Identification and quantification of N6-methyladenosine by chemical derivatization coupled with 19F NMR spectroscopy.

N 6-Methyladenosine (6mA) is a well-known prokaryotic DNA modification that has been shown to play epigenetic roles in eukaryotic DNA. Accurate detection and quantification of 6mA are prerequisites for molecular understanding of the impact of 6mA modification on DNA. However, the existing methods have several problems, such as high false-positive rate, time-consuming and complex operating procedures. Chemical sensors for the selective detection of 6mA modification are rarely reported in the literature. Fluorinated phenylboronic acid combined with 19F NMR analysis is an effective method for determining DNA or RNA modification. In this study, we presented a simple and fast chemical method for labelling the 6th imino group of 6mA using a boric-acid-derived probe. Besides, the trifluoromethyl group of trifluoromethyl phenylboronic acid (2a) could detect 6mA modification through 19F NMR. Combined with this sensor system, 6mA modification could be detected well and quickly in 6 types of deoxynucleoside mixtures and DNA samples. Taken together, the method developed in the current study has potential for specific detection of 6mA in biological samples.

Cirrhotic-extracellular matrix attenuates aPD-1 treatment response by initiating immunosuppressive neutrophil extracellular traps formation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is closely associatedwith chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified. METHODS: In silico, proteomic and pathological assessment of alteration of cirrhotic-ECM were applied in clinical cohort. Multiple pre-clinical models with ECM manipulation were used to evaluate cirrhotic-ECM's effect on ICI treatment. In silico, flow cytometry and IHC were applied to explore how cirrhotic-ECM affect HCC microenvironment. In vitro and in vivo experiments were carried out to identify the mechanism of how cirrhotic-ECM undermined ICI treatment. RESULTS: We defined "a pro-tumor cirrhotic-ECM" which was featured as the up-regulation of collagen type 1 (Col1). Cirrhotic-ECM/Col1 was closely related to impaired T cell function and limited anti PD-1 (aPD-1) response of HCC patients from the TCGA pan cancer cohort and the authors' institution, as well as in multiple pre-clinical models. Mechanically, cirrhotic-ECM/Col1 orchestrated an immunosuppressive microenvironment (TME) by triggering Col1-DDR1-NFκB-CXCL8 axis, which initiated neutrophil extracellular traps (NETs) formation to shield HCC cells from attacking T cells and impede approaching T cells. Nilotinib, an inhibitor of DDR1, reversed the neutrophils/NETs dominant TME and efficiently enhanced the response of HCC to aPD-1. CONCLUSIONS: Cirrhotic-ECM modulated a NETs enriched TME in HCC, produced an immune suppressive TME and weakened ICI efficiency. Col1 receptor DDR1 could be a potential target synergically used with ICI to overcome ECM mediated ICI resistance. These provide a mechanical insight and novel strategy to overcome the ICI resistance of HCC.

Correlation Between Improvement in Pain After Ultrasound-Guided Intra-articular Hip Injection and Outcomes After Arthroscopy in Patients With Femoroacetabular Impingement.

Background: An accurate and objective criterion is needed to determine candidates who are suitable for hip arthroscopy in patients with femoroacetabular impingement (FAI). Purpose: To determine whether improvement in pain after ultrasound (US)-guided intra-articular hip injection during standardized examinations can be used to predict the outcomes of hip arthroscopy in patients with FAI. Study Design: Cohort study; Level of evidence, 3. Methods: We enrolled 119 patients with FAI who underwent US-guided intra-articular hip injection of local anesthesia during standardized examinations, carried out from May 2018 to February 2020 (within 2 weeks before hip arthroscopy). All patients had undergone a minimum of 6 months of nonoperative treatment without remission and had 2-year follow-up data. Pain visual analog scale (VAS) scores (0-10) were recorded for 7 different physical examination tests, and a total score (0 [best] to 70 [worst]) was obtained. In addition, International Hip Outcome Tool-12 (iHOT-12) and modified Harris Hip Score (mHHS) scores were recorded before hip arthroscopy and at final follow-up. According to whether patients achieved the substantial clinical benefit (SCB) on the iHOT-12, they were divided into SCB and non-SCB groups, and the improvement in VAS pain scores from preinjection to postinjection (ΔVAS pain) was compared between the 2 groups. Logistic regression analysis was used to predict the achievement of SCB, and the area under the receiver operating characteristic curve (AUC) was used to estimate the accuracy of the prediction. Results: There was a significant pre- to postoperative increase in iHOT-12 (31.6 points; P < .001) and mHHS (20.0 points; P < .001) scores, and 84 (70.6%) patients achieved the SCB. The ΔVAS pain score was significantly greater in the SCB versus the non-SCB group (16.0 vs 7.0 points; respectively; P < .001). Logistic regression analysis demonstrated an optimal cutoff value of 8.5 points for ΔVAS pain (AUC, 0.772; 95% CI, 0.687-0.858). For patients with more severe symptoms (total preinjection VAS pain score of >10 out of 70), the accuracy of the prediction for ΔVAS pain had a better evaluation value (AUC, 0.834; 95% CI, 0.676-0.992). Conclusion: Improvement in pain after US-guided intra-articular hip injection predicted the outcomes of hip arthroscopy in patients with FAI in this study, especially for patients with more severe pain.

Stomatin-like protein 2 promotes cell proliferation and survival under 5-Fluorouracil stress in hepatocellular carcinoma.

BACKGROUND: The crucial role of STOML2 in tumor progression has been documented recently in various cancers. Previous studies have shown that STOML2 promoted cancer cell proliferation, but the underlying mechanism is not fully illustrated. METHODS AND RESULTS: The expression and clinical relevance of STOML2 in pan-cancer was analyzed by TIMER2 web platform in pan-cancer. The prognostic significance of STOML2 in HCC was evaluated utilizing KM curve and a nomogram model. Signaling pathways associated with STOML2 expression were discovered by GSEA. CCK-8 assay was performed to evaluate the proliferative capacity of HCC cells after manipulating STOML2 expression. Flow cytometry was utilized to analyze cell cycle progression. Results indicated that increased STOML2 expression in HCC linked to unfavorable clinical outcomes. Cell cycle and cell division related terms were enriched under conditions of elevated STOML2 expression via GSEA analysis. A notable decrease in cell proliferation was observed in MHCC97H with STOML2 knocked-down, accompanied by G1-phase arrest, up-regulation of p21, down-regulation of CyclinD1 and its regulatory factor MYC, while STOML2 overexpression in Huh7 showed the opposite results. These results indicated that STOML2 was responsible for HCC proliferation by regulating the expression level of MYC/cyclin D1 and p21. Furthermore, an inverse correlation was found between STOML2 expression and 5-FU sensitivity. CONCLUSIONS: STOML2 promotes cell cycle progression in HCC which is associated with activation of MYC/CyclinD1/p21 pathway, and modulates the response of HCC to 5-FU.

Ferric Chloride-Mediated Transacylation of N-Acylsulfonamides.

Transacylation of N-acylsulfonamides, which replaces the N-acyl group with a new one, is a challenging and underdeveloped fundamental transformation. Herein, a general method for transacylation of N-acylsulfonamides is presented. The transformation is enabled by coincident catalytic reactivities of FeCl3 for nonhydrolytic deacylation of N-acylsulfonamides and subsequent acylation of the resultant sulfonamides and can be conducted either stepwise or in a one-pot manner. GaCl3 and RuCl3·xH2O are similarly effective for the reaction. This method is mild, efficient, and operationally simple. A variety of functional groups such as halogeno, keto, nitro, cyano, ether, and ester are well tolerated, providing the transacylation products in good to excellent yields.

A single center retrospective study: Comparison between centrifugal separation plasma exchange with ACD-A and membrane separation plasma exchange with heparin on acute liver failure and acute on chronic liver failure.

The purpose of this retrospective study is to compare the efficacy and safety of the centrifugal separation therapeutic plasma exchange (TPE) using citrate anticoagulant (cTPEc) with membrane separation TPE using heparin anticoagulant (mTPEh) in liver failure patients. The patients treated by cTPEc were defined as cTPEc group and those treated by mTPEh were defined as mTPEh group, respectively. Clinical characteristics were compared between the two groups. Survival analyses of two groups and subgroups classified by the model for end-stage liver disease (MELD) score were performed by Kaplan-Meier method and were compared by the log-rank test. In this study, there were 51 patients in cTPEc group and 18 patients in mTPEh group, respectively. The overall 28-day survival rate was 76% (39/51) in cTPEc group and 61% (11/18) in mTPEh group (P > .05). The 90-day survival rate was 69% (35/51) in cTPEc group and 50% (9/18) in mTPEh group (P > .05). MELD score = 30 was the best cut-off value to predict the prognosis of patients with liver failure treated with TPE, in mTPEh group as well as cTPEc group. The median of total calcium/ionized calcium ratio (2.84, range from 2.20 to 3.71) after cTPEc was significantly higher than the ratio (1.97, range from 1.73 to 3.19) before cTPEc (P < .001). However, there was no significant difference between the mean concentrations of total calcium before cTPEc and at 48 h after cTPEc. Our study concludes that there was no statistically significant difference in survival rate and complications between cTPEc and mTPEh groups. The liver failure patients tolerated cTPEc treatment via peripheral vascular access with the prognosis similar to mTPEh. The prognosis in patients with MELD score < 30 was better than in patients with MELD score ≥ 30 in both groups. In this study, the patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) treated with cTPEc tolerated the TPE frequency of every other day without significant clinical adverse event of hypocalcemia with similar outcomes to the mTPEh treatment. For liver failure patients treated with cTPEc, close clinical observation and monitoring ionized calcium are necessary to ensure the patients' safety.

How does environmental regulation affect carbon productivity? The role of green technology progress and pollution transfer.

This empirical study examines the impact of environmental regulations on carbon productivity under varying conditions using panel data from Chinese provinces from 2011 to 2019. Prior research has reported inconsistent results regarding the relationships between these variables. We developed a spatial Durbin model (SDM) and tested the non-linear effects of environmental regulation on carbon productivity from a spatial linkage perspective. The results demonstrate a U-shaped curve representing the local-neighborhood effect of environmental regulations on carbon productivity. This curve is further dissected into two components: the average direct effect (ADE) and the average indirect effect (AIE). Furthermore, the findings indicate that green technology progress and pollution transfer act as moderating factors in shaping the U-shaped curve. Green technological progress has steepened the U-shape curve, whereas pollution transfer has flattened it. Based on these findings, we propose three recommendations for the formulation of environmental regulation policies.

A biocompatible polyethylene glycol/alginate composite hydrogel with significant reactive oxygen species consumption for promoting wound healing.

In areas of wound inflammation, excessive reactive oxygen species (ROS) may worsen the infection and lead to tissue damage, resulting in a vicious circle. Therefore, many hydrogels with sensitive ROS consumption capabilities and antibacterial properties have been widely developed and applied. These hydrogels usually achieve their ROS consumption capacity by introducing reactive active groups: however, these materials normally require complicated preparation procedures and have high potential toxicity. Inspired by these limitations, an integrated polyethylene glycol/alginate-based hydrogel (itg-PEGDA@SA) has been developed via a simple two-step process, where the inner PEGDA hydrogel (hdg-PEGDA) acts as a ROS scavenger and the outer sodium alginate hydrogel (SA) can be degraded to act as a recombinant human epidermal growth factor (rhEGF)-loaded platform to enhance the functionality of this composite hydrogel. Altogether, the itg-PEGDA@SA hydrogel showed significant ROS consumption and biocompatibility in vitro, and when applied for wound healing, the formation of uniform and ordered collagen fibers (stained using aniline blue) can be achieved. This hydrogel showed favorable attributes in ROS scavenging, and it can be a promising material for use in wound dressings and biomaterial fields.

Dissecting Sperm Mitochondrial G-Quadruplex Structures Using a Fluorescent Probe Biomarker to Monitor and Regulate Fertilization Capability.

To monitor the levels of mitochondrial DNA G-quadruplexes (mtDNA G4s) in spermatozoa and to explore the possibility using mtDNA G4s as a reliable marker in patients with multiple clinical insemination failures, a novel chemical TPE-mTO probe engineered in our previous work was used on both samples from the mice sperm and from patients with fertilization failure. Expression of valosin-containing protein and the zona-free hamster egg assay were used to evaluate mitophagy and human sperm penetration. RNA-sequencing was used to explore expression changes of key genes affected by mtDNA G4s. Results showed that the probe can track mtDNA G4s in spermatozoa easily and quickly with fewer backgrounds. Significantly increased mtDNA G4s were also found in patients with fertilization failure, using the flow-cytometry-based TPE-mTO probe detection method. A sperm-hamster egg penetration experiment showed that abnormal fertilization caused by increased mtDNA G4s can be effectively restored by a mitophagy inducer. This study provides a novel method for monitoring etiological biomarkers in patients with clinical infertility and treatment for patients with abnormal fertilization caused by mtDNA G4 dysfunction.

In Vitro Neurotrophic Properties and Structural Characterization of a New Polysaccharide LTC-1 from Pyrola corbieri Levl (Luticao).

Pyrola corbieri Levl has been used to strengthen bones and nourish the kidney (the kidney governs the bone and is beneficial to the brain) by the local Miao people in China. However, the functional components and neurotrophic activity have not been reported. A new acidic homogeneous heteropolysaccharide named LTC-1 was obtained and characterized by periodate oxidation, Smith degradation, partial acid hydrolysis, GC-MS spectrometry, methylation analysis, and Fourier transform infrared spectroscopy, and its molecular weight was 3239 Da. The content of mannuronic acid (Man A) in LTC-1 was 46%, and the neutral sugar was composed of L-rhamnose (L-Rha), L-arabinose (L-Ara), D-xylose (D-Xyl), D-mannose (D-Man), D-glucose (D-Glc) and D-galactose (D-Gal) with a molar ratio of 1.00:3.63:0.86:1.30:6.97:1.30. The main chain of LTC-1 was composed of Glc, Gal, Man, Man A and the branched chain Ara, Glc, Gal. The terminal residues were composed of Glc and Gal. The main chain and branched chains were linked by (1→5)-linked-Ara, (1→3)-linked-Glc, (1→4)-linked-Glc, (1→6)-linked-Glc, (1→3)-linked-Gal, (1→6)-linked-Gal, (1→3, 6)-linked-Man and ManA. Meanwhile, neurotrophic activity was evaluated through PC12 and primary hippocampal neuronal cell models. LTC-1 exhibited neurotrophic activity in a concentration-dependent manner, which significantly induced the differentiation of PC12 cells, promoted the neurite outgrowth of PC12 cells, enhanced the formation of the web architecture of dendrites, and increased the density of dendritic spines in hippocampal neurons and the expression of PSD-95. These results displayed significant neurotrophic factor-like activity of LTC-1, which suggests that LTC-1 is a potential treatment option for neurodegenerative diseases.

G-Quadruplex Structures as a "Switch" Regulate ATF4 Expression in Ferroptotic HepG2 Cells.

G-quadruplex (G4) is a noncanonical structure folded in a widespread manner by guanine-rich tandem repeated sequences. As a key response factor, activating transcription factor 4 (ATF4) has dual functions in managing iron-dependent ferroptosis by regulating amino acid synthesis and antioxidant-related gene expression. In our study, the activity of ATF4 expression was elevated in HepG2 cells induced by erastin. Based on preliminary bioinformatics analyses, the G-tract region, named WT, had high potential to form G4, and it was found that PDS could markedly weaken the increase of ATF4 expression by reducing the sensitivity of HepG2 cells toward erastin. In circular dichroism spectra, WT oligonucleotides showed characteristic molar ellipticity at specific wavelengths of parallel G4 structures, while corresponding single-base mutants possessed a weaker ability to form G4, which were consistent with immunostaining results. In addition, endogenous G4 formed by the WT motif was significantly destroyed in HepG2 cells treated with erastin. After being transfected with WT oligonucleotides, the levels of ATF4 mRNA decreased significantly regardless of being treated with erastin or not. Meanwhile, mutations of G-tracts could advantageously impact the luciferase expression downstream of an ATF4 promoter in reporter assays, manifesting that the decrease of endogenous G4 in the ATF4 promoter was positively associated with the expression enhanced by erastin in HepG2 cells.

Vertical distribution, environmental occurrence, and risk assessment of organic pollutants in lacustrine sediments in southeast China.

To clarify the impact of human activities on the natural environment, as well as the current ecological risks to the environment surrounding Zhushan Bay in Taihu Lake, the characteristics of deposited organic materials, including elements and 16 polycyclic aromatic hydrocarbons (∑16PAHs), in a sediment core from Taihu Lake were determined. The nitrogen (N), carbon (C), hydrogen (H), and sulfur (S) contents ranged from 0.08 to 0.3%, 0.83 to 3.6%, 0.63 to 1.12%, and 0.02 to 0.24%, respectively. The most abundant element in the core was C followed by H, S, and N, while elemental C and the C/H ratio displayed a decreasing trend with depth. The ∑16PAH concentration was in the range of 1807.48-4674.83 ng g-1, showing a downward trend with depth, with some fluctuations. Three-ring PAHs dominated in surface sediment, while 5-ring PAHs dominated at a depth of 55-93 cm. Six-ring PAHs appeared in the 1830s and gradually increased over time before slowly decreasing from 2005 onward due to the establishment of environmental protection measures. The ratio of PAH monomers indicated that PAHs in samples from a depth of 0 to 55 cm were mainly derived from the combustion of liquid fossil fuels, while the PAHs in the deeper samples mainly originated from petroleum. The results of a principal component analysis (PCA) showed that the PAHs in the sediment core of Taihu Lake were mainly derived from the combustion of fossil fuels, such as diesel, petroleum, gasoline, and coal. The contributions of biomass combustion, liquid fossil fuel combustion, coal combustion, and unknown source were 8.99%, 52.68%, 1.65%, and 36.68%, respectively. The results of a toxicity analysis indicated that most of the PAH monomers had little impact on the ecology, and the annual increase of a small number of monomers might have toxic effects on the biological community, resulting in a serious ecological risks, that requires the imposition of control measures.

A novel triple-network hydrogel based on borate ester groups: from structural modulation to rapid wound hemostasis.

Supramolecular hydrogels have received widespread attention due to their soft texture, strong hygroscopicity, and good biocompatibility. These materials have become particularly attractive for sensing, tissue engineering, fluorescence encoding, wound healing, etc. Inspired by the assembly of G-quadruplexes, we choose the boric acid/polyvinyl alcohol/guanosine system to construct a novel triple-network supramolecular hydrogel "tri-BA@PVA/G" via non-covalent cross-linking, and the effect of the concentration of each component on the hydrogel stability was systematically revealed at the same time. Then, the biocompatibility, shape adaption and optical information storage capacity, the rapid hemostatic ability and the ability of the hydrogel to promote wound healing were confirmed both in vitro and in vivo. These results that predict the properties and reveal prospective applications in the field of wound hemostasis have a certain guiding significance for the subsequent preparation of borate-based triple network hydrogels which can be used as wound hemostatic materials.

Nucleotide sugar transporter SLC35A2 is involved in promoting hepatocellular carcinoma metastasis by regulating cellular glycosylation.

PURPOSE: Recently, aberrant glycosylation has been recognized to be relate to malignant behaviors of cancer and outcomes of patients with various cancers. SLC35A2 plays an indispensable role on glycosylation as a nucleotide sugar transporter. However, effects of SLC35A2 on malignant behaviors of cancer cells and alteration of cancer cells surface glycosylation profiles are still not fully understood, particularly in hepatocellular carcinoma (HCC). Hence, from a glycosylation perspective, we investigated the effects of SLC35A2 on metastatic behaviors of HCC cells. METHODS: SLC35A2 expression in clinical samples and HCC cells was examined by immunohistochemical staining or Western blot/quantitative PCR and was regulated by RNA interference or vectors-mediated transfection. Effects of SLC35A2 expression alteration on metastatic behaviors and membrane glycan profile of HCC cells were observed by using respectively invasion, migration, cell adhesion assay, in vivo lung metastatic nude mouse model and lectins microarray. Co-location among proteins in HCC cells was observed by fluorescence microscope and detected by an in vitro co-immunoprecipitation assay. RESULTS: SLC35A2 was upregulated in HCC tissues, and is associated with poor prognosis of HCC patients. SLC35A2 expression alteration significantly affected the invasion, adhesion, metastasis and membrane glycan profile and led to the dysregulated expressions or glycosylation of cell adhesion-related molecules in HCC cells. Mechanistically, the maintenance of SLC35A2 activity is critical for the recruitment of the key galactosyltransferase B4GalT1, which is responsible for complex glycoconjugate and lactose biosynthesis, to Golgi apparatus in HCC cells. CONCLUSION: SLC35A2 plays important roles in promoting HCC metastasis by regulating cellular glycosylation modification and inducing the cell adhesive ability of HCC cells.

Traceability of nitrate polluted hotspots in plain river networks of the Yangtze River delta by nitrogen and oxygen isotopes coupling bayesian model.

The adverse effects of increased nitrate (NO3-) pollution especially from the non-point source on the hydrosphere and anthroposphere are becoming more prominent. The non-point-derived NO3- in the rivers supplying the upstream threatens the aquatic ecosystem of Taihu Lake. Here, dual-stable isotopes (δ15N and δ18O) of NO3- were applied to the Bayesian model (SIAR) for quantitative source identification of reactive nitrogen (Nr) in a mixed agricultural and urban region along the complex river network of the Yangze River delta. The results showed that the NO3- concentrations in the rivers ranged from 1.09 to 4.44 mg L-1 and decreased from the highly urbanized areas to the lakeside rural areas. The specific isotopic characteristics of four sources (atmospheric deposition, AD; chemical fertilizer, CF; manure and sewage, MS; and soil leachate, SL) by the SIAR isotope model indicated that the MS source made the greatest contribution (46.56%) to the total NO3- load, followed by SL (27.86%), CF (23.77%), and AD (1.81%). The highly urbanized areas and the hybrid areas, which contained a mix of industrialized, populated, and agricultural areas, were identified as hotspot areas with heavy Nr pollution, responsible for spatial patterns of δ15N-NO3- and δ18O-NO3-. These hotspot areas were characterized by a less well-developed sewage pipeline system with high Nr emissions from cash crops. The changes in wastewater treatment level, the agricultural production structure, and meteorological changes were the main factors of spatial variation of Nr concentration and source in the upstream Taihu Lake Basin. The variation in Nr concentration across Taihu Lake would respond to these anthropogenic-driven Nr loads. These findings suggest that MS was the predominant source had the strongest effect on the overall riverine NO3- source which was the primary problem that needed to be solved.

Sex differences in hepatocellular carcinoma indicated BEX4 as a potential target to improve efficacy of lenvatinib plus immune checkpoint inhibitors.

Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer, and significant sex disparities have been observed in HCC. We aim to explore the potential sex-biased mechanisms involved in hepatocarcinogenesis. Methods: Based on TCGA data, we compared clinical features, genetic alterations, and immune cell infiltrations between male and female HCC patients. In addition, we performed sex-based differential expression analysis and functional enrichment analysis. Finally, GSE64041 dataset and another HCC cohort were engaged to validate our findings. Results: Significant differences of genetic alterations and TME were observed between male and female HCC patients. Enhanced metabolism of lipids was associated with hepatocarcinogenesis in men, while ECM-organization-related pathways were correlated to HCC development in women. BEX4 was upregulated in female but downregulated in male HCC patients, and was positively correlated with immune checkpoint molecules and infiltrated immune cell. These findings were further validated in dataset GSE64041 and our HCC cohort. More importantly, a negative correlation was found between BEX4 expression and lenvatinib sensitivity. Conclusion: Distinct biological processes were involved in sex-biased tumorigenesis of HCC. BEX4 can be targeted to improve the efficacy of lenvatinib plus immune checkpoint inhibitors.

Methyl butyrate attenuates concanavalin A-induced autoimmune hepatitis by inhibiting Th1-cell activation and homing to the liver.

Con A-induced hepatitis is the most commonly used animal model for simulating autoimmune hepatitis (AIH). In this study, we investigated whether methyl butyrate (MB) alleviates Con A-induced hepatitis and how it affects Con A-stimulated lymphocytes. MB improves liver function in AIH mice, reducing the expression of several inflammatory cytokines and Th1 cell-associated chemokines in the liver, while significantly inhibiting toll-like receptor signaling pathway. Also in the liver, we verified that infiltrating Th1 cells were fewer after MB treatment. In vitro, we found that the activation of both human and mouse Th1 cells by Con A were inhibited by MB and the human-derived cells were even more sensitive. And MB caused a reduction in IFN-γ secretion together with TNF-α and IL-6. The above findings suggest that MB inhibits the activation and homing of Th1 cells to the liver, thereby attenuating Con A-induced liver injury, and may be a potential therapeutic agent for AIH.

Intrahepatic transcriptomics reveals gene signatures in chronic hepatitis B patients responded to interferon therapy.

Chronic hepatitis B virus (HBV) infection remains a substantial public health burden worldwide. Alpha-interferon (IFNα) is one of the two currently approved therapies for chronic hepatitis B (CHB), to explore the mechanisms underlying IFNα treatment response, we investigated baseline and 24-week on-treatment intrahepatic gene expression profiles in 21 CHB patients by mRNA-seq. The data analyses demonstrated that PegIFNα treatment significantly induced antiviral responses. Responders who achieved HBV DNA loss and HBeAg or HBsAg seroconversion displayed higher fold change and larger number of up-regulated interferon-stimulated genes (ISGs). Interestingly, lower expression levels of certain ISGs were observed in responders in their baseline biopsy samples. In HBeAg+ patients, non-responders had relative higher baseline HBeAg levels than responders. More importantly, HBeAg- patients showed higher HBsAg loss rate than HBeAg+ patients. Although a greater fold change of ISGs was observed in HBeAg- patients than HBeAg+ patients, upregulation of ISGs in HBeAg+ responders exceeded HBeAg- responders. Notably, PegIFNα treatment increased monocyte and mast cell infiltration, but decreased CD8 T cell and M1 macrophage infiltration in both responders and non-responders, while B cell infiltration was increased only in responders. Moreover, co-expression analysis identified ribosomal proteins as critical players in antiviral response. The data also indicate that IFNα may influence the production of viral antigens associated with endoplasmic reticulum. Collectively, the intrahepatic transcriptome analyses in this study enriched our understanding of IFN-mediated antiviral effects in CHB patients and provided novel insights into the development of potential strategies to improve IFNα therapy.

Occurrence and driving forces of different nitrogen forms in the sediments of the grass and algae-type zones of Taihu Lake.

Excessive nitrogen (N) load in sediments is at risk of release resulting in the degradation of grass-type lake ecosystems. At present, the occurrence characteristics of N forms and the driving forces of organic N (ON) hydrolysis in the sediments of Taihu Lake were still unclear. Here, 52 sampling sites in 7 lake areas in Taihu Lake were investigated to compare the spatial occurrence characteristics of the sedimentary free N (FN), exchangeable N (EN), acid hydrolyzable N (HN), and residual N (RN) and their associated driving forces. The results showed that the total N contents in the dry sediment ranged from 1811.56 to 5594.06 mg kg-1, and the contribution was in the order of RN > HN > EN > FN. Spatially, RN and total organic carbon were significantly consistently influenced by dam construction and deposition algal residue. The HN concentration was high in the estuaries affected by N inputs from the rivers. The coupling relationship of spatial distribution between ON and N forms was revealed. The factors, i.e., algal residue deposition and terrigenous N inputs, were considered as the main driving forces stimulating the ON hydrolysis in the algae-type lake zones. It can be deduced that controlling terrigenous N inputs and sediment suspension may be the key to inhibiting the transformation from grass-type to algae-type lake ecosystem.