The inhibitory effects of Dracocephalum moldavica L. (DML) on rat cerebral ischemia reperfusion injury.

Ischemia reperfusion injury (IRI) is closely associated with oxidative stress and inflammatory responses. Dracocephalum moldavica L. (DML), a Chinese herbal medicine is known to exert protective effects on myocardial ischemia reperfusion injury in rats by inhibiting oxidation damage and inflammatory reactions. However, the effectiveness of DML in cerebral ischemia reperfusion injury (CIRI) as a protective substance and the underlying mechanisms remain to be determined. The aim of this study was thus to examine the influence of DML on CIRI using a rat model induced by 2-h transient middle cerebral artery occlusion (MCAO) produced by intraluminal suture blockade followed by 22 h reperfusion. The parameters determined include neurological behavior, histochemical assessment of cerebral infarct volume, and determination of various metabolic biomarkers. Data showed that DML markedly improved neurobehavioral scores and reduced cerebral edema and infarction. In addition, DML significantly reduced malondialdehyde (MDA) content and elevated activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), in addition, marked decrease in levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). Data suggest that the protective effects of DML on CIRI may be related to processes involving antioxidation and anti-inflammation.

[The effects of repetitive extragenic palindromic sequences from Brucella melitensis DNA on the toll-like receptor 9-mediated interferon-α production].

OBJECTIVE: To screen the repetitive extragenic palindromic sequences with activation of toll-like receptor 9 (TLR9) activity from Brucella melitensis DNA, providing new ideas and new targets for prevention and treatment of brucellosis. METHODS: Bioinformatics methods were used to detect repetitive extragenic palindromic (REP) sequences from Brucella melitensis DNA. The studied REPs were selected and synthesized. RAW264.7 was cultured and transfected with REPs mediated by lipofectamine 3000. Additionally, TLR9-siRNA was used to downregulate TLR9 expression. The content of interferon-α (IFN-α) in the supernatant was then measured by ELISA. RESULTS: A total of 2 200 REP sequences in Brucella melitensis DNA were identified. Twelve REP sequences were synthesized for further detecting of the TLR9 agonistic activity. IFN-α expression in RAW264.7 treated with M2, M3, M4, M5, M6, M7, M9, M12 were (26.944 ± 1.868), (46.461 ± 2.562), (34.980 ± 2.055), (43.016 ± 2.162), (62.533 ± 4.031), (67.125 ± 5.069), (18.908 ± 1.633), (39.572 ± 2.465) pg/ml respectively, which significantly increased when compared with the negative control group [(12.594 ± 1.338) pg/ml, t=10.817, 20.295, 15.812, 20.724, 20.365, 18.016, 5.180, 16.660, all P<0.05]. Additionally, TLR9-siRNA can significantly decrease the levels of IFN-α in RAW264.7 treated with M6. CONCLUSION: REP sequences presented in Brucella melitensis DNA are able to induce IFN-α expression through TLR9, which can be helpful for the understanding of pathogenesis and immunity of Brucella melitensis.

Polymerase chain reaction-based assays for the diagnosis of human brucellosis.

Polymerase chain reaction (PCR) is an in vitro technique for the nucleic acid amplification, which is commonly used to diagnose infectious diseases. The use of PCR for pathogens detection, genotyping and quantification has some advantages, such as high sensitivity, high specificity, reproducibility and technical ease. Brucellosis is a common zoonosis caused by Brucella spp., which still remains as a major health problem in many developing countries around the world. The direct culture and immunohistochemistry can be used for detecting infection with Brucella spp. However, PCR has the potential to address limitations of these methods. PCR are now one of the most useful assays for the diagnosis in human brucellosis. The aim of this review was to summarize the main PCR techniques and their applications for diagnosis and follow-up of patients with brucellosis. Moreover, advantages or limitation of the different PCR methods as well as the evaluation of PCR results for treatment and follow-up of human brucellosis were also discussed.

Cutting force predication based on integration of symmetric fuzzy number and finite element method.

In the process of turning, pointing at the uncertain phenomenon of cutting which is caused by the disturbance of random factors, for determining the uncertain scope of cutting force, the integrated symmetric fuzzy number and the finite element method (FEM) are used in the prediction of cutting force. The method used symmetric fuzzy number to establish fuzzy function between cutting force and three factors and obtained the uncertain interval of cutting force by linear programming. At the same time, the change curve of cutting force with time was directly simulated by using thermal-mechanical coupling FEM; also the nonuniform stress field and temperature distribution of workpiece, tool, and chip under the action of thermal-mechanical coupling were simulated. The experimental result shows that the method is effective for the uncertain prediction of cutting force.

Brucella infection and Toll-like receptors.

Brucella consists of gram-negative bacteria that have the ability to invade and replicate in professional and non-professional phagocytes, and its prolonged persistence in the host leads to brucellosis, a serious zoonosis. Toll-like receptors (TLRs) are the best-known sensors of microorganisms implicated in the regulation of innate and adaptive immunity. In particular, TLRs are transmembrane proteins with a typical structure of an extracellular leucine-rich repeat (LRR) region and an intracellular Toll/interleukin-1 receptor (TIR) domain. In this review, we discuss Brucella infection and the aspects of host immune responses induced by pathogens. Furthermore, we summarize the roles of TLRs in Brucella infection, with substantial emphasis on the molecular insights into its mechanisms of action.

Tumor microenvironment characteristics of lipid metabolism reprogramming related to ferroptosis and EndMT influencing prognosis in gastric cancer.

BACKGROUND: Gastric cancer (GC) is a refractory malignant tumor with high tumor heterogeneity, a low rate of early diagnosis, and poor patient prognosis. Lipid metabolism reprogramming plays a critical role in tumorigenesis and progression, but its prognostic role and regulatory mechanism in GC are rarely studied. Thus, the identification of signatures related to lipid metabolism is necessary and may present a new avenue for improving the overall prognosis of GC. METHODS: Lipid metabolism-associated genes (LMAGs) with differential expression in tumor and tumor-adjacent tissue were acquired to identify lipid metabolism-associated subtypes. The differentially expressed genes (DEGs) between the two clusters were then utilized for prognostic analysis and signature construction. Additionally, pathway enrichment analysis and immune cell infiltration analysis were employed to identify the characteristics of the prognostic model. Further analyses were conducted at the single-cell level to better understand the model's prognostic mechanism. Finally, the prediction of immunotherapy response was used to suggest potential treatments. RESULTS: Two lipid metabolism-associated subtypes were identified and 9 prognosis-related genes from the DEGs between the two clusters were collected for the construction of the prognostic model named lipid metabolism-associated signature (LMAS). Then we found the low LMAS patients with favorable prognoses were more sensitive to ferroptosis in the Cancer Genome Atlas of Stomach Adenocarcinoma (TCGA-STAD). Meanwhile, the tumor cells exhibiting high levels of lipid peroxidation and accumulation of reactive oxygen species (ROS) in single-cell levels were primarily enriched in the low LMAS group, which was more likely to induce ferroptosis. In addition, endothelial cells and cancer-associated fibroblasts (CAFs) facilitated tumor angiogenesis, proliferation, invasion, and metastasis through endothelial-mesenchymal transition (EndMT), affecting the prognosis of the patients with high LMAS scores. Moreover, CD1C- CD141- dendritic cells (DCs) also secreted pro-tumorigenic cytokines to regulate the function of endothelial cells and CAFs. Finally, the patients with low LMAS scores might have better efficacy in immunotherapy. CONCLUSIONS: A LMAS was constructed to guide GC prognosis and therapy. Meanwhile, a novel anti-tumor effect was found in lipid metabolism reprogramming of GC which improved patients' prognosis by regulating the sensitivity of tumor cells to ferroptosis. Moreover, EndMT may have a negative impact on GC prognosis.

Fragment-based Drug Discovery Strategy and its Application to the Design of SARS-CoV-2 Main Protease Inhibitor.

Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) emerged at the end of 2019, causing a highly infectious and pathogenic disease known as 2019 coronavirus disease. This disease poses a serious threat to human health and public safety. The SARS-CoV-2 main protease (Mpro) is a highly sought-after target for developing drugs against COVID-19 due to its exceptional specificity. Its crystal structure has been extensively documented. Numerous strategies have been employed in the investigation of Mpro inhibitors. This paper is primarily concerned with Fragment-based Drug Discovery (FBDD), which has emerged as an effective approach to drug design in recent times. Here, we summarize the research on the approach of FBDD and its application in developing inhibitors for SARS-CoV-2 Mpro.

Rehabilitation Evaluation of Upper Limb Motor Function for Stroke Patients Based on Belief Rule Base.

In the process of rehabilitation treatment for stroke patients, rehabilitation evaluation is a significant part in rehabilitation medicine. Researchers intellectualized the evaluation of rehabilitation evaluation methods and proposed quantitative evaluation methods based on evaluation scales, without the clinical background of physiatrist. However, in clinical practice, the experience of physiatrist plays an important role in the rehabilitation evaluation of patients. Therefore, this paper designs a 5 degrees of freedom (DoFs) upper limb (UL) rehabilitation robot and proposes a rehabilitation evaluation model based on Belief Rule Base (BRB) which can add the expert knowledge of physiatrist to the rehabilitation evaluation. The motion data of stroke patients during active training are collected by the rehabilitation robot and signal collection system, and then the upper limb motor function of the patients is evaluated by the rehabilitation evaluation model. To verify the accuracy of the proposed method, Back Propagation Neural Network (BPNN) and Support Vector Machines (SVM) are used to evaluate. Comparative analysis shows that the BRB model has high accuracy and effectiveness among the three evaluation models. The results show that the rehabilitation evaluation model of stroke patients based on BRB could help physiatrists to evaluate the UL motor function of patients and master the rehabilitation status of stroke patients.

Facile decoration of Au nanoparticles on CdS nanorods by polyoxometalate with enhanced photocatalytic activities toward hydrogen evolution.

The tri-component hybrid CdS nanorods (NRs)/Au nanoparticles (NPs)@polyoxometalate (POM) was successfully prepared by a facile, efficient and green method. The structural properties and component analysis were studied by Transmission electron microscopy (TEM), X-ray Diffraction (XRD) and UV-Vis spectra. The POMs sever as not only reductant and bridge molecules, but also as co-catalyst to play an important role in the photocatalytic process. The as-prepared nanohybrid shows obviously enhanced photocatalytic activity toward photocatalytic evolution of hydrogen.

Pharmacological actions of multi-target-directed evodiamine.

Evodiamine, a naturally occurring indole alkaloid, is one of the main bioactive ingredients of Evodiae fructus. With respect to the pharmacological actions of evodiamine, more attention has been paid to beneficial effects in insults involving cancer, obesity, nociception, inflammation, cardiovascular diseases, Alzheimer's disease, infectious diseases and thermo-regulative effects. Evodiamine has evolved a superior ability to bind various proteins, so we also argue that it is good starting point for multi-target drugs. This review is primarily addressed to the description of the recent advances in the biological activity studies of evodiamine, with a focus on pharmacological mechanism. The present review also includes the pharmacokinetics and the detailed exploration of target-binding properties of evodiamine in an attempt to provide a direction for further multi-target drug design.

Response of Soil Detachment Rate to Sediment Load and Model Examination: A Key Process Simulation of Rill Erosion on Steep Loessial Hillslopes.

The rate of soil detachment by water flow indicates soil erosion intensity directly. The exact relation between soil detachment rate and actual sediment load in water flow, however, is still unclear, and the existing relationships have not been adequately tested. The aims of the present study were to investigate the response of soil detachment rate to sediment load using rill flume data with loessial soil and to quantitatively examine the soil detachment equations in the WEPP and EUROSEM soil erosion models. Six slopes were combined with seven flow discharges to measure detachment rates under seven sediment loads using a rill flume with a soil-feeding hopper. Significant differences were found among the soil detachment rate by different sediment loads in low sediment load levels, but an insensitive response of soil detachment rate to sediment load was found under high levels of sediment load. The soil detachment rate was proved to be negatively linearly correlated with sediment load. The rill detachment equation in the WEPP model predicted the soil detachment rate by rill flow very well under our experiment condition. The soil detachment equation in the EUROSEM model underestimated the detachment rates under controlled conditions, but removing the setting velocity from the equation greatly improved prediction. Further experiments that could reflect the dynamic convective detachment and deposition process need to be conducted to compare with the present examination results and to further understand rill erosion processes.

Toll-like receptors in cardiac hypertrophy.

Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) that can identify pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). TLRs play an important role in the innate immune response, leading to acute and chronic inflammation. Cardiac hypertrophy, an important cardiac remodeling phenotype during cardiovascular disease, contributes to the development of heart failure. In previous decades, many studies have reported that TLR-mediated inflammation was involved in the induction of myocardium hypertrophic remodeling, suggesting that targeting TLR signaling might be an effective strategy against pathological cardiac hypertrophy. Thus, it is necessary to study the mechanisms underlying TLR functions in cardiac hypertrophy. In this review, we summarized key findings of TLR signaling in cardiac hypertrophy.

Research progress on complications of Brucellosis.

Brucellosis is a common zoonotic disease that is widely spread worldwide and poses a major threat to human health. Clinically, it often presents with non-specific symptoms such as fever, excessive sweating, malaise, myalgia, arthralgia, loss of appetite, weight loss, and enlarged liver, spleen and lymph nodes. The disease has a long and recurrent course, often accumulating in multiple systems and organs. Of these, osteoarticular involvement is the most common complication, with a prevalence of approximately 2-77%, usually manifesting as spondylitis, sacroiliac arthritis and peripheral arthritis. Hepatosplenomegaly is seen in about 50% of patients with brucellosis, and gastrointestinal disturbances such as abdominal pain, nausea, and vomiting are common. Although respiratory involvement is less common, pneumonia, pleurisy, pleural effusion, and pulmonary nodules have been reported. Besides, approximately 2-20% of cases involve infections of the male genitourinary system, mainly manifesting as unilateral epididymal-orchitis and orchitis. The most serious complication facing brucellosis is cardiovascular involvement, and although the overall mortality rate of brucellosis is about 1% and the incidence of brucellosis endocarditis is less than 2%, more than 80% of deaths are associated with endocarditis. Furthermore, brucellosis is complicated by hematologic disease, with anemia occurring in approximately 20-53% of children during the acute phase. In addition, the neurological incidence of brucellosis is about 0.5-25%, mainly manifested as meningitis. In this study, we review the multisystem complications of brucellosis with the aim of improving early diagnosis, timely treatment and prevention of long-term complications.

Small molecule inhibitors against the bacterial pathogen Brucella.

Brucellosis remains one of the major zoonotic diseases worldwide. As a causative agent of brucellosis, it has many ways to evade recognition by the immune system, allowing it to replicate and multiply in the host, causing significant harm to both humans and animals. The pathogenic mechanism of Brucella has not been elucidated, making the identification of drug targets from the pathogenic mechanism a challenge. Metalloenzymatic targets and some protein targets unique to Brucella are exploitable in the development of inhibitors against this disease. The development of specific small molecule inhibitors is urgently needed for brucellosis treatment due to the antibiotic resistance of Brucella. This review summarizes the research on small molecule inhibitors of Brucella, which could be instructive for subsequent studies.

Dracocephalum moldavica L. extract alleviates experimental colitis in rats by modulating gut microbiome and inflammatory pathways.

Several studies have revealed that an imbalance of the intestinal microbiota is involved in intestinal inflammation associated with ulcerative colitis (UC). Therefore, regulating the homeostasis of gut microbiota is critical for treating UC. Dracocephalum moldavica L. (DML) extract, a common traditional Chinese medicine, has been demonstrated to possess numerous pharmacological effects, such as antioxidative, anti­inflammatory, and antibacterial properties. The aim of the present study was to evaluate the beneficial effects of DML extract and the probable mechanism of action in a dextran sulfate sodium­induced chronic colitis model. It was found that DML extract ameliorated UC by improving disease activity index, weight loss, colon length, and histological scoring. DML extract administration also enhanced the count of Lactobacillus and reduced the count of Romboutsia. Furthermore, the results of network pharmacology analysis revealed that the active ingredients (including luteolin, rosmarinic acid, oleanolic acid, ursolic acid, apigenin, acacetin, kaempferol, and isorhamnetin) in the DML extract were closely associated with anti­inflammatory activity via various signaling pathways, including the NF­κB, IL­17, TNF, and Toll­like receptor (TLR) signaling pathways. Western blot analysis further indicated that DML extract downregulated the expression of members of the TLR4/NF­κB signaling pathway, which was associated with colitis. Thus, it was hypothesized that DML extract exerted its anti­colitis effects by modulating the gut microbiota and inflammatory pathways.

Binding mode pediction of evodiamine within vanilloid receptor TRPV1.

Accurate assessment of the potential binding mode of drugs is crucial to computer-aided drug design paradigms. It has been reported that evodiamine acts as an agonist of the vanilloid receptor Transient receptor potential vanilloid-1 (TRPV1). However, the precise interaction between evodiamine and TRPV1 was still not fully understood. In this perspective, the homology models of TRPV1 were generated using the crystal structure of the voltage-dependent shaker family K(+) channel as a template. We then performed docking and molecular dynamics simulation to gain a better understanding of the probable binding modes of evodiamine within the TRPV1 binding pocket. There are no significant interspecies differences in evodiamine binding in rat, human and rabbit TRPV1 models. Pharmacophore modeling further provided confidence for the validity of the docking studies. This study is the first to shed light on the structural determinants required for the interaction between TRPV1 and evodiamine, and gives new suggestions for the rational design of novel TRPV1 ligands.

[Application of Qu single abdominal aorta clamping for bloodless hepatectomy and Pringle hepatectomy in 118 cases of liver tumors].

OBJECTIVE: To compare the results of application of Qu single abdominal aorta clamping for bloodless hepatectomy and Pringle hepatectomy in 118 cases of liver tumors. METHODS: The clinical data of 118 patients, including 59 patients undergoing Qu single abdominal aorta clamping for bloodless hepatectomy (Group QG) and 59 patients undergone Pringle first hepatic portal clamping hepatectomy (Group PG) since March 2009 in the Ningbo Tumor Hospital and Jiangxi Provincial Hospital were retrospectively reviewed. The changes of blood pressure, oxygen saturation, urine volume, intravenous fluid volume, amount of bleeding, time of abdominal aorta (or first hepatic portal) clamping, duration of operation and anesthesia, and other intraoperative indexes of the two groups were compared, and the changes of peritoneal drainage, blood tests, liver functions, etc. before operation and 1, 3, 7, 14 days after the hepatectomy in the two groups were also analyzed. RESULTS: After taking appropriate measures for intraoperative blood pressure control, only small fluctuations of blood pressure, which could be safely adjusted and controlled with stable vital signs, was observed in the group QG. The amount of intraoperative bleeding in the group QG was (96.25 ± 18.45) ml, significantly less than (536.25 ± 35.65) ml in the group PG (P < 0.05). In the group QG, both the duration of operation time [(227.58 ± 28.20) min] and duration of anesthesia [(249.48 ± 31.35) min] were significantly shorter than that [(261.46 ± 32.12) min and (286.58 ± 35.62) min, respectively] in the group PG (both P < 0.05). The postoperative liver dysfunction in the group QG was also milder than that in the group PG (P < 0.05). CONCLUSIONS: For liver tumor patients, Qu single abdominal aorta clamping for bloodless hepatectomy can basically achieve the goal of bloodless hepatectomy. This surgical operation is simple and safe, worthy of recommendation to skillful liver surgeons in hospitals there are some difficulties of blood supply.

Applications of polymerase chain reaction-based methods for the diagnosis of plague (Review).

Plague is an acute bacterial infection caused by Yersinia pestis. The three major clinical forms of plague are bubonic, pneumonic and septicemic, which have high case-mortality rates. Therefore, rapid and reliable diagnostic tools are crucial. Currently, bacteriological means and traditional serological assays are used for detecting infection with Y. pestis. However, such methods have their limitations. Polymerase chain reaction (PCR) is one of the most useful tools for rapid diagnosis of plague. The present review introduced the main PCR techniques and their applications for detecting and confirmation of Y. pestis. The advantages and disadvantages of the different PCR methods were also summarized.

Effects of polysaccharides on the hydrodynamic parameters of sheet erosion on loessial slopes.

The variations in hydrodynamic parameters at different polysaccharides rates and the relationships between sheet erosion modulus and hydrodynamic parameters were analyzed to reveal the hydrodynamic mechanism of sheet erosion on loessial slopes. Artificially simulated rainfall experiments were carried out under three slope gradients (10°, 15°, and 20°), three rainfall intensities (1.0, 1.5, and 2.0 mm·min-1), and four dry-spreading rates of polysaccharides (0, 1, 3, and 5 g·m-2). The results showed that (1) four hydrodynamic parameters (flow velocity, shear stress, stream power, and unit stream power) all increased with both rainfall intensities and slope gradients at four rates of polysaccharides. (2) Polysaccharides could effectively reduce hydrodynamic parameters. In contrast to the bare slope, the average flow velocity, shear stress, stream power, and unit stream power diminished by 27.11~41.18%, 9.53~18.67%, 31.82~50.24%, and 27.11~41.18%, respectively. (3) Polysaccharides could effectively reduce the growth rate of the sheet erosion modulus with hydrodynamic parameters, and there were few differences among the different rates (1, 3, and 5 g·m-2). The increasing rates of the sheet erosion modulus with flow velocity, shear stress, stream power, and unit stream power were 14.0~65.7%, 14.8~33.9%, 7.8~23.7%, and 9.7~29.5%, respectively. (4) At different polysaccharides rates, the relationships between sheet erosion modulus and hydrodynamic parameters were all in logarithmic functions. Moreover, flow velocity (R2 ≥ 0.920) and stream power (R2 ≥ 0.876) were better hydrodynamic parameters than shear stress (R2 ≥ 0.598) or unit stream power (R2 ≥ 0.537). Polysaccharides decreased the hydrodynamic parameters and the response rates of sheet erosion to hydrodynamics.

Influence of warm acupuncture on gut microbiota and metabolites in rats with insomnia induced by PCPA.

BACKGROUND: Insomnia is the most common of the sleep disorders. Current pharmacotherapy treatment options are usually associated with adverse effects and withdrawal phenomena. Therapeutic alternatives with a more favorable safety profile for patients are needed. Mongolian medical warm acupuncture (MMWA) is an emerging therapeutic option for treating insomnia. However, the underlying mechanisms responsible for the anti-insomnia efficacy of the MMWA remain unclear. This study aims to investigate the effect of the MMWA on the alterations of the gut microbiota and serum metabolome in rats with insomnia. RESULTS: We found that the relative abundances of gut bacteria and the concentrations of several serum metabolites were obviously altered in PCPA-induced insomnia rats. The MMWA treatment exerted an anti-insomnia effect. In addition, the dysbiosis of the gut microbiota and the serum metabolites were ameliorated by the MMWA. Correlation analysis between the gut microbiota and metabolites suggested that the levels of Amide c18, Benzoyl chloride, Cytosine, and N, n-dimethylarginine were positively correlated with the relative abundance of Clostridium XlVa and Blautia, which characterized the insomnia rats. KEGG enrichment analysis identified the cAMP signaling pathway involving anti-insomnia effect of the MMWA. Moreover, the MMWA intervention significantly increased contents of butyrate in feces, while effectively inhibited the expression level of GAT-1 in brain tissues. CONCLUSION: This study reveals that the MMWA intervention might have a major impact on the modulation of host gut microbiota and metabolites, which in turn have a crucial role in the regulation of the host's signaling pathways associated with insomnia. The present study could provide useful ideas for the study of the intervention mechanisms of the MMWA in insomnia rat models.