Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients.

Gastric mucosal samples were procured and underwent the sequencing of 16S ribosomal RNA (16S rRNA) via Illumina high-throughput sequencing technology to explore the impact of Helicobacter pylori (H. pylori) infection on the composition of gastric flora in chronic gastritis (CG) patients. In the results, the operational taxonomic unit (OTU) analysis revealed an overlap of 5706 OTUs shared between the two groups. The top 5 abundance ranking (TOP5) phyla comprised Bacteroidetes, Proteobacteria, Firmicutes, Actinobacteria, and Epsilonbacteraeota, while the TOP5 genus was Lachnospiraceae_NK4A136_group, Helicobacter, Bacteroides, Klebsiella, and Pseudomonas. In the metabolic pathways at the Kyoto Encyclopedia of Genes and Genomes (KEGG)_L3 level, conspicuous variations across seven functions were observed between the H. pylori-positive (HP_Pos) and H. pylori-negative (HP_Neg) groups. Subsequently, functional gene enrichment in KEGG pathways was further validated through animal experimentation. In contrast to the mice in the HP_Neg group, those infected with H. pylori manifested an infiltration of inflammatory cells, an augmentation in gastric acid secretion, and conspicuously elevated scores regarding gastric activity, along with heightened levels of malondialdehyde. In conclusion, CG patients infected with H. pylori displayed a disorder in gastric flora, furnishing a theoretical basis for the prophylaxis of H. pylori infection and its associated pathogenic ramifications.

Gut microbial network signatures of early colonizers in preterm neonates with extrauterine growth restriction.

BACKGROUND: Extrauterine growth restriction (EUGR) represents a prevalent condition observed in preterm neonates, which poses potential adverse implications for both neonatal development and long-term health outcomes. The manifestation of EUGR has been intricately associated with perturbations in microbial and metabolic profiles. This study aimed to investigate the characteristics of the gut microbial network in early colonizers among preterm neonates with EUGR. METHODS: Twenty-nine preterm infants participated in this study, comprising 14 subjects in the EUGR group and 15 in the normal growth (AGA) group. Meconium (D1) and fecal samples were collected at postnatal day 28 (D28) and 1 month after discharge (M1). Subsequently, total bacterial DNA was extracted and sequenced using the Illumina MiSeq system, targeting the V3-V4 hyper-variable regions of the 16S rRNA gene. RESULTS: The outcomes of principal coordinates analysis (PCoA) and examination of the microbial network structure revealed distinctive developmental trajectories in the gut microbiome during the initial three months of life among preterm neonates with and without EUGR. Significant differences in microbial community were observed at the D1 (P = 0.039) and M1 phases (P = 0.036) between the EUGR and AGA groups, while a comparable microbial community was noted at the D28 phase (P = 0.414). Moreover, relative to the AGA group, the EUGR group exhibited significantly lower relative abundances of bacteria associated with secretion of short-chain fatty acids, including Lactobacillus (P = 0.041) and Parabacteroides (P = 0.033) at the D1 phase, Bifidobacterium at the D28 phase, and genera Dysgonomonas (P = 0.042), Dialister (P = 0.02), Dorea (P = 0.042), and Fusobacterium (P = 0.017) at the M1 phase. CONCLUSION: Overall, the present findings offer crucial important insights into the distinctive gut microbial signatures exhibited by earlier colonizers in preterm neonates with EUGR. Further mechanistic studies are needed to establish whether these differences are the cause or a consequence of EUGR.

Genetic and clinical characteristics of ZNF408-related familial exudative vitreoretinopathy.

OBJECTIVE: To analyze the clinical and genetic characteristics of zinc finger protein 408 (ZNF408)-related familial exudative vitreoretinopathy (FEVR) in a Chinese cohort. METHODS: Ninety families from Chongqing and 16 families from Xinjiang were selected according to fundus lesion characteristics. Peripheral venous blood was collected from patients and their families; genomic DNA was extracted for whole exome sequencing. Relationships between genotype and phenotype in patients with ZNF408-related FEVR were analyzed. RESULTS: ZNF408 variants were detected in three patients (2.83%, 3/106). ZNF408 variants in these three probands were all missense mutations at novel sites. One proband had a ZNF408 and LRP5 double-gene variant, and two probands had ZNF408 single-gene variants. Patients with double-gene variants did not display more severe clinical manifestations. CONCLUSIONS: This study expands the spectrum of known ZNF408 variants and confirms that ZNF408 variants can cause FEVR. Most variants detected in this study have not been reported in the literature and are suspected pathogenic variants of FEVR. In patients with FEVR, phenotype and genotype do not necessarily display a direct one-to-one relationship.

Controlling the electrochemical activity of dahlia-like ß-NiS@rGO by interface polarization.

Transition metal sulfides have become more and more important in the field of energy storage due to their superior chemical and physical properties. Herein, dahlia ß-NiS with a rough surface and ß-NiS@reduced graphene oxide (rGO) have been green synthesized by a one-step hydrothermal method. The interface characteristics of ß-NiS@ rGO composites have been systematically studied by XPS, Raman, and first-principles calculations. It is found that the residual O atoms in the interface and the polarization charge generated by them play an important role in performance enhancement. The NiS@rGO composite material has the best electrochemical performance when the C/O ratio is 6.48. Furthermore, we designed a NiS@rGO//rGO asymmetric supercapacitor with a potential window of 1.7 V. Its excellent energy density and power density demonstrate the advantages of the optimized NiS@rGO electrode. When the power density is 850 W kg-1, the energy density can reach 40.4 W h kg-1. Even at a power density of up to 6800 W kg-1, the energy density can be maintained at 17.6 W h kg-1. These encouraging results provide a possible pathway for designing asymmetric supercapacitors with ultra-high performance and a feasible strategy for the precise control of electrochemical performance.

Overexpression of circ PTK2 suppresses the progression of nonalcoholic fatty liver disease via the miR-200c/SIK2/PI3K/Akt axis.

Excessive hepatic lipid accumulation is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A previous study showed that the circular RNA (circRNA) PTK2 was significantly downregulated in NAFLD mice. However, the detailed function of circ PTK2 in NAFLD remains unclear. A high-fat diet (HFD) was used to establish a mouse model of NAFLD, and free fatty acid (FFA) treatment was used to establish an in vitro model of NAFLD. Oil red O staining was used to evaluate lipid accumulation. The pathological changes in mice were observed by HE staining. Western blotting and RT-qPCR were applied to assess protein and mRNA levels, respectively. A dual luciferase reporter assay and RIP were used to explore the relationship among circ PTK2, miR-200c and SIK2. Circ PTK2 and SIK2 were downregulated and miR-200c was upregulated in NAFLD. Upregulation of circ PTK2 reversed lipid accumulation in FFA-treated HepG2 cells. Moreover, circ PTK2 bound to miR-200c, and SIK2 was identified as the direct target of miR-200c. Moreover, the miR-200c inhibitor-induced decrease in lipid accumulation was reversed by SIK2 knockdown. Furthermore, the impact of circ PTK2 overexpression on PI3K/Akt signaling was partially reversed by SIK2 silencing. Circ PTK2 overexpression alleviates NAFLD development via the miR-200c/SIK2/PI3K/Akt axis. Thus, our work might provide new methods for NAFLD treatment.

Comprehensive Evaluation of Anti-PD-1, Anti-PD-L1, Anti-CTLA-4 and Their Combined Immunotherapy in Clinical Trials: A Systematic Review and Meta-analysis.

Immunotherapy with immune checkpoint inhibitor (ICI) drugs is gradually becoming a hot topic in cancer treatment. To comprehensively evaluate the safety and efficacy of ICI drugs, we employed the Bayesian model and conducted a network meta-analysis in terms of progression-free survival (PFS), overall survival (OS) and severe adverse events (AEs). Our study found that treatment with ipilimumab was significantly worse than standard therapies in terms of PFS, whereas treatment with cemiplimab significantly improved PFS. The results also indicated that cemiplimab was the best choice for PFS. Treatment with nivolumab, pembrolizumab and nivolumab plus ipilimumab significantly improved OS compared to standard therapies. In terms of OS, cemiplimab was found to be the best choice, whereas avelumab was the worst. In terms of severe AEs, atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab all significantly reduced the risk of grade 3 or higher AEs compared to standard therapy. The least likely to be associated with severe AEs were as follows: cemiplimab, avelumab, nivolumab, atezolizumab, and camrelizumab, with nivolumab plus ipilimumab to be the worst. Therefore, different ICI drug therapies may pose different risks in terms of PFS, OS and severe AEs. Our study may provide new insights and strategies for the clinical practice of ICI drugs.

Utilization of hepatitis B virus surface antigen positive grafts in liver transplantation: A matched study based on a national registry cohort.

BACKGROUND AND AIM: Donor shortage has become worldwide limitation in liver transplantation (LT). Use of hepatitis B virus surface antigen positive (HBsAg+) donors could be an alternative source of donor organs. This study aims to investigate the safety and efficacy of LT using HBsAg+ liver grafts and associated long-term outcome. METHODS: This was a retrospective study of adults LT registered in the database of the China Liver Transplant Registry between January 2015 and September 2018. By propensity score matching (1:1), 503 eligible patients who received HBsAg+ liver grafts were compared with 503 matched patients who received HBsAg- liver grafts. RESULTS: The 1-, 3-, and 5-year patient survival rates were 81.52%, 72.04%, and 66.65% in HBsAg+ donor group, which were comparable with 83.93%, 77.27%, and 65.73% in HBsAg- donor group (P = 0.222). The 1-, 3-, and 5-year graft survival rates were also comparable between the two groups (81.49%, 71.45%, and 67.26% vs 83.62%, 77.11%, and 65.81%, respectively, P = 0.243). Most main complications were not increased in HBsAg+ donor group except for the retaining of HBsAg positivity after LT. Furthermore, transplanting HBsAg+ liver grafts did not result in inferior outcomes either in HBsAg+ or HBsAg- recipients. The risk of tumor recurrence after LT was not increased in hepatocellular carcinoma patients. CONCLUSIONS: The outcomes of using HBsAg+ liver grafts were comparable with those of HBsAg- liver grafts. Our study provided strong evidence for the safe use of HBsAg+ grafts in LT to expand the donor liver pool.

Comparison and development of advanced machine learning tools to predict nonalcoholic fatty liver disease: An extended study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a public health challenge and significant cause of morbidity and mortality worldwide. Early identification is crucial for disease intervention. We recently proposed a nomogram-based NAFLD prediction model from a large population cohort. We aimed to explore machine learning tools in predicting NAFLD. METHODS: A retrospective cross-sectional study was performed on 15 315 Chinese subjects (10 373 training and 4942 testing sets). Selected clinical and biochemical factors were evaluated by different types of machine learning algorithms to develop and validate seven predictive models. Nine evaluation indicators including area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), accuracy, positive predictive value, sensitivity, F1 score, Matthews correlation coefficient (MCC), specificity and negative prognostic value were applied to compare the performance among the models. The selected clinical and biochemical factors were ranked according to the importance in prediction ability. RESULTS: Totally 4018/10 373 (38.74%) and 1860/4942 (37.64%) subjects had ultrasound-proven NAFLD in the training and testing sets, respectively. Seven machine learning based models were developed and demonstrated good performance in predicting NAFLD. Among these models, the XGBoost model revealed the highest AUROC (0.873), AUPRC (0.810), accuracy (0.795), positive predictive value (0.806), F1 score (0.695), MCC (0.557), specificity (0.909), demonstrating the best prediction ability among the built models. Body mass index was the most valuable indicator to predict NAFLD according to the feature ranking scores. CONCLUSIONS: The XGBoost model has the best overall prediction ability for diagnosing NAFLD. The novel machine learning tools provide considerable beneficial potential in NAFLD screening.

Effects of matrine in combination with cisplatin on liver cancer.

Matrine, an alkaloid isolated from Sophora flavescens, promotes tumor cell apoptosis and strengthens the anticancer capacity of chemotherapeutic drugs. The present study aimed to investigate the inhibitory effect and underlying mechanism of matrine in combination with cisplatin on liver cancer progression. Tumor progression was studied in nude mice. The human liver cancer cell line HepG2 was injected into BALB/c nude mice subcutaneously to establish a tumor model. Mice were subsequently treated with matrine, cisplatin, matrine + cisplatin or normal saline. Nude mice and tumor growth were monitored. Tumors were excised and the expression of survivin, caspase-3, caspase-7 and caspase-9 was detected by immunohistochemistry. Western blotting was used to determine the expression of survivin, caspase-3, caspase-7, caspase-9 and X-linked inhibitor of apoptosis protein (XIAP) in tumor tissues. The results demonstrated that matrine exerted anticancer effects in liver cancer-transplanted tumors, as evidenced by decrease in tumor weight and volume. Furthermore, the tumor inhibition rate in mice treated with matrine + cisplatin was 83.3%, whereas it was of 37.5 and 75% in mice treated with matrine or cisplatin alone, respectively. In addition, the expression of survivin and XIAP was significantly downregulated, whereas the expression of caspase-3, caspase-7 and caspase-9 was significantly upregulated in tumor tissues from nude mice treated with matrine + cisplatin, compared with those treated with cisplatin, matrine or normal saline. These findings suggested that the combination of matrine and cisplatin may promote tumor cell apoptosis in liver cancer by activating the caspase apoptosis pathway and suppressing the survivin-associated inhibition of caspase-9.

SP1-induced ZFAS1 aggravates sepsis-induced cardiac dysfunction via miR-590-3p/NLRP3-mediated autophagy and pyroptosis.

BACKGROUND: Sepsis-induced cardiac dysfunction is one of the leading complications of sepsis, contributing to the high morbidity and mortality of septic patients. Several lines of evidence have demonstrated that autophagy and pyroptosis may be involved in septic cardiac dysfunction. In this study, we examined the impact of zinc finger antisense 1 (ZFAS1) on sepsis-induced myocardial dysfunction via regulating pyroptosis and autophagy. METHOD: Mice with cecal ligation and puncture (CLP)-induced sepsis was constructed in vivo. Myocardial injury was assessed by H&E staining, immunohistochemistry (IHC) for NLRP3, caspase 1, and interleukin (IL)-1ß, as well as ELISA assay for serum levels of creatine kinase (CK), CK-MB, tumor necrosis factor α (TNF-α), and IL-1ß. Primary cardiomyocytes exposed to lipopolysaccharide (LPS) were established to simulate sepsis-induced cardiac dysfunction in vitro. Cell viability was examined by MTT assay and concentration of TNF-α and IL-1ß was measured by ELISA. Flow cytometry, immunofluorescent staining and western blotting were performed to assess pyroptosis and autophagy. The transcriptional regulation of SP1 on ZFAS1 was determined using ChIP assay. Luciferase reporter assay was performed to verify the ZFAS1/miR-590-3p interaction. Besides, activation of AMPK/mTOR signaling was detected using western blotting. RESULTS: Highly expressed ZFAS1 was observed in sepsis-induced cardiac dysfunction in the in vivo and in vitro model. Knockdown of ZFAS1 robustly abolished LPS-induced pyroptosis and attenuated the inhibition of autophagy. SP1 was identified to be an essential transcription factor to positively regulate ZFAS1 expression. Moreover, miR-590-3p functioned as a downstream effector to reverse ZFAS1-mediated sepsis-induced cardiac dysfunction. AMPK/mTOR signaling was involved in miR-590-3p-regulated autophagy and pyroptosis of cardiomyocytes. Furthermore, the regulatory network of ZFAS1/miR-590-3p on AMPK/mTOR signaling was verified in vivo. CONCLUSION: ZFAS1, activated by SP1, aggravates the progression of sepsis-induced cardiac dysfunction via targeting miR-590-3p/AMPK/mTOR signaling-mediated autophagy and pyroptosis of cardiomyocytes.

Atom-Pair Catalysts Supported by N-Doped Graphene for the Nitrogen Reduction Reaction: d-Band Center-Based Descriptor.

Achieving an effective nitrogen reduction reaction (NRR) under mild conditions is a great challenge for industrial ammonia synthesis. NRR is often accompanied by a competing hydrogen evolution reaction (HER), which causes an extremely low Faraday efficiency. We systematically investigated the NRR reactivity of atom-pair catalysts (APCs) formed by 20 transition metal (TM) elements supported by N-doped graphene via three reaction pathways. By analyzing the correlation among the limiting potential, Gibbs free energy, and d-band center, we evaluated the activity trends of the TM APCs. Our computations revealed that the enzymatic pathway is the most suitable reaction pathway for the TM APCs, and the intrinsic activity trend of these APCs can be determined by the d-band center-based descriptor, which has a simple linear correlation with the bonding/antibonding orbital population. In addition, the NRR APCs with excellent performance have been screened out through selective analysis of the competing HER in the electrocatalytic NRR process.

Development and validation of a clinical and laboratory-based nomogram to predict nonalcoholic fatty liver disease.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of chronic liver disease in China. The early identification and management of patients at risk are essential. We aimed to develop a novel clinical and laboratory-based nomogram (CLN) model to predict NAFLD with high accuracy. METHODS: We designed a retrospective cross-sectional study and enrolled 21,468 participants (16,468 testing and 5000 validation). Clinical information and laboratory/imaging results were retrieved. Significant variables independently associated with NAFLD were identified by a logistic regression model, and a NAFLD prediction CLN was constructed. The CLN was then compared with four existing NAFLD-related prediction models: the fatty liver index (FLI), the hepatic steatosis index (HSI), the visceral adiposity index (VAI) and the triglycerides and glucose (TyG) index. Area under the receiver operator characteristic curve (AUROC) and decision curve analysis (DCA) were performed. RESULTS: A total of 6261/16,468 (38.02%) and 1759/5000 (35.18%) participants in the testing and validation datasets, respectively, had ultrasound-proven NAFLD. Six variables were selected to build the CLN: body mass index (BMI), diastolic blood pressure (DBP), uric acid (UA), fasting blood glucose (FBG), triglyceride (TG), and alanine aminotransferase (ALT). The diagnostic accuracy of the CLN for NAFLD (AUROC 0.857, 95% CI 0.852-0.863) was significantly superior to that of the FLI (AUROC 0.849, 95% CI 0.843-0.855), the VAI (AUROC 0.752, 95% CI 0.745-0.760), the HSI (AUROC 0.828, 95% CI 0.822-0.834), and the TyG index (AUROC 0.774, 95% CI 0.767-0.781) (all p < 0.001). DCA confirmed the clinical utility of the CLN. CONCLUSIONS: This physical examination and laboratory test-based, nonimage-assisted novel nomogram has better performance in predicting NAFLD than the FLI, the VAI, the HSI and the TyG index alone. This model can be used as a quick screening tool to assess NAFLD in the general population.

LncRNA HULC induces the progression of osteosarcoma by regulating the miR-372-3p/HMGB1 signalling axis.

BACKGROUND: Osteosarcoma is a malignancy that normally affects children, adolescents, and young adults. Although accumulating evidence has demonstrated the importance of HULC in osteosarcoma, little is reported about its functional roles and molecular mechanisms. METHODS: The expression of HULC and miR-372-3p in osteosarcoma tissues was quantified by qRT-PCR. The regulatory roles of HULC and miR-372-3p on cell proliferation, apoptosis, migration and invasion were determined by CCK-8, colony formation, flow cytometry, wound healing, and transwell assays, respectively. The bioinformatics prediction software RAID v2.0 was used to predict the putative binding sites. The interactions among HULC, miR-372-3p and HMGB1 were explored by luciferase assay and western blot assay. RESULTS: Our results revealed elevated HULC and decreased miR-372-3p expression in both osteosarcoma tissues and cell lines. Overexpression of HULC or knockdown of miR-372-3p promoted osteosarcoma cell proliferation, migration and invasion and induced cell apoptosis. Bioinformatics and luciferase assays verified that HULC directly interacted with miR-372-3p to attenuate miR-372-3p binding to the HMGB1 3'-UTR. Furthermore, mechanistic investigations confirmed that activation of the miR-372-3p/HMGB1 regulatory loop by knockdown of miR-372-3p or overexpression of HMGB1 reversed the in vitro roles of HULC in promoting osteosarcoma cell proliferation, migration and invasion. CONCLUSION: Our study is the first to demonstrate that HULC may act as a ceRNA to modulate HMGB1 expression by competitively sponging miR-372-3p, leading to the regulation of osteosarcoma progression, which provides new insight into osteosarcoma diagnosis and treatment.

Correction: Mechanistic study on NO reduction by sludge reburning in a pilot scale cement precalciner with different CO2 concentrations.

[This corrects the article DOI: 10.1039/C9RA04065J.].

Glucose- and pH-Responsive Supramolecular Polymer Vesicles Based on Host-Guest Interaction for Transcutaneous Delivery of Insulin.

Smart insulin delivery platforms having the ability of mimicking pancreatic cells are highly expected for diabetes treatment. Herein, a smart glucose-sensitive insulin delivery platform on the basis of transcutaneous microneedles has been designed. The as-prepared microneedles are composed of glucose- and pH-responsive supramolecular polymer vesicles (PVs) as the drug storage and water soluble polymers as the matrix. The well-defined PVs are constructed from the host-guest inclusion complex between water-soluble pillar[5]arene (WP5) with pH-responsiveness and paraquat-ended poly(phenylboronic acid) (PPBA-G) with glucose-sensitivity. The drug-loaded PVs, including insulin and glucose oxidase (GOx) can quickly respond to elevated glucose level, accompanied by the disassociation of PVs and fast release of encapsulated insulin. Moreover, the insulin release rate is further accelerated by GOx, which generates gluconic acid at high glucose levels, thus decreasing the local pH. Therefore, the host-guest interaction between WP5 and PPBA-G is destroyed and a total structure disassociation of PVs takes place, contributing to a fast release of encapsulated insulin. The in vivo insulin delivery to diabetic rats displays a quick response to hyperglycemic levels and then can fast regulate the blood glucose concentrations to normal levels, which demonstrates that the obtained smart insulin device has a highly potential application in the treatment of diabetes.

Electron-Phonon Scattering Is Much Weaker in Carbon Nanotubes than in Graphene Nanoribbons.

Carbon nanotubes (CNTs) and graphene nanoribbons (GNRs) are lower-dimensional derivatives of graphene. Similar to graphene, they exhibit high charge mobilities; however, in contrast to graphene, they are semiconducting and thus are suitable for electronics, optics, solar energy devices, and other applications. Charge carrier mobilities, energies, and lifetimes are governed by scattering with phonons, and we demonstrate, using ab initio nonadiabatic molecular dynamics, that charge-phonon scattering is much stronger in GNRs. Focusing on a GNR and a CNT of similar size and electronic properties, we show that the difference arises because of the significantly higher stiffness of the CNT. The GNR undergoes large-scale undulating motions at ambient conditions. Such thermal geometry distortions localize wave functions, accelerate both elastic and inelastic charge-phonon scattering, and increase the rates of energy and carrier losses. Even though, formally, both CNTs and GNRs are quantum confined derivatives of graphene, charge-phonon scattering differs significantly between them. Showing good agreement with time-resolved photoconductivity and photoluminescence measurements, the study demonstrates that GNRs are quite similar to molecules, such as conjugated polymers, while CNTs exhibit extended features attributed to bulk materials. The state-of-the-art simulations alter the traditional view of graphene nanostructures and demonstrate that the performance can be tuned not only by size and composition but also by stiffness and response to thermal excitation.

MicroRNA­223 promotes hepatocellular carcinoma cell resistance to sorafenib by targeting FBW7.

Hepatocellular carcinoma (HCC) is a globally prevalent malignancy associated with a poor patient prognosis. We investigated the relationship between microRNA­223 (miR­223) expression and the sensitivity of HCC cells to sorafenib treatment. miR­223 expression was determined in HCC cell lines with differential sorafenib sensitivity using reverse transcription­quantitative PCR. miR­223 inhibitor, miR­223 mimic, and F­box and WD repeat domain­containing 7 (FBW7) short interfering RNAs (siRNAs) were transfected into the HCC cells to regulate the expression levels of miR­223 and FBW7. Cell proliferation was evaluated using an ethynyl deoxyuridine (EdU) incorporation assay and Cell Counting Kit­8. FBW7 protein expression levels were observed using western blotting. miR­223 expression was increased in the HCC cells with sorafenib resistance. HCC cells with miR­223 knockdown had significantly increased sorafenib sensitivity, but the miR­223 mimic had the opposite effect. The TargetScan web server predicted that FBW7 is a target of miR­223, which was confirmed by western blotting. Furthermore, FBW7 siRNA transfection increased HCC cell resistance to sorafenib in an obvious manner, and entirely eliminated the effect of the miR­223 inhibitor on enhancing sorafenib sensitivity. To conclude, miR­223 expression is upregulated in sorafenib­resistant HCC cells, and miR­223 knockdown significantly enhances HCC cell sensitivity to sorafenib by increasing expression of the target gene, FBW7, suggesting that miR­223 may be a new therapeutic target for overcoming sorafenib resistance.

Mechanistic study on NO reduction by sludge reburning in a pilot scale cement precalciner with different CO2 concentrations.

An experimental study on the effects of CO2 concentration on the release of reducing gases and the NO reduction efficiency by sludge reburning was carried out in a pilot scale cement precalciner. The results indicate that sludge reburning shows an ideal NO reduction activity. The best NO reduction efficiency of 54% is reached when the CO2 concentration is 25 vol%. Characteristic analysis of the sludge shows that the main types of reducing gases generated by sludge reburning are HCN, NH3, CO and CH4. Among them, CO2 concentration plays a crucial role in the release of HCN, CO and CH4. The mechanistic study indicates that NO reduction is dominated by homogeneous reduction during the sludge reburning process, in particular the reducing gases of CO and NH3 have significant influences on the NO reduction. Meanwhile, the effect of CO2 concentration on NO reduction is mainly due to the difference in CO release. The results of the present study not only provide insight into the mechanism of NO reduction by sludge reburning, but could also contribute to the development of NO X removal technology in the cement industry.

The Electrode Modality Development in Pulsed Electric Field Treatment Facilitates Biocellular Mechanism Study and Improves Cancer Ablation Efficacy.

Pulsed electric field treatment is now widely used in diverse biological and medical applications: gene delivery, electrochemotherapy, and cancer therapy. This minimally invasive technique has several advantages over traditional ablation techniques, such as nonthermal elimination and blood vessel spare effect. Different electrodes are subsequently developed for a specific treatment purpose. Here, we provide a systematic review of electrode modality development in pulsed electric field treatment. For electrodes invented for experiment in vitro, sheet electrode and electrode cuvette, electrodes with high-speed fluorescence imaging system, electrodes with patch-clamp, and electrodes with confocal laser scanning microscopy are introduced. For electrodes invented for experiment in vivo, monopolar electrodes, five-needle array electrodes, single-needle bipolar electrode, parallel plate electrodes, and suction electrode are introduced. The pulsed electric field provides a promising treatment for cancer.

Isoglycyrrhizinate Magnesium Enhances Hepatoprotective Effect of FK506 on Ischemia-Reperfusion Injury Through HMGB1 Inhibition in a Rat Model of Liver Transplantation.

BACKGROUND: Ischemia-reperfusion injury after liver transplantation (LT) impairs graft function and affects prognosis of recipients. Isoglycyrrhizinate magnesium (Iso) is a hepatoprotective drug usually used after liver injury. In this study, we intended to explore whether Iso alone have protective effect after ischemia-reperfusion injury in a rat model of liver transplantation. We also aimed to study whether Iso could enhance the hepatoprotective effect of FK506 (tacrolimus) and underlying mechanism. METHODS: Rats after LT were treated with different concentration of FK506 with or without, Iso or lower-dose FK506 plus Iso. Alanine transaminase, aspartate transaminase, and albumin level were measured after 48 hours, 72 hours, and 7 days. A cell ischemic/reperfusion model was established to further study the mechanism of hepatoprotective effect of FK506 and Iso. RESULTS: Iso treatment alone had no effect on liver grafts after LT, but lower-dose FK506 + Iso was better for maintenance of liver function than lower-dose FK506 alone at 48 hours, 72 hours, and 7 days after LT. In terms of mechanism, FK506 induced autophagy which resulted in significantly reduced apoptosis and maintained proliferative potential. However, autophagy induced by FK506 also lead to high-mobility group box (HMGB) 1 release from nuclei, resulting in hepatocyte injury through triggering of p38 phosphorylation and chemokine release. Iso effectively inhibited the release of HMGB1 and downstream inflammatory cytokines. CONCLUSIONS: Iso could inhibit release of HMGB1 by FK506 and enhance the hepatoprotective effect of FK506 in rat LT. Combining Iso with FK506 would be promising for the patients after LT.