NY-ESO-1-specific T cell receptor-engineered T cells and Tranilast, a TRPV2 antagonist bivalent treatment enhances the killing of esophageal cancer: a dual-targeted cancer therapeutic route.

BACKGROUND: Esophageal cancer (EC) is a global canker notorious for causing high mortality due to its relentless incidence rate, convoluted with unyielding recurrence and metastasis. However, these intricacies of EC are associated with an immoderate expression of NY-ESO-1 antigen, presenting a lifeline for adoptive T cell therapy. We hypothesized that naturally isolated higher-affinity T cell receptors (TCRs) that bind to NY-ESO-1 would allow T lymphocytes to target EC with a pronounced antitumor response efficacy. Also, targeting TRPV2, which is associated with tumorigenesis in EC, creates an avenue for dual-targeted therapy. We exploited the dual-targeting antitumor efficacy against EC. METHODS: We isolated antigen-specific TCRs (asTCRs) from a naive library constructed with TCRs obtained from enriched cytotoxic T lymphocytes. The robustness of our asTCRs and their TCR-T cell derivatives, Tranilast (TRPV2 inhibitor), and their bivalent treatment were evaluated with prospective cross-reactive human-peptide variants and tumor cells. RESULTS: Our study demonstrated that our naive unenhanced asTCRs and their TCR-Ts perpetuated their cognate HLA-A*02:01/NY-ESO-1(157-165) specificity, killing varying EC cells with higher cytotoxicity compared to the known affinity-enhanced TCR (TCRe) and its wild-type (TCR0) which targets the same NY-ESO-1 antigen. Furthermore, the TCR-Ts and Tranilast bivalent treatment showed superior EC killing compared to any of their monovalent treatments of either TCR-T or Tranilast. CONCLUSION: Our findings suggest that dual-targeted immunotherapy may have a superior antitumor effect. Our study presents a technique to evolve novel, robust, timely therapeutic strategies and interventions for EC and other malignancies.

A Rationally Designed CRISPR/Cas12a Assay Using a Multimodal Reporter for Various Readouts.

The CRISPR/Cas systems offer a programmable platform for nucleic acid detection, and CRISPR/Cas-based diagnostics (CRISPR-Dx) have demonstrated the ability to target nucleic acids with greater accuracy and flexibility. However, due to the configuration of the reporter and the underlying labeling mechanism, almost all reported CRISPR-Dx rely on a single-option readout, resulting in limitations in end-point result readouts. This is also associated with high reagent consumption and delays in diagnostic reports due to protocol differences. Herein, we report for the first time a rationally designed Cas12a-based multimodal universal reporter (CAMURE) with improved sensitivity that harnesses a dual-mode reporting system, facilitating options in end-point readouts. Through systematic configurations and optimizations, our novel universal reporter achieved a 10-fold sensitivity enhancement compared to the DETECTR reporter. Our unique and versatile reporter could be paired with various readouts, conveying the same diagnostic results. We applied our novel reporter for the detection of staphylococcal enterotoxin A due to its high implication in staphylococcal food poisoning. Integrated with loop-mediated isothermal amplification, our multimodal reporter achieved 10 CFU/mL sensitivity and excellent specificity using a real-time fluorimeter, in-tube fluorescence, and lateral flow strip readouts. We also propose, using artificially contaminated milk samples, a fast (2-5 min) Triton X-100 DNA extraction approach with a comparable yield to the commercial extraction kit. Our CAMURE could be leveraged to detect all gene-encoding SEs by simply reprogramming the guide RNA and could also be applied to the detection of other infections and disease biomarkers.

Sulforaphane activates anti-inflammatory microglia, modulating stress resilience associated with BDNF transcription.

Sulforaphane (SFN) is an organic isothiocyanate and an NF-E2-related factor-2 (Nrf2) inducer that exerts prophylactic effects on depression-like behavior in mice. However, the underlying mechanisms remain poorly understood. Brain-derived neurotrophic factor (BDNF), a neurotrophin, is widely accepted for its antidepressant effects and role in stress resilience. Here, we show that SFN confers stress resilience via BDNF upregulation and changes in abnormal dendritic spine morphology in stressed mice, which is accompanied by rectifying the irregular levels of inflammatory cytokines. Mechanistic studies demonstrated that SFN activated Nrf2 to promote BDNF transcription by binding to the exon I promoter, which is associated with increased Nrf2, and decreased methyl-CpG binding protein-2 (MeCP2), a transcriptional suppressor of BDNF, in BV2 microglial cells. Furthermore, SFN inhibited the pro-inflammatory phenotype and activated the anti-inflammatory phenotype of microglia, which was associated with increased Nrf2 and decreased MeCP2 expression in microglia of stressed mice. Hence, our findings support that Nrf2 induces BDNF transcription via upregulation of Nrf2 and downregulation of MeCP2 in microglia, which is associated with changes in the morphology of damaged dendritic spines in stressed mice. Meanwhile, the data presented here provide evidence for the application of SFN as a candidate for the prevention and intervention of depression.

Expression of Human Uncoupling Protein-1 in Escherichia coli Decreases its Survival Under Extremely Acidic Conditions.

Uncoupling protein-1 (UCP1), located at the inner membrane of mitochondria, is expressed primarily in brown adipose tissue and mediates the permeability of protons through the inner mitochondrial membrane. This research examines whether human UCP1 can uncouple oxidative phosphorylation in E. coli. Recombinant human UCP1 that includes an N terminus signal peptide for the bacterial inner membrane was expressed in E. coli. Our testing showed that UCP1 functions as a proton transporter in the bacterial membrane, increasing its permeability, decrease ATP synthesis at neutral pH and reducing the viability of E. coli in markedly acidic environments. These results suggest that UCP1 can uncouple oxidative phosphorylation in E. coli. The decreased acid resistance (AR) of E. coli with UCP1 expressed in the membranes confirmed that oxidative phosphorylation plays a role in AR through the pumping of protons to regulate the intracellular pH, and demonstrate that UCP1 can be used as an uncoupler protein for bacterial metabolic research.

Effects of national ecological restoration projects on carbon sequestration in China from 2001 to 2010.

The long-term stressful utilization of forests and grasslands has led to ecosystem degradation and C loss. Since the late 1970s China has launched six key national ecological restoration projects to protect its environment and restore degraded ecosystems. Here, we conducted a large-scale field investigation and a literature survey of biomass and soil C in China's forest, shrubland, and grassland ecosystems across the regions where the six projects were implemented (∼16% of the country's land area). We investigated the changes in the C stocks of these ecosystems to evaluate the contributions of the projects to the country's C sink between 2001 and 2010. Over this decade, we estimated that the total annual C sink in the project region was 132 Tg C per y (1 Tg = 1012 g), over half of which (74 Tg C per y, 56%) was attributed to the implementation of the projects. Our results demonstrate that these restoration projects have substantially contributed to CO2 mitigation in China.

Ralstonia solanacearum fatty acid composition is determined by interaction of two 3-ketoacyl-acyl carrier protein reductases encoded on separate replicons.

BACKGROUND: FabG is the only known enzyme that catalyzes reduction of the 3-ketoacyl-ACP intermediates of bacterial fatty acid synthetic pathways. However, there are two Ralstonia solanacearum genes, RSc1052 (fabG1) and RSp0359 (fabG2), annotated as encoding putative 3-ketoacyl-ACP reductases. Both FabG homologues possess the conserved catalytic triad and the N-terminal cofactor binding sequence of the short chain dehydrogenase/reductase (SDR) family. Thus, it seems reasonable to hypothesize that RsfabG1 and RsfabG2 both encode functional 3-ketoacyl-ACP reductases and play important roles in R. solanacearum fatty acid synthesis and growth. METHODS: Complementation of Escherichia coli fabG temperature-sensitive mutant with R. solanacearum fabGs encoded plasmids was carried out to test the function of RsfabGs in fatty acid biosynthesis. RsFabGs proteins were purified by nickel chelate chromatography and fatty acid biosynthetic reaction was reconstituted to investigate the 3-ketoacyl-ACP reductase activity of RsFabGs in vitro. Disruption of both RsfabG genes was done via DNA homologous recombination to test the function of both RsfabG in vivo. And more we also carried out pathogenicity tests on tomato plants using RsfabG mutant strains.  RESULTS: We report that expression of either of the two proteins (RsFabG1 and RsFabG2) restores growth of the E. coli fabG temperature-sensitive mutant CL104 under non-permissive conditions. In vitro assays demonstrate that both proteins restore fatty acid synthetic ability to extracts of the E. coli strain. The RsfabG1 gene carried on the R. solanacearum chromosome is essential for growth of the bacterium, as is the case for fabG in E. coli. In contrast, the null mutant strain with the megaplasmid-encoded RsfabG2 gene is viable but has a fatty acid composition that differs significantly from that of the wild type strain. Our study also shows that RsFabG2 plays a role in adaptation to high salt concentration and low pH, and in pathogenesis of disease in tomato plants. CONCLUSION: R. solanacearum encodes two 3-ketoacyl-ACP reductases that both have functions in fatty acid synthesis. We supply the first evidence that, like other enzymes in the bacterial fatty acid biosynthetic pathway, one bacterium may simultaneously possess two or more 3-oxoacyl-ACP reductase isozymes.

Potential Target of CDK6 Signaling Pathway for Cancer Treatment.

BACKGROUND: Cancer involves uncontrolled cell growth due to genetic mutations. Tumors can form when CDK6, a gene essential for controlling cell growth, isn't working correctly. Researchers are investigating drugs that inhibit CDK6; some of them appear promising. Nevertheless, CDK6 is advantageous and harmful to cancer because it controls other cellular processes. By inhibiting CDK6 and CDK4, CDK4/6 inhibitors offer a novel therapeutic strategy that stops cell proliferation. The study investigates the function of CDK6 in cancer, the difficulties in targeting CDK6, and possible remedies. OBJECTIVE: Scientists have developed drugs designed to block CDK6 and prevent it from altering other proteins. These drugs, also known as CDK6 inhibitors, help treat cancer. Finding the best drugs for CDK6 is still tricky, though. The drugs' selectivity, potency, and cost are some difficulties. These factors depend on CDK6's structure and interactions with other proteins. The structure of CDK6 and how it influences its function and regulation are explained in this review. It also describes CDK6's function in cancer and its interaction with other molecules and proteins, which is crucial for cell division. Moreover, this review describes how CDK6 interacts with the drugs that block it and what the current and future treatments that target CDK6 are. CONCLUSION: This review presents the structure, current research, and overview of CDK6. It also reviews the role of CDK6 in cancer, function, and regulation. Additionally, it explores its role in cancer signaling networks and its interaction with CDK6 inhibitors. Lastly, it discusses the current status and prospects of therapies targeting CDK6.

Network Pharmacology-Based Virtual Screening of Chemical Constituents from Vitexnegundo Linn's Discovered Novel Molecular Targets for Breast Cancer Treatment.

BACKGROUND: The Chinese chaste tree Vitexnegundo (VN) is a popular herb in South and Southeast Asia that has several health benefits, including the ability to inhibit tumor growth and induce apoptosis in multiple tumors. Literature revealed scanty research on breast cancer, with little focus on the molecular mechanism of the disease and an emphasis on targets, biological networks, and active components. Exploring natural compounds as possible therapeutic options is an old but still promising approach for drug discovery and development. This study used a thorough computational and statistical method to screen potential drug candidates. METHODS: The active ingredients and targets of VN were identified using SwissADME, SwissTargetPrediction, STITCH, IMPPAT database, KNapSAcK database, and literature. The OMIM and GeneCards databases were searched for possible targets related to breast cancer. The PASS online server was used to check the probability of active metabolite (Pa) against breast cancer. To build protein-protein interactions (PPI) networking, the intersection of disease and drug targets was uploaded to the STITCH database. Cytoscape software was used to analyze the topology parameters of networking to identify hub targets. Gene Ontology (GO) was analyzed using Metascape and ShinyGO, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed using the David database and SR plot, and the site of expression and protein domain were studied using FunRich. We employed AutoDockvina, Discovery Studio, and UCSF ChimeraX software and auxiliary tools for molecular docking and analysis. Zincpharmer was used for pharmacophore mapping. ADMET analysis was conducted using ADMETsar, Swiss ADME, ADMETLab servers, and mypresto using GROMACS for molecular dynamics simulation (MDS). RESULTS: A total of 65 targets and 21 active ingredients were identified. Further investigation was conducted on 20 hub targets selected through PPI networking construction. The enrichment analysis results indicated that the key factors were P, amyloid-beta response, cellular response to amyloid- beta, Pos. reg. of G2/M transition of the mitotic cell cycle, and response to a toxic substance. The molecular docking, pharmacophore mapping, and MD simulation results indicated that apigenin, kaempferol, and luteolin positively interacted with CDK1 and CDK6 proteins. CONCLUSION: This study is the first to use network pharmacology, molecular docking, pharmacophore mapping, and MD simulation to identify the active ingredients, molecular targets, and critical biological pathways responsible for VN anti-breast cancer. The study provides a theoretical basis for further research in this area.

STING agonist diABZI enhances the cytotoxicity of T cell towards cancer cells.

Antigen-specific T cell receptor-engineered T cell (TCR-T) based immunotherapy has proven to be an effective method to combat cancer. In recent years, cross-talk between the innate and adaptive immune systems may be requisite to optimize sustained antigen-specific immunity, and the stimulator of interferon genes (STING) is a promising therapeutic target for cancer immunotherapy. The level of expression or presentation of antigen in tumor cells affects the recognition and killing of tumor cells by TCR-T. This study aimed at investigating the potential of innate immune stimulation of T cells and engineered T cells to enhance immunotherapy for low-expression antigen cancer cells. We systematically investigated the function and mechanism of cross-talk between STING agonist diABZI and adaptive immune systems. We established NY-ESO-1 full knockout Mel526 cells for this research and found that diABZI activated STING media and TCR signaling pathways. In addition, the results of flow cytometry showed that antigens presentation from cancer cells induced by STING agonist diABZI also improved the affinity of TCR-T cells function against tumor cells in vitro and in vivo. Our findings revealed that diABZI enhanced the immunotherapy efficacy of TCR-T by activating STING media and TCR signaling pathways, improving interferon-γ expression, and increasing antigens presentation of tumor cells. This indicates that STING agonist could be used as a strategy to promote TCR-T cancer immunotherapy.

Small RNA sequencing provides insights into molecular mechanism of flower development in Rhododendron pulchrum Sweet.

Rhododendron pulchrum sweet, a member of the Ericaceae family possessing valuable horticultural properties, is widely distributed in the temperate regions. Though serving as bioindicator of metal pollution, the molecular mechanism regulating flowering in R. pulchrum is very limited. Illumina sequencing was performed to identify critical miRNAs in the synthesis of flavonoids at different developmental stages. Totally, 722 miRNAs belonging to 104 families were screened, and 84 novel mature miRNA sequences were predicted. The miR166, miR156, and miR167-1 families were dominant. In particular, 126 miRNAs were significantly differentially expressed among four different flowering stages. Totally, 593 genes were differentially regulated by miRNAs during the flower development process, which were mostly involved in "metabolic pathways", "plant hormone signal transduction", and "mitosis and regulation of biosynthetic processes". In pigment biosynthesis and signal transduction processes, gra-miR750 significantly regulated the expression of flavonoid 3',5'-hydroxylase; aof-miR171a, aof-miR171b, aof-miR171c, cas-miR171a-3p, and cas-miR171c-3p could regulate the expression of DELLA protein; aof-miR390, aof-miR396b, ath-miR3932b-5p, cas-miR171a-3p, aof-miR171a, and aof-miR171b regulated BAK1 expression. This research showed great potentials for genetic improvement of flower color traits for R. pulchrum and other Rhododendron species.

InSitu Integrated Fabrication for Multi-Interface Stabilized and Highly Durable Polyaniline@Graphene Oxide/Polyether Ether Ketone Special Separation Membranes.

Special separation membranes are widely employed for separation and purification purposes under challenging operating conditions due to their low energy consumption, excellent solvent, and corrosion resistance. However, the development of membranes is limited by corrosion-resistant polymer substrates and precise interfacial separation layers. Herein, polyaniline (PANI) is employed to achieve insitu anchoring of multiple interfaces, resulting in the fabrication of polyaniline@graphene oxide/polyether ether ketone (PANI@GO/PEEK) membranes. Insitu growth of PANI achieves the adequate bonding of the PEEK substrate and GO separation interface, which solves the problem of solution processing of PEEK and the instability of GO layers. By bottom-up confined polymerization of aniline, it could control the pore size of the separation layer, correct defects, and anchor among polymer, nano-separation layer, and nano-sheet. The mechanism of membrane construction within the confined domain and micro-nano structure modulation is further explored. The membranes demonstrate exceptional stability realizing over 90% rejection in 2 m HCl, NaOH, and high temperatures. Additionally, -membranes exhibit remarkable durability after 240 days immersion and 100 h long-term operation, which display the methanol flux of 50.2 L m-2 h-1 and 92% rejection of AF (585 g mol-1 ). This method substantially contributes to special separation membranes by offering a novel strategy.

Large-scale expansion of human umbilical cord-derived mesenchymal stem cells using PLGA@PLL scaffold.

Mesenchymal stem cells (MSCs) are highly important in biomedicine and hold great potential in clinical treatment for various diseases. In recent years, the capabilities of MSCs have been under extensive investigation for practical application. Regarding therapy, the efficacy usually depends on the amount of MSCs. Nevertheless, the yield of MSCs is still limited due to the traditional cultural methods. Herein, we proposed a three-dimensional (3D) scaffold prepared using poly lactic-co-glycolic acid (PLGA) nanofiber with polylysine (PLL) grafting, to promote the growth and proliferation of MSCs derived from the human umbilical cord (hUC-MSCs). We found that the inoculated hUC-MSCs adhered efficiently to the PLGA scaffold with good affinity, fast growth rate, and good multipotency. The harvested cells were ideally distributed on the scaffold and we were able to gain a larger yield than the traditional culturing methods under the same condition. Thus, our cell seeding with a 3D scaffold could serve as a promising strategy for cell proliferation in the large-scale production of MSCs. Moreover, the simplicity and low preparation cost allow this 3D scaffold to extend its potential application beyond cell culture. Supplementary Information: The online version contains supplementary material available at 10.1186/s40643-023-00635-6.

Harnessing enhanced CRISPR/Cas12a trans-cleavage activity with extended reporters and reductants for early diagnosis of Helicobacter pylori, the causative agent of peptic ulcers and stomach cancer.

Developing rapid and non-invasive diagnostics for Helicobacter pylori (HP) is imperative to prevent associated diseases such as stomach gastritis, ulcers, and cancers. Owing to HP strain heterogeneity, not all HP-infected individuals incur side effects. Cytotoxin-associated gene A (CagA), and vacuolating cytotoxin A (VacA) genes predominantly drive HP pathogenicity. Therefore, diagnosing CagA and VacA genotypes could alert active infection and decide suitable therapeutics. We report an enhanced LbCas12a trans-cleavage activity with extended reporters and reductants (CEXTRAR) for early detection of HP. We demonstrate that extended ssDNA reporter acts as an excellent signal amplifier, making it a potential alternative substrate for LbCas12a collateral activity. Through a systematic investigation of various buffer components, we demonstrate that reductants improve LbCas12a trans-cleavage activity. Overall, our novel reporter and optimal buffer increased the trans-cleavage activity to an order of 16-fold, achieving picomolar sensitivity (171 pM) without target pre-amplification. Integrated with loop-mediated isothermal amplification (LAMP), CEXTRAR successfully attained attomolar sensitivity for HP detection using real-time fluorescence (43 and 96 aM), in-tube fluorescence readouts (430 and 960 aM), and lateral flow (4.3 and 9.6 aM) for CagA and VacA, respectively. We also demonstrate a rapid 2-min Triton X-100 lysis for clinical sample analysis, which could provide clinicians with actionable information for rapid diagnosis. CEXTRAR could potentially spot the 13C urea breath test false-negatives. For the first time, our study unveils an experimental outlook to manipulate reporters and reconsider precise cysteine substitution via protein engineering for Cas variants with enhanced catalytic activities for use in diagnostics and genetic engineering.

Complete plastome sequence of Monoon laui (Merr.) B. Xue and R.M.K. Saunders, 2012: an endemic species in Hainan.

Monoon laui (Merr.) B. Xue and R.M.K. Saunders 2012 is produced in Hainan province. The trunk is straight, the wood texture is straight, and the material is slightly soft, which is suitable for furniture and building materials. In our study, we report and characterize the complete plastome of M. laui The complete length of the plastome of M. laui possesses 161,181 bp, including a large single-copy (LSC) of 89,556 bp, small single-copy (SSC) of 18,977 bp, and two inverted repeats (IRs) of 26,313 bp. The overall G/C content in the plastome of M. laui is 39.13%. The plastome contains 257 genes, consisting of 130 protein-coding genes (16 of which are duplicated in the IR), 37 tRNA genes (seven of which are duplicated in the IR), and eight rRNA genes (5S rRNA, 4.5S rRNA, 16S rRNA, and 23S rRNA). Here, we explore the phylogenetic relationships and make contributions to the conservation genetics of the specie of M. laui using the complete plastome sequence.

Based On Confined Polymerization: In Situ Synthesis of PANI/PEEK Composite Film in One-Step.

Confined polymerization is an effective method for precise synthesis, which can further control the micro-nano structure inside the composite material. Polyaniline (PANI)-based composites are usually prepared by blending and original growth methods. However, due to the strong rigidity and hydrogen bonding of PANI, the content of PANI composites is low and easy to agglomerate. Here, based on confined polymerization, it is reported that polyaniline /polyether ether ketone (PANI/PEEK) film with high PANI content is synthesized in situ by a one-step method. The micro-nano structure of the two polymers in the confined space is further explored and it is found that PANI grows in the free volume of the PEEK chain, making the arrangement of the PEEK chain more orderly. Under the best experimental conditions, the prepared 16 µm-PANI/PEEK film has a dielectric constant of 205.4 (dielectric loss 0.401), the 75 µm-PANI/PEEK film has a conductivity of 3.01×10-4 S m-1 . The prepared PANI/PEEK composite film can be further used as electronic packaging materials, conductive materials, and other fields, which has potential application prospects in anti-static, electromagnetic shielding materials, corrosion resistance, and other fields.

ATP requirement for acidic resistance in Escherichia coli.

ATP participates in many cellular metabolic processes as a major substrate to supply energy. Many systems for acidic resistance (AR) under extremely acidic conditions have been reported, but the role of ATP has not been examined. To clarify whether or not ATP is necessary for the AR in Escherichia coli, the AR of mutants deficient in genes for ATP biosynthesis was investigated in this study. The deletion of purA or purB, each of which encodes enzymes to produce AMP from inosinate (IMP), markedly decreased the AR. The content of ATP in these mutants decreased rapidly at pH 2.5 compared to that of the wild type. The AR was again decreased significantly by the mutation of adk, which encoded an enzyme to produce ADP from AMP. The DNA damage in the purA and purB mutants was higher than that in the wild type. These results demonstrated that metabolic processes that require ATP participate in survival under extremely acidic conditions, and that one such system is the ATP-dependent DNA repair system.

Efficacy and Safety of Traditional Chinese Medicine in the Treatment of Immune Infertility Based on the Theory of "Kidney Deficiency and Blood Stasis": A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aims to evaluate the efficacy and safety of traditional Chinese medicine (TCM) therapy of tonifying kidney and activating blood circulation (TKABC) based on the theory of "kidney deficiency and blood stasis" for the treatment of immune infertility. METHODS: Six electronic databases, including the Cochrane Library, PubMed, EMBASE, the China National Knowledge Infrastructure, Wanfang Data, and VIP information database, were searched from inception to January 2021 to identify eligible studies of randomized controlled trials (RCTs). The primary outcome measurements were the total effective rate and pregnancy rate, and the secondary outcome measurements included the negative conversion rate of serum antibodies and the incidence of adverse effects. The quantitative synthesis was performed using the Review Manager 5.3 software. The chi-square statistic and I 2 statistic were employed to investigate statistical heterogeneity. The fixed-effects model was used for a low heterogeneity (I 2 < 50%), and the random-effects model was applied if heterogeneity was moderate (50% < I 2 < 75%). Funnel plots were used to evaluate potential reporting bias when more than ten eligible studies were included. RESULTS: Thirteen RCTs involving 1298 patients with immune infertility of kidney deficiency and blood stasis were included. Compared with conventional group, TCM TKABC therapy showed a significant improvement on the total effective rate (RR: 1.38; 95% CI: 1.30,1.47; and I 2 = 0%), pregnancy rate (RR: 2.04; 95% CI: 1.73, 2.40; and I 2 = 30%), negative conversion rates of AsAb (RR: 1.42; 95% CI: 1.12,1.79; and I 2 = 62%), AEmAb rates (RR: 1.21; 95% CI: 1.04,1.41; and I2 = 0%), and AhCGAb with less adverse effects (RR: 0.24; 95% CI: 1.73, 2.40; and I 2 = 55%). However, the negative conversion rate of AoAb and ACAb showed no significant statistical difference. CONCLUSIONS: Our review suggests that TCM TKABC therapy based on the theory of kidney deficiency and blood stasis appears to be an effective and safe approach for patients with immune infertility. However, the methodological quality of included RCTs was unsatisfactory, and it is necessary to verify its effectiveness with more well-designed and high-quality multicenter RCTs.

Escherichia Coli Increases its ATP Concentration in Weakly Acidic Environments Principally through the Glycolytic Pathway.

Acid resistance is an intrinsic characteristic of intestinal bacteria in order to survive passage through the stomach. Adenosine triphosphate (ATP), the ubiquitous chemical used to power metabolic reactions, activate signaling cascades, and form precursors of nucleic acids, was also found to be associated with the survival of Escherichia coli (E. coli) in acidic environments. The metabolic pathway responsible for elevating the level of ATP inside these bacteria during acid adaptation has been unclear. E. coli uses several mechanisms of ATP production, including oxidative phosphorylation, glycolysis and the oxidation of organic compounds. To uncover which is primarily used during adaptation to acidic conditions, we broadly analyzed the levels of gene transcription of multiple E. coli metabolic pathway components. Our findings confirmed that the primary producers of ATP in E. coli undergoing mild acidic stress are the glycolytic enzymes Glk, PykF and Pgk, which are also essential for survival under markedly acidic conditions. By contrast, the transcription of genes related to oxidative phosphorylation was downregulated, despite it being the major producer of ATP in neutral pH environments.

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The relationship between the structure and function of forest ecosystems is the main intere-sts in the research area of forest ecology and management. However, over complex terrains in particular, these studies had been challenged as uneasy tasks due to the limitations in the forest survey and measurement techniques and other supporting technologies. Chinese Academy of Sciences (CAS) funded "Multi-Tower LiDAR/ECFlux Platform for Monitoring the Structure and Function of Secondary Forest Ecosystems" (Multi-Tower Platform, MTP) as a field station network corner-stone research infrastructure project, which was completed by Qingyuan Forest CERN (Chinese Ecosystem Research Network). In a distinctively-bounded and monitored-outlet watershed, the MTP was integrated by light detection and ranging (LiDAR) scanners, eddy covariance (EC) flux instrument systems, whole- and sub-watershed hydrology station network, long-term forest plot arrays, and live data center. Using LiDAR scanning, the MTP can get cloud data for holographic information on canopy structure. The EC-flux instrument system and hydrology station network along with forest plot arrays could ensure the reliability of water and carbon observations over this complex terrain, which allows to verify the studies on flux measurement technologies and methods, as well as to understand the processes of ecohydrology and CO2 exchange between forest ecosystem and the atmosphere. Further, we can also assess the primary ecosystem services, including water conservation and carbon sequestration. All the data from "tower-station" were streamed through wireless network, which would facilitate data monitoring, management, and sharing. There are three tasks of MTP team: 1) defining innovative methods and descriptors to quantify three-dimensional forest structure; 2) developing theories and techniques to measure CO2/H2O fluxes and other trace gases over complex terrains; 3) understanding the relationship between structure and function of forest ecosystems, providing information and rationales for forest management practices to assure broad and sustainable benefits from forests.

High-level expression of Humicola insolens cutinase in Pichia pastoris without carbon starvation and its use in cotton fabric bioscouring.

Huimcola insolens cutinase (HiC) was heterologously expressed in Pichia pastoris. To avoid a carbon starvation step, fermentation was conducted using combinations of sorbitol with glycerol and methanol in the cell growth and induction phases, respectively. The cutinase productivity (27.71 U mL-1 h-1) was 9.93 U mL-1 h-1 greater than that achieved using traditional two-phase methods, and a cutinase activity of 2660 U mL-1, using p-nitrophenyl butyrate as substrate, was achieved after only 96 h in a 3-L bioreactor. Subsequently, the combination of HiC with Thermobifida fusca cutinase (TfC) in cotton fabric bioscouring was evaluated by monitoring the wettability and dyeability of the fabric. Treatment with 20 U mL-1 of HiC at 80 °C for 5 min followed by 30 U mL-1 of TfC at 50 °C for 1 h gave the best results. The total treatment time was shorter and performance was better than those seen with the alkali method.