Expression patterns and pathogenesis of Semaphorin class 4 subfamily proteins in solid tumors.

Semaphorins are originally described as regulators of nervous system development. Besides, members of the semaphorin family play important roles in the growth, metastasis, and angiogenesis of solid tumors. In contrast to the other semaphorin subclasses, semaphorin class 4 has both membrane-bound and active soluble forms. Soluble class 4 semaphorins in body fluids (blood and saliva) may serve as potential biomarkers for early diagnosis and prognosis prediction of specific cancers. The class 4 semaphorins also transduce signal in cancer cells in a cell membrane-bound form, thereby regulating cancer progression. In solid tumors, class 4 semaphorins can act as ligands in active soluble forms, regulating cancer progression via autocrine and paracrine to activate signal transduction in cancer cells or endothelial cells in the tumor microenvironment. Targeting class 4 semaphorins may be a novel strategy for specific cancer therapy. However, the expression of class 4 semaphorins in solid tumors and the responsive pathogenesis are still controversial. Therefore, this review summarizes the specific expression regulation of class 4 semaphorin members in different types of solid tumors and the mechanisms involved in cancer progression.

Lignin-xylan nanospheres prepared by green and quick method from lignocellulose and used as additive in PVA films.

Lignin, as an amorphous three-dimensional aromatic polymer, was able to self-assemble into lignin nanoparticles (LNPs) to realize valorization of lignin. Here, lignin-xylan extractives were extracted from grape seed (GS) and poplar by acidic THF at room temperature, and effectively produced lignin-xylan nanospheres via spin evaporation. The morphology and chemical properties of nanospheres were determined by its natural origins, consequently influencing its application. For the lignin-xylan extractive from grape seed, the lignin was composed of guaiacyl (G) and p-hydroxylphenyl (H) units and the hollowed nanospheres (GS-LNPs) with 362.72 nm diameter was produced. The extractive from poplar was composed of G-syringyl (S) typed lignin (80.30 %) and xylan (12.33 %), that can assemble into LNPs with smaller size (229.87 nm), better PDI (0.1), and light color. The hybrid particles showed the qualities of lignin and xylan, that properties led to the LNPs@PVA composite films with UV-blocking capability, strong mechanical strength and hydrophobicity, and transparency ability of visible light. P-LNPs showed better performance as the film additives, due to its lower particles size and high content of unconjugated -OH from xylan. Xylan was significant in the composite films, and lowering the xylan content resulted in the decrease of the composite film's mechanical properties and hydrophobicity.

Production of single cell protein from brewer's spent grain through enzymatic saccharification and fermentation enhanced by ammoniation pretreatment.

Brewer's spent grain (BSG) is a major low-value by-product of beer industry. To realize the high value application of BSG, this work proposed a strategy to produce single cell protein (SCP) with oligosaccharide prebiotics from BSG, via ammoniation pretreatment, enzymatic hydrolysis, and fermentation. The optimum conditions of ammoniation pretreatment obtained by response surface method were 11 % ammonia dosage (w/w), 63 °C for 26 h. Suitable enzyme and yeast were screened to enhance the conversion of cellulose and hemicellulose in BSG into sugars and maximize the SCP yield. It was shown that using lignocellulolytic enzyme SP from Penicillium oxalicum and Trichosporon cutaneum, about 310 g of SCP with 80 g of arabinoxylo-oligosaccharides were obtained from 1000 g of BSG. This process is low cost, high efficiency, and easy to implement, which has good industrial application prospects.

Transmission risk assessment of HIV/AIDS epidemic resulting from sexual transmission in China, 2013-2017.

To estimate the risk of human immunodeficiency virus (HIV) infection through sexual transmission in China from 2013 to 2017 accurately, we divide the total population into three groups, namely, men who have sex with men (MSM) group; non-marital and commercial sex group: female sex workers (FSW) and their clients (FSWC); non-marital and non-commercial sex group: general women (GW) and general men (GM). First, the risks of HIV infection among men who have contacts with infected men or infected women decrease annually. Second, the number of contacts between susceptible FSWC and infected FSW per unit time is greater than that between susceptible MSM and infected MSM, and also greater than that between susceptible FSW and infected FSWC, which suggests that the intervention for commercial sex of heterosexual men should be strengthened. Third, the effective reproduction numbers of the MSM group and non-commercial sex group decrease annually, while the effective reproduction number of the commercial sex group decreases first, then increases, because the risk of women being infected by men decreases first, then increases. Additionally, the effective reproduction number of the commercial sex group exceeds that of the MSM group after 2015, which indicates that commercial sex contributes more and more to the HIV/AIDS epidemic.

Rhubarb charcoal-crosslinked chitosan/silk fibroin sponge scaffold with efficient hemostasis, inflammation, and angiogenesis for promoting diabetic wound healing.

Diabetic patients often experience long-term risks due to chronic inflammation and delayed re-epithelialization during impaired wound healing. Although the severity of this condition is well known, the treatment options for diabetic wounds are limited. Rhubarb charcoal, a well-known traditional Chinese medicine, has been used to treat skin wounds for thousands of years. We produced a chitosan/silk fibroin sponge scaffold loaded with natural carbonized rhubarb and crosslinked it by freeze-drying to create a highly efficient RCS/SF scaffold. Rhubarb carbon and carboxymethyl chitosan exhibit antibacterial activity and promote wound healing. Owing to its 3D porous structure, this scaffold is antibacterial and pro-angiogenic. It also possesses remarkable properties, such as excellent swelling and biocompatibility. The supportive effect of carbonized rhubarb on mouse fibroblast migration is mediated at the cellular/tissue level by increased skin neovascularization and re-epithelization. Compared to the control group, RCS/SF scaffolds promoted faster healing, increased neovascularization, enhanced collagen deposition, and re-epithelialization within two weeks. The scaffold's pro-healing properties and efficient release of carbonized rhubarb, with rapid hemostatic and good sterilization effects, make it an outstanding candidate for treating diabetic wounds and novel therapeutic interventions for diabetic ulcers.

[Electroacupuncture intervention improves lipid metabolism and promotes browning of white adipose tissue by activating AMPK/Sirt1 pathway and up-regulating Nrg4 content in middle-aged and aged obese rats].

OBJECTIVE: To investigate the mechanism of electroacupuncture （EA） in promoting the browning of white adipose tissue in middle-aged and aged obese rats induced by high fat by regulating AMP-activated protein kinase （AMPK） /silence-information regulatory factor 1 （Sirt1） pathway and neuregulin 4 （Nrg4）. METHODS: Twenty-four male SD rats were randomized into blank control, model and EA groups （n=8 per group）. The obesity model was established by feeding the rats with high-fat diet for 6 weeks. For the EA group, EA （2 Hz/15 Hz, 1.5 mA） was applied to "Guanyuan" （CV4） and bilateral "Shenshu" （BL23）, "Fenglong" （ST40） and "Tianshu" （ST25） for 20 min, once a day, 5 days a week for 6 weeks. Rats of the blank control and model groups were also restrained for 20 min. The body mass and food intake were measured every week, and the Lee's index, epididymal fat, perirenal fat and brown adipose tissue were weighed. The contents of serum total cholesterol （TC）, triglyceride （TG）, high density lipoprotein cholesterol （HDL-C）, low density lipoprotein cholesterol （LDL-C） and norepinephrine （NE） were determined by ELISA. H.E. staining was used to observe the morphological changes of white and brown adipose tissue. The mRNA expression levels of mitochondrial uncoupling protein 1 （UCP1）, peroxisome proliferator activated receptor γ co-activator 1α （PGC-1α）, PR-domain protein 16 （PRDM16）, peroxisome proliferator activated receptor γ （PPARγ） and Nrg4 in the adipose tissue were detected by quantitative real time PCR, and the protein expression levels of Nrg4, AMPKα, Sirt1 and interleukin-6 （IL-6） in the white and brown adipose tissue were detected by Western blot. RESULTS: Compared with the blank control group, the body mass, food intake, the Lee's index, epididymal fat and perirenal fat mass, and serum TG, TC and LDL-C contents and the expression level of IL-6 protein were significantly increased （P<0.01, P<0.05, P<0.001）, and the brown adipose mass, serum HDL-C and NE contents, the expression levels of UCP1, PGC-1α, PRDM16, PPARγ and Nrg4 mRNAs, and the protein expression levels of AMPKα, Sirt1 and Nrg4 proteins in both white and brown adipose tissues were significantly decreased in the model group （P<0.01, P<0.05）. After EA intervention, the increased levels of body mass, food intake, Lee's index, epididymal fat and perirenal fat mass, serum TG, TC and LDL-C contents, and the expression of IL-6 protein, and the decreased levels of brown adipose mass, serum HDL-C and NE contents, expression levels of UCP1, PGC-1α, PRDM16, PPARγ and Nrg4 mRNAs, and those of AMPKα, Sirt1 and Nrg4 proteins in both white and brown adipose tissues were apparently reversed（P<0.05, P<0.01, P<0.001）. H.E. staining showed an increase of the volume and content of intracellular vacuoles of both white and brown adipose tissues, disordered arrangement of cells with vague boundary in the model group, which was relatively milder including a decrease of volume and content of vacuoles of both white and brown adipose, neat arrangement of cells with clear boundary. CONCLUSION: EA intervention can improve lipid metabolism and promote white adipose tissue browning in middle-aged and aged obese rats, which is possibly associated with its functions in activating AMPK/Sirt1 signaling pathway and up-regulating the level of Nrg4.

Production and Characterization of Cellulose Nanocrystals from Eucalyptus Dissolving Pulp Using Endoglucanases from Myceliophthora thermophila.

Endoglucanase (EG) is a key enzyme during enzymatic preparation of cellulose nanocrystals (CNCs). Myceliophthora thermophila is a thermophilic fungus that has thermal properties and a high secretion of endoglucanases (EGs), and could serve as potential sources of EGs for the preparation of CNCs. In this work, four different GH families (GH5, GH7, GH12, and GH45) of EGs from M. thermophila were expressed and purified, and their enzymatic characteristics and feasibility of application in CNC preparation were investigated. It was shown that the MtEG5A from M. thermophila has good potential in the enzymatic preparation of CNCs using eucalyptus dissolving pulp as feedstock. It was also observed that there was a synergistic effect between the MtEG5A and other MtEGs in the preparation of CNCs, which improved the yield and properties of CNCs obtained by enzymatic hydrolysis. This study provides a reference for understanding the enzymatic characteristics of different families of EGs from M. thermophile and their potential application in nanocellulose production.

Therapeutic potential of icariin in rats with letrozole and high-fat diet-induced polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is characterized by reproductive, endocrine, and metabolic disorders. Icariin has been shown to regulate endocrine and metabolic imbalances. This study aimed to determine the therapeutic effect and pharmacological mechanism of icariin in PCOS rats. Rats were fed a high-fat diet and gavaged with letrozole to induce PCOS. Thirty-six female rats were randomly divided into four groups: control, model, low-dose, and high-dose icariin. After 30 days of treatment, we evaluated the therapeutic effects on weight and diet, sex hormone levels, ovarian morphology, estrous cycle, inflammatory factors, and indicators of glucolipid metabolism. Combined with the ovarian transcriptome, we verified the key markers of apoptosis and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway by RT-qPCR for mRNA level, western blot, and immunohistochemistry for protein expression. Icariin significantly improved ovarian function and reproductive endocrine disorders by regulating sex hormones, restoring the estrous cycle, and reducing ovarian morphological damage in PCOS rats. Icariin-treated rats had lower weight gain and reduced triglycerides, fasting insulin, HOMA-IR, TNF-α, and interleukin-6 with higher high-density lipoprotein cholesterol levels than PCOS rats. TUNEL staining showed icariin improved apoptosis in the ovaries. This was supported by an increase in Bcl2 and a decrease in Bad and Bax. Icariin decreased the ratios of p-JAK2/JAK2, p-STAT1/STAT1, p-STAT3/STAT3, and p-STAT5a/STAT5a, decreased IL-6, gp130 expression, and increased cytokine-inducible SH2-containing protein (CISH) and suppressor of cytokine signaling 1 (SOCS1) expression. The pharmacological mechanism may be related to the reduction in ovarian apoptosis and inhibition of the IL-6/gp130/JAK2/STATs pathway.

Elucidating structure of pectin in ramie fiber to customize enzyme cocktail for high-efficiency enzymatic degumming.

Pectin is one of the main components of bast fiber including ramie fiber, and must be removed before use. Enzymatic degumming is the preferred process as it is an environment-friendly, simple and controllable process for ramie degumming. However, an important problem limiting wide application of this process is the high cost due to the low efficiency of enzymatic degumming. In this study, pectin samples were extracted from raw ramie fiber and degummed ramie fiber, respectively, and their structures were characterized and compared to allow tailoring of an enzyme cocktail for degrading the pectin. It was elucidated that pectin from ramie fiber is composed of low esterified homogalacturonan (HG) and low branched rhamnogalacturonan I (RG-I), and the ratio of HG/RG-I is 1.72:1. Based on the pectin structure, potential enzymes to be used for enzymatic degumming of ramie fiber were proposed and an enzyme cocktail was customized. Degumming experiments confirmed that the customized enzyme cocktail can effectively remove pectin from ramie fiber. To our knowledge, this is the first time the structural characteristics of pectin in ramie fiber have been clarified, and it also provides an example of tailoring a specific enzyme system to achieve high-efficiency degumming for biomass containing pectin.

Multilayer directionally arranged silver nanowire networks for flexible transparent conductive films.

Silver nanowire (AgNW) networks have excellent optoelectronic properties and have important applications in various optoelectronic devices. However, the random distribution of AgNWs coated on the substrate will cause problems such as uneven resistance and high surface roughness, which will affect the properties of the film. In order to solve these problems, this paper adopts the method of directional arrangement of AgNWs to prepare conductive films, by mixing AgNW aqueous solution with hydroxypropyl methyl cellulose (HPMC) to prepare conductive ink, and then the AgNWs are oriented on the flexible substrate by using the shear force generated during the Mayer rod coating process. The multilayer crossed three-dimensional (3D) AgNW conductive network is prepared, achieving a sheet resistance of 12.9 Ω sq-1 and a transmittance of 92.2% (λ = 550 nm). In addition, the roughness RMS value of the layered and ordered AgNW/HPMC composite film is only 6.96 nm, which is much lower than that of the randomly arranged AgNW film (RMS = 19.8 nm), and the composite film also has excellent bending resistance and environmental stability. This adjustable coating method is simple to prepare and can realize the large-scale manufacturing of conductive films, which is important for the future development of flexible transparent conductive films.

Structural characterization of corn fiber hemicelluloses extracted by organic solvent and screening of degradation enzymes.

An integrated treatment coupling peracetic acid delignification, dimethyl sulfoxide extraction, and ethanol precipitation were performed to isolate hemicellulose from de-starched corn fiber. Based on chemical composition, molecular weight distribution, methylation, and nuclear magnetic resonance spectroscopy, it is proposed that hemicelluloses in corn fiber were composed of two polysaccharides, glucuronoarabinoxylan (about 80 %) and xyloglucan (about 20 %). Xylose (about 46 %) and arabinose (about 32 %) were the main components in glucuronoarabinoxylan. More than half of the xylose units in the glucuronoarabinoxylan backbone chain were substituted at O-2 and/or O-3 by various monomers or oligomeric side chains. Based on structure analysis, five hemicellulases were selected and added to Penicillium oxalicum MCAX enzymes for enzymatic hydrolysis of corn fiber. The results showed that the addition of hemicellulases increased the sugar yield of corn fiber. These results demonstrate the effectiveness of enzyme consortium constructed by elucidating the chemical structure of hemicellulose in corn fiber for the degradation of corn fiber and also provide a general solution for the rational construction of targeted and efficient enzyme systems for the degradation of lignocellulosic biomass.

Metabolomics profile of plasma in acute diquat-poisoned patients using gas chromatography-mass spectrometry.

Diquat (DQ) has been confirmed to be toxic to humans and responsible for severe health impairment. While to date, very little is known about the toxicological mechanisms of DQ. Thus, investigations to discover the toxic targets and potential biomarkers of DQ poisoning are urgently needed. In this study, a metabolic profiling analysis was conducted to reveal the changes of metabolites of plasma and find out the potential biomarkers of DQ intoxication by GC-MS. First, multivariate statistical analysis demonstrated that acute DQ poisoning can lead to metabolomic changes in human plasma. Then, metabolomics studies showed that 31 of the identified metabolites were significantly altered by DQ. Pathway analysis indicated that three primarily metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine metabolism, and phenylalanine metabolism were affected by DQ, resulting in the perturbations of phenylalanine, tyrosine, taurine, and cysteine. Finally, the results of receiver operating characteristic analysis showed the above four metabolites could be used as reliable tools for the diagnosis and severity assessments of DQ intoxication. These data provided the theoretical basis for basic research to understand the potential mechanisms of DQ poisoning, and also identified the desirable biomarkers with great potential for clinical applications.

Effects of Pomegranate Peel Polyphenols Combined with Inulin on Gut Microbiota and Serum Metabolites of High-Fat-Induced Obesity Rats.

Pomegranate peel polyphenols (PPPs) and inulin have been reported to have lipid-lowering effects. Here, the effects of PPPs combined with inulin on obesity traits and the change of the gut microbiota, short-chain fatty acids (SCFAs), and serum metabolomics profiles in rats with a high-fat diet (HFD) were investigated. According to the experimental results, PPPs were most effective in reducing the body weight and serum and liver lipid levels. Besides, PPPs ameliorated the disorder of gut microbiota, in particular, the enrichment of SCFA producers, such as Lactobacillus, Roseburia, Christensenellaceae_R-7_group, Ruminococcaceae_UCG-005, Bacteroides, and Allobaculum, and the depletion of the Blautia and unclassified Lachnospiraceae population. PPPs also regulated the levels of metabolites changed by HFD feeding via tryptophan metabolism, valine, leucine, and isoleucine biosynthesis, and arachidonic acid metabolism pathways. The correlation analysis showed that PPPs remitted HFD-induced elevation in triglycerides (TGs), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels and lowered high-density lipoprotein (HDL) levels through regulating the gut microbiota, SCFAs, and related metabolites. These findings elucidated that PPPs have a good anti-obesity effect. This study extends the understanding of PPP effects on high-fat-induced obesity, which includes the relationship among gut microbiota, SCFAs, serum metabolites, and TG-, IL-6- and TNF-α- lowering and HDL-elevating functions.

Modeling Syphilis and HIV Coinfection: A Case Study in the USA.

Syphilis and HIV infections form a dangerous combination. In this paper, we propose an epidemic model of HIV-syphilis coinfection. The model always has a unique disease-free equilibrium, which is stable when both reproduction numbers of syphilis and HIV are less than 1. If the reproduction number of syphilis (HIV) is greater than 1, there exists a unique boundary equilibrium of syphilis (HIV), which is locally stable if the invasion number of HIV (syphilis) is less than 1. Coexistence equilibrium exists and is stable when all reproduction numbers and invasion numbers are greater than 1. Using data of syphilis cases and HIV cases from the US, we estimated that both reproduction numbers for syphilis and HIV are slightly greater than 1, and the boundary equilibrium of syphilis is stable. In addition, we observed competition between the two diseases. Treatment for primary syphilis is more important in mitigating the transmission of syphilis. However, it might lead to increase of HIV cases. The results derived here could be adapted to other multi-disease scenarios in other regions.

Preparation of nanocellulose crystal from bleached pulp with an engineering cellulase and co-production of ethanol.

The study investigated the feasibility of co-production of nanocellulose crystal (CNC) and ethanol using the bleached pine kraft pulp (BPKP) as a substrate by enzymatic hydrolysis. An engineering strain Penicillum oxalicum cEES-XM was constructed to produce suitable cellulase used in enzymatic hydrolysis of BPKP for preparing CNC. The cellulase from Trichoderma reesei SCB18 was used for simultaneous saccharification and fermentation of residues and hydrolysates from enzymatic hydrolysis for producing ethanol. The result showed that the CNC yield reached 7.35 % (w/w) by hydrolysis at 10 % solid content, and the final ethanol concentration was 13.27 mg/mL in fermentation liquor. Using SEM, XRD, TGA, and DLS methods, the characteristics of CNC including, morphology, crystallinity, thermal stability and particle size distribution, were also examined. This work provided a reference for realizing high-efficient application of cellulose in the pulp.

Analysis of an environmental epidemic model based on voluntary vaccination policy.

With the worsening of the environment and the increasing international trade, indirect transmission from exposure to contaminants in the surrounding environment has become an overlooked mode of transmission. This paper proposes a new game-theoretic model considering voluntary vaccination against imperfection and the unique integration of human-to-human and virus-to-human transmission routes. Based on the individual-based risk assessment update rule (IB-RA), the strategy-based risk assessment update rule (SB-RA), and the direct commitment update rule (DC), the different effects of individuals' behaviors on disease prevalence are analyzed. To find the effect of indirect transmission on epidemic transmission, we compare our model with the traditional SVIR model. Finally, it can be seen that indirect transmission mechanisms will aggravate the spread of epidemics.

Preparation of cellulose nanocrystals from commercial dissolving pulp using an engineered cellulase system.

There is increasing attention to the production of cellulose nanocrystals (CNCs) from lignocellulosic biomass by enzymatic hydrolysis with cellulase. In this study, the feasibility of the application of a cellulase system from engineered strain Penicillium oxalicum cEES in the production of CNCs was assessed. Using commercial eucalyptus dissolving pulp (EDP) as substrate, the CNCs were successfully obtained by enzymatic hydrolysis with the cellulase cEES, and the total yields of CNCs reached 15.7% through three-step enzymatic hydrolysis of total 72 h (24 h for each step). The prepared CNCs were characterized and found that their crystallinity and thermal stability were higher than that of EDP. In the later stage of enzymatic hydrolysis, the process efficiency of enzymatic preparation of CNCs greatly decreased because of the high crystallinity of cellulosic substrate, and a simple homogenization treatment can promote the enzymatic hydrolysis, as well as produce fusiform CNCs with more uniform size and more fermentable sugar that could be further converted into fuels and bulk chemicals through fermentation. This study provides a feasible enzymatic preparation process for CNCs with engineered cellulase and commercial cellulosic materials.

The Potential Role of R4 Regulators of G Protein Signaling (RGS) Proteins in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a complex and heterogeneous disease that primarily results from impaired insulin secretion or insulin resistance (IR). G protein-coupled receptors (GPCRs) are proposed as therapeutic targets for T2DM. GPCRs transduce signals via the Gα protein, playing an integral role in insulin secretion and IR. The regulators of G protein signaling (RGS) family proteins can bind to Gα proteins and function as GTPase-activating proteins (GAP) to accelerate GTP hydrolysis, thereby terminating Gα protein signaling. Thus, RGS proteins determine the size and duration of cellular responses to GPCR stimulation. RGSs are becoming popular targeting sites for modulating the signaling of GPCRs and related diseases. The R4 subfamily is the largest RGS family. This review will summarize the research progress on the mechanisms of R4 RGS subfamily proteins in insulin secretion and insulin resistance and analyze their potential value in the treatment of T2DM.

Pretreatment Strategies to Enhance Enzymatic Hydrolysis and Cellulosic Ethanol Production for Biorefinery of Corn Stover.

There is a rising interest in bioethanol production from lignocellulose such as corn stover to decrease the need for fossil fuels, but most research mainly focuses on how to improve ethanol yield and pays less attention to the biorefinery of corn stover. To realize the utilization of different components of corn stover in this study, different pretreatment strategies were used to fractionate corn stover while enhancing enzymatic digestibility and cellulosic ethanol production. It was found that the pretreatment process combining dilute acid (DA) and alkaline sodium sulfite (ASS) could effectively fractionate the three main components of corn stover, i.e., cellulose, hemicellulose, and lignin, that xylose recovery reached 93.0%, and that removal rate of lignin was 85.0%. After the joint pretreatment of DA and ASS, the conversion of cellulose at 72 h of enzymatic hydrolysis reached 85.4%, and ethanol concentration reached 48.5 g/L through fed-batch semi-simultaneous saccharification and fermentation (S-SSF) process when the final concentration of substrate was 18% (w/v). Pretreatment with ammonium sulfite resulted in 83.8% of lignin removal, and the conversion of cellulose and ethanol concentration reached 86.6% and 50 g/L after enzymatic hydrolysis of 72 h and fed-batch S-SSF, respectively. The results provided a reference for effectively separating hemicellulose and lignin from corn stover and producing cellulosic ethanol for the biorefinery of corn stover.