LARS1 is a Prognostic Biomarker and Exhibits a Correlation with Immune Infiltrates in Hepatocellular Carcinoma.

Purpose: To study the relationship between LARS1 expression and immune infiltration and prognosis in hepatocellular carcinoma (HCC). Patients and Methods: The clinical characteristics together with LARS1 expression levels were obtained from the TCGA database. Immunohistochemistry confirmed LARS1 expression levels in paraneoplastic and tumor tissues. To investigate LARS1-related downstream molecules, a network of protein-protein interactions (PPIs) and the Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) were built. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathways associated with LARS1 expression, whereas Single-sample GSEA (ssGSEA) was applied to perform an association study between immune infiltration and LARS1 gene expression. The TISCH Database and the TISIDB database were used to compare the difference of LARS1 expression in hepatocellular carcinoma and immunomodulators. Results: In comparison to that in normal tissues, the LARS1 expression level was elevated in tumor tissues. LARS1 expression exhibited substantial correlation with AFP, Histologic grade, pathologic stage, Residual tumor, and Vascular invasion in HCC. Higher LARS1 expression in HCC was linked to lower progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). According to the GO/KEGG study, the important biological process (neutral lipid metabolic process), cellular component (triglyceride-rich plasma lipoprotein), molecular functions (lipase inhibitor activity), and KEGG pathway (cholesterol metabolism) could be a probable function mechanism in promoting HCC. Various pathways as per GSEA revealed that they were enriched in samples with elevated LARS1 expression. The expression level of LARS1 in malignant tumor cells after immunotherapy was significantly higher than that before immunotherapy. LARS1 was also remarkably linked to the infiltration level and the immunomodulators. Conclusion: LARS1 can be used as a biomarker of HCC, which is associated to immune infiltration of HCC.

Neutrophil extracellular traps promote acetaminophen-induced acute liver injury in mice via AIM2.

Excessive acetaminophen (APAP) can induce neutrophil activation and hepatocyte death. Along with hepatocyte dysfunction and death, NETosis (a form of neutrophil-associated inflammation) plays a vital role in the progression of acute liver injury (ALI) induced by APAP overdose. It has been shown that activated neutrophils tend to migrate towards the site of injury and participate in inflammatory processes via formation of neutrophil extracellular traps (NETs). In this study we investigated whether NETs were involved in hepatocyte injury and contributed to APAP-induced ALI progression. ALI mouse model was established by injecting overdose (350 mg/kg) of APAP. After 24 h, blood and livers were harvested for analyses. We showed that excessive APAP induced multiple programmed cell deaths of hepatocytes including pyroptosis, apoptosis and necroptosis, accompanied by significantly increased NETs markers (MPO, citH3) in the liver tissue and serum. Preinjection of DNase1 (10 U, i.p.) for two consecutive days significantly inhibited NETs formation, reduced PANoptosis and consequently alleviated excessive APAP-induced ALI. In order to clarify the communication between hepatocytes and neutrophils, we induced NETs formation in isolated neutrophils, and treated HepaRG cells with NETs. We found that NETs treatment markedly increased the activation of GSDMD, caspase-3 and MLKL, while pre-treatment with DNase1 down-regulated the expression of these proteins. Knockdown of AIM2 (a cytosolic innate immune receptor) abolished NETs-induced PANoptosis in HepaRG cells. Furthermore, excessive APAP-associated ALI was significantly attenuated in AIM2KO mice, and PANoptosis occurred less frequently. Upon restoring AIM2 expression in AIM2KO mice using AAV9 virus, both hepatic injury and PANoptosis was aggravated. In addition, we demonstrated that excessive APAP stimulated mtROS production and mitochondrial DNA (mtDNA) leakage, and mtDNA activated the TLR9 pathway to promote NETs formation. Our results uncover a novel mechanism of NETs and PANoptosis in APAP-associated ALI, which might serve as a therapeutic target.

Unveiling the activity difference cause and ring-opening reaction routes of typical radicals induced degradation of toluene.

This study employs five UV-AOPs (PMS, PDS, H2O2, NaClO and NaClO2) to produce radicals (•OH, SO4•-, ClO•, O2•- and 1O2) and further comparatively studies their activity sequence and activity difference cause in toluene degradation. The toluene mineralization efficiency as a descending order is 73 % (UV-PMS) > 71 % (UV-PDS) > 70 % (acidified-UV-NaClO) > 55 % (UV-H2O2) > 36 % (UV-NaClO) > 35 % (UV-NaClO2); that of conversion efficiency is 99 % (acidified-UV-NaClO) > 95 % (UV-PMS) > 90 % (UV-PDS) > 74 % (UV-H2O2) > 44 % (UV-NaClO) > 41 % (UV-NaClO2). Acidic pretreatment significantly boosts the reactivity of UV-NaClO. ESR combined with radical quenching tests reveals the radicals' generation and evolution, and their contribution rates to toluene conversion, i.e. ClO• > SO4•- > O2•- > 1O2 > â€¢OH. Theoretical calculations further unveil the ring-opening reaction routes and the nature of the activity difference of different radicals. The minimum energy required for ring-opening reaction is 116.77, 150.63, 168.29 and 191.92 kJ/mol with respect to ClO•, SO4•-, 1O2 and •OH, and finding that the ClO•-HO• pair is the best for toluene mineralization. The difficulty for eliminating typical VOCs by using UV-AOPs method is determined as toluene > chlorobenzene > benzene > ethyl acetate.

The cGAS-Ku80 complex regulates the balance between two end joining subpathways.

As the major DNA sensor that activates the STING-TBK1 signaling cascade, cGAS is mainly present in the cytosol. A number of recent reports have indicated that cGAS also plays critical roles in the nucleus. Our previous work demonstrated for the first time that cGAS is translocated to the nucleus upon the occurrence of DNA damage and inhibits homologous recombination (HR), one of the two major pathways of DNA double strand break (DSB) repair. However, whether nuclear cGAS regulates the other DSB repair pathway, nonhomologous end joining (NHEJ), which can be further divided into the less error-prone canonical NHEJ (c-NHEJ) and more mutagenic alternative NHEJ (alt-NHEJ) subpathways, has not been characterized. Here, we demonstrated that cGAS tipped the balance of the two NHEJ subpathways toward c-NHEJ. Mechanistically, the cGAS-Ku80 complex enhanced the interaction between DNA-PKcs and the deubiquitinase USP7 to improve DNA-PKcs protein stability, thereby promoting c-NHEJ. In contrast, the cGAS-Ku80 complex suppressed alt-NHEJ by directly binding to the promoter of Polθ to suppress its transcription. Together, these findings reveal a novel function of nuclear cGAS in regulating DSB repair, suggesting that the presence of cGAS in the nucleus is also important in the maintenance of genome integrity.

Pharmacokinetic and pharmacodynamic evaluation study of etomidate: a randomized, open-label, 2-period crossover study in healthy Chinese subjects.

Etomidate is a sedative and hypnotic drug through intravenous administration that act on the central nervous system through GABA (Gamma-Amino Butyric Acid) receptors, which is widely used in anesthesia induction and maintenance and long-term sedation in severe patients. The study aimed to evaluate the pharmacokinetic and pharmacodynamic properties of two etomidate fat emulsions after administration through the intravenous infusion pump in healthy Chinese subjects. A randomized, open-label, 2-period crossover study was performed in 52 healthy subjects. The wash-out period was 7 days. Blood samples and pharmacodynamic index values were collected at the specified time points. Etomidate concentrations were measured using validated liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were analyzed using a non-compartment model method. Pharmacodynamic parameters were calculated using pharmacodynamic index values. The study also evaluated the safety of the etomidate. Both the pharmacokinetic parameters and pharmacodynamic parameters result of the test and reference formulation were very similar. The 90% confidence intervals (CI) of the geometric least-squares mean (GLSM) ratios of the test to reference formulation were 91.33-104.96% for the maximum plasma concentration (Cmax), 97.21-102.03% for the area under the plasma concentration time curve from time 0 to the time of the last measurable concentration (AUC0-t), and 97.22-102.33% for the area under the plasma concentration time curve from time 0 to infinity (AUC0-∞). Meanwhile, the 90% CI of the GLSM ratios of the test to reference formulation were 102.28-110.69% for the minimal BIS value (BISmin), 99.23-101.17% for the area under the BIS time curve from time 0-60 min after administration (BISAUC0-60 min), respectively. The 90% CI of these pharmacokinetic and pharmacodynamic parameters all fall in the accepted bioequivalence range of 80.00-125.00%. No serious adverse events occurred during the study. This study has shown that the etomidate fat emulsion test and reference formulation had similar pharmacokinetic and pharmacodynamic characteristics in vivo. The two formulations exhibited good safety and well-tolerance.Clinical trials registration number: http://www.chinadrugtrials.org.cn/index.html . # CTR20191836.

High-Density Au Anchored to Ti3C2-Based Colorimetric-Fluorescence Dual-Mode Lateral Flow Immunoassay for All-Domain-Enhanced Performance and Signal Intercalibration.

In this work, a novel MXene-Au nanoparticle (Ti3C2@Au) was synthesized with a high molar extinction coefficient, strong fluorescence quenching ability, ultrahigh antibody affinity, high stability, and good dispersibility, and it was used to develop a colorimetric-fluorescence dual-mode lateral flow immunoassay (LFIA). The detection limits of this method for the detection of dexamethasone in milk, beef, and pork were 0.0018, 0.12, and 0.084 µg/kg in the "turn-off" mode (colorimetric signal), and 0.0013, 0.080, and 0.070 µg/kg in the "turn-on" mode (fluorescent signal), respectively, which was up to 231-fold more sensitive compared with that of the reported LFIAs. The recovery rates ranged from 81.1-113.7%, and 89.2-115.4%, with the coefficients of variation ranging from 1.4-15.0%, and 1.9-14.8%, respectively. The results of the LC-MS/MS confirmation test on 30 real samples had a good correlation with that of our established method (R2 > 0.97). This work not only developed novel nanocarriers for antibody-based LFIA but also ensured high-performance detection.

Cs3In(In4Se7)(P2Se6): A Multi-Chromophore Chalcogenide with Excellent Nonlinear Optical Property Designed by Group Grafting.

Non-centrosymmetric (NCS) and polar materials capable of exhibiting many important functional properties are indispensable for electro-optical technologies, yet their rational structural design remains a significant challenge. Here, we report a "group grafting" strategy for designing the first multi-chromophore selenophosphate, Cs3In(In4Se7)(P2Se6), that crystallizes in a NCS and polar space group of Cm. The structure features a unique basic building unit (BBU) [In(In4Se10)(P2Se6)], formed through "grafting [In4Se10] supertetrahedra on the root of [In(P2Se6)2] groups". Theoretical calculations confirm that this [In(In4Se10)(P2Se6)] BBU can achieve a "1+1>2" combination of properties from two chromophores, [In4Se10] supertetrahedron and ethane-like [P2Se6] dimer. That makes Cs3In(In4Se7)(P2Se6) exhibit excellent linear and nonlinear optical (NLO) properties, including a strong second harmonic generation (SHG) response (~6×AgGaS2), a large band gap (2.45 eV), broad infrared (IR) transmission (up to 19.5 µm), a significant birefringence (0.26 @1064 nm) as well as the congruently-melting property at ~700 °C. Therefore, Cs3In(In4Se7)(P2Se6) will be a promising NLO crystal, especially in the IR region, and this research also demonstrates that "group grafting" will be an effective strategy for constructing novel polar BBUs with multi-chromophore to design NCS structures and high-performance IR NLO materials.

Formation and Detection of Gizzerosine in Animal Feed Matrices: Progress and Perspectives.

Gizzerosine is responsible for gizzard erosion and black vomit, owing to excessive gastric acid secretion in poultry. It is a biogenic amine that forms during feed processing. Gizzerosine, a derivative of histamine, is a serious threat to animal feed safety and poultry production because it is more potent after ingestion and more harmful to poultry than histamine. The difficulty of obtaining gizzerosine and the lack of simple, rapid, and sensitive in vitro detection techniques have hindered studies on the effects of gizzerosine on gizzard health and poultry production. In this review, we evaluated the natural formation and the chemical synthesis methods of gizzerosine and introduced seven detection methods and their principles for analyzing gizzerosine. This review summarizes the issues of gizzerosine research and suggests methods for the future development of gizzerosine detection methods.

Electrochemical Reduction of Flue Gas Denitrification Wastewater to Ammonia Using a Dual-Defective Cu2O@Cu Heterojunction Electrode.

Wet flue gas denitrification offers a new route to convert industrial nitrogen oxides (NOx) into highly concentrated nitrate wastewater, from which the nitrogen resource can be recovered to ammonia (NH3) via electrochemical nitrate reduction reactions (NITRRs). Low-cost, scalable, and efficient cathodic materials need to be developed to enhance the NH3 production rate. Here, in situ electrodeposition was adopted to fabricate a foamy Cu-based heterojunction electrode containing both Cu-defects and oxygen vacancy loaded Cu2O (OVs-Cu2O), which achieved an NH3 yield rate of 3.59 mmol h-1 cm-2, NH3 Faradaic efficiency of 99.5%, and NH3 selectivity of 100%. Characterizations and theoretical calculations unveiled that the Cu-defects and OVs-Cu2O heterojunction boosted the H* yield, suppressed the hydrogen evolution reaction (HER), and served as dual reaction sites to coherently match the tandem reactions kinetics of NO3-to-NO2 and NO2-to-NH3. An integrated system was further built to combine wet flue gas denitrification and desulfurization, simultaneously converting NO and SO2 to produce the (NH4)2SO4 fertilizer. This study offers new insights into the application of low-cost Cu-based cathode for electrochemically driven wet denitrification wastewater valorization.

Combined treatment of human mesenchymal stem cells and green tea extract on retinal ganglion cell regeneration in rats after optic nerve injury.

Retinal ganglion cell (RGC) death and axonal loss cause irreversible vision loss upon optic nerve (ON) injury. We have independently demonstrated that mesenchymal stem cells (MSCs) and green tea extract (GTE) promote RGC survival and axonal regeneration in rats with ON injury. Here we aimed to evaluate the combined treatment effect of human bone marrow-derived MSCs (hBM-MSCs) and GTE on RGC survival and axonal regeneration after ON injury. Combined treatment of hBM-MSCs and GTE promoted RGC survival and neurite outgrowth/axonal regeneration in ex vivo retinal explant culture and in rats after ON injury. GTE increased Stat3 activation in the retina after combined treatment, and enhanced brain-derived neurotrophic factor secretion from hBM-MSCs. Treatment of 10 µg/mL GTE would not induce hBM-MSC apoptosis, but inhibited their proliferation, migration, and adipogenic and osteogenic differentiation in vitro with reducing matrix metalloproteinase secretions. In summary, this study revealed that GTE can enhance RGC protective effect of hBM-MSCs, suggesting that stem cell priming could be a prospective strategy enhancing the properties of stem cells for ON injury treatment.

Propolis alleviates ulcerative colitis injury by inhibiting the protein kinase C - transient receptor potential cation channel subfamily V member 1 - calcitonin gene-related peptide/substance P (PKC-TRPV1-CGRP/SP) signaling axis.

This study investigated the protective effect of water-soluble propolis (WSP) on colonic tissues in ulcerative colitis (UC) and the role of the protein kinase C - transient receptor potential cation channel subfamily V member 1 - calcitonin gene-related peptide/substance P (PKC-TRPV1-CGRP/SP) signaling pathway. Male SD rats were divided into a control group, a UC model group, various WSP groups (Low-WSP, Medium-WSP, and High-WSP) with UC, and a salazosulfapyridine (SASP) positive control group with UC. After UC was established, the WSP and SASP groups were treated with WSP or SASP, respectively, for 7 d. Each day, body weight measurements were obtained, and the disease activity index (DAI) was recorded by observing fecal characteristics and blood in the stool. After the experiment, hematoxylin and eosin (HE) colonic tissue staining was performed to observe pathological changes, western blotting and immunohistochemistry were performed to detect PKC, TRPV1, CGRP, and SP expression in colonic tissues, and laser confocal microscopy was performed to observe the fluorescence colocalization of PKC/TRPV1, TRPV1/CGRP, and TRPV1/SP. HE staining showed significant colonic tissue structure disruption and inflammatory infiltration in the UC group. Western blotting and immunohistochemistry showed that the expression of PKC, TRPV1, CGRP, and SP in the colonic tissues of the UC group increased significantly compared with that of the control group. Compared with the UC group, the expression of PKC, TRPV1, CGRP, and SP in colonic tissues was significantly reduced in the High-WSP, Medium-WSP, and SASP groups. Immunofluorescence showed the colocalized expression of PKC/TRPV1, TRPV1/CGRP, and TRPV1/SP proteins in the colon tissue of the UC group was significantly reduced after WSP and SASP interventions compared with that of the control group. The results suggest that the mechanism of UC alleviation by propolis may inhibit the PKC-TRPV1-CGRP/SP signaling pathway and the release of inflammatory mediators, thus alleviating inflammation.

Ileal perforation involvement in Wegener granulomatosis comorbid with COVID-19 infection: A case report and review of the literature.

RATIONALE: Granulomatosis with polyangiitis (GPA) is a systematic autoimmune disease. The typical clinical involvement of GPA entails the upper and lower respiratory tracts, and the kidneys. Gastrointestinal (GI) involvement is uncommon and unless detected and treated promptly, may lead to life-threatening complications such as perforation. We aim to review all available publications since the first description in 1982 dealing with GI perforation in patients with Wegener granulomatosis and draw attention to this serious situation. PATIENT CONCERNS: We present a 54-year-old man diagnosed with GPA who presented initially with nasal symptoms and suffered ileal perforation following Corona Virus Disease 2019 infection. We also review previously reported patients with Wegener granulomatosis who had GI perforation to investigate the perforation site and period, pathology, diagnosis, and treatment methods. DIAGNOSES AND INTERVENTIONS: The case of a GPA-diagnosed patient who presented initially with nasal symptoms and suffered ileal perforation following Corona Virus Disease 2019 infection. We recommended a renal puncture biopsy, steroids, and immunosuppressants to improve the patient condition. The patient and his family refused these treatment recommendations. OUTCOMES: Our patient exhibited continued progressive vascular inflammatory changes and eventual irreversible systemic damage. These sequelae were attributed to the patient declining prednisolone and immunosuppressant therapy. LESSONS: GI perforation is rare in GPA but severe complication. Consequently, we recommend that early diagnosis and treatment with steroid hormones and immunosuppressants for GPA patients with GI perforation.

Multimedia Mercury Recovery from Coal-Fired Power Plants Utilizing N-Containing Conjugated Polymer Functionalized Fly Ash.

To recover multimedia mercury from coal-fired power plants, a novel N-containing conjugated polymer (polyaniline and polypyrrole) functionalized fly ash was prepared, which could continuously adsorb 99.2% of gaseous Hg0 at a high space velocity of 368,500 h-1 and nearly 100% of aqueous Hg2+ in the solution pH range of 2-12. The adsorption capacities of Hg0 and Hg2+ reach 1.62 and 101.36 mg/g, respectively. Such a kind of adsorbent has good environmental applicability, i.e. good resistance to coexisting O2/NO/SO2 and coexisting Na+/K+/Ca2+/Mg2+/SO42-. This adsorbent has very low specific resistances (6 × 106-5 × 109 Ω·cm) and thus can be easily collected by an electrostatic precipitator under low-voltage (0.1-0.8 kV). The Hg-saturated adsorbent can desorb almost 100% Hg under relatively low temperature (<250 °C). Characterization and theoretical calculations reveal that conjugated-N is the critical site for adsorbing both Hg0 and Hg2+ as well as activating chlorine. Gaseous Hg0 is oxidized and adsorbed in the form of HgXClX(ad), while aqueous Hg2+ is adsorbed to form a complex with conjugated-N, and parts of Hg2+ are reduced to Hg+ by conjugated-N. This adsorbent can be easily large-scale manufactured; thus, this novel solid waste functionalization method is promising to be applied in coal-fired power plants and other Hg-involving industrial scenes.

Longitudinal in vivo evaluation of retinal ganglion cell complex layer and dendrites in mice with experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE), induced by the immunization of myelin oligodendrocyte glycoprotein (MOG), is related to human MOG antibody-associated disease (MOGAD). Neuroinflammation and demyelination of the optic nerve can lead to retinal ganglion cell (RGC) death and axonal damage in MOGAD. Here, we aimed to evaluate the structural changes in RGCs longitudinally by in vivo imaging in mice with RGCs expressing yellow fluorescent protein along the course of EAE. Successful induction of EAE was confirmed by the neurological function scores and histology analyses. The changes in the thickness of ganglion cell complex (GCC) layer and RGC survival and dendrites were monitored longitudinally along the course of EAE. Before the onset of EAE, there were no significant changes in the number and morphology of RGCs and the thickness of the GCC layer as compared to the mice without EAE induction. After the onset of EAE, the thickness of the GCC layer and the RGC number and dendritic network all gradually decreased along the course of EAE. Notably, dendritic shrinkage could be detected earlier than the thinning of the GCC layer. In summary, this study delineated the longitudinal profile of RGC structural changes in EAE mice, providing an assessment platform for monitoring outcomes of RGC treatments.

Qualitative and Quantitative Analysis of Five Indoles or Indazole Amide Synthetic Cannabinoids in Suspected E-Cigarette Oil by GC-MS.

OBJECTIVES: To establish the GC-MS qualitative and quantitative analysis methods for the synthetic cannabinoids, its main matrix and additives in suspicious electronic cigarette (e-cigarette) oil samples. METHODS: The e-cigarette oil samples were analyzed by GC-MS after diluted with methanol. Synthetic cannabinoids, its main matrix and additives in e-cigarette oil samples were qualitatively analyzed by the characteristic fragment ions and retention time. The synthetic cannabinoids were quantitatively analyzed by using the selective ion monitoring mode. RESULTS: The linear range of each compound in GC-MS quantitative method was 0.025-1 mg/mL, the matrix recovery rate was 94%-103%, the intra-day precision relative standard deviations (RSD) was less than 2.5%, and inter-day precision RSD was less than 4.0%. Five indoles or indazole amide synthetic cannabinoids were detected in 25 e-cigarette samples. The main matrixes of e-cigarette samples were propylene glycol and glycerol. Additives such as N,2,3-trimethyl-2-isopropyl butanamide (WS-23), glycerol triacetate and nicotine were detected in some samples. The content range of synthetic cannabinoids in 25 e-cigarette samples was 0.05%-2.74%. CONCLUSIONS: The GC-MS method for synthesizing cannabinoid, matrix and additive in e-cigarette oil samples has good selectivity, high resolution, low detection limit, and can be used for simultaneous qualitative and quantitative analysis of multiple components; The explored fragment ion fragmentation mechanism of the electron bombardment ion source of indole or indoxamide compounds helps to identify such substances or other compounds with similar structures in cases.

[Evidence mapping analysis of clinical research on traditional Chinese medicine in treatment of vertigo].

In this study, the evidence map system was used to sort out the clinical research evidence on traditional Chinese medicine(TCM) treatment of vertigo and understand the evidence distribution in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Web of Science were searched for the clinical randomized controlled trial(RCT) and systematic reviews/Meta-analysis on TCM treatment of vertigo in recent five years, and the evidence was analyzed and presented in the form of text and charts. The Cochrane handbook for systematic reviews of interventions was used to evaluate the quality of the clinical RCT, and the AMSTAR mea-surement tool was used to evaluate the quality of the systematic reviews/Meta-analysis. A total of 382 RCTs and eight systematic reviews/Meta-analysis were included. In recent five years, the number of published articles has been on the rise. There were many intervention measures and TCM therapies for vertigo. Outcome indicators mainly included clinical efficacy, TCM syndrome score, vertigo score, occurrence of adverse reactions, and effective rate. The overall quality of clinical RCT and systematic reviews/Meta-analysis was low. Most studies have proven the potential efficacy of TCM in treating vertigo, but there was still no clear clinical evidence of efficacy. The results show that TCM has advantages in the treatment of vertigo, but there are also problems. More high-quality studies are still lacking, suggesting that more large-sample and multi-center RCT should be conducted in the future, and the quality of relevant syste-matic reviews/Meta-analysis should be improved to fully explore the advantages of TCM in the treatment of vertigo, and provide strong support for the effectiveness and safety of TCM in the treatment of vertigo.

Identification and Analysis of a Four-Gene Set for Diagnosing SFTS Virus Infection Based on Machine Learning Methods and Its Association with Immune Cell Infiltration.

Severe Fever with thrombocytopenia syndrome (SFTS) is a highly fatal viral infectious disease that poses a significant threat to public health. Currently, the phase and pathogenesis of SFTS are not well understood, and there are no specific vaccines or effective treatment available. Therefore, it is crucial to identify biomarkers for diagnosing acute SFTS, which has a high mortality rate. In this study, we conducted differentially expressed genes (DEGs) analysis and WGCNA module analysis on the GSE144358 dataset, comparing the acute phase of SFTSV-infected patients with healthy individuals. Through the LASSO-Cox and random forest algorithms, a total of 2128 genes were analyzed, leading to the identification of four genes: ADIPOR1, CENPO, E2F2, and H2AC17. The GSEA analysis of these four genes demonstrated a significant correlation with immune cell function and cell cycle, aligning with the functional enrichment findings of DEGs. Furthermore, we also utilized CIBERSORT to analyze the immune cell infiltration and its correlation with characteristic genes. The results indicate that the combination of ADIPOR1, CENPO, E2F2, and H2AC17 genes has the potential as characteristic genes for diagnosing and studying the acute phase of SFTS virus (SFTSV) infection.

Effect of a novel tyrosine kinase inhibitor nintedanib on bFGF and VEGF concentrations in a rabbit retinal vein occlusion model.

AIM: To evaluate whether a novel tyrosine kinase inhibitor nintedanib could inhibit basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) simultaneously for retinal vascular disease in vivo. METHODS: After a laser induced rabbit retinal vein occlusion (RVO) model was made, 0.5 mg of nintedanib was injected intravitreally in the left eye on the third day while the right eye was as a control. Intracameral samples were taken on the day before laser treatment and days 1, 3, 7, 14, 21, and 28 after treatment. Enzyme-linked immunosorbent assay (ELISA) was used to test the bFGF and VEGF-A concentrations in the aqueous humor. RESULTS: Both bFGF and VEGF-A rose significantly on the third day after laser treatment in both eyes. In the control eye the bFGF concentration peaked on the 14th day while the VEGF-A concentration dropped rapidly soon after the third day. After nintadanib injection in the study eye, both bFGF and VEGF-A showed a significant reduction on the 4th day (7th day after laser treatment) when compared to the control eye, and kept on low level in the following several weeks. CONCLUSION: Intravitreal injection of nintedanib can inhibit the expression of bFGF and VEGF in the process of RVO model to a certain extent, which is expected to become a new method for the treatment of retinal vascular diseases or fibrotic diseases.

Investigation of lacrimal sac space-occupying lesions using color doppler ultrasound, computed tomography, and computed tomography dacryocystography.

AIM: To observe the imaging features of color Doppler ultrasound (CDU) and computed tomography (CT) or computed tomography dacryocystography (CT-DCG) in different types of lacrimal sac space-occupying lesions (SOLs). METHODS: This retrospective case series study included 21 patients with lacrimal sac SOLs who underwent lacrimal sac surgery between January 2018 and March 2022. The imaging features of CDU and CT or CT-DCG in these patients were extracted from the examination cloud system. The images were observed and analyzed. RESULTS: The detection rate of lacrimal SOLs between CDU (21/21, 100%) and CT or CT-DCG (20/21, 95.2%) had no statistically significant difference (P=1.0). CDU could detect the blood flow signals in all SOLs except mucocele and mucopeptide concretion. Among them, polyps had characteristic imaging changes on CDU and CT-DCG. The mucoceles and mucopeptide concretions had characteristic imaging changes on CDU, which could provide more information for differential diagnosis. CONCLUSION: The morphology and internal blood flow signals of lacrimal sac SOLs can be observed using CDU. CT or CT-DCG has advantages in observing structural damage around the lacrimal sac mass. Therefore, CDU may be used as a routine examination to exclude lacrimal sac SOLs before dacryocystorhinostomy in the absence of preoperative CT or CT-DCG.

Tanshinone I suppresses hepatocellular carcinoma cells growth through targeting DNA double-strand break repair.

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors with increasing incidence rates and high mortality rates. The currently available methods for treating HCC include surgery, radiotherapy or chemotherapy, but all of them have limitations. Therefore, developing novel therapeutic methods for HCC is in great need. Here, in this study, we found that tanshinone I, a small molecule compound, inhibited the proliferation of HCC cells in a dose-dependent manner. We also observed that Tanshinone I destabilized genomes by inhibiting both NHEJ and HR repair pathways, which are responsible for repairing DNA double strand breaks (DSBs). Mechanistically, this compound suppressed the expression of 53BP1, and the recruitment of RPA2 to DNA damage sites. Importantly, we demonstrated that combining Tanshinone I with radiotherapy exhibited better therapeutic potential for treating HCC.