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.

Background: Feline panleukopenia virus (FPV) is a widespread and highly infectious pathogen in cats with a high mortality rate. Although Yanji has a developed cat breeding industry, the variation of FPV locally is still unclear. Objectives: This study aimed to isolate and investigate the epidemiology of FPV in Yanji between 2021 and 2022. Methods: A strain of FPV was isolated from F81 cells. Cats suspected of FPV infection (n = 80) between 2021 and 2022 from Yanji were enrolled in this study. The capsid protein 2 (VP2) of FPV was amplified. It was cloned into the pMD-19T vector and transformed into a competent Escherichia coli strain. The positive colonies were analyzed via VP2 Sanger sequencing. A phylogenetic analysis based on a VP2 coding sequence was performed to identify the genetic relationships between the strains. Results: An FPV strain named YBYJ-1 was successfully isolated. The virus diameter was approximately 20–24 nm, 50% tissue culture infectious dose = 1 × 10 −4.94 /mL, which caused cytopathic effect in F81 cells. The epidemiological survey from 2021 to 2022 showed that 27 of the 80 samples were FPV-positive. Additionally, three strains positive for CPV-2c were unexpectedly found. Phylogenetic analysis showed that most of the 27 FPV strains belonged to the same group, and no mutations were found in the critical amino acids. Conclusions A local FPV strain named YBYJ-1 was successfully isolated. There was no critical mutation in FPV in Yanji, but some cases with CPV-2c infected cats were identified.

Humans ; Pancreatic Neoplasms/metabolism* ; Prognosis ; Adenosine Triphosphatases/metabolism* ; Chromosomal Proteins, Non-Histone/metabolism*

AIM: To study the correlation between meibomian gland dysfunction(MGD)patients and their sleep quality.METHODS: Retrospective case-control study. A total of 150 MGD patients treated in our hospital from January 2021 to October 2022 were selected and divided into sleep disorder group(75 cases, PSQI>10 points)and control group(75 cases, PSQI≤10 points)according to the Pittsburgh sleep quality index(PSQI). Both groups were scored using the ocular surface disease index(OSDI), underwent meibomian gland-related examinations(eyelid margin morphology, meibomian gland secretion ability, meibomian gland secretion quality score), corneal fluorescein staining(FL)score, Schirmer Ⅰ test(SⅠt), tear film break-up time(BUT)was measured, and sleep indicators(sleep quality, sleep latency, subjective sleep quality, sleep time)were evaluated.RESULTS: There were significant differences in OSDI score, FL score, SⅠt, BUT, eyelid margin morphology score, meibomian gland secretion ability score, and meibomian gland secretion quality score between the two groups(P<0.05). In the sleep disorder group, PSQI score, sleep latency score, subjective sleep quality score, and sleep time score were significantly positively correlated with OSDI score, FL score, meibomian gland secretion ability score, and meibomian gland secretion quality score(P<0.05); PSQI score, subjective sleep quality score, and sleep time score were significantly positively correlated with eyelid margin morphology score(P<0.05); PSQI score, sleep latency score, and subjective sleep quality score were significantly negatively correlated with BUT and SⅠt(P<0.05); sleep time score was significantly negatively correlated with BUT(P<0.05); sleep latency score was not significantly correlated with eyelid margin morphology score(P>0.05); sleep time score was not significantly correlated with SⅠt(P>0.05).CONCLUSION:The ocular surface condition of MGD patients is correlated with multiple sleep quality indicators, and a decline in sleep quality may increase the risk of MGD.

The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/ kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7rNLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.

Posterior cataract opacification(PCO)is the epithelial-mesenchymal transformation(EMT)of residual lens epithelial cells(LECs)after cataract surgery, resulting in opaque scar which is one of the main complications of cataract surgery. A large amount of fibronectin(FN)produced by LECs after cataract surgery binds to a variety of cell surface receptors, matrix components and growth factors to regulate cell behavior. The purpose of this article is to review the literatures on the treatment of PCO targeting fibronectin and provide references for clinical treatment of PCO. In this paper, the research status of fibronectin in PCO in recent years is reviewed.

Cerebellar Purkinje cells (PCs) exhibit two types of discharge activities: simple spike (SS) and complex spike (CS). Previous studies found that noradrenaline (NA) can inhibit CS and bidirectionally regulate SS, but the enhancement of NA on SS is overwhelmed by the strong inhibition of excitatory molecular layer interneurons. However, the mechanism underlying the effect of NA on SS discharge frequency is not clear. Therefore, in the present study, we examined the mechanism underlying the increasing effect of NA on SS firing of PC in mouse cerebellar cortex in vivo and in cerebellar slice by cell-attached and whole-cell recording technique and pharmacological methods. GABA_A receptor was blocked by 100 µmol/L picrotoxin in the whole process. In vivo results showed that NA significantly reduced the number of spikelets of spontaneous CS and enhanced the discharge frequency of SS, but did not affect the discharge frequency of CS. In vitro experiments showed that NA reduced the number of CS spikelets and after hyperpolarization potential (AHP) induced by electrical stimulation, and increased the discharge frequency of SS. NA also reduced the amplitude of excitatory postsynaptic current (EPSC) of parallel fiber (PF)-PC and significantly increased the paired-pulse ratio (PPR). Application of yohimbine, an antagonist of α2-adrenergic receptor (AR), completely eliminated the enhancing effect of NA on SS. The α2-AR agonist, UK14304, also increased the frequency of SS. The β-AR blocker, propranolol, did not affect the effects of NA on PC. These results suggest that in the absence of GABA_A receptors, NA could attenuate the synaptic transmission of climbing fiber (CF)-PC via activating α2-AR, inhibit CS activity and reduce AHP, thus enhancing the SS discharge frequency of PC. This result suggests that NA neurons of locus coeruleus can finely regulate PC signal output by regulating CF-PC synaptic transmission.
Action Potentials/physiology* ; Animals ; Cerebellar Cortex/metabolism* ; Cerebellum/metabolism* ; Mice ; Norepinephrine/pharmacology* ; Purkinje Cells/metabolism* ; Receptors, Adrenergic, alpha-2/metabolism* ; Receptors, GABA-A/metabolism*

Objective:To investigate the effect of long-term alcohol intake on sensory information synaptic transmission of mossy fiber-granular cells in the cerebellar cortex of mice.Methods:Twenty healthy male ICR mice aged 6 to 8 weeks were divided into normal saline group(control group) and alcohol intake group(alcohol group) according to random number table, with 10 mice in each group. The mice in alcohol group were injected intraperitoneally with 20% alcohol and the mice in control group were injected with the same amount of saline for 28 days.After the injection, the scalp, muscle tissue and skull were removed in turn, and the dura mater was removed to fully expose the crus II area of cerebellum. The mice were stimulated by air blowing at 30 mm of the ipsilateral tentacle pad with a gas jet device.When the the maximal response site was determined, the NMDA receptor antagonist (D-APV), metabolic glutamate receptor 1 antagonist (JNJ16259685) and N-methyl-D-aspartic acid (NMDA) were perfused on the brain surface of mice. Each drug was perfused for 20 minutes and ACSF was used between the two drugs until the waveform was recovered. Patch clamp amplifier was used to record the changes of potential waveform in mouse cerebellar granule layer. The data were analyzed by the softwares of Clampfit 10.3 and SPSS 22.0.Results:After exposure to wind stimulation, the latency of field potential response in granular layer of mice in alcohol group (11.8±0.7)ms was significantly longer than that in the control group (10.1±0.2)ms ( t=-8.041, P<0.05), and the amplitude of N1 (1.2±0.1) MV was significantly lower than that in the control group (0.6±0.1) MV ( t=-12.728, P<0.05). Compared with the control group, the rise time of P1 waveform((4.4±0.2)ms, (3.2±0.2)ms), duration ((12.1±0.5)ms, (10.3±0.2)ms), extinction time((7.8±0.2)ms, (6.9± 0.2)ms), volume under waveform ((7.3±0.2)ms, (4.3±0.2)ms) were significantly increased in the alcohol group ( t=16.100, - 11.840, -11.673, -35.576, all P<0.05). There were no significant differences in the amplitude, half width, rise time and decay time of Roff wave between the two groups ( t=-1.909, -0.910, -0.789, 1.462, all P>0.05). When JNJ16259685 was perfused on the brain surface of mice in alcohol group, the amplitude of field potential evoked by five blowing stimuli had no significant difference compared with that before administration (all P>0.05). When D-APV was perfused into the brain surface of mice in the alcohol group, the amplitude of P1 ((42.3±1.5) Mv)was significantly lower than that before administration ((101.1±0.9)mV) and after elution ((100.1±2.2) mV) ( t=106.762, - 69.605, both P<0.05), and the area under waveform of P1 ((42.6±1.3)%) was also significantly lower than that before administration ((100.6±1.6)%) and after elution ((97.6±2.2)%) ( t=88.862, -67.791, both P<0.05).The ratio of N2 / N1 (0.3±0.1) was significantly lower than that before administration (0.4±0.1) and after elution (0.3±0.1) ( t=2.242, 2.121, both P<0.05). When NMDA was perfused on the brain surface of mice in the control group, compared with before administration and after elution, the amplitude of P1 ((110.7±3.2) mV, (100.1±0.9) mV, (102.0±1.7) mV, t=-10.173, 7.669, both P<0.05), the area under the waveform of P1 ((127.9±3.5)%, (100.0±3.1)%, (115.0±5.3)%, t=-18.698, 6.447, both P<0.05), the ratio of N2 / N1 ((0.5±0.1), (0.3±0.1), (0.3±0.1), t=-5.669, 5.669, both P<0.05) were all significantly increased. When D-APV was perfused on the brain surface of mice in control group, the field potential evoked by blowing stimuli had no significant difference compared with that before administration and after elution (all P>0.05). Conclusion:Long-term alcohol intake significantly suppresses the synaptic transmission of excitatory glutamate in MF-GC, and enhances the inhibitory response mediated by GABAA receptor in cerebellar cortex. The inhibitory component is enhanced by NMDA receptor, but not by type 1 metabolic glutamate receptor.

Background: The accessory tendon of the extensor hallucis longus (ATEHL) muscle is a common abnormal structure, and its clinical significance remains debatable. In this study, we provide the incidence of the ATEHL and characterize its morphological types in Asian cadavers and investigate its clinical applications. Methods: The tendons from 50 adult cadaveric feet, fixed in 10% formalin, were analyzed. We measured the length and width of both the ATEHL and the extensor hallucis brevis (EHB). Results: All dissected specimens had an ATEHL. The first metatarsophalangeal joint was surrounded by an accessory tendon that inserted onto the joint capsule and the dorsal base of the proximal phalanx. We classified the ATEHL into 3 types based on their directions. Differences in ATEHL type based on sex were not statistically significant. Conclusions We found an ATEHL in all cadaveric specimens in this study. We surmise that the ATEHL acts as an antagonist with the EHB when the toe is extending, which might help prevent the occurrence of hallux valgus deformity.

The study is to investigate the effect of glaucocalyxin A (GLA) on mast cell-mediated anaphylaxis. The animal welfare and experimental process of this experiment followed the regulations of the Animal Ethics Committee of Yanbian University. BALB/c mice were used in the animal experiment and randomly divided into five groups, control group, model group, and GLA low, medium, and high dose groups (10, 20, and 40 mg·kg^-1). Mice were sensitized by intradermal injection of anti-dinitrophenyl-immunoglobulin E (DNP-IgE) into the ears and challenged with a mixture of DNP-human serum albumin (HSA) and 4% evans blue into the tail veins to prepare an animal skin passive cutaneous anaphylaxis (PCA) model, which was collected from both ears for measurement of dye staining and histology. Rat peritoneal mast cells (RPMCs) were used in the cell experiment and divided into control, IgE + antigen (Ag), and IgE + Ag + GLA groups to determine histamine release as well as calcium influx levels. High-affinity IgE receptor (FcεRI)-mediated signaling pathway proteins and HMGB1/TLR4/NF-κB (high mobility group box 1/toll like receptor 4/nuclear transcription factor kappa B) signaling proteins were detected by Western blot. The results of animal experiments suggest that GLA inhibits PCA, reduces evans blue dye exudation, and reduces ear inflammation and ear thickness in mice. The results of cellular experiments suggested that GLA could reduce histamine release and calcium influx, and inhibit tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-13, and IL-1β production; Western blot results showed that GLA inhibited FcεRI-mediated phosphorylation levels of spleen tyrosine kinase (Syk), Lck/Yes novel tyrosine kinase (Lyn), tyrosine kinase Fyn (Fyn), growth-factor receptor-bound protein 2 (Gab2), and phospholipase C (PLC) γ1, while GLA inhibited HMGB1/TLR4 signaling pathway to limit NF-κB p65 nuclear metastasis. The results indicate that GLA inhibits mast cell degranulation and attenuates allergic inflammation through the HMGB1/TLR4/NF-κB signaling pathway.