Enhancing ROS-Inducing Nanozyme through Intraparticle Electron Transport.

Iron oxide nanoparticles (IONPs) have garnered significant attention as a promising platform for reactive oxygen species (ROS)-dependent disease treatment, owing to their remarkable biocompatibility and Fenton catalytic activity. However, the low catalytic activity of IONPs is a major hurdle in their clinical translation. To overcome this challenge, IONPs of different compositions are examined for their Fenton reaction under pharmacologically relevant conditions. The results show that wüstite (FeO) nanoparticles exhibit higher catalytic activity than magnetite (Fe3 O4 ) or maghemite (γ-Fe2 O3 ) of matched size and coating, despite having a similar surface oxidation state. Further analyses suggest that the high catalytic activity of wüstite nanoparticles can be attributed to the presence of internal low-valence iron (Fe0 and Fe2+ ), which accelerates the recycling of surface Fe3+ to Fe2+ through intraparticle electron transport. Additionally, ultrasmall wüstite nanoparticles are generated by tuning the thermodecomposition-based nanocrystal synthesis, resulting in a Fenton reaction rate 5.3 times higher than that of ferumoxytol, an FDA-approved IONP. Compared with ferumoxytol, wüstite nanoparticles substantially increase the level of intracellular ROS in mouse mammary carcinoma cells. This study presents a novel mechanism and pivotal improvement for the development of highly efficient ROS-inducing nanozymes, thereby expanding the horizons for their therapeutic applications.

The enhancement of energy supply in syngas-fermenting microorganisms.

After the second industrial revolution, social productivity developed rapidly, and the use of fossil fuels such as coal, oil, and natural gas increased greatly in industrial production. The burning of these fossil fuels releases large amounts of greenhouse gases such as CO2, which has caused greenhouse effects and global warming. This has endangered the planet's ecological balance and brought many species, including animals and plants, to the brink of extinction. Thus, it is crucial to address this problem urgently. One potential solution is the use of syngas fermentation with microbial cell factories. This process can produce chemicals beneficial to humans, such as ethanol as a fuel while consuming large quantities of harmful gases, CO and CO2. However, syngas-fermenting microorganisms often face a metabolic energy deficit, resulting in slow cell growth, metabolic disorders, and low product yields. This problem limits the large-scale industrial application of engineered microorganisms. Therefore, it is imperative to address the energy barriers of these microorganisms. This paper provides an overview of the current research progress in addressing energy barriers in bacteria, including the efficient capture of external energy and the regulation of internal energy metabolic flow. Capturing external energy involves summarizing studies on overexpressing natural photosystems and constructing semiartificial photosynthesis systems using photocatalysts. The regulation of internal energy metabolic flows involves two parts: regulating enzymes and metabolic pathways. Finally, the article discusses current challenges and future perspectives, with a focus on achieving both sustainability and profitability in an economical and energy-efficient manner. These advancements can provide a necessary force for the large-scale industrial application of syngas fermentation microbial cell factories.

Sustainable production of astaxanthin in microorganisms: the past, present, and future.

Astaxanthin (3,3'-dihydroxy-4,4'-diketo-ß-carotene) is a type of C40 carotenoid with remarkable antioxidant characteristics, showing significant application prospects in many fields. Traditionally, the astaxanthin is mainly obtained from chemical synthesis and natural acquisition, with both approaches having many limitations and not capable of meeting the growing market demand. In order to cope with these challenges, novel techniques, e.g., the innovative cell engineering strategies, have been developed to increase the astaxanthin production. In this review, we first elaborated the biosynthetic pathway of astaxanthin, with the key enzymes and their functions discussed in the metabolic process. Then, we summarized the conventional, non-genetic strategies to promote the production of astaxanthin, including the methods of exogenous additives, mutagenesis, and adaptive evolution. Lastly, we reviewed comprehensively the latest studies on the synthesis of astaxanthin in various recombinant microorganisms based on the concept of microbial cell factory. Furthermore, we have proposed several novel technologies for improving the astaxanthin accumulation in several model species of microorganisms.

Low-cost compact optical spectroscopy and novel spectroscopic algorithm for point-of-care real-time monitoring of nanoparticle delivery in biological tissue models.

Objective: Real-time monitoring of nanoparticle delivery in biological models is essential to optimize nanoparticle-mediated therapies. However, few techniques are available for convenient real-time monitoring of nanoparticle concentrations in tissue samples. This work reported novel optical spectroscopic approaches for low-cost point-of-care real-time quantification of nanoparticle concentrations in biological tissue samples. Methods: Fiber probe measured diffuse reflectance can be described with a simple analytical model by introducing an explicit dependence on the reduced scattering coefficient. Relying on this, the changes on the inverse of diffuse reflectance are proportional to absorption change when the scattering perturbation is negligible. We developed this model with proper wavelength pairs and implemented it with both a standard optical spectroscopy platform and a low-cost compact spectroscopy device for near real-time quantification of nanoparticle concentrations in biological tissue models. Results: Both tissue-mimicking phantom and ex vivo tissue sample studies showed that our optical spectroscopic techniques could quantify nanoparticle concentrations in near real-time with high accuracies (less than 5% error) using only a pair of narrow wavelengths (530 nm and 630 nm). Conclusion: Novel low-cost point-of-care optical spectroscopic techniques were demonstrated for rapid accurate quantification of nanoparticle concentrations in tissue-mimicking medium and ex vivo tissue samples using optical signals measured at a pair of narrow wavelengths. Significance: Our methods will potentially facilitate real-time monitoring of nanoparticle delivery in biological models using low-cost point-of-care optical spectroscopy platforms, which will significantly advance nanomedicine in cancer research.

Characterization of a fungal competition factor: Production of a conidial cell-wall associated antifungal peptide.

Competition is one of the fundamental driving forces of natural selection. Beauveria bassiana is a soil and plant phylloplane/root fungus capable of parasitizing insect hosts. Soil and plant environments are often enriched with other fungi against which B. bassiana competes for survival. Here, we report an antifungal peptide (BbAFP1), specifically expressed and localized to the conidial cell wall and is released into the surrounding microenvironment inhibiting growth of competing fungi. B. bassiana strains expressing BbAFP1, including overexpression strains, inhibited growth of Alternaria brassicae in co-cultured experiments, whereas targeted gene deletion of BbAFP1 significantly decreased (25%) this inhibitory effect. Recombinant BbAFP1 showed chitin and glucan binding abilities, and growth inhibition of a wide range of phytopathogenic fungi by disrupting membrane integrity and eliciting reactive oxygen species (ROS) production. A phenylalanine residue (F50) contributes to chitin binding and antifungal activity, but was not required for the latter. Expression of BbAFP1 in tomato resulted in transgenic plants with enhanced resistance to plant fungal pathogens. These results highlight the importance of fungal competition in shaping primitive competition strategies, with antimicrobial compounds that can be embedded in the spore cell wall to be released into the environment during the critical initial phases of germination for successful growth in its environmental niche. Furthermore, these peptides can be exploited to increase plant resistance to fungal pathogens.

Evasion of Cas9 toxicity to develop an efficient genome editing system and its application to increase ethanol yield in Fusarium venenatum TB01.

The clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas9) system is a powerful genome editing tool that has been successfully established in some filamentous fungi due to its high flexibility and efficiency. However, the potential toxicity of Cas9 restricts the further popularization and application of this system to some degree. The AMA1 element is a self-replicator derived from Aspergillus nidulans, and its derived vectors can be readily lost without selection. In this study, we eliminated Cas9 toxicity to Fusarium venenatum TB01 based on 100% AMA1-based Cas9 expression vector loss. Meanwhile, two available endogenous Pol III promoters (FvU6374 and Fv5SrRNA) used for sgRNA expression of the CRISPR/Cas9 system were excavated. Compared to FvU6374 (40-50%), Fv5SrRNA exhibited higher single-gene editing efficiency (> 85%), and the efficiency of simultaneous editing of the two genes using Fv5SrRNA was over 75%. Based on this system, a butanediol dehydrogenase encoding gene FvBDH was deleted, and the ethanol yield in variants increased by 52% compared with that of the wild-type. The highly efficient CRISPR/Cas9 system developed here lays the technical foundation for advancing the development of F. venenatum TB01 through metabolic engineering, and the obtained FvBDH gene-edited variants have the potential to simultaneously produce mycoprotein and ethanol by further gene modification and fermentation process optimization in the future.Key points• Cas9 toxicity disappeared and DNA-free gene-edited strains obtained after vector loss• Promoter Fv5SrRNA conferred TB01 higher gene editing efficiency than FvU6374•Deletion of the FvBDH gene resulted in a 52% increase in ethanol yield.

In silico screening of off-line comprehensive two-dimensional counter-current chromatography with liquid chromatography for four saponins isolation.

Being restrained by the limited peak capacity, one-dimensional chromatography usually leads to an unsatisfactory separation with low purity of compounds in a complex mixture. To obtain more highly pure targets for standard reference and to discover new substances for structural elucidation, two-dimensional chromatography is more and more prevalent in many fields. As few metrics on assessment of the preparative capability of two-dimensional chromatographic separations are reported, a methodology of in silico screening of various two-dimensional chromatographic separations with a minimal number of experiments was demonstrated in this work, which was based on three descriptors including the occupation rate of peaks and system homogeneity of a two-dimensional separation space, and the minimal distance of all nearest-neighbor distances of peaks. Combining the advantages of counter-current chromatography and liquid chromatography, we elaborated the methodology by employing off-line comprehensive two-dimensional counter-current chromatography with liquid chromatography to be in silico screened for separation of four saponins from Panax notoginseng at an analytical scale to simulate the case of preparative scale transfer. The predictive results were presented by two-dimensional contour plots and verified by experiments. The result showed that the experimental results were in general accord with the predictive results.

Manipulation of host ecdysteroid hormone levels facilitates infection by the fungal insect pathogen, Metarhizium rileyi.

Entomopathogenic fungi such as Metarhizium rileyi and Beauveria bassiana are widely used insect biological control agents. Little, however, is known concerning genetic or enzymatic factors that differentiate the mechanisms employed by these two fungal pathogens to infect target hosts. Infection by either of these organisms is known to increase levels of the growth and molting hormone, ecdysone, which also regulates the expression of a number of innate immune pathways. M. rileyi, but not B. bassiana, has apparently evolved an ecdysteroid-22-oxidase (MrE22O) that inactivate ecdysone. We show that deletion of MrE22O impaired virulence compared with the wild-type strain, with an increase in ecdysone titer seen in hosts that was coupled to an increase in the expression of antimicrobial genes. An M. rileyi strain engineered to overexpress MrE22O (MrE22OOE ), as well as trans-expression in B. bassiana (Bb::MrE220OE ) resulted, in strains displaying enhanced virulence and dampening of host immune responses compared with their respective wild-type parental strains. These results indicate that ecdysone plays an important role in mediating responses to fungal infection and that some insect pathogenic fungi have evolved mechanisms for targeting this hormone as a means for facilitating infection.

Ergosterol-targeting fusion antifungal peptide significantly increases the Verticillium wilt resistance of cotton.

Increasing the targeting ability of antifungal proteins towards specific components of fungal cells has the potential to improve their antifungal activity and reduce harmful effects to nontarget cells. To obtain effective disease resistance genes against cotton Verticillium wilt, we constructed several fusion genes, in which binding domains targeting chitin, sphingolipid or ergosterol in the fungal cell wall or cell membrane were individually fused to the antifungal peptide BbAFP1 from entomopathogenic fungus Beauveria bassiana. Transient expression of fusion genes in cotton cotyledons indicated that the BbAFP1::ErBD fusion peptide with an ergosterol binding domain exhibited better disease resistance against V. dahliae than wild-type BbAFP1 and other fusion genes. BbAFP1::ErBD and BbAFP1 transgenic cotton were obtained and verified by Southern and Western blotting. Compared with BbAFP1-expressing cotton, BbAFP1::ErBD-expressing cotton showed higher disease resistance against V. dahliae, with smaller lesion areas (0.07 cm2 vs. 0.16 cm2 ) on the leaves and a lower disease index (23.9 vs. 34.5). Overexpression of BbAFP1::ErBD by transgenic tobacco also showed enhanced disease resistance against V. dahliae compared with that of the wild-type gene. These results indicated that construction of fusion antifungal peptides that target fungal cells is a powerful strategy to obtain new anti-disease genes, and the obtained fusion gene BbAFP1::ErBD has the potential to defend against plant fungal diseases.

Impact of Radiotherapy on Prognosis in Patients Diagnosed with Metastatic Prostate Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: It has been reported that compared with no local therapy (NLT), patients treated with local therapy (LT) using radiotherapy (RT) possess higher survival rate in metastatic prostate cancer (mPCa). The aim of this meta-analysis was to evaluate the impact of RT on prognosis in patients with mPCa. METHODS: We retrieved the literature in PubMed, Embase, and Cochrane Library databases until June 2019 using structured search terms. Several studies were included, which evaluated patients with mPCa who received RT versus NLT. RESULTS: A total of 14,542 patients were analyzed in 7 included papers (2 randomized controlled trials [RCTs] and 5 cohort retrospective studies [CRS]), and 2,232 mPCa patients were treated with RT and 12,310 with NLT. The data of RCTs and CRS were analyzed separately. In RCTs, RT was associated with no significant difference in overall survival (OS) (pooled hazard ratio [HR] = 0.96; 95% confidence interval [CI]: 0.85-1.09; p = 0.55; I2 = 42%) relative to NLT, while survival benefit was observed in the low-metastatic burden group (pooled HR = 0.68; 95% CI: 0.54-0.86; p = 0.001; I2 = 0%), and no survival benefit was observed in the high-metastatic burden group (pooled HR = 1.07; 95% CI: 0.92-1.24; p = 0.39; I2 = 0%). In CRS, RT results in lower cancer-specific mortality (CSM) (pooled HR = 0.49; 95% CI: 0.34-0.75; p < 0.00001; I2 = 0%) and higher OS (pooled HR = 0.61; 95% CI: 0.55-0.68; p < 0.00001; I2 = 0%) relative to NLT. Subsequent analysis demonstrated that high level of M-stage or N-stage was associated with increased CSM (pooled HR = 2.08; 95% CI: 1.69-2.55; p < 0.00001; I2 = 0% and pooled HR = 1.16; 95% CI: 1.03-1.30; p < 0.00001; I2 = 0%; respectively). CONCLUSIONS: Our observations in aggregate indicated that RT at least does not appear to be harmful and may be beneficial for low-metastatic burden patients and better condition patients. More prospective and randomized studies evaluating RT for mPCa are warranted.

[Definitive screening design combined with design space for optimizing purification process of Scutellariae Radix extract].

In the pharmacopoeia, many process parameters for the purification process of Scutellariae Radix are unclear. In this study, deterministic screening design combined with design space method was used to optimize the purification process of Scutellariae Radix extract. Nine method parameters such as mass fraction of solution(X_1), first acid precipitation pH(X_2) and first holding time(X_3) in the purification process were firstly studied by definitive screening design. The yield of baicalin was defined as the evaluation index. A stepwise regression method was used then to build quantitative models between evaluation index and method parameters and the three most critical impact parameters were determined. Probability-based design space was calculated and successfully verified with the experimental error simulation method. Finally, the second standing temperature, the first standing temperature and the pH value of the second acid precipitation were determined as the three most critical method parameters. The recommended operating space was as follows: the second standing temperature 5-7 ℃, the first standing temperature 13-15 ℃, and the pH of the second acid precipitation 1.5-1.7. Within this operating space, the baicalin yield in the purification process was over 80%, and the probability of reaching the standard was over 0.96. In this study, we optimized the effect of various parameters for the purification process of the Scutellariae Radix extract in the pharmacopoeia on the yield of baicalin and provided a reference for industrial production of the exact of Scutellariae Radix.

Expression of a Beauveria bassiana chitosanase (BbCSN-1) in Pichia pastoris and enzymatic analysis of the recombinant protein.

Chitosanase (EC 3.2.1.132) is an important chitosan-degrading enzyme involved in industrial applications. In this study, a chitosanase gene (BbCSN-1) from Beauveria bassiana, an insect fungal pathogen, was cloned and expressed in Pichia pastoris. The amount of BbCSN-1 in the fermentation broth of P. pastoris gradually increased after induction with methanol from one to 6 d, reaching 398 µg/ml on the 6th day. The molecular characteristics of BbCSN-1 were measured with colloidal chitosan as a substrate. The purified BbCSN-1 exhibited optimum activity at pH 5 and 30 °C and was stable at pH 2-8 and below 40 °C. The Km value of BbCSN-1 was approximately 0.8 mg/ml at 30 °C (pH 6.0). The activity of BbCSN-1 was significantly enhanced by Mn2+ but inhibited by Co2+ and Cu2+. These results indicated that BbCSN-1 from B. bassiana could be easily expressed in P. pastoris, which provided a basis for further study on its application.

A polyketide synthase, BbpksP, contributes to conidial cell wall structure and UV tolerance in Beauveria bassiana.

Conidial pigments of filamentous fungi play vital roles in fungal biotic/abiotic stress tolerance and are usually synthesized by polyketide synthases or other pigment synthesis proteins. Beauveria bassiana, an important insect pathogenic fungus used worldwide for pest biocontrol, produces white conidia on artificial media, while no conidial pigment has been observed or reported in it. However, real-time PCR and promoter-report analyses reveal a polyketide gene of B. bassiana (named BbpksP), homologous to melanin synthesis genes, is specifically expressed in aerial conidia. We show that deletion of BbpksP does not result in changes in conidial yield, germination rate or colony radial growth; however, the defect impairs conidial cell wall structure. A dense electron layer appears in the outer edge of the cell envelope in wild-type conidia, as observed by TEM, but this dense layer is absent in the ΔBbpksP mutant. The lack of BbpksP gene also reduces the UV-B tolerance of B. bassiana conidia. Bioassay reveals that deletion of BbpksP decreased virulence of B. bassiana against Galleria mellonella larvae via topical infection. These data indicate that the product(s) of BbpksP contributes to the integrity of the B. bassiana conidial cell wall and further affects the tolerance of UV-B stress and insecticidal activity.

Regulatory cascade and biological activity of Beauveria bassiana oosporein that limits bacterial growth after host death.

The regulatory network and biological functions of the fungal secondary metabolite oosporein have remained obscure. Beauveria bassiana has evolved the ability to parasitize insects and outcompete microbial challengers for assimilation of host nutrients. A novel zinc finger transcription factor, BbSmr1 (B. bassiana secondary metabolite regulator 1), was identified in a screen for oosporein overproduction. Deletion of Bbsmr1 resulted in up-regulation of the oosporein biosynthetic gene cluster (OpS genes) and constitutive oosporein production. Oosporein production was abolished in double mutants of Bbsmr1 and a second transcription factor, OpS3, within the oosporein gene cluster (ΔBbsmr1ΔOpS3), indicating that BbSmr1 acts as a negative regulator of OpS3 expression. Real-time quantitative PCR and a GFP promoter fusion construct of OpS1, the oosporein polyketide synthase, indicated that OpS1 is expressed mainly in insect cadavers at 24-48 h after death. Bacterial colony analysis in B. bassiana-infected insect hosts revealed increasing counts until host death, with a dramatic decrease (∼90%) after death that correlated with oosporein production. In vitro studies verified the inhibitory activity of oosporein against bacteria derived from insect cadavers. These results suggest that oosporein acts as an antimicrobial compound to limit microbial competition on B. bassiana-killed hosts, allowing the fungus to maximally use host nutrients to grow and sporulate on infected cadavers.

Investigating the theragnostic potential of 131I-caerin peptide in thyroid cancer.

OBJECTIVE: Caerin is a new peptide with tumour toxicity and its uptake by tumour cells is independent of the sodium iodide symporter (NIS). Thyroid cancer is the most common cancers of endocrine malignancy. Radioiodine (131I)-refractory thyroid cancer is the most lethal subtype of the thyroid cancers and remains a clinical challenge. In the current study, we investigated the 131I radiolabeling efficiency of Caerin and the effects of Caerin, 131I-Caerin and free 131I on differentiated and undifferentiated human thyroid cancer cell lines (B-CPAP and CAL-62) in vitro. MATERIALS AND METHODS: Cell Counting Kit-8 was used to assess the cytotoxic effect of Caerin, 131I-Caerin and free 131I on B-CPAP and CAL-62 cells. Laser scanning confocal microscope was exploited to evaluate the uptake and internalization of Caerin by thyroid cancer cells. The Chloramine-T method was used to label the peptide with 131I. And the stability and water partition coefficient (Log P) of 131I-Caerin were studied. RESULTS: Our results demonstrated that Caerin and 131I-Caerin could be accumulated by B-CPAP and CAL-62 cells, resulting in killing of the thyroid cancer cells in vitro. The efficacy of 131I-Caerin is much higher than 131I, especially to undifferentiated CAL-62 cells. The results prove the feasibility of radioiodination of the 131I-Caerin via the Chloramine-T method. Moreover, the result indicate the hydrophobic 131I-Caerin was stable in 72 hours. CONCLUSION: Iodine-131-Caerin can inhibit the cell viability of thyroid cancer and hold certain promise as a theragnostic tool for human thyroid cancers.

Magnetic Iron Oxide Nanoparticles for Disease Detection and Therapy.

Magnetic iron oxide nanoparticles (MIONs) are among the first generation of nanomaterials that have advanced to clinic use. A broad range of biomedical techniques has been developed by combining the versatile nanomagnetism of MIONs with various forms of applied magnetic fields. MIONs can generate imaging contrast and provide mechanical/thermal energy in vivo in response to an external magnetic field, a special feature that distinguishes MIONs from other nanomaterials. These properties offer unique opportunities for nanomaterials engineering in biomedical research and clinical interventions. The past few decades have witnessed the evolution of the applications of MIONs from conventional drug delivery and hyperthermia to the regulation of molecular and cellular processes in the body. Here we review the most recent development in this field, including clinical studies of MIONs and the emerging techniques that may contribute to future innovation in medicine.

The Impact of Vitamin D on Cognitive Dysfunction in Mice with Systemic Lupus Erythematosus.

BACKGROUND A growing body of evidence suggests that systemic lupus erythematosus (SLE) may result in reversible cognitive dysfunction. Vitamin D is considered important for neurons. The therapeutic effect of vitamin D was evaluated in a rat model of SLE. MATERIAL AND METHODS There were 20 male MRL/lpr mice randomly divided into the SLE model group and the vitamin D group, in addition, 10 male C57BL 6J mice were used as the control (CON) group. Vitamin D was administered intraperitoneally (2 µg/kg) for 4 weeks. After 4 weeks of continuing intervention, we tested the cognitive function using the Morris water maze. The expression of vitamin D receptor (VDR), amyloid-ß, caspase-3, and Bcl-2 were detected by western blot analysis. RESULTS In the present study, we observed that vitamin D treatment alleviated neurobehavioral deficits in the mice with SLE. At the molecular levels, administration of vitamin D activated the expression of VDR and reduced the number of dead cells in the CA1 region of the hippocampus as well as regulated caspase-3 and Bcl-2 expression. CONCLUSIONS In conclusion, our results indicated that vitamin D played a protective role by suppressing inflammatory cytokines, thereby ultimately inhibiting the progression of apoptosis in a mouse model of SLE. Vitamin D may be promising as a protective intervention in SLE with cognitive dysfunction, and more and more experiments are warranted for its clinical testing in the near future.

Mimengosides J and K: two new neuroprotective triterpenoids from the fruits of Buddleja lindleyana.

Two new 11-methoxyl substituted triterpenoids, named as mimengosides J (1) and K (2), along with seven known compounds, were isolated from the fruits of Buddleja lindleyana. Their structures were elucidated on the basis of spectroscopic analysis. In addition, the new ones were evaluated for protective effects against damage of SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium ion (MPP+) and the results indicated that those may be one of the candidate compositions of Buddleja lindleyana for the treatment of neurodegenerative disease.

[Overview on hypoglycemic active constituents of traditional Chinese medicine based on insulin receptor signaling pathway].

Insulin resistance,as the main link in the pathogenesis of type 2 diabetes mellitus( T2 DM),runs through the whole process of occurrence and development of T2 DM and is closely related to the insulin receptor signaling pathway. Insulin stimulation causes autophosphorylation of the insulin receptor( IR),which then activates tyrosine phosphorylation of insulin receptor substrate( IRS).Phosphorylation of IRS can induce and activate phosphatidylinositol 3-kinase( PI3 K),subsequently activate downstream 3-phosphoinositide-dependent protease 1( PDK1) and Akt/PKB,and finally promote expression and translocation of glucose transporter 4 to increase glucose uptake of insulin-sensitive tissues and alleviate insulin resistance. Currently,oral hypoglycemic agents for clinical treatment of T2 DM have different side effects on the human body. Traditional Chinese medicine not only has a wide range of sources and abundant types,but also has comprehensive multi-component,multi-link and multi-target effects,showing unique advantages in the treatment of diabetes. In recent years,more and more researchers at home and abroad pay attention to the active ingredients in traditional Chinese medicine for alleviating insulin resistance. In this paper,we would summarize the active hypoglycemic ingredients of traditional Chinese medicine associated with the insulin receptor signaling pathway,which may provide some theoretical guidance for the development of traditional Chinese medicine in the treatment of diabetes.

Charge gradient microscopy.

Here we present a simple and fast method to reliably image polarization charges using charge gradient microscopy (CGM). We collected the current from the grounded CGM probe while scanning a periodically poled lithium niobate single crystal and single-crystal LiTaO3 thin film on the Cr electrode. We observed current signals at the domains and domain walls originating from the displacement current and the relocation or removal of surface charges, which enabled us to visualize the ferroelectric domains at a scan frequency above 78 Hz over 10 µm. We envision that CGM can be used in high-speed ferroelectric domain imaging and piezoelectric energy-harvesting devices.