Bletilla striata carbon dots with alleviating effect of DSS-induced ulcerative colitis.

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that significantly affected quality of life for patients. In this study, carbon dots based on Bletilla striata (BS-CDs) were synthesized by hydrothermal method and characterized by optical property analysis. In addition, the study measured the potential effect of BS-CDs on colonic histopathology and inflammation in dextran sulfate sodium (DSS)-induced ulcerative colitis. The results suggested that BS-CDs significantly increased colon length, improved colonic histopathology, and reduced the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in colitis mice. Taken together, BS-CDs alleviate clinical inflammation by blocking pro-inflammatory cytokines which were expected to be a potential agent for the treatment of colitis.

Male vitellogenin regulates gametogenesis through a testis-enriched big protein in Chrysopa pallens.

In insects, vitellogenin (Vg) is generally viewed as a female-specific protein. Its primary function is to supply nutrition to developing embryos. Here, we reported Vg from the male adults of a natural predator, Chrysopa pallens. The male Vg was depleted by RNAi. Mating with Vg-deficient male downregulated female Vg expression, suppressed ovarian development and decreased reproductive output. Whole-organism transcriptome analysis after male Vg knockdown showed no differential expression of the known spermatogenesis-related regulators and seminal fluid protein genes, but a sharp downregulation of an unknown gene, which encodes a testis-enriched big protein (Vcsoo). Separate knockdown of male Vg and Vcsoo disturbed the assembly of spermatid cytoplasmic organelles in males and suppressed the expansion of ovary germarium in mated females. These results demonstrated that C. pallens male Vg signals through the downstream Vcsoo and regulates male and female reproduction.

Temperature regulates synaptic subcellular specificity mediated by inhibitory glutamate signaling.

Environmental factors such as temperature affect neuronal activity and development. However, it remains unknown whether and how they affect synaptic subcellular specificity. Here, using the nematode Caenorhabditis elegans AIY interneurons as a model, we found that high cultivation temperature robustly induces defects in synaptic subcellular specificity through glutamatergic neurotransmission. Furthermore, we determined that the functional glutamate is mainly released by the ASH sensory neurons and sensed by two conserved inhibitory glutamate-gated chloride channels GLC-3 and GLC-4 in AIY. Our work not only presents a novel neurotransmission-dependent mechanism underlying the synaptic subcellular specificity, but also provides a potential mechanistic insight into high-temperature-induced neurological defects.

[Prospective,multi-center,and large-scale hospital centralized monitoring of clinical safety of Reduning Injection in 100249 children cases].

This study utilized a prospective, large-sample, multi-center, and registered key specialty approach of hospitals to monitor the application of Reduning Injection. A total of 100 249 adolescent patients aged 14 years and below who received Reduning Injection were monitored, resulting in 83 cases of adverse events, with 76 of them being classified as adverse drug reaction(ADR). The calculated incidence rate of ADR for Reduning Injection was 0.076%, indicating a very rare ADR. The main symptoms of ADR were pruritus, diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsion, and chills. All ADR cases were reported for the first time, including three new ADR cases and 73 known ADR cases. The categories of ADR was general ADR. All ADR was mild in severity. There were more males than females in ADR patients. One patient had a history of ADR, and the drug causing ADR was buprofen. The largest number of ADR cases occurred when the dosage of Reduning injection was 5-10 mL. The dropping speed was 30 drops or less per min, and the solvent type was 5% glucose injection. The most common manifestation of ADR patients was pruritus, followed by diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsions, and chills. 72 patients(94.74% of ADR patients) discontinued the drug, and three patients(3.95% of ADR patients) were given oxygen inhalation. 47 cases(61.84% of ADR patients) were treated with medication, of which dexamethasone was the most used(24 cases, 46.15% of ADR patients). 76 ADR patients were cured or improved. ADRs are more likely to occur when diagnosed with acute bronchitis by western medicine and cough by traditional Chinese medicine(TCM), TCM syndrome type is wind heat syndrome, and the combination medicine is ambroxol hydrochloride and bromhexine hydrochloride injection, ascorbic acid/vitamin C injection. This result provides an evidence-based safety basis for active pharmacovigilance of Reduning Injection in adolescents aged 14 years and below.

The influence of verapamil on the pharmacokinetics of the pan-HER tyrosine kinase inhibitor neratinib in rats: the role of P-glycoprotein-mediated efflux.

Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has been approved for the treatment of HER2-positive (HER2+) early-stage and brain metastatic breast cancer. Thus far, the pharmacology effects and pharmacodynamics of neratinib have been well studied. However, the disposition of neratinib and its influencing factors in vivo remain unclear. P-glycoprotein (P-gp), one of the most extensively studied transporters, substantially restricts penetration of drugs into the body or deeper compartments (i.e., blood-brain barrier, BBB), regarding drug resistance and drug-drug interactions. Thereby, the aim of this study was to investigate the influence of verapamil (a P-gp inhibitor) on the pharmacokinetics of neratinib in rats. Here, we have established a high specific, selective and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to quantify plasma concentrations of neratinib in rats. Pharmacokinetic results showed that verapamil significantly increased the system exposure of neratinib, as Cmax increased by 2.09-fold and AUC0-t increased by 1.64-fold, respectively. Additionally, the in vitro transport of neratinib was evaluated using Madin-Darby canine kidney II (MDCK II) and human MDR1 gene overexpressed MDCK (MDCK-MDR1) cell line models. As a result, the net flux ratio was over than 2 and decreased over 50% by verapamil, suggesting that neratinib was a substrate of P-gp. Hence, our findings have highlighted the important role of P-gp in the system exposure of neratinib in vivo, and drug-drug interaction should be considered when coadministration of P-gp inhibitors with neratinib. These findings may support the further clinical development and application of neratinib.

Physiological and iTRAQ-based quantitative proteomics analyses reveal the similarities and differences in stress responses between short-term boron deficiency and toxicity in wheat roots.

BACKGROUND: Boron (B) is a trace element that is essential for normal wheat development, such as root growth. In wheat, roots are important organs that absorb nutrients and water. However, at present, there is insufficient research on the molecular mechanism underlying how short-term B stress affects wheat root growth. METHODS AND RESULTS: Here, the optimal concentration of B for wheat root growth was determined, and the proteomic profiles of roots under short-term B deficiency and toxicity were analyzed and compared by the isobaric tag for relative and absolute quantitation (iTRAQ) technique. A total of 270 differentially abundant proteins (DAPs) that accumulated in response to B deficiency and 263 DAPs that accumulated in response to B toxicity were identified. Global expression analysis revealed that ethylene, auxin, abscisic acid (ABA), and Ca2+ signals were involved in the responses to these two stresses. Under B deficiency, DAPs related to auxin synthesis or signaling and DAPs involved in calcium signaling increased in abundance. In striking contrast, auxin and calcium signals were repressed under B toxicity. Twenty-one DAPs were detected under both conditions, including RAN1 that played a core role in the auxin and calcium signals. Overexpression of RAN1 was shown to confer plant resistance to B toxicity by activating auxin response genes, including TIR and those identified by iTRAQ in this research. Moreover, growth of the primary roots of tir mutant was significantly inhibited under B toxicity. CONCLUSION: Taken together, these results indicate that some connections were present between RAN1 and the auxin signaling pathway under B toxicity. Therefore, this research provides data for improving the understanding of the molecular mechanism underlying the response to B stress.

Xiebai Zengye decoction improves respiratory function and attenuates inflammation in juvenile rats with postinfection cough via regulating ERK signaling pathway.

This study aimed to determine the effects of Xiebai Zengye decoction (XBZY) on airway inflammation and respiratory function in rats with postinfectious cough (PIC), and its regulatory effects on the extracellular signal-regulated kinase (ERK) signaling pathway. Compared with the normal group, the rats from the PIC group had significantly shortened expiratory time (TE) and enhanced pause (EEP), increased resistance (RT), and enhanced pause (Penh), along with increased levels of serum interleukin-4 (IL-4) and IL-6, and decreased levels of IL-10. The lung and colon tissues of rats from the PIC group showed histopathological changes, including inflammatory cell infiltration, damaged mucosal epithelium, and crypt structure, with significantly increased ERK mRNA and protein expression levels. Treatment with XBZY and montelukast sodium (MAS) improved the respiratory function and serum cytokine levels, reduced tissue inflammation, and decreased ERK mRNA and protein expression levels in the lung and colon tissues. In the lung tissues, XBZY treatment significantly decreased the expression of phosphorylated-ERK (p-ERK) protein, as well as p-MEK1/2, p-ERK1/2, and p-c-Fos proteins, while in the colon tissues, XBZY significantly decreased the expression of p-ERK1/2 and p-c-Fos proteins. However, MAS treatment only showed significant improvement in the lung tissue inflammation score, and the expression level of p-ERK protein in the lung tissue was decreased. In conclusion, the present study suggests that XBZY has a potential therapeutic effect on PIC by improving respiratory function and attenuating inflammation, and this effect may be associated with the inhibition of the ERK signaling pathway. These findings could provide a new direction for the development of treatments for PIC. However, further research is needed to elucidate the underlying molecular mechanisms of XBZY and to confirm its safety and efficacy in clinical trials.

Chemical profiling and identification of Radix Cudramiae and their metabolites in rats using an ultra-high-performance liquid chromatography method coupled with time-of-flight tandem mass spectrometry.

Radix Cudramiae, known as "Chuan-Po-Shi" in China, is a herbal medicine widely used in the southwest of the country, especially applied by the Miao and Zhuang nationalities for the treatment of liver diseases, such as acute liver injury and liver fibrosis. As a kind of ethnomedicine, the report on its chemical analysis was still blank, which restricted its clinical application. Therefore, this paper aimed to illustrate the chemical characteristics of Radix Cudramiae. A rapid analytical strategy based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was developed to profile the natural small-molecular compounds in Radix Cudramiae, as well as the related prototypes and their metabolites in rats after drug administration. As a result, a total of 74 compounds were detected in the aqueous exact of Radix Cudramiae. In vivo, 45 chemicals including 16 prototypes and 29 metabolites in rat serum, along with 35 chemicals including 17 prototypes and 18 metabolites in rat liver, were screened out and identified. For the first time, the chemical constituents of Radix Cudramiae and their metabolic characteristics were discovered. It was hoped that this work would be beneficial for the safe and effective application of Radix Cudramiae in a clinic.

The green lacewing Chrysopa formosa as a potential biocontrol agent for managing Spodoptera frugiperda and Spodoptera litura.

Understanding predator-prey interactions is essential for successful pest management by using predators, especially for the suppression of novel invasive pest. The green lacewing Chrysopa formosa is a promising polyphagous predator that is widely used in the biocontrol of various pests in China, but information on the control efficiency of this predator against the seriously invasive pest Spodoptera frugiperda and native Spodoptera litura is limited. Here we evaluated the predation efficiency of C. formosa adults on eggs and first- to third-instar larvae of S. frugiperda and S. litura through functional response experiments and determined the consumption capacity and prey preference of this chrysopid. Adults of C. formosa had a high consumption of eggs and earlier instar larvae of both prey species, and displayed a type II functional response on all prey stages. Attack rates of the chrysopid on different prey stages were statistically similar, but the handling time increased notably as the prey developed. The highest predation efficiency and shortest-handling time were observed for C. formosa feeding on Spodoptera eggs, followed by the first-instar larvae. C. formosa exhibited a significant preference for S. litura over S. frugiperda in a two-prey system. In addition, we summarized the functional response and predation efficiency of several chrysopids against noctuid pests and made a comparison with the results obtained from C. formosa. These results indicate that C. formosa has potential as an agent for biological control of noctuid pests, particularly for the newly invasive pest S. frugiperda in China.

Synthesis of NaA zeolite from foundry dust and its adsorption capacity of ammonia.

Eutrophication of water bodies due to excess ammonia nitrogen (NH4+-N) is harmful to aquatic organisms and human health. In this study, foundry dust (FD) from foundry industry was used to synthesize NaA zeolite to use as an adsorbent to remove NH4+-N from wastewater. Results demonstrate that FD could be successfully synthesized to form a foundry dust-based NaA zeolite (FZA) through adjustment of the silica-alumina ratio of n (SiO2)/n (Al2O3) at 2 at 95 °C. Specific surface area, total pore volume, and cation exchange capacity (CEC), and maximum adsorption NH4+-N of FZA was respectively 43.185 cm2/g, 0.0364 cm3/g, 212.35 mmol/100 g and 37.81 mg/g, which was 4.74, 1.54, 1.52 and 1.62 times as much as the NaA zeolite (SZA). FZA with higher adsorption NH4+-N capacity was related to higher specific surface area and CEC. The NH4+-N adsorption amount of 28.57 mg/g by FZA was obtained after the fourth regeneration, which was notably higher than that of SZA (23.27 mg/g). The desorption rate of NH4+-N from FZA was 87% by the fourth regeneration. FZA effectively removed NH4+-N from swine wastewater containing 153.32 mg/L NH4+-N. Results suggest that FZA could be used as absorbent to removal NH4+-N from wastewater.

Elevation of spermine remodels immunosuppressive microenvironment through driving the modification of PD-L1 in hepatocellular carcinoma.

BACKGROUND: Spermine is frequently elevated in tumor tissues and body fluids of cancer patients and is critical for cancer cell proliferation, migration and invasion. However, the immune functions of spermine in hepatocellular carcinoma progression remains unknown. In the present study, we aimed to elucidate immunosuppressive role of spermine in hepatocellular carcinoma and to explore the underlying mechanism. METHODS: Whole-blood spermine concentration was measured using HPLC. Human primary HCC tissues were collected to examine the expression of CaSR, p-Akt, ß-catenin, STT3A, PD-L1, and CD8. Mouse model of tumorigenesis and lung metastasis were established to evaluate the effects of spermine on hepatocellular carcinoma. Western blotting, immunofluorescence, real time PCR, digital Ca2+ imaging, and chromatin immunoprecipitation assay were used to investigate the underlying mechanisms by which spermine regulates PD-L1 expression and glycosylation in hepatocellular carcinoma cells. RESULTS: Blood spermine concentration in the HCC patient group was significantly higher than that in the normal population group. Spermine could facilitate tumor progression through inducing PD-L1 expression and decreasing the CD8+ T cell infiltration in HCC. Mechanistically, spermine activates calcium-sensing receptor (CaSR) to trigger Ca2+ entry and thereby promote Akt-dependent ß-catenin stabilization and nuclear translocation. Nuclear ß-catenin induced by spermine then activates transcriptional expression of PD-L1 and N-glycosyltransferase STT3A, while STT3A in turn increases the stability of PD-L1 through inducing PD-L1 protein N-glycosylation in HCC cells. CONCLUSIONS: This study reveals the crucial function of spermine in establishing immune privilege by increasing the expression and N-glycosylation of PD-L1, providing a potential strategy for the treatment of hepatocellular carcinoma. Video Abstract.

Contribution to understanding the evolution of holometaboly: transformation of internal head structures during the metamorphosis in the green lacewing Chrysopa pallens (Neuroptera: Chrysopidae).

BACKGROUND: Metamorphosis remains one of the most complicated and poorly understood processes in insects. This is particularly so for the very dynamic transformations that take place within the pupal sheath of holometabolous insects. Only few studies address these transformations especially with regard to cranial structures of those holometabolous species where the larval and adult forms have a similar diet. It thus remains unclear to what extent the internal structures undergo histolysis and rebuilding. Here, the development of the brain and skeleto-muscular system of the head of Chrysopa pallens (Rambur, 1838) is studied. This species is a predator of aphids in the larval and adult stage. RESULTS: We used micro-computed-tomography (µ-CT) to study the transformations of the larval, prepupal and pupal head within the cocoon. We first assessed the morphological differences and similarities between the stages. We then determined the point in time when the compound eyes appear and describe the re-orientation of the head capsule which transforms the prognathous larva into a hypognathous adult. The internal head muscles are distinctly more slender in larvae than adults. In addition, the adults have a significantly larger brain which is likely needed for the processing of the signals obtained by the adults vastly expanded sensory organs that are presumably needed for dispersal and mating. Our study shows that the histolysis and modification of the inner muscles and skeletal elements take place within the prepupa. The central nervous system persists throughout metamorphosis but its morphology changes significantly. CONCLUSION: Our study reveals that not only the inner structures, but also the outer morphology continues to change after the final larval moult. The adult cuticle and internal structures form gradually within the cocoon. The histolysis and rebuilding begin with the skeletal elements and is followed by changes in the central nervous system before it concludes with modifications of the musculature. This order of events is likely ancestral for Holometabola because it is also known from Hymenoptera, Diptera, Mecoptera, and Coleoptera.

The Necessity of Clinical Rh Phenotypic Serological Detection and Homotypic Infusion in Patients with Repeated Blood Transfusion.

BACKGROUND This study analyzed the distribution of Rh serological phenotype in people living in Hangzhou, China, and assessed the necessity of its routine clinical detection and homotypic infusion. MATERIAL AND METHODS Blood donors and patients who might need blood transfusion were enrolled into the study, and ABO and 5 major Rh serological antigens (C, c, D, E, and e) were routinely detected. The consistent ABO and Rh serological phenotype blood was transfused between the blood donors and recipients. Irregular antibodies were screened and identified in patients before the blood transfusion. Then, the transfusion adverse effects were monitored and compared with the previous data in the hospital. RESULTS The phenotypic frequencies of Rh blood groups were D>C>E>c>e. The CCDee was the most common phenotype and CcdEe was the least common. The detection rate of unexpected antibodies gradually increased, while the unexpected antibodies slowly decreased in the Rh system. There was a correlation between the isotypic infusion of 5 Rh antigens and the detection rate of antibodies in the Rh system (R=0.845). The adverse effects of blood transfusion declined from 19.95% in 2011 with just homotypic ABO infusion to 3.098% in 2019 with the transfusion of homotypic ABO and the 5 major Rh serological antigens. CONCLUSIONS The consistency of the transfusion with ABO and 5 significant Rh serological antigens could prevent and decrease the high frequency production of isoantibodies, which is of vital importance in reducing the incidence rate of adverse effects in patients receiving transfusions.

Wuhu Decoction Regulates Dendritic Cell Autophagy in the Treatment of Respiratory Syncytial Virus (RSV)-Induced Mouse Asthma by AMPK/ULK1 Signaling Pathway.

BACKGROUND Dendritic cell autophagy plays a pivotal role in asthma. Wuhu decoction can significantly improve respiratory syncytial virus (RSV) bronchiolitis and delay its development into asthma. The aim of the present study was to explore the therapeutic effect and mechanism of Wuhu decoction on RSV -induced asthma in mice. MATERIAL AND METHODS Establishment of asthmatic mice model was induced by RSV. Hematoxylin-eosin staining, periodic acid-Schiff (PAS) staining, and Masson trichrome staining were performed to observe pathological changes in the lungs. The levels of CD4⁺ T, CD8⁺ T, and CD4⁺ CD25⁺ T in blood were analyzed by flow cytometry. The contents of interleukin (IL)-4, interferon-gamma (IFN-γ), IL-10, and IL-13 in serum were measured by enzyme-linked immunosorbent assay (ELISA). The number of autophagosomes in dendritic cells (DCs) of lung tissue was observed by transmission electron microscope. The DCs of lung tissue were isolated by magnetic bead sorting. The levels of LC3-II, Beclin-1, and LC3-I in DCs and MMP-9, TIMP-1, AMPK, p-AMPK, ULK1, and LK1 expression in lung tissues were detected by western blot. Real-time polymerase chain reaction (PCR) detected the expression of AMPK and ULK1 genes. RESULTS Wuhu decoction can effectively alleviate chronic airway inflammation and airway remodeling and reduce airway hyperresponsiveness. Moreover, Wuhu decoction can significantly enhance the level of autophagy in DCs of lung tissue and promote the expression of AMPK and ULK1 in lung tissue. CONCLUSIONS Wuhu decoction may improve the RSV-induced asthmatic symptoms by enhancing autophagy of DCs in lung tissue dependent on the AMPK/ULK1 signaling pathway.

Complete Mitochondrial Genome of Dinorhynchus dybowskyi (Hemiptera: Pentatomidae: Asopinae) and Phylogenetic Analysis of Pentatomomorpha Species.

Dinorhynchus dybowskyi (Hemiptera: Pentatomidae: Asopinae) is used as a biological control agent against various insect pests for its predatory. In the present study, the complete mitochondrial genome (mitogenome) of the species was sequenced using the next-generation sequencing technology. The results showed that the mitogenome is 15,952 bp long, including 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs), and a control region. Furthermore, the gene order and orientation of this mitogenome are identical to those of most heteropterans. There are 21 intergenic spacers (of length 1-28 bp) and 13 overlapping regions (of length 1-23 bp) throughout the genome. The control region is 1,291 bp long. The start codon of the PCGs is ATN, except cox1 (TTG), and stop codon is TAA, except nad1 (TAG). The 22 tRNAs exhibit a typical cloverleaf secondary structure, except trnS1, which lacks a dihydrouridine (DHU) arm and trnV, where the DHU arm forms a simple loop. The analyses based on nucleotide sequences of the 13 PCGs by Bayesian Inference and maximum likelihood methods. The results support the monophyly of five superfamilies Aradoidea, Pentatomoidea, Pyrrhocoroidea, Lygaeoidea, and Coreoidea. Within Pentatomoidea, the relationship observed is as follows: (Plataspidae + Urostylididae) + (Pentatomidae + (Acanthosomatidae + (Cydnidae + (Scutelleridae + (Dinidoridae + Tessaratomidae))))), and D. dybowskyi was placed in Pentatomidae and close to Eurydema gebleri.

Sterol content in the artificial diet of Mythimna separata affects the metabolomics of Arma chinensis (Fallou) as determined by proton nuclear magnetic resonance spectroscopy.

Insects cannot synthesize sterols and must obtain them from plants. Therefore, reducing plant sterol content or changing sterol type might be an effective pest control strategy. However, the impacts of these changes on pests' natural predators remain unknown. Here, we fed artificial diets with reduced sterol content to Mythimna separata (Walker) (Lepidoptera: Noctuidae) and investigated the effects on its natural predator, Arma chinensis (Fallou) (Hemiptera: Pentatomidae). Reduced sterol content in M. separata (MS1, MS2, and MS5) was achieved by feeding them artificial diets prepared from a feed base subjected to one, two, or five cycles of sterol extractions, respectively. The content of most substances increased in A. chinensis (AC) groups feeding on MS2 and MS5. The content of eight substances (alanine, betaine, dimethylamine, fumarate, glutamine, glycine, methylamine, and sarcosine) differed significantly between the control (AC0) and treated (AC1, AC2, and AC5) groups. Metabolic profiling revealed that only AC5 was significantly distinct from AC0; the major substances contributing to this difference were maltose, glucose, tyrosine, proline, O-phosphocholine, glutamine, allantoin, lysine, valine, and glutamate. Furthermore, only two metabolic pathways, that is, nicotinate and nicotinamide metabolism and ubiquinone and other terpenoid-quinone biosynthesis, differed significantly between AC1 and AC5 and the control, albeit with an impact value of zero. Thus, the sterol content in the artificial diet fed to M. separata only minimally affected the metabolites and metabolic pathways of its predator A. chinensis, suggesting that A. chinensis has good metabolic self-regulation with high resistance to sterol content changes.

The genus Neurigona Rondani, 1856 (Diptera, Dolichopodidae) from Yunnan, China, with descriptions of seven new species and a key to the species of China.

Previously, only three species of the genus Neurigona Rondani of the subfamily Neurigoninae were known from Yunnan Province. Here, we reviewed the species of Neurigona from Yunnan and added the following seven new species: N.apicilatasp. nov., N.basicurvasp. nov., N.brevidigitatasp. nov., N.convexasp. nov., N.huanglianshanasp. nov., N.quadrimaculatasp. nov., and N.ventriprocessasp. nov. All seven new species are sympatric and were collected from below a reservoir in the Huanglianshan Nature Reserve in Yunnan using three Malaise traps in 2019. This suggests a very high species richness in the Yunnan fauna. A key to the species of Neurigona from Chinese mainland is provided.

Cellular and Molecular Mechanisms Underlying Synaptic Subcellular Specificity.

Chemical synapses are essential for neuronal information storage and relay. The synaptic signal received or sent from spatially distinct subcellular compartments often generates different outcomes due to the distance or physical property difference. Therefore, the final output of postsynaptic neurons is determined not only by the type and intensity of synaptic inputs but also by the synaptic subcellular location. How synaptic subcellular specificity is determined has long been the focus of study in the neurodevelopment field. Genetic studies from invertebrates such as Caenorhabditis elegans (C. elegans) have uncovered important molecular and cellular mechanisms required for subcellular specificity. Interestingly, similar molecular mechanisms were found in the mammalian cerebellum, hippocampus, and cerebral cortex. This review summarizes the comprehensive advances in the cellular and molecular mechanisms underlying synaptic subcellular specificity, focusing on studies from C. elegans and rodents.

Molecular identification of two thioredoxin genes and their function in antioxidant defense in Arma chinensis diapause.

Thioredoxin (Trx), an important part of thioredoxin systems, plays crucial role in maintaining the intracellular redox balance by scavenging reactive oxygen species (ROS). However, few Trxs have been functionally characterized in Arma chinensis, especially in diapause. In this study, diapause induction condition promoted hydrogen peroxide accumulation and increased CAT enzymatic activity and ascorbate content, suggesting that A. chinensis was exposed to high level of ROS. Therefore, we identified AcTrx2 and AcTrx-like, and investigated the relationship with antioxidant defense. It was found that AcTrx2 expression was significantly induced, whereas AcTrx-like expression was the highest on day 10 under diapause conditions. The expression of AcTrx2 and AcTrx-like in fat body, a central metabolic organ of resisting oxidative stress, was significantly increased under diapause conditions, and was significantly improved by 5/15°C (diapause temperature). We investigated the knockdown of AcTrx2 and AcTrx-like in A. chinensis and found that some selected antioxidant genes were upregulated, indicating that the upregulated genes may be functional compensation for AcTrx2 and AcTrx-like silencing. We also found that the enzymatic activities of SOD and CAT, and the metabolite contents of hydrogen peroxide, ascorbate increased after AcTrx2 and AcTrx-like knockdown. These results suggested the AcTrx2 and AcTrx-like may play critical roles in antioxidant defense of A. chinensis diapause.

Exposure to ephedrine attenuates Th1/Th2 imbalance underlying OVA-induced asthma through airway epithelial cell-derived exosomal lnc-TRPM2-AS.

Although various anti-inflammatory medications, such as ephedrine, are employed to manage cough-variant asthma, their underlying mechanisms are yet to be fully understood. Recent studies suggest that exosomes derived from airway epithelial cells (AECs) contain components like messenger RNAs (mRNAs), micro-RNAs (miRNAs), and long noncoding RNA (lncRNA), which play roles in the occurrence and progression of airway inflammation. This study investigates the influence of AEC-derived exosomes on the efficacy of ephedrine in treating cough-variant asthma. We established a mouse model of asthma and measured airway resistance and serum inflammatory cell levels. Real-time polymerase chain reaction (RT-qPCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA) analyses were used to assess gene and protein expression levels. Exosomes were isolated and characterized. RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to examine the interaction between hnRNPA2B1 and lnc-TRPM2-AS1. In the ovalbumin (OVA)-challenged mouse model, ephedrine treatment reduced inflammatory responses, airway resistance, and Th1/Th2 cell imbalance. Exosomes from OVA-treated AECs showed elevated levels of lnc-TRPM2-AS1, which were diminished following ephedrine treatment. The exosomal lnc-TRPM2-AS1 mediated the Th1/Th2 imbalance in CD4+ T cells, with its packaging into exosomes being facilitated by hnRNPA2B1. This study unveils a novel mechanism by which ephedrine ameliorates OVA-induced CD4+ T cell imbalance by suppressing AEC-derived exosomal lnc-TRPM2-AS1. These findings could provide a theoretical framework for using ephedrine in asthma treatment.