Decreased LDHB expression in breast tumor cells causes NK cell activation and promotes tumor progression

Objective: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B(LDHB) has been detected in breast cancer but the function of LDHB remains unknown.Methods: Western blot was used to analyze LDHB expression in breast cancer cells. The impact of LDHB on tumor cell migration and invasion was determined using Transwell assays, wound healing assays, and a mouse lung metastasis model. Subcutaneous tumor formation, a natural killer(NK) cell cytotoxicity assay, and flow cytometry evaluated NK cell activation. Immunofluorescence and quantitative real-time PCR detected NK cell activation markers. Kaplan-Meier analysis evaluated the effect of immune cell infiltration on prognosis. Single-sample gene set enrichment analysis determined NK cell activation scores. A support vector machine predicted the role of LDHB in NK cell activation.Results: In this study we showed that LDHB inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that LDHB-mediated lactic acid clearance in breast cancer cells triggers NK cell activation within the tumor microenvironment. Our findings, which were confirmed in a murine model, demonstrated that LDHB in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that LDHB affects immune cell infiltration and function. Specifically, its expression has been linked to enhanced NK cell-mediated cytotoxicity and improved patient survival. Furthermore, we identified LDHB expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some cancers.Conclusions: Our results suggest that LDHB is a promising target for activating the tumor immune microenvironment in breast cancer, where LDHB-associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of LDHB in regulating immune responses and its potential as a therapeutic target for breast cancer.

Veratrilla baillonii Franch alleviate the symptoms of diabetes in type 2 diabetic rats induced by high-fat diet and streptozotocin

Our previous research studies have shown that Veratrilla baillonii Franch,a food supplement used by ethnic minorities in Southwest China,has multiple pharmacological activities,such as detoxification,antiinflammatory,antioxidant,and anti-insulin resistance.However,the detailed signal pathways for its salutary effect on damages in multiple organs due to type 2 diabetes mellitus(T2DM)remains unclear.The current study is to evaluate the therapeutic effects of V.baillonii on T2DM rats and to explore the underlying mechanisms.The T2DM rat model was successfully established by a high-sugar and high-fat diet(HFD)combination with intraperitoneal injection of a small dose of streptozotocin(STZ,35 mg/kg).Biochemical analysis and histopatholgical examinations were conducted to evaluate the anti-diabetic potential of water extracts of V.baillonii(WVBF).The results showed that the WVBF treatment can improve hyperglycemia and insulin resistance,ameliorate the liver,kidney and pancreas injuries via decreasing inflammatory cytokines such as IL-6 and TNF-α,and oxidative damages.Further investigation suggested that WVBF modulates the signal transductions of the IRS1/PI3K/AKT/GLUT4 and AMPK pathways.These findings demonstrate potentials of WVBF in the treatment of T2DM and possible mechanisms for its hepatoprotective activities.

基于PMA-LAMP技术可视化检测消毒产品消毒效果

探讨建立一种氮溴化丙锭(Propidium monoazide,PMA)染料与环介导等温扩增法(Loop-mediated isothermal amplification,LAMP)联用的技术,实现可视化判断消毒产品消毒效果的目的。随机选取5种成分不同的市售消毒产品,回收消毒产品消毒处理后的菌液并进行PMA处理,并对处理后的菌液进行细菌基因组DNA提取。将大肠杆菌作为消毒效果检测的指示菌,针对大肠杆菌的fecA基因以及针对存在于所有细菌的16S rRNA基因进行LAMP扩增,并在反应体系中加入钙黄素染料。通过肉眼观察反应管颜色变化即可对消毒产品的消毒效果进行判断。将PMA-LAMP方法与PMA-qPCR方法进行比较后发现PMA-LAMP方法在操作步骤、检测时长、灵敏度方面均优于PMA-qPCR方法。在对消毒产品消毒效果的实际检测中,PMA-LAMP方法与《消毒技术规范(2002年版)》规定的标准方法的结果基本一致,两者杀灭对数值偏差在±0.5以内。该方法不依赖大型精密温控仪器,检测过程为45 min(不包括前处理步骤),实现了对消毒产品消毒效果现场快速可视化检测,具有良好的基层应用前景,将为消毒产品的性能评价提供参考、为行业市场监管提供技术支持。

Development of the general chapters of the Chinese Pharmacopoeia 2020 edition: A review

The Chinese Pharmacopoeia 2020 edition was reviewed and approved by the National Medical Products Administration and the National Health Commission of the People’s Republic of China in July 2020.The current edition was officially implemented on December 30,2020.The general chapters of the Chinese Pharmacopoeia discuss the general testing methods and guidelines,which are the common requirements and basis for the implementation of drug standards in the Chinese Pharmacopoeia.Owing to adherence to the principles of scientificity,versatility,operability,and sustainable development,there is an improvement in the general chapters of the 2020 edition over those of the previous editions.Further,the application of advanced and mature analytical techniques has expanded,the development of testing methods for exogenous pollutants in traditional Chinese medicines has been strengthened,and technical requirements are now better harmonized with international standards.The updated edition provides technical and methodological support to ensure safety,effectiveness,and control of pharmaceuticals in China and will play an important and active role in encouraging the application of advanced technologies,improving the quality control of medicines,and strengthening the means of drug regulation in China.This review provides a comprehensive introduction of the main features of and changes to the general chapters in the Chinese Pharmacopoeia 2020 edition and aims to provide reference for its correct understanding and accurate implementation.

Silicon prepared by electro-reduction in molten salts as new energy materials

Silicon has a large impact on the energy supply and economy in the modern world. In industry, high purity silicon is firstly prepared by carbothermic reduction of silica with the produced raw silicon being further refined by a modified Siemens method. This process suffers from the disadvantages of high cost and contaminant release and emission. As an alternative, the molten salt electrolysis approach, particularly the FFC Cambridge Process(FFC: Fray-Farthing-Chen), could realize high purity silicon products with morphology-controllable nanostructures at low or mild temperatures(generally 650–900 ℃). In this article, we review the development, reaction mechanisms, and electrolysis conditions of silicon production by the FFC Cambridge Process. Applications of the silicon products from electrolysis in molten salts are also discussed in terms of energy applications, including using them as the photovoltaic element in solar cells and as the charge storage phase in the negative electrode(negatrode) of lithium ion batteries.

Modulatory effects of Lactiplantibacillus plantarum on chronic metabolic diseases

The increased global incidence of chronic metabolic diseases,a vital threat to human health and a burden on our healthcare systems,includes a series of clinical metabolic syndromes such as obesity,diabetes,hypertension,and dyslipidemia.One of the well-known probiotic microorganisms,Lactiplantibacillus plantarum plays an important role in promoting human health,including inhibiting the occurrence and development of a variety of chronic metabolic diseases.The present study provides an overview of the preventive and therapeutic effects of L.plantarum on diabetes,obesity,non-alcoholic fatty liver disease,kidney stone disease,and cardiovascular diseases in animal models and human clinical trials.Ingesting L.plantarum demonstrated its ability to reduce inflammatory and oxidative stress levels by regulating the production of cytokines and short-chain fatty acids(SCFAs),the activity of antioxidant enzymes,and the balance of intestinal microbial communities to alleviate the symptoms of chronic metabolic diseases.Furthermore,updated applications and technologies of L.plantarum in food and biopharmaceutical industries are also discussed.Understanding the characteristics and functions of L.plantarum will guide the development of related probiotic products and explore the modulatory benefit of L.plantarum supplementations on the prevention and treatment of multiple chronic metabolic diseases.

Simulation of stimulated Raman scattering signal generation in scattering tissues excited by Bessel beams

Stimulated Raman scattering(SRS)microscopy has the ability of noninvasive imaging of specific chemical bonds and been increasingly used in biomedicine in recent years.Two pulsed Gaussian beams are used in traditional SRS microscopes,providing with high lateral and axial spatial resolution.Because of the tight focus of the Gaussian beam,such an SRS microscopy is difficult to be used for imaging deep targets in scattering tissues.The SRS microscopy based on Bessel beams can solve the imaging problem to a certain extent.Here,we establish a theoretical model to calculate the SRS signal excited by two Bessel beams by integrating the SRS signal generation theory with the fractal propagation method.The fractal model of refractive index turbulence is employed to generate the scattering tissues where the light transport is modeled by the beam propagation method.We model the scattering tissues containing chemicals,calculate the SRS signals stimulated by two Bessel beams,discuss the influence of the fractal model parameters on signal generation,and compare them with those generated by the Gaussian beams.The results show that,even though the modeling parameters have great influence on SRS signal generation,the Bessel beams-based SRS can generate signals in deeper scattering tissues.

Mechanochemical synthesis of oxygenated alkynyl carbon materials with excellent Hg(Ⅱ) adsorption performance from CaC2 and carbonates

Adsorptive removal of heavy metal ions from wastewater is very important,and the key is the development of efficient sorbents.In this work,oxygenated alkynyl carbon materials(OACMs)were synthesized via mechanochemical reaction of CaC_(2) and a carbonate(CaCO_(3),Na2CO_(3),or NaHCO_(3))at ambient temperature.The resultant OACMs are micro mesoporous carbon nanomaterials with high specific area(>648 m2 g^(-1)),highly crosslinked texture,and rich alkynyl and oxygenated groups.The OACMs exhibit excellent Hg(Ⅱ)adsorption due to the soft acid-soft base interaction between alkynyl and Hg(Ⅱ),and OACM-3 derived from CaC_(2) and NaHCO_(3) has the saturated Hg(Ⅱ)adsorbance of 483.9 mg g^(-1)along with good selectivity and recyclability.The adsorption is mainly chemisorption following the Langmuir mode.OACM-3 also shows high adsorbance for other heavy metal ions,e.g.256.6 mg g^(-1)for Pb(II),232.4 mg g^(-1)for Zn(II),and 198.7 mg g^(-1)for Cu(II).This work expands the mechnochemical reaction of CaC_(2)with carbonates and possibly other oxyanionic salts,provides a new synthesis approach for functional alkynyl carbon materials with excellent adsorption performance for heavy metal ions,as well as a feasible approach for CO2 resource utilization.

Supercontinuum fiber laser-based coherent anti-Stokes Raman scattering microscopy for label-free chemical imaging

Coherent anti-Stokes Raman scattering(CA RS)microscopy can resolve the chemical compo-nents and distribution of living biological systems in a label-firee manner and is favored in several disciplines.Current CA RS microscopes typically use bulky,high-performance solid-state lasers,which are expensive and sensitive to environmental changes.With their relatively low cost and environmental sensitivity,supercontinum fiber(SF)lasers with a small footprint have found increasing use in biomedical applications.Upon these features,in this paper,we homebuilt a low-cost CARS microscope based on a SF laser module(scCA RS microscope).This SF laser module is specially customized by adding a time synchronized seed source channel to the SF laser to form a dual-channel output laser.The performance of the scCARS microscope is evaluated with dimethyl sulfoxide,whose results confirm a spatial resolution of better than 500nm and a detection sensitivity of millimolar concentrations.The dual-color imaging capability is further demonstrated by imaging different species of mixed microspheres.We finally explore the potential of our scCARS microscope by mapping lipid droplets in different cancer cells and corneal stromal lenses.

Study on Polyphenol Oxidase Activity and Total Phenol Content of Docynia indica

[Objectives] To study the polyphenol oxidase (PPO) activity and total phenol content of Docynia indica .[Methods] The tender branches and petioles of the medicinal and edible plant D. indica were used as experimental materials, and the annual changes of total phenol content and polyphenol oxidase (PPO) activity were analyzed.[Results] pH 7.0 was the optimum value of polyphenol oxidase activity in D. indica plants;the best substrate was catechol with the concentration of 0.15 mol/L;the optimum temperature was 25 ℃.[Conclusions] The total phenol content of D. indica plants was the lowest in April, May and September of each year. The polyphenol oxidase activity of D. indica plants at flowering and fruiting stage was significantly higher than that at pre-flowering stage.

Nano transdermal system combining mitochondria-targeting cerium oxide nanoparticles with all-trans retinoic acid for psoriasis

Psoriasis is an inflammatory skin disease that is intricately linked to oxidative stress.Antioxidation and inhibition of abnormal proliferation of keratinocytes are pivotal strategies for psoriasis.Delivering drugs with these effects to the site of skin lesions is a challenge that needs to be solved.Herein,we reported a nanotransdermal delivery system composed of all-trans retinoic acid(TRA),triphenylphosphine(TPP)-modified cerium oxide(CeO2)nanoparticles,flexible nanoliposomes and gels(TCeO_(2)-TRA-FNL-Gel).The results revealed that TCeO_(2)synthesized by the anti-micelle method,with a size of approximately 5 nm,possessed excellent mitochondrial targeting ability and valence conversion capability related to scavenging reactive oxygen species(ROS).TCeO_(2)-TRA-FNL prepared by the film dispersion method,with a size of approximately 70 nm,showed high drug encapsulation efficiency(>96%).TCeO_(2)-TRA-FNL-Gel further showed sustained drug release behaviors,great transdermal permeation ability,and greater skin retention than the free TRA.The results of in vitro EGF-induced and H2O2-induced models suggested that TCeO_(2)-TRA-FNL effectively reduced the level of inflammation and alleviated oxidative stress in HaCat cells.The results of in vivo imiquimod(IMQ)-induced model indicated that TCeO_(2)-TRA-FNL-Gel could greatly alleviate the psoriasis symptoms.In summary,the transdermal drug delivery system designed in this study has shown excellent therapeutic effects on psoriasis and is prospective for the safe and accurate therapy of psoriasis.

Study on Callus Induction and Tissue Culture Regeneration System of Malus toringoides

[Objectives]To study the culture of callus produced by the leaves of the ethnic medicine‘E Se’,the induction of adventitious buds and the regeneration system of tissue culture seedlings.[Methods]Multi-factor orthogonal experiment was used to design and analyze.[Results]The best medium for callus induction was MS+2.0 mg/L 6-BA+0.1 mg/L 2,4-D.By comparing the effects of cytokinin 6-BA,KT and TDZ on induction of adventitious bud differentiation,it was found that the optimum medium for adventitious bud regeneration was MS+0.5 mg/L 6-BA+0.5 mg/L KT+0.15 mg/L IBA.Finally,adding 0.2 mg/L IBA(0.1 or 0.2 mg/L)to MS medium could effectively make regenerated seedlings produce roots,and the efficiency was more than 70%.[Conclusions]It laid a foundation for the large-scale cultivation of the seedlings of the ethnic medicine‘E Se’and the promotion of their artificial cultivation.

Isothermal Adsorption and Desorption Properties of Marine Shales on Longmaxi Shale in South China

The investigation of adsorption and desorption properties of shale are important for estimating reserves and exploitation. The shale samples used in this paper were from the marine shale on Longmaxi shale in Sichuan and Hubei province, China. A series of analyses, such as organic carbon content test, vitrinite reflectance test, rock pyrolysis, X-ray diffraction, and N2/CO2 adsorption were performed. Gravimetric method with magnetic suspension balance was used to conduct isothermal adsorption and desorption experiments. The Langmuir, Freundlich, Langmuir-Freundlich, D-R, semi-pore, and Tothequations were used to fit the isothermal adsorption and desorption curves. And adsorption potential theory was used to explain the adsorption and desorption process. According to the results, the shale samples have a high level of organic carbon content with the same organic matter type II1 and high degree of maturation. The volume of adsorption increases rapidly and slows down to stable with the pressure increasing. Desorption is the inverse process of adsorption and 10 MPa - 0.5 MPa is the main period of shale gas desorption. The fitting results show that three-parameter isotherm equations are better than the two-parameter ones. The adsorption temperature has a great influence on adsorption volume, little effect on potential energy. Adsorption potential varies under different TOC to affect adsorption properties. Moreover, a large adsorption potential means that the gas molecule is easy to adsorb but difficult to desorb.

The Current Development and Theories about Dark Matter

Dark matter has been in the discussion of important theories for long time. As technology developed, more and more particles have been suggested to be the candidate of dark matter. This review will first discuss the observation evidence of the existence of dark matter in the aspect of cosmic microwave background, galaxy rotation curves, velocity dispersions and gravitational lensing. We then focus on some important collider researches, such as HL-LHC and CEPC about dark matter candidates: WIMPs. Finally, we extend the topic considering dark energy and inflation.

T cell receptor signaling and cell immunotherapy

As the major sensor of adaptive immune system,T cell receptor(TCR)can recognize diverse antigens and initiate specific immune responses against invading pathogens and cancer cells.Understanding the mechanisms of TCR signaling has led to the development of engineered T cell therapies,which have extensive applications in the treatment of diseases such as cancer,infection and autoimmunity.Here,we review the current understanding of antigen-induced TCR signaling and discuss its applications in T cell therapies.

L-鸟氨酸发酵菌种的代谢工程研究进展

L-鸟氨酸是一种非蛋白类氨基酸参与尿素代谢及生物多胺类的合成,其对人体具有治疗肝脏疾病、增强免疫力等作用,被广泛应用于医疗、保健、食品等领域。工业上生产鸟氨酸主要有化学法、酶法及工业发酵法。其中,发酵法因其生产成本及环境保护等方面的优势而逐渐成为研究的焦点。本文归纳了近年来采用基因工程技术选育鸟氨酸高产菌种最新研究进展,重点讨论了产鸟氨酸谷氨酸棒杆菌的代谢工程改造策略,并对未来的研究方向进行了预测。

Structural understanding of T cell receptor triggering

The T cell receptor(TCR)is one of the most complicated receptors in mammalian cells,and its triggering mechanism remains mysterious.As an octamer complex,TCR comprises an antigen-binding subunit(TCRαβ)and three CD3 signaling subunits(CD3ζζ,CD3δε,and CD3γε).Engagement of TCRαβwith an antigen peptide presented on the MHC leads to tyrosine phosphorylation of the immunoreceptor tyrosine-based activation motif(ITAM)in CD3 cytoplasmic domains(CDs),thus translating extracellular binding kinetics to intracellular signaling events.Whether conformational change plays an important role in the transmembrane signal transduction of TCR is under debate.Attracted by the complexity and functional importance of TCR,many groups have been studying TCR structure and triggering for decades using diverse biochemical and biophysical tools.Here,we synthesize these structural studies and discuss the relevance of the conformational change model in TCR triggering.

Production of L-glutamate family amino acids in Corynebacterium glutamicum:Physiological mechanism,genetic modulation,and prospects

L-glutamate family amino acids(GFAAs),consisting of L-glutamate,L-arginine,L-citrulline,L-ornithine,L-proline,L-hydroxyproline,γ-aminobutyric acid,and 5-aminolevulinic acid,are widely applied in the food,pharmaceutical,cosmetic,and animal feed industries,accounting for billions of dollars of market activity.These GFAAs have many functions,including being protein constituents,maintaining the urea cycle,and providing precursors for the biosynthesis of pharmaceuticals.Currently,the production of GFAAs mainly depends on microbial fermentation using Corynebacterium glutamicum(including its related subspecies Corynebacterium crenatum),which is substantially engineered through multistep metabolic engineering strategies.This review systematically summarizes recent advances in the metabolic pathways,regulatory mechanisms,and metabolic engineering strategies for GFAA accumulation in C.glutamicum and C.crenatum,which provides insights into the recent progress in L-glutamate-derived chemical production.

Study of CH_(4)and CO_(2)competitive adsorption on shale in Yibin,Sichuan Province of China

Shale gas is an unconventional gas source with substantial development potential.In this study,Longmaxi Formation shale from the Silurian system in Yibin,Sichuan Province was collected for characterizing total organic carbon(TOC),clay mineral content,and other reservoir properties.The pore structure of shale was analyzed by field-emission scanning electron microscopy and low-temperature N_(2) adsorption–desorption method.Isothermal adsorption experiments for CH_(4)and CO_(2)mixtures in shale samples were performed.The second Virial coefficient was used to calculate for the compressibility factor of the gas mixture.The influencing factors of gas adsorption capacity of shale were analyzed.Finally,the CH_(4)and CO_(2)adsorption capacities and selection of shale samples were investigated.Under low pressure,the total gas mixture capacity of shale samples was positively correlated with pressure.When the pressure increased to a certain extent,the growth trend of gas mixture adsorption capacity of shale samples decreased.The mixed gas adsorption volume is high at 50℃ for all the proportion.Given the same temperature and pressure,the CO_(2)adsorption of shale samples is higher than the CH_(4)adsorption.In competitive adsorption,shale prefers to adsorb CO_(2).Therefore,CO_(2)is easier to be adsorbed by shale and this causes CH_(4)to be released from the adsorption site.

Antibacterial activity of the ethyl acetate part of Abrus cantoniensis against Staphylococcus aureus

Objective:The aim of this work was to measure the antibacterial activity(against Escherichia coli and Staphylococcus aureus[S.aureus])of the ethyl acetate part of Abrus cantoniensis and assess their potential as medicines.Methods:The experiment was divided into four groups:negative control group[with Mueller-Hinton broth(MHB)],positive control group(with 75%ethanol),blank group(with MHB)and test group(with the ethyl acetate part of Abrus cantoniensis).The antibacterial activities of the extracts were evaluated by the Oxford cup assay and minimum inhibitory concentration(MIC).Time-kill curve experiments,scanning electron microscopy,the content of DNA,RNA and protein were used to study the antibacterial mechanism of the ethyl acetate extract part on the growth and viability of S.aureus.The study procedures were approved by the Animal Care and Use Committee of Xi’an Jiaotong University(approval No.XJTULAC2016-412)on January 22,2016.Results:The ethyl acetate part of Abrus cantoniensis extract exhibited the highest inhibitory activity against the growth of S.aureus with an inhibition zone diameter of 16.4mm and MIC value of 0.5mg/mL.The general activity range of the ethyl acetate part,determined using a time-killing curve,was found to be 0.5mg/mL to 40mg/mL(MIC to 80
MIC).Changes in the scanning electron microscopy images and of DNA,RNA and proteins of S.aureus indicated possible mechanisms of the inhibitory activity of the ethyl acetate part.Conclusion:The ethyl acetate part of Abrus cantoniensis damaged bacterial cell structures,which results in protoplasm leakage,and eventually bacterial cell death.