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Peanut (Arachis hypogaea L.) is an important cash crop and oil crop around the world. In August 2021, symptoms of leaf spot were found on nearly 50% of peanut plants in the peanut planting base of Xuzhou Academy of Agriculture Sciences, Jiangsu, China. Symptoms began as small, round or oval, dark brown spots on the leaf. As the spot expanded, the center of the spot became gray to light brown and the spot was covered with small black dots. Fifteen leaves with typical symptoms were randomly collected from fifteen plants in three fields about a kilometer apart from each other. Leaf pieces (5 × 5 mm) were cut from the junction part of diseased and healthy leaf tissue, sterilized with 75% ethanol for 30 s and 5% NaClO for 30 s, washed 3 times with sterile water, placed on full strength potato dextrose agar (PDA) and incubated at 28°C in darkness. Five days after incubation, 12 isolates were obtained. Fungal colonies were white to gray on the upper surface and orange to gray on the reverse side. Conidia were single-celled, cylindrical and colorless after maturation, and were 12 - 16.5 × 4.5 - 5.5 μm (n = 50) in size. Ascospores were one-celled, hyaline, with tapering ends and one or two large guttulates at the center, and measured 9.4 - 21.5 × 4.3 - 6.4 μm (n = 50). Based on morphological characteristics, the fungi were preliminarily identified as Colletotrichum fructicola (Prihastuti et al. 2009; Rojas et al. 2010). Single spore isolates were cultured on PDA medium and two representative strains (Y18-3 and Y23-4) were selected for DNA extraction. The internal transcribed spacer (ITS) rDNA region, partial actin gene (ACT), partial calmodulin gene (CAL), partial chitin synthase gene (CHS), partial glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH), and partial beta-tubulin 2 gene (TUB2) were amplified. The nucleotide sequences were submitted to Genbank (accession numbers of strain Y18-3: ITS: ON619598; ACT: ON638735; CAL: ON773430; CHS: ON773432; GAPDH: ON773436; TUB2: ON773434; accession numbers of strain Y23-4: ITS: ON620093; ACT: ON773438; CAL: ON773431; CHS: ON773433; GAPDH: ON773437; TUB2: ON773435). The phylogenetic tree was constructed using MEGA 7 based on the tandem of six genes (ITS-ACT-CAL-CHS-GAPDH-TUB2). The result showed that isolates Y18-3 and Y23-4 reside in the clade of C. fructicola species. To determine pathogenicity, conidial suspensions (107/mL) of isolate Y18-3 and Y23-4 were sprayed on ten 30-day-old healthy peanut seedlings per isolate. Five control plants were sprayed with sterile water. All plants were kept moist at 28°C in the dark (> 85% RH) for 48 h and then transferred to a moist chamber at 25°C with a 14-h photoperiod. After two weeks, typical anthracnose symptoms similar to those observed in the field appeared on leaves of inoculated plants, whereas controls remained asymptomatic. C. fructicola was re-isolated from symptomatic leaves but not from controls. Koch’s postulates verified that C. fructicola was the pathogen of peanut anthracnose. C. fructicola is a well-known fungus causing anthracnose on many plant species worldwide. In recent years, new plant species infected by C. fructicola have been reported, like cherry, water hyacinth and Phoebe sheareri (Tang et al. 2021; Huang et al. 2021; Huang et al. 2022). To our knowledge, this is the first report of C. fructicola causing peanut anthracnose in China. Thus, it is recommended to pay close attention and take necessary prevention and control measures against potential spread of peanut anthracnose in China. more...

To standardize the effective prevention, surveillance, and diagnosis of primary liver cancer, the Chinese Society of Hepatology, Chinese Medical Association, invited clinical experts and methodologists to develop the Consensus on the Secondary Prevention of Primary Liver Cancer, which was based on the clinical and scientific advances on hepatocellular carcinoma. The purpose is to provide a current basis for the prevention, surveillance, and early diagnosis of primary liver cancer in patients with chronic liver diseases. more...

The cutting forces will generally suffer massive complex factors, such as material deformation, tool eccentricity and system vibration, which will inevitably induce many great difficulties in accurately modeling the cutting force predictions that are very significant to investigate cutting processes. Therefore, the genetic algorithm optimized back-propagation and particle swarm optimization neural networks will be adopted to effectively construct cutting force prediction models. In these two back-propagation prediction models, the main milling parameters will be defined into their input vectors, and the transient milling forces along three different directions will be selected as their output vectors, then the implicit relationships between input and output vectors can be directly generated through practically training and learning these two built back-propagation models with a set of experimental milling force data. Meanwhile, the finite element analysis method will be also used to predict milling forces through programming two easy-to-operate plug-ins that can efficiently construct finite element analysis models, conveniently define processing parameters, and automatically perform mesh generation. Subsequently, the milling forces predicted by the established genetic algorithm optimized back-propagation and particle swarm optimization back-propagation models will be analytically compared with finite element analysis simulations and experiments; also the stress distribution and chip formations of finite element analysis and experiments will be comparatively investigated. Finally, the obtained results clearly indicate that these two back-propagation models built by artificial neural networks can well agree with finite element analysis simulations and experiments, but the particle swarm optimization back-propagation model is superior to the genetic algorithm optimized back-propagation model, which clearly demonstrate the particle swarm optimization back-propagation model has higher efficiencies and accuracies in predicting the average and transient cutting forces for different milling processes on aluminum alloy 7050. more...

Background and Aim. Heme oxygenase-1 (HO-1) has been verified to play an important role in nonalcoholic steatohepatitis (NASH), but the mechanism remains unclear. In this study, we aimed to clarify whether induction of HO-1 reverses steatofibrosis via suppression of the Wnt signaling pathway and to explore the potential mechanism of HO-1 on NASH-related liver fibrosis. Methods. Mice were fed with a methionine-choline-deficient (MCD) diet for 8 weeks to induce steatohepatitis-related liver fibrosis and were treated with HO-1 inducer Hemin and inhibitor ZnPP. Mouse sera were collected for the biochemical analysis, and livers were obtained for further histological observation and gene expression analysis. HSC-T6 cells were cultured for the in vitro study and were administrated with Hemin and si-HO-1 to induce or inhibit the expression of HO-1. qPCR and Western blot were used to assess the mRNA and protein levels of genes. Results. MCD-fed mice developed marked macrovesicular steatosis, focal necrosis, and inflammatory infiltration and pericellular fibrosis in liver sections. Administration of Hemin could significantly ameliorate the severity of steatosis, inflammation, and fibrosis and also could decrease the serum ALT and AST. We demonstrated that HO-1 induction was able to downregulate the key regulator of the canonical Wnt pathway Wnt1 and the noncanonical Wnt pathway Wnt5a. The downstream factors of the Wnt pathway β-catenin and NFAT5 were inhibited by Hemin, but GSK-3β was upregulated compared to the MCD group, which were consistent with the in vitro study. Hemin markedly inhibited the TGF-β1/Smad signaling pathway in both in vivo and in vitro studies. Conclusion. Our study demonstrated that HO-1 inhibited the activation of canonical and noncanonical Wnt signaling pathways in NASH-related liver fibrosis. Thus, these results may suggest a new therapeutic strategy for NASH-related liver fibrosis. more...

Since the outbreak of SARS-CoV-2, numerous compounds against COVID-19 have been derived by computer-aided drug design (CADD) studies. They are valuable resources for the development of COVID-19 therapeutics. In this work, we reviewed these studies and analyzed 779 compounds against 16 target proteins from 181 CADD publications. We performed unified docking simulations and neck-to-neck comparison with the solved co-crystal structures. We computed their chemical features and classified these compounds aiming to provide insights for subsequent drug design. Through detailed analyses, we recommended a batch of compounds that are worth further study. Moreover, we organized all the abundant data and constructed a freely available database, DrugDevCovid19 (http://clab.labshare.cn/covid/php/index.php), to facilitate the development of COVID-19 therapeutics. more...

Objectives: To enhance understanding of COVID-19 in clinical characteristics, related organ system dysfunctions and therapies. Methods: We enrolled patients with COVID-19 admitted to two Chinese hospitals from 19 January 2020 to 15 March 2020 and collected demographic and clinical data. Results: We retrospectively enrolled 130 patients: 7 mild, 103 moderate, and 20 severe cases. Severe patients were older than mild/moderate patients (60.1 vs 52.9 years; P = 0.028) and had more comorbidities (85.0% vs 52.7%; p = 0.006). 116 patients (89.2%) were 2019-noval coronavirus RNA-positive with a median detectable time of 10 days. Obvious absorbed of pneumonia in chest imaging occurred in 20 days. The most common symptoms were fever (n = 87, 66.9%), cough (n = 74, 56.9%), fatigue (n = 73, 56.2%), and chest tightness (n = 54, 41.5%). The incidence of liver, kidney, heart, and coagulation dysfunction was 38.4%, 24.5%, 30.1%, and 24.6%, respectively. The most frequently used antiviral therapies were arbidol (n = 64, 49.2%), oseltamivir (n = 73, 56.2%), and Lianhua Qingwen (n = 73, 56.2%). All patients recovered being hospitalized with a median duration of 15 days. Conclusions: Middle-aged and elderly with comorbidities are more likely to be infected with COVID-19 and develop severe symptoms. The lung, liver, heart, kidney, and coagulation system all may sustain injury, especially in severe cases. more...

Flexure hinges, which serve as the crucial joints in a large number of compliant mechanisms, have been widely applied in a variety of significant fields where there is high demand for the micro/nano motions with high resolution and high precision. Currently, an increasing number of notched flexure hinges with different structures and performances have been rapidly developed, but the existing performance comparisons on different notched flexure hinges were only conducted on seldom typical structures and are far from the comprehensiveness and fairness due to the different comparative conditions and discrepant evaluating indexes. Therefore, the finite beam-based matrix modeling method and nondimension precision factors will be employed in comprehensive comparing and ranking of 13 types of frequently-used notched flexure hinges in terms of their main compliances, motion accuracies, and stress concentrations, further providing useful practical guidelines to develop the compliant mechanisms with excellent overall performances. more...

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell-in-cell structures that is a potential histological hallmark associated with chronic hepatitis B. This study aimed to clarify the pathogenesis and characteristics of emperipolesis in PBC liver injury. Sixty-six PBC patients, diagnosed by liver biopsy combined with laboratory test, were divided into early-stage PBC (stages I and II, n = 39) and late-stage PBC (stages III and IV, n = 27). Emperipolesis was measured in liver sections stained with haematoxylin-eosin. The expressions of CK19, CD3, CD4, CD8, CD20, Ki67 and apoptosis of BECs were evaluated by immunohistochemistry or immunofluorescence double labelling. Emperipolesis was observed in 62.1% of patients with PBC, and BECs were predominantly host cells. The number of infiltrating CD3+ and CD8+ T cells correlated with the advancement of emperipolesis (R2 = 0.318, P more...

In view of various piezoelectric-actuated flexural mechanisms (FMs) can be widely found in many significant precision fields, such as sensors, instruments and micro-machines, this paper will introduce a new stochastic compliance model to theoretically investigate their planar parasitic motions (PPM) induced by uncertain manufacturing imperfectness, which will be constructed by the matrix-based compliance modeling (MCM) method from the viewpoint of statistics and probability. Firstly, a new dimensionless PPM relative ratio, which is mathematically defined to be the relative ratio of parasitic motions to the primary motions, will be introduced to more effectively characterize the adverse PPMs of designed FMs. Secondly, a novel eligible probability (EP), which means the acceptance possibility that the dimensionless PPM relative ratios of imperfect FMs can totally satisfy their allowable designed values, will be innovatively introduced to investigate the influences of uncertain manufacturing imperfectness on the motion accuracies of different FMs from the viewpoint of probability. Then taking two types of powerful FMs as examples, the influences of their dominant dimension parameters on the PPM relative ratios, eligible probabilities (EPs) and output stiffnesses will be analytically revealed and compared based on the built stochastic PPM models. In addition, a novel type of probability and stiffness contours (PSCs) method will be also proposed to design the FMs that have strong robustness to their manufacturing imperfects. Finally, a series of experimental measurements will be conducted on different double parallelogram compliant mechanisms (DPCM) consist of the right circular and leaf spring flexure hinges to validate the feasibility and effectiveness of the proposed stochastic PPM model and PSC method. more...

The aim of the present study was to elucidate the effect of resveratrol on non‑alcoholic steatohepatitis (NASH), and the molecular basis in mice and Hepa1‑6 cells, in order to verify its therapeutic effect. C57BL/6J mice were fed a methionine‑choline‑deficient (MCD) diet to induce steatohepatitis and were treated with resveratrol. Mouse sera were collected for biochemical analysis and enzyme‑linked immunosorbent assay, and livers were obtained for histological observation, and mmu‑microRNA (miR)‑599 and inflammation‑related gene expression analysis. Hepa1‑6 cells were treated with palmitic acid to establish a NASH cell model, and were then treated with resveratrol, or transfected with mmu‑miR‑599 mimic, mmu‑miR‑599 inhibitor or recombinant pregnane X receptor (PXR) plasmid. Subsequently, the cells were collected for mmu‑miR‑599 and inflammation‑related gene expression analysis. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to assess mmu‑miR‑599 expression levels, and the mRNA and protein expression levels of PXR and inflammation‑related genes. The binding site of mmu‑miR‑599 in the PXR mRNA was verified by the luciferase activity assay. Mice fed an MCD diet for 4 weeks exhibited steatosis, focal necrosis and inflammatory infiltration in the liver. Resveratrol significantly reduced serum aminotransferase and malondialdehyde levels, and ameliorated hepatic injury. These effects were associated with reduced mmu‑miR‑599 expression, enhanced PXR expression, and downregulated levels of nuclear factor‑κB, tumour necrosis factor‑α, interleukin (IL)‑1β, IL‑6, NOD‑like receptor family pyrin domain‑containing protein 3 and signal transducer and activator of transcription 3. Administration of the mmu‑miR‑599 mimic inhibited PXR expression in Hepa1‑6 cells, whereas the mmu‑miR‑599 inhibitor exerted the opposite effect. A binding site for mmu‑miR‑599 was identified in the PXR mRNA sequence. Furthermore, overexpression of PXR inhibited the expression of inflammatory factors in Hepa1‑6 cells. The present study provided evidence for the protective role of resveratrol in ameliorating steatohepatitis through regulating the mmu‑miR‑599/PXR pathway and the consequent suppression of related inflammatory factors. Resveratrol may serve as a potential candidate for steatohepatitis management. more...

Non-alcoholic steatohepatitis (NASH) has no approved therapy. The farnesoid X nuclear receptor (FXR) agonist obeticholic acid (OCA) has shown promise as a drug for NASH, but can adversely affect plasma lipid profiles. Therefore, the present study aimed to investigate the effects and underlying mechanisms of OCA in combination with simvastatin (SIM) in a high-fat diet (HFD)-induced model of NASH. C57BL/6J mice were fed with a HFD for 16 weeks to establish the NASH model. The mice were randomly divided into the following five groups: HFD, HFD + OCA, HFD + SIM, HFD + OCA + SIM and control. After 16 weeks, the mice were sacrificed under anesthesia. The ratios of liver weight to body weight (Lw/Bw) and of abdominal adipose tissue weight to body weight were calculated. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol, triglycerides and low-density lipoprotein were measured. Liver sections were stained with hematoxylin and eosin. The protein levels of FXR, small heterodimeric partner (SHP) and cytochrome P450 family 7 subfamily A member 1 (CYP7A1) in the liver were detected by western blotting, while the mRNA levels of FXR, SHP, CYP7A1, bile salt export pump, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), sterol regulatory element binding protein-1 (SREBP1) and fatty acid synthase (FASN) were examined by reverse transcription-quantitative polymerase chain reaction. The administration of OCA with or without SIM reduced the liver inflammation score compared with those of the HFD and HFD + SIM groups, with no significant difference between the HFD + OCA and HFD + OCA + SIM groups. The steatosis score followed similar trends to the inflammation score. In HFD-fed mice, OCA combined with SIM prevented body weight gain compared with that in HFD and HFD + OCA groups, and reduced the Lw/Bw ratio compared with that in the HFD and HFD + SIM groups. In addition to preventing HFD-induced increases of ALT and AST, the combination of OCA and SIM reduced the mRNA levels of IL-6, TNF-α, SREBP1 and FASN. On the basis of these results, it may be concluded that the strategy of combining OCA with SIM represents an effective pharmacotherapy for NASH. more...

Fatty liver disease associated with metabolic dysfunction is of increasing concern in mainland China, the world's most populous country. The incidence of fatty liver disease is highest in China, surpassing the incidence in European countries and the USA. An international consensus panel recently published an influential report recommending a novel definition of fatty liver disease associated with metabolic dysfunction. This recommendation includes a switch in name from non-alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction)-associated fatty liver disease (MAFLD) and adoption of a set of positive criteria for disease diagnosis that are independent of alcohol intake or other liver diseases. Given the unique importance of this proposal, the Chinese Society of Hepatology (CSH) invited leading hepatologists and gastroenterologists representing their respective provinces and cities to reach consensus on alternative definitions for fatty liver disease from a national perspective. The CSH endorses the proposed change from NAFLD to MAFLD (supported by 95.45% of participants). We expect that the new definition will result in substantial improvements in health care for patients and advance disease awareness, public health policy, and political, scientific and funding outcomes for MAFLD in China. more...

Objective: To investigate the correlation between the serum hepcidin levels and the viral loads in hepatitis C virus (HCV) infected patients. Methods: Sixty HCV-infected patients (the study group) and 50 healthy controls (the control group) were recruited as the study cohort. The liver function and inflammation-related parameters were compared, and the 60 HCV patients were divided into mild (G1-G2), moderate (G3), and severe (G4) groups according to each patient’s inflammatory activity grade (G). The serum iron (SI), ferritin (SF), and transferrin (TRF), hepcidin levels were compared. The relationships between the HCV-RNA, HCV Ag, HCV Ab, albumin (ALB), total bilirubin (TBIL), aminotransferase (ALT), and aspartate aminotransferase (AST) levels and the hepcidin levels was analyzed. The SI, SF, IL-6, ALT, AST, and TBIL levels were significantly higher, and the hepcidin, TRF, and ALB levels were significantly lower in the study group than they were in the control group (P0.05). Conclusion: The HCV patients’ serum hepcidin levels showed an abnormal decrease, suggesting that HCV patients may have an iron metabolism disorder, which indicates that there is a possibility of evaluating the HCV patients’ conditions by measuring the hepcidin levels and of improving HCV patients’ prognoses by regulating the iron metabolism. more...

The present study aimed to construct a novel signature for indicating the prognostic outcomes of hepatocellular carcinoma (HCC). Gene expression profiles were downloaded from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. The prognosis-related genes with differential expression were identified with weighted gene co-expression network analysis (WGCNA), univariate analysis, the least absolute shrinkage and selection operator (LASSO). With the stepwise regression analysis, a risk score was constructed based on the expression levels of five genes: Risk score = (−0.7736* CCNB2) + (1.0083* DYNC1LI1) + (−0.6755* KIF11) + (0.9588* SPC25) + (1.5237* KIF18A), which can be applied as a signature for predicting the prognosis of HCC patients. The prediction capacity of the risk score for overall survival was validated with both TCGA and ICGC cohorts. The 1-, 3- and 5-year ROC curves were plotted, in which the AUC was 0.842, 0.726 and 0.699 in TCGA cohort and 0.734, 0.691 and 0.700 in ICGC cohort, respectively. Moreover, the expression levels of the five genes were determined in clinical tumor and normal specimens with immunohistochemistry. The novel signature has exhibited good prediction efficacy for the overall survival of HCC patients. more...

Gear eccentricity, one of the most common defects of gear systems, affects not only dynamic behavior but also mesh stiffness. Accurate mesh stiffness under defect conditions is vital for the dynamic simulation and fault diagnosis of gear systems. Hence, the timevarying mesh stiffness affected by gear eccentricity, which is commonly neglected in most studies, is incorporated in the proposed twostage spur gear dynamic model and calculated by a novel gear mesh model with an improved potential energy method. The effects of mesh stiffness with and without gear eccentricity on the gear system are compared on the basis of the constructed dynamic model. The influences of gear eccentricity on dynamic transverse and torsional responses, as well as dynamic transmission errors, are also quantitatively studied. Some helpful analytical results are then presented. more...

The traditional elliptical vibration cutting (EVC) approaches have been widely employed in cost-effectively machining various complex optical surfaces on many difficult-to-cut materials, but the stiff usages of fixed phase difference and constant vibration frequency will have great limitations on improving performances and extending applications. Therefore, this paper will firstly concentrate on the innovations of a novel type of elliptical vibration cutting with a different frequency (DF-EVC) for several significant benefits, such as improving finish quality, extending tool life, and suppressing scattering effect. As modifications of DF-EVC, another novel type of elliptical vibration cutting with a varying phase difference (VPD-EVC) will be further developed, which can effectively enhance the machining capacities of DF-EVC processes by changing their unfixed phase differences within an available angle range. Beyond the conventional applications, like machining the microstructure and freeform surfaces, the improved VPD-EVC approaches can be elaborately adopted to fabricate two different microgrooves with U-shaped and V-shaped cross-sections, which integrate the high-frequency elliptical vibrations into the cross-feed motions instead of the up-feed motions of traditional EVC. In addition, the mechanism of how the VPD-EVC extends tool life will be discussed in detail, and the dependences of machining capacities to the phase difference amplitudes will be investigated by introducing a dimensionless relative cutting ratio (RCR). Subsequently, the toolpath generations and surface topography simulations of VPD-EVC will be performed and compared to traditional EVC; the suppressing capacity of the scattering effect will be further investigated based on the power spectral density (PSD). Finally, a series of cutting experiments will be practically conducted on the copper materials (T2) with poor machinability, the obtained results can well demonstrate the feasibility and effectiveness of the developed DF-EVC and VPD-EVC approaches for achieving various expected benefits, and several crucial conclusions on current research can be briefly summarized in the end. more...

Novel conformationally constrained BET bromodomain inhibitors have been developed. These inhibitors were optimized in two similar, yet distinct chemical series, the 6-methyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-ones (A) and the 1-methyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-ones (B). Each series demonstrated excellent activity in binding and cellular assays, and lead compounds from each series demonstrated significant efficacy in in vivo tumor xenograft models. more...

The development of bromodomain and extraterminal domain (BET) bromodomain inhibitors and their examination in clinical studies, particularly in oncology settings, has garnered substantial recent interest. An effort to generate novel BET bromodomain inhibitors with excellent potency and drug metabolism and pharmacokinetics (DMPK) properties was initiated based upon elaboration of a simple pyridone core. Efforts to develop a bidentate interaction with a critical asparagine residue resulted in the incorporation of a pyrrolopyridone core, which improved potency by 9-19-fold. Additional structure-activity relationship (SAR) efforts aimed both at increasing potency and improving pharmacokinetic properties led to the discovery of the clinical candidate 63 (ABBV-075/mivebresib), which demonstrates excellent potency in biochemical and cellular assays, advantageous exposures and half-life both in animal models and in humans, and in vivo efficacy in mouse models of cancer progression and inflammation. more...

Aims To explore the potential regulatory mechanism of differentially expressed mRNAs in Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Main methods Patients with HCV-related HCC and age- and gender-matched healthy subjects were enrolled. Differentially expressed mRNAs in the plasma were detected by digital gene expression (DGE) profile analysis. HepG2 and SMMC7721 cells stably transfected with HCV-core protein and the control plasmid were established. And small interfering RNA (siRNA) was used to knockdown the target gene in HCV core-expressing HCC cell lines. mRNA expression was determined by qRT-PCR. Protein expression was measured by Western blot and immunohistochemistry staining. Key findings DGE profile data showed aberrant mRNA expression contributed to the progression of HCV-HCC, and clusterin (CLU), which was significantly highly expressed, was chosen as a candidate gene. Further evidence showed CLU was highly expressed in tumor tissues of HCV-HCC patients and HCV core-expressing HCC cell lines, accompanied with enhanced autophagy and upregulation of pro-autophagy genes. And knockdown of CLU in HCC cell lines suppressed cell autophagy, which was indicated by decreased expression of autophagy marker light chain 3B (LC3B) ІІ/І ratio, and downregulated pro-autophagy genes like Beclin1, autophagy-related protein 7 (Atg7) and Lamp2. On the other hand, anti-autophagy genes or regulators, including p62 and phosphorylated mammalian target of rapamycin (p-mTOR), were notably upregulated. Significance CLU could promote the progression of HCV-related HCC by regulating autophagy, which might be a potential therapeutic target of HCV-HCC. more...

Cereal crops accumulate large amounts of starch which is synthesized and stored in amyloplasts in the form of starch grains (SGs). Despite significant progress in deciphering starch biosynthesis, our understanding of amyloplast development in rice (Oryza sativa) endosperm remains largely unknown. Here, we report a novel rice floury mutant named enlarged starch grain1 (esg1). The mutant has decreased starch content, altered starch physicochemical properties, slower grain-filling rate and reduced 1000-grain weight. A distinctive feature in esg1 endosperm is that SGs are much larger, mainly due to an increased number of starch granules per SG. Spherical and loosely assembled granules, together with those weakly stained SGs may account for decreased starch content in esg1. Map-based cloning revealed that ESG1 encodes a putative permease subunit of a bacterial-type ABC (ATP-binding cassette) lipid transporter. ESG1 is constitutively expressed in various tissues. It encodes a protein localized to the chloroplast and amyloplast membranes. Mutation of ESG1 causes defective galactolipid synthesis. The overall study indicates that ESG1 is a newly identified protein affecting SG development and subsequent starch biosynthesis, which provides novel insights into amyloplast development in rice. more...

The optics with micro-structures and freeform surfaces, which have a broader range of applications, can be generally fabricated by the single-point diamond turning (SPDT) with fast tool servo. But the cutting chatters caused by the cutting force fluctuations (CFFs) will greatly deteriorate the processing qualities like forming accuracy and surface finish; thus, this paper will build an improved chip load model (CLM) to simply characterize the cutting forces. Based on the modified CLM, two types of turning approaches with constant chip load (CCL) are developed to suppress CFFs, but which have some serious limitations in their practical applications. As an improvement, a type of simple-yet-effective virtual tool radius (VTR) method is further developed for practically generating the pre-turning toolpaths of the blank surfaces, which can ensure the uniform cutting allowances in finish turning. Taking two typical surfaces as examples, the proposed VTR method is analytically compared to the traditional processes in terms of chip load, and their resistances to the undulations of chip loads are also examined in detail. Finally, the VTR approach and traditional process are experimentally investigated by turning the sinusoidal radial surface on brass cylinders, and their cutting forces are measured for validating the CFF rejection capacities. more...

MicroRNA (miRNA) play a pivotal role in the development of liver fibrosis. However, the functions of miRNA in hepatitis C virus (HCV)-related liver fibrosis remain unclear. In this study, we systematically analyzed the microarray data of the serum miRNA in patients with HCV-induced hepatic fibrosis. Among 41 dysregulated miRNA, miR-1273g-3p was the most significantly upregulated miRNA and correlated with the stage of liver fibrosis. Overexpression of miR-1273g-3p could inhibit translation of PTEN, increase the expression of α-SMA, Col1A1, and reduce apoptosis in HSCs. Hence, we conclude that miR-1273g-3p might affect the activation and apoptosis of HSCs by directly targeting PTEN in HCV-related liver fibrosis. more...

Objective To investigate the regulation mechanism of T cell immunoglobulin and mucin domain-3 (Tim-3) combined with toll-like receptor 3 (TLR3) or TLR4 on antiviral immune and inflammatory response in patients with chronic hepatitis C virus (HCV) infection. Methods Patients with chronic HCV infection and healthy control subjects were recruited. Patients received interferon (IFN)-α based therapy. Plasma galectin-9 (Gal-9) was quantitated. Peripheral blood mononuclear cells (PBMCs) were cultured with TLR3 or TLR4 agonists, alone or in combination with Tim-3 antagonist. Levels of IFN-α, TNF-α, and 2′-5′ oligoadenylate synthetase (2′-5′OAS), myxovirus resistance protein A (MxA) and suppressor of cytokine 1 (SOCS1) RNA in PBMC cultures were evaluated. Results Plasma Gal-9 levels were increased in patients ( n = 52) compared with controls ( n = 20) and significantly declined at treatment week 12 and 24 weeks post-treatment. IFN-α, 2′-5′OAS, MxA, TNF-α and SOCS1 were upregulated by TLR3 and TLR4 agonists. TNF-α and SOCS1 levels were suppressed by the addition of Tim-3 antagonist. Conclusions Tim-3 blockade in combination with TLR activation induces the expression of antiviral molecules without a significant increase in TNF-α or SOCS1. more...

Hepatic fibrosis is a crucial pathological process involved in the development of chronic hepatitis C (CHC) and may progress to liver cirrhosis and hepatocellular carcinoma. Activated peripheral blood monocytes and intrahepatic macrophages further promote hepatic fibrogenesis by releasing proinflammatory and profibrogenic cytokines. The present study aimed to investigate the role of peripheral CD14+ monocytes and intrahepatic CD163+ macrophages in hepatitis C virus (HCV)-associated liver fibrosis and clarify whether serum soluble CD163 (sCD163) may serve as a fibrosis marker in patients with CHC. A total of 87 patients with CHC and 20 healthy controls were recruited. Serum sCD163 levels were measured by ELISA. Frequencies of peripheral CD14+ monocytes and inflammatory cytokines expressed by CD14+ monocytes were analyzed by flow cytometry. The degree of fibrosis in human liver biopsies was graded using the Metavir scoring system and patients were stratified into two groups based on those results (F more...

In order to obtain stable returns, this paper aims to establish a quantitative model with higher prediction accuracy. According to the time series characteristics of financial data, the prediction model with financial time series data is constructed by using the time-memory sequence model LSTM, which is applied to the representative SSE 50 series stocks. And based on this, the LSTM model with Encoder-Decoder mode and a hybridized framework of LSTM with CNN are built to improve the original model. Feature extraction is performed on the input data by using CNN, and then as an input to the LSTM, the extracted features are used for sequence prediction with the LSTM model. more...

Currently, the elliptical vibration cutting/coining (EVC2) has been widely employed in fabricating various functional microstructure surfaces applied in many significant engineering fields. Therefore, for this study, a novel type of two-degree-of-freedom (2-DOF) piezoelectrically actuated pseudo-decoupled compliant mechanisms (PDCMs) with non-orthogonal decoupling structures, which can exactly generate the strict ellipse trajectories, was developed for improving the forming accuracies of the EVC2 microstructures. First, the compliance matrices of 2-DOF PDCMs were theoretically modeled using the popular finite beam-based matrix modeling (FBMM) and the matrix-based compliance modeling (MCM) methods, then finite element analysis (FEA) was adopted to verify the effectiveness of the built compliance model for the 2-DOF PDCM with arbitrary structure parameters. Second, the static FEA method was employed to systematically reveal the dependencies of the tracking accuracies of the elliptical trajectories on the decoupling structures of 2-DOF PDCMs. Moreover, their main dynamic performances were also investigated through the FEA-based harmonic response analysis and modal analysis. On these bases, the critical angle of the decoupling structure was optimally set at 102.5&deg, so that the PDCMs had minimum shape distortions of the ellipse trajectories. Thirdly, a series of experiments was conducted on this PDCM system for practically investigating its kinematic and dynamic performances. The actual aspect ratio between the major axis and minor axis of the ellipse trajectory was approximately 1.057, and the first-order and second-order resonant frequencies were 863 Hz and 1893 Hz, respectively. However, the obtained testing results demonstrated well the effectiveness and feasibility of 2-DOF PDCM systems in precisely tracking the ellipse trajectories with different geometric parameters. Several critical conclusions on this study are summarized in detail in the final section of this paper. more...

Previous studies using microRNA (miRNA or miR) microarrays have demonstrated that miR-1273g-3p is upregulated in patients with hepatitis C virus (HCV)-associated fibrosis. As miRNAs have been suggested to be promising non-invasive biomarkers, the aim of the present study was to assess whether miR-1273g-3p may be useful as a potential indicator of fibrosis progression in patients with HCV. Liver biopsies were performed on 112 patients with chronic hepatitis C (CHC) and liver stiffness measurements (LSM) were performed using FibroTouch. Liver fibrosis was determined based on Meta-analysis of Histological Data in Viral Hepatitis classification, and the aspartate aminotransferase (AST)-to-platelet count (PLT) ratio index (APRI) and Fibrosis-4 score (FIB-4) were calculated. The diagnostic performance of miR-1273g-3p, LSM, APRI and FIB-4 in predicting fibrosis stage were evaluated and compared by receiver operating characteristic (ROC) analysis. It was demonstrated that miR-1273g-3p levels were significantly positively correlated with the liver fibrosis stage (r=0.657, P more...

The surfaces with textures have been widely used as functional surfaces, and the textures are usually generated on flat or cylindrical surfaces. Textured freeform surfaces will have more potential applications. The authors have proposed the double-frequency elliptical vibration cutting (DFEVC) method to machine freeform surfaces on steel materials. Based on this method, a new diamond turning method is developed, in which the variable-frequency modulations are utilized to control the tool marks left on the machined surface to generate the micro/nano dimple textures with high uniformity on the freeform surface. Different from the conventional surface topography model based on the ideal tool cutting edge with zero cutting edge radius, a new modeling approach based on the tool surface profiles is proposed, in which the rake face, the flank face, and the cutting edge surface with actual non-zero cutting edge radius instead of the ideal cutting edge are included for the tool model, the tool surfaces during the machining process are analytically described as a function of the tool geometry and the machining parameters, and the influences of the tool surface profiles on the topography generation of the machined surface are considered. A typical freeform surface is textured on die steel, and the measured results verify the feasibility of the proposed turning method. Compared with the topography prediction results based on the ideal cutting edge, the results considering the tool surfaces show improved simulation accuracy, and are consistent with the experimental results, which validates the proposed topography prediction approach. more...