identified between January 2020 and March 2021 at the Affiliate Hospital of Guangdong Medical University. Forty-three patients in the observation group (OG) received tislelizumab plus nano albumin-paclitaxel and cisplatin (nab-TP) regimen, followed by CCRT, while forty-seven patients in the control group (CG) received nab-TP regimen followed by CCRT. RESULTS: The complete response rate after neoadjuvant therapy was significantly higher in the OG compared to the CG (37.2% vs. 12.8 %). The objective response rates were 88.4 % in the OG and 70.2 % in the CG. The 3-year progression-free survival (PFS) rates for OG and CG patients were 93.0 % and 78.7 %, respectively (P = 0.04, HR = 0.31). The overall survival (OS) rates for the OG and the CG were 95.3 % and 87.2 %, respectively (P = 0.15, HR = 0.36). Locoregional relapse-free survival (LRFS) rates were 90.7 % for the OG and 72.3 % for the CG (P = 0.04, HR = 0.38), and distant metastasis-free survival (DMFS) rates were 95.3 % for the OG, and 80.9 % for the CG (P = 0.04, HR = 0.30). For PD-L1 high-expression and low-expression rates, the 3-year PFS rates were 89.2 % and 85.7 % (P = 0.77, HR = 1.21), and the OS rates were 90.2 % and 89.2 % (P = 0.65, HR = 1.36), respectively. CONCLUSION: Tislelizumab combined with neoadjuvant chemotherapy and CCRT showed encouraging therapeutic effects and good tolerability in patients with LA-NPC compared to the standard treatment.

Weiwei Decoction alleviates gastric intestinal metaplasia through the olfactomedin 4/nucleotide-binding oligomerization domain 1/caudal-type homeobox gene 2 signaling pathway.

BACKGROUND: Gastric intestinal metaplasia (IM) is a precancerous lesion that is associated with an elevated risk of gastric carcinogenesis. Weiwei Decoction (WWD) is a promising traditional Chinese herbal formula widely employed in clinical for treating IM. Previous studies suggested the potential involvement of the olfactomedin 4 (OLFM4)/nucleotide-binding oligomerization domain 1 (NOD1)/caudal-type homeobox gene 2 (CDX2) signaling pathway in IM regulation. AIM: To verify the regulation of the OLFM4/NOD1/CDX2 pathway in IM, specifically investigating WWD's effectiveness on IM through this pathway. METHODS: Immunohistochemistry for OLFM4, NOD1, and CDX2 was conducted on tissue microarray. GES-1 cells treated with chenodeoxycholic acid were utilized as IM cell models. OLFM4 short hairpin RNA (shRNA), NOD1 shRNA, and OLFM4 pcDNA were transfected to clarify the pathway regulatory relationships. Protein interactions were validated by co-immunoprecipitation. To explore WWD's pharmacological actions, IM rat models were induced using N-methyl-N'-nitro-N-nitrosoguanidine followed by WWD gavage. Gastric cells were treated with WWD-medicated serum. Cytokines and chemokines content were assessed by enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction. RESULTS: The OLFM4/NOD1/CDX2 axis was a characteristic of IM. OLFM4 exhibited direct binding and subsequent down-regulation of NOD1, thereby sustaining the activation of CDX2 and promoting the progression of IM. WWD improved gastric mucosal histological lesions while suppressing intestinal markers KLF transcription factor 4, villin 1, and MUCIN 2 expression in IM rats. Regarding pharmacological actions, WWD suppressed OLFM4 and restored NOD1 expression, consequently reducing CDX2 at the mRNA and protein levels in IM rats. Parallel regulatory mechanisms were observed at the protein level in IM cells treated with WWD-medicated serum. Furthermore, WWD-medicated serum treatment strengthened OLFM4 and NOD1 interaction. In case of anti-inflammatory, WWD restrained interleukin (IL)-6, interferon-gamma, IL-17, macrophage chemoattractant protein-1, macrophage inflammatory protein 1 alpha content in IM rat serum. WWD-medicated serum inhibited tumor necrosis factor alpha, IL-6, IL-8 transcriptions in IM cells. CONCLUSION: The OLFM4/NOD1/CDX2 pathway is involved in the regulation of IM. WWD exerts its therapeutic efficacy on IM through the pathway, additionally attenuating the inflammatory response.

Mg-gallate metal-organic framework-based sprayable hydrogel for continuously regulating oxidative stress microenvironment and promoting neurovascular network reconstruction in diabetic wounds.

Chronic diabetic wounds are the most common complication for diabetic patients. Due to high oxidative stress levels affecting the entire healing process, treating diabetic wounds remains a challenge. Here, we present a strategy for continuously regulating oxidative stress microenvironment by the catalyst-like magnesium-gallate metal-organic framework (Mg-GA MOF) and developing sprayable hydrogel dressing with sodium alginate/chitosan quaternary ammonium salts to treat diabetic wounds. Chitosan quaternary ammonium salts with antibacterial properties can prevent bacterial infection. The continuous release of gallic acid (GA) effectively eliminates reactive oxygen species (ROS), reduces oxidative stress, and accelerates the polarization of M1-type macrophages to M2-type, shortening the transition between inflammation and proliferative phase and maintaining redox balance. Besides, magnesium ions adjuvant therapy promotes vascular regeneration and neuronal formation by activating the expression of vascular-associated genes. Sprayable hydrogel dressings with antibacterial, antioxidant, and inflammatory regulation rapidly repair diabetic wounds by promoting neurovascular network reconstruction and accelerating re-epithelialization and collagen deposition. This study confirms the feasibility of catalyst-like MOF-contained sprayable hydrogel to regulate the microenvironment continuously and provides guidance for developing the next generation of non-drug diabetes dressings.

Investigation of folate-modified EGCG-loaded thermosensitive nanospheres inducing immunogenic cell death and damage-associated molecular patterns in hepatocellular carcinoma.

BACKGROUND: The systemic treatment of advanced hepatocellular carcinoma is currently facing a bottleneck. EGCG, the primary active compound in green tea, exhibits anti-tumor effects through various pathways. However, there is a lack of study on EGCG-induced immunogenic cell death (ICD) in hepatocellular carcinoma. METHODS: In a previous study, we successfully synthesized folate-modified thermosensitive nano-materials, encapsulated EGCG within nanoparticles using a hydration method, and established the EGCG nano-drug delivery system. The viability of HepG2 cells post-EGCG treatment was assessed via the MTT and EdU assays. Cell migration and invasion were evaluated through wound healing experiments, Transwell assays, and Annexin V-FITC/PI assay for apoptosis detection. Additionally, the expression levels of damage-associated molecular patterns (DAMPs) were determined using immunofluorescence, ATP measurement, RT-qPCR, and Western Blot. RESULTS: The drug sensitivity test revealed an IC50 value of 96.94 µg/mL for EGCG in HepG2 cells after 48 h. EGCG at a low concentration (50 µg/mL) significantly impeded the migration and invasion of HepG2 cells, showing a clear dose-dependent response. Moreover, medium to high EGCG concentrations induced cell apoptosis in a dose-dependent manner and upregulated DAMPs expression. Immunofluorescence analysis demonstrated a notable increase in CRT expression following low-concentration EGCG treatment. As EGCG concentration increased, cell viability decreased, leading to CRT exposure on the cell membrane. EGCG also notably elevated ATP levels. RT-qPCR and Western Blot analyses indicated elevated expression levels of HGMB1, HSP70, and HSP90 following EGCG intervention. CONCLUSION: EGCG not only hinders the proliferation, migration, and invasion of hepatocellular carcinoma cells and induces apoptosis, but also holds significant clinical promise in the treatment of malignant tumors by promoting ICD and DAMPs secretion.

TLR4 TIR domain and nucleolin GAR domain synergistically mediate RSV infection and induce neuronal inflammatory damage in SH-SY5Y cells.

Previous research results of our group showed that Toll-like receptor 4 (TLR4) and nucleolin synergistically mediate respiratory syncytial virus (RSV) infection in human central neuron cells, but the specific mechanism remains unclear. Here we designed and synthesized lentiviruses with TIR (674-815 aa), TLR4 (del 674-815 aa), GAR (645-707 aa), and NCL (del 645-707 aa) domains, and obtained stable overexpression cell lines by drug screening, and subsequently infected RSV at different time points. Laser confocal microscopy and coimmunoprecipitation were used for the observation of co-localization and interaction of TIR/GAR domains. Western blot analysis was used for the detection of p-NF-κB and LC3 protein expression. Real-time PCR was used for the detection of TLR4/NCL mRNA expression. ELISA assay was used to measure IL-6, IL-1ß, and TNF-α concentrations and flow cytometric analysis was used for the study of apoptosis. Our results suggest that overexpression of TIR and GAR domains can exacerbate apoptosis and autophagy, and that TIR and GAR domains can synergistically mediate RSV infection and activate the NF-κB signaling pathway, which regulates the secretion of downstream inflammatory factors, such as IL-6, IL-1ß, and TNF-α, and ultimately leads to neuronal inflammatory injury.

Investigating the Influence of Diverse Functionalized Carbon Nanotubes as Conductive Fibers on Paper-Based Sulfur Cathodes in Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are expected to be one of the next generations of high-energy-density battery systems due to their high theoretical energy density of 2600 Wh kg-1. Embracing the trends toward flexibility, lightweight design, and cost-effectiveness, paper-based electrodes offer a promising alternative to traditional coated cathodes in Li-S batteries. Within paper-based electrodes, conductive fibers such as carbon nanotubes (CNTs) play a crucial role. They help to form a three-dimensional network within the paper matrix to ensure structural integrity over extended cycling while mitigating the shuttle effect by confining sulfur within the cathode. Herein, we explore how variously functionalized CNTs, serving as conductive fibers, impact the physical and electrochemical characteristics of paper-based sulfur cathodes in Li-S batteries. Specifically, graphitized hydroxylated carbon nanotubes (G-CNTs) exhibit remarkable capacity at low currents owing to their excellent conductivity and interaction with lithium polysulfide (LiPS), achieving the highest initial specific capacity of 1033 mAh g-1 at 0.25 C (1.1 mA cm-2). Aminated multi-walled carbon nanotubes (NH2-CNTs) demonstrate an enhanced affinity for LiPS due to the -NH2 groups. However, the uneven distribution of these fibers may induce electrode surface passivation during charge-discharge cycles. Notably, hydroxylated multi-walled carbon nanotubes (OH-CNTs) can establish a uniform and stable 3D network with plant fibers, showcasing superior mechanical properties and helping to mitigate Li2S agglomeration while preserving the electrode porosity. The paper-based electrode integrated with OH-CNTs even retains a specific capacity of approximately 800 mAh g-1 at about 1.25 C (5 mA cm-2), demonstrating good sulfur utilization and rate capacity compared to other CNT variants.

Tumor-Derived Exosomal Circular RNA Pinin Induces FGF13 Expression to Promote Colorectal Cancer Progression through miR-1225-5p.

Background/Aims: : Colorectal cancer (CRC) is a common malignant tumor, and circular RNAs (circRNAs) are abnormally expressed in CRC. However, the function and underlying mechanism of circRNA pinin (circ-PNN; hsa_circ_0101802) in CRC remain unclear. Methods: : Exosomes were isolated from the plasma of CRC patients and identified by transmission electron microscopy and Western blotting. The RNA expression levels of circ-PNN, miR-1225-5p, and fibroblast growth factor 13 (FGF13) were measured by quantitative real-time polymerase chain reaction. Cell proliferation was detected by Cell Counting K-8, colony formation, and 5-ethynyl-2'-deoxyuridine assays. Cell apoptosis was assessed by flow cytometry. The expression of apoptosis and metastasis-related proteins was evaluated by Western blotting. The associations among circ-PNN, miR-1225-5p, and FGF13 were confirmed by dual-luciferase report assay and RNA immunoprecipitation assay. A xenograft model was used to verify the function of circ-PNN in tumor formation in vivo. Results: : circ-PNN expression was upregulated in plasmic exosomes derived from CRC patients. The expression of circ-PNN and FGF13 was upregulated, while miR-1225-5p expression was downregulated in CRC cells incubated with plasmic exosomes derived from CRC patients. Tumor-derived exosomes promoted the proliferation, migration, and invasion but inhibited apoptosis of CRC cells. Moreover, the addition of tumor-derived exosomes partly reversed the inhibitory effect of circ-PNN knockdown on CRC tumor progression in vitro and in vivo. Thus, circ-PNN acts as a sponge for miR-1225-5p to regulate FGF13 expression. Conclusions: : Tumor-derived exosomal circ-PNN promoted CRC progression through the regulation of the miR-1225-5p/FGF13 pathway, providing a potential therapeutic target for CRC.

Prediction and verification of the prognostic biomarker SLC2A2 and its association with immune infiltration in gastric cancer.

Gastric cancer (GC) is the fifth most common cause of cancer-associated deaths; however, its treatment options are limited. Despite clinical improvements, chemotherapy resistance and metastasis are major challenges in improving the prognosis and quality of life of patients with GC. Therefore, effective prognostic biomarkers and targets associated with immunological interventions need to be identified. Solute carrier family 2 member 2 (SLC2A2) may serve a role in tumor development and invasion. The present study aimed to evaluate SLC2A2 as a prospective prognostic marker and chemotherapeutic target for GC. SLC2A2 expression in several types of cancer and GC was analyzed using online databases, and the effects of SLC2A2 expression on survival prognosis in GC were investigated. Clinicopathological parameters were examined to explore the association between SLC2A2 expression and overall survival (OS). Associations between SLC2A2 expression and immune infiltration, immune checkpoints and IC50 were estimated using quantification of the tumor immune contexture from human RNA-seq data, the Tumor Immune Estimation Resource 2.0 database and the Genomics of Drug Sensitivity in Cancer database. Differential SLC2A2 expression and the predictive value were validated using the Human Protein Atlas, Gene Expression Omnibus, immunohistochemistry and reverse transcription-quantitative PCR. SLC2A2 expression was downregulated in most types of tumor but upregulated in GC. Functional enrichment analysis revealed an association between SLC2A2 expression and lipid metabolism and the tumor immune microenvironment. According to Gene Ontology term functional enrichment analysis, SLC2A2-related differentially expressed genes were enriched predominantly in 'chylomicron assembly', 'plasma lipoprotein particle assembly', 'high-density lipoprotein particle', 'chylomicron', 'triglyceride-rich plasma lipoprotein particle', 'very-low-density lipoprotein particle'. 'intermembrane lipid transfer activity', 'lipoprotein particle receptor binding', 'cholesterol transporter activity' and 'intermembrane cholesterol transfer activity'. In addition, 'cholesterol metabolism', and 'fat digestion and absorption' were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Patients with GC with high SLC2A2 expression had higher levels of neutrophil and M2 macrophage infiltration and a significant inverse correlation was observed between SLC2A2 expression and MYC targets, tumor mutation burden, microsatellite instability and immune checkpoints. Furthermore, patients with high SLC2A2 expression had worse prognosis, including OS, disease-specific survival and progression-free interval. Multivariate regression analysis demonstrated that SLC2A2 could independently prognosticate GC and the nomogram model showed favorable performance for survival prediction. SLC2A2 may be a prospective prognostic marker for GC. The prediction model may improve the prognosis of patients with GC in clinical practice, and SLC2A2 may serve as a novel therapeutic target to provide immunotherapy plans for GC.

Effects of protoscoleces excretory-secretory products of Echinococcus granulosus on hepatocyte growth, function, and glucose metabolism.

Cystic echinococcosis (CE) is one of the most widespread and harmful zoonotic parasitic diseases, which most commonly affects the liver. In this study, we characterized multiple changes in mouse hepatocytes following treatment with excretory-secretory products (ESPs) of Echinococcus granulosus protoscoleces (Eg-PSCs) by a factorial experiment. The cell counting kit-8 assay (CCK-8), the 5-ethynyl-2'-deoxyuridine (EdU) assay, and flow cytometry were used to detect the growth of hepatocytes. Inverted microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were used to observe the morphology and ultrastructure of hepatocytes. An automatic biochemical analyzer and an ELISA detection kit were used to determine six conventional hepatocyte enzymatic indices, the levels of five hepatocyte-synthesized substances, and the contents of glucose and lactate. Western blot analysis was conducted to analyze the protein expression of three apoptosis-related proteins, Bax, Bcl-2, cleaved caspase-3, and six glucose metabolism pathways rate-limiting enzymes in hepatocytes. The results showed that ESPs inhibited hepatocyte proliferation and promoted hepatocyte apoptosis. The cell membrane and microvilli of hepatocytes changed, and the nucleus, mitochondria and rough endoplasmic reticulum were damaged to varying degrees. The contents of iron, albumin (ALB), uric acid (UA) and urea were increased, and the activities of six enzymes in hepatocytes were increased except for the decrease of transferrin (TRF). The expression levels of all six key enzymes in the glucose metabolism pathway in hepatocytes were reduced. Our characterization provides a basis for further research on the pathogenesis, prevention and treatment of CE.

ZnCl2-Promoted Three-Component Reaction of 2-Aminochromenones, Aromatic Aldehydes, and Quinone Monoketals: Access to 5,6-Dihydro-12H-chromeno[2,3-c]isoquinolin-12-one Derivatives.

A three-component reaction of 2-amino-4H-chromen-4-ones, aromatic aldehydes, and 4,4-dialkoxycyclohexa-2,5-dien-1-ones for the concise synthesis of chromeno[2,3-c]dihydroisoquinoline derivatives has been investigated. This reaction involved consecutive ZnCl2-promoted Micheal addition and intramolecular Friedel-Crafts alkylation. This synthetic protocol offered several advantages, including the readily accessible starting materials, good functional group tolerance, and simplicity of operation. Additionally, the structures of products obtained were determined based on X-ray diffraction studies.

Acetic Acid-Catalyzed (3 + 2) Cyclization of 2-Aroyl-3-aryl-1,1-dicyanocyclopropanes with Arylhydrazines: To trans-4-Dicyanomethyl-1,3,5-triaryl-4,5-dihydropyrazoles.

Acetic acid-catalyzed (3 + 2) cyclization reaction of substituted 2-aroyl-3-aryl-1,1-dicyanocyclopropanes with arylhydrazines was investigated for the efficient synthesis of 4-dicyanomethyl-1,3,5-triaryl-4,5-dihydropyrazoles in good yields, in which 4,5-double substituents are predominantly trans selective. This approach included the consecutive condensation, ring opening, and double nucleophilic cyclization reaction.

Dysregulation of Type I Interferon (IFN-I) Signaling: A Potential Contributor to Racial Disparity in Hepatocellular Carcinoma (HCC).

African-American (AA)/Black hepatocellular carcinoma (HCC) patients have increased incidence and decreased survival rates compared to non-Hispanic (White) patients, the underlying molecular mechanism of which is not clear. Analysis of existing RNA-sequencing (RNA-seq) data in The Cancer Genome Atlas (TCGA) and in-house RNA-sequencing of 14 White and 18 AA/Black HCC patients revealed statistically significant activation of type I interferon (IFN-I) signaling pathway in AA/Black patients. A four-gene signature of IFN-stimulated genes (ISGs) showed increased expression in AA/Black HCC tumors versus White. HCC is a disease of chronic inflammation, and IFN-Is function as pro-inflammatory cytokines. We tested efficacy of ginger extract (GE), a dietary compound known for anti-inflammatory properties, on HCC cell lines derived from White (HepG2), AA/Black (Hep3B and O/20) and Asian (HuH-7) patients. GE exhibited a significantly lower IC50 on Hep3B and O/20 cells than on HepG2 and HuH-7 cells. The GE treatment inhibited the activation of downstream mediators of IFN-I signaling pathways and expression of ISGs in all four HCC cells. Our data suggest that ginger can potentially attenuate IFN-I-mediated signaling pathways in HCC, and cells from AA/Black HCC patients may be more sensitive to ginger. AA/Black HCC patients might benefit from a holistic diet containing ginger.

Analysis of severe fever with thrombocytopenia syndrome cluster in east China.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a common tick-borne, natural focal disease. SFTS virus (SFTSV) transmission can occur between family members through close contact with an infected patient. In this study, we explored the possible transmission route of an outbreak cluster in east China. METHOD: A case-control study was carried out to analyze the potential risk factors for person-to-person transmission. Bunia virus was detected by IgM antibody, enzyme-linked immunosorbent assay, and reverse transcription polymerase chain reaction. Chi-square, univariate, and multivariate analyses were performed to calculate the association of possible risk factors for SFTSV transmission. RESULTS: Two patients had a clear history of blood and aerosols contact, and one may be exposed to aerosols in a closed environment. Five close contacts of the Index patient were IgM-positive and three were IgM and SFTSV RNA positive. Exposure to a poorly ventilated space where the corpse was stored (χ2 = 5.49, P = 0.019) and contact with the Index patient's contaminated items (χ2 = 15.77, P < 0.001) significantly associated with SFTSV infection. CONCLUSION: We suspect that the cluster outbreak was possibly a person-to-person transmission of SFTSV, which may have been transmitted by directly contacting with blood of SFTS patient. The propagation of aerosols in closed environments is also an undeniable transmission.

Helicobacter pylori plays a key role in gastric adenocarcinoma induced by spasmolytic polypeptide-expressing metaplasia.

Heliobacter pylori (H. pylori), a group 1 human gastric carcinogen, is significantly associated with chronic gastritis, gastric mucosal atrophy, and gastric cancer. Approximately 20% of patients infected with H. pylori develop precancerous lesions, among which metaplasia is the most critical. Except for intestinal metaplasia (IM), which is characterized by goblet cells appearing in the stomach glands, one type of mucous cell metaplasia, spasmolytic polypeptide-expressing metaplasia (SPEM), has attracted much attention. Epidemiological and clinicopathological studies suggest that SPEM may be more strongly linked to gastric adenocarcinoma than IM. SPEM, characterized by abnormal expression of trefoil factor 2, mucin 6, and Griffonia simplicifolia lectin II in the deep glands of the stomach, is caused by acute injury or inflammation. Although it is generally believed that the loss of parietal cells alone is a sufficient and direct cause of SPEM, further in-depth studies have revealed the critical role of immunosignals. There is controversy regarding whether SPEM cells originate from the transdifferentiation of mature chief cells or professional progenitors. SPEM plays a functional role in the repair of gastric epithelial injury. However, chronic inflammation and immune responses caused by H. pylori infection can induce further progression of SPEM to IM, dysplasia, and adenocarcinoma. SPEM cells upregulate the expression of whey acidic protein 4-disulfide core domain protein 2 and CD44 variant 9, which recruit M2 macrophages to the wound. Studies have revealed that interleukin-33, the most significantly upregulated cytokine in macrophages, promotes SPEM toward more advanced metaplasia. Overall, more effort is needed to reveal the specific mechanism of SPEM malignant progression driven by H. pylori infection.