Synthesis of α-Carbonyl-α'-sulfenyl Sulfoxonium Ylides in Water at Room Temperature.

An efficient synthesis of α-carbonyl-α'-sulfenyl sulfoxonium ylides through a KIO3-promoted cross-dehydrogenative coupling reaction of aryl thiols and α-carbonyl sulfoxonium ylides in an aqueous medium at room temperature has been described. The α-carbonyl sulfoxonium ylides and aryl thiols adorned with various functional groups were well-tolerated and afforded moderate to high yields of α-carbonyl-α'-sulfenyl sulfoxonium ylide derivatives. Finally, by converting synthesized ylide 3a into other valuable compounds, we demonstrated the practicality of this synthetic method.

The Antibacterial Efficacy and Mechanism of Tea Polyphenol Against Drug-Resistant Aeromonas veronii TH0426 In Vitro.

The emergence of Motile Aeromonas Septicemia (MAS) caused by Aeromonas veronii in sturgeon farming has become a significant concern due to its high mortality impact on the aquaculture industry. The threat posed by MAS highlights the urgent need for effective control measures to combat bacterial infections in sturgeon populations. Tea polyphenol (TP) has demonstrated promising antibacterial properties against livestock and poultry bacterial infections. However, its antibacterial efficacy and mechanism in bacterial diseases of aquatic animals remain largely unexplored. This study aimed to investigate the in vitro antibacterial effect and mechanism of TP on fish-borne drug-resistant A. veronii TH0426 by assessing the impact of TP on TH0426 cell growth, antibiofilm activity, morphology, as well as measuring electrical conductivity, DNA extravasation, lactate dehydrogenase (LDH) activity, protein, and DNA contents. Results demonstrated that the minimum inhibitory concentration and the minimum bactericidal concentration of TP on TH0426 were 1024 and 2048 µg/mL, respectively. After a 4 h treatment, the growth of TH0426 was completely inhibited at the concentration of 1024 and 2048 µg/mL of TP. Meanwhile, TP exhibited a significant antibiofilm activity. Both scanning electron microscope and transmission electron microscope analyses revealed disrupted cell membrane structure, irregular cell morphology, and loss of intracellular contents following TP treatment. Moreover, increased cell membrane permeability induced by TP led to intracellular ion and DNA leakage, resulting in elevated electrical conductivity and DNA extravasation. Furthermore, TP decreased LDH activity, protein concentration and content, DNA fluorescence intensity, and density in a time-dependent manner, indicating inhibition of protein metabolism and DNA synthesis. In conclusion, TP exhibits potent antibacterial properties by inhibiting biofilm formation, disrupting cell membrane integrity, and interfering with protein metabolism and DNA synthesis in drug-resistant A. veronii TH0426 in vitro.

A Retrospective Study on the Clinical Characteristics and Computed Tomography, Biochemical, and Blood Parameters of Duodenal Papillary Diseases.

OBJECTIVE: This study was conducted to investigate the imaging information, laboratory data, and clinical characteristics of duodenal papillary malignancies, aiming to contribute to the early diagnosis of these diseases. METHODS: The clinical characteristics, laboratory data, and computed tomography (CT) findings of 17 patients with adenoma of the major duodenal papilla (the adenoma group) and 58 patients with cancer of the major duodenal papilla (the cancer group) were retrospectively analyzed. The measurement data were analyzed using t test and expressed as mean ± standard deviation. The counting data were analyzed using the χ2 test and expressed in n (%). Pearson correlation analysis was also conducted, and a scatter plot was drawn. RESULTS: There were significant differences in the diameter, shape, margin, and target sign of the major duodenal papilla, pancreatic duct diameter, common bile duct diameter, enhancement uniformity, fever, direct bilirubin, total bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9, and jaundice between the adenoma group and the cancer group (P < .01). The enhancement magnitude of the duodenal papilla was correlated with the lesion size, and the venous phase CT value of the enhanced scan was correlated with the duodenal papilla diameter (P < .05). Additionally, 12 patients in the cancer group suffered from malignant transformation of adenomas. CONCLUSION: Firstly, CT is of high value in the diagnosis of duodenal papilla diseases. Secondly, the enhancement magnitude of the duodenal papilla is correlated with the lesion size. Thirdly, patients with duodenal papilla adenomas have a risk of progression into adenocarcinoma, thereby requiring close follow-up.

Recent Advances of Mitochondrial Alterations in Alzheimer's Disease: A Perspective of Mitochondrial Basic Events.

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders and is characterized by a decrease in learning capacity, memory loss and behavioral changes. In addition to the well-recognized amyloid-ß cascade hypothesis and hyperphosphorylated Tau hypothesis, accumulating evidence has led to the proposal of the mitochondrial dysfunction hypothesis as the primary etiology of AD. However, the predominant molecular mechanisms underlying the development and progression of AD have not been fully elucidated. Mitochondrial dysfunction is not only considered an early event in AD pathogenesis but is also involved in the whole course of the disease, with numerous pathophysiological processes, including disordered energy metabolism, Ca2+ homeostasis dysfunction and hyperactive oxidative stress. In the current review, we have integrated emerging evidence to summarize the main mitochondrial alterations- bioenergetic metabolism, mitochondrial inheritance, mitobiogenesis, fission- fusion dynamics, mitochondrial degradation, and mitochondrial movement- underlying AD pathogenesis; precisely identified the mitochondrial regulators; discussed the potential mechanisms and primary processes; highlighted the leading players; and noted additional incidental signaling pathway changes. This review may help to stimulate research exploring mitochondrial metabolically-oriented neuroprotection strategies in AD therapies, leading to a better understanding of the link between the mitochondrial dysfunction hypothesis and AD pathogenesis.

Preparation and evaluation of microencapsulated delivery system of recombinant interferon alpha protein from rainbow trout.

Diseases caused by viruses pose a significant risk to the health of aquatic animals, for which there are presently no efficacious remedies. Interferon (IFN) serving as an antiviral agent, is frequently employed in clinical settings. Due to the unique living conditions of aquatic animals, traditional injection of interferon is cumbersome, time-consuming and labor-intensive. This study aimed to prepare IFN microcapsules through emulsion technique by using resistant starch (RS) and carboxymethyl chitosan (CMCS). Optimization was achieved using the Box-Behnken design (BBD) response surface technique, followed by the creation of microcapsules through emulsification. With RS at a concentration of 1.27 %, a water­oxygen ratio of 3.3:7.4, CaCl2 at 13.67 %, CMCS at 1.04 %, the rate of encapsulation can escalate to 80.92 %. Rainbow trout infected with Infectious hematopoietic necrosis virus (IHNV) and common carp infected with Spring vireemia (SVCV) exhibited a relative survival rate (RPS) of 65 % and 60 % after treated with IFN microcapsules, respectively. Moreover, the microcapsules effectively reduced the serum AST levels and enhanced the expression of IFNα, IRF3, ISG15, MX1, PKR and Viperin in IHNV-infected rainbow trout and SVCV-infected carp. In conclusion, this integrated IFN microcapsule showed potential as an antiviral agent for treatment of viral diseases in aquaculture.

Blood-brain barrier dysfunction and Alzheimer's disease: associations, pathogenic mechanisms, and therapeutic potential.

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aß), hyperphosphorylation of tau, and neuroinflammation in the brain. The blood-brain barrier (BBB) limits solutes from circulating blood from entering the brain, which is essential for neuronal functioning. Focusing on BBB function is important for the early detection of AD and in-depth study of AD pathogenic mechanisms. However, the mechanism of BBB alteration in AD is still unclear, which hinders further research on therapeutics that target the BBB to delay the progression of AD. The exact timing of the vascular abnormalities in AD and the complex cause-and-effect relationships remain uncertain. Thus, it is necessary to summarize and emphasize this process. First, in this review, the current evidence for BBB dysfunction in AD is summarized. Then, the interrelationships and pathogenic mechanisms between BBB dysfunction and the risk factors for AD, such as Aß, tau, neuroinflammation, apolipoprotein E (ApoE) genotype and aging, were analyzed. Finally, we discuss the current status and future directions of therapeutic AD strategies targeting the BBB. We hope that these summaries or reviews will allow readers to better understand the relationship between the BBB and AD.

Spring Viremia of Carp Virus Infection Induces Carp IL-10 Expression, Both In Vitro and In Vivo.

Interleukin-10 (IL-10) is a pleiotropic cytokine with both immune enhancement and immunosuppression activities, but the main role is immunosuppression and anti-inflammatory ability. In order to use the immunosuppressive function of IL-10, many viruses, such as SARS-CoV-2, hepatitis B virus and EB virus, can evade the host's immune surveillance and clearance by increasing the expression of host IL-10. However, it has not been reported whether the aquatic animal infection virus can upregulate the expression of host IL-10 and the mechanisms are still unknown. Spring viremia of carp (SVC) is a fatal viral disease for many fish species and is caused by spring viremia of carp virus (SVCV). This disease has caused significant economic losses in the aquaculture industry worldwide. In this study, the expression of carp IL-10 with or without infection of SVCV in epithelioma papulosum cyprinid (EPC) cells, carp head kidney (cHK) primary cells and common carp tissues were analyzed using RT-PCR and ELISA. The results show that SVCV infection induced carp IL-10 mRNA and protein expression, both in vitro and in vivo. However, the upregulation of carp IL-10 by SVCV was hindered by specific inhibitors of the JAK inhibitor (CP-690550), STAT3 inhibitor (STA-21), NF-κB inhibitor (BAY11-7082) and p38 MAPK (mitogen-activated protein kinase) inhibitor (SB202190), but not JNK inhibitor (SP600125). Furthermore, the results demonstrated that JAK1, JAK2, JAK3, TYK2 and STAT5 played important roles in carp IL-10 production induced by SVCV infection. Taken together, SVCV infection significantly induced carp IL-10 expression and the upregulation trigged in JAK-STAT, NF-κB and p38MAPK pathways. To our knowledge, this is the first time that a fish infection virus upregulated the host IL-10 expression through the JAK-STAT, NF-κB and p38MAPK pathways. Altogether, fish viruses may have a similar mechanism as human or other mammalian viruses to escape host immune surveillance and clearance.

Effect of Dietary Fiber on Reproductive Performance, Intestinal Microorganisms and Immunity of the Sow: A Review.

Dietary fiber is a substance that cannot be digested by endogenous digestive enzymes but can be digested by the cellulolytic enzymes produced by intestinal microorganisms. In the past, dietary fiber was considered an anti-nutrient component in diets because it could resist digestion by endogenous enzymes secreted by the intestine and has a negative effect on the digestion of energy-producing nutrients. However, due to its functional properties, potential health benefits to animals, and innate fermentability, it has attracted increasing attention in recent years. There are a plethora of studies on dietary fiber. Evidence suggests that dietary fiber can provide energy for pigs through intestinal microbial fermentation and improve sow welfare, reproductive performance, intestinal flora, and immunity. This is a brief overview of the composition and classification of dietary fiber, the mechanism of action and effects of dietary fiber on reproductive performance, intestinal microorganisms, and the immune index of the sow. This review also provides scientific guidance for the application of dietary fiber in sow production.

Apolipoprotein E and viral infection: Risks and Mechanisms.

Apolipoprotein E (ApoE) is a multifunctional protein critical for lipid metabolism and cholesterol homeostasis. In addition to being a well known genetic determinant of both neurodegenerative and cardiovascular diseases, ApoE is frequently involved in various viral infection-related diseases. Human ApoE protein is functionally polymorphic with three isoforms, namely, ApoE2, ApoE3, and ApoE4, with markedly altered protein structures and functions. ApoE4 is associated with increased susceptibility to infection with herpes simplex virus type-1 and HIV. Conversely, ApoE4 protects against hepatitis C virus and hepatitis B virus infection. With the outbreak of coronavirus disease 2019, ApoE4 has been shown to determine the incidence and progression of severe acute respiratory syndrome coronavirus 2 infection. These findings clearly indicate the critical role of ApoE in viral infection. Furthermore, ApoE polymorphism has various or even opposite effects in these infection processes, which are partly related to the structural features that distinguish the different ApoE statuses. In the current review, we summarize the emerging relationship between ApoE and viral infection, discuss the potential mechanisms, and identify future directions that may help to advance our understanding of the link between ApoE and viral infection.

The effect of maternal consumption of high-fat diet on ovarian development in offspring.

The environment encountered by the fetus during its development exerts a profound influence on its physiological function and disease risk in adulthood. Women's intake of high-fat diet during pregnancy and lactation has gradually become an issue of widespread concern. Maternal high-fat diet will not only cause abnormal neurological development and metabolic syndrome symptoms in the offspring, but also affect the fertility of female offspring. Maternal high-fat diet affects the expression of genes related to follicle growth in offspring, such as AAT, AFP and GDF-9, which reduces the number of follicles and impairs follicle development. Additionally, maternal high-fat diet also affects ovarian health by inducing ovarian oxidative stress and cell apoptosis, which collectively can impair the reproductive potential of female offspring. Reproductive potential carries significant importance for both humans and animals. Therefore, this review aims to describe the effect of maternal exposure to high-fat diet on the ovarian development of offspring and to discuss possible mechanisms by which maternal diet affects the growth and metabolism of offspring.

Effects of yeast-derived postbiotic supplementation in late gestation and lactation diets on performance, milk quality, and immune function in lactating sows.

This experiment was conducted to determine the effects of yeast-derived postbiotic (YDP) supplementation in sow diets during late gestation and lactation on the performance of sows and their offspring. At 90-d gestation, 150 sows (Landrace × Large White, parity: 3.93 ±â€…0.11) were allocated to three dietary treatments (n = 50 per treatment): 1) basal diet (control [CON]), 2) basal diet with 1.25 g/kg YDP (0.125 group), and 3) basal diet with 2.00 g/kg YDP (0.200 group). The experiment continued until the end of weaning (day 21 of lactation). Supplementation with YDP resulted in greater deposition of backfat in sows during late gestation and an increasing trend in average weaning weight of piglets than observed in the CON group (P < 0.01, P = 0.05). Supplementation with YDP decreased piglet mortality and diarrhea index in piglets (P < 0.05). In farrowing sows' serum, the glutathione peroxide content in the YDP group was lower than that in the CON group (P < 0.05); the content of immunoglobulin A (IgA) in the 0.200 group or YDP group was higher than that in the CON group (P < 0.05). In lactating sows' serum, malondialdehyde content was higher in the YDP group (P < 0.05). In day 3 milk of sows, the 0.200 group tended to increase the lactose content (P = 0.07), and tended to decrease the secretory immunoglobulin A (sIgA) content (P = 0.06) with respect to that in the CON group. The sIgA content in the YDP group was lower than that in the CON group (P < 0.05). In the milk of sows, the 0.200 group tended to increase the lactose content with respect to that in the CON group (P = 0.08); the immunoglobulin G (IgG) content in the 0.125 group or YDP group was higher than that in the CON group (P < 0.05). YDP supplementation increased the IgA content in the milk (P < 0.01). In sow placenta, the content of total anti-oxidant capacity in the YDP group was higher than that in the CON group (P = 0.05); and the content of transforming growth factor-ß in the YDP group was higher than that in the CON group (P < 0.05). In piglet serum, the content of IgG and immunoglobulin M in the 0.125 group was higher than that in the CON and 0.200 groups (P < 0.05). In summary, this study indicated that feeding sows diets supplemented with YDP from late gestation through lactation increased sows' backfat deposition in late gestation and piglets' weaning weight; decreased piglet mortality and diarrhea index in piglets; and improved maternal and offspring immunity.

Rapid fetal and reproductive tissue development in late gestation poses a challenge to sow health. Nutritional interventions have been shown to effectively improve animal performance. The present study investigated whether dietary supplementation with a yeast-derived postbiotic (YDP) during late gestation and lactation might improve the health and production performance of sows and piglets. At two tested dose levels (1.25 and 2.00 g/kg in the diet), dietary YDP supplementation increased backfat deposition in sows during late gestation and weaning weight in piglets, and decreased the diarrhea index in piglets. YDP supplementation tended to increase lactose content in sow milk. Dietary YDP supplementation improved immunity in sows at farrowing and piglets at weaning. These findings indicated that YDP use improves sows' production performance and may serve as an important approach to optimizing nutrient programs in sow production.

MicroRNA-186-5p inhibits H9c2 cells apoptosis induced by oxygen-glucose deprivation by targeting ERK1/2.

Background: Serum miR-186-5p levels are increased in acute myocardial infarction (AMI) patients and might contribute to assessing the prognosis of AMI patients. In this study, we further investigated the underlying molecular mechanism of miR-186-5p that participated in the pathological processes of myocardial ischemia. Methods: The AMI models of rats and oxygen-glucose deprivation (OGD) models of H9c2 cells were established. Bioinformatics databases, luciferase reporting, and western blotting assays were performed to identify the regulatory target of miR-186-5p. Transfection and functional experiments were conducted to further define the possible molecular mechanism of miR-186-5p during the process of glucose deficiency and hypoxia. Results: The level of miR-186-5p was found to significantly decrease in H9c2 cells after OGD treatment, while it increased in the culture medium from OGD-treated H9c2 cells. Using bioinformatics databases, luciferase reporting, and western blotting assays, we identified that ERK1/2 might serve as the negative regulatory target of miR-186-5p. Combined with further transfection experiments, we indicated that miR-186-5p might inhibit the expression and activation of ERK1/2. This finding was also reflected in the reduction of their downstream cleaved caspase-3. Through functional experiments, we revealed that miR-186-5p might inhibit apoptosis and promote proliferation in OGD-treated H9c2 cells. Conclusions: We demonstrated that miR-186-5p might suppress OGD-induced apoptosis in H9c2 cells by targeting the ERK1/2 pathway.

Research and analysis on computed tomography signs and clinical characteristics of chronic duodenal papilla mucositis and duodenal papillary carcinoma.

Objective: To investigate the computed tomography (CT) findings of chronic duodenal papilla mucositis and duodenal papillary carcinoma, and provide more imaging information for early diagnosis of duodenal malignant diseases.Methods: CT findings and clinical data of 40 patients with chronic duodenal papilla mucositis and 46 patients with duodenal papillary carcinoma were retrospectively analyzed. Observation and measuring of direct duodenal papilla signs (including size, shape, density, enhancement uniformity, etc.), indirect duodenal papilla signs (including pancreaticobiliary dilatation) and clinical indicators (including tumor markers CA19-9, CA125, CEA, blood routine white blood cell count, bilirubin, age, gender, etc.) were carried out according to CT as well as statistical analysis.Results: There were significant differences in duodenal papilla regular morphology, age and CA19-9 (p < .05), and significant differences in duodenal papilla maximum transverse diameter, diameter of common bile duct, diameter of pancreatic duct, total bilirubin, direct bilirubin, and jaundice in duodenal papillary carcinoma group (p < 0.01). There were no significant differences in duodenal papilla enhancement uniformity, plain CT value, arterial CT value, portal CT value, enhancement uniformity, presence or not of calculus at the lower end, gender, CEA, CA125, white blood cell count, and abdominal pain with fever (all p > .05).Conclusion: CT is helpful for the diagnosis of duodenal papilla disease, but the CT findings of patients with duodenal papillary carcinoma tend to be similar to findings of chronic duodenal papilla mucositis, which is easy to lead to misdiagnosis, so comprehensive diagnosis should be made according to the direct and indirect CT signs as well as laboratory and clinical manifestations of duodenal papilla, so as to improve the diagnosis of duodenal papillary carcinoma, and reduce missed diagnosis and misdiagnosis.

Epstein-Barr virus infection-associated cholangiocarcinoma: a report of one case and the review of literature.

The clinical data of a patient with Epstein-barr virus (EBV) associated with cholangiocarcinoma was reported in this paper: a case of a 36-year-old female presented with abdominal pain and systemic skin yellowing combined with skin itching. Laboratory studies showed increase in alanine aminotransferase 242 U/L, aspartate aminotransferase 404 U/L, r-glutamyltransferase 1516 U/L, total bilirubin 308.2 µmol/L and CA199 (101.0 U/ml). AFP (4.5 ng/ml) was normal. CT revealed multiple space-occupying lesions in the liver. PET-CT revealed liver malignant tumor and lymph node metastasis. Liver puncture pathology revealed infiltrative growth of significant heterocyst nests in the liver tissue, which was morphologically consistent with malignant tumors, considering poorly differentiated carcinoma. Pathology suggestion: combining liver puncture with morphology, immunohistochemistry, and EBV in situ hybridization results, it was consistent with EB virus-associated poorly differentiated carcinoma, therefore, consider EBV infection-associated poorly differentiated cholangiocarcinoma (CCA) (LELC morphology). The patient underwent liver transplantation in Hangzhou Shulan Hospital on June 8, 2021 successfully. After surgery, the patient orally took tacrolimus for anti-rejection, entecavir for antiviral therapy, gemcitabine 1.2 g + cis-platinum 30 mg for chemotherapy. After following up for more than 5 months post liver transplantation, the condition of the patient deteriorated. The patient subsequently died. Based on the case of our patient and the review of existing literature, when the patient's serum CA199 increased, AFP did not change significantly, and there was no previous history of hepatitis B. CT revealed a low-density mass in the liver, ring enhancement in the arterial phase, and heterogeneous enhancement of the tumor in the delayed phase. Ring enhancement of the liver lesion mass was observed on MRI. Consider the might possibility of hepatic CCA. When patients showed recurrent tonsillitis at an early age, EBV virus infection should be vigilant and oropharyngeal tissue should persist, diagnosis of EBV-associated liver cancer should be considered. In particular, EBV infection-related liver cancer is relatively rare, the clinician should improve the recognition of the disease to strive for early diagnosis and therapy.

The Antibacterial Activity of Thymol Against Drug-Resistant Streptococcus iniae and Its Protective Effect on Channel Catfish (Ictalurus punctatus).

Streptococcus iniae is a zoonotic pathogen, which seriously threatens aquaculture and human health worldwide. Antibiotics are the preferred way to treat S. iniae infection. However, the unreasonable use of antibiotics leads to the enhancement of bacterial resistance, which is not conducive to the prevention and treatment of this disease. Therefore, it is urgent to find new efficient and environmentally friendly antibacterial agents to replace traditional antibiotics. In this study, the antibacterial activity and potential mechanism of thymol against S. iniae were evaluated by electron microscopy, lactate dehydrogenase, DNA and protein leakage and transcriptomic analysis. Thymol exhibited potent antibacterial activity against S. iniae in vitro, and the MIC and MBC were 128 and 256µg/mL, respectively. SEM and TEM images showed that the cell membrane and cell wall were damaged, and the cells were abnormally enlarged and divided. 2MIC thymol disrupted the integrity of cell walls and membranes, resulting in the release of intracellular macromolecules including nucleotides, proteins and inorganic ions. The results of transcriptomic analysis indicated that thymol interfered with energy metabolism and membrane transport, affected DNA replication, repair and transcription in S. iniae. In vivo studies showed that thymol had a protective effect on experimental S. iniae infection in channel catfish. It could reduce the cumulative mortality of channel catfish and the number of S. iniae colonization in tissues, and increase the activities of non-specific immune enzymes in serum, including catalase, superoxide dismutase, lysozyme and acid phosphatase. Taken together, these findings suggested that thymol may be a candidate plant agent to replace traditional antibiotics for the prevention and treatment of S. iniae infection.

Protective effect of cinnamaldehyde on channel catfish infected by drug-resistant Aeromonas hydrophila.

The protective effect of cinnamaldehyde on channel catfish infected by drug-resistant Aeromonas hydrophila CW strain was explored by observing the clinical signs and histopathology, measuring the cumulative mortality, serum biochemical and non-specific immune indicators, and intestinal microbiota in this study. The cumulative survival rate of the cinnamaldehyde within 14 days was significantly higher than that of the challenge group, which was 70% and 20%, respectively. Compared with the challenge group, the activities of lysozyme, superoxide dismutase, and glutathione peroxidase in the treatment group were increased, while there was no significant difference in catalase activity. Compared with the challenge group, the histopathology results showed that the injury of liver, spleen, and kidney was significantly alleviated after cinnamaldehyde treatment. The results of intestinal microbiota showed that the proportion of Proteobacteria in the challenge group was significantly increased, and the proportion of Aeromonas sp. reached 30% based on the analysis of species classification level. The composition of dominant species in the treatment group was similar to the control group. In conclusion, cinnamaldehyde increased the cumulative survival rate of channel catfish infected by A. hydrophila. It could protect channel catfish through improving the non-specific immune function of channel catfish, alleviating the pathological lesions of liver, spleen, kidney, and intestine, and maintaining the relative balance of the intestinal microbiota. Therefore, cinnamaldehyde could be a candidate drug for the treatment of A. hydrophila infection.

Molecular recognition of the interaction between ApoE and the TREM2 protein.

Alzheimer's disease (AD) is the most common type of dementia. The ε4 allele of the apolipoprotein E (ApoE) gene is the strongest known genetic risk factor for late-onset AD. Triggering receptor expressed on myeloid cells 2 (TREM2) is another important risk factor affecting the AD process after ApoE. Emerging evidence has identified TREM2 as a putative receptor for ApoE, raising the possibility that interactions between ApoE and TREM2 modulate the pathogenesis of AD. In this study, we performed molecular docking and molecular dynamics (MD) analyses to characterize the ApoE-TREM2 interaction and further investigated the effect of the major TREM2 disease-associated mutation (R47H) on the affinity of TREM2 for ApoE. The results indicate that the binding energy between ApoE and TREM2 occurs in an isoform-dependent manner with the following potency rank order: ApoE4 > ApoE3 > ApoE2. In addition, the R47H mutant reduced the interaction between ApoE and TREM2 protein, which may be attributed to decreased hydrogen-bonding interactions, hydrophobic interactions, and electrostatic forces between ApoE and TREM2. Our study analyzed the molecular pattern of the interactions between ApoE and TREM2 and how the variants affect these interactions based on in silico modeling, and the results might help to elucidate the interaction mechanism between ApoE and TREM2. Additional experimental studies will be needed to verify and explore the current findings.

A study of the antibacterial mechanism of pinocembrin against multidrug-resistant Aeromonas hydrophila.

Aeromonas hydrophila is a common pathogen in fish that has caused severe economic losses in aquaculture worldwide. With the emergence of bacterial resistance, it is necessary to develop new drugs to combat bacterial infection, particularly for multidrug-resistant bacteria. In this study, the antibacterial activity of pinocembrin was investigated by observing bacterial growth and microscopic structure, and its mechanism of action was identified by investigating its effect on protein and DNA. The antibacterial susceptibility test indicated that pinocembrin inhibits A. hydrophila growth. The minimal inhibitory concentration and minimum bactericidal concentration were 256 µg/mL and 512 µg/mL, respectively. Ultrastructurally, the bacteria treated with pinocembrin showed surface roughness and plasmolysis. When bacteria were treated with 512 µg/mL pinocembrin, lactate dehydrogenase activity and soluble protein content decreased significantly, and electrical conductivity and DNA exosmosis levels increased by 4.21 ± 0.64% and 15.98 ± 1.93 mg/L, respectively. Staining with 4', 6-Diamidino-2-phenylindole showed that the nucleic acid fluorescence intensity and density decreased after the treatment with pinocembrin. Pinocembrin may inhibit the growth of A. hydrophila by increasing cell membrane permeability and affecting protein and DNA metabolism. Thus, pinocembrin is a candidate drug for the treatment of A. hydrophila infection in aquaculture.

Serum MicroRNA Expression Patterns in Subjects After the 5-km Exercise Are Strongly Associated With Cardiovascular Adaptation.

Circulating microRNAs (miRNAs) have been reported dysregulated during exercise. However, the changes of specific serum miRNAs during the 5-km run test with intensity of 51-52% maximum oxygen uptake (V̇O2max) and their association with traditional cardiovascular-related indicators remain well-characterized. Levels of miR-1, miR-21, miR-146a, miR-155, miR-181, and miR-210 were detected in 120 young subjects before and after the exercise training by quantitative reverse-transcription PCR (RT-qPCR). Besides, the levels of cardiac troponin I (cTNI), myoglobin (Myo), creatine kinase (CK), creatine kinase-MB (CK-MB), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), ischemia-modified albumin (IMA), interleukin-6 (IL-6), and C-reactive protein (CRP) were measured and the correlation between levels of serum miRNAs and biochemical parameters was also analyzed. Compared with resting state, the serum levels of miR-1, miR-146a, miR-155, miR-181, and miR-210 were significantly increased after exercise training. Serum levels of miR-146a, miR-155, and miR-210 after exercise training were positively correlated with Myo, CK-MB, and LDH, respectively, while miR-1, miR-146a, miR-181, and miR-155 were positively correlated with the levels of IL-6. Additionally, all the five miRNAs were negatively correlated with IMA levels. The multivariate logistic regression analysis showed that high levels of miR-146a, AST, LDH, and IL-6 in serum were risk factors, while low IMA contents were a protective factor for cardiovascular adaptation during exercise. In conclusion, the dynamic changes of miRNAs under the condition of the 5-km continuous running contribute to the adaptive regulation of the cardiovascular function of the body.

Exosomes Protect Against Acute Myocardial Infarction in Rats by Regulating the Renin-Angiotensin System.

The renin-angiotensin system (RAS) has been suggested to play an important role in cardiac remodeling after acute myocardial infarction (AMI). We have confirmed that bone marrow mesenchymal stem cell-derived exosomes (BMSC-EX) had similar types of repair like effects upon tissues as BMSC, but the mechanisms remain unknown. BMSC were cultured to the third generation and were induced to release exosomes. Rats were injected with exosomes (100 µg/mL) or stem cells (1 × 106/mL) through the tail vein immediately after AMI was built, compared to those treated with physiological saline. Thereafter, all groups were analyzed for cardiac function, infarction sizes, and the levels of expression of BNP, ACE, ACE2, AngII, Ang1-7, and other factors in the plasma. After H2O2 makes contact with H9C2 cardiomyocytes, cell proliferation activity and apoptotic rates were measured by using CCK8 kits, to facilitate investigation of the effect of exosomes on H9C2 cells. In vivo, the index of cardiac remodeling and cardiac function was improved in both groups of exosomes and stem cells after AMI. Furthermore, exosomes may have helped to regulate the balance of the RAS system, upregulate ACE2-Ang1-7-Mas, and downregulate the ACE-AngII-ATIR pathway. Therefore, its effects were such as to accelerate the conversion of Ang II to Ang 1-7, thereby improving cardiac remodeling and forming sustained myocardial protection. In vitro, exosomal intervention was found to have increased the levels of activity of H9C2 cardiomyocytes under H2O2 injury and improved adverse effects of AngII upon H9C2 cells. All procedures for this study were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at Guangdong Medical University. BMSC-EX improved cardiac remodeling and cardiac function, and had effects upon RAS system-related factors in plasma. Similarly, BMSC-EX also helped to protect H9C2 cells under attack from H2O2 or AngII, and may thus play beneficial roles by facilitating regulation of the balance of the RAS system.