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Li-Li Liu,1,2,* Ji-Min Zhu,1,2,* Xiang-Nan Yu,1,2 Hai-Rong Zhu,1,2 Xuan Shi,1,2 Enkhnaran Bilegsaikhan,1,2 Hong-Ying Guo,1,2 Jian Wu,1–3 Xi-Zhong Shen1–3 1Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China; 2Shanghai Institute of Liver Diseases, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Department of Medical Microbiology and Parasitology, Ministry of Education/National Health Commission/Chinese Academy of Medical Sciences, Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xi-Zhong ShenDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, People’s Republic of ChinaTel +86 216 404 1990Email shen.xizhong@zs-hospital.sh.cn Jian WuDepartment of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, 138 Yixue Yuan Road, P.O. Box 228, Shanghai 200032, People’s Republic of ChinaTel +86 21 5423 7705Email jian.wu@fudan.edu.cnBackground: Growing evidence suggests that the ubiquitin-proteasome system is involved in the pathogenesis and recurrence of hepatocellular carcinoma (HCC); yet, little is known about the role of ubiquitin-conjugating enzyme E2T (UBE2T) in HCC.Materials and methods: UBE2T levels were detected in HCC tissues and hepatoma cell lines using quantitative reserve transcriptase-polymerase chain reaction and Western blot analysis. Next, the changes of phenotypes after UBE2T knockdown or overexpression were evaluated using in vitro methods. Finally, the mechanism of UBE2T in HCC was tested using ex vivo and in vivo methods.Results: In the present study, we reported that UBE2T mRNA and protein levels were significantly upregulated in HCC tissues compared to adjacent non-tumor tissues. Additionally, suppression of UBE2T expression inhibited proliferation, colony formation, tumorigenesis, migration, and invasion of hepatoma cells, whereas UBE2T overexpression led to the opposite outcomes. Moreover, suppression of UBE2T expression resulted in an increase in G2/M phase and a decrease in the percentage of cells in G1 phase, which indicated a cell cycle arrest at the G2/M phase. In contrast, the percentage of cells in G2/M phase decreased following UBE2T overexpression. Further study indicated that UBE2T regulated the G2/M transition by modulating cyclin B1 and cyclin-dependent kinase 1.Conclusion: Taken together, the findings of the present study uncover biological functions of UBE2T in hepatoma cells, and delineate preliminary molecular mechanisms of UBE2T in modulating HCC development and progression.Keywords: hepatocellular carcinoma, UBE2T, ubiquitination, cell cycle

Hong Chen,1 Hai-Rong Zhu,2 Xiang-Nan Yu,2 Xuan Shi,2 Enkhnaran Bilegsaikhan,2 Hong-Ying Guo,2 Ren-Zheng Huang,2 Tao-Tao Liu,2 Xi-Zhong Shen,2–4 Ji-Min Zhu2,31Department of Endocrinology, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Gastroenterologyand Hepatology, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China; 3Shanghai Institute of Liver Disease, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China; 4Key Laboratory of Medical Molecular Virology, Shanghai Medical College of Fudan University, Shanghai, People’s Republic of ChinaBackground: Aberrant expression of pepsinogen C (PGC) has been observed in human cancers. However, its role in hepatocellular carcinoma (HCC) remains to be established. The goal of this study is to illustrate PGC expression and to evaluate its clinical relevance in HCC.Materials and methods: PGC expression was examined in 75 pairs of HCC and adjacent non-tumor tissues using tissue microarray. The correlations between its expression and clinical parameters were also analyzed.Results: PGC overexpression was significantly associated with larger tumor size (≥5 cm; P=0.017) and incomplete encapsulation (P

Zinc-air batteries (ZABs) have the advantages of high energy density and rich zinc raw materials. It is a low-cost, green and sustainable energy storage device. At present, one of the key technologies that hinder the large-scale application of ZABs is the design and fabrication oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) bifunctional catalysts with excellent performance, especially the non-platinum-based catalysts. Here N-doped carbon-coated Fe-based selenium oxide catalyst Fe 2 O(SeO 3 ) 2 /Fe 3 C@NC with high performance has been fabricated by a one-step pyrolysis and then the electrochemical oxidization. The experimental results confirmed that the existence of Fe-O-Se bonds in Fe 2 O(SeO 3 ) 2 crystal phase of Fe 2 O(SeO 3 ) 2 /Fe 3 C@NC, and the Fe-O-Se bonds could obviously enhance ORR and OER catalytic performance of Fe 2 O(SeO 3 ) 2 /Fe 3 C@NC. Density functional theoretical calculations (DFT) confirmed that the Fe 2 O(SeO 3 ) 2 in Fe 2 O(SeO 3 ) 2 /Fe 3 C@NC had a higher d-band center of Fe atom and a lower p-orbital coupling degree with its own lattice O atom than Fe 2 O 3 , which leads to Fe site of Fe 2 O(SeO 3 ) 2 being more likely to adsorb external oxygen intermediates. The Fe-O-Se bonds in Fe 2 O(SeO 3 ) 2 results in the modification of coordination environment of Fe atoms and optimizes the adsorption energy of Fe site for oxygen intermediates. Compared with Fe 2 O 3 /Fe 3 C@NC, the Fe 2 O(SeO 3 ) 2 /Fe 3 C@NC showed the obvious enhancements of ORR/OER catalytic activities with a half-wave potential of 0.91 V for ORR in 0.1 M KOH electrolyte and a low overpotential of 345 mV for OER at 10 mA cm -2 in a 1.0 M KOH electrolyte. The peak power density and specific capacity of Fe 2 O(SeO 3 ) 2 /Fe 3 C@NC-based ZABs are higher than those of Pt/C+RuO 2 -ZABs. The above results demonstrate that the asymmetrical Fe-O-Se bonds in Fe 2 O(SeO 3 ) 2 plays a key role in improving the bifunctional catalytic activities of ORR/OER for ZABs., (© 2024 Wiley-VCH GmbH.)

Background: Cyclic vomiting syndrome (CVS) is a chronic functional gastrointestinal disorder involving the gut-brain interaction that is characterized by recurring episodes of nausea, vomiting, abdominal pain, and interspersed complete normal periods. Superior mesenteric artery (SMA) syndrome (SMAS) is a vascular condition in which the horizontal portion of the duodenum is compressed due to a reduced angle between the aorta and the SMA. This condition presents with symptoms similar to CVS, posing challenges in distinguishing between the two and often resulting in misdiagnosis or inappropriate treatment., Case Summary: A 20-year-old female patient presented with recurrent episodes of vomiting and experienced a persistent fear of vomiting for the past 2 years. She adopted conscious dietary restrictions, which led to severe malnutrition. Initially, she was diagnosed with SMAS, as revealed by computed tomography angiography. Despite efforts to increase the angle between the aorta and the SMA through weight gain, her vomiting did not improve. Finally, she was diagnosed with comorbidities including CVS, SMAS and anxiety disorder. She underwent comprehensive interventions, including enteral and parenteral nutritional supplementation, administration of antiemetic and anti-anxiety agents, and participation in mindfulness-based cognitive therapy. The patient eventually experienced a notable improvement in both body weight and clinical symptoms., Conclusion: We present a rare case of CVS in an adult complicated with SMAS and propose additional treatment with nutritional support, pharmacological intervention, and psychotherapy., Competing Interests: Conflict-of-interest statement: No conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Double-negative T (DNT) cells comprise a distinct subset of T lymphocytes that have been implicated in immune responses. The aim of this study was to characterize the peripheral DNT population in breast cancer (BC) patients., Methods: DNT cells were isolated from the peripheral blood samples of BC patients and healthy controls by flow cytometry. The sorted DNT cells were analyzed by the Smart-seq2 for single-cell full-length transcriptome profiling. The differentially expressed genes (DEGs) between the BC and control groups were screened and functionally annotated by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using R. The protein-protein interaction (PPI) network of the DEGs was constructed using the CytoHubba and MCODE plug-in of Cytoscape software to identify the core genes. Survival status, DNA methylation level, immune infiltration and immune checkpoint expression were analyzed using Kaplan-Meier Plotter, UALCAN, MethSeuvr, TIMER, and TISIDB respectively. The sequencing results were verified by RT-qPCR., Result: The percentage of DNT cells was higher in the BC patients compared to healthy controls. We identified 289 DEGs between the DNT populations of both groups. GO and KEGG pathway analyses revealed that the DEGs were mainly related to immunoglobulin mediated immune response, complement activation, and B cell receptor signaling. The PPI networks of the common DEGs were constructed using Cytoscape, and 10 core genes were identified, including TMEM176B, C1QB, C1QC, RASD2, and IFIT3. The expression levels of these genes correlated with the prognosis and immune infiltration in BC patients, and were validated by RT-qPCR (P < 0.05)., Conclusions: DNT cells are abundant in patients with BC, and might exert anti-tumor immune responses by regulating genes such as TMEM176B and EGR1., (© 2024. The Author(s).)

Water electrolysis has become an attractive hydrogen production method. Oxygen evolution reaction (OER) is a bottleneck of water splitting as its four-electron transfer procedure presents sluggish reaction kinetics. Designing composite catalysts with high performance for efficient OER still remains a huge challenge. Here, the P-doped cobalt oxide/NiFe layered double hydroxides (P-CoO X /NiFe LDHs) composite catalysts with amorphous/crystalline interfaces are successfully prepared for OER by hydrothermal-electrodeposition combined method. The results of electrochemical characterizations, operando Raman spectra, and DFT theoretical calculations have demonstrated the electrons in the P-CoO X /NiFe LDHs heterointerfaces are easily transferred from Ni 2+ to Co 3+ because that the amorphous configuration of P-CoO X can well induce Ni-O-Co orbital coupling. The electron transfer of Ni 2+ to the surrounding Fe 3+ and Co 3+ will lead to the unoccupied e g orbitals of Ni 3+ that can promote water dissociation and accelerate * OOH migration to improve OER catalytic performance. The optimized P-CoO X /NiFe LDHs exhibit superior catalytic performance for OER with a very low overpotential of 265 mV at 300 mA cm -2 and excellent long-term stability of 500 h with almost no attenuation at 100 mA cm -2 . This work will provide a new method to design high-performance NiFe LDHs-based catalysts for OER., (© 2024 Wiley‐VCH GmbH.)

Objective: To evaluate the T-lymphocyte subset distribution and the diagnostic and prognosis value of double-negative T (DNT) cells in colorectal cancer (CRC)., Methods: This retrospective study compared the T-lymphocyte subsets and DNT of 114 patients with CRC with those of 107 healthy controls (HC). The diagnostic potential of DNT and T-lymphocyte subsets was assessed using the receiver operating characteristic (ROC) curve, and prognostic values were evaluated using the Kaplan-Meier curve and the Cox regression model., Results: The percentages of CD8 + T cells and DNT cells, and value of carcinoembryonic antigen (CEA), were remarkably higher in patients with CRC than in those with HC, but the ratio of CD4 + /CD8 + was decreased. Using ROC curve analysis, DNT cell percentage, CEA, and CD4 + /CD8 + ratio all had good diagnostic efficacy, with areas under the curve (AUCs) of 0.865, 0.786 and 0.624, respectively. The combination of DNT cell percentage and CEA had an AUC of 0.905, which was significantly higher than that of any single biomarker ( p  < 0.05). In univariate analysis, the Tumor Node Metastasis (TNM) clinical stage, CD4 + /CD8 + ratio, and DNT cell percentage were significantly associated with overall survival (OS) ( p  < 0.05). In multivariate analysis, TNM clinical staging (HR = 2.37, 95 % CI: 1.15-4.90), a decreased CD4 + /CD8 + ratio (HR = 0.33, 95 % CI: 0.15-0.74), and an increased DNT cell percentage (HR = 2.29, 95 % CI: 1.11-4.73) were independent prognostic factors for CRC., Conclusion: The percentage of DNT cells may be useful as an evaluation index for CRC diagnosis and prognosis, which was even better when combined with serum CEA., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Multidrug resistance is a substantial obstacle in treating non-small cell lung cancer (NSCLC) with therapies like cisplatin (DDP)-based adjuvant chemotherapy and EGFR-tyrosine kinase inhibitors (TKIs). Aaptamine-7 (AP-7), a benzonaphthyridine alkaloid extracted from Aaptos aaptos sponge, has been shown to exhibit a broad spectrum of anti-tumor activity. However, the anti-cancer activity of AP-7 in combination with DDP and its molecular mechanisms in multidrug-resistant NSCLC are not yet clear. Our research indicates that AP-7 bolsters the growth inhibition activity of DDP on multidrug-resistant NSCLC cells. AP-7 notably disrupts DDP-induced cell cycle arrest and amplifies DDP-induced DNA damage effects in these cells. Furthermore, the combination of AP-7 and DDP downregulates Chk1 activation, interrupts the DNA damage repair-dependent Chk1/CDK1 pathway, and helps to overcome drug resistance and boost apoptosis in multidrug-resistant NSCLC cells and a gefitinib-resistant xenograft mice model. In summary, AP-7 appears to enhance DDP-induced DNA damage by impeding the Chk1 signaling pathway in multidrug-resistant NSCLC, thereby augmenting growth inhibition, both in vitro and in vivo . These results indicate the potential use of AP-7 as a DDP sensitizer in the treatment of multidrug-resistant NSCLC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guan, Liao, Cao, Liu, Xue, Zhu, Bian, Yang, Lin, Liao and Sun.)

The development of efficient urea oxidation reaction (UOR) catalysts helps UOR replace the oxygen evolution reaction (OER) in hydrogen production from water electrolysis. Here, we prepared Fe-doped Ni 2 P/NiSe 2 composite catalyst (Fe-Ni 2 P/NiSe 2 -12) by using phosphating-selenizating and acid etching to increase the intrinsic activity and active areas. Spectral characterization and theoretical calculations demonstrated that electrons flowed through the Ni-P-Fe-interface-Ni-Se-Fe, thus conferring high UOR activity to Fe-Ni 2 P/NiSe 2 -12, which only needed 1.39 V vs RHE to produce the current density of 100 mA cm -2 . Remarkably, this potential was 164 mV lower than that required for the OER under the same conditions. Furthermore, EIS demonstrated that UOR driven by the Fe-Ni 2 P/NiSe 2 -12 exhibited faster interfacial reactions, charge transfer, and current response compared to OER. Consequently, the Fe-Ni 2 P/NiSe 2 -12 catalyst can effectively prevent competition with OER and NSOR, making it suitable for efficient hydrogen production in UOR-assisted water electrolysis. Notably, when water electrolysis is operated at a current density of 40 mA cm -2 , this UOR-assisted system can achieve a decrease of 140 mV in the potential compared to traditional water electrolysis. This study presents a novel strategy for UOR-assisted water splitting for energy-saving hydrogen production.

A long-term goal of rechargeable zinc-air batteries (ZABs) has always been to design bifunctional electrocatalysts that are robust, effective, and affordable for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). It has become a feasible method to construct metal/metal oxide interfaces to achieve superior electrocatalytic performance for ORR and OER by enhanced charge transfer. In this study, Co/Co 3 O 4 heterojunctions were successfully prepared and encased in porous N-doped mesoporous carbon (Co/Co 3 O 4 @NC) via a simple condensation-carbonization-etching method. The extensive specific surface area of Co/Co 3 O 4 @NC facilitates effective interaction between the electrolyte and the catalyst, thereby enabling sufficient exposure of active sites for the ORR and the OER, consequently enhancing the rate of transport of active species. The well-designed Co/Co 3 O 4 @NC delivers superior ORR catalytic activity with a half-wave potential of 0.82 V (vs RHE) and a low overpotential of 347 mV at 10 mA cm -2 for OER in alkaline solution. The power density of Co/Co 3 O 4 @NC-based alkaline aqueous ZAB (156.5 mW cm -2 ) is superior to the commercial Pt/C + IrO 2 -based alkaline aqueous ZAB, and the cycling stability of ZAB is up to 220 h. In addition, Co/Co 3 O 4 @NC-based ZAB shows a high power density (50.1 mW cm -2 ). The construction of metal/metal oxide heterojunction encased in N-doped mesoporous carbon provides a novel route for the design of bifunctional electrocatalysts for high-performance ZABs.

Early diagnosis and pharmacological treatment of central nervous system (CNS) diseases has been a long-standing challenge for clinical research due to the presence of the blood-brain barrier. Specific proteins and RNAs in brain-derived extracellular vesicles (EVs) usually reflect the corresponding state of brain disease, and therefore, EVs can be used as diagnostic biomarkers for CNS diseases. In addition, EVs can be engineered and fused to target cells for delivery of cargo, demonstrating the great potential of EVs as a nanocarrier platform. We review the progress of EVs as markers and drug carriers in the diagnosis and treatment of neurological diseases. The main areas include visual imaging, biomarker diagnosis and drug loading therapy for different types of CNS diseases. It is hoped that increased knowledge of EVs will facilitate their clinical translation in CNS diseases., (© 2023. The Author(s).)

Background: Delayed or missed dosages caused by poor medication compliance significantly affected the treatment of diseases in children., Aims: The present study aimed to investigate the influence of delayed or missed dosages on sirolimus pharmacokinetics (PK) in pediatric tuberous sclerosis complex (TSC) patients and to recommend remedial dosages for nonadherent patients., Methods: A published sirolimus population PK model in pediatric TSC patients was used to assess the influence of different nonadherence scenarios and recommend optimally remedial dosages based on Monte Carlo simulation. Thirteen nonadherent scenarios were simulated in this study, including delayed 2h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 23.5 h, and missed one dosage. Remedial dosing strategies contained 10-200% of scheduled dosages. The optimal remedial dosage was that with the maximum probability of returning the individual therapeutic range., Results: For delayed or missed sirolimus dosages in pediatric TSC patients, when the delayed time was 0-8 h, 8-10 h, 10-18 h, 18-22.7 h, 22.7-24 h, 70%, 60%, 40%, 30%, 20% scheduled dosages were recommended to take immediately. When one dosage was missed, 120% of scheduled dosages were recommended at the next dose., Conclusion: It was the first time to recommend remedial dosages for delayed or missed sirolimus therapy caused by poor medication compliance in pediatric TSC patients based on Monte Carlo simulation. Meanwhile, the present study provided a potential solution for delayed or missed dosages in clinical practice., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Identifying biomarkers to predict lapse of alcohol-dependence (AD) is essential for treatment and prevention strategies, but remains remarkably challenging. With an aim to identify neuroimaging features for predicting AD lapse, 66 male AD patients during early-abstinence (baseline) after hospitalized detoxification underwent resting-state functional magnetic resonance imaging and were then followed-up for 6 months. The relevance-vector-machine (RVM) analysis on baseline large-scale brain networks yielded an elegant model for differentiating relapsing patients (n = 38) from abstainers, with the area under the curve of 0.912 and the accuracy by leave-one-out cross-validation of 0.833. This model captured key information about neuro-connectome biomarkers for predicting AD lapse., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objective To explore the cell subsets and characteristics related to the prognosis of osteosarcoma by analyzing the cellular composition of tumor tissue samples from different osteosarcoma patients.Methods The single-cell sequencing data and bulk sequencing data of different osteosarcoma patients were downloaded.We extracted the information of cell samples for dimensionality reduction,annotation,and cell function analysis,so as to identify the cell subsets and clarify the cell characteristics related to the prognosis of osteosarcoma.The development trajectory of macrophages with prognostic significance was analyzed,and the prognostic model of osteosarcoma was established based on the differentially expressed genes of macrophage differentiation.Results The cellular composition presented heterogeneity in the patients with osteosarcoma.The infiltration of mononuclear phagocytes in osteosarcoma had prognostic significance( P =0.003).Four macrophage subsets were associated with prognosis,and their signature transcription factors included RUNX3(+),ETS1(+),HOXD11(+),ZNF281(+),and PRRX1(+).Prog&#95;Macro2 and Prog&#95;Macro4 were located at the end of the developmental trajectory,and the prognostic ability of macrophage subsets increased with the progression of osteosarcoma.The prognostic model established based on the differentially expressed genes involved in macrophage differentiation can distinguish the survival rate of osteosarcoma patients with different risks( P <0.001).Conclusion Macrophage subsets are closely related to the prognosis of osteosarcoma and can be used as the key target cells for the immunotherapy of osteosarcoma.

It is generally believed that high-quality Bupleurum scorzonerifolium roots possess specific morphological characteristics, being red, robust, and long with strong odor. However, the scientific connotation of these characteristics has not been elucidated. According to the theory of &quot;quality evaluation through morphological identification&quot;, we studied the correlations between appearance traits(the RGB value of root surface, root length, root diameter, dry weight, and ratio of phloem to xylem) and content of main chemical components(volatile oils, total saponins, total flavonoids, total polysaccharides, and seven saikosaponins) of B. scorzonerifolium roots. Epson Scanner and ImageJ were used to scan the root samples and measure the appearance traits. Ultraviolet spectrophotometry and HPLC were employed to determine the content of chemical components. The correlation, regression, and cluster analyses were performed to study the correlations between the appearance traits and the content of chemical components. The results showed that the content of volatile oils and saikosaponins were significantly correlated with RGB value, root length, and root diameter, indicating that within a certain range, the roots being redder, longer, and thicker had higher content of volatile oils and saikosaponins. According to the appearance traits and chemical component content, the 14 samples from different producing areas were classified into four grades, and the differences in morphological traits and chemical component content were consistent among different grades. The findings in this study demonstrate that appearance traits(RGB value, root length, and root diameter) can be used to evaluate the quality of B. scorzonerifolium roots. Meanwhile, this study lays a foundation for establishing an objective quality evaluation method for B. scorzonerifolium roots.

To explore the effect and persistent effect of thiolated montmorillonite (TM) on safe production in cadmium (Cd) contaminated cropland, a two-year field experiment was conducted with different application amounts of TM. By adding to highly contaminated soils containing 2.46-3.81 mg·kg -1 Cd with no replenishment, the impacts of TM on concentrations of Cd in different parts of rice and available Cd in soils were investigated. The results showed that TM could significantly reduce the contents of Cd in brown rice as well as the contents and proportions of available Cd in soils, and its persistent effects on the passivation of Cd were obvious. After applying 0.5% or 1% TM to soils, the contents of Cd in different parts of the rice decreased significantly in the first season compared with that in the control. The contents of Cd in brown rice in the first season decreased to 0.16 mg·kg -1 and 0.08 mg·kg -1 , respectively, by 84.0% and 91.9% compared with that of the control (0.98 mg·kg -1 ). Contents of Cd in brown rice were significantly lower than the maximum allowable amount (0.2 mg·kg -1 ) set by China (GB 2762-2017). Under the 0.5% and 1% treatments, the contents of Cd in brown rice of the subsequent three seasons under successive planting decreased by 50.2%-67.8% and 56.0%-81.6%, respectively, which were within the allowable amount. The proportions of available Cd in soils in the first season decreased from 48.4% under the control to 27.9% and 18.4%, respectively, which decreased by 20.5% and 29.9% under the 0.5% and 1% treatments. Compared with that in the control, proportions of available Cd in soils of the following three seasons decreased by 10.0%-17.1% and 12.4%-20.8%. There was a significant positive correlation between available Cd contents in soils and Cd contents in various parts of the rice. TM mainly reduced available Cd contents in soils, then reduced the absorption and accumulation of Cd in rice. The results of the two-year field experiment showed significant and continuous effects of TM on inhibiting Cd uptake by rice, which could be applied to the safe production in heavily Cd contaminated cropland.

Plant-derived monoterpene indole alkaloids (MIAs) from Uncaria rhynchophylla (UR) have huge medicinal properties in treating Alzheimer's disease, Parkinson's disease, and depression. Although many bioactive UR-MIA products have been isolated as drugs, their biosynthetic pathway remains largely unexplored. In this study, untargeted metabolome identified 79 MIA features in UR tissues (leaf, branch stem, hook stem, and stem), of which 30 MIAs were differentially accumulated among different tissues. Short time series expression analysis captured 58 pathway genes and 12 hub regulators responsible for UR-MIA biosynthesis and regulation, which were strong links with main UR-MIA features. Coexpression networks further pointed to two strictosidine synthases (UrSTR1/5) that were coregulated with multiple MIA-related genes and highly correlated with UR-MIA features (r > 0.7, P < 0.005). Both UrSTR1/5 catalyzed the formation of strictosidine with tryptamine and secologanin as substrates, highlighting the importance of key residues (UrSTR1: Glu309, Tyr155; UrSTR5: Glu295, Tyr141). Further, overexpression of UrSTR1/5 in UR hairy roots constitutively increased the biosynthesis of bioactive UR-MIAs (rhynchophylline, isorhynchophylline, corynoxeine, etc), whereas RNAi of UrSTR1/5 significantly decreased UR-MIA biosynthesis. Collectively, our work not only provides candidates for reconstituting the biosynthesis of bioactive UR-MIAs in heterologous hosts but also highlights a powerful strategy for mining natural product biosynthesis in medicinal plants., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment and the deposition of amyloid plaques in the brain. In a transgenic mouse model of AD, cognitive impairment and synaptic dysfunction were revealed to be associated with soluble amyloid oligomers and to occur prior to plaque formation. The results of our previous studies revealed that striatal-enriched protein tyrosine phosphatase (STEP) 61 negatively regulated the β-amyloid protein-mediated ERK/cAMP-response element-binding protein (CREB) signaling pathway. Dl-3-n-butylphthalide (NBP) is a synthetic compound approved by the Food and Drug Administration of China for the treatment of ischemic stroke in 2002. Studies have shown that the neuroprotective effects of NBP involve multiple mechanisms. The present study further explored the mechanism of NBP therapy in amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice, and the involvement of the STEP/ERK/CREB signaling pathway. The results suggested that NBP treatment effectively ameliorated the spatial learning and memory impairment of the APP/PS1 transgenic mice, which was assessed using a Morris water maze. In addition, NBP reduced amyloid-induced activation of STEP 61 levels, while increasing phosphorylated (p)-ERK1/2 and p-CREB levels in the cerebral cortex and hippocampus of APP/PS1 transgenic mice by western blotting and immunostaining. In conclusion, the present study provided evidence to suggest that the new drug NBP improved amyloid-induced learning and memory deficits, likely through the regulation of the STEP/ERK/CREB pathway. The results revealed that NBP, as a multi-target drug, may exert a neuroprotective effect. Therefore, NBP may serve as an effective treatment for AD., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Zhao et al.)

Asperfloketals A ( 1 ) and B ( 2 ), two 1(10 → 6)- abeo -14,15-secosteroids featuring a novel trioxahexaheterocyclic ring system, were isolated from the sponge-associated fungus Aspergillus flocculosus 16D-1. Their structures were elucidated by extensive spectroscopic analysis and NMR chemical shifts calculations, supported by DP4+ probability analysis, and their absolute configurations were determined by ECD calculations and the modified Mosher's method. Asperfloketals A and B showed strong anti-inflammatory activity in the CuSO 4 -induced transgenic fluorescent zebrafish but displayed no cytotoxicity against HeLa, HepG2, and SW480 cell lines.

Objective: To evaluate the efficiency of a recombinase-aided amplification (RAA) assay for the detection of Schistosoma japonicum infections in Oncomelania hupensis snails., Methods: A group test was employed. Fifty Oncomelania snails were collected as a detection sample. The detection samples without infected snails were designated as negative specimens, while the detection samples that contained different numbers of infected snails were designated as positive specimens. A total of 10 negative specimens, 10 positive specimens containing 1 infected snail, 20 positive specimens containing 2 infected snails and 10 positive specimens containing 3 infected snails were assigned. Following random grouping, 40 specimens were subject to the florescent RAA assay using a blind method. The miradium shedding method served as a gold standard, and the sensitivity, specificity, Youden's index and coincidence rate of the florescent RAA assay were estimated. In addition, 20 samples consisted of 5 negative specimens and 15 positive specimens with 1, 2 and 3 infected snails respectively were grouped randomly. The same specimens were detected using the crushing method and fluorescent RAA assay with the blind method in a paired-design manner. Then, the test results were compared and analyzed., Results: Florescent RAA assay detected 29 positives in the 30 specimens containing different numbers of infected snails, with a sensitivity of 96.67%, and 8 negatives in the 10 detection specimens without infected snails, with a specificity of 80.00%, showing a Youden's index of 0.77. The coincidence rate was 100% among 10 repeated assays for a detection specimen. In addition, there was no significant difference in the detection of infected snails between the florescent RAA assay and the crushing method ( χ 2 = 0, P > 0.05), and the actual coincidence rates of the florescent RAA assay and crushing method were 95.00% (19/20) and 90.00% (18/20) with the real results, respectively., Conclusion: Fluorescent RAA assay has a favorable efficiency for the detection of S. japonicum infections in Oncomelania snails, which shows a potential in screening of S. japonicum -infected Oncomelania snails.

Background: Immune cell infiltration and neuroinflammation are heavily associated with spinal cord injury (SCI). C-C motif chemokine ligand 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis has been identified as a critical role player during the invasion of immune cells to lesions in many diseases. γδ T cells, a subgroup of T cells, manage the course of inflammation response in various diseases; however, it remains unknown whether γδ T cells are recruited to injury site through CCL2/CCR2 signaling and exert the regulation effect on neuroinflammation after SCI., Methods: Basso Mouse Scale (BMS), regularity index, cadence, max contact area, and motor-evoked potential testing (MEP) were measured to determine the neurological function recovery after spinal cord injury. Nissl staining was performed to identify the number of surviving motor neurons at lesion epicenter. Immunofluorescence, Western blot, enzyme-linked immunosorbent assays (ELISA), and quantitative real-time polymerase chain reaction (QRT-PCR) also were employed to evaluate the expression of associated proteins and genes., Results: In this study, we demonstrated that TCRδ -/- mice present improved neurological recovery after SCI. γδ T cell recruitment to the SCI site was significantly reduced and motor functional improvement enhanced in CCL2 -/- and CCR2 -/- mouse strains. Furthermore, reconstitution of TCRδ -/- mice with γδ T cells extracted from CCR2 -/- mice also showed similar results to CCL2 and CCR2 deficient mice., Conclusions: In conclusion, γδ T cell recruitment to SCI site promotes inflammatory response and exacerbates neurological impairment. CCL2/CCR2 signaling is a vital recruitment mechanism of γδ T cells to the SCI site, and it may be taken as a novel therapeutic target for future SCI.

The structural evolutions and electronic properties of AulPtm (l + m ≤ 10) clusters are investigated by using the first-principles methods. We use the inverse design of materials using the multi-objective differential evolution (IM2ODE) package to globally search the equilibrium structures and investigate the evolving trend from a two-dimensional structure to a three-dimensional structure on horizontal extension and vertical extension for AulPtm (l + m ≤ 10) clusters. The three-dimensional stable geometry of Au8Pt and Au8Pt2 is discovered for the first time in our work. We also notice that the equilibrium structures of AulPtm (l + m = 10 and l ≤ 8) tend to form a tetrahedral geometry and can be obtained by replacing the Au atom in the most stable structure of Aul+1Ptm-1 with the Pt atom, where Pt atoms assemble together and occupy the center of clusters and Au atoms prefer to lie on the vertex or edge position. The average binding energy (Eb) is mostly decided by Pt-Pt bond numbers, namely the numbers of Pt atoms, followed by Au-Pt bond numbers. The second-order energy difference (Δ2Ev and Δ2Eh) and the nearest-neighbor energy difference (Δ4Enn) show that Au6Pt, Au4Pt2, Au3Pt3, Au2Pt4 and AuPt7 clusters exhibit high relative physical stability, so we suggest that these clusters could be defined as the magic number clusters for AulPtm (l + m ≤ 10) clusters. The HOMO-LUMO energy gap (Eg), adiabatic ionization potential (AIP) and the adiabatic electron affinity (AEA) are also investigated to elaborate the relative electronic stability of all the clusters.

LC-HRMS/MS molecular networking enabled the targeted isolation of three new neoantimycin analogs (1, 3, 5) and two known ones (2, 4) from the culture broth of Streptomyces conglobatus RJ8. After derivatization into C1-hydroxyl form compounds (6-10) respectively, the absolute structures of 1-5 were clearly determined by analyzing the hydrolyzed components from 6-10. Compounds 2 and 3 were confirmed to be a pair of epimers with different stereochemistry at C-2, and so were 4 and 5. This is the first report of the isolation and characterization of epimers of NATs. The most abundant eight compounds we obtained were subjected to a cytotoxicity assay, 1 and 6 exhibited excellent cytotoxicity with the lowest IC 50 value in the picomolar range against six human carcinoma cell lines while 7 and 8 showed potent cytotoxicity against PC-9 and PC-9/GR cell lines., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Vagus nerve stimulation (VNS) restores autonomic balance, suppresses inflammation action and minimizes cardiomyocyte injury. However, little knowledge is known about the VNS' role in cardiomyocyte phenotype, sarcomere organization, and energy metabolism of infarcted hearts. VNS in vivo and acetylcholine (ACh) in vitro optimized the levels of α/β-MHC and α-Actinin positive sarcomere organization in cardiomyocytes while reducing F-actin assembly of cardiomyocytes. Consistently, ACh improved glucose uptake while decreasing lipid deposition in myocytes, correlating both with the increase of Glut4 and CPT1α and the decrease of PDK4 in infarcted hearts in vivo and myocytes in vitro, attributing to improvement in both glycolysis by VEGF-A and lipid uptake by VEGF-B in response to Ach. This led to increased ATP levels accompanied by the repaired mitochondrial function and the decreased oxygen consumption. Functionally, VNS improved the left ventricular performance. In contrast, ACh-m/nAChR inhibitor or knockdown of VEGF-A/B by shRNA powerfully abrogated these effects mediated by VNS. On mechanism, ACh decreased the levels of nuclear translocation of FoxO3A in myocytes due to phosphorylation of FoxO3A by activating AKT. FoxO3A overexpression or knockdown could reverse the specific effects of ACh on the expression of VEGF-A/B, α/β-MHC, Glut4, and CPT1α, sarcomere organization, glucose uptake and ATP production. Taken together, VNS optimized cardiomyocytes sarcomere organization and energy metabolism to improve heart function of the infarcted heart during the process of delaying and/or blocking the switch from compensated hypertrophy to decompensated heart failure, which were associated with activation of both P13K/AKT-FoxO3A-VEGF-A/B signaling cascade.

Objective: To investigate the effect of occupational factor exposures on carotid atherosclerosis (CAS) in steel workers. Methods: A frequency matched case-control study was conducted by age and factory proportion. A total of 1 033 workers with carotid atherosclerosis diagnosed by ultrasonography examination from February to June 2017 were selected as case group, and 1 033 workers without carotid atherosclerosis indicated by physical examination at the same time were selected as control group. The basic information of the workers, such as diet pattern, lifestyle, serum biochemical index and occupation history, were collected. The effects of occupational hazards on carotid atherosclerosis were analyzed by univariate and multivariate logistic regression analyses. The combined effects of various occupational hazards on carotid atherosclerosis were evaluated by environmental risk score (ERS). Results: High temperature, noise, occupational stress and night shift days increased the risk of CAS. With the increase of cumulative high temperature and noise exposure, occupational stress and night shift days, the risk of CAS increased (trend text: χ (2)=37.53, P <0.01; χ (2)=16.98, P <0.01; χ (2)=13.93, P <0.01; χ (2)=5.59, P <0.05). After adjustment of covariates, compared with P(20) group, the risk of carotid artery in P(40) , P(60) , P(80) and P(100) groups were as follows: high temperature 1.61 (1.19-2.18), 1.69 (1.25-2.30), 1.84 (1.36-2.49), 2.43 (1.77-3.34); noise 1.70 (1.15-2.52), 1.68 (1.20-2.35), 1.80 (1.34-2.42), 2.23 (1.53-3.26); occupational stress 1.39 (1.04- 1.86), 1.41 (1.06-1.89), 1.45(1.09-1.95), 1.48 (1.10-1.98); night shift days 1.58 (1.08-2.33), 1.66 (1.12-2.47), 1.55 (1.04-2.31), 1.76 (1.17-2.64). The results of the environmental risk score showed that the risk of carotid atherosclerosis increased with the increase of ERS (ERS trend text χ (2)=51.61, P <0.01); RCS results showed that there was a linear relationship between ERS and CAS in steel workers( P <0.01). Linear dose-response relationship existed between ERS and CAS (nonlinear test P >0.05). Conclusions: High temperature, noise, occupational stress and night shift days were related to carotid atherosclerosis. Linear dose-response relationship existed between ERS and CAS in steel workers.

A neutral-loss scanning mass method was used to explore new kynurenine-containing cycloheptapeptides, phakefustatins A-C ( 1 - 3 ), from the marine sponge Phakellia fusca . Their structures were elucidated by spectroscopic analysis and the advanced Marfey's method. 1 was total synthesized via a final-stage ozonolysis strategy by the combination of solid/solution-phase synthesis. Phakefustatin A ( 1 ) was identified as a RXRα modulator to inhibit cancer cell growth, and its pharmacophores could be Kyn and guanidine groups.

Cumulative evidence suggests that microRNAs (miRNAs) promote gene expression in cancers. However, the pathophysiologic relevance of miRNA-mediated RNA activation in hepatocellular carcinoma (HCC) remains to be established. Our previous miRNA expression profiling in seven-paired HCC specimens revealed miR-93-5p as an HCC-related miRNA. In this study, miR-93-5p expression was assessed in HCC tissues and cell lines by quantitative real-time PCR and fluorescence in situ hybridization. The correlation of miR-93-5p expression with survival and clinicopathological features of HCC was determined by statistical analysis. The function and potential mechanism of miR-93-5p in HCC were further investigated by a series of gain- or loss-of-function experiments in vitro and in vivo. We identified that miR-93-5p, overexpressed in HCC specimens and cell lines, leads to poor outcomes in HCC cases and promotes proliferation, migration, and invasion in HCC cell lines. Mechanistically, rather than decreasing target mRNA levels as expected, miR-93-5p binds to the 3'-untranslated region (UTR) of mitogen-activated protein kinase kinase kinase 2 (MAP3K2) to directly upregulate its expression and downstream p38 and c-Jun N-terminal kinase (JNK) pathway, thereby leading to cell cycle progression in HCC. Notably, we also demonstrated that c-Jun, a downstream effector of the JNK pathway, enhances miR-93-5p transcription by targeting its promoter region. Besides, downregulation of miR-93-5p significantly retarded tumor growth, while overexpression of miR-93-5p accelerated tumor growth in the HCC xenograft mouse model. Altogether, we revealed a miR-93-5p/MAP3K2/c-Jun positive feedback loop to promote HCC progression in vivo and in vitro, representing an RNA-activating role of miR-93-5p in HCC development.

Objective: To investigate the prevalence of pre-diabetes mellitus (PDM) and the impact of occupation-related factors on PDM, among workers from a steel company in Tangshan city, Hebei province. Methods: Clustering sampling method was used to select a steel company and to carry out occupational health-related physical checkup programs for eligible workers who had working in this company for longer than one year. The study began in February and ended up in June, 2017. Workers who were with FPG level as ≤6.9 mmol/L, and free from diabetes, were selected as the subjects for this study. Questionnaires were used and physical examinations and FPG testing conducted. Results: The total number of subjects in this study was 4 173, of which 2 648 appeared as pre-diabetic, with the prevalence rate as 63.4 % . Increase of the PDM prevalence was in parallel with the length of service, among the workers. The risk for the pre-diabetes in those who worked more than 8 hours per day was 1.696 times higher than those who worked less than or equal to 8 h/d (95 %CI :1.517-1.937). Compared with those workers without exposures to heat, noise or carbon monoxides, the proportion of pre-diabetes appeared higher in workers exposed to heat, noise or CO with OR =1.782 (95 %CI : 1.205-2.636), 1.815 (95 %CI : 1.209-2.794) and 1.653 (95 %CI : 1.158-2.361), respectively. Risks for those who were exposed to heat or noise were higher than those who were free from exposure to any occupational hazards ( OR =2.098, 95 %CI : 1.296-3.397). Prevalence rates of pre-diabetes in those who were exposed to heat, noise or CO, were higher than that those who were not. Conclusion: Working hours and exposures to heat, noise or CO appeared as influential factors on PDM.

Background: The mechanistic target of rapamycin (mTOR) pathway, containing mTOR complex 1 (mTORC1) and mTORC2, is dysregulated in multiple cancers, including hepatocellular carcinoma (HCC). Mammalian lethal with sec-13 protein 8 (mLST8) is a shared constituent of both mTORC1 and mTORC2, yet little is known regarding its role in HCC development., Methods: mLST8 expression was detected in a total of 186 pairs of HCC and adjacent non-tumor specimens. The correlation between mLST8 level and clinicopathological features or prognostic significance were analyzed. The role of mLST8 on biological functions was also preliminarily studied., Results: The study revealed that the mLST8 level was dramatically higher in HCC specimens than in adjacent non-tumor specimens. mLST8 overexpression positively correlated with tumor size, differentiation, and vessel invasion. Cases with elevated mLST8 level had more unfavorable overall survival (OS) and disease-free survival (DFS) than those with downregulated mLST8 level. Multivariate analysis demonstrated that mLST8 upregulation was an independent predictive marker for OS and DFS. Calibration curves from nomogram models indicated an excellent coherence between nomogram prediction and actual situation. Decision curve analysis proved that mLST8-based nomograms presented much higher predictive accuracy when compared with conventional clinical staging systems. Mechanistically, mLST8 enhanced cell proliferation and invasion through the AKT (protein kinase B) pathway., Conclusions: Our study demonstrates that mLST8 exerts an oncogenic role in HCC and may become a promising prognostic biomarker and therapeutic target for HCC patients.

Background: Calcium-binding tyrosine phosphorylation-regulated protein (CABYR) is a group of isoforms produced by alternative splicing and is overexpressed in human malignancies including hepatocellular carcinoma (HCC). However, the prognostic value and biological functions of its major protein isoforms, named CABYR-a/b (combined CABYR-a and CABYR-b), in HCC remain to be established., Methods: CABYR-a/b expression was detected in HCC tissues and cell lines by quantitative real-time polymerase chain reaction and Western blot analysis. The correlation of CABYR-a/b expression with clinical characteristics and its prognosis impact were determined by statistical analysis. Finally, the biological functions and molecular mechanism of CABYR-a/b were also investigated using molecular biology approaches., Results: The present research found that CABYR-a/b was markedly elevated in HCC specimens and cell lines. Upregulated CABYR-a/b level had positive association with tumor size and differentiation in patients. Moreover, cases with elevated CABYR-a/b level had poorer overall survival (OS) and disease-free survival (DFS) than those with reduced CABYR-a/b level. Multivariate analysis and prognostic nomograms demonstrated that CABYR-a/b overexpression was an independent predictive indicator for OS and DFS. The calibration curve for the odds of OS and DFS demonstrated that the prediction by nomograms was in excellent accordance with actual situation. CABYR-a/b downregulation suppressed cell proliferation and induced G1-phase arrest via decreasing cyclin D1 and cyclin dependent kinase 4, while promoted apoptosis by reducing B-cell lymphoma 2 (Bcl-2) and increasing Bcl-2-associated death promoter., Conclusion: Our research indicates that CABYR-a/b exerts an oncogenic effect on HCC development and may become a new prognostic indicator for patients with HCC., (© 2019 Wiley Periodicals, Inc.)

Three unusual chlorinated PKS-NRPS hybrid metabolites, flavipesides A-C ( 1 - 3 ), were isolated from a strain of marine sponge symbiotic fungus Aspergillus flavipes 164013. Their structures were determined by spectroscopic data analysis, and absolute configurations were assigned by single-crystal X-ray diffraction with ECD spectral analysis. Flavipesides A-C showed potent pancreatic lipase (PL) inhibitory activity with IC 50 values of 0.07-0.23 μM.

Objective: To investigate the heterogeneity of the developmental trajectory of posttraumatic stress disorder symptoms (PTS) among children and adolescents after Lushan earthquake and to explore the effect of gender and age on the trajectory., Methods: A total of 1 623 participants completed three assessments at 2 weeks, 3 months and 6 months after the earthquake. Latent growth mixture model (LGMM) was used for statistical analysis in the software Mplus 8.0., Results: The PTS developmental trajectories among children and adolescents exposed to the earthquake had four categories: the normal stress group (31.1%, class 1), the persistent impairment group (4.5%, class 2), the psychological recovery group (46.8%, class 3) and the persistent mild symptom group (17.6%, class 4). The PTS development trajectories were significantly different in two gender groups, and the proportion of girls in the persistently injured group was higher than other three groups. The PTS development trajectories had no difference in two age groups., Conclusion: The developmental trajectories of PTS in children and adolescents after the earthquake have significant population heterogeneity, which is affected by gender., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

A general AzePhenol dinuclear zinc catalytic system has been successfully developed and applied into the asymmetric Michael addition of 4-hydroxyl pyrones and 4-hydroxycoumarins to β,γ-unsaturated α-keto esters. Excellent yields (up to 99%) and high enantioselectivities (up to 94% ee) are obtained for a wide range of substrates under mild conditions in the absence of additives. This bimetallic catalytic approach represents a new and effective asymmetric synthetic protocol to access a variety of bioactive compounds with pharmacological interest. The possible mechanism is proposed to explain the origin of the asymmetric induction.

Long non‑coding RNAs (lncRNAs) have been shown to contribute to progression and prognosis of hepatocellular carcinoma (HCC). However, expression profiling and interaction of lncRNAs with messenger RNAs (mRNAs) and microRNAs (miRNAs) remain largely unknown in HCC. The expression profiling of lncRNAs, mRNA and miRNAs was obtained using microarray. The Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to characterize potential functions of differentially expressed mRNAs. Cytoscape was applied to construct an lncRNA‑miRNA‑mRNA co‑expression network and candidate lncRNAs were validated via quantitative PCR in 30 pairs of HCC and adjacent tumor‑free tissues. In this study, 1,056 upregulated and 1,288 downregulated lncRNAs were identified, while 2,687 mRNAs and 6 miRNAs were aberrantly expressed in HCC compared with adjacent tumor‑free tissues. Potential functions of differentially expressed mRNAs were demonstrated to significantly participate in modulating critical genes in the cell cycle, such as cyclin E1 and cyclin B2. After screening, 95 lncRNAs, 5 miRNAs and 36 mRNAs were recruited for construction of lncRNA‑mRNA‑miRNA co‑expression network in the cell cycle pathway. Subsequently, the top 5 lncRNAs that potentially modulate critical genes in the cell cycle were selected as the candidates for further verification. Kaplan‑Meier curves using the Cancer Genome Atlas database showed that 13 targeted mRNAs were associated with overall survival of HCC patients. Finally, three lncRNAs, including ENST00000522221, lnc‑HACE1‑6:1 and lnc‑ICOSLG‑11:1, are significantly upregulated in HCC tissues compared with adjacent tumor‑free tissues. These findings suggest that lncRNAs play essential roles in the pathogenesis of HCC via regulating coding genes and miRNAs, and may be important targets for diagnosis and treatment of this disease.

Four new cycloheptapeptides, fuscasins A-D (1-4), were isolated from the marine sponge Phakellia fusca collected from the South China Sea. Their planar structures were fully characterized by spectroscopic methods, and the absolute configurations of amino acid residues were determined using the advanced Marfey's method. Structurally, 1 is a unique cycloheptapeptide with a backbone bearing a pyrrolidine-2,5-dione unit. Among the isolated compounds, 1 exhibited potent growth-inhibitory activity against HepG2 cells with an IC 50 value of 4.6 μM, whereas it did not show apparent inhibitory effects against the other five human cancer cell lines, MCF-7, HeLa, NCI-H460, PC9, and SW480. Encouragingly, 1 exhibited no cytotoxicity against nonmalignant cells even with a concentration up to 100 μM. These findings suggest that 1 may display a selective inhibitory effect on the growth of HepG2 cells.

A novel marine actinomycete, designated LHW63014 T , isolated from a marine sponge, Craniella species, collected in the South China Sea, was examined using a polyphasic approach. The 16S rRNA gene sequence of strain LHW63014 T showed highest similarities to Jishengella endophytica 202201 T (98.9 %), Micromonospora olivasterospora DSM 43868 T (98.7 %), Micromonospora maris AB-18-032 T (98.6 %) and Micromonospora gifhornensis DSM 44337 T (98.6 %). Phylogenetic analyses of the family Micromonosporaceae based on the 16S rRNA and gyrB gene sequences indicated that strain LHW63014 T and J. endophytica 202201 T located within the genus Micromonospora. Morphological and chemotaxonomic characteristics confirmed their affiliation to the genus Micromonospora. Based on phenotypic characteristics, phylogenetic data and digital DNA-DNA hybridization results, strain LHW63014 T could be distinguished from its closest taxa, representing a novel species of the genus Micromonospora, for which the name Micromonospora craniellae sp. nov., is proposed, with the type strain LHW63014 T (=DSM 106193 T =CCTCC AA 2018012 T ). It is also proposed that J. endophytica be transferred to genus Micromonospora as Micromonospora endophytica comb. nov. (type strain 202201 T =CGMCC 4.5597 T =DSM 45430 T ).

Three unusual meroterpenoids, septosones A-C (1-3), were isolated from the marine sponge Dysidea septosa. The structures were determined by analysis of spectroscopic data combined with single-crystal X-ray diffraction and ECD calculations. Septosone A (1) features an unprecedented "septosane" carbon skeleton, whereas septosones B (2) and C (3) share a rare spiro[4.5]decane motif. Septosone A showed in vivo anti-inflammatory activity in CuSO 4 -induced transgenic fluorescent zebrafish likely through inactivation of the NF-κB signaling pathway.

microRNA-19a-3p (miR-19a-3p) has been reported to regulate cell proliferation in hepatocellular carcinoma (HCC), but its role in HCC metastasis remains unknown. In this study, miR-19a-3p was noted to be upregulated in HCC specimens and cell lines. Aberrant expression of miR-19a-3p stimulated HCC cell metastasis, and phosphatase and tensin homolog (PTEN) was shown to be a direct target of miR-19a-3p. miR-19a-3p-mediated HCC metastasis was reversed by restoration of PTEN or could be imitated by silencing of PTEN. Modulation of miR-19a-3p also altered expression of phosphorylated Akt, a downstream mediator of PTEN. Moreover, aberrant expression of miR-19a-3p induced sorafenib resistance by regulating the PTEN/Akt pathway. In conclusion, ectopic expression of miR-19a-3p contributes to HCC metastasis and chemoresistance by modulating PTEN expression and the PTEN-dependent pathways., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Hepatocellular carcinoma (HCC) remains a major health problem for delayed diagnosis, inefficient surveillance and poor prognosis. Recent studies have indicated that non-coding RNAs contribute to the development of new strategies for diagnosis and treatment of HCC. In the present study, we employed 18 pairs of HCC and matched non-tumor tissues for the identification of differentially expressed microRNAs (miRNAs) in HCC, among which 7 paired specimens were selected randomly for microarray detection. Totally, twenty-three miRNAs were screened out to have statistically significant differences with the threshold of P < 0.01 and fold-change ≥ 2.0 or ≤ 0.5 using miRNA microarray. In the validation stage, two miRNAs exhibited higher expression levels in the HCC tissues compared with those in the matched non-tumor tissues, whereas the expression levels of ten miRNAs were lower in the HCC tissues than those in the matched non-tumor tissues. In further analysis, eight miRNAs, including miR-4270, miR-125b-5p, miR-199a-3p, miR-10a-5p, miR-424-5p, miR-195-5p, miR-106b-5p and miR-3651, were retained, when another constraint about the signal intensity of microarray probes was established. Among these miRNAs, our study was the first to show the higher expression level of miR-3651 and the lower expression level of miR-4270 in HCC. The areas under the receiver-operating-characteristic curve values of miR-3651 and miR-4270 were 0.730 and 0.967, respectively, indicating their potential diagnostic values. Our results may help provide the context for expanded interpretations of miRNA studies involved in the progression of liver disease, potentially serving as a diagnostic tool of HCC.

A winter air pollution episode was observed in Hangzhou, South China, during the Second World Internet Conference, 2015. To study the pollution characteristics and underlying causes, the Weather Research and Forecasting with Chemistry model was used to simulate the spatial and temporal evolution of the pollution episode from December 8 to 19, 2015. In addition to scenario simulations, analysis of the atmospheric trajectory and synoptic weather conditions were also performed. The results demonstrated that control measures implemented during the week preceding the conference reduced the fine particulate matter (PM 2.5 ) pollution level to some extent, with a decline in the total PM 2.5 concentration in Hangzhou of 15% (7%-25% daily). Pollutant long-range transport, which occurred due to a southward intrusion of strong cold air driven by the Siberia High, led to severe pollution in Hangzhou on December 15, 2015, accounting for 85% of the PM 2.5 concentration. This study provides new insights into the challenge of winter pollution prevention in Hangzhou. For adequate pollution prevention, more regional collaborations should be fostered when creating policies for northern China., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The catalytic properties of the magic gold-platinum bimetallic clusters (Au 4 Pt 2 and Au 6 Pt) for the reduction of SO 2 by CO, without or with preadsorbing CO molecules, are firstly investigated using density functional theory calculations. We find that the catalytic activities improve effectively with the preadsorption of CO onto the catalysts and that the catalytic activities of Au 6 Pt(CO) n are better than those of Au 4 Pt 2 (CO) n as more CO molecules are adsorbed onto the catalysts. During the reaction process, the Au 4 Pt 2 (CO) n clusters always keep two-dimensional morphologies except for when n = 5 and the Au 6 Pt(CO) n clusters have three-dimensional geometries except for when n = 0. The most stable adsorption site for SO 2 molecules on the catalysts is the site of preadsorbing the next CO molecule on the corresponding catalysts. The largest activation energy (E) is related to the metal 5d (M-5d) band center and the charge transfer (C t ) as well as the bond length (R b ) between COS and the catalyst contribute to the desorption energy (E d ) of COS corporately. We propose that Au 6 Pt(CO) 6 is a cost-effective gold-platinum bimetallic catalyst for the reduction of SO 2 by CO.

Objective: To evaluate the effect of group cognitive behavioral therapy (GCBT) on social anxiety disorders (SAD)., Methods: A total of 50 patients with SAD were recruited in this study. A survey containing the Liebowitz social anxiety scale (LSAS),the automatic thoughts questionnaire (ATQ),the fear of negative evaluation questionnaire (FNE),the social support rating scale (SSRS),the tridimensional personality questionnaire (TPQ),and the egna minnen barndoms uppfostran (EMBU) was administered before and (one week) after the GCBT,including in the 50 healthy controls. About 21 patients completed the eight-week GCBT (once a week,2 h a session). Follow-up surveys were conducted on 40 patients (22 patients treated with GCBT and 18 untreated) over a 1-5 year period., Results: Significant differences were found between the SAD patients and healthy controls in thinking mode,personality characteristics,social support,parental rearing styles,and social anxiety symptoms. Significant decrease in social anxiety symptom ( t =4.06, P =0.000) , negative automatic thoughts ( t =4.58, P =0.000) and fear for rejection ( t =3.85, P =0.000) were observed after the GCBT therapy. Such improvement was positively correlated with subjective social support ( r =0.361, P =0.022) ,and negatively correlated with rejection of father ( r =-0.431, P =0.005) . There was also statistical difference between the patients with and without the GCBT therapy ( P =0.033) ., Conclusion: GCBT treatment can relieve SAD symptoms by changing the negative cognitive of SAD patients. Social support and rejection of father affects the prognosis of SAD.

Water samples were collected in summer, autumn, winter, and spring in Beihai Lake for the analysis of water quality and microbial community structure. It was found that the water quality in summer and autumn was worse than in winter and spring, and TN and TP were the most important factors affecting the water quality. The microbial community structure was investigated using MiSeq high-throughput sequencing. It was found that the phyla Cyanobacteria, Proteobacteria, Actinobacteria, and Bacteroidetes were abundant in all the samples, whereas their relative abundances differed among the four seasons. In summer and autumn, the microbial diversities were higher, and the phylum Cyanobacteria was most abundant, with the genus Synechococcus dominant. In winter, the phylum Proteobacteria was dominant. In spring, Actinobacteria and Bacteroidetes were abundant, accounting for 51.5%-64.3% of the bacterial community. The redundancy analysis (RDA) results showed that the microbial communities were mostly affected by water temperature in Beihai Lake. Overall, the water quality of Beihai Lake was qualified for the use of landscape water. However, the abundance of Synechococcus in summer may lead to algal blooms. Thus, it is necessary to strengthen the monitoring and estimation of water quality in Beihai Lake.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death worldwide. However, current strategies curing HCC are far from satisfaction. The Hippo pathway is an evolutionarily conserved tumor suppressive pathway that plays crucial roles in organ size control and tissue homeostasis. Its dysregulation is commonly observed in various types of cancer including HCC. Recently, the prominent role of non-coding RNAs in the Hippo pathway during normal development and neoplastic progression is also emerging in liver. Thus, further investigation into the regulatory network between non-coding RNAs and the Hippo pathway and their connections with HCC may provide new therapeutic avenues towards developing an effective preventative or perhaps curative treatment for HCC. Herein we summarize the role of non-coding RNAs in the Hippo pathway, with an emphasis on their contribution to carcinogenesis, diagnosis, treatment and prognosis of HCC., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Schistosomiasis is a global snail-transmitted infectious disease of poverty. Transmission control had been achieved in China in 2015 after the control efforts for over 60 years. Currently, the remaining core regions endemic for Schistosoma japonicum are mainly located in the marshland and lake regions along the Yangtze River basin., Methods: During the period from 2001 through 2015, an integrated environmental improvement of the marshlands was carried out through the implementation of industrial, agricultural and resources development projects in Yizheng County along the Yangtze River. S. japonicum infection in humans, livestock and snails was estimated by serology, stool examination, hatching technique and microscopy during the 15-year study period to evaluate the effect of the integrated environmental improvement on control and elimination of schistosomiasis., Results: A 0.05% overall rate of S. japonicum infection was observed in snails during the 15-year study period, and no infected snails were detected since 2012. The overall prevalence of S. japonicum infection was 0.09% in humans during the study period, and no human infection was found since 2012. In addition, only 13 bovines were identified with S. japonicum infection in 2003 during the 15-year study period, and since 2004, no infection was found in livestock., Conclusion: The results of the present study demonstrate that the implementation of industrial, agricultural and water resources development projects, not only alters snail habitats in marshland regions, and promotes local economic development, which appears a win-to-win strategy to block the transmission of S. japonicum and accelerate socio-economic development along the Yangtze River.

The expression of cell factors of schizophrenia and the effect of the modified electric convulsive treatment (MECT) were studied. In total, 156 patients with schizophrenia were selected, and divided into the drug group (70 cases) and the drug combined with MECT group (combined group) (86 cases) according to the treatment methods. In addition, 70 cases of healthy volunteers (control group) were selected according to the closest matching method based on 1:1 of age and gender. The drug treatment, consisted of anti-psychotic drugs, such as risperidone 2-8, quetiapine 300-750, ziprasidone 80-160 or aripiprazole 10-30 mg/day, and for the control group, we used the electric spasm therapeutic instrument, Thymatron ® IV Systems up to 6 times, 3 times a week. The levels of interleukin (IL)-10, IL-4, IL-6 and IL-1 were detected before and after treatment by ELISA. The positive and negative symptom scale (PANSS) was used to evaluate the efficiency. Before the treatment, IL-1 and IL-6 levels of drug and combined groups were significantly higher than those of the control group (P<0.05), while IL-4 and IL-10 had no difference with the control group. There was no significant difference of each factor between the drug and combined groups. After treatment, IL-1, IL-6 and IL-10 of the drug group did not change compared to the levels before treatment, but IL-4 increased significantly; IL-1 and IL-10 of the combined group did not change, while IL-4 and IL-6 increased significantly; IL-1, IL-4 and IL-6 of the drug and combined groups were significantly (P<0.05) higher than those in the control group, but not IL-10. IL-1, IL-4 and IL-6 levels of the combined group were significantly higher (P<0.05) than those of the drug group. After treatment, the PANSS scores of the two groups decreased and the combined group decreased more significantly (P<0.05). The reduction rate of the combined group was significantly higher (P<0.05) than that of the drug group. The total efficiency of the combined group was significantly higher than that of the drug group, and after comparing these levels, there was statistical significance (P<0.05). IL-1, IL-4, IL-6 and IL-10 levels of the drug and combined groups before treatment were not associated with PANSS scores and the variation of IL-1, IL-4, IL-6 and IL-10 of the drug and combined groups had no correlation with the reduction rate of the PANSS. The results showed that, cell factors of schizophrenia had an abnormal expression, and medication and MECT can affect the expression level. In addition, MECT can improve the effect in the treatment of schizophrenia, but had no obvious correlation with the change of cell factors.