Discovery of novel ocotillol derivatives modulating glucocorticoid receptor/NF-κB signaling for the treatment of sepsis.

Glucocorticoids (GCs) have been used in the treatment of sepsis because of their potent anti-inflammatory effects. However, their clinical efficacy against sepsis remains controversial because of glucocorticoid receptor (GR) downregulation and side effects. Herein, we designed and synthesized 30 ocotillol derivatives and evaluated their anti-inflammatory activities. Ocotillol 24(R/S) differential isomers were stereoselective in their pharmacological action. Specifically, 24(S) derivatives had better anti-inflammatory activity than their corresponding 24(R) derivatives. Compound 20 most effectively inhibited NO release (85.97% reduction), and it exerted dose-dependent inhibitory effects on interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels. Mechanistic studies revealed that compound 20 reduces the degradation of GR mRNA and GR protein. Meanwhile, compound 20 inhibited the activation of nuclear factor-κB (NF-κB) signaling, thereby inhibiting the nuclear translocation of p65 and attenuating the inflammatory response. In vivo studies revealed that compound 20 attenuated hepatic, pulmonary, and renal pathology damage in mice with sepsis and suppressed the production of inflammatory mediators. These results indicated that compound 20 is a promising lead compound for designing and developing anti-sepsis drugs.

[Advances in clinical anatomy of the transnasal approaches to the parapharyngeal segment of the internal carotid artery].

The intracranial segment of the internal carotid artery located inside the skeleton structure of skull base or inside the skull has clear anatomical landmarks and fixed anatomical structure. However, the parapharyngeal segment of the internal carotid artery located outside the cranial is surrounded by soft tissues, lacks clear and recognizable anatomical landmarks and sometimes has anatomical variation, which is closely related to transnasal endoscopic surgery. Intraoperative accidental injury can lead to serious complications or even death. Currently, clinical anatomical studies related to the parapharyngeal segment of the internal carotid artery under transnasal endoscopic surgery mainly focus on its anatomical variation and anatomical landmarks. This article reviews on these two aspects in order to provide anatomical reference for surgeons to reduce surgical risks during transnasal endoscopic surgery.

Crab microRNA-381-5p regulates prophenoloxidase activation and phagocytosis to promote intracellular bacteria Spiroplasma eriocheiris infection by targeting mannose-binding protein.

Mannose-binding lectin plays an essential role in bacteria or virus-triggered immune response in mammals. Previous proteomic data revealed that in Eriocheir sinensis, the mannose-binding protein was differentially expressed after Spiroplasma eriocheiris infection. However, the function of mannose-binding protein against pathogen infection in invertebrates is poorly understood. In this study, a crab mannose-binding protein (EsMBP) was characterized and enhanced the host resistance to S. eriocheiris infection. The application of recombinant C-type carbohydrate recognition domain (CTLD) of EsMBP led to increased crab survival and decreased S. eriocheiris load in hemocytes. Meanwhile, the overexpression of CTLD of EsMBP in Raw264.7 cells inhibited S. eriocheiris intracellular replication. In contrast, depletion of EsMBP by RNA interference or antibody neutralization attenuated phenoloxidase activity and hemocyte phagocytosis, rendering host more susceptible to S. eriocheiris infection. Furthermore, miR-381-5p in hemocytes suppressed EsMBP expression and negatively regulated phenoloxidase activity to exacerbate S. eriocheiris invasion of hemocytes. Taken together, our findings revealed that crab mannose-binding protein was involved in host defense against S. eriocheiris infection and targeted by miR-381-5p, providing further insights into the control of S. eriocheiris spread in crabs.

Total synthesis and structural modification of the dibenzylbutane lignan LCA as a potent anti-inflammatory agent against LPS-induced acute lung injury.

Acute lung injury (ALI) is a serious public health problem associated with high morbidity and mortality. However, few efficacious drugs are clinically available. Inhibition of proinflammatory cytokines is considered to be a promising method for the treatment of inflammatory diseases. Herein, the total synthesis of a dibenzylbutane lignan, 9'-O-di-(E)-feruloyl-meso-5,5'-dimethoxysecoisolariciresinol (LCA), was completed. A series of LCA derivatives were designed and synthesized, and their anti-inflammatory activities were evaluated. Derivative 14r significantly inhibited LPS-induced expression of NO and the proinflammatory cytokines TNF-α, IL-6, and IL-1ß in RAW 264.7 cells and inhibited activation of the NF-κB pathway. Compound 14r reduced LPS-induced pulmonary inflammation and ALI in mice. It showed significant protective effects against LPS-induced ALI in mice and significantly reduced levels of proinflammatory cytokines in serum and bronchoalveolar lavage fluid. The ratio of wet weight to dry weight of lung tissue was normalized by compound 14r, which was consistent with suppression of neutrophil infiltration and production of proinflammatory cytokines. Compound 14r reduced the mRNA expression of some proinflammatory cytokines, improved histopathologic changes, and reduced macrophage infiltration in lung tissues. Collectively, these results suggest a new series of LCA derivatives that could be promising anti-inflammatory agents for ALI treatment.

Effects of different salinity reduction intervals on osmoregulation, anti-oxidation and apoptosis of Eriocheir sinensis megalopa.

Eriocheir sinensis megalopa has a special life history of migrating from seawater to freshwater. In order to investigate how the megalopa adapt themselves to the freshwater environment, we designed an experiment to reduce the salinity of water from 30 ppt to 0 at rates of 30 ppt, 15 ppt, 10 ppt, and 5 ppt per 24 h to evaluate the effects of different degrees of hyposaline stress on the osmotic regulation ability and antioxidant system of the megalopa. Experimental results related to osmotic pressure regulation show that the gill tissue of megalopa in the treatment group of 30 ppt/24 h rapid reduction of salinity was damaged, while in the treatment group of 5 ppt/24 h it was intact. At the same time, the experiment also found that in each treatment group with different salinity reduction rates, compared with the control salinity, the NKA activity of megalopa increased significantly after the salinity was reduced to 20 ppt (p < 0.05). In addition, two genes involved in chloride ion transmembrane absorption have different expression patterns in the treatment groups with different salinity reduction rates. Among them, Clcn2 was significantly highly expressed only in the rapid salinity reduction intervals of 30 ppt/24 h and 15 ppt/24 h (p < 0.05). Slc26a6 was significantly highly expressed only in the slow salinity reduction intervals of 10 ppt/24 h and 5 ppt/24 h (p < 0.05). On the other hand, the results of antioxidant and apoptosis related experiments showed that in all treatment groups with different rates of salinity reduction, the activities of T-AOC, GSH-PX, and CAT basically increased significantly after salinity reduction compared to the control salinity. Moreover, the activities of T-AOC and CAT were significantly higher in the 10 ppt/24 h and 5 ppt/24 h treatment groups than in the 30 ppt/24 h and 15 ppt/24 h treatment groups. Finally, the experimental results related to apoptosis showed that the expression trends of Capase3 and Bax-2 were basically the same in the treatment groups with different salinity reduction rates, and their expressions were significantly higher in the 10 ppt/24 h and 5 ppt/24 h treatment groups than in the 30 ppt/24 h and 15 ppt/24 h treatment groups. In summary, the present study found that megalopa had strong hyposaline tolerance and were able to regulate osmolality at different rates of salinity reduction, but the antioxidant capacity differed significantly between treatment groups, with rapid salinity reduction leading to oxidative damage in the anterior gills and reduced antioxidant enzyme activity and apoptosis levels.

Sufficient driving force for quinoidal isoindigo-based diradicaloids with tunable diradical characters.

Stable organic π-conjugated diradcialoids with tunable diradical characters can profoundly affect emerging technology. Over the past years, great efforts have been devoted to studying the structure-diradical character relationship in diradicaloids. Herein, a series of quinoidal isoindigo (IID) compounds with different attached terminal end groups were designed. Detailed analysis focuses on elucidating the driving force for evoking and enhancing the diradical character in the quinoidal IID systems. The arylene units of the IID core and the bridged aromatic units determine the contribution of the open-shell diradical form in the ground state. Diradical character y0 correlates well with bond length alternation (BLA), the total HOMA, and the total NICS(1)zz, and it is tuned by bridged aromatic units and terminal end groups in symmetric systems. The zwitterionic character weakens the diradical character in asymmetric systems to different extents. This work contributes to the deep understanding of evoking and enhancing the diradical character in quinoidal IID-based diradcialoids, providing useful guidelines to produce new molecules with desirable properties.

Hemolymph exosomes inhibit Spiroplasma eriocheiris infection by promoting Tetraspanin-mediated hemocyte phagocytosis in crab.

Exosomes released from infected cells are thought to play an important role in the dissemination of pathogens, as well as in host-derived immune molecules during infection. As an intracellular pathogen, Spiroplasma eriocheiris is harmful to multiple crustaceans. However, the immune mechanism of exosomes during Spiroplasma infection has not been investigated. Here, we found exosomes derived from S. eriocheiris-infected crabs could facilitate phagocytosis and apoptosis of hemocytes, resulting in increased crab survival and suppression of Spiroplasma intracellular replication. Proteomic analysis revealed the altered abundance of EsTetraspanin may confer resistance to S. eriocheiris, possibly by mediating hemocyte phagocytosis in Eriocheir sinensis. Specifically, knockdown of EsTetraspanin in E. sinensis increased susceptibility to S. eriocheiris infection and displayed compromised phagocytic ability, whereas overexpression of EsTetraspanin in Drosophila S2 cells inhibited S. eriocheiris infection. Further, it was confirmed that intramuscular injection of recombinant LEL domain of EsTetraspanin reduced the mortality of S. eriocheiris-infected crabs. Blockade with anti-EsTetraspanin serum could exacerbate S. eriocheiris invasion of hemocytes and impair hemocyte phagocytic activity. Taken together, our findings prove for the first time that exosomes modulate phagocytosis to resist pathogenic infection in invertebrates, which is proposed to be mediated by exosomal Tetraspanin, supporting the development of preventative strategies against Spiroplasma infection.

A retrospective study of 3D measurement and analysis applied in the morphological evaluation of achalasia cardia.

Background: Achalasia cardia (AC) is defined as a disorder of esophageal motility whose diagnostic gold standard depends on high-resolution manometry (HRM). The invasiveness of HRM can cause difficulties in diagnosis, treatment, and follow-up for patients with AC. Thus, we aimed to investigate the function of 3D reconstruction and measurement to prove the wide application of this alternative non-invasive approach for AC. Methods: A total of 126 patients with AC and 40 healthy subjects in Tianjin Medical University General Hospital from January 2018 to October 2022 were enrolled in this retrospective study. Chest CT images of these subjects were used to reconstruct the 3D models of the esophagus, stomach, spine, left crus, and right crus. Measurements of esophagus length, volume of esophagus, gastroesophageal insertion angle (His angle), max thickness of esophageal wall, esophagus maximum transverse and longitudinal diameter, esophagus-spine angle, and spine-lower esophageal sphincter (LES) angle were applied based on the models. Results: Retrocardiac esophagus length, volume of esophagus, max thickness of esophageal wall, esophagus maximum transverse and longitudinal diameter, thoracic esophagus-spine angle, and spine-LES angle in the AC group were higher than those in the control group (all P values <0.05). Among the three subtypes of AC, thoracic esophagus length, intra-abdominal LES length, volume of esophagus, His angle, esophagus maximum transverse and longitudinal diameter, and thoracic esophagus-spine angle all presented statistical differences (all P values <0.05). Correlation analysis revealed that manometric types were positively associated with His angle [r=0.196; 95% confidence interval (CI): 0.009, 0.372; P=0.028] but negatively associated with volume of esophagus (r=-0.480; 95% CI: -0.639, -0.310; P<0.001), esophagus maximum transverse diameter (r=-0.551; 95% CI: -0.679, -0.400; P<0.001), esophagus maximum longitudinal diameter (r=-0.518; 95% CI: -0.649, -0.366; P<0.001), and thoracic esophagus-spine angle (r=-0.324; 95% CI: -0.479, -0.157; P<0.001). Conclusions: This study successfully presented the differences in esophageal length, volume, thickness, and angles between healthy subjects and different AC subtypes on the basis of 3D reconstruction and measurement. Thus, 3D model and measurement can be regarded as a good support for further research and make a valuable contribution to developing non-invasive approaches for AC management.

Design, synthesis, evaluation and optimization of novel azole analogues as potent antifungal agents.

In order to develop antifungal drugs, a series of novel azole analogues were designed and synthesized based on our previous work. Most of the target compounds had broad-spectrum antifungal activity, which showed excellent to moderate inhibitory activity against the tested strains, except A. fum 0504656. Among these, compounds B3, B7, B8, B11, B12 and E9 showed excellent activity against C. alb Y0109 and C. alb SC5314 (with the MIC80: 0.0156 ug/mL). In addition, compound B3 showed the best inhibitory activity against fluconazole-resistant strains C. alb 901 and C. alb 904, and had low toxicity against NIH/3T3 cells at the effective MIC range against fungi. Structure-activity relationship and docking studies of the derivatives suggest that the presence of the 2-fluoro-4-hydroxyphenyl and 1,2,3-triazole group enhance the antifungal activity of the compounds, which may be related to the interaction of the key groups with the amino acids surrounding the target enzyme.

Houttuynia Cordata Thunb.: A comprehensive review of traditional applications, phytochemistry, pharmacology and safety.

BACKGROUND: Houttuynia Cordata Thunb. (H. cordata; Saururaceae) is a medicine food homology plant that is grown in many Asian countries. Its main phytochemical constituents are volatile oils, flavonoids, polysaccharides and alkaloids. It has considerable clinical applications and health benefits. PURPOSE: This paper reviews the existing literatures and patents, summarizes the phytochemistry, pharmacological activity, safety and economic botanical applications of H. cordata, and provides a reference for systematic study of the pharmacological effects of H. cordata, improvement of quality standards and further development of its medicinal resources. METHODS: A comprehensive search of literature and patents on H. cordata and its active ingredients published before June 2023 was conducted using PubMed, Google Scholar, Web of Science, and China Knowledge Network. RESULTS: H. cordata is not only edible and medicinal but also used in various aspects of daily life such as fermented beverages, nutraceuticals, feed and cosmetics. The main phytochemical constituents of H. cordata are volatile oils, flavonoids, organic acids and alkaloids. Several in vitro and in vivo studies and clinical trials have found that H. cordata extracts possess antioxidant, anti-inflammatory, antitumor, antibacterial, hepatoprotective and renal, immunomodulatory and potent antiviral effects. The mechanisms of expression of these pharmacological effects are related to the blood-brain barrier, lipophilicity, cAMP signaling and skin permeability, including blocking the MAPK signaling pathway, inhibiting the secretion of inflammatory factors such as TNF-α and IL-1ß, and activating the AMPK pathway. CONCLUSION: This paper provides a comprehensive review of the progress of research on the traditional applications, botany, chemical composition, pharmacological effects and safety of H. cordata and discusses for the first time the economic botanical aspects, which were not explored in the previous reviews. H. cordata has a wide range of bioactive substances whose therapeutic potential has not been fully exploited, and it could provide a new non-toxic approach to many diseases. This traditional medicinal food plant should receive more attention and in-depth research in the future.

Dynamic Interplay of Metabolic and Transcriptional Responses in Shrimp during Early and Late Infection Stages of Enterocytozoon hepatopenaei (EHP).

Enterocytozoon hepatopenaei (EHP) is a microsporidian parasite that infects Litopenaeus vannamei, causing severe hepatopancreatic microsporidiosis (HPM) and resulting in significant economic losses. This study utilizes a combined analysis of transcriptomics and metabolomics to unveil the dynamic molecular interactions between EHP and its host, the Pacific white shrimp, during the early and late stages of infection. The results indicate distinct immunological, detoxification, and antioxidant responses in the early and late infection phases. During early EHP infection in shrimp, immune activation coincides with suppression of genes like Ftz-F1 and SEPs, potentially aiding parasitic evasion. In contrast, late infection shows a refined immune response with phagocytosis-enhancing down-regulation of Ftz-F1 and a resurgence in SEP expression. This phase is characterized by an up-regulated detoxification and antioxidant response, likely a defense against the accumulated effects of EHP, facilitating a stable host-pathogen relationship. In the later stages of infection, most immune responses return to baseline levels, while some immune genes remain active. The glutathione antioxidant system is suppressed early on but becomes activated in the later stages. This phenomenon could facilitate the early invasion of EHP while assisting the host in mitigating oxidative damage caused by late-stage infection. Notably, there are distinctive events in polyamine metabolism. Sustained up-regulation of spermidine synthase and concurrent reduction in spermine levels suggest a potential role of polyamines in EHP development. Throughout the infection process, significant differences in genes such as ATP synthase and hexokinase highlight the continuous influence on energy metabolism pathways. Additionally, growth-related pathways involving amino acids such as tryptophan, histidine, and taurine are disrupted early on, potentially contributing to the growth inhibition observed during the initial stages of infection. In summary, these findings elucidate the dynamic interplay between the host, Litopenaeus vannamei, and the parasite, EHP, during infection. Specific phase differences in immune responses, energy metabolism, and antioxidant processes underscore the intricate relationship between the host and the parasite. The disruption of polyamine metabolism offers a novel perspective in understanding the proliferation mechanisms of EHP. These discoveries significantly advance our comprehension of the pathogenic mechanisms of EHP and its interactions with the host.

Research Advances in Clinical Applications, Anticancer Mechanism, Total Chemical Synthesis, Semi-Synthesis and Biosynthesis of Paclitaxel.

Paclitaxel, a natural secondary metabolite isolated and purified from the bark of the Taxus tree, is considered one of the most successful natural anticancer drugs due to its low toxicity, high potency and broad-spectrum anticancer activity. Taxus trees are scarce and slow-growing, and with extremely low paclitaxel content, the contradiction between supply and demand in the market is becoming more and more intense. Therefore, researchers have tried to obtain paclitaxel by various methods such as chemical synthesis, artificial culture, microbial fermentation and tissue cell culture to meet the clinical demand for this drug. This paper provides a comprehensive overview of paclitaxel extraction, combination therapy, total synthesis, semi-synthesis and biosynthesis in recent years and provides an outlook, aiming to provide a theoretical basis and reference for further research on the production and application of paclitaxel in the future.

Development and application of the MIRA and MIRA-LFD detection methods of Spiroplasma eriocheiris.

The tremor disease (TD) caused by Spiroplasma eriocheiris is the most destructive disease of the Chinese mitten crab, Eriocheir sinensis. This study attempts to construct Multienzyme Isothermal Rapid Amplification (MIRA), a quick and simple nucleic acid amplification method that operates at room temperature. Based on the gene sequences of S. eriocheiris, appropriate amplification primers were constructed and screened in this investigation. Both the relevant specific probe and the chosen specific amplification primers were designed and labeled. The MIRA and MIRA-LFD reaction conditions were then optimized. The result showed MIRA and MIRA-FFD could identify S. eriocheiris at 37 °C in 30 min and 15 min, respectively. To investigate the specificity of MIRA and MIRA-LFD, three Gram-negative bacteria (Bacillus subtilis, Bacillus thuringiensis, and Staphylococcus aureus), three Gram-positive bacteria (Escherichia coli, Aeromonas hydrophila, and Salmonella typhimurium) and S. eriocheiris were selected. The result showed MIRA and MIRA-LFD were highly specific to S. eriocheiris and did not react with other six pathogens. The sensitivities of PCR, MIRA, and MIRA-LFD were then evaluated. The result showed the detection limit of PCR is 1 ng/L whereas the detection limit of MIRA and MIRA-LFD is 10 pg/L. Finally, the established MIRA and MIRA-LFD detection methods had the advantages of being quick, sensitive, and specific for S. eriocheiris detection, as well as not requiring any specialized equipment.

A comparative transcriptome analysis of how shrimp endure and adapt to long-term symbiosis with Enterocytozoon hepatopenaei infection.

Enterocytozoon hepatopenaei (EHP) is a prevalent microsporidian pathogen responsible for hepatopancreatic microsporidiosis (HPM) in Litopenaeus vannamei. This infection not only leads to slowed growth in shrimp abut aslo inflicts substantial economic losses in the global aquaculture industry. However, the molecular mechanisms by which EHP influences the host during various infection stages remain unclear. This study employed comparative transcriptomics to examine the effects of EHP infection on Litopenaeus vannamei between early and late stage of infection groups. Utilizing transcriptomic approaches, we identified differentially expressed genes (DEGs) with notable biological significance through the COG, GO, KEGG, GSEA, and Mufzz time-series methodologies. The results reveal that EHP infection considerably influences host gene expression, with marked differences between early and late infection across distinct timeframes. Key processes such as detoxification, cell apoptosis, and lipid metabolism are pivotal during host-parasite interactions. Hexokinase and phosphatidic acid phosphatase emerge as key factors enabling invasion and sustained effects. Cytochrome P450 and glucose-6-phosphate dehydrogenase could facilitate infection progression. EHP significantly impacts growth, especially through ecdysteroids and 17ß-estradiol dehydrogenase. By delineating stage-specific effects, we gain insights into interaction between EHP and Litopenaeus vannamei, showing how intracellular pathogens reprogram host defenses into mechanisms enabling long-term persistence. This study provides a deeper understanding of host-pathogen dynamics, emphasizing the interplay between detoxification, metabolism, immunity, apoptosis and growth regulation over the course of long-term symbiosis.

Molecular Dynamics Simulation of the Three-Phase Equilibrium Line of CO2 Hydrate with OPC Water Model.

The three-phase coexistence line of the CO2 hydrate was determined using molecular dynamics (MD) simulations. By using the classical and modified Lorentz-Berthelot (LB) parameters, the simulations were carried out at 10 different pressures from 3 to 500 MPa. For the OPC water model, simulations with the classic and the modified LB parameters both showed negative deviations from the experimental values. For the TIP4P/Ice water model, good agreement with experimental equilibrium data can be achieved when the LB parameter is adjusted based on the solubility of CO2 in water. Our results also show that the influence of the water model on the equilibrium prediction is much larger than the CO2 model. Current simulations indicated that the H2O-H2O and H2O-CO2 cross-interactions' parameters might contribute equally to the accurate prediction of T3. According to our simulations, the prediction of T3 values showed relatively higher accuracy while using the combination of TIP4P/Ice water and EPM2 CO2 with modified LB parameter. Furthermore, varied χ values are recommended for accurate T3 estimation over a wide pressure range. The knowledge obtained in this study will be helpful for further accurate MD simulation of the process of CO2/CH4 replacement.

Discovery of anti-neuroinflammatory agents from 1,4,5,6-tetrahydrobenzo[2,3]oxepino[4,5-d]pyrimidin-2-amine derivatives by regulating microglia polarization.

Neuroinflammation mediated by microglia activation leads to various neurodegenerative and neurological disorders. In order to develop more and better options for this disorders, a series of 3,4-dihydrobenzo[b]oxepin-5(2H)-one derivatives (BZPs, 6-19) and novel 1,4,5,6-tetrahydrobenzo[2,3]oxepino[4,5-d]pyrimidin-2-amine derivatives (BPMs, 20-33) were synthesized and screened the anti-neuroinflamamtion effects. 3,5-bis-trifluoromethylphenyl-substituted BPM 29 showed more potent anti-neuroinflammatory activity and no toxicity to BV2 microglia cells in vitro. 29 significantly reduced the number of M1 phenotype of microglia cells, but significantly increased the number of M2 phenotype of microglia cells in lipopolysaccharide (LPS)-induced BV2 microglia cells. 29 significantly reduced the secretion of inflammatory cytokines (IL-18, IL-1ß, TNF-α), but increased the secretion of anti-inflammatory cytokines (IL-10) from LPS-induced BV2 microglia cells. Also, 29 inhibited the NOD-like receptor NLRP3 inflammasome formation, and down-regulated the expression of M2 isoform of pyruvate kinase in LPS-induced BV2 microglia cells. In vivo, 29 reduced the neuroinflammation in cuprizone-induced inflammatory and demyelinating mice by reducing the expression of inducible nitric-oxide synthase, but increased the expression of CD206. Taken together, 29 might be a prospective anti-neuroinflammatory compound for neuroinflammatory and demyelinating disease by alleviating microglia activation.

Phytochemistry, nutritional composition, health benefits and future prospects of Passiflora: A review.

Passiflora, also known as "passion fruit", is widely grown in tropical and subtropical regions. It is not only eaten raw but is also widely used in processed foods. Various extracts, juices and isolated compounds show a wide range of health effects and biological activities, such as antioxidant, anti-inflammatory, sedative, and neuroprotective effects. In this review, we not only review the phytochemical properties of Passiflora but also highlight the potential of Passiflora for food applications and the use of all parts as a source of ingredients for medicines and cosmetics that promote health and well-being. This will provide theoretical support for the integrated use of such natural products.

Assessment of left ventricular energy loss in patients with mild coronary artery stenosis by using vector flow mapping combined with exercise stress echocardiography.

OBJECTIVES: To evaluate the left ventricular energy loss (EL), energy loss reserve (EL-r), and energy loss reserve rate in patients with mild coronary artery stenosis by using vector flow mapping (VFM) combined with exercise stress echocardiography. METHODS: A total of 34 patients (case group) with mild coronary artery stenosis and 36 sex and age matched patients (control group) without coronary artery stenosis according to coronary angiogram were prospectively enrolled. The total energy loss (ELt), basal segment energy loss (ELb), middle segment energy loss (ELm), apical segment energy loss (ELa), energy loss reserve (EL-r), and energy loss reserve rate were recorded in the isovolumic systolic period (S1), rapid ejection period (S2), slow ejection period (S3), isovolumic diastolic period (D1), rapid filling period (D2), slow filling period (D3), and atrial contraction period (D4). RESULTS: Compared with the control group, some of the EL in the resting case group were higher; some of the EL in the case group were lower after exercise, and those during D1 ELb and D3 ELb were higher. Compared with the resting state, the total EL and the EL within the time segment in the control group were higher after exercise, except during D2 ELb. In the case group, except for during D1 ELt, ELb and D2 ELb, the total and segmental EL of each phase was mostly higher after exercise (p < .05). Compared with the control group, most of the EL-r and EL reserve rates in the case group were lower (p < .05). CONCLUSION: The EL, EL-r, and energy loss reserve rate have a certain value in the evaluation of cardiac function in patients with mild coronary artery stenosis.

Screening and functional analysis of three Spiroplasma eriocheiris glycosylated protein interactions with Macrobrachium nipponense C-type lectins.

N-glycosylation, one of the main protein posttranslational modifications (PTMs), plays an important role in the pathogenic process of pathogens through binding and invasion of host cells or regulating the internal environment of host cells to benefit their survival. However, N-glycosylation has remained mostly unexplored in Spiroplasma eriocheiris, a novel type of pathogen which has serious adverse effects on aquaculture. In most cases, N-glycoproteins can be detected and analyzed by lectins dependent on sugar recognition domains. In this study, three Macrobrachium nipponense C-type lectins, namely, MnCTLDcp1, MnCTLDcp2 and MnCTLDcp3, were used to screen S. eriocheiris glycosylated proteins. First, qRT-PCR results showed that the expression levels of the three kinds of lectins were all significantly up-regulated in prawn hearts when the host was against S. eriocheiris infection. A bacterial binding assay showed that purified recombinant MnCTLDcp1, MnCTLDcp2 and MnCTLDcp3 could directly bind to S. eriocheiris in vitro. Second, three S. eriocheiris glycosylated proteins, ATP synthase subunit beta (ATP beta), molecular chaperone Dnak (Dnak) and fructose bisphosphate aldolase (FBPA), were screened and identified using the three kinds of full-length C-type lectins. Far-Western blot and coimmunoprecipitation (CO-IP) further demonstrated that there were interactions between the three lectins with ATP beta, Dnak and FBPA. Furthermore, antibody neutralization assay results showed that pretreatment of S. eriocheiris with ATP beta, Dnak and FBPA antibodies could significantly block this pathogen infection. All the above studies showed that the glycosylated protein played a vital role in the process of S. eriocheiris infection.

The role of small intestinal bacterial overgrowth in obesity and its related diseases.

Obesity has become a major public health problem worldwide and its occurrence is increasing globally. Obesity has also been shown to be involved in the occurrence and development of many diseases and pathological conditions, such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), insulin resistance (IR). In recent years, gut microbiota has received extensive attention as an important regulatory part involved in host diseases and health status. A growing body of evidence suggests that gut microbiota dysbiosis has a significant adverse effect on the host. Small intestinal bacterial overgrowth (SIBO), a type of intestinal microbial dysbiosis, has been gradually revealed to be associated with obesity and its related diseases. The presence of SIBO may lead to the destruction of intestinal barrier integrity, increased intestinal permeability, increased endotoxin levels, activation of inflammatory responses, and translocation of bacteria from the colon to the small intestine. However, the causal relationship between SIBO and obesity and the specific mechanisms have not been well elucidated. This review discusses the cross-talk between SIBO and obesity and its related diseases, and expounds its potential mechanisms and interventions, which may help to discover new therapeutic targets for obesity and its related diseases and develop treatment options.