Role of bitter contributors and bitter taste receptors:a comprehensive review of their sources,functions and future development

Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review provided an updated overview of the main bitter contributors of typical bitter fruits and vegetables and their health benefits.The main bitter contributors,including phenolics,terpenoids,alkaloids,amino acids,nucleosides and purines,were summarized.The bioactivities and wide range of beneficial effects of them on anti-cancers,anti-inflammations,anti-microbes,neuroprotection,inhibiting chronic and acute injury in organs,as well as regulating behavior performance and metabolism were reported.Furthermore,not only did the bitter taste receptors(taste receptor type 2 family,T2Rs)show taste effects,but extra-oral T2Rs could also be activated by binding with bitter components,regulating physiological activities via modulating hormone secretion,immunity,metabolism,and cell proliferation.This review provided a new perspective on exploring and explaining the nutrition of bitter foods,revealing the relationship between the functions of bitter contributors from food and T2Rs.Future trends may focus on revealing the possibility of T2Rs being targets for the treatment of diseases,exploring the mechanism of T2Rs mediating the bioactivities,and making bitter foods more acceptable without getting rid of bitter contributors.

Femtosecond laser fabrication of 3D vertically aligned micro-pore network on thick-film Li_(4)Ti_(5)O_(12)electrode for high-performance lithium storage

The development of energy storage devices with high energy density relies heavily on thick film electrodes,but it is challenging due to the limited ion transport kinetics inherent in thick electrodes.Here,we report on the preparation of a directional vertical array of micro-porous transport networks on LTO electrodes using a femtosecond laser processing strategy,enabling directional ion rapid transport and achieving good electrochemical performance in thick film electrodes.Various three-dimensional(3D)vertically aligned micro-pore networks are innovatively designed,and the structure,kinetics characteristics,and electrochemical performance of the prepared ion transport channels are analyzed and discussed by multiple characterization and testing methods.Furthermore,the rational mechanisms of electrode performance improvement are studied experimentally and simulated from two aspects of structural mechanics and transmission kinetics.The ion diffusion coefficient,rate performance at 60 C,and electrode interface area of the laser-optimized 60-15%micro-porous transport network electrodes increase by 25.2 times,2.2 times,and 2.15 times,respectively than those of untreated electrodes.Therefore,the preparation of 3D micro-porous transport networks by femtosecond laser on ultra-thick electrodes is a feasible way to develop high-energy batteries.In addition,the unique micro-porous transport network structure can be widely extended to design and explore other high-performance energy materials.

High-Quality and Wafer-Scale Cubic Silicon Carbide Single Crystals

Cubic silicon carbide(3C-SiC)has superior mobility and thermal conduction over that of widely applied hexagonal 4H-SiC.Moreover,much lower concentration of interfacial traps between insulating oxide gate and 3C-SiC helps fabricate reliable and long-life devices like metal-oxidesemiconductor field effect transistors.However,the growth of high-quality and wafer-scale 3C-SiC crystals has remained a big challenge up to now despite decades-long efforts by researchers because of its easy transformation into other polytypes during growth,limiting the development of 3C-SiC-based devices.Herein,we report that 3C-SiC can be made thermodynamically favored from nucleation to growth on a 4H-SiC substrate by top-seeded solution growth technique,beyond what is expected by classical nucleation theory.This enables the steady growth of high-quality and large-size 3C-SiC crystals(2-4-inch in diameter and 4.0-10.0 mm in thickness)sustainable.The as-grown 3C-SiC crystals are free of other polytypes and have high-crystalline quality.Our findings broaden the mechanism of hetero-seed crystal growth and provide a feasible route to mass production of 3C-SiC crystals,offering new opportunities to develop power electronic devices potentially with better performances than those based on 4H-SiC.

Mechanisms and active substances of targeting lipid peroxidation in ferroptosis regulation

Ferroptosis is a novel form of cell death driven by iron-dependent lipid peroxidation and it is implicated in various diseases,such as liver disease,acute kidney injury,cardiovascular disease,neurodegenerative disease and cancer.Lipid-based reactive oxygen species(ROS),particularly lipid hydroperoxides in the cellular membrane can lead to membrane disruption and cell death mediated by ferroptosis.There are three necessary stages involving in the process of lipid peroxidation regulation in ferroptosis,including the synthesis of membrane phospholipids,initiation of lipid peroxidation and clearance of lipid peroxides.In this review,we summarized the molecular modulation mechanisms of lipid peroxidation in ferroptosis from the above three stages,as well as various ferroptosis modulators targeting lipid peroxidation,including commonly used products,natural bioactive compounds and selenocompounds.Collectively,these findings suggest the vital role of lipid peroxidation in ferroptosis,and targeting lipid peroxidation in ferroptosis is potential to treat ferroptosis-associated diseases.

Fabrication of taxifolin loaded zein-caseinate nanoparticles and its bioavailability in rats

Taxifolin loaded zein-caseinate nanoparticles(TZP)were fabricated by the anti-solvent method and were used as an oral delivery vehicle to improve their bioavailability in the rat.The formulations of TZP were optimized.With mass ratio of 1:1:2 between taxifolin,zein and sodium caseinate,the particle size andζpotential of TZP were(168.74±0.35)nm and−(57.67±0.25)mV,while the encapsulation and loading efficiency of taxifolin were(85.83±0.89)%and(17.11±0.88)%,respectively.After freeze-drying,TZP exhibited excellent redispersibility in water without aggregation.Physicochemical characterization showed that taxifolin existed in amorphous form in TZP and its interaction with the protein was observed.After encapsulating in TZP,the excellent dispersion of taxifolin in water signifi cantly improve its diffusion velocity through a semipermeable membrane.After oral administration,taxifolin and its 5 metabolites were identifi ed in rat plasma by ultra high performance liquid chromatography(UPLC)with quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS).The dynamic variation of taxifolin and its metabolites in plasma were then quantifi ed by UPLC with a triple-quadrupole typemass spectroscopy(UPLC-QqQ-MS/MS).A pharmacokinetic study showed that the bioavailability of taxifolin increased from 0.35%to 0.52%through TZP fabrication.The plasma concentration of taxifolin glucuronide and methylated taxifolin glucuronide was much higher than taxifolin.Glucuronidation was the dominating metabolism pathway of taxifolin in vivo.

小学道德与法治课程教育教学中地方红色文化资源的运用研究——以陇南红色文化资源为例

《义务教育道德与法治课程标准(2022年版)》的显著变化在于以五个核心素养为统领细化培养目标,并细化道德与法治课程的学段目标、学段内容、学业质量描述、教学评价,以此回应新时代下义务教育阶段道德与法治课程“培养什么人、怎样培养人、为谁培养人”的根本问题。陇南红色文化资源具有多元价值,是小学道德与法治课程的鲜活素材。本研究致力于义务教育道德与法治课程标准(2022年版)视域下,陇南红色文化资源与小学道德与法治课程五个核心素养教育教学的融入与运用研究。

Nonlinear analysis on electrical properties in a bended composite piezoelectric semiconductor beam

In this paper,the interactions between the transverse loads and the electrical field quantities are investigated based on the nonlinear constitutive relation.By considering a composite beam consisting of a piezoelectric semiconductor and elastic layers,the nonlinear model is established based on the phenomenological theory and Euler’s beam theory.Furthermore,an iteration procedure based on the differential quadrature method(DQM)is developed to solve the nonlinear governing equations.Before analysis,the convergence and correctness are surveyed.It is found that the convergence of the proposed iteration is fast.Then,the transverse pressure induced electrical field quantities are investigated in detail.From the calculated results,it can be found that the consideration of nonlinear constitutive relation is necessary for a beam undergoing a large load.Compared with the linear results,the consideration of the nonlinear constitutive relation breaks the symmetry for the electric potential,the electric field,and the perturbation carrier density,and has little influence on the electric displacement.Furthermore,the non-uniform pressures are considered.The results show that the distributions of the electric field quantities are sensitively altered.It indicates that the electrical properties can be manipulated with the design of different transverse loads.The conclusions in this paper could be the guidance on designing and manufacturing electronic devices accurately.

Morphological characteristics and atomic evolution behavior of nanojoints in Ag nanowire interconnect network

Ag nanowires(AgNWs)have shown great application value in the field of flexible electronics due to their excellent optical and electrical properties,and the quality of its joints of AgNWs in the thin film network directly plays a key role in its performance.In order to further improve the joint quality of AgNWs under thermal excitation,the thermal welding process and atomic evolution behavior of AgNWs were investigated through a combination of in situ experimental and molecular dynamics simulations.The influence of processing time,temperature,and stress distribution due to spatial arrangement on nanojoints was systematically explored.What is more,the failure mechanisms and their atomic interface behavior of the nanojoints were also investigated.

Chimonanthus nitens Oliv. leaves flavonoids alleviate hyperuricemia by regulating uric acid metabolism and intestinal homeostasis in mice

This study aimed to evaluate the alleviating effect of Chimonanthus nitens Oliv.leaves flavonoids(CLF)on hyperuricemia induced by potassium oxonate in mice.The results showed that CLF lowered the serum levels of uric acid(UA),creatinine and blood urea nitrogen,downregulated hepatic mRNA expressions of xanthine oxidase(XO),phosphate ribose pyrophosphate synthetase(PRPS)and adenosine deaminase(ADA)in hyperuricemia mice.In addition,CLF repaired renal injury by significantly down-regulating mRNA and protein expressions of renal UA reabsorption-related proteins and up-regulating the mRNA and protein expressions of UA secretory-related proteins.Finally,CLF inhibited UA synthesis and promoted UA excretion to alleviate hyperuricemia.Besides,CLF supplementation repaired the intestinal barrier function as demonstrated by significant increased mRNA levels of intestinal zonula occludens-1(ZO-1),Occludin,mucin 2(MUC2)and mucin 4(MUC4),as well as decreased mRNA levels of toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88)in mice.Further research showed that CLF treatment restored intestinal homeostasis mediated by improving the composition of gut microbiota and elevating the abundance of beneficial bacteria like Lactobacillus,Alistipes,Prevotellaceae_UCG-001 and Parasutterella.Overall,our findings revealed a novel function of CLF as a promising therapeutic candidate for the treatment of hyperuricemia.

A retrospective prognostic evaluation analysis using the 8th edition of American Joint Committee on Cancer(AJCC)cancer staging system for luminal A breast cancer

Objective： We retrospectively analyzed the clinical prognostic value of the 8th edition of the American Joint Committee on Cancer （AJCC） staging system for luminal A breast cancer. Methods： Using both the anatomic and prognostic staging in the 8th edition of AJCC cancer staging system, we restaged patients with luminal A breast cancer treated at the Breast Disease Center, Peking University First Hospital from 2008 to 2014. Follow-up data including 5-year disease free survival （DFS）, overall survival （OS） and other clinic-pathological data were collected to analyze the differences between the two staging subgroups. Results： This study included 421 patients with luminal A breast cancer （median follow-up, 61 months）. The 5- year DFS and OS rates were 98.3% and 99.3%, respectively. Significant differences in 5-year DFS but not OS were observed between different anatomic disease stages. Significant differences were observed in both 5-year DFS and O S between different prognostic stages. Application of the prognostic staging system resulted in assignment of 175 of 421 patients （41.6%） to a different group compared to their original anatomic stages. In total, 102 of 103 patients with anatomic stage IlA changed to prognostic stage IB, and 24 of 52 patients with anatomic stage lib changed to prognostic stage IB, while 1 changed to prognostic stage liIB. Twenty-two of 33 patients with anatomic stage IliA were down-staged to IlA when staged by prognostic staging system, and the other 11 patients were down-staged to liB. Two patients with anatomic stage IIIB were down-staged to IliA. Among seven padents with anatomic stage IIIC cancer, two were down-staged to IliA and four were down-staged to stage I]IB. Conclusions： The 8th edition of AJCC prognostic staging system is an important supplement to the breast cancer staging system. More clinical trials are needed to prove its ability to guide selection of proper systemic therapy and predict prognosis of breast cancer.

Development of Gelatin-Based Active Packaging and Its Application in Bread Preservation

The issue of plastic pollution has attracted widespread social attention.Gelatin is valued as a degradable bio-based material,especially as an edible active packaging material.However,the commonly used solution-casting filmforming technology limits the mass production of gelatin films.In order to improve the production efficiency and enhance the commercial value of gelatin films,in this study,fish gelatin(FG)particles were successfully blended with essential oils(EOs)to prepare active films by melt extrusion technique,a common method for commercial plastics,and applied to bread preservation.FG and EOs showed good compatibility with each other.The elongation at break was enhanced in all samples of films containing EOs.The addition of EOs weakened the oxygen barrier properties of the FG films.The gelatin films containing clove EO showed the highest DPPH radical scavenging rate of 39.38%.The films containing oregano EO showed the highest antibacterial activity,with 98.84%and 99.86% against S.aureus and E.coli,respectively.The bread preservation results showed a slower microbial growth rate in the samples preserved by the active films.The bread samples preserved in commercial PE film showed mold on day 3,and the bread samples preserved in active gelatin film showed mold visible to the naked eye by day 7.This study demonstrates the potential of gelatin-based activated films for commercial application in baked goods preservation.

The Effect of TCM Herbs on Mitochondrial Functions: The Linkage between Qi and Mitochondria

The linkage between Qi and mitochondria was investigated by exploring the effect of Traditional Chinese Medicine (TCM) Qi-invigorating herbs on mitochondrial function at the biochemical and molecular levels. Three Chinese herbs (Astragali radix, Herba cistanche, Panax ginseng) were used to treat cultured mouse kidney cells and the generation of adenosine triphosphate (ATP) was measured. The Qi-invigorating herb, Astragali radix, was selected for further study using additional biological and molecular parameters, including ATP, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mtDNA copies, superoxide dismutase (SOD), glutathione (GSH), cell growth, cell viability and transcriptomes. We also chose two concentrations of Astragali radix to study the hormetic effect. The results indicated that: 1) Qi-invigorating herbs have significant effects on the function of mitochondria, with ATP production and the antioxidant capacity being significantly enhanced, and ROS levels being reduced, allowing for a more optimal oxidation environment. The effect of the herbs followed a hormetic curve with a stimulating effect at lower doses but an inhibiting effect at high doses;2) The growth of the cells was not affected despite numerous biochemical changes associated with mitochondrial function, indicating the powerful ability of mitochondria to maintain cellular homeostasis;3) The up-regulation of NOCT gene, related to nicotinamide adenine dinucleotide (NADH) synthesis, offers a molecular basis for the ATP-promoting effect of the Qi-invigorating herbs. This work provides additional insight into the efficacy of TCM herbs from a western perspective.

Screening and Characterization of Nitrite Degrading <i>Lactobacillus plantarum</i>in Chinese Traditional Pickles

A Gram-positive, non-spore, round ended, straight rod Lactic acid bacteria were screened. The strain was screened out from the traditional pickle jar in Yutang soy sauce garden of Jining. In order to degrade the nitrate content in the fermentation process of traditional pickles and improve the quality of pickles, it is necessary to screen out nitrite degrading strains from pickles, and preliminarily locate nitrite reductase, and find out the most suitable pH, temperature and culture time to degrade nitrite. Lactobacillus plantarum was screened by MRS medium in advance. After 48 hours of culture in a shaking table with Bacillus subtilis, the cell components were separated by centrifugation, wall breaking and other operations. After 20 hours at 30°C, the content of nitrite in each component was determined by the naphthalene ethylenediamine hydrochloride method (NIR). The culture conditions were as follows: inoculation amount 3%, 6%, 9%, 12%, 15%;salinity 2%, 4%, 6%, 8%, 10%;temperature 15°C, 20°C, 25°C, 30°C, 35°C for 20 h. The results showed that the best degradation effect of nitrite was obtained under the conditions of 9% inoculum, salinity 5% and 30°C. Under the conditions of 9% inoculum, 5% salinity and 30°C for 5 h, 10 h, 20 h, 48 h, 66 h and 78 h, the results showed that the degradation amount gradually increased with the extension of time, and gradually maintained a stable state. Lactobacillus plantarum JBA-3 is a new type of lactic acid bacteria which can degrade nitrite and produce nitrite reductase.

基于核质遗传原理建立多重PCR检测方法鉴定阿胶中马、驴源性成分及皮张种源

阿胶(Asini Colla Corii)及其原料皮张源性成分的鉴定是对阿胶真实性的一种保障,阿胶生产企业和市场监管部门急需马、驴、骡皮张以及阿胶中源性成分鉴别的有效检测方法。本研究基于马、驴核基因组和线粒体基因组筛选物种特异性DNA序列作为检测靶标,设计马、驴特异性引物,建立了鉴别马、驴、骡皮张以及鉴定阿胶中马和驴源性成分的多重PCR方法。结果显示,本文所建立的方法可用于阿胶源性成分及皮张种源的鉴别,其特异性强,只在目标物种中扩增出目的条带,而非目标物种中没有任何扩增产物,而且灵敏度能达到0.2 ng,可为阿胶生产企业和市场监管部门提供技术支撑。

Recent Advances in Tumor Microenvironment Hydrogen Peroxide-Responsive Materials for Cancer Photodynamic Therapy

Photodynamic therapy(PDT),as one of the noninvasive clinical cancer phototherapies,suffers from the key drawback associated with hypoxia at the tumor microenvironment(TME),which plays an important role in protecting tumor cells from damage caused by common treatments.High concentration of hydrogen peroxide(H2O2),one of the hallmarks of TME,has been recognized as a double-edged sword,posing both challenges,and opportunities for cancer therapy.The promising perspectives,strategies,and approaches for enhanced tumor therapies,including PDT,have been developed based on the fast advances in H2O2-enabled theranostic nanomedicine.In this review,we outline the latest advances in H2O2-responsive materials,including organic and inorganic materials for enhanced PDT.Finally,the challenges and opportunities for further research on H2O2-responsive anticancer agents are envisioned.

Improvement of center segregation in high-carbon steel billets using soft reduction

Center segregation is the main reason for cup fracture of high-carbon wire rod during drawing. Therefore, to continuously produce cast billets with very low center segregation is an important objective. The soft reduction technology is considered to be an effective method to minimize center segregation. To elucidate the effect of soft reduction on the internal quality of high-carbon steel billets, soft reduction was applied with different solid fractions in the core area of billets in a laboratory casting machine. A coupled temperature/displacement finite element model was developed to calculate the solid fraction using the commercial software ABAQUS. Center segregation, center porosity, homogeneity of elements, and equiaxed crystal zone were obviously improved by applying soft reduction, especially when the solid fraction was less than 1.0. The optimal results were obtained when the solid fraction was approximately 0.9.

Development of an In-Situ Laser Machining System Using a Three-Dimensional Galvanometer Scanner

In this study, a three-dimensional (3D) in-situ laser machining system integrating laser measurement and machining was built using a 3D galvanometer scanner equipped with a side-axis industrial camera. A line structured light measurement model based on a galvanometer scanner was proposed to obtain the 3D information of the workpiece. A height calibration method was proposed to further ensure measurement accuracy, so as to achieve accurate laser focusing. In-situ machining software was developed to realize time-saving and labor-saving 3D laser processing. The feasibility and practicability of this in-situ laser machining system were verified using specific cases. In comparison with the conventional line structured light measurement method, the proposed methods do not require light plane calibration, and do not need additional motion axes for 3D reconstruction;thus they provide technical and cost advantages. The insitu laser machining system realizes a simple operation process by integrating measurement and machining,which greatly reduces labor and time costs.

基于“超星泛雅平台+学习通”快速完善课程的技巧和实践

由于新冠疫情的影响,全国高校均延期开学,教育部要求积极开展线上教学,做到“停课不停学”。线上教学实施已近八周,教师基本熟悉线上教学方法,接下来如何做好线上课程和完善课程资源,成为教师要面对的主要任务。本文阐述了基于“超星泛雅平台+学习通”快速完善课程和互动教学的技巧和实践,不仅可以减少教师工作量,还可以建设高水平线上课程,保证教学质量和教学效果,是值得推广的方法。

Involvement of CsWRKY70 in salicylic acid-induced citrus fruit resistance against Penicillium digitatum

Penicillium digitatum causes serious losses in postharvest citrus fruit.Exogenous salicylic acid(SA)can induce fruit resistance against various pathogens,but the mechanism remains unclear.Herein,a transcriptome-based approach was used to investigate the underlying mechanism of SA-induced citrus fruit resistance against P.digitatum.We found that CsWRKY70 and genes related to methyl salicylate(MeSA)biosynthesis(salicylate carboxymethyltransferase,SAMT)were induced by exogenous SA.Moreover,significant MeSA accumulation was detected in the SA-treated citrus fruit.The potential involvement of CsWRKY70 in regulating CsSAMT expression in citrus fruit was studied.Subcellular localization,dual luciferase,and electrophoretic mobility shift assays and an analysis of transient expression in fruit peel revealed that the nucleus‐localized transcriptional activator CsWRKY70 can activate the CsSAMT promoter by recognizing the W-box element.Taken together,the findings from this study offer new insights into the transcriptional regulatory mechanism of exogenous SA-induced disease resistance in Citrus sinensis fruit.

Stretchable supercapacitor based on a hierarchical PPy/CNT electrode and hybrid hydrogel electrolyte with a wide operating temperature

Hydrogel is frequently used as a solid electrolyte for all solid-state supercapacitors(SCs)because of its liquid-like ion-transport property and high conformability.However,due to the higher water content,the hydrogel electrolyte undergoes inevitable freezing and/or dehydration with climate change.Herein,polypyrrole/carbon all-solid-state SCs(PCSCs)were developed based on a hierarchical polypyrrole/carbon nanotube electrode and a highly stretchable double-network polymer hydrogel electrolyte with LiCl/ethylene glycol as a mixed solvent.The PCSCs showed excellent electrochemical performance and cycle stability with a wide operating temperature.The specific capacitances could reach 202.2 and 112.3 mF cm^(−2) at current densities of 0.5 and 3.0 mA cm^(−2),respectively.Meanwhile,the PCSCs showed outstanding mechanical properties in maintaining a high areal capacitance under deformations of bending and tension.The excellent water retention of the device also ensured the stable electrochemical performance of PCSCs in a wide temperature range(30–80℃),which could potentially represent a reliable application in various harsh environments.