Triple motif proteins 19 and 38 correlated with treatment responses and HBsAg clearance in HBeAg-negative chronic hepatitis B patients during peg-IFN-α therapy.

OBJECTIVE: To investigate whether the expression of triple motif protein 19/38 (TRIM19/38) mRNA in peripheral blood mononuclear cells (PBMCs) of HBeAg-negative chronic hepatitis B virus (HBV) carriers is associated with the response to pegylated interferon alpha (peg-IFN-α) treatment and HBsAg clearance. METHODS: In this prospective study, HBeAg-negative chronic HBV carriers treated with peg-IFN-α completed 48 weeks of follow-up. After treatment with peg-IFN-α, the patients were divided into responders (R group) and nonresponders (NR group) according to the changes in HBV DNA and HBsAg levels at week 48 of treatment. According to whether serum HBsAg loss or seroconversion occurred, the patients were divided into a serological response group (SR group) and a nonserological response group (NSR group). The level of TRIM19/38 mRNA in PBMCs was detected by real-time fluorescence quantitative PCR. The diagnostic performance of TRIM19/38 was analysed by calculating the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). RESULTS: 43 HBeAg-negative chronic HBV carriers, 35 untreated CHB patients and 19 healthy controls were enrolled in this study. We found that TRIM19/38 mRNA levels were significantly lower in untreated CHB patients than in healthy controls. In HBeAg-negative chronic HBV carriers who underwent prospective follow-up, TRIM19/38 mRNA levels were negatively correlated with HBV DNA and ALT at baseline. Among the patients treated with peg-IFN-α, 16 patients achieved a treatment response (R group) and 27 patients did not achieve a treatment response (NR group). Compared with baseline, HBsAg levels in the R group decreased significantly at 12 and 24 weeks of treatment; at the early stage of peg-IFN-α treatment, the dynamic changes in TRIM19/38 mRNA levels in the R and NR groups were different, and the TRIM19/38 mRNA levels in the R group were significantly higher than those in the NR group, especially at 24 weeks of treatment. ROC curve analysis showed that the changes in mRNA levels of TRIM19 and TRIM38 predicted the treatment response, with AUCs of 0.694 and 0.757, respectively. Among the patients treated with peg-IFN-α, 11 patients achieved a serological response (SR group) and 32 patients did not achieve a serological response (NSR group). Compared with baseline, HBsAg levels in the SR group decreased significantly at 12 and 24 weeks of treatment; TRIM19/38 mRNA levels were significantly higher in the SR group than in the NSR group at week 24. CONCLUSION: The higher level of TRIM19/38 mRNA in PBMCs of HBeAg-negative chronic HBV carriers may be related to the early treatment effect of peg-IFN-α and HBsAg clearance. TRIM19 and TRIM38 have clinical significance in predicting virological response and guiding treatment regimens.

The expression of interleukin-1ß in patients with chronic hepatitis B treated with pegylated-interferon-alpha combined with tenofovir disoproxil fumarate and monotherapy.

BACKGROUND: Anti-hepatitis B virus (HBV) treatment uses tenofovir disoproxil fumarate (TDF) along with Pegylated-interferon-alpha (Peg-IFN-α), which is more effective than TDF/Peg-IFN-α monotherapy. We have previously shown that interleukin-1beta (IL-1ß) is related to the effectiveness of IFN-α treatment in chronic hepatitis B (CHB) patients. The aim was to investigate the expression of IL-1ß in CHB patients treated with Peg-IFN-α combination with TDF and TDF/Peg-IFN-α monotherapy. METHODS: Huh7 cells infected with HBV were stimulated by Peg-IFN-α and/or Tenofovir (TFV) for 24h. A single-center cohort study of prospective recruitment of CHB patients: untreated CHB (Group A), TDF combined with Peg-IFN-α therapy (Group B), Peg-IFN-α monotherapy (Group C), TDF monotherapy (Group D). Normal donors served as controls. The clinical datas and blood of patients were collected at 0, 12, and 24 weeks. According to the early response criteria, Group B and C were divided into two subgroups: the early response group (ERG) and the non-early response group (NERG). Stimulation of HBV-infected hepatoma cells with IL-1ß to validate the antiviral activity of IL-1ß. To test the blood sample, cell culture supernatant, and cell lysates and to assess the expression of IL-1ß and HBV replication levels in various treatment protocols, Enzyme-Linked Immunosorbent Assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used. SPSS 26.0 and GraphPad Prism 8.0.2 software were used for statistical analysis. P values < 0.05 was considered to be statistically significant. RESULTS: In vitro experiments, Peg-IFN-α plus TFV treatment group expressed higher IL-1ß and inhibited HBV more effectively than monotherapy. Finally, 162 cases were enrolled for observation (Group A (n = 45), Group B (n = 46), Group C (n = 39), and Group D (n = 32)), and normal donors (n = 20) were enrolled for control. The early virological response rates of Group B, C, and D were 58.7%, 51.3%, and 31.2%. At 24 weeks, IL-1ß in Group B(P = 0.007) and C(P = 0.034) showed higher than at 0 week. In Group B, the IL-1ß showed an upward trend at 12w and 24w in the ERG. IL-1ß significantly reduced HBV replication levels in hepatoma cells. CONCLUSION: The increased expression of IL-1ß may enhance the efficacy of TDF combined with Peg-IFN-α therapy in achieving an early response for CHB patients.

[Anti-fibrotic mechanism of Sedum sarmentosum total flavanones in inhibiting activation of HSC by regulating Smads].

This paper was aimed to observe the interventional effect of Sedum sarmentosum total flavanones on hepatic fibrosis and its possible mechanism through the subcutaneous injection of CCl_4 in rats. Sixty male SD rats were randomly divided into normal control group, model group, low-dose, medium-dose, high-dose S. sarmentosum total flavanones groups(100, 200, 400 mg·kg~(-1)) and silymarin group(200 mg·kg~(-1)). The model of liver fibrosis was established by subcutaneous injection of rats with 40% CCl_4. After the modeling, the drug groups were intragastrically administered with corresponding drugs once a day for consecutively five weeks, while the normal group and the model group were given 0.9% sodium chloride solution during the same period. After the experiment, the general conditions of rats and the pathological changes of liver tissues were observed, and the contents of serum ALT, AST, HA and LN were measured. Besides, the expressions of the protein and relevant mRNA of Smad2/3, Smad4 and α-SMA in rats were detected. Compared with model group, S. sarmentosum total flavanones could significantly increase the rats' body weight, inhibit the increase of liver and spleen index in rats of liver fibrosis, reduce the levels of ALT, AST, HA and LN, and alleviate pathological changes. Meanwhile, compared with the model group, the protein expressions of Smad2/3, Smad4 and α-SMA as well as relevant mRNA expressions in S. sarmentosum total flavanones group were obviously decreased, while Smad7 expression was markedly increased. As a result, S. sarmentosum total flavanones could significantly alleviate CCl_4-induced liver fibrosis, and its anti-hepatic fibrosis mechanism may be related to intervention with Smads pathway, so as to inhibit the activation of HSC.

Compound and heterozygous mutations of DSG2 identified by Whole Exome Sequencing in arrhythmogenic right ventricular cardiomyopathy/dysplasia with ventricular tachycardia.

BACKGROUNDS: This study was designed to identify the pathogenic mutations in two Chinese families of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) using the Whole Exome Sequencing (WES). METHODS AND RESULTS: The proband 1 (Family 1, II:1) and proband 2 (Family 2, II:1) underwent the WES of DNA from peripheral blood. The genes susceptible to arrhythmias and cardiomyopathies were analyzed and both the probands carried the same exonic mutation of DSG2 p.F531C (NM_001943, exon 11: c.T1592G). The proband 1 also carried the splicing mutation of DSG2 (NM_001943: exon 4:c.217-1G>T), and proband 2 carried the intronic mutation of DSG2 (NM_001943: exon 6: c.524-3C>G) that potentially influenced the splicing function predicted by Human Splicing Finder. The compound heterozygous mutations of the two probands inherited from their paternal and maternal side, respectively. The carriers with DSG2 p.F531C showed early abnormal electrocardiograms, characterized as the subclinical phenotype of ARVC/D. CONCLUSIONS: The DSG2 p.F531C was the main reason for ARVC/D. More severe phenotypes of ARVC/D occurred when coexisting with 217-1G>T or 524-3C>G mutation that potentially affecting the splicing function, as a compound heterozygous recessive inheritance.

Microgravity activates p38 MAPK-C/EBPß pathway to regulate the expression of arginase and inflammatory cytokines in macrophages.

OBJECTIVE AND DESIGN: Molecular mechanisms of microgravity-caused immunosuppression are not fully elucidated. In the present study, we investigated the effects of simulated microgravity on macrophage functions and tried to identify the related intracellular signal pathways. MATERIAL OR SUBJECTS: Primary mouse macrophages were used in the present study. The gene expression and function of IL-4-treated mouse macrophages were detected after simulated microgravity or 1 g control. METHODS: Freshly isolated primary mouse macrophages were cultured in a standard simulated microgravity situation using a rotary cell culture system (RCCS-1) and 1 g control conditions. Real-time PCR, western blots and flow cytometry were used to investigate the related intracellular signals and molecule expression. RESULTS: The arginase mRNA and protein levels in freshly isolated primary mouse macrophages under simulated microgravity using RCCS-1 were significantly higher than those under normal gravity. Meanwhile, simulated microgravity induced over-expression of C/EBPß, a transcription factor of arginase promoter, and activation of p38 MAPK, which could increase C/EBPß expression. Furthermore, up-regulation of Interleukin-6 (IL-6) and down-regulation of IL-12 p40 (IL-12B) in LPS-stimulated macrophages were also detected after simulated microgravity, which is regulated by C/EBPß. CONCLUSIONS: Simulated microgravity activates a p38 MAPK-C/EBPß pathway in macrophages to up-regulate arginase and IL-6 expression and down-regulate IL-12B expression. Both increased arginase expression and decreased IL-12B expression in macrophages during inflammation could result in immunosuppression under microgravity.

Phosphatase Wip1 is essential for the maturation and homeostasis of medullary thymic epithelial cells in mice.

Thymic epithelial cells (TECs) are a key cell type in the thymic microenvironment essential for T cell development. However, intrinsic molecular mechanisms controlling TEC differentiation and activities are poorly defined. In this study, we found that deficiency of p53-induced phosphatase 1 (Wip1) in mice selectively caused severe medullary TEC (mTEC) maturation defects in an intrinsic manner. Wip1 knockout (KO) mice had decreased mature epithelial cell adhesion molecule⁺Ulex europaeus agglutinin-1 (UEA-1)⁺mTECs, including UEA-1⁺MHC class II(high), UEA-1⁺CD80⁺, UEA-1⁺CD40⁺, and UEA-1⁺Aire⁺ cells, but not decreased numbers of cortical epithelial cell adhesion molecule⁺BP-1⁺ TECs, in the postnatal stage but not in the fetal stage. Wip1-deficient mTECs express fewer tissue-restricted Ags and UEA-1⁺involucrin⁺ terminal-differentiated cells. Animal models, including grafting fetal Wip1-deficient thymic tissue into T cell-deficient nude mice and reconstitution of lethally irradiated Wip1KO mouse recipients with wild-type bone marrow cells, also showed the impaired mTEC components in Wip1KO thymi, indicating the intrinsic regulatory role of Wip1 in mTEC maturation. Furthermore, thymus regeneration was significantly less efficient in adult Wip1KO mice than in wild-type mice after cyclophosphamide treatment. Wip1 deficiency resulted in elevated p38 MAPK activity in mTECs. Activated p38 MAPK has the ability to suppress CD40 expression on mTECs. Wip1-deficient thymi displayed poor response to CD40L in the fetal thymus organ culture system. Thus, Wip1 positively controls mTEC maturation, homeostasis, and regeneration through limiting the p38 MAPK pathway.

[Attenuated total reflection-fourier transform infrared spectroscopic study of dried shark fin products].

Sixty-four pieces of shark fin dried products (including real, fake and artificial shark fin products) and real products coated with gelatin were rapidly and nondestructively analyzed by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). The characteristic of IR spectrograms among the above four kinds of samples were systematically studied and comparied, the results showed that the spectrograms of the same kind of samples were repeatable, and different kinds of shark fin products presented significant differences in the spectrograms, which mainly manifested as the specific absorption peaks of amido bonds in protein (1650, 1544 cm(-1)) and skeletal vibration in polysaccharide (1050 cm(-1)). The spectrograms of real shark fins were characterized by the strong absorption peaks of protein characteristic amide I and II absorbent (1650, 1544 cm(-1)) and relatively weak C--O--C vibration absorbent (1050 cm(-1)) owing to the high content of protein and relatively low level of polysaccharide. For fake shark fin products that were molded form by mixing together with the offcut of shark, collagen and other substances, the introduction of non-protein materials leaded to the weaker amido bonds absorbent than real products along with a 30 cm(-1) blue shift of amide I absorbent. Opposite to the real sample, the relatively strong absorption peak of polysaccharide (approximately 1047 cm(-1)) and barely existed amide absorbent were the key features of the spectrogram of artificial samples, which was synthersized by polysaccharide like sodium alginate. Real samples coated with gelatin, the peak strength of protein and polysaccharide were decreased simultaneously when the data collection was taken at the surface of sample, while the spectrogram presented no significant difference to real samples when the data was collected in the section. The results above indicated that by analyzing the characteristic of IR spectrograms and the value range of Apro/Apol collected by ATR-FTIR method could perform the undamaged and rapid identification for shark fins.

[Study on effect of total flavanones of Sedum sarmentosum on apoptosis of hepatic stellate cells and its mechanism].

OBJECTIVE: To study the effect of total flavanones of Sedum sarmentosum (SSTF) on the apoptosis of rat hepatic stellate cells (HSC-T6) and its mechanism. METHOD: Different concentrations of SSTF and HSC-T6 cells were co-cultured for different period of time. The MTT assay was used to detect the inhibitory effect of SSTF on the proliferation of HSC-T6 cells. The flow cytometry Annexin-V/PI double staining method was adopted to detect SSTF's effect on HSC-T6 cell apoptosis. Western blotting and Real-time PCR methods were applied to observe the effect on the protein and mRNA expressions of apoptosis-related cytokines Bcl-2, Bax and Caspase-3. RESULT: SSTF significantly inhibited HSC-T6 cell proliferation and induced cell apoptosis in a dose and time dependent manner. According to Western blotting result, SSTF promoted apoptosis by inhibiting Bcl-2, Bax and promoting the protein expression of Caspase-3; according to a further Real-time PCR study, Bcl-2 mRNA levels can inhibit Bcl-2 and promote Bax and Caspase-3 expressions. CONCLUSION: SSTF has the effect of promoting the apoptosis of HSC-T6 mainly by inhibiting Bcl-2 and promoting protein and mRNA expressions of Bax and caspase-3.

Microgravity inhibition of lipopolysaccharide-induced tumor necrosis factor-α expression in macrophage cells.

OBJECTIVE AND DESIGN: Microgravity environments in space can cause major abnormalities in human physiology, including decreased immunity. The underlying mechanisms of microgravity-induced inflammatory defects in macrophages are unclear. MATERIAL OR SUBJECTS: RAW264.7 cells and primary mouse macrophages were used in the present study. Lipopolysaccharide (LPS)-induced cytokine expression in mouse macrophages was detected under either simulated microgravity or 1g control. METHODS: Freshly isolated primary mouse macrophages and RAW264.7 cells were cultured in a standard simulated microgravity situation using a rotary cell culture system (RCCS-1) and 1g control conditions. The cytokine expression was determined by real-time PCR and ELISA assays. Western blots were used to investigate the related intracellular signals. RESULTS: LPS-induced tumor necrosis factor-α (TNF-α) expression, but not interleukin-1ß expression, in mouse macrophages was significantly suppressed under simulated microgravity. The molecular mechanism studies showed that LPS-induced intracellular signal transduction including phosphorylation of IKK and JNK and nuclear translocation of NF-κB in macrophages was identical under normal gravity and simulated microgravity. Furthermore, TNF-α mRNA stability did not decrease under simulated microgravity. Finally, we found that heat shock factor-1 (HSF1), a known repressor of TNF-α promoter, was markedly activated under simulated microgravity. CONCLUSIONS: Short-term treatment with microgravity caused significantly decreased TNF-α production. Microgravity-activated HSF1 may contribute to the decreased TNF-α expression in macrophages directly caused by microgravity, while the LPS-induced NF-κB pathway is resistant to microgravity.

Microgravity inhibits resting T cell immunity in an exposure time-dependent manner.

BACKGROUND: Decline immune function is well documented after spaceflights. Microgravity is one of the key factors directly suppressing the function of immune system. Though T cell immune response was inhibited by microgravity, it is not clearly whether activation would be inhibited after a pre-exposure of microgravity on T lymphocytes at the resting state. METHODS: We herein investigated the response ability of resting CD4⁺ and CD8⁺ T cells experiencing pre-exposure of modeled microgravity (MMg) for 0, 8, 16 and 24 hrs to concanavalin A (ConA) stimulation. The phenotypes and subsets of immune cells were determined by flow cytometry. RESULTS: Both CD4⁺ and CD8⁺ T cells with an MMg pre-exposure exhibited decreased expressions of activation-markers including CD25, CD69 and CD71, inflammatory cytokine secretion and cell proliferation in response to ConA compared with T cells with 1g controls in an MMg exposure time- dependent manner. Moreover, short term MMg treatment caused more severe decreased proliferation in CD4⁺ T cells than in CD8⁺ T cells. CONCLUSIONS: MMg can directly impact on resting T cell subsets. CD4⁺ T cells were more sensitive to the microgravity inhibition than CD8⁺ T cells in respect of cell proliferation. These results offered new insights for the MMg-caused T cell functional defects.

Dispersive liquid-liquid microextraction combined with ultrahigh performance liquid chromatography/tandem mass spectrometry for determination of organophosphate esters in aqueous samples.

A new technique was established to identify eight organophosphate esters (OPEs) in this work. It utilised dispersive liquid-liquid microextraction in combination with ultrahigh performance liquid chromatography/tandem mass spectrometry. The type and volume of extraction solvents, dispersion agent, and amount of NaCl were optimized. The target analytes were detected in the range of 1.0-200 µ g/L with correlation coefficients ranging from 0.9982 to 0.9998, and the detection limits of the analytes were ranged from 0.02 to 0.07 µg/L (S/N = 3). The feasibility of this method was demonstrated by identifying OPEs in aqueous samples that exhibited spiked recoveries, which ranged between 48.7% and 58.3% for triethyl phosphate (TEP) as well as between 85.9% and 113% for the other OPEs. The precision was ranged from 3.2% to 9.3% (n = 6), and the interprecision was ranged from 2.6% to 12.3% (n = 5). Only 2 of the 12 selected samples were tested to be positive for OPEs, and the total concentrations of OPEs in them were 1.1 and 1.6 µg/L, respectively. This method was confirmed to be simple, fast, and accurate for identifying OPEs in aqueous samples.

Reactive Carbonyl Species Scavenger: Epigallocatechin-3-Gallate.

Epigallocatechin-3-gallate (EGCG), a prominent polyphenol found abundantly in tea, has garnered significant attention for its potential in preventing and ameliorating a wide range of diseases. Its remarkable antioxidant properties and ability to capture reactive carbonyl species make it a key player among tea's polyphenolic components. This paper delves into the synthesis and origins of both EGCG and reactive carbonyl species (RCS), emphasizing the toxicity of RCS in various food sources and their formation during food processing. Understanding EGCG's capability to capture and metabolize RCS is crucial for harnessing its health benefits. Thus, this paper explores the underlying mechanisms of EGCG for RCS inhibition and its role in capturing these compounds to generate EGCG-RCS adducts. And the absorption and metabolism of EGCG-RCS adducts is also discussed.

A Forward Learning Algorithm for Neural Memory Ordinary Differential Equations.

The deep neural network, based on the backpropagation learning algorithm, has achieved tremendous success. However, the backpropagation algorithm is consistently considered biologically implausible. Many efforts have recently been made to address these biological implausibility issues, nevertheless, these methods are tailored to discrete neural network structures. Continuous neural networks are crucial for investigating novel neural network models with more biologically dynamic characteristics and for interpretability of large language models. The neural memory ordinary differential equation (nmODE) is a recently proposed continuous neural network model that exhibits several intriguing properties. In this study, we present a forward-learning algorithm, called nmForwardLA, for nmODE. This algorithm boasts lower computational dimensions and greater efficiency. Compared with the other learning algorithms, experimental results on MNIST, CIFAR10, and CIFAR100 demonstrate its potency.

Guanylate-Binding Protein 1 (GBP1) Enhances IFN-α Mediated Antiviral Activity against Hepatitis B Virus Infection.

Interferon-alpha (IFN-α) is a first-line drug for treating chronic hepatitis B (CHB). Guanylate-binding protein 1 (GBP1) is one of the interferon-stimulating factors, which participates in the innate immunity of the host and plays an antiviral and antibacterial role. In this study, we explored how GBP1 is involved in IFN-α antiviral activity against HBV. Before being gathered, HepG2-NTCP and HepG2 2.15 cells were transfected with the wild-type hGBP1 plasmid or si-GBP1, respectively, and followed by stimulation with Peg-IFNα-2b. We systematically explored the role of GBP1 in regulating HBV infection in cell models. Additionally, we also examined GBP1 levels in CHB patients. GBP1 activity increased, and its half-life was prolonged after HBV infection. Overexpression of GBP1 inhibited the production of HBsAg and HBeAg, as well as HBs protein and HBV total RNA levels, whereas silencing of GBP1 inhibited its ability to block viral infections. Interestingly, overexpressing GBP1 co-treatment with Peg-IFNα-2b further increased the antiviral effect of IFN-α, while GBP1 silencing co-treatment with Peg-IFNα-2b partly restored its inhibitory effect on HBV. Mechanistically, GBP1 mediates the anti-HBV response of Peg-IFNα-2b by targeting HBs. Analysis of clinical samples revealed that GBP1 was elevated in CHB patients and increased with Peg-IFNα-2b treatment, while GBP1 showed good stability in the interferon response group. Our study demonstrates that GBP1 inhibits HBV replication and promotes HBsAg clearance. It is possible to achieve antiviral effects through the regulation of IFN-α induced immune responses in response to HBV.

18F-FDG PET/CT and contrast-enhanced CT in the diagnosis of Castleman disease.

OBJECTIVE: Castleman disease (CD) is a rare group of lymphoproliferative disorders, which is easily confused with lymphoma or other solid tumors. Hence, this study aimed to investigate the diagnostic role of 18F-FDG PET/CT and contrast-enhanced CT (CECT) in patients with CD. METHODS: Clinicopathological characteristics, and 18F-FDG PET/CT and CECT findings and parameters were retrospectively reviewed in 32 patients with CD. RESULTS: These 32 patients (12 males, 20 females; median age, 41 years) consisted of 17 unicentric CD (UCD) patients and 15 multicentric CD (MCD) patients. Compared with MCD, UCD had a higher prevalence in female (82.4% vs. 40.0%) and hyaline vascular subtype (94.1% vs. 40.0%) (P < 0.05). FDG uptake was avid in all cases, including moderate uptake in 7 cases and intense uptake in 25 cases. The median SUVmax, SUVmean, MLV, and TLG of all cases were 4.4 (range, 1.4-23.6), 2.7 (range, 1.1-15.2), 26.6 (range, 4.8-393.0), and 78.8 (range, 9.4-1545.6), respectively. The lesions of 29 cases showed homogeneous enhancement, and marked enhancement was observed in 27 cases. 18F-FDG PET/CT corrected 6.3% CECT diagnoses, while CECT corrected 37.5% PET/CT diagnosis. The accuracy of combined PET/CT and CECT was superior to PET/CT or CECT alone (78.1%, 31.3%, and 62.5%). Besides, higher SUVmax and SUVmean were found in male subjects, MCD, and plasma cell subtype (P < 0.05), while higher MLV and TLG were observed in larger lesion size and volume (P < 0.05). CONCLUSION: Castleman disease most commonly appears as marked and homogeneous enhancement meanwhile with moderate or intense FDG uptake. 18F-FDG PET/CT combined with CECT was the effectively diagnostic modality for CD. The glucose metabolism of CD was associated with gender, clinical classification, histopathological classification, and lesion size and volume.

The antiviral activity of tripartite motif protein 38 in hepatitis B virus replication and gene expression and its association with treatment responses during PEG-IFN-α antiviral therapy.

Hepatitis B virus (HBV) infection represents one of the most critical health problems worldwide. Tripartite motif protein 38 (TRIM38) is an interferon-stimulated gene (ISG) that inhibits various DNA and RNA viruses.In this study, we found a mechanistic correlation between TRIM38 expression levels and the efficacy of HBV infection and IFN-α therapy in patients with CHB. TRIM38 was highly induced by IFN-alpha (IFN-α) in vivo and in vitro. TRIM38 overexpression inhibited HBV replication and gene expression in HepG2 and HepG2.2.15 cells, whereas knockdown of TRIM38 increased these processes. Further experiments indicated that TRIM38 protein enhanced the antiviral effect of IFN-α by enhancing the expression of antiviral proteins. A prospective study revealed high TRIM38 levels in peripheral blood PBMCs were from early responders, and increased TRIM38 expression correlated with a better response to PEG-IFN-α therapy. Taken together, our study suggests that TRIM38 plays a vital role in HBV replication and gene expression.

Development and Validation of a Novel Prognosis Model Based on a Panel of Three Immunogenic Cell Death-Related Genes for Non-Cirrhotic Hepatocellular Carcinoma.

Purpose: The accurate prediction of non-cirrhotic hepatocellular carcinoma (NCHCC) risk facilitates improved surveillance strategy and decreases cancer-related mortality. This study aimed to explore the correlation between immunogenic cell death (ICD) and NCHCC prognosis using The Cancer Genome Atlas (TCGA) datasets, and the potential prognostic value of ICD-related genes in NCHCC. Methods: Clinical and transcriptomic data of patients with NCHCC patients were retrieved from TCGA database. Weighted gene co-expression network analysis was performed to obtain the NCHCC phenotype-related module genes. Consensus clustering analysis was performed to classify the patients into two clusters based on intersection genes among differentially expressed genes (DEGs) between cancer and adjacent tissues, NCHCC phenotype-related genes, and ICD-related genes. NCHCC-derived tissue microarray was used to evaluate the correlation of the expression levels of key genes with NCHCC prognosis using immunohistochemical staining. Results: Cox regression analyses were performed to construct a prognostic risk score model comprising three genes (TMC7, GRAMD1C, and GNPDA1) based on DEGs between two clusters. The model stratified patients with NCHCC into two risk groups. The overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group. Univariable and multivariable Cox regression analyses revealed that these signature genes are independent predictors of OS. Functional analysis revealed differential immune status between the two risk groups. Next, a nomogram was constructed, which demonstrated the potent distinguishing ability of the developed model based on receiver operating characteristic curves. In vitro functional validation revealed that the migration and invasion abilities of HepG2 and Huh7 cells were upregulated upon GRAMD1C knockdown but downregulated upon TMC7 knockdown. Conclusion: This study developed a prognostic model comprising three genes, which can aid in predicting the survival of patients with NCHCC and guide the selection of drugs and molecular markers for NCHCC.

A mathematical model for cell cycle control: graded response or quantized response.

Cell cycle is an important and complex biological system. A lot of efforts have been put in understanding cell cycle arrest for its vital role in clinical therapies. The cell-cycle-arrest outcomes upon stimulation are complicated. The response could be stringent or relaxed, and graded or quantized. A model fully addressing various cell-cycle-arrest outcomes is to be developed. Here, we developed a mathematical model of cell cycle control incorporating distinct characteristics of various cell-cycle-arrest outcomes. The model can simulate two typical properties of cell cycle arrest, quantized and graded. We also characterized the inheritable quiescence and refractory state, which were crucial in long-term response of the population. Then, we monitored cells respond to multiple stimulations, and the results indicated that cells responded to stimulations with small interval did not induce significantly sustained cell cycle arrest as the existence of refractory state. Our work will benefit fundamental research and make efforts to predicting outcomes of clinical therapeutics.

Mechanistic considerations for the advanced oxidation treatment of fluoroquinolone pharmaceutical compounds using TiO(2) heterogeneous catalysis.

Pharmaceutical compounds and metabolites are being found in surface and ground waters which is indicative of inefficient removal by conventional wastewater treatment technologies. Advanced oxidation processes (AOPs), which utilize free-radical reactions to degrade chemical contaminates, are an alternative to traditional water treatment. Three fluoroquinolone pharmaceutical compounds were studied and the absolute rate constants for hydroxyl radical (*OH) and hydrated electron (e(-)(aq)) are reported. For norfloxacin, levofloxacin, and lomefloxacin, the bimolecular reaction rate constants with *OH were determined as (6.18 +/- 0.18) x 10(9), (7.59 +/- 0.16) x 10(9) and (8.04 +/- 0.62) x 10(9) M(-1) s(-1), and with e(-)(aq) were (1.18 +/- 0.10) x 10(10), (2.46 +/- 0.05) x 10(10) and (2.79 +/- 0.05) x 10(10) M(-1) s(-1), respectively. To provide insights into the chemistry of destruction of these three target pharmaceuticals, transient spectra were obtained for the reaction of hydroxyl radicals with the three compounds. Photocatalysis was chosen as a representative advanced oxidation technology to degrade these three fluoroquinolones and their degradation pathways were proposed. Elimination of piperazynilic ring in fluoroquinolone molecules, addition of hydroxyl radical to quinolone ring, and ipso attack at the F atoms on the aromatic ring by hydroxyl radicals occurred. These results indicate that AOPs involving production of *OH radicals are efficiently alternative treatment technologies for degradation of fluoroquinolones in aqueous solution.

A series of new hybrid chalcogenogermanates: the rare examples of chalcogenogermanates combined with trivalent vanadium complexes.

A series of new hybrid chalcogenogermanates [Mn2(en)4Ge2S6]n (1, en = ethylenediamine), [Mn2(dap)4Ge2S6]n (2, dap = 1,2-diaminopropane), [H2dien]n[MnGeS4]n (3, dien = diethylenetriamine), [V(en)2(ea)]2[Ge2Se6] (4, Hea = ethanolamine), [V(teta)(ea)]2[Ge2Se6] (5, teta = triethylenetetramine) and [V2(en)6(µ-O)][Ge2Se6] (6) were solvothermally synthesized and structurally characterized. Both 1 and 2 contain dimeric [Ge2S6]4- anions and [Mn(en)2]2+/[Mn(dap)2]2+ complex cations, which are interconnected to generate 1-D neutral chain-like structures [Mn2(en)4Ge2S6]n and [Mn2(dap)4Ge2S6]n, respectively. 3 consists of a protonated H2dien2+ cation and a 1-D straight chain built from [MnS4] and [GeS4] tetrahedra sharing opposite edges, and is the only example of a chelating amine uncoordinated to a transition metal ion. Both 4 and 5 consist of [Ge2Se6]4- anions constructed by two [GeSe4] tetrahedra sharing a common edge and discrete complex cations [V(en)2(ea)]2+/[V(teta)(ea)]2+. 6 is composed of a [Ge2Se6]4- anion and dinuclear complex cation [V2(en)6(µ-O)]4+ containing an en molecule as a rare monodentate ligand. Although some selenidogermanates with transition metal complexes have been successfully prepared, no selenidogermanates with trivalent vanadium complexes have been documented. Therefore, 4-6 offer the first examples of selenidogermanates with trivalent vanadium complexes under solvothermal conditions. Their optical and photocurrent response properties were studied.