Association between computed tomography-quantified respiratory muscles and chronic obstructive pulmonary disease: a retrospective study.

BACKGROUND: This study examined the association between chest muscles and chronic obstructive pulmonary disease (COPD) and the relationship between chest muscle areas and acute exacerbations of COPD (AECOPD). METHODS: There were 168 subjects in the non-COPD group and 101 patients in the COPD group. The respiratory and accessory respiratory muscle areas were obtained using 3D Slicer software to analysis the imaging of  computed tomography (CT). Univariate and multivariate Poisson regressions were used to analyze the number of AECOPD cases during the preceding year. The cutoff value was obtained using a receiver operating characteristic (ROC) curve. RESULTS: We scanned 6342 subjects records, 269 of which were included in this study. We then measured the following muscle areas (non-COPD group vs. COPD group): pectoralis major (19.06 ± 5.36 cm2 vs. 13.25 ± 3.71 cm2, P < 0.001), pectoralis minor (6.81 ± 2.03 cm2 vs. 5.95 ± 1.81 cm2, P = 0.001), diaphragmatic dome (1.39 ± 0.97 cm2 vs. 0.85 ± 0.72 cm2, P = 0.011), musculus serratus anterior (28.03 ± 14.95 cm2 vs.16.76 ± 12.69 cm2, P < 0.001), intercostal muscle (12.36 ± 6.64 cm2 vs. 7.15 ± 5.6 cm2, P < 0.001), pectoralis subcutaneous fat (25.91 ± 13.23 cm2 vs. 18.79 ± 10.81 cm2, P < 0.001), paravertebral muscle (14.8 ± 4.35 cm2 vs. 13.33 ± 4.27 cm2, P = 0.007), and paravertebral subcutaneous fat (12.57 ± 5.09 cm2 vs. 10.14 ± 6.94 cm2, P = 0.001). The areas under the ROC curve for the pectoralis major, intercostal, and the musculus serratus anterior muscle areas were 81.56%, 73.28%, and 71.56%, respectively. Pectoralis major area was negatively associated with the number of AECOPD during the preceding year after adjustment (relative risk, 0.936; 95% confidence interval, 0.879-0.996; P = 0.037). CONCLUSION: The pectoralis major muscle area was negative associated with COPD. Moreover, there was a negative correlation between the number of AECOPD during the preceding year and the pectoralis major area.

Impact of bi-directional electric vehicle and demand response on residential distributed PV capacity planning based on TOU pricing.

The widespread deployment of residential distributed photovoltaic (RDPV) remains complex and challenging due to photovoltaic output intermittency, fluctuating electricity demand, and rising electric vehicle (EV) adoption. Simultaneously, the energy storage capabilities of EVs and residential demand response (DR) offer solutions for optimizing RDPV applications. This study proposes an integrated RDPV capacity planning model by encompassing EV charging, vehicle-to-home, and flexible load DR. Five scenarios are established to reveal the impact of various factors on the optimal photovoltaic installation capacity, electricity cost, self-consumption and self-sufficiency rate. A case study of three typical residential electricity demand patterns indicates that DR and vehicle-to-home significantly reduce the optimal photovoltaic installation capacity and total electricity cost. When the feed-in tariff during photovoltaic generation periods is higher than the off-peak pricing, DR results in a reduction in photovoltaic self-sufficiency rate and an increase in photovoltaic self-consumption rate. EV charging and vehicle-to-home have minimal impact on photovoltaic self-consumption rate, while EV charging significantly decreases self-sufficiency rate and vehicle-to-home exacerbates this effect.

Development of a Multivariate Prognostic Model for Lenvatinib Treatment in Hepatocellular Carcinoma.

BACKGROUND: Lenvatinib is a first-line agent for advanced hepatocellular carcinoma (HCC), but individual responses to treatment are highly heterogeneous. The aim of this study was to investigate the clinical parameters that influence the efficacy of Lenvatinib and to develop a prognostic model. METHODS: We retrospectively enrolled 333 Lenvatinib-treated patients with HCC with a median age of 57 years. Two hundred nd sixty-three of these patients had BCLC (2022) stage C. The median overall survival (mOS) time within the cohort was 12.1 months, and the median progression-free survival (mPFS) time was 4.7 months. Univariate Cox regression, best subset regression, and Lasso regression were used to screen primary variables for possible contribution to OS, multivariate Cox analysis was used to fit selected models, and the final model was selected using the maximum area under the curve (AUC) and minimum AIC. Receiver operating curves (ROC), calibration curves, and decision curve analysis were plotted to assess model performance, and 5-fold cross-validation was performed for internal validation. X-tile software was used to select the best cutoff points and to divide the study cohort into 3 different risk groups. RESULTS: Seven variables were included in the final model: BCLC stage, prior transarterial chemoembolization and immunotherapy history, tumor number, prognostic nutritional index, log (alpha-fetoprotein), and log (platelet-to-lymphocyte ratio). We named this final model the "multivariate prognostic model for Lenvatinib" (MPML), and a nomogram was constructed to predict the probability of survival at 6, 9, and 12 months. The MPML had good discrimination, calibration, and applicability. Cross-validation showed mean AUC values of 0.7779, 0.7738, and 0.7871 at 6, 9, and 12 months, respectively. According to nomogram points, mOS time was 21.57, 8.70, and 5.37 months in the low, medium, and high-risk groups, respectively (P < .001), and these differences were also observed in the PFS survival curve (P < .001). CONCLUSIONS: The MPML stratified patients according to baseline clinical characteristics had a strong performance in predicting Lenvatinib efficacy and has the potential for use as an auxiliary clinical tool for individualized decision-making.

Treatment options for unresectable hepatocellular carcinoma with hepatitis virus infection following sorafenib failure.

BACKGROUND: Currently, there are a few treatment options for unresectable hepatocellular carcinoma (HCC) after progression following sorafenib (SOR) therapy, but with limited benefit. The purpose of this study was to investigate the efficacy and safety of tyrosine kinase inhibitors (TKIs) combined with immune checkpoint inhibitors (ICIs) as second-line treatment. METHODS: From May 2018 to May 2021, a total of 93 HCCs who failed SOR treatment were included in this study and divided into TKI group (n = 37) and TKI-ICI group (n = 56). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety were estimated among the two groups. In addition, univariate and multivariate Cox regression analyses were performed for OS and PFS to identify possible prognostic factors. RESULTS: With a median follow-up time of 13.7 months, the median age of patients was 56 (range, 50-64) years and most were male. All of the patients were hepatitis virus-related HCC. Both median OS (7.63 months vs 19.23 months, P < 0.001) and median PFS (2.97 months vs 8.63 months, P < 0.001) were significantly improved in the TKI-ICI group compared to the TKI group. A significant increase in DCR was demonstrated in the TKI-ICI group compared to the TKI group (83.9% vs 45.9%, P = 0.0003), although no significant difference in ORR was reported (21.4% vs 8.1%, P = 0.1552). Multivariate Cox regression analysis of OS and PFS revealed that second-line regimen was an independent protective factor affecting death and progression in HCCs after SOR failure. In addition, Child-Pugh B7 was an independent risk factor of OS. Finally, there was no significant difference in the incidence of any grade or grade 3/4 adverse events (AEs) between the two groups, and no treatment-related deaths were observed. CONCLUSION: This real-world study suggests that the combination of TKIs and ICIs benefits more than mono-TKIs and is well tolerated in HCCs with hepatitis virus infection after SOR failure.

Theoretical Design of an Mox W1-x S2 /Graphene (x=0.25/0.75) Heterojunction with Adjustable Band Gap: Potential Candidate Materials for the Next Generation of Optoelectronic Devices.

Multicomponent two-dimensional (2D) transition metal dichalcogenides (TMDCs) semiconductors based on adjustable band gap are increasingly used to design optoelectronic devices with specific spectral response. Here, we have designed the Mox W1-x S2 /graphene heterostructure with adjustable band gap by adopting the combination idea of alloying and multiple heterogeneous recombination. The contact type, stability and photoelectric properties of Mox W1-x S2 /graphene heterojunction were investigated theoretically. At the same time, by applying external vertical electric field to Mox W1-x S2 /graphene, the regulate of heterojunction Schottky contact type was realized. The results show that Mox W1-x S2 /graphene heterojunction has broad application prospects in the field of photocatalysis and Schottky devices, and is suitable for being a potential candidate material for next generation of optoelectronic devices. The design of Mox W1-x S2 /graphene heterostructure enables it to obtain the advanced characteristics that are lacking in the one-component intrinsic 2D TMDCs semiconductors or graphene materials, and provides a theoretical basis for the experimental preparation of such heterojunctions.

Evolution of a Synthetic Strategy for Garsubellin A.

Garsubellin A is a thirty-carbon meroterpenoid capable of enhancing the enzyme choline acetyltransferase whose decreased level is associated with the symptoms of Alzheimer's disease. Due to the potentially useful biological activity along with the novel molecular architecture, this plant metabolite has remained a popular synthetic target. Herein we report a full account of our synthetic investigations that have led to the enantioselective total synthesis of garsubellin A, establishing its absolute stereostructure. The protecting group-free, twelve-step synthetic route has enabled the syntheses of the natural (-)-garsubellin A and its unnatural (+)-antipode.

Prognostic models for outcome prediction in patients with advanced hepatocellular carcinoma treated by systemic therapy: a systematic review and critical appraisal.

OBJECTIVE: To describe and analyze the predictive models of the prognosis of patients with hepatocellular carcinoma (HCC) undergoing systemic treatment. DESIGN: Systematic review. DATA SOURCES: PubMed and Embase until December 2020 and manually searched references from eligible articles. ELIGIBILITY CRITERIA FOR STUDY SELECTION: The development, validation, or updating of prognostic models of patients with HCC after systemic treatment. RESULTS: The systematic search yielded 42 eligible articles: 28 articles described the development of 28 prognostic models of patients with HCC treated with systemic therapy, and 14 articles described the external validation of 32 existing prognostic models of patients with HCC undergoing systemic treatment. Among the 28 prognostic models, six were developed based on genes, of which five were expressed in full equations; the other 22 prognostic models were developed based on common clinical factors. Of the 28 prognostic models, 11 were validated both internally and externally, nine were validated only internally, two were validated only externally, and the remaining six models did not undergo any type of validation. Among the 28 prognostic models, the most common systemic treatment was sorafenib (n = 19); the most prevalent endpoint was overall survival (n = 28); and the most commonly used predictors were alpha-fetoprotein (n = 15), bilirubin (n = 8), albumin (n = 8), Child-Pugh score (n = 8), extrahepatic metastasis (n = 7), and tumor size (n = 7). Further, among 32 externally validated prognostic models, 12 were externally validated > 3 times. CONCLUSIONS: This study describes and analyzes the prognostic models developed and validated for patients with HCC who have undergone systemic treatment. The results show that there are some methodological flaws in the model development process, and that external validation is rarely performed. Future research should focus on validating and updating existing models, and evaluating the effects of these models in clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020200187 .

Vanadium-Doped Molybdenum Diselenide Atomic Layers with Room-Temperature Ferromagnetism.

Diluted two-dimensional magnetic semiconductors with high Curie temperature are highly sought after because of their potential applications in spintronics. Development of new techniques for preparation of high quality diluted magnetic semiconductors is critical for their applications. In this study, vanadium-doped molybdenum selenide, a new diluted magnetic semiconductor, was synthesized by a single-step chemical vapor deposition method. The merit of this method is that the molybdenum and vanadium precursors can be supplied to the growth substrate uniformly. Photoluminescence measurements reveal that the band gap of MoSe2 decreases after doping, which can be attributed to the formation of impurity energy band caused by p-type doping at the valence band maximum. Thus, the V-doped MoSe2 still maintains the semiconducting characteristics. Vibrating sample magnetometer studies clearly show the ferromagnetism of V-doped MoSe2 at room temperature. DFT calculations illustrates the joint contribution of V dopants and nearby atoms to the magnetic moments. This study provides future prospects for the multifunctional application of two-dimensional materials.

Theoretical design of SnS2-graphene heterojunctions with vacancy and impurity defects for multi-purpose photoelectric devices.

SnS2 with atomic thickness has attracted extensive attention in the field of photocatalysis due to its special physicochemical properties, suitable band gap, low cost and low environmental toxicity. However, the application of SnS2 in the field of optoelectronics is restricted by its low photocatalytic efficiency and carrier mobility. In this study, vacancies and transition metal atoms are introduced into a SnS2 monolayer to modulate its physicochemical properties. Meanwhile, the SnS2 monolayer modified by vacancies and transition metal atoms is combined with graphene to form a heterostructure, which promotes the separation of photogenerated electron-hole pairs. The results of theoretical calculations show that the SnS2/graphene heterojunction can promote the separation of photogenerated carriers in intrinsic monolayer SnS2, and improve the photocatalytic efficiency and carrier mobility. The modification of Sn vacancies and Fe, Co atoms not only expands the visible light response range of the SnS2/graphene heterojunction, but also introduces magnetism, which is expected to be applied in spin optoelectronic materials. In this work, defects, doping and heterojunction assembly are rationally integrated, which provides a new idea for the design and development of spin optoelectronic devices based on monolayer SnS2.

Characteristics of Lung Microbiota in Children's Refractory Mycoplasma pneumoniae Pneumonia Coinfected with Human Adenovirus B.

BACKGROUND: Both M. pneumoniae and human adenovirus (HAdV) are common causative agents of lower respiratory tract infection in children; nonetheless, the lung microbiota in patients with coinfection of HAdV and M. pneumoniae remain unexplored. METHODS: Thirty-two children, diagnosed with refractory M. pneumoniae pneumonia (RMPP), entered into the one-year study from July 1, 2019 to June 30, 2020. Among them, twenty-one entered into the M. pneumoniae monoinfection (MP) group and eleven entered into the M. pneumoniae and HAdV coinfection (MP&ADV) group. The characteristics of the clinical findings were examined, and the lung microbiota was analyzed by metagenomic next generation sequencing (mNGS). RESULTS: Eleven patients in the MP&ADV group were coinfected with human mastadenovirus species B. The fever days lasted for significantly longer periods in the MP&ADV group than in the MP group (P < 0.05). The percentage of CD16+CD56+ cells was significantly higher in the MP&ADV group than that in the MP group (P < 0.05). There were no significant differences in α-diversity between the MP and MP&ADV groups, but the ß-diversity was clearly higher in the MP&ADV group than that in the MP group (P < 0.05). At the microbial level, the top phylum of the MP BALF microbiota was Tenericutes; in contrast, it was Preplasmiviricota in the MP&ADV BALF. There were significant differences in the relative abundance of Tenericutes and Preplasmiviricota between the two groups (P < 0.001). There was a strong positive correlation between human mastadenovirus B and fever days, M. pneumoniae and level of IgA, and a strong negative correlation between Mycoplasma pneumoniae and PCT. CONCLUSIONS: In RMPP, the BALF microbiota in children with mono M. pneumoniae infection was simpler than those with coinfection with human mastadenovirus B. Prolonged fever days were associated with human mastadenovirus B coinfection.

Transarterial chemoembolization plus lenvatinib versus transarterial chemoembolization plus sorafenib as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A prospective randomized study.

BACKGROUND: The efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) have not been evaluated. METHODS: In this open-label, single-center, randomized trial (ClinicalTrials.gov identifier: NCT04127396), participants with previously untreated HCC and type I-IV PVTT were randomized 1:1 to receive TACE plus lenvatinib (arm L; orally once daily, 12 mg for body weight ≥60 kg or 8 mg for body weight <60 kg) or TACE plus sorafenib (arm S; 400 mg orally twice daily in 28-day cycles). The primary end point was time-to-progression (TTP; time from randomization to disease progression) and secondary end points included objective response rate and toxicity. Prognostic factors were evaluated using a multivariable Cox proportional hazards model. RESULTS: Between December 30, 2018 and May 31, 2020, 64 patients were randomized (arm L, n = 32; arm S, n = 32); most patients had type I/II PVTT (71.9%), and the median target tumor diameter was 9.8 cm (range, 3.8-21.8). After a median follow-up of 16.1 months, patients in arm L had a higher median TTP (4.7 vs 3.1 months; hazard ratio [HR], 0.55; 95% CI, 0.32-0.95; P = .029) and objective response rate (53.1% vs 25.0%, P = .039) versus arm S. Multivariable analysis showed that TACE plus lenvatinib was significantly associated with higher TTP versus TACE plus sorafenib (HR, 0.50; 95% CI, 0.28-0.90; P = .021). Comparable safety profiles were observed in arms L and S. CONCLUSIONS: TACE plus lenvatinib was safe, well tolerated, and had favorable efficacy versus TACE plus sorafenib in patients with advanced HCC with PVTT and large tumor burden. LAY SUMMARY: Hepatocellular carcinoma with portal vein tumor thrombus has a poor prognosis. In addition, most phase 3 trials of drugs for hepatocellular carcinoma exclude patients with major portal vein invasion, and treatment options for these patients are limited. Transarterial chemoembolization has shown promising efficacy in these patients, especially in combination with systemic treatment or radiotherapy. However, transarterial chemoembolization plus lenvatinib has not been investigated in this setting. This open-label, single-center, randomized trial showed that transarterial chemoembolization plus lenvatinib is safe, well tolerated, and has favorable efficacy versus transarterial chemoembolization plus sorafenib for the treatment of hepatocellular carcinoma with portal vein tumor thrombus.

DHA Protects Hepatocytes from Oxidative Injury through GPR120/ERK-Mediated Mitophagy.

Oxidative stress occurs in a variety of clinical liver diseases and causes cellular damage and mitochondrial dysfunction. The clearance of damaged mitochondria by mitophagy may facilitate mitochondrial biogenesis and enhance cell survival. Although the supplementation of docosahexaenoic acid (DHA) has been recognized to relieve the symptoms of various liver diseases, the antioxidant effect of DHA in liver disease is still unclear. The purpose of our research was to investigate the antioxidant effect of DHA in the liver and the possible role of mitophagy in this. In vitro, H2O2-induced injury was caused in AML12 cells. The results showed that DHA repressed the level of reactive oxygen species (ROS) induced by H2O2 and stimulated the cellular antioxidation response. Most notably, DHA restored oxidative stress-impaired autophagic flux and promoted protective autophagy. In addition, PINK/Parkin-mediated mitophagy was activated by DHA in AML12 cells and alleviated mitochondrial dysfunction. The ERK1/2 signaling pathway was inhibited during oxidative stress but reactivated by DHA treatment. It was proven that the expression of ERK1/2 was involved in the regulation of mitophagy by the ERK1/2 inhibitor. We further proved these results in vivo. DHA effectively alleviated the liver oxidative damage caused by CCl4 and enhanced antioxidation capacity; intriguingly, autophagy was also activated. In summary, our data demonstrated that DHA protected hepatocytes from oxidative damage through GPR120/ERK-mediated mitophagy.

Enantioselective Total Synthesis of (+)-Garsubellin†A.

Garsubellin A is a meroterpene capable of enhancing the enzyme choline acetyltransferase whose decreased level is believed to play a central role in the symptoms of Alzheimer's disease. Due to the potentially useful biological activity together with the novel bridged and fused cyclic molecular architecture, garsubellin A has garnered substantial synthetic interest, but its absolute stereostructure has been undetermined. We report here the first enantioselective total synthesis of (+)-garsubellin A. Our synthesis relies on stereoselective fashioning of a cyclohexanone framework and double conjugate addition of 1,2-ethanedithiol that promotes aldol cyclization to build the bicyclic [3.3.1] skeleton. The twelve-step, protecting group-free synthetic route has enabled the syntheses of both the natural (-)-garsubellin A and its unnatural (+)-antipode for biological evaluations.

Retraction Note to: IL­2 augments the sorafenib­induced apoptosis in liver cancer by promoting mitochondrial fission and activating the JNK/TAZ pathway.

[This retracts the article DOI: 10.1186/s12935-018-0671-3.].

Prognostic significance of the CRP/Alb and neutrophil to lymphocyte ratios in hepatocellular carcinoma patients undergoing TACE and RFA.

BACKGROUND: The C-reactive protein (CRP)/albumin (Alb) ratio (CAR) is a basic inflammatory factor that has been related to poor survival of patients with various tumors. Our research retrospectively examined the relationship between the CAR and the prognosis of hepatocellular carcinoma (HCC). METHODS: This study included 172 patients with HCC who were treated with transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA). RESULTS: The CAR was weakly related to the neutrophil/lymphocyte ratio (NLR, r = .159, P = .037) and the lymphocyte/monocyte ratio (LMR, r = -.263, P = .001). The Glasgow Prognostic Score (GPS) (0/1-2) was related to liver cirrhosis (P = .003), tumor number (P = .02), Child-Pugh grade (P = .001), the platelet/lymphocyte ratio (PLR, P = .006), and the LMR (P = .021). Correlation analysis demonstrated that an elevated CAR was markedly correlated with the tumor size (P = .019), alpha-fetoprotein (AFP) level (P = .033), thrombosis of the portal vein (P = .004), the NLR (P = .036), and the LMR (P = .001). Multivariate analysis indicated that the prognosis of the CAR-High and NLR-High cohort (mOS = 7 months) was significantly worse than those of the CAR-High or NLR-High cohort (mOS = 15 months) and the CAR-Low and NLR-Low cohort (mOS = 26.5 months). CONCLUSIONS: Combination of the NLR and the CAR represents a convenient, quick, and noninvasive biological marker that could improve prognostic prediction in patients with HCC.

Effect of norepinephrine treatment on Haemonchus contortus and its excretory products.

Haemonchus contortus is a highly pathogenic gastrointestinal nematode of small ruminant animals. In modern intensive farming, livestock often suffer from different types of stress. However, whether host stress hormones influence H. contortus infection is largely unknown. Therefore, we treated H. contortus with norepinephrine (NE) and analyzed the changes in its excretory/secretory products (ESPs). Label-free quantitative proteomic analysis was used to identify differences in body proteins and ESPs between the control and NE-treated groups. We also investigated the changes in ESP action by analyzing cytokine secretion and goat peripheral blood mononuclear cell (PBMC) proliferation after incubation with ESPs secreted by NE-treated H. contortus. Thirty-two proteins in the body samples and 137 in the ESPs were differentially expressed between the groups. Gene ontology (GO) annotation showed that the functions of these different proteins might be involved in energy metabolism, protein metabolism, lipid metabolism, redox homeostasis, ion channel, and cell structure. NE treatment caused oxidative stress in H. contortus and changed the expression levels of some immunogenic proteins, such as the 15-kDa ESP. Meanwhile, the ESPs secreted by NE-treated H. contortus significantly decreased PBMC proliferation and the interleukin (IL)-2, IL-4, and interferon-gamma contents. Thus, NE treatment significantly affected the H. contortus body and ESP expression, and changes in the ESPs influenced PBMC function. The results reveal a relationship between host hormones and parasites and provide new clues to explain some of the variation in individual responses to infection.

IL-2 augments the sorafenib-induced apoptosis in liver cancer by promoting mitochondrial fission and activating the JNK/TAZ pathway.

BACKGROUND: Sorafenib is the standard targeted drug used to treat hepatocellular carcinoma (HCC), but the therapeutic response between individuals varies markedly. Recently, cytokine-based immunotherapy has been a topic of intense discussion in the fight against cancer. The aim of this study was to explore whether cytokine IL-2 could augment the anti-tumour effects of sorafenib on HCC. METHODS: HepG2 and Huh7 cells were co-treated with sorafenib and IL-2 in vitro, and cellular viability and death were analysed through the MTT assay, TUNEL staining, LDH release assay, and western blotting. Mitochondrial function was measured via ELISA, immunofluorescence, and western blotting. Pathway blockers were used to establish the role of the JNK-TAZ pathways in regulating cancer cell phenotypes. RESULTS: Our data demonstrated that sorafenib treatment increased the HCC apoptotic rate, repressed cell proliferation, and inhibited migratory responses, and these effects were enhanced by IL-2 supplementation. Mechanistically, the combination of IL-2 and sorafenib interrupted mitochondrial energy metabolism by downregulating mitochondrial respiratory proteins. In addition, IL-2 and sorafenib co-treatment promoted mitochondrial dysfunction, as evidenced by the decreased mitochondrial potential, elevated mitochondrial ROS production, increased leakage of mitochondrial pro-apoptotic factors, and activation of the mitochondrial death pathway. A molecular investigation revealed that mitochondrial fission was required for the IL-2/sorafenib-mediated mitochondrial dysfunction. Mitochondrial fission was triggered by sorafenib and was largely amplified by IL-2 supplementation. Finally, we found that IL-2/sorafenib regulated mitochondrial fission via the JNK-TAZ pathways; blockade of the JNK-TAZ pathways abrogated the inhibitory effects of L-2/sorafenib on cancer survival, growth and mobility. CONCLUSIONS: Altogether, these data strongly suggest that additional supplementation with IL-2 enhances the anti-tumour activity of sorafenib by promoting the JNK-TAZ-mitochondrial fission axis. This finding will pave the way for new treatment modalities to control HCC progression by optimizing sorafenib-based therapy.

Gold(i)-catalyzed synthesis of 2-substituted indoles from 2-alkynylnitroarenes with diboron as reductant.

An efficient method for the synthesis of 2-substituted indoles via a diboron/base promoted tandem reductive cyclization of o-alkynylnitroarene under Au catalysis conditions has been disclosed. This reaction is efficient and convenient, affording 2-substituted indoles with broad functional groups tolerance and excellent yields.

Lipid raft-mediated miR-3908 inhibition of migration of breast cancer cell line MCF-7 by regulating the interactions between AdipoR1 and Flotillin-1.

BACKGROUND: The mechanisms of lipid raft regulation by microRNAs in breast cancer are not fully understood. This work focused on the evaluation and identification of miR-3908, which may be a potential biomarker related to the migration of breast cancer cells, and elucidates lipid-raft-regulating cell migration in breast cancer. METHODS: To confirm the prediction that miR-3908 is matched with AdipoR1, we used 3'-UTR luciferase activity of AdipoR1 to assess this. Then, human breast cancer cell line MCF-7 was cultured in the absence or presence of the mimics or inhibitors of miR-3908, after which the biological functions of MCF-7 cells were analyzed. The protein expression of AdipoR1, AMPK, and SIRT-1 were examined. The interaction between AdipoR1 and Flotillin-1, or its effects on lipid rafts on regulating cell migration of MCF-7, was also investigated. RESULTS: AdipoR1 is a direct target of miR-3908. miR-3908 suppresses the expression of AdipoR1 and its downstream pathway genes, including AMPK, p-AMPK, and SIRT-1. miR-3908 enhances the process of breast cancer cell clonogenicity. miR-3908 exerts its effects on the proliferation and migration of MCF-7 cells, which are mediated by lipid rafts regulating AdipoR1's ability to bind Flotillin-1. CONCLUSIONS: miR-3908 is a crucial mediator of the migration process in breast cancer cells. Lipid rafts regulate the interactions between AdipoR1 and Flotillin-1 and then the migration process associated with miR-3908 in MCF-7 cells. Our findings suggest that targeting miR-3908 and the lipid raft, may be a promising strategy for the treatment and prevention of breast cancer.

Maternal sodium butyrate supplement elevates the lipolysis in adipose tissue and leads to lipid accumulation in offspring liver of weaning-age rats.

BACKGROUND: Sodium butyrate (SB) is reported to regulate lipid metabolism in mammals, and the relationship between maternal nutrition and offspring growth has drawn much attention in the last several years. METHODS: To elucidate the effects of maternal dietary SB supplementation on hepatic lipid metabolism in weaning rats, we fed 16 primiparous purebred female SD rats either a chow-diet or a 1 % sodium butyrate diet throughout pregnancy and lactation. At weaning age, samples of the maternal subcutaneous adipose tissue and offspring liver were taken. The serum indexes and expressions of proteins related to lipid metabolism were detected in the mother and offspring, respectively. RESULTS: The results showed that the maternal SB supplement increased the concentration of non-esterified fatty acid (NEFA) in the maternal and offspring serum (P < 0.05). Total cholesterol (Tch) increased significantly in the weaning-rat serum (P < 0.05). Maternal adipose tissue from the SB-supplemented rats showed higher content of protein G-coupled protein (GPR43) and protein kinase A (PKA) (P < 0.05). The expression of protein adipose triglyceride lipase (ATGL), and of total and phosphorylated hormone sensitive lipase (HSL), in the maternal adipose tissue increased significantly (P < 0.05) compared to the control group. However the proteins related to lipogenesis showed no significant changes. Moreover, the concentration of triglyceride in the offspring liver increased significantly, and this likely resulted from an increase in the levels of fatty acids binding protein (FABP) and fatty acid translocase (CD36) protein (P < 0.05). SB exposure during pregnancy and lactation increased the hepatic total cholesterol (Tch) content (P < 0.01), which was related to a significantly up-regulated offspring hepatic expression of low density lipoprotein receptor (LDLR) protein (P < 0.05). CONCLUSION: These results indicate that a maternal SB supplement during pregnancy and the lactation period promotes maternal fat mobilization, which may result in fatty acid uptake and lipid accumulation in the liver of the offspring.