An insight into structure-activity relationships in subclass IIb bacteriocins: Plantaricin EvF.

This study reports the structure-activity relationships of a unique subclass IIb bacteriocin, plantaricin EvF, which consists of two peptide chains and possesses potent antimicrobial activity. Because the plantaricin Ev peptide chain lacks an α-helix structure, plantaricin EvF is unable to exert its antimicrobial activity through helix-helix interactions like typical subclass IIb bacteriocins. We have shown by various structural evaluation methods that plantaricin Ev can be stabilized by hydrogen bonding at amino acid residues R3, V12, and R13 to the N-terminal region of plantaricin F. This binding gives plantaricin EvF a special spade-shaped structure that exerts antimicrobial activity. In addition, the root-mean-square deviations (RMSDs) of the amino acid residues Y6, F8, and R13 of plantaricin Ev pre- and post-binding were 1.512, 1.723, and 1.369, respectively, indicating that they underwent large structural changes. The alanine scanning experiments demonstrated the important role of the above key amino acids in maintaining the structural integrity of plantaricin EvF. This study not only reveals the unique structural features of plantaricin EvF, but also provides an insight into the structure-activity relationships of subclass IIb bacteriocins.

Metabolic determinants of germinal center B cell formation and responses.

Germinal center (GC) B cells are crucial for the generation of GCs and long-lived humoral immunity. Here we report that one-carbon metabolism determines the formation and responses of GC B cells. Upon CD40 stimulation, GC B cells selectively upregulate methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) expression to generate purines and the antioxidant glutathione. MTHFD2 depletion reduces GC B cell frequency and antigen-specific antibody production. Moreover, supplementation with nucleotides and antioxidants suffices to promote GC B cell formation and function in vitro and in vivo through activation of the mammalian target of rapamycin complex 1 signaling pathway. Moreover, we found that antigen stimulation enhances YY1 binding to the Mthfd2 promoter and promotes MTHFD2 transcription. Interestingly, these findings can be generalized to the pentose phosphate pathway, which is another major source of reducing power and nucleotides. Therefore, these results suggest that an increased capacity for nucleotide synthesis and redox balance is required for GC B cell formation and responses, revealing a key aspect of GC B cell fate determination.

Gut dysbiosis impairs intestinal renewal and lipid absorption in Scarb2 deficiency-associated neurodegeneration.

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease (GD) and Parkinson's disease (PD). Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.

Clinical sequencing defines the somatic and germline mutation landscapes of Chinese HER2-Low Breast Cancer.

More than half of the breast cancer initially labeled as human epidermal growth factor receptor 2 (HER2)-negative actually exhibited low HER2 levels (IHC 1+ or IHC 2+/FISH-) and were classified as HER2-low breast cancer. Previous research emphasized the significant biological heterogeneity in HER2-low breast cancer, highlighting the importance of accurately characterizing HER2-low tumors to promote the precise management of antibody‒drug conjugates. In this study, we established a large-scale targeted sequencing cohort (N = 1907) representing Chinese HER2-low breast cancer patients with detailed clinical annotation. Our research findings revealed that HER2-low breast cancer demonstrated distinct clinical pathological characteristics and mutation landscapes compared to HER2-zero group. When compared to HER2-zero tumors, HER2-low tumors exhibited a higher proportion of Luminal B subtypes and better disease-free survival. In hormone receptor (HR)-positive breast cancer, HER2-low group showed a higher frequency of GATA3 somatic mutations, BRCA2 germline mutations, and mutations in the DNA damage repair pathway. In contrast, in HR-negative breast cancer, the HER2-low group displayed a higher frequency of PIK3CA mutations and PI3K pathway alterations. These findings offered valuable insights for the precise targeted treatment of HER2-low breast cancer in different HR statuses.

Intestinal lysozyme1 deficiency alters microbiota composition and impacts host metabolism through the emergence of NAD+-secreting ASTB Qing110 bacteria.

The intestine plays a pivotal role in nutrient absorption and host defense against pathogens, orchestrated in part by antimicrobial peptides secreted by Paneth cells. Among these peptides, lysozyme has multifaceted functions beyond its bactericidal activity. Here, we uncover the intricate relationship between intestinal lysozyme, the gut microbiota, and host metabolism. Lysozyme deficiency in mice led to altered body weight, energy expenditure, and substrate utilization, particularly on a high-fat diet. Interestingly, these metabolic benefits were linked to changes in the gut microbiota composition. Cohousing experiments revealed that the metabolic effects of lysozyme deficiency were microbiota-dependent. 16S rDNA sequencing highlighted differences in microbial communities, with ASTB_g (OTU60) highly enriched in lysozyme knockout mice. Subsequently, a novel bacterium, ASTB Qing110, corresponding to ASTB_g (OTU60), was isolated. Metabolomic analysis revealed that ASTB Qing110 secreted high levels of NAD+, potentially influencing host metabolism. This study sheds light on the complex interplay between intestinal lysozyme, the gut microbiota, and host metabolism, uncovering the potential role of ASTB Qing110 as a key player in modulating metabolic outcomes. IMPORTANCE: The impact of intestinal lumen lysozyme on intestinal health is complex, arising from its multifaceted interactions with the gut microbiota. Lysozyme can both mitigate and worsen certain health conditions, varying with different scenarios. This underscores the necessity of identifying the specific bacterial responses elicited by lysozyme and understanding their molecular foundations. Our research reveals that a deficiency in intestinal lysozyme1 may offer protection against diet-induced obesity by altering bacterial populations. We discovered a strain of bacterium, ASTB Qing110, which secretes NAD+ and is predominantly found in lyz1-deficient mice. Qing110 demonstrates positive effects in both C. elegans and mouse models of ataxia telangiectasia. This study sheds light on the intricate role of lysozyme in influencing intestinal health.

Potential antimicrobial activity of camel milk as a traditional functional food against foodborne pathogens in vivo and in vitro.

Foodborne pathogens are a leading cause of mortality worldwide. Therefore, strategies focused on functional foods are urgently required to tackle this issue. As a result, camel milk is one of the most important traditional functional foods since it contains a variety of bioactive components, which all have antimicrobial activity against foodborne pathogens. The study aims to investigate the potential antimicrobial activity of raw camel milk against foodborne pathogens in both in vitro agar well diffusion and infected mice, especially Listeria monocytogenes, Staphylococcus aureus, Salmonella Typhimurium and Escherichia coli, particularly in societies that rely on consuming camel milk in its raw form. A total of eighty C57BL/6 mice were divided into ten groups and gavaged with or without camel milk for two consecutive weeks. A blood plasma analysis and serum insulin levels were measured. Histological investigations of the liver, pancreas, kidney, spleen, lung and testicles were also performed. In both in vivo and in vitro studies when compared to other pathogenic bacteria, E. coli was the most affected by raw camel milk, with a significant clear zone of 2.9 ± 0.13 cm in vitro and in all measured parameters in vivo (p < 0.05). As a result, we advocated for further research to improve camel breeding, raise milk yield and extend its reproductive capability as one of the most important farm animals.

Establishment and Application of a Duplex Real Time Fluorogenic Quantitative PCR Assay System for miR-451a and miR-21-5p / 生物化学与生物物理进展

ObjectiveBody fluid stains left at crime scenes are frequently trace amounts, while the identification of body fluids through real time fluorogenic quantitative technique often necessitates the repeated detection within the limited sample, as multiple miRNA markers are the basis for the identification. Based on the goal of both the throughput and efficiency improvement of miRNA analysis in trace samples, a duplex real time fluorogenic quantitative PCR assay system was designed to accurately quantify two miRNAs simultaneously, and the system should be further verified by actual sample for the body fluid identification. MethodsThe duplex real time fluorogenic quantitative PCR system of miR-451a to miR-21-5p was established with specially designed primers and probes, and the concentrations of the primers and probes were both optimized. The specificity, sensitivity and reproducibility of the system were validated, while its capability for body fluid identification was assessed using the miR-451a to miR-21-5p ratio. ResultsThe optimized assay system exhibited excellent specificity and repeatability, with coefficients of variation consistently below 8% for both intra- and inter-batch variability. The amplification efficiency of miR-451a and miR-21-5p reached 71.77% and 74.81%, respectively, with high and relatively consistent results. By utilizing this duplex real time fluorogenic quantitative PCR assay system, a total of 58 body fluid samples were analyzed, exhibiting a discrimination rate of 100% between blood and non-blood samples, as well as between peripheral blood and menstrual blood samples. Moreover, the results, obtained from single real time fluorogenic quantitative PCR assay system and duplex real time fluorogenic quantitative PCR assay system, showed no statistically significant difference with randomly selected blood samples (n=20). Compared to previous single real time fluorogenic quantitative PCR assay system, the sensitivity of duplex real time fluorogenic quantitative PCR assay system exhibited remarkable improvement. A minimum input of only 0.1 ng total RNA was sufficient for accurate detection of peripheral blood and menstrual blood samples, while saliva, semen, and vaginal secretion required only 1 ng total RNA for precise identification purposes. Additionally, the duplex real time fluorogenic quantitative PCR assay system successfully differentiated between different types of body fluids in simulated samples under natural outdoor conditions. ConclusionThe duplex real time fluorogenic quantitative PCR assay system effectively reduced both the time and material costs by half compared to the single system, especially suitable for the examination of body fluid stains left at crime scenes, solving the contradiction between the trace amount and the multiple sample volumes demand of repeated real time fluorogenic quantitative PCR. The duplex real time fluorogenic quantitative PCR assay successfully distinguished blood and other body fluid, as well as peripheral blood and menstrual blood samples, which maintains an equivalent capability for body fluid identification with half sample, time and reagent consumption. This system provides an efficient tool for identifying suspicious body fluids, as well as a foundation for more multiplexed real time fluorogenic quantitative PCR assay system research.

Clinical application status of multiple localization methods in the treatment of pulmonary nodules by sub-lobectomy / 中国胸心血管外科临床杂志

@#The precise localization of pulmonary nodules has become an important technical key point in the treatment of pulmonary nodules by thoracoscopic surgery, which is a guarantee for safe margin and avoiding removal of too much normal lung parenchyma. With the development of medical technology and equipment, the methods of locating pulmonary nodules are also becoming less trauma and convenience. There are currently a number of methods applied to the preoperative or intraoperative localization of pulmonary nodules, including preoperative percutaneous puncture localization, preoperative transbronchial localization, intraoperative palpation localization, intraoperative ultrasound localization, and localization according to anatomy. The most appropriate localization method should be selected according to the location of the nodule, available equipment, and surgeon鈥檚 experience. According to the published literatures, we have sorted out a variety of different theories and methods of localization of pulmonary nodules in this article, summarizing their advantages and disadvantages for references.

Clinical Study on the Fu's Subcutaneous Needling Combined with Western Medicine in the Treatment of Irritable Bowel Syndrome / 广州中医药大学学报

Objective To explore the clinical effect of Fu's subcutaneous needling combined with western medicine in the treatment of irritable bowel syndrome(IBS).Methods A total of 112 patients with IBS were randomly divided into the observation group and the control group,with 56 patients in each group.The control group was given conventional western medicine treatment,and the observation group was treated with Chinese medicine Fu's subcutaneous needling on the basis of the treatment in the control group.Both groups were treated for 4 consecutive weeks.After 1 month of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the IBS system severity system(IBS-SSS)scores were observed before and after the treatment,as well as the time of the symptoms of abdominal pain,bloating and diarrhoea subsiding in the two groups,and the changes in the defecation thresholds,pain thresholds,sensory thresholds and the changes in the numbers of intestinal flora such as Bifidobacterium,Lactobacillus,Enterobacteriaceae,and Bacteriodendrobacteriaceae in the two groups were compared.The changes in the levels of vasoactive intestinal peptide,gastric motility and substance P were observed in the two groups.The safety and occurrence of adverse reactions were also evaluated in the two groups.Results(1)The total effective rate of the observation group was 96.43%(54/56),and the control group was 83.93%(47/56).The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)The time for abdominal pain,abdominal distension and diarrhoea to subside was significantly shorter in the observation group than in the control group,and the difference was statistically significant when compared with the control group(P＜0.05).(3)After treatment,the defecation threshold,pain threshold,and sensation threshold of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in terms of improving defecation threshold,pain threshold,and sensation threshold,and the difference was statistically significant(P＜0.05).(4)After treatment,the numbers of Bifidobacterium,Lactobacillus,Enterobacter,Bacteroides were significantly improved in the two groups(P＜0.05),and the observation group was significantly superior to the control group in terms of improving the numbers of Bifidobacterium,Lactobacillus,Enterobacter and Bacteroides,and the difference was statistically significant(P＜0.05).(5)After treatment,the levels of vasoactive intestinal peptide,gastric actin,and substance P of the patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the levels of vasoactive intestinal peptide,gastric actin,and substance P,and the differences were all statistically significant(P＜0.05).(6)There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Fu's subcutaneous needling combined with western medicine in the treatment of IBS can significantly shorten the relief time of patients'clinical symptoms,strengthen patients'gastrointestinal function,regulate the number of intestinal flora and improve the function of gastrointestinal mucous membrane barrier,and the therapeutic efficacy is remarkable.

Interventional embolization using vascular plug together with spring coil for the treatment of varicocele / 介入放射学杂志

Objective To discuss the curative effect of interventional embolization using vascular plug together with spring coil in treating varicocele.Methods A total of 15 patients with varicocele,who were admitted to authors'hospital between March 2022 and October 2022 to receive treatment,were enrolled in this study.Interventional embolization therapy by using vascular plug together with spring coil via the left elbow vein access or via the femoral vein access was carried out in all the 15 patients.The instant surgical success rate,complications,time spent for operation,average hospital stay,and postoperative clinical efficacy were recorded and analyzed.Results Successful interventional embolization using vascular plug together with spring coil was accomplished in all the 15 patients,and no complications occurred during the perioperative period.The time spent for operation was(19±12)min,and the average hospital stay was 2.3 days.The patients were followed up for one month,the degree of the scrotal varices was obviously improved,and the swelling feeling of the perineum was significantly reduced.Conclusion For the treatment of varicocele,the interventional embolization using vascular plug together with spring coil carries certain advantages,such as reliable curative effect,easy to operate,patient being more comfortable,fast recovery,and less complications.Therefore,this technique is a therapeutic approach worth further investigation.(J Intervent Radiol,2024,32:73-76)

Role of inflammatory factors in diabetic ulcers and prospects of traditional Chinese medicine intervention / 中国组织工程研究

BACKGROUND:Diabetic ulcers are a common complication of diabetes mellitus,which is manifested as foot ulcers complicated with infection,long treatment cycle,high disability rate and mortality rate,and brings a heavy burden to patients and social care. OBJECTIVE:To review the mechanism of action and the latest treatment progress of traditional Chinese medicine(TCM)in the treatment of diabetic ulcers,and to provide a basis for further theoretical research and clinical application. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature using the keywords of"diabetic ulcer,medicinal herb,inflammation,interleukin-1β,interleukin-6,tumor necrosis factor,hypersensitive C-reactive protein,γ-interferon,interleukin-4,interleukin-10"in Chinese and English,respectively.The relevant literature in recent years was searched,and finally 75 articles were included for review. RESULTS AND CONCLUSION:The high glucose environment of the body will increase the level of pro-inflammatory cytokines,so that diabetic ulcer wounds are in a state of chronic inflammatory response for a long time,and difficult to heal or even not heal.TCM has summed up a lot of experience in the long-term struggle with diabetic ulcer.At present,TCM divides diabetic ulcers into four syndrome types:dampness and heat poison syndrome,blood and blood stasis obstruction pattern,heat poison injury Yin pattern,and Qi and blood deficiency syndrome,as well as representative prescriptions for treatment.According to their clinical characteristics,diabetic ulcers can be also divided into three stages:primary,middle and late stages.Different treatment methods are proposed:"clear method,""warm and clear combined use"and"maintenance method."Under the guidance of dialectical typing and staging of TCM,TCM monomers,extracts and compounds inhibit the inflammatory response and promote the healing of diabetic ulcers by down-regulating the expression of pro-inflammatory factors and/or up-regulating the expression of anti-inflammatory factors.Compared with modern medicine,TCM has significant advantages in the treatment of diabetic ulcers.There are many TCM monomers,extracts and compounds for the treatment of diabetic ulcers,such as angelica,curcumin,improved Chonghe ointment,Sanhuang blood exhaustion prescription and sore-ulcer I.formula,etc.It has been found that TCM for the treatment of diabetic ulcers is mainly heat-clearing and detoxifying,invigorating blood circulation and removing blood stasis,and amassing sores and muscle-building drugs,and the frequency of use,treatment scope and therapeutic effect of TCM compounds are obviously better than those of TCM monomers and extracts.Among them,the most commonly used are the Sanhuang blood exhaustion prescription and the sore-ulcer I as well as prescription for the treatment of damp heat toxicity syndrome and Zizhu ointment for the treatment of non-ischemic diabetic ulcers.However,there are also some shortcomings in the treatment of diabetic ulcers with TCM.First,there are few clinical syndrome studies on diabetic ulcers.Secondly,there are a wide variety of TCM monomers,extracts and compounds for the treatment of diabetic ulcers,and the relevant research is insufficiently in-depth.Finally,the research on the mechanism underlying TCM treatment of diabetic ulcers is still in the preliminary exploration stage,and the mechanism of action still needs to be further explored.In the future,it is necessary to strengthen the research on the pharmacology of TCM and the clinical syndrome of diabetic ulcers,analyze the potential targets and related signaling pathways of TCM in the treatment of diabetic ulcers,give full play to the therapeutic advantages of TCM with multiple targets,multiple pathways,multiple levels and multiple systems,and develop TCM with significant efficacy,active ingredients and clear targets.

Posture planning method for complex feature measurement using a single-line laser scanner.

A single-line laser scanner is commonly utilized for measuring complex surfaces and contours. However, achieving automatic implementation of this scanner poses challenges in terms of designing a measurement posture that considers measurement accuracy, path planning, and the positioning of auxiliary equipment. This ensures non-interference during the measurement process. In this study, we focus on the application of T-SCAN. First, we construct a measurement posture parameter model for T-SCAN and analyze the viewpoint position's coverage of the measurement area. Second, we propose a measurement path planning method based on scanning posture to minimize overlapping areas. Lastly, we present a measurement station planning method based on scanning postures and analyze the transfer error of the measurement targets to establish a unified measurement field. Experimental results demonstrate that, after the posture adjustment process, the average distance deviation between the measurement data and the theoretical model is significantly reduced.

Structural Characterization and Immunomodulatory Activity of a Mannose-Rich Polysaccharide Isolated from Bifidobacterium breve H4-2.

In this study, a novel homogeneous mannose-rich polysaccharide named EPS-1 from the fermentation broth of Bifidobacterium breve H4-2 was isolated and purified by anion exchange column chromatography and gel column chromatography. The primary structure of EPS-1 was analyzed by high-performance liquid chromatography, Fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry, and nuclear magnetic resonance. The results indicated that EPS-1 had typical functional groups of polysaccharides. EPS-1 with an average molecular weight of 3.99 × 104 Da was mainly composed of mannose (89.65%) and glucose (5.84%). The backbone of EPS-1 was →2,6)-α-d-Manp-(1→2)-α-d-Manp-(1→2,6)-α-d-Manp-(1→2)-α-d-Manp-(1→2,6)-α-d-Manp-(1→6)-α-d-Glcp-(1→ simultaneously containing two kinds of branched chains (α-d-Manp-(1→3)-α-d-Manp-(1→ and α-d-Manp-(1→). Besides, EPS-1 had a triple-helical conformation and exhibited excellent thermal stability. Moreover, the immunomodulatory activity of EPS-1 was evaluated by RAW 264.7 cells. Results indicated that EPS-1 significantly enhanced the viability of RAW 264.7 cells. EPS-1 could also be recognized by toll-like receptor 4, thereby activating the nuclear factors-κB (NF-κB) signaling pathway, promoting phosphorylation of related nuclear transcription factors, improving cell phagocytic activity, and promoting the secretion of NO, IL-6, IL-1ß, and TNF-α. Thus, EPS-1 could activate the TLR4-NF-κB signaling pathway to emerge immunomodulatory activity on macrophages. The above results indicate that EPS-1 can serve as a potential immune-stimulating polysaccharide.

Trichomonas gallinae Kills Host Cells Using Trogocytosis.

Trichomonas gallinae (T. gallinae) is an infectious parasite that is prevalent worldwide in poultry and can cause death in both poultry and wild birds. Although studies have shown that T. gallinae damages host cells through direct contact, the mechanism is still unclear. In this study, we found that T. gallinae can kill host cells by ingesting fragments of the host cells, that is, by trogocytosis. Moreover, we found that the PI3K inhibitor wortmannin and the cysteine protease inhibitor E-64D prevented T. gallinae from destroying host cells. To the best of our knowledge, our study has demonstrated for the first time that T. gallinae uses trogocytosis to kill host cells. Understanding this mechanism is crucial for the prevention and control of avian trichomoniasis and will contribute to the development of vaccines and drugs for the prevention and control of avian trichomoniasis.

Development of a tetra-primer ARMS-PCR for identification of sika and red deer and their hybrids.

Accurate identification of deer-derived components is significant in food and drug authenticity. Over the years, several methods have been developed to authenticate these products; however, identifying whether female deer products are hybrids is challenging. In this study, the zinc finger protein X-linked (ZFX) gene sequences of sika deer (Cervus nippon), red deer (Cervus elaphus) and their hybrid offspring were amplified and sequenced, the X221 and X428 species-specific single nucleotide polymorphisms (SNP) loci were verified, and a tetra-primer amplification refractory mutation system (T-ARMS-PCR) assay was developed to identify the parent-of-origin of female sika deer, red deer, and their hybrid deer. The T-ARMS-PCR developed based on the X221 locus could identify sika deer, red deer, and their hybrid offspring according to the presence or absence of PCR product sizes of 486 bp, 352 bp, and 179 bp, respectively, just as X428 locus could identify sika deer, red deer, and their hybrid offspring according to the presence or absence of PCR product sizes of 549 bp, 213 bp, and 383 bp, respectively. Forty products labeled deer-derived ingredients randomly purchased were tested using this assay, and the results showed that the identification results based on the two SNP loci were utterly consistent with the actual sources. In addition, this method was found to be accurate, simple, convenient, and with high specificity, thus providing an essential technical reference for deer product species identification. It is also an important supplement to the identification methods of the original ingredients of existing deer products.

Identification of new drug candidates against Trichomonas gallinae using high-throughput screening.

Trichomonas gallinae is a protozoan parasite that is the causative agent of trichomoniasis, and infects captive and wild bird species throughout the world. Although metronidazole has been the drug of choice against trichomoniasis for decades, most Trichomonas gallinae strains have developed resistance. Therefore, drugs with new modes of action or targets are urgently needed. Here, we report the development and application of a cell-based CCK-8 method for the high-throughput screening and identification of new inhibitors of Trichomonas gallinae as a beginning point for the development of new treatments for trichomoniasis. We performed the high-throughput screening of 173 anti-parasitic compounds, and found 16 compounds that were potentially effective against Trichomonas gallinae. By measuring the median inhibitory concentration (IC50) and median cytotoxic concentration (CC50), we identified 3 potentially safe and effective compounds against Trichomonas gallinae: anisomycin, fumagillin, and MG132. In conclusion, this research successfully established a high-throughput screening method for compounds and identified 3 new safe and effective compounds against Trichomonas gallinae, providing a new treatment scheme for trichomoniasis.

Glucose metabolism profile recorded by flash glucose monitoring system in patients with hypopituitarism during prednisone replacement.

BACKGROUND: Commonly used glucocorticoids replacement regimens in patients with hypopituitarism have difficulty mimicking physiological cortisol rhythms and are usually accompanied by risks of over-treatment, with adverse effects on glucose metabolism. Disorders associated with glucose metabolism are established risk factors of cardiovascular events, one of the life-threatening ramifications. AIM: To investigate the glycometabolism profile in patients with hypopituitarism receiving prednisone (Pred) replacement, and to clarify the impacts of different Pred doses on glycometabolism and consequent adverse cardiovascular outcomes. METHODS: Twenty patients with hypopituitarism receiving Pred replacement [patient group (PG)] and 20 normal controls (NCs) were recruited. A flash glucose monitoring system was used to record continuous glucose levels during the day, which provided information on glucose-target-rate, glucose variability (GV), period glucose level, and hypoglycemia occurrence at certain periods. Islet ß-cell function was also assessed. Based on the administered Pred dose per day, the PG was then regrouped into Pred > 5 mg/d and Pred ≤ 5 mg/d subgroups. Comparative analysis was carried out between the PG and NCs. RESULTS: Significantly altered glucose metabolism profiles were identified in the PG. This includes significant reductions in glucose-target-rate and nocturnal glucose level, along with elevations in GV, hypoglycemia occurrence and postprandial glucose level, when compared with those in NCs. Subgroup analysis indicated more significant glucose metabolism impairment in the Pred > 5 mg/d group, including significantly decreased glucose-target-rate and nocturnal glucose level, along with increased GV, hypoglycemia occurrence, and postprandial glucose level. With regard to islet ß-cell function, PG showed significant difference in homeostasis model assessment (HOMA)-ß compared with that of NCs; a notable difference in HOMA-ß was identified in Pred > 5 mg/d group when compared with those of NCs; as for Pred ≤ 5 mg/d group, significant differences were found in HOMA-ß, and fasting glucose/insulin ratio when compared with NCs. CONCLUSION: Our results demonstrated that Pred replacement disrupted glycometabolic homeostasis in patients with hypopituitarism. A Pred dose of > 5 mg/d seemed to cause more adverse effects on glycometabolism than a dose of ≤ 5 mg/d. Comprehensive and accurate evaluation is necessary to consider a suitable Pred replacement regimen, wherein, flash glucose monitoring system is a kind of promising and reliable assessment device. The present data allows us to thoroughly examine our modern treatment standards, especially in difficult cases such as hormonal replacement mimicking delicate natural cycles, in conditions such as diabetes mellitus that are rapidly growing in worldwide prevalence.

Activation of CREB-binding protein ameliorates spinal cord injury in tabersonine treatment by suppressing NLRP3/Notch signaling.

Introduction: Spinal cord injury (SCI) alters the integrity of the spinal cord, which leads to loss of multiple organs' function including locomotor function. The present study evaluates the protective effect of tabersonine against SCI. Material and methods: SCI was induced by traumatic injury and animals were treated with tabersonine 20 and 40 mg/kg, intraperitoneally for the period of 10 days. Tabersonine's effect was determined by estimating locomotor and neurological function in spinal cord injured rats. Moreover, mediators of inflammation were estimated using enzyme-linked immunosorbent assay (ELISA) and the effect of tabersonine on Notch/inflammasome signaling was estimated by reverse transcription polymerase chain reaction (RT-PCR), western blot assay and immunohistochemistry. Apoptosis of neuronal cells was estimated by staining with Nissl stain on spinal cord tissue in SCI rats. Results: Data of the study suggest that neurological and motor functions were improved in the tabersonine treated group compared to the spinal cord injured (SI) group. There was a decrease in the mediators of inflammation in the spinal cord tissue of the tabersonine treated group compared to the SI group. Treatment with tabersonine ameliorates the altered expression of NICD, Nestin and Hes-1 protein and mRNA expression of Notch-1 and Hes-1 in the SCI rats. It was also observed that the tabersonine treated group showed activation of CREB and inhibition of the NLRP-3 pathway in SCI rats. Moreover, apoptosis of neuronal cells was reduced in the tabersonine treated group compared to the SI group. Conclusions: Data of the investigation suggest that tabersonine protects against spinal cord injury by activating CREB and reducing NLRP3/Notch signaling.

Male-Biased Parasitism of Brandt's Voles (Lasiopodomys brandtii) in Inner Mongolia, China.

The abundance and prevalence of parasitic infection often vary in different host sexes, and this phenomenon has been named sex-biased parasitism. Brandt's voles are the dominant rodent species in typical steppe habitat and are widely distributed in Inner Mongolia, China, but the prevalence of parasites in Brandt's voles are poorly reported. In this study, we investigated the prevalence of six intestinal parasites in Brandt's voles in May, June, July, and August 2022 around the Xilingol Grassland in Inner Mongolia, China. The results showed that Syphacia obvelata, Aspiculuris tetraptera, and Trichostrongylidae family were the dominant intestinal parasites in Brandt's voles that we captured in this study, and the infection rates of the three parasites were significantly higher in males than females, which showed obvious male-biased parasitism. Season and human activities such as grazing had no significant effect on the infection rates for different parasites, while the parasite reproduction level was higher when the ambient temperature was around 18 °C. Sexual size dimorphism was ubiquitous in Brandt's voles, and it was mainly manifested by the differences in body weight and length between males and females. Simple linear regression analysis showed a significant positive correlation between bodyweight and parasite infection rates, so the sex-biased parasitism in Brandt's voles could be explained by the body size hypothesis, as a larger body could provide more ecological niches for parasitic infection.