Unveiling Dynamic Structure and Bond Evolutions in BiOIO3 Photocatalysts during CO2 Reduction.

We have established a correlation between photocatalytic activity and dynamic structure/bond evolutions of BiOIO3-based photocatalysts during CO2 reduction by combining operando X-ray diffraction with photoelectron spectroscopy. More specifically, the selective photo-deposition of PtOx species on BiOIO3 (010) facets could effectively promote the electron enrichment on Bi active sites of (100) facets for facilitating the adsorption/activation of CO2 molecules, leading to the formation of Bi sites with high oxidation state and the shrink of crystalline structures. With introducing light irradiation to drive CO2 reduction, the Bi active sites with high oxidation states transformed into normal Bi3+ state, accompanying with the expansion of crystalline structures. Owing to the dynamic structure, bond, and chemical-state evolutions, a significant improvement of photocatalytic activity for CO evolution has been achieved on PtOx-BiOIO3 (195.0 µmol g-1•h-1), much higher than the pristine (61.9 µmol g-1•h-1) as well as metal-Pt decorated BiOIO3 (70.3 µmol g-1•h-1) samples. This work provides new insights to correlate the intrinsically dynamic structure/bond evolutions with CO2 reduction activity, which may help to guide future photocatalyst design.

Two-point immobilization of M3 muscarinic receptor: a method for recognizing receptor antagonists in natural products.

In the investigation of active ingredients from natural products, current technologies relying on drug-target affinity recognition analysis face significant challenges. This is primarily due to their limited specificity and inability to provide downstream pharmacodynamic information, such as agonistic or antagonistic activity. In this study, a two-point method was developed by immobilizing M3 acetylcholine receptor (M3R) through the combination of the conformation-specific peptide BJ-PRO-13a and the HaloTag trap system. We systematically assessed the specificity of the immobilized M3R using known M3R antagonists (pirenzepine and atropine) and agonists (cevimeline and pilocarpine). By frontal analysis and nonlinear chromatography, the performance of immobilized M3R was evaluated in terms of binding kinetics and thermodynamics of four drugs to the immobilized M3R. Additionally, we successfully identified two M3R antagonists within an extract from Daturae Flos (DF), specifically hyoscyamine and scopolamine. Our findings demonstrate that this immobilization method effectively captures receptor-ligand binding interactions and can discern receptor agonists from antagonists. This innovation enhances the efficiency of receptor chromatography to determine binding-affinity in the development of new drugs, offering promise for the screening and characterization of active compounds, particularly within complex natural products.

Acupuncture for functional dyspepsia: Bayesian meta-analysis.

BACKGROUND: Acupuncture stands out as a prominent complementary and alternative medicine therapy employed for functional dyspepsia (FD). We conducted a Bayesian meta-analysis to ascertain both the relative effectiveness and safety of various acupuncture methods in the treatment of functional dyspepsia. METHODS: We systematically searched eight electronic databases, spanning from their inception to April 2023. The eligibility criteria included randomized controlled trials investigating acupuncture treatments for FD. Study appraisal was conducted using the Cochrane risk of bias tool. Pairwise and network meta-analyses were conducted using RevMan 5.3 and ADDIS V.1.16.6 software. Bayesian network meta-analysis was performed to compare and rank the efficacy of different acupuncture therapies for FD symptoms. RESULTS: This study found that combining different acupuncture methods or using acupuncture in conjunction with Western medicine is more effective in improving symptoms of functional dyspepsia compared to using Western medicine alone. According to the comprehensive analysis results, notably, the combination of Western medicine and acupuncture exhibited superior efficacy in alleviating early satiation and postprandial fullness symptoms. For ameliorating epigastric pain, acupuncture combined with moxibustion proved to be the most effective treatment, while moxibustion emerged as the optimal choice for addressing burning sensations. Warming needle was identified as the preferred method for promoting motilin levels. CONCLUSION: The findings of this study demonstrate that acupuncture, both independently and in conjunction with other modalities, emerged as a secure and effective treatment option for patients with functional dyspepsia.

Caffeine improves mitochondrial dysfunction in the white matter of neonatal rats with hypoxia-ischemia through deacetylation: a proteomic analysis of lysine acetylation.

Aims: White matter damage (WMD) is linked to both cerebral palsy and cognitive deficits in infants born prematurely. The focus of this study was to examine how caffeine influences the acetylation of proteins within the neonatal white matter and to evaluate its effectiveness in treating white matter damage caused by hypoxia-ischemia. Main methods: We employed a method combining affinity enrichment with advanced liquid chromatography and mass spectrometry to profile acetylation in proteins from the white matter of neonatal rats grouped into control (Sham), hypoxic-ischemic (HI), and caffeine-treated (Caffeine) groups. Key findings: Our findings included 1,999 sites of lysine acetylation across 1,123 proteins, with quantifiable changes noted in 1,342 sites within 689 proteins. Analysis of these patterns identified recurring sequences adjacent to the acetylation sites, notably YKacN, FkacN, and G * * * GkacS. Investigation into the biological roles of these proteins through Gene Ontology analysis indicated their involvement in a variety of cellular processes, predominantly within mitochondrial locations. Further analysis indicated that the acetylation of tau (Mapt), a protein associated with microtubules, was elevated in the HI condition; however, caffeine treatment appeared to mitigate this over-modification, thus potentially aiding in reducing oxidative stress, inflammation in the nervous system, and improving mitochondrial health. Caffeine inhibited acetylated Mapt through sirtuin 2 (SITR2), promoted Mapt nuclear translocation, and improved mitochondrial dysfunction, which was subsequently weakened by the SIRT2 inhibitor, AK-7. Significance: Caffeine-induced changes in lysine acetylation may play a key role in improving mitochondrial dysfunction and inhibiting oxidative stress and neuroinflammation.

Knockdown of Ubiquitin-Conjugating Enzyme E2 T Abolishes the Progression of Head and Neck Squamous Cell Carcinoma by Inhibiting NF-Κb Signaling and inducing Ferroptosis.

BACKGROUND: Ubiquitin-conjugating enzyme 2T (UBE2T) has been reported to be associated with uncontrolled cell growth and tumorigenesis in multiple cancer types. However, the understanding of its regulatory role in the carcinogenesis of Head And Neck Squamous Cell Carcinoma (HNSC) is limited. METHODS: UBE2T expression in HNSC patient samples and the correlation between its expression and patients' survival rates were evaluated using The Cancer Genome Atlas (TCGA) database. Cell survival and proliferation were investigated in UM-SCC1 and UM-SCC15 cells infected with control and shUBE2T lentivirus. The xenograft mouse model was established using UM-SCC15 cells to examine HNSC tumorigenesis with or without UBE2T. Western blot, qRT-PCR, and ferroptosis assays were carried out to disclose the interaction between UBE2T and NF-κB signaling and ferroptosis. RESULTS: The increased expression of UBE2T was noted in tumor tissues of patients with HNSC, correlating with a significantly reduced overall survival time in this patient cohort. Knockdown of UBE2T inhibited HNSC tumorigenesis and tumor growth. Mechanistically, inhibition of UBE2T suppressed NF-ΚB signaling and induced ferroptosis in HNSC. CONCLUSION: Our study underscores the multifaceted role of UBE2T in HNSC, illuminating its potential as a biomarker and therapeutic target.

LINC01133 regulates MARCKS expression via sponging miR-30d-5p to promote the development of lung squamous cell carcinoma.

LncRNAs are vital regulators for lung squamous cell carcinoma (LUSC). However, the detailed role that LINC01133 plays in LUSC is unclear. This work sought to explore the potential function of LINC01133.Levels of LINC01133, miR-30d-5p, and MARCKS were separately tested in both tissues and cells using qRT-PCR. Proliferation was assessed through MTT experiment and apoptosis was detected upon flow cytometry. Transwell experiments were implemented to evaluate migratory and invasive abilities. The interaction between two genes was affirmed through luciferase reporter assay and RNA pull-down experiment. Western blotting measured the protein level of MARCKS. Animal models were established and tissues were taken for IHC analysis of MARCKS and Ki67.LINC01133 was elevated in LUSC and its downregulation could suppress proliferation, migration and invasion but induced apoptosis. LINC01133 interacted with and regulated the binding of miR-30d-5p to MARCKS. LINC01133/miR-30d-5p axis mediated proliferation, apoptosis, migration and invasion in LUSC cells, as well as modulated tumor growth in animal models. LINC01133 interacted with miR-30d-5p to modulate MARCKS expression, contributes to promoted cell proliferation, migration, invasion, and inhibited cell apoptosis in vitro, and promoted tumor growth in vivo. These findings could provide possible therapeutic targets in view of LUSC treatment in the future.

The efficacy and safety of electroacupuncture for diabetic peripheral neuropathy: A protocol for a systematic review and meta-analysis.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus, which is the most common neuropathy worldwide. Owing to the inadequacies of existing treatment methods, managing DPN remains a significant challenge. Studies suggest that electroacupuncture (EA) could potentially serve as a beneficial alternative treatment for this condition. Nevertheless, there is still inadequate proof of its therapeutic effectiveness and safety. As a result, the goal of this protocol is to methodically compile the data pertaining to the effectiveness and security of EA in the management of DPN. METHODS: To find appropriate randomized controlled trials (RCTs), nine reliable databases in the English and Chinese languages will be examined. RevMan5.3 will be used to combine the retrieved data and perform meta-analyses. The methodological quality of the included RCTs will be evaluated using the Cochrane Risk of Bias Assessment 2.0 tool. The Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) system will be utilized to evaluate the degree of strength and certainty of the evidence. We will also perform publication bias, sensitivity and subgroup analyses. DISCUSSION: This protocol describes the intended scope and approach for a forthcoming systematic review and meta-analysis that will inform therapeutic decision-making by offering current information on the efficacy and safety of EA in the treatment of DPN. The results of the study will help standardize strategies for EA in the treatment of DPN.

Can the heptapeptide ASSIVSF of the ß2-adrenoceptor recognize ephedrine and pseudoephedrine epimers in a complex system?

Epimer separation is crucial in the field of analytical chemistry, separation science, and the pharmaceutical industry. No reported methods could separate simultaneously epimers or even isomers and remove other unwanted, co-existing, interfering substances from complex systems like herbal extracts. Herein, we prepared a heptapeptide-modified stationary phase for the separation of 1R,2S-(-)-ephedrine [(-)-Ephe] and 1S,2S-(+)-pseudoephedrine [(+)-Pse] epimers from Ephedra sinica Stapf extract and blood samples. The heptapeptide stationary phase was comprehensively characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The separation efficiency of the heptapeptide column was compared with an affinity column packed with full-length ß2-AR functionalized silica gel (ß2-AR column). The binding affinity of the heptapeptide with (+)-Pse was 3-fold greater than that with (-)-Ephe. Their binding mechanisms were extensively characterized by chromatographic analysis, ultraviolet spectra, circular dichroism analysis, isothermal titration calorimetry, and molecule docking. An enhanced hydrogen bonding was clearly observed in the heptapeptide-(+)-Pse complex. Such results demonstrated that the heptapeptide can recognize (+)-Pse and (-)-Ephe epimers in a complex system. This work, we believe, was the first report to simultaneously separate epimers and remove non-specific interfering substances from complex samples. The method was potentially applicable to more challenging sample separation, such as chiral separation from complex systems.

Long-term trends in housefly (Musca domestica L.) insecticide resistance in China.

Controlling housefly populations relies on the use of insecticides, which inevitably leads to the development of resistance. A better and more comprehensive understanding of the spatial and temporal distribution of resistance could guide the control of houseflies. However, most studies on housefly resistance in China are scattered and poorly coordinated. We collected resistance data from houseflies in the published literature and from the vector biomonitoring system of the Chinese Center for Disease Control and Prevention. A 5- or 10-year resolution was used to study the temporal dynamics of resistance to five commonly used insecticides: deltamethrin, permethrin, beta-cypermethrin, dichlorvos, and propoxur. ArcGIS was used to visualize their spatial distributions. The correlation between year and resistance coefficient was determined using SPSS 26.0 and RStudio to explore the changes in resistance over the years. A total of 2128 data were included in this study, ranging from 1982 to 2022, based on which we found significant increases in resistance over the past forty years for the five studied insecticides. Among them, pyrethroids had the most strikingly elevated resistance level and were mainly distributed in the northern and southeastern coastal areas. Dichlorvos and propoxur had intermediate increases in resistance, and most of these increases were identified in North China and the Yangtze River. Housefly resistance to commonly used insecticides in China is increasing and spatially heterogeneous. This finding also highlights the necessity of continuous routine surveillance of housefly resistance, which could guide future housefly control operations and slow the development of resistance.

Evaluating the efficacy and acceptability of vagus nerve stimulation for fibromyalgia: a PRISMA-compliant protocol for a systematic review and meta-analysis.

Background: Fibromyalgia has imposed substantial burdens on patients' health and well-being, yet effective therapeutic options for this condition remain limited. Recently, vagus nerve stimulation (VNS) has emerged as a promising therapy for fibromyalgia. Nonetheless, despite the increasing number of randomized clinical trials (RCTs), current evidence remains inconclusive. Therefore, this protocol of a systematic review and meta-analysis aims to synthesize the existing evidence to clarify the efficacy and acceptability of VNS for treating fibromyalgia. Methods: A comprehensive search for eligible RCTs will be conducted across nine bibliographic databases, namely PubMed, Cochrane Library, Embase, AMED, PsycINFO, PEDro, Chinese BioMedical Literature Database, Chinese National Knowledge Infrastructure, and Wangfang database. Data obtained from the included studies will be synthesized quantitively using RevMan 5.4.1 for meta-analyses. The methodological soundness of included RCTs will be assessed via the Cochrane's updated risk of bias tool (version 2.0). Additionally, sensitivity analyses, publication bias assessment, and subgroup analyses will be conducted as appropriate. Finally, we will utilize the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to evaluate the certainty for the body of evidence. Conclusion: The findings of our study are anticipated to ascertain the efficacy and acceptability of VNS as a promising treatment option for fibromyalgia. This will not only fill current research gap but also identify potential areas for future research. The findings will provide essential guidance for evidence-based treatment decisions for fibromyalgia, benefiting both patients and clinicians.

A Modular and Cost-Effective Droplet Microfluidic Device for Controlled Emulsion Production.

The droplet microfluidic device has become a widely used tool in fields such as physics, chemistry, and biology, but its complexity has limited its widespread application. This report introduces a modular and cost-effective droplet microfluidic device for the controlled production of complex emulsions, including oil and aqueous single emulsions, and double emulsions with varying numbers of encapsulated droplets. The droplet sizes can be precisely controlled by easily replacing flat needles and adjusting the needle position within an axially accelerated co-flow field. This modular device not only allows for easy repair and maintenance in case of device clogging or damage but can also be readily expanded to produce complex emulsions. The low-cost and user-friendly nature of the device greatly facilitates the widespread adoption and utilization of droplet microfluidics.

Loss of Ezh2 in the medial ganglionic eminence alters interneuron fate, cell morphology and gene expression profiles.

Introduction: Enhancer of zeste homolog 2 (Ezh2) is responsible for trimethylation of histone 3 at lysine 27 (H3K27me3), resulting in repression of gene expression. Here, we explore the role of Ezh2 in forebrain GABAergic interneuron development. Methods: We removed Ezh2 in the MGE by generating Nkx2-1Cre;Ezh2 conditional knockout mice. We then characterized changes in MGE-derived interneuron fate and electrophysiological properties in juvenile mice, as well as alterations in gene expression, chromatin accessibility and histone modifications in the MGE. Results: Loss of Ezh2 increases somatostatin-expressing (SST+) and decreases parvalbumin-expressing (PV+) interneurons in the forebrain. We observe fewer MGE-derived interneurons in the first postnatal week, indicating reduced interneuron production. Intrinsic electrophysiological properties in SST+ and PV+ interneurons are normal, but PV+ interneurons display increased axonal complexity in Ezh2 mutant mice. Single nuclei multiome analysis revealed differential gene expression patterns in the embryonic MGE that are predictive of these cell fate changes. Lastly, CUT&Tag analysis revealed that some genomic loci are particularly resistant or susceptible to shifts in H3K27me3 levels in the absence of Ezh2, indicating differential selectivity to epigenetic perturbation. Discussion: Thus, loss of Ezh2 in the MGE alters interneuron fate, morphology, and gene expression and regulation. These findings have important implications for both normal development and potentially in disease etiologies.

The association of GNB5 with Alzheimer disease revealed by genomic analysis restricted to variants impacting gene function.

Disease-associated variants identified from genome-wide association studies (GWASs) frequently map to non-coding areas of the genome such as introns and intergenic regions. An exclusive reliance on gene-agnostic methods of genomic investigation could limit the identification of relevant genes associated with polygenic diseases such as Alzheimer disease (AD). To overcome such potential restriction, we developed a gene-constrained analytical method that considers only moderate- and high-risk variants that affect gene coding sequences. We report here the application of this approach to publicly available datasets containing 181,388 individuals without and with AD and the resulting identification of 660 genes potentially linked to the higher AD prevalence among Africans/African Americans. By integration with transcriptome analysis of 23 brain regions from 2,728 AD case-control samples, we concentrated on nine genes that potentially enhance the risk of AD: AACS, GNB5, GNS, HIPK3, MED13, SHC2, SLC22A5, VPS35, and ZNF398. GNB5, the fifth member of the heterotrimeric G protein beta family encoding Gß5, is primarily expressed in neurons and is essential for normal neuronal development in mouse brain. Homozygous or compound heterozygous loss of function of GNB5 in humans has previously been associated with a syndrome of developmental delay, cognitive impairment, and cardiac arrhythmia. In validation experiments, we confirmed that Gnb5 heterozygosity enhanced the formation of both amyloid plaques and neurofibrillary tangles in the brains of AD model mice. These results suggest that gene-constrained analysis can complement the power of GWASs in the identification of AD-associated genes and may be more broadly applicable to other polygenic diseases.

Ordered sulfonated polystyrene particle chains organized through AC electroosmosis as reinforcing phases in Polyacrylamide hydrogels.

Polyacrylamide (PAM) hydrogels have garnered significant attention due to their unique swelling properties, biocompatibility, and stability, resulting in them being promising candidates for various applications, ranging from drug delivery to tissue engineering. However, traditional PAM hydrogels suffer from low strength and poor toughness, which limits their widespread use. In this study, based on the theory of filler-reinforced composites, we introduced ordered sulfonated polystyrene (SPS) particles into PAM hydrogels using electric field-assisted techniques. The effects of the geometric dimensions and filling concentration of SPS particles on thermal stability, swelling/deswelling behavior, and mechanical properties of composite hydrogels were investigated. When filled with ordered 100 nm SPS particles at a concentration of 2.0 g·L-1, the resulting SPS/PAM composite exhibited improved water retention capacity, as well as a fracture elongation of 316 % and a tensile strength of 23 kPa. These findings in the paper provide valuable insights into the understanding of PAM hydrogels and open up new avenues for the development of advanced hydrogel-based systems with enhanced performance and functionality.

Antihypertensive effect and mechanism of the traditional recipe of medicine food homology (Buyang Huanwu Decoction) in China: Meta analysis and network pharmacological exploration.

Background: Hypertension has become a part of the lives of many people worldwide. With the development, an increasing number of people have begun to control their hypertension through products of medicine food homology, such as Buyang Huanwu Decoction (BYHWD). However, there has been no objective review of the regulation of hypertension by BYHWD. Methods: As of 9 October 2023, this review made a detailed search of nine databases to look for random controlled trials (RCTs) focused on the use of BYHWD for treating hypertension. This was followed by network pharmacological analysis, and molecular docking assessment using AutoDockTools to explore the mode of action. Results: BYHWD was effective in reducing SBP (MD: 0.767; 95 % CI: 0.629, 0.905; p = 0.000), DBP (MD: 0.427; 95 % CI: 0.292, 0.561; p = 0.000), 24h SBP (MD: 0.665; 95 % CI: 0.368, 0.962; p = 0.000), 24h DBP (MD: 0.547; 95 % CI: 0.318, 0.777; p = 0.000), dSBP (MD: 0.625; 95 % CI: 0.395, 0.855; p = 0.000), dDBP (MD: 0.632; 95 % CI: 0.401, 0.862; p = 0.000), nSBP (MD: 0.859; 95 % CI: 0.340, 1.377; p = 0.001), nDBP (MD: 0.704; 95 % CI: 0.297, 1.112; p = 0.001), pv (MD: 1.311; 95 % CI: 0.363, 2.259; p = 0.007) and NIHSS (MD: 1.149; 95 % CI: 0.100, 2.199; p = 0.032), and elevating CER (OR = 2.848; 95 % CI: 1.388, 5.843; p = 0.004). However, BYHWD did not significantly reduce HCY, and there was no significant difference in the incidence of AE. In terms of the mechanism of action, the main active ingredient of BYHWD is quercetin, and the core targets are AKT1, MMP9, and others. Molecular docking also showed that quercetin mainly interacts with the amino acid residue CYS-28 of MMP2. Second, the KEGG analysis showed that BYHWD mainly act on HIF-1, Apelin, and cGMP-PKG signalling pathways, and GO analysis showed that it related to the apical part of the cell, circulatory system processes, and nuclear receptor activity. Conclusion: BYHWD can lowered blood pressure, reduced plasma viscosity, and restored neurological function with good tolerability, and had no significant effect on HCY levels. This study further demonstrated that quercetin is the main active ingredient of BYHWD that acts via the AKT1 and HIF-1 signalling pathways. These results provide new guidance for people's dietary choices by the general public.

A Versatile Strategy for the Generation of Air-stable Radical-functionalized Materials.

The exploration of a facile approach to create structurally versatile substances carrying air-stable radicals is highly desired, but still a huge challenge in chemistry and materials science. Herein, a non-contact method to generate air-stable radicals by exposing pyridine/imidazole ring-bearing substances to volatile cyanuric chloride vapor, harnessed as a chemical fuel is reported. This remarkable feat is accomplished through a nucleophilic substitution reaction, wherein an intrinsic electron transfer event transpires spontaneously, originating from the chloride anion (Cl- ) to the cationic nitrogen (N+ ) atom, ultimately giving rise to pyridinium/imidazolium radicals. Impressively, the generated radicals exhibit noteworthy stability in the air over one month owing to the delocalization of the unpaired electron through the extended and highly fused π-conjugated pyridinium/imidazolium-triazine unit. Such an approach is universal to diverse substances, including organic molecules, metal-organic complexes, hydrogels, polymers, and organic cage materials. Capitalizing on this versatile technique, surface radical functionalization can be readily achieved across diverse substrates. Moreover, the generated radical species showcase a myriad of high-performance applications, including mimicking natural peroxidase to accelerate oxidation reactions and achieving high-efficiency near-infrared photothermal conversion and photothermal bacterial inhibition.

Circ_0030042 inhibits trophoblast cell growth, invasion and epithelial-mesenchymal transition process in preeclampsia via miR-942-5p/LITAF.

BACKGROUND: There is increasing evidence that circular RNAs (circRNAs) are involved in the processes of preeclampsia (PE). Circ_0030042 was found to be abnormally expressed in PE patients. However, the role and molecular mechanism of circ_0030042 in PE progression remains unclear. METHODS: Quantitative real-time PCR was used for determining the expression of circ_0030042, microRNA (miR)- 942-5p and lipopolysaccharide induced TNF-α factor (LITAF). Trophoblast cell functions were determined using cell counting kit 8 assay, EdU assay, flow cytometry and transwell assay. The protein levels of epithelial-mesenchymal transition (EMT)-related markers and LITAF were examined using western blot analysis. Dual-luciferase reporter assay and RNA pull-down assay were used to verify RNA interaction. RESULTS: Circ_0030042 had an elevated expression in PE patients, and its overexpression inhibited trophoblast cell growth, invasion, and EMT process. Circ_0030042 served as miR-942-5p sponge, and miR-942-5p inhibitor also reversed the regulation of circ_0030042 on trophoblast cell growth, invasion and EMT process. LITAF was targeted by miR-942-5p, and its knockdown abolished the inhibition effect of miR-942-5p on trophoblast cell growth, invasion, and EMT process. Also, circ_0030042 regulated LITAF expression via sponging miR-942-5p. CONCLUSION: Circ_0030042 regulated trophoblast cell growth, invasion, and EMT process via the miR-942-5p/LITAF axis, providing a novel insight for PE treatment.

Gastrodin alleviates NTG-induced migraine-like pain via inhibiting succinate/HIF-1α/TRPM2 signaling pathway in trigeminal ganglion.

BACKGROUND: Increasing evidence highlights the involvement of metabolic disorder and calcium influx mediated by transient receptor potential channels in migraine; however, the relationship between these factors in the pathophysiology of migraine remains unknown. Gastrodin is the major component of the traditional Chinese medicine Tianma, which is extensively used in migraine therapy. PURPOSE: Our work aimed to explore the analgesic action of gastrodin and its regulatory mechanisms from a metabolic perspective. METHODS/RESULTS: After being treated with gastrodin, the mice were given nitroglycerin (NTG) to induce migraine. Gastrodin treatment significantly raised the threshold of sensitivity in response to both mechanical and thermal stimulus evidenced by von Frey and hot plate tests, respectively, and decreased total contact numbers in orofacial operant behavioral assessment. We found that the expression of transient receptor potential melastatin 2 (TRPM2) channel was increased in the trigeminal ganglion (TG) of NTG-induced mice, resulting in a sustained Ca2+ influx to trigger migraine pain. The content of succinate, a metabolic biomarker, was elevated in blood samples of migraineurs, as well as in the serum and TG tissue from NTG-induced migraine mice. Calcium imaging assay indicated that succinate insult elevated TRPM2-mediated calcium flux signal in TG neurons. Mechanistically, accumulated succinate upregulated hypoxia inducible factor-1α (HIF-1α) expression and promoted its translocation into nucleus, where HIF-1α enhanced TRPM2 expression through transcriptional induction in TG neurons, evidenced by luciferase reporter measurement. Gastrodin treatment inhibited TRPM2 expression and TRPM2-dependent Ca2+ influx by attenuating succinate accumulation and downstream HIF-1α signaling, and thereby exhibited analgesic effect. CONCLUSION: This work revealed that succinate was a critical metabolic signaling molecule and the key mediator of migraine pain through triggering TRPM2-mediated calcium overload. Gastrodin alleviated NTG-induced migraine-like pain via inhibiting succinate/HIF-1α/TRPM2 signaling pathway in TG neurons. These findings uncovered the anti-migraine effect of gastrodin and its regulatory mechanisms from a metabolic perspective and provided a novel theoretical basis for the analgesic action of gastrodin.

Subnanometric Bismuth Clusters Confined in Pyrochlore-Bi2 Sn2 O7 Enable Remarkable CO2 Photoreduction.

The development of highly efficient photocatalysts for conversion of carbon dioxide (CO2 ) with water (H2 O) into chemical fuels is of great importance for energy sustainability and carbon resource utilization. Herein, we demonstrated a facile hydrothermal method for in situ construction of subnanometric Bi metallic clusters in pyrochlore-Bi2 Sn2 O7 frameworks, leading to the remarkable improvements of photocatalytic performances for CO2 reduction into CO in the absence of sacrificial reagent. More specifically, an outstanding CO evolution activity of 114.1 µmol g-1 h-1 has been achieved, more than 20-fold improvement compared with the pristine Bi2 Sn2 O7 (5.7 µmol g-1 h-1 ). Detailed experiments together with in situ characterizations reveal that the spatially confined Bi clusters could significantly promote charge-separation/electron-enrichment and adsorption/activation of CO2 molecules, which provides highly efficient reaction channels to facilitate the generation of *COOH intermediate as well as the subsequent desorption of *CO towards CO formation. These demonstrations provide an important knowledge for precise design and fabrication of highly efficient photocatalysts for CO2 conversion into solar fuels.

Progress in Fabrication and Applications of Cholesteric Liquid Crystal Microcapsules.

Liquid crystals (LCs) are well known for inherent responsiveness to external stimuli, such as light, thermal, magnetic, and electric fields. Cholesteric LCs are among the most fascinating, since they possess distinctive optical properties due to the helical molecular orientation. However, the good flow, easy contamination, and poor stability of small-molecule LCs limit their further applications, and microencapsulation as one of the most effective tools can evade these disadvantages. Microencapsulation can offer shell-core structure with LCs in the core can strengthen their stability, avoiding interference with the environment while maintaining the stimuli-responsiveness and optical properties. Here, we report recent progress in the fabrication and applications of cholesteric LC microcapsules (CLCMCs). We summarize general properties and basic principles, fabrication methods including interfacial polymerization, in-situ polymerization, complex coacervation, solvent evaporation, microfluidic and polymerization of reactive mesogens, and then give a comprehensive overview of their applications in various popular domains, including smart fabrics, smart sensor, smart displays, anti-counterfeiting, information encryption, biomedicine and actuators. Finally, we discuss the currently facing challenges and the potential development directions in this field.