Contriving a novel of CHB therapeutic vaccine based on IgV_CTLA-4 and L protein via immunoinformatics approach.

Chronic infection induced by immune tolerance to hepatitis B virus (HBV) is one of the most common causes of hepatic cirrhosis and hepatoma. Fortunately, the application of therapeutic vaccine can not only reverse HBV-tolerance, but also serve a potentially effective therapeutic strategy for treating chronic hepatitis B (CHB). However, the clinical effect of the currently developed CHB therapeutic vaccine is not optimistic due to the weak immunogenicity. Given that the human leukocyte antigen CTLA-4 owns strong binding ability to the surface B7 molecules (CD80 and CD86) of antigen presenting cell (APCs), the immunoglobulin variable region of CTLA-4 (IgV_CTLA-4) was fused with the L protein of HBV to contrive a novel therapeutic vaccine (V_C4HBL) for CHB in this study. We found that the addition of IgV_CTLA-4 did not interfere with the formation of L protein T cell and B cell epitopes after analysis by means of immunoinformatics approaches. Meanwhile, we also found that the IgV_CTLA-4 had strong binding force to B7 molecules through molecular docking and molecular dynamics (MD) simulation. Notably, our vaccine V_C4HBL showed good immunogenicity and antigenicity by in vitro and in vivo experiments. Therefore, the V_C4HBL is promising to again effectively activate the cellular and humoral immunity of CHB patients, and provides a potentially effective therapeutic strategy for the treatment of CHB in the future.Communicated by Ramaswamy H. Sarma.

Effects of Circadian Rhythm and Feeding Modes on Rumen Fermentation and Microorganisms in Hu Sheep.

All organisms have a biological clock system which is strongly tied to how well an organism digests food and develops. This study aimed to understand the effects of circadian rhythm and feeding modes on rumen fermentation and microorganisms in Hu sheep. Forty-five healthy Hu sheep were randomly divided into three treatment groups of 15 sheep in each group, wherein they were fed the same concentrate and roughage. Under the condition that the nutrient-feeding amount was consistent throughout the day, the concentrate-to-forage ratio was dynamically adjusted during the day and night. Rumen fluid collected after the feeding experiment was used to determine the study parameters; the results showed a connection between rumen fermentation and the circadian clock. Volatile fatty acids (VFAs), pH, and NH3-N were significantly influenced by the fermentation duration (p < 0.05). The activities of digestive enzymes also showed a relationship with nutrition and circadian rhythm, and there were differences in the digestive enzyme activities of amylase, lipase, and cellulase (p < 0.05). Dominant microorganisms, such as Saccharomycetes and Mucor, were more abundant in the daytime of the high-concentrate fed group. The correlation among the study objectives was evident from the differences in enzyme activity and microbial diversity among the treatment groups. On the basis of the circadian rhythm characteristics of Hu sheep, changes in the feeding mode of Hu sheep and only adjusting the proportion of concentrate and forage in the morning and evening showed that feeding diets with the high-concentrate ratio in the day significantly reduced rumen PH and increased NH3-N concentration (p < 0.05). Under this feeding pattern, the activities of major digestive enzymes in the rumen, such as amylase and lipase, were significantly increased (p < 0.05), and the microbial diversity was also improved.

Effects of the presence of triclocarban on the degradation and migration of co-occurring pesticides in soil.

Triclocarban (TCC), a bactericide widely used in personal care products, is frequently detected in soil and surface water, which may affect the environmental behavior of other environmental pollutants by changing the community structure of environmental microorganisms. This work evaluated the effects of TCC on the degradation and migration of seven herbicides and five fungicides in soil under co-occurrence conditions. TCC significantly increased the persistence of the pesticides in soil, and this effect increased with TCC concentration. For example, the half-life of metolachlor, atrazine, metribuzin, and metamitron increased 44%, 38%, 153%, and 33%, respectively, with 10 mg/kg TCC and increased 60%-640% with 100 mg/kg TCC. After 90 days, the residue of the pesticides in soil treated with TCC was significantly elevated relative to the control. TCC treatment could also increase the potential leaching risk of the herbicides in the soil, as indicated by an increased Groundwater Ubiquity Score (GUS) index. The reduced abundance of soil bacteria by TCC might be an essential reason for the impacts on the environmental behavior of the pesticides. This study confirmed that TCC could slow down the degradation of pesticides in soil, increase their persistence and even affect the leaching behavior, thus influencing the risks of the pesticides to the environment.

Enabling dual valorization of lignocellulose by fluorescent lignin carbon dots and biochar-supported persulfate activation: Towards waste-treats-pollutant.

The rationally-designed lignocellulose valorization that promotes a novel "waste-treats-pollutant" standpoint is highly desired yet still challenging for the spread of biomass industry. At this point, a cascade technique with the assistance of deep eutectic solvent (DES) fractionation is tailored to dually valorize wheat straw into fluorescent lignin carbon dots (LCDs) and bimetallic Mg-Fe oxide-decorated biochar (MBC) via solvothermal engineering and co-precipitation/pyrolysis respectively. Benefitting from the abundance of ß-aryl ether and hydroxyl groups in DES-extracted lignin, the photoluminescence LCDs emit blue color in a wide excitation span, which can be adopted to selectively detect ferric ions (Fe3+) in a broad dosage scale with a highly linear correlation of 10-50 µM. Taking advantages of the MBC-aided persulfate activation, we propose the efficient arbidol removal system with a universal concentration of 20-200 ppm in the scalable pH ranging from 3 to 11. The dominate migration pathways involving with active oxygen species and surface electron transfer are comprehensively studied via electron paramagnetic resonance, radical-quenching experiments, and theoretical arithmetic. With the endeavor of biorefineries, this full-scale platform ignites the dazzling wildfire from dual lignocellulose valorization that will also seek its accurate position in the kingdoms of functional materials and wastewater restoration.

Perioperative Management and Long-Term Outcomes in Ocular Cicatricial Pemphigoid Patients Undergoing Cataract Surgery.

Objective: To observe the outcomes of cataract surgery in ocular cicatricial pemphigoid (OCP) patients and explore routine perioperative medical treatments. Design: Retrospective case series. Methods: Fourteen eyes of 8 patients were included in the study. Foster's stage 1-4 OCP patients were given human intravenous immunoglobulin, whereas patients with active inflammation were treated with prednisone tablets and methotrexate. Those who were intolerant to methotrexate and had severe inflammatory symptoms were treated with cyclophosphamide. Cataract surgery was performed for all patients after three months of systemic treatment under stable conditions. The conjunctival biopsy was evaluated by immunofluorescence microscopy. Then, patients were divided into individuals with or without ankyloblepharon. Records were reviewed for OCP stage, type of surgery, best-corrected visual acuity (BCVA), Schirmer I test, corneal fluorescein sodium staining, meibomian gland coloboma range, and ocular surface disease index (OSDI) scores. Follow-up was for the duration of taking topical and systemic medication. Results: Nine female (64.29%) and 4 male (35.71%) eyes were diagnosed with OCP by biopsy. The mean follow-up time was 60.64 ± 35.62 months. Thirteen eyes (92.86%) of 7 patients underwent phacoemulsification. One eye underwent phacoemulsification combined with amniotic membrane transplantation. The intracapsular extraction of cataract was applied to one eye. The BCVA improved significantly in all the patients, which remained stable until the last follow-up. The Schirmer I test was higher than that before the surgery. Corneal fluorescein sodium staining after surgery showed a decrease in score compared to the preoperative score. The BCVA of the patients after surgery increased significantly. The OSDI scores of patients with ankyloblepharon were significantly higher than for those without it. Postoperative symblepharon showed no significant difference compared to the preoperative symblepharon. Conclusions: In this series, OCP patients with cataracts were able to undergo phacoemulsification surgery, whereas routine use of immunosuppression and closed postoperative follow-up were necessary.

Enantioselective degradation of prothioconazole in soil and the impacts on the enzymes and microbial community.

In this work, the stereoselective degradation of prothioconazole in five soils was investigated and the metabolite prothioconazole-desthio was determined. The effects of prothioconazole on soil enzymes activities and microbial community were also studied. The dissipation of prothioconazole fitted with a first-order kinetic equation with half-lives ranging from 3.45 to 9.90 days. In addition, R-prothioconazole degraded preferentially than S-prothioconazole in all soils with EF values >0.5. Prothioconazole-desthio formed rapidly with preference in R-enantiomer, and the concentration kept at a considerable level even at the end of the incubation, indicating it was relatively persistent in soil. Prothioconazole and its metabolite inhibited the activity of dehydrogenase, catalase and urease in soils, and could affect the diversity of the soil microbiota as well. Redundancy analysis (RDA) and Spearman analysis showed the abundance of Proteobacteria, Fusobacteria, Firmicutes, Thaumarchaeota, Saccharibacteria, Chloroflexi, Chlorobi, Actinobacteria and Nitrospirae might be related to the enantioselective degradation. The work was helpful for understanding the environmental behavior of the fungicide prothioconazole and its primary metabolite on an enantiomeric level.

C6-structural optimizations of 2-aryl-1H-pyrazole-S-DABOs: From anti-HIV to anti-DENV activity.

Both HIV and DENV are serious threats to human life, health and social economy today. So far, no vaccine for either HIV or DENV has been developed successfully. The research on anti-HIV or DENV drugs is still of great significance. In this study we developed a series of novel 2-Aryl-1H-pyrazole-S-DABOs with C6-strucutral optimizations as potent NNRTIs, among which, 8 compounds had low cytotoxicity and EC50 values in the range of 0.0508 âˆ¼ 0.0966 µM, and their selectivity index was SI > 1415 âˆ¼ 3940. In particular, two compounds 4a and 4b were identified to have good inhibitory effects on DENV of four serotypes. The EC50 of compound 4a and 4b against DENV-II (13.2 µM and 9.23 µM, respectively) were better than that of the positive control ribavirin (EC50 = 40.78 µM). In addition, the effect of C-6 substituents on the anti-HIV or anti-DENV activity of these compounds was also discussed.

Multicenter assessment of shotgun metagenomics for pathogen detection.

BACKGROUND: Shotgun metagenomics has been used clinically for diagnosing infectious diseases. However, most technical assessments have been limited to individual sets of reference standards, experimental workflows, and laboratories. METHODS: A reference panel and performance metrics were designed and used to examine the performance of shotgun metagenomics at 17 laboratories in a coordinated collaborative study. We comprehensively assessed the reliability, key performance determinants, reproducibility, and quantitative potential. FINDINGS: Assay performance varied significantly across sites and microbial classes, with a read depth of 20 millions as a generally cost-efficient assay setting. Results of mapped reads by shotgun metagenomics could indicate relative and intra-site (but not absolute or inter-site) microbial abundance. INTERPRETATION: Assay performance was significantly impacted by the microbial type, the host context, and read depth, which emphasizes the importance of these factors when designing reference reagents and benchmarking studies. Across sites, workflows and platforms, false positive reporting and considerable site/library effects were common challenges to the assay's accuracy and quantifiability. Our study also suggested that laboratory-developed shotgun metagenomics tests for pathogen detection should aim to detect microbes at 500 CFU/mL (or copies/mL) in a clinically relevant host context (10^5 human cells/mL) within a 24h turn-around time, and with an efficient read depth of 20M. FUNDING: This work was supported by National Science and Technology Major Project of China (2018ZX10102001).

Tandem Character of Liquid Hot Water and Deep Eutectic Solvent to Enhance Lignocellulose Deconstruction.

Pretreatment with efficient fractionation, eco-friendliness, and low-cost brings high security to future biorefinery systems. Synergistic pretreatment is a compelling blueprint to tackle the compact structure of lignocellulose towards a high-level valorization. Here, a stepwise approach was designed using hydrothermal and deep eutectic solvent (DES) pretreatments to hierarchically extract hemicelluloses and lignin from poplar, while delivering a cellulose-rich substrate that could easily undergo enzymatic hydrolysis to obtain fermentable glucose and residual lignin. The lifetime of recyclable DES showed that the pretreatment efficiency was still largely maintained after the fourth recycling. An enhancement of enzymatic digestibility from 13.9 to 90.4 % was initiated by the deconstruction of amorphous portions and robust cell wall. 23.7 % Xylooligosaccharides (degree of polymerization 2-6), 47.5 % DES-isolated lignin, and 19.2 % cellulose enzymatic lignin were harvested via this coupled process. This study could promote the precise design of sustainable tandem pretreatment that can boost the frontier of highly available biorefinery.

The effect of combined transcranial pulsed current stimulation and transcutaneous electrical nerve stimulation on lower limb spasticity in children with spastic cerebral palsy: a randomized and controlled clinical study.

BACKGROUND: In the current study, we applied a combination of non-invasive neuromodulation modalities concurrently with multiple stimulating electrodes. Specifically, we used transcranial pulsed current stimulation (tPCS) and transcutaneous electrical nerve stimulation (TENS) as a novel strategy for improving lower limb spasticity in children with spastic cerebral palsy (SCP) categorized on levels III-V of the Gross Motor Function Classification System (GMFCS) with minimal side effects. METHODS: Sixty-three SCP children aged 2-12 years, who were classified on levels III-V of the GMFCS were randomly assigned to one of two groups, resulting in 32 children in the experimental group and 31 children in the control group. The experimental group underwent a combination therapy of tPCS (400 Hz, 1 mA cerebello-cerebral stimulation) and TENS (400 Hz, max 10 mA) for 30 min, followed by 30 min of physiotherapy five times per week for 12 weeks. The control group underwent physiotherapy only 30 mins per day five times per week for 12 weeks. In total, all groups underwent 60 treatment sessions. The primary outcome measures were the Modified Ashworth Scale (MAS) and Modified Tardieu Scale (MTS). Evaluations were performed 3 days before and after treatment. RESULTS: We found a significant improvement in MAS and MTS scores of the lower limbs in the experimental group compared to the control group in the hip adductors (Left: p = 0.002; Right: p = 0.002), hamstrings (Left: p = 0.001; Right: p < 0.001, and gastrocnemius (Left: p = 0.001; Right: p = 0.000). Moreover, MTS scores of R1, R2 and R2-R1 in left and right hip adduction, knee joint, and ankle joint all showed significant improvements (p ≤ 0.05). Analysis of MAS and MTS scores compared to baseline scores showed significant improvements in the experimental group but declines in the control group. CONCLUSION: These results are among the first to demonstrate that a combination of tPCS and TENS can significantly improve lower limb spasticity in SCP children classified on GMFCS levels III-V with minimal side effects, presenting a novel strategy for addressing spasticity challenges in children with severe SCP. TRIAL REGISTRATION: ChiCTR.org, ChiCTR1800020283, Registration: 22 December 2018 (URL: http://www.chictr.org.cn/showproj.aspx?proj=33953 ).

Clinical outcome of phacoemulsification combined with intraocular lens implantation for primary angle closure/glaucoma (PAC/PACG) with cataract.

OBJECTIVE: To evaluate the efficacy of phacoemulsification (Phaco) combined with intraocular lens implantation for treatment of primary angle-closure glaucoma (PACG) patients with cataract. METHODS: A total of 62 patients treated in our hospital meeting the inclusion criteria were included, including 62 eyes (26 PAC eyes and 36 PACG eyes). PACG patients were divided into early, middle, and advanced stages based on the HPA visual field staging system. The subjects were also grouped according to the extent of peripheral anterior synechia (PAS). Patients received topical medical treatment preoperatively and Phaco performed by the same surgeon. The visual acuity, intraocular pressure (IOP), anterior chamber depth (ACD), medication used, visual field and retinal nerve fiber layer (RNFL) were observed before and 6-24 months after surgery. RESULTS: The mean age of the patients was 68±8.91 years old, and postoperative follow-up was 13.1±5.5 months. Postoperative visual acuity was improved in all patients (P<0.001). Postoperatively, the IOP decreased significantly (P<0.001), the number of medications was reduced (P<0.001), and the ACD was deeper than that before operation (P<0.001). There was no significant difference in visual field (P=0.973) or RNFL (P=0.268) after surgery during the follow-up. There was no statistical difference in postoperative changes of various indexes between PAC and PACG patients. The decrease of IOP in patients with early stage PACG was significantly higher than that in patients in the middle and advanced stages (F=3.519, P=0.041), and the number of medications used in early-stage PACG patients was also significantly lower than that of advanced patients (P=0.020). There was no significant difference in postoperative visual acuity (X2=0.139, P=0.987) or IOP decline (F=0.260, P=0.854) among patients with different extents of preoperative PAS, nor was there any correlation between postoperative IOP control and preoperative PAS. No serious complications were observed in any subject. CONCLUSION: In PAC/PACG patients, Phaco can significantly control IOP, and prevent visual field defect and progressive loss of RNFL, indicating that the procedure has a protective effect on the optic nerve. Phaco is more effective in the treatment of early stage PACG than in middle or advanced stage, and can be used in PAC/PACG patients with different extents of PAS, but close follow-up is necessary.

Analysis of craniocerebral injury in facial collision accidents.

Considering that the Pc-Crash multibody dynamics software can reproduce the accident process accurately and obtain the collision parameters of pedestrian heads at the moment of head landing, the finite element analysis method can accurately analyze the injury of the pedestrian head when the boundary conditions are known. This paper combines the accident reconstruction method with the finite element analysis method to study the injury mechanism of pedestrian head impact on the ground in vehicle pedestrian collision accidents to provide a theoretical basis for pedestrian protection and the improvement of vehicle shapes. First, a real-life vehicle pedestrian collision is reproduced by Pc-Crash. The simulation results show that the rigid multibody model can accurately simulate the scene of the accident, then the speed and angle of the pedestrian head landing moment can be obtained at the same time. Second, the finite element model of human heads with a detailed facial structure is established and verified. Finally, the collision parameters obtained from the accident reconstruction are used as the boundary conditions to analyze the collision between the pedestrian head and the ground, and the biomechanical parameters, such as intracranial pressure, von Mises stress, shear stress and strain, can be determined. The results show that the stress wave will propagate inside and outside the skull and cause stress concentration in the skull and the brain tissue to varying degrees after the pedestrian head strikes the ground. When the stress exceeds a certain limit, it will cause different degrees of brain tissue injury.

Bioinformatics analysis of candidate proteins Omp2b, P39 and BLS for Brucella multivalent epitope vaccines.

This study focuses on analyzing the physicochemical properties, structural characteristics and dominant epitopes of Brucella outer membrane protein 2b (Omp2b), periplasmic binding protein (P39) and Brucella lumazine synthase (BLS) proteins by bioinformatics methods, and to provide a theoretical basis for constructing multi-epitope vaccines. The amino acid sequences of three kinds of proteins were obtained from the UniProt database. The highest frequency alleles in northern China were obtained from the AlleleFrequencies database. Analysis of the physicochemical properties of the proteins by ProtParam online software. Analysis of the secondary structure of the proteins were predicted by SOMPA online software. Using SWISS-MODEL online software constructed and analyzed the tertiary structure of the proteins. Using ABCpred, BepiPred, BCPred and SVMTrip online software analyzed linear B cell epitopes of proteins, The T cell dominant epitope of the protein was analyzed using SYFPEITHI, RANKPEP and IEDB online software. Omp2b was identified three linear B cell dominant epitopes, five CD8+ T cell dominant epitopes, and three CD4+ T cell dominant epitopes. P39 was identified three linear B cell dominant epitopes, two CD8+ T cell dominant epitopes, and two CD4+ T cell dominant epitopes. BLS was identified one linear B cell dominant epitope, one CD8+ T cell dominant epitope, and two CD4+ T cell dominant epitopes. The results indicated that epitope prediction of three Brucella vaccine candidate proteins can provide a theoretical basis for the construction of an ideal multivalent epitope vaccine against Brucella.

The New NNRTI ACC007 Combined with Lamivudine and Tenofovir Disoproxil Fumarate Show Synergy Anti-HIV Activity In Vitro.

BACKGROUND: Acquired immunodeficiency syndrome can hardly be cured currently and people with human immunodeficiency virus (HIV) need lifelong treatment that may result in the emergence of drug resistance which leads to failed treatment. Thus, the development of new anti- HIV drugs and new treatment regimens are necessary. OBJECTIVE: The aim of this study is to analyze the combined anti-HIV activity of tenofovir disoproxil fumarate, lamivudine and ACC007, a new non-nucleoside reverse transcriptase inhibitor. METHODS: The antiviral activity of tenofovir disoproxil fumarate, lamivudine and ACC007 alone or in combination against different HIV-1 strains was determined by the detection of HIV-1 p24 level through enzyme-linked immunosorbent assay. RESULT: ACC007 showed EC50 of nanomolar range (from 3.03 nM to 252.59 nM) against all HIV-1 strains used in this study except the HIV-1A17, with EC50 of 1.57 µM. The combined antiviral activity of ACC007, lamivudine and tenofovir disoproxil fumarate showed synergy antiviral activity against all HIV-1 strains used in this study. The three-drug combination showed moderate synergism against HIV-1A17, HIV-14755-5, HIV-1K103N and HIV-1V106M, with a combination index value ranging from 0.71 to 0.87, and showed synergism against the other HIV-1 strains with combination index value from 0.35 to 0.67. The combination with ACC007 significantly increases the dose reduction index value of lamivudine and tenofovir disoproxil fumarate, compared with two-drug combination. CONCLUSION: ACC007 exhibits potent antiviral activity alone or with 3TC and TDF, and exerts synergistic effect against all HIV strains used in our investigation in vitro.

Mitochondrial stress-activated cGAS-STING pathway inhibits thermogenic program and contributes to overnutrition-induced obesity in mice.

Obesity is a global epidemic that is caused by excessive energy intake or inefficient energy expenditure. Brown or beige fat dissipates energy as heat through non-shivering thermogenesis by their high density of mitochondria. However, how the mitochondrial stress-induced signal is coupled to the cellular thermogenic program remains elusive. Here, we show that mitochondrial DNA escape-induced activation of the cGAS-STING pathway negatively regulates thermogenesis in fat-specific DsbA-L knockout mice, a model of adipose tissue mitochondrial stress. Conversely, fat-specific overexpression of DsbA-L or knockout of STING protects mice against high-fat diet-induced obesity. Mechanistically, activation of the cGAS-STING pathway in adipocytes activated phosphodiesterase PDE3B/PDE4, leading to decreased cAMP levels and PKA signaling, thus reduced thermogenesis. Our study demonstrates that mitochondrial stress-activated cGAS-STING pathway functions as a sentinel signal that suppresses thermogenesis in adipose tissue. Targeting adipose cGAS-STING pathway may thus be a potential therapeutic strategy to counteract overnutrition-induced obesity and its associated metabolic diseases.

Prevalence and causes of visual impairment in population more than 50 years old: The Shaanxi Eye Study.

To assess the prevalence and causes of visual impairment (VI) in the elderly Chinese rural population in Shaanxi Province.A population-based, cross-sectional study design was used to determine the extent of VI in Chinese people over the age of 50 years in Shaanxi Province. Visual acuity and best-corrected visual acuity were measured using the logarithm of minimum angle of resolution chart. Blindness and low vision were defined according to WHO criteria. The major cause of VI was identified for all participants who were visually impaired.A total of 1912 residents completed a standard questionnaire and underwent a detailed eye examination, and the response rate was 90%. The overall prevalence of blindness and low vision were 1.5% and 8.2%. There was no statistically significant differences between genders in the prevalence of blindness and low vision (P > .05). The prevalence of blindness and low vision was higher among older individuals (P < .05) and lower (P < .05) among those with the highest education level. Cataract, corneal opacity, and glaucoma were considered as the main causes of blindness, which accounted for 67.9%, 10.7%, and 7.1%, respectively. Cataract, refractive error, and age-related macular degeneration were always considered as the leading causes of low vision, which accounted for 66%, 14.7%, and 5.8%, respectively.Cataract, corneal opacity, and glaucoma were the main causes of blindness and low vision in the population aged 50 years or more. The prevalence of these diseases that causes blindness and low vision was higher than that reported in other studies.

Ionic liquid-aided hydrothermal treatment of lignocellulose for the synergistic outputs of carbon dots and enhanced enzymatic hydrolysis.

How to propel an efficient exploitation of waste streams is a pivotal tache for the long-range augment of hydrothermal biomass valorization. A facile approach was proposed to simultaneously produce carbon dots (CDs), fermentable sugar, and cellulose enzymatic lignin from agricultural straw with the aid of ionic liquid (IL, 1-aminoethyl-3-methylimidazolium nitrate, [C2NH2MIm][NO3]) catalyzed hydrothermal treatment. The graphite N-doped CDs with bright-blue fluorescence, which was mainly derived from the incorporation of hemicellulose (e.g. xylooligosaccharides), lignin and [C2NH2MIm][NO3], exhibited an average-diameter of 8.14 nm. The exfoliation of amorphous parts and robust fibers was formed to improve cellulose digestibility from 14.7 to 81.6%. The efficient recovery and checkup of lignin pave a way for its potential depolymerization into arenes. This protocol offers a significant benefit for large-scale hydrothermal biorefinery where reduction of process waste is a prime concern, and leads to high-value products (i.e., CDs and lignin) that also fosters the feasibility of bioethanol.

Study on the association between TGF-ß1 and liver fibrosis in patients with hepatic cystic echinococcosis.

The present study aimed to determine the role of the cytokine transforming growth factor-ß1 (TGF-ß1) in liver fibrosis among patients with hepatic cystic echinococcosis (hepatic CE). Hepatic tissue specimens and serum samples from 30 patients with hepatic CE were collected and TGF-ß1 levels were compared between the two groups. The degree of liver fibrosis was assessed by Masson staining. The expression levels of cytokine TGF-ß1 in liver tissue and serum were detected by immunohistochemistry and ELISA, respectively. Masson staining of liver lesion tissue in patients with hepatic CE indicated different degrees of fibrosis in the liver and the World Health Organization classification was positively correlated with the severity of liver fibrosis (P<0.05). In addition, the expression of cytokine TGF-ß1 was higher in liver lesion tissue specimens compared with that in the adjacent control samples (P<0.05). At the same time, cytokine TGF-ß1 in serum specimens of patients was higher than that in the healthy control group (P<0.05). In conclusion, the expression of TGF-ß1 is upregulated in patients with hepatic CE, which was closely associated to liver fibrosis.

Synergistic benefits from a lignin-first biorefinery of poplar via coupling acesulfamate ionic liquid followed by mild alkaline extraction.

A novel mind-set, termed lignin-first biorefinery, is bewitching to synchronously boost lignin output for entirely lignocellulosic utilization. A lignin-first fractionation, using a food-additive derived ionic liquid (1-ethyl-3-methylimidazolium acesulfamate, emimAce) and mild alkaline pretreatments, was formed for the purposely isolating poplar lignin, whilst delivering a cellulose-rich substrate that can be easily available for enzymatic digestion. The emimAce-driven lignin, alkali-soluble lignin and hemicellulose, and accessible cellulose were sequentially gained. We introduce a lignin-first approach to extract the amorphous fractions, destroy the robust architecture, and reform cellulose-I to II, thereby advancing the cellulose bioconversion from 15.4 to 90.5%. A harvest of 70.7% lignin, 52.1% hemicellulose, and 330.1 mg/g glucose was fulfilled from raw poplar. A structural ''beginning-to-end'' analysis of lignin inferred that emimAce ions are expected to interact with lignin ß-aryl-ether due to their aromatic character. It was reasonable to derive benefits from lignin-first technique that can substantially augment the domain of biorefinering.

[Challenges and considerations on quality control and evaluation of pathogen metagenomic next-generation sequencing].

Metagenomic next-generation sequencing (mNGS) could be used for pathogen detection from nearly all types of clinical samples. Especially, the unique diagnostic capability of pathogen mNGS detecting unknown causative agent of infectious diseases makes this method become an importation complement and irreplaceable component for conventional routine laboratory test. However, the complexity of the testing process, the rapid product update, and the insufficiency in quality control and evaluation methods that all make clinical transformation, industry development, and regulation of this technology full of challenge and uncertainty. This review briefly introduces the technical advantages and challenges, and describes the general workflow and quality control steps in details. Finally, it focuses on current considerations regarding quality evaluation methods and standards for pathogen mNGS.