With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

The auxin/indole-3-acetic acid (Aux/IAA) gene family is an important regulator for plant growth hormone signaling, involved in plant growth, development, as well as response to environmental stresses. In the present study, we identified SmIAA7 which is potentially associated with Salvia miltiorrhiza leaf development through comparatively analyzed the transcriptome data from different pinnate leaves. SmIAA7 was successfully isolated from S. miltiorrhiza using the specific primers. Then subsequent bioinformatic analysis, prokaryotic expression and purification, subcellular localization, and induction expression analysis under auxin and abiotic stress were performed. The full-length of SmIAA7 contained an ORF of 684 bp encoding a protein of 227 amino acid with a molecular weight of 25.3 kD. Conserved domain analysis showed that SmIAA7 contains the conserved Aux_IAA domain (pfam02309). Sequence analysis and phylogenetic tree analysis results indicated SmIAA7 was phylogenetically close to IAA7 and IAA14 from other plants, suggesting SmIAA7 involved in plant growth and development as well as response to environmental stresses. The prokaryotic expression vector pET28a-SmIAA7 was constructed and SmIAA7 recombinant protein was successfully expressed in E. coli Rosetta (DE3) strain. Subcellular localization experiment demonstrated that SmIAA7 localized in the nucleus of plant cells. Real-time fluorescence quantitative PCR results showed that the expression level of SmIAA7 was upregulated in response to auxin. Drought, low temperature, and salt stress significantly increased the transcript level of SmIAA7 gene. This study lays a foundation for further elucidating the role of SmIAA7 in leaf development, signal transduction, and stress defense in S. miltiorrhiza.

ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

Parkinson’s disease (PD), the second most common neurodegenerative disease after Alzheimer’s disease, manifests a variety of motor symptoms, such as bradykinesia, resting tremor, rigidity, postural balance disorder, and also presents non-motor symptoms, including cognitive decline, depression, constipation, and sleep disorders. Currently, treatment for PD primarily encompasses pharmacological interventions, with levodopa being the first-line therapy, and non-pharmacological approaches such as deep brain stimulation (DBS). However, both approaches exhibit therapeutic limitations, with potential adverse reactions emerging from long-term use. Levodopa is associated with dyskinesia, while DBS may lead to mental confusion, cognitive decline, and depression. Exercise, as an effective adjuvant strategy for drug treatment of PD, can significantly improve PD motor disorders. Recently, studies have found that the mechanisms of exercise improving PD motor symptoms are associated with exerkines. Exerkine refers to signalling moieties secreted in response to acute and/or chronic exercise. This review mainly summarizes the improvement of PD motor disorders by various exerkines and the underlying mechanisms. Firstly, exercise can trigger the secretion of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in the substantia nigra (SN) and the striatum, potentially improving PD. Recent evidence has suggested that both BDNF and GDNF could improve motor symptoms of PD via restoring the number of dopaminergic neurons in the SN and striatum, increasing striatal dopamine contents, and reducing α-synuclein (α-syn) accumulation in the SN. In addition, BDNF also alleviates motor symptoms of PD by enhancing long-term potentiation and increasing the spine density of spiny projection neurons in the striatum, while GDNF by inhibiting neuroinflammation in the SN via suppressing the activation of microglia, reducing interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) expressions, reducing the phosphorylation of inhibitor of nuclear factor kappa Bα (IκBα), and increasing the anti-inflammatory factors IL-10 and transforming growth factor-β (TGF-β). Secondly, exercise, a main trigger for irisin secretion from skeletal muscle, can improve PD motor symptoms by stimulating the irisin/adenosine monophosphate-activated protein kinase (AMPK)/Sirtuin-1 (SIRT1) pathway. Specifically, irisin alleviates motor symptoms in PD through multiple mechanisms, including inhibiting excessive mitochondrial fission by reducing the expressions of dynamin-related protein 1 (Drp1) and mitochondrial fission protein 1 (Fis1), alleviating the apoptosis of dopaminergic neurons by increasing B-cell lymphoma 2 (Bcl-2) expression and reducing Bcl-2-associated X protein (Bax) and caspase 3 expressions, and restoring the number of dopaminergic neurons. Thirdly, new biomarkers of PD (cathepsin B and Fetuin-A) also play roles in PD development. Cathepsin B can promote the clearance of pathogenic α-syn in PD by enhancing the function of lysosomes, including strengthening the lysosomal degradation capacity, elevating the transport rate, and increasing the activity of lysosomal glucocerebrosidase (GCase). Fetuin-A has been demonstrated to improve PD by restoring the number and the morphology of Purkinje cells, which are the only efferent neurons in the cerebellar cortex and play an important role in maintaining motor coordination. This review aims to facilitate a deep understanding of the mechanism by which exercise improves PD motor symptoms and provide a theoretical basis for promotion of exercise in PD.

ObjectiveTo investigate the material basis of homologous and heterogeneous effect of Aurantii Fructus Immaturus（AFI） and Aurantii Fructus（AF） based on the total statistical moment analysis and molecular connectivity index（MCI）. MethodRelevant literature at home and abroad and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） were consulted to establish the chemical composition database of AFI and AF， and set up their fingerprints by ultra-high performance liquid chromatography（UPLC）， and the total statistical moments and similarity parameters of the fingerprint were calculated. According to MCI， all components of AFI and AF were divided into different component groups， the average values of 0-8^th order（⁰χ-⁸χ） MCI of the common component groups of AFI and AF were calculated. ResultThe values of total zero-order moment（AUC_T） of AFI and AF were （10.57±2.45）×10⁶， （5.09±0.89）×10⁶ μV·s， the values of total first-order moment（MCRT_T） were （11.57±1.58）， （12.10±1.29） min， the values of total second-order moments（VCRT_T） were（24.49±2.30）， （26.49±2.54） min²， respectively. It showed that qualitative and quantitative parameters of AFI and AF were significantly different. The components with high similarity such as neohesperidin， hesperidin and narirutin were screened as the common potential pharmacodynamic components of AFI and AF. The non-common components of AFI， such as alysifolinone and imperatorin， and the non-common components of AF， such as neoeriocitrin and isosakuranin， with high similarity were screened out as potential heterogeneous components of AFI and AF. The composition groups of AFI and AF were classified into six categories， and the similarities between the composition groups of AFI and AF and the total constituents were 0.872-0.979 and 0.918-0.997， the average values of ⁰χ-⁸χ MCI of alkaloids in AFI and AF were 3.65 and 3.14， the average values of ⁰χ-⁸χ MCI of flavonoids were 8.47 and 8.47， the average values of ⁰χ-⁸χ MCI of volatile oils were 2.71 and 3.48， respectively. It showed that there were some differences in MCI of chemical constituents（groups） between AFI and AF. ConclusionThe chemical constituents（groups） of AFI and AF not only differ in content and species， but also in structural characteristics and structure-activity relationship， which can provide a basis for further explaining the scientific connotation of homologous and heterogeneous effect of AFI and AF.

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10^-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Objective To observe the influence of Qishen Yiqi Guttate Pills(mainly composed of Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Notoginseng Radix et Rhizoma,and Dalbergiae Odoriferae Lignum)on the clinical efficacy of patients with acute myocardial infarction after percutaneous coronary intervention(PCI).Methods Sixty post-PCI patients with acute myocardial infarction of qi deficiency and blood stasis type who met the inclusion criteria were randomly divided into a treatment group and a control group,with 30 patients in each group.The control group was treated with conventional western medicine,and the treatment group was treated with Qishen Yiqi Guttate Pills on the basis of treatment for the control group.The course of treatment for the two groups lasted for 3 months.The changes of cardiac function indicators and serum levels of hypersensitive C-reactive protein(hs-CRP)and N-terminal B-type natriuretic peptide precursor(NT-pro BNP)were observed before and after the treatment in the two groups,and the incidence of cardiovascular adverse events during the treatment in the two groups were also compared.Results(1)After treatment,the serum hs-CRP and NT-pro BNP levels of patients in the two groups were significantly decreased(P＜0.05)and the left ventricular ejection fraction(LVEF)was significantly increased(P＜0.05)compared with those before treatment.And the effects on lowering the levels of serum hs-CRP and NT-pro BNP and on increasing LVEF of the treatment group were significantly superior to those of the control group,the differences being statistically significant(P＜0.05).(2)During the treatment period,the incidence of cardiovascular adverse events in the treatment group was 6.67%(2/30),which was significantly lower than 26.67%(8/30)of the control group,and the difference was statistically significant when comparing the two groups(P＜0.05).Conclusion Qishen Yiqi Guttate Pills can effectively improve cardiac function,decrease serum hs-CRP and NT-pro BNP levels,and reduce the occurrence of adverse cardiovascular events in post-PCI patients with acute myocardial infarction of qi deficiency and blood stasis type.

Objective To analyze the antigen recognition sites of commercial and homemade antibodies against aquaporin(AQP)9,and to identify the application effect.Methods Western blotting was used to compare the efficacy of three commercial antibodies and self-made antibody in identifying AQP9 genotypes.The antigen recognition sites of four antibodies and their specificities in practical applications were analyzed.Results Western blotting showed that protein bands of three commercial antibodies were detected in both WT and Aqp9-/-mice.The keyhole limpet hemocyanin(KLH)conjugated synthetic peptides corresponding to the three commercial antibodies were derived from rat,human and human,respectively.And The sequences of these three synthetic peptides were different from those of mice.AQP3/7 and AQP9 have similar molecular weight and were expressed in the liver with high homology.An obvious band of self-made antibody was observed at the 27 kD position in WT mice,but no band was observed at the corresponding position in Aqp9-/-mice.Conclusion Commercial antibodies 1 and 3 can be used to assist in the identification of genotypes in Aqp9-/-mice.Homemade antibodies can accurately identify genotypes at the protein level.