CXCL4/CXCR3 axis regulates cardiac fibrosis by activating TGF-ß1/Smad2/3 signaling in mouse viral myocarditis.

BACKGROUND: Severe myocarditis is often accompanied by cardiac fibrosis, but the underlying mechanism has not been fully elucidated. CXCL4 is a chemokine that has been reported to have pro-inflammatory and profibrotic functions. The exact role of CXCL4 in cardiac fibrosis remains unclear. METHODS: Viral myocarditis (VMC) models were induced by intraperitoneal injection of Coxsackie B Type 3 (CVB3). In vivo, CVB3 (100 TCID50) and CVB3-AMG487 (CVB3: 100 TCID50; AMG487: 5 mg/kg) combination were administered in the VMC and VMC+AMG487 groups, respectively. Hematoxylin and eosin staining, severity score, Masson staining, and immunofluorescence staining were performed to measure myocardial morphology in VMC. Enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed to quantify inflammatory factors (IL-1ß, IL-6, TNF-α, and CXCL4). Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase-myocardial band (CK-MB) levels were analyzed by commercial kits. CXCL4, CXCR3B, α-SMA, TGF-ß1, Collagen I, and Collagen III were determined by Western blot and immunofluorescence staining. RESULTS: In vivo, CVB3-AMG487 reduced cardiac injury, α-SMA, Collagen I and Collagen III levels, and collagen deposition in VMC+AMG487 group. Additionally, compared with VMC group, VMC+AMG group decreased the levels of inflammatory factors (IL-1ß, IL-6, and TNF-α). In vitro, CXCL4/CXCR3B axis activation TGF-ß1/Smad2/3 pathway promote mice cardiac fibroblasts differentiation. CONCLUSION: CXCL4 acts as a profibrotic factor in TGF-ß1/Smad2/3 pathway-induced cardiac fibroblast activation and ECM synthesis, and eventually progresses to cardiac fibrosis. Therefore, our findings revealed the role of CXCL4 in VMC and unveiled its underlying mechanism. CXCL4 appears to be a potential target for the treatment of VMC.

Soluble E-cadherin participates in BLM-induced pulmonary fibrosis by promoting EMT and lung fibroblast migration.

Soluble E-cadherin (sE-cad) is an 80 kDa fragment derived from E-cadherin that is shed from the cell surface through proteolytic cleavage and is a biomarker in various cancers that promotes invasion and migration. Alveolar epithelial destruction, aberrant lung fibroblast migration and inflammation contribute to pulmonary fibrosis. Here, we hypothesized that E-cadherin plays an important role in lung fibrosis. In this study, we found that E-cadherin was markedly increased in the bronchoalveolar lavage fluid (BALF) and serum of mice with pulmonary fibrosis and that blocking sE-cad with HECD-1, a neutralizing antibody targeting the ectodomain of E-cadherin, effectively inhibited myofibroblast accumulation and collagen deposition in the lungs after bleomycin (BLM) exposure. Moreover, transforming growth factor-ß (TGF-ß1) induced the shedding of sE-cad from A549 cells, and treatment with HECD-1 inhibited epithelial-mesenchymal transition (EMT) stimulated by TGF-ß1. Fc-E-cadherin (Fc-Ecad), which is an exogenous form of sE-cad, robustly promoted lung fibroblast migration. E-cadherin participates in bleomycin (BLM)-induced lung fibrosis by promoting EMT in the alveolar epithelium and fibroblast activation. E-cadherin may be a novel therapeutic target for lung fibrosis.

Terpenoids from Euphorbia helioscopia and Their Cytotoxic Activities against H1975 Cells.

Three previously undescribed diterpenoids, helioscopnoids A-C, and eight known compounds were isolated from the whole plants of Euphorbia helioscopia. Their structures were established by extensive analysis of spectra and data comparison with previous literatures. Among them, compound 4 was identified as 24,24-dimethoxy-25,26,27-trinoreuphan-3ß-ol with revised configurations of C-13, C-14, and C-17 (13R*, 14R*, 17R*). Cytotoxicity assays revealed that all compounds exhibited varying levels of cytotoxicity against H1975 cells, with compound 9 displaying the most potent activity, as indicated by cell viability rates of 18.13 % and 20.76 % at concentrations of 20 µM and 5 µM, respectively. This study expands the understanding of E. helioscopia terpenoids' structural diversity and biological activities, contributing to the exploration of potential therapeutic applications.

Intrathecal delivery of AAV-NDNF ameliorates disease progression of ALS mice.

Amyotrophic lateral sclerosis (ALS) is a uniformly lethal neurodegenerative disease characterized by progressive deterioration of motor neurons and neuromuscular denervation. Adeno-associated virus (AAV)-mediated delivery of trophic factors is being considered as a potential disease-modifying therapeutic avenue. Here we show a marked effect of AAV-mediated over-expression of neuron-derived neurotrophic factor (NDNF) on SOD1G93A ALS model mice. First, we adopt AAV-PHP.eB capsid to enable widespread expression of target proteins in the brain and spinal cord when delivered intrathecally. Then we tested the effects of AAV-NDNF on SOD1G93A mice at different stages of disease. Interestingly, AAV-NDNF markedly improved motor performance and alleviated weight loss when delivered at early post-symptomatic stage. Injection in the middle post-symptomatic stages still improved the locomotion ability, although it did not alleviate the loss of body weight. Injection in the late stage also extended the life span of SOD1G93A mice. Furthermore, NDNF expression promoted the survival of spinal motoneurons, reduced abnormal protein aggregation, and preserved the innervated neuromuscular functions. We further analyzed the signaling pathways of NDNF expression and found that it activates cell survival and growth-associated mammalian target of rapamycin signaling pathway and downregulates apoptosis-related pathways. Thus, intrathecally AAV-NDNF delivery has provided a potential strategy for the treatment of ALS.

Advances and Applications of Brain Organoids.

Understanding the fundamental processes of human brain development and diseases is of great importance for our health. However, existing research models such as non-human primate and mouse models remain limited due to their developmental discrepancies compared with humans. Over the past years, an emerging model, the "brain organoid" integrated from human pluripotent stem cells, has been developed to mimic developmental processes of the human brain and disease-associated phenotypes to some extent, making it possible to better understand the complex structures and functions of the human brain. In this review, we summarize recent advances in brain organoid technologies and their applications in brain development and diseases, including neurodevelopmental, neurodegenerative, psychiatric diseases, and brain tumors. Finally, we also discuss current limitations and the potential of brain organoids.

Effect of preoperative inspiratory muscle training on postoperative outcomes in patients undergoing cardiac surgery: A systematic review and meta-analysis.

BACKGROUND: Cardiovascular disease is the most prevalent disease worldwide and places a great burden on the health and economic welfare of patients. Cardiac surgery is an important way to treat cardiovascular disease, but it can prolong mechanical ventilation time, intensive care unit (ICU) stay, and postoperative hospitalization for patients. Previous studies have demonstrated that preoperative inspiratory muscle training could decrease the incidence of postoperative pulmonary complications. AIM: To explore the effect of preoperative inspiratory muscle training on mechanical ventilation time, length of ICU stay, and duration of postoperative hospitalization after cardiac surgery. METHODS: A literature search of PubMed, Web of Science, Cochrane Library, EMBASE, China National Knowledge Infrastructure, WanFang, and the China Science and Technology journal VIP database was performed on April 13, 2022. The data was independently extracted by two authors. The inclusion criteria were: (1) Randomized controlled trial; (2) Accessible as a full paper; (3) Patients who received cardiac surgery; (4) Preoperative inspiratory muscle training was implemented in these patients; (5) The study reported at least one of the following: Mechanical ventilation time, length of ICU stay, and/or duration of postoperative hospitalization; and (6) In English language. RESULTS: We analyzed six randomized controlled trials with a total of 925 participants. The pooled mean difference of mechanical ventilation time was -0.45 h [95% confidence interval (CI): -1.59-0.69], which was not statistically significant between the intervention group and the control group. The pooled mean difference of length of ICU stay was 0.44 h (95%CI: -0.58-1.45). The pooled mean difference of postoperative hospitalization was -1.77 d in the intervention group vs the control group [95%CI: -2.41-(-1.12)]. CONCLUSION: Preoperative inspiratory muscle training may decrease the duration of postoperative hospitalization for patients undergoing cardiac surgery. More high-quality studies are needed to confirm our conclusion.

An integrated approach of network pharmacology, molecular docking, and experimental verification uncovers kaempferol as the effective modulator of HSD17B1 for treatment of endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is one of the most common gynecological malignancies globally, and the development of innovative, effective drugs against EC remains a key issue. Phytoestrogen kaempferol exhibits anti-cancer effects, but the action mechanisms are still unclear. METHOD: MTT assays, colony-forming assays, flow cytometry, scratch healing, and transwell assays were used to evaluate the proliferation, apoptosis, cell cycle, migration, and invasion of both ER-subtype EC cells. Xenograft experiments were used to assess the effects of kaempferol inhibition on tumor growth. Next-generation RNA sequencing was used to compare the gene expression levels in vehicle-treated versus kaempferol-treated Ishikawa and HEC-1-A cells. A network pharmacology and molecular docking technique were applied to identify the anti-cancer mechanism of kaempferol, including the building of target-pathway network. GO analysis and KEGG pathway enrichment analysis were used to identify cancer-related targets. Finally, the study validated the mRNA and protein expression using real-time quantitative PCR, western blotting, and immunohistochemical analysis. RESULTS: Kaempferol was found to suppress the proliferation, promote apoptosis, and limit the tumor-forming, scratch healing, invasion, and migration capacities of EC cells. Kaempferol inhibited tumor growth and promotes apoptosis in a human endometrial cancer xenograft mouse model. No significant toxicity of kaempferol was found in human monocytes and normal cell lines at non-cytotoxic concentrations. No adverse effects or significant changes in body weight or organ coefficients were observed in 3-7 weeks' kaempferol-treated animals. The RNA sequencing, network pharmacology, and molecular docking approaches identified the overall survival-related differentially expressed gene HSD17B1. Interestingly, kaempferol upregulated HSD17B1 expression and sensitivity in ER-negative EC cells. Kaempferol differentially regulated PPARG expression in EC cells of different ER subtypes, independent of its effect on ESR1. HSD17B1 and HSD17B1-associated genes, such as ESR1, ESRRA, PPARG, AKT1, and AKR1C1\2\3, were involved in several estrogen metabolism pathways, such as steroid binding, 17-beta-hydroxysteroid dehydrogenase (NADP+) activity, steroid hormone biosynthesis, and regulation of hormone levels. The molecular basis of the effects of kaempferol treatment was evaluated. CONCLUSIONS: Kaempferol is a novel therapeutic candidate for EC via HSD17B1-related estrogen metabolism pathways. These results provide new insights into the efficiency of the medical translation of phytoestrogens.

Volumetric analysis of effectiveness of embolization for preventing type II endoleaks following endovascular aortic aneurysm repair.

OBJECTIVE: The presence of endoleak was associated with the failure of endovascular aortic aneurysm repair (EVAR) treatment. The key to eliminating type II endoleak has shifted from reintervention to prevention. This study aimed to evaluate the effectiveness and safety of applying fibrin sealant to prevent type II endoleak in conjunction with EVAR. METHODS: All patients with abdominal aortic aneurysm who underwent EVAR from June 2019 to July 2021 were reviewed. Patients were grouped as Group A: standard EVAR with preemptive embolization and Group B: standard EVAR alone. The primary endpoint was the incidence of type II endoleak. The secondary endpoints were aneurysm sac regression, the inferior mesenteric artery patency, the numbers of patent lumbar arteries, and all-cause mortality. RESULTS: A total of 104 patients were included in Group A, and 116 were included in Group B. Technical success rate was 100%. The overall incidence of type II endoleak in Group A was significantly lower than that in Group B (4.8% vs 19.0%). The mean time of freedom from type II endoleak was 22.71 months for Group A (95% confidence interval, 21.59-23.83 months) and 19.89 months for Group B (95% confidence interval, 18.08-21.70 months). The Kaplan-Meier estimate of freedom from type II endoleak showed a significantly longer duration of freedom from type II endoleak in Group A (81.0% vs 95.2%). Group A showed a continuous sac regression tendency. In Group B, the sac volume decreased within 12 months but increased by 3.07 cm3 at 24 months. No complications were noted in both groups. CONCLUSIONS: Nonselective preemptive embolization with porcine fibrin sealant during EVAR was safe and effective in preventing type II endoleak in the short and mid-term. Preemptive embolization can lead to a significantly higher sac regression rate. Larger patient populations and longer follow-ups with randomized control designed trials are expected to verify the long-term effectiveness and safety of preemptive embolization in preventing type II endoleak.

Efficacy and safety of Chinese herbal medicine Wuwei Xiaodu Drink for wound infection: A protocol for systematic review and meta-analysis.

BACKGROUND: Wound infection (WI) is a disease in which pathogenic bacteria invade and multiply in a wound after trauma or surgery, causing a systemic inflammatory response. WI triggers an immune response in the body, resulting in inflammation and tissue damage, as well as slowing down the healing process. The traditional Chinese medicine prescription of Wuwei Xiaodu Drink (WWXDD) has been widely used in clinical practice with good results. However, there is no high-level evidence to support this result. The purpose of this study was to evaluate the efficacy and safety of WWXDD in the treatment of WI. METHODS: We will search articles in 7 electronic databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang Data (WF), Chinese Scientific Journals Database (VIP), Chinese databases SinoMed (CBM), PubMed, Embase, and Cochrane Library databases. All the publications, with no time restrictions, will be searched without any restriction on language and status, the time from the establishment of the database to October 2022. Two reviewers will independently assess the quality of the selected studies, NoteExpress and Excel software will be used to extract data, and the content will be stored in an electronic chart. Different researchers will separately screen the titles and abstracts of records acquired potential eligibility which comes from the electronic databases. Full-text screening and data extraction will be conducted afterward independently. Statistical analysis will be conducted using RevMan 5.4 software (Cochrane Collaboration). RESULTS: What this study will do is evaluate the efficacy and safety of WWXDD in the treatment of WI in order to provide high quality, evidence-based clinical recommendations. CONCLUSION: This research provides a trusted clinical foundation for the treatment of WI with WWXDD.

Identification of key candidate genes and biological pathways in neuropathic pain.

BACKGROUND: Neuropathic pain is a common chronic pain, characterized by spontaneous pain and mechanical allodynia. The incidence of neuropathic pain is on the rise due to infections, higher rates of diabetes and stroke, and increased use of chemotherapy drugs in cancer patients. At present, due to its pathophysiological process and molecular mechanism remaining unclear, there is a lack of effective treatment and prevention methods in clinical practice. Now, we use bioinformatics technology to integrate and filter hub genes that may be related to the pathogenesis of neuropathic pain, and explore their possible molecular mechanism by functional annotation and pathway enrichment analysis. METHODS: The expression profiles of GSE24982, GSE2884, GSE2636 and GSE30691 were downloaded from the Gene Expression Omnibus（GEO）database, and these datasets include 93 neuropathic pain Rattus norvegicus and 59 shame controls. After the four datasets were all standardized by quantiles, the differentially expressed genes (DEGs) between NPP Rattus norvegicus and the shame controls were finally identified by the robust rank aggregation (RRA) analysis method. In order to reveal the possible underlying biological function of DEGs, the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis of DEGs were performed. In addition, a Protein-protein Interaction (PPI) network was also established. At the end of our study, a high throughput sequencing dataset GSE117526 was used to corroborate our calculation results. RESULTS: Through RRA analysis of the above four datasets GSE24982, GSE2884, GSE2636, and GSE30691, we finally obtained 231 DEGs, including 183 up-regulated genes and 47 down-regulated genes. Arranging 231 DEGs in descending order according to |log2 fold change (FC)|, we found that the top 20 key genes include 14 up-regulated genes and 6 down-regulated genes. The most down-regulated hub gene abnormal expressed in NPP was Egf17 (P-value = 0.008), Camk2n2 (P-value = 0.002), and Lep (P-value = 0.02), and the most up-regulated hub gene abnormal expressed in NPP was Nefm (P-value = 1.08E-06), Prx (P-value = 2.68E-07), and Stip1 (P-value = 4.40E-07). In GO functional annotation analysis results, regulation of ion transmembrane transport (GO:0034765; P-value = 1.45E-09) was the most remarkable enriched for biological process, synaptic membrane (GO:0097060; P-value = 2.95E-08) was the most significantly enriched for cellular component, channel activity (GO:0015267; P-value = 2.44E-06) was the most prominent enriched for molecular function. In KEGG pathway enrichment analysis results, the top three notable enrichment pathways were Neuroactive ligand-receptor interaction (rno04080; P-value = 3.46E-08), Calcium signaling pathway (rno04020; P-value = 5.37E-05), and Osteoclast differentiation (rno04380; P-value = 0.000459927). Cav1 and Lep appeared in the top 20 genes in both RRA analysis and PPI analysis, while Nefm appeared in RRA analysis and datasets GSE117526 validation analysis, so we finally identified these three genes as hub genes. CONCLUSIONS: Our research identified the hub genes and signal pathways of neuropathic pain, enriched the pathophysiological mechanism of neuropathic pain to some extent, and provided a possible basis for the targeted therapy of neuropathic pain.

The VraSR two-component signal transduction system contributes to the damage of blood-brain barrier during Streptococcus suis meningitis.

Streptococcus suis (S. suis) is an important zoonotic pathogen that can cause high morbidity and mortality in both humans and swine. As the most important life-threatening infection of the central nervous system (CNS), meningitis is an important syndrome of S. suis infection. The vancomycin resistance associated sensor/regulator (VraSR) is a critical two-component signal transduction system that affects the ability of S. suis to resist the host innate immune system and promotes its ability to adhere to brain microvascular endothelial cells (BMECs). Prior work also found mice infected with ΔvraSR had no obvious neurological symptoms, unlike mice infected with wild-type SC19. Whether and how VraSR participates in the development of S. suis meningitis remains unknown. Here, we found ΔvraSR-infected mice did not show obvious meningitis, compared with wild-type SC19-infected mice. Moreover, the proinflammatory cytokines and chemokines in serum and brains of ΔvraSR-infected mice, including IL-6, TNF-α, MCP-1 and IFN-γ, were significantly lower than wild-type infected group. Besides, blood-brain barrier (BBB) permeability also confirmed that the mutant had lower ability to disrupt BBB. Furthermore, in vivo and in vitro experiments showed that SC19 could increase BBB permeability by downregulating tight junction (TJ) proteins such as ZO-1, ß-Catenin, Occludin, and Clauidn-5, compared with mutant ΔvraSR. These findings provide new insight into the influence of S. suis VraSR on BBB disruption during the pathogenic process of streptococcal meningitis, thereby offering potential targets for future preventative and therapeutic strategies against this disease.

Elevated pH-mediated mitigation of aluminum-toxicity in sweet orange (Citrus sinensis) roots involved the regulation of energy-rich compounds and phytohormones.

For the first time, we used targeted metabolome to investigate the effects of pH-aluminum (Al) interactions on energy-rich compounds and their metabolites (ECMs) and phytohormones in sweet orange (Citrus sinensis) roots. The concentration of total ECMs (TECMs) was reduced by Al-toxicity in 4.0-treated roots, but unaffected significantly in pH 3.0-treated roots. However, the concentrations of most ECMs and TECMs were not lower in pH 4.0 + 1.0 mM Al-treated roots (P4AR) than in pH 3.0 + 1.0 mM Al-treated roots (P3AR). Increased pH improved the adaptability of ECMs to Al-toxicity in roots. For example, increased pH improved the utilization efficiency of ECMs and the conversion of organic phosphorus (P) from P-containing ECMs into available phosphate in Al-treated roots. We identified upregulated cytokinins (CKs), downregulated jasmonic acid (JA), methyl jasmonate (MEJA) and jasmonates (JAs), and unaltered indole-3-acetic acid (IAA) and salicylic acid (SA) in P3AR vs pH 3.0 + 0 mM Al-treated roots (P3R); upregulated JA, JAs and IAA, downregulated total CKs, and unaltered MEJA and SA in P4AR vs pH 4.0 + 0 mM Al-treated roots (P4R); and upregulated CKs, downregulated JA, MEJA, JAs and SA, and unaltered IAA in P3AR vs P4AR. Generally viewed, raised pH-mediated increments of JA, MEJA, total JAs, SA and IAA concentrations and reduction of CKs concentration in Al-treated roots might help to maintain nutrient homeostasis, increase Al-toxicity-induced exudation of organic acid anions and the compartmentation of Al in vacuole, and reduce oxidative stress and Al uptake, thereby conferring root Al-tolerance. In short, elevated pH-mediated mitigation of root Al-stress involved the regulation of ECMs and phytohormones.

Perioperative respiratory muscle training improves respiratory muscle strength and physical activity of patients receiving lung surgery: A meta-analysis.

BACKGROUND: The clinical role of perioperative respiratory muscle training (RMT), including inspiratory muscle training (IMT) and expiratory muscle training (EMT) in patients undergoing pulmonary surgery remains unclear up to now. AIM: To evaluate whether perioperative RMT is effective in improving postoperative outcomes such as the respiratory muscle strength and physical activity level of patients receiving lung surgery. METHODS: The PubMed, EMBASE (via OVID), Web of Science, Cochrane Library and Physiotherapy Evidence Database (PEDro) were systematically searched to obtain eligible randomized controlled trials (RCTs). Primary outcome was postoperative respiratory muscle strength expressed as the maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). Secondary outcomes were physical activity, exercise capacity, including the 6-min walking distance and peak oxygen consumption during the cardio-pulmonary exercise test, pulmonary function and the quality of life. RESULTS: Seven studies involving 240 participants were included in this systematic review and meta-analysis. Among them, four studies focused on IMT and the other three studies focused on RMT, one of which included IMT, EMT and also combined RMT (IMT-EMT-RMT). Three studies applied the intervention postoperative, one study preoperative and the other three studies included both pre- and postoperative training. For primary outcomes, the pooled results indicated that perioperative RMT improved the postoperative MIP (mean = 8.13 cmH2O, 95%CI: 1.31 to 14.95, P = 0.02) and tended to increase MEP (mean = 13.51 cmH2O, 95%CI: -4.47 to 31.48, P = 0.14). For secondary outcomes, perioperative RMT enhanced postoperative physical activity significantly (P = 0.006) and a trend of improved postoperative pulmonary function was observed. CONCLUSION: Perioperative RMT enhanced postoperative respiratory muscle strength and physical activity level of patients receiving lung surgery. However, RCTs with large samples are needed to evaluate effects of perioperative RMT on postoperative outcomes in patients undergoing lung surgery.

Postoperative Pulmonary Complications in Patients With Transcatheter Tricuspid Valve Implantation-Implications for Physiotherapists.

Objectives: To investigate the incidence of postoperative pulmonary complications (PPCs) and short-term recovery after transcatheter tricuspid valve implantation (TTVI). Methods: A total of 17 patients diagnosed with severe tricuspid regurgitation who received a LuX-valve TTVI were included in this study. Spirometry lung function, maximal inspiratory pressure (MIP), and 6-min walk test distance (6MWD) were recorded. Prior to surgery, patients were stratified into high or low pulmonary risk groups based on published predefined criteria. A physiotherapist provided all patients with education on thoracic expansion exercises, effective cough and an inspiratory muscle training protocol at 50% of MIP for 3 days preoperatively. All patients received standard post-operative physiotherapy intervention including positioning, thoracic expansion exercises, secretion removal techniques and mobilization. Patients were assessed for PPCs as defined by the Melbourne-Group Score-version 2. Clinical characteristics and hospital stay, cost, functional capacity, and Kansas City Cardiomyopathy Questionnaire (KCCQ) heart failure score were recorded at admission, 1-week, and 30-days post-op. Results: The mean (SD) age of the 17 patients was 68.4 (8.0) years and 15 (88%) were female. Pre-surgical assessment identified 8 patients (47%) at high risk of PPCs. A total of 9 patients (53%) developed PPCs between the 1st and 3rd day post-surgery, and 7 of these 9 patients were amongst the 8 predicted as "high risk" prior to surgery. One patient died before the 30 day follow up. Pre-operative pulmonary risk assessment score, diabetes mellitus, a low baseline MIP and 6MWD were associated with a high incidence of PPCs. Compared to those without PPCs, patients with PPCs had longer ICU and hospital stay, and higher hospitalization cost. At 30 days post-surgery, patients without PPCs maintained higher MIP and 6MWD compared to those with PPCs, but there were no significant between-group differences in other lung function parameters nor KCCQ. Conclusion: This is the first study to report the incidence of PPCs post TTVI. Despite a 3-day prehabilitation protocol and standard post-operative physiotherapy, PPCs were common among patients after TTVI and significantly impacted on hospital and short-term recovery and outcomes. In the majority of patients, PPCs could be accurately predicted before surgery. A comprehensive prehabilitation program should be considered for patients prior to TTVI. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2000039671].

Complete Endovascular Repair for Abdominal Aortic Aneurysm With Concomitant Aorto-Left Retroaortic Renal Vein Fistula.

BACKGROUND: Abdominal aortic aneurysm (AAA) with concomitant aorto-retroarotic left renal vein fistula (ALRVF) is an extremely rare clinical condition. With the recent development of endovascular techniques, repair of such conditions with a complete minimal invasive approach is now possible. We reported here a case of endovascular repair of AAA with concomitant ALRVF. CASE PRESENTATION: A 62-year-old gentleman presenting with AAA and concomitant ALRVF underwent complete endovascular repair, including an endovascular aortic aneurysm repair (EVAR) with bifurcated aortic graft as well as embolization of the aneurysm sac and deployment of a covered stent in the left retroarotic renal vein to achieve sealing of the arterial-venous fistula. The patient required no blood transfusion and no ICU stay. He has been followed up closely for 4 years and has been well clinically. Aneurysm sac size has remained stable. CONCLUSIONS: Endovascular repair can be a safe and reliable surgical alternative to treat AAA with concomitant ALRVF. But long-term follow up and more clinical data are required to verify the durability of endovascular repair for such conditions.

Behavioral Responses to Familiar Versus Unfamiliar Older People as a Source of Disgust.

Disgust, as a part of the behavioral immune system, leads people to avoid behaviors of pathogens so as to reduce the probability of infection. Disgust also shows the source effects based on familiarity. However, these source effects have not been tested on the older population. Thus, we tested the source effects of emotional and behavioral reactions from the disgust toward older adults and the possible moderating effects of filial piety on disgust. In the first study, we employed the self-report method to test the source effects of emotional feelings of disgust amongst undergraduates. In the second study, we measured whether filial piety among community adults produced moderating effects of the disgust toward older adults. In the third study, we employed the shape discrimination task to test the source effects of behavioral avoidance to older adults among undergraduates. The first and third studies show stronger negative emotional/avoidance reactions towards unfamiliar older adults than familiar older adults, affirming the source effects of disgust towards older adults that we expected. However, we did not find moderating effects of filial piety associated with disgust. These findings can help us understand the evolutionary origin of disgust toward older adults, which is likely activated more intensely and quickly in response to unfamiliar individuals as compared with familiar individuals.

Structure of Vibrio collagenase VhaC provides insight into the mechanism of bacterial collagenolysis.

The collagenases of Vibrio species, many of which are pathogens, have been regarded as an important virulence factor. However, there is little information on the structure and collagenolytic mechanism of Vibrio collagenase. Here, we report the crystal structure of the collagenase module (CM) of Vibrio collagenase VhaC and the conformation of VhaC in solution. Structural and biochemical analyses and molecular dynamics studies reveal that triple-helical collagen is initially recognized by the activator domain, followed by subsequent cleavage by the peptidase domain along with the closing movement of CM. This is different from the peptidolytic mode or the proposed collagenolysis of Clostridium collagenase. We propose a model for the integrated collagenolytic mechanism of VhaC, integrating the functions of VhaC accessory domains and its collagen degradation pattern. This study provides insight into the mechanism of bacterial collagenolysis and helps in structure-based drug design targeting of the Vibrio collagenase.

Preliminary study of hemodynamics of iliac venous compression syndrome using magnetic resonance imaging.

OBJECTIVE: In clinical practice, the degree of iliac vein stenosis has often been inconsistent with the symptoms of chronic venous disease (CVD). To the best of our knowledge, no clinical studies have evaluated the hemodynamic changes associated with iliac vein stenosis. Magnetic resonance imaging (MRI) can noninvasively provide hemodynamic information. In the present study, we assessed the degree of stenosis associated with iliac venous compression syndrome and the relationships between iliac venous compression syndrome-induced, MRI-determined hemodynamic changes and lower limb symptoms. METHODS: Stenosis severity, the presence of collateral vessels, and flow rate (FR) differences between the common and external iliac veins secondary to iliac vein stenosis were measured using MRI in 69 patients with CVD. Villalta scores were used as a measure of symptom severity for all patients, and the percentage of change in the Villalta score was used as a measure of symptom improvement for the patients who had received iliac vein stents. Symptom severity for all patients, a subgroup of patients with iliac vein compression (affected limbs), and a group of patients with unilateral iliac vein compression treated with stents was correlated with stenosis, differences in the external and common iliac vein FRs (<0-mL/s group, indicating stenosis-induced decreased common iliac vein flow, and ≥0-mL/s group), and stenosis-induced collateral vessel formation. RESULTS: Iliac vein stenosis severity and FR differences in all affected limbs were correlated with the Villalta scores of the affected limbs (stenosis: r = 0.38, P < .001, n = 95; FR difference: r = -0.44, P < .001). In the unilateral compression subgroup, stenosis severity, FR differences, and the presence of collateral vessels were not associated with significant changes in contralateral symptoms. In the endovascular treatment subgroup, both lower limbs exhibited significant improvement after stent implantation (affected limb symptom remission, 64.6% ± 18.2%, n = 15; contralateral limb symptom remission, 49.1% ± 29.1%, n = 11). The rate of symptom remission was greater for patients with decreased iliac vein flow in the affected limbs (<0-mL/s group: 74.6% ± 16.4%, n = 7; ≥0-mL/s group: 52.2% ± 16.6%, n = 6; P = .032). CONCLUSIONS: Iliac vein stenosis, the presence of collateral vessels, and decreased FRs due to stenosis correlated significantly with lower limb symptom severity. Endovascular treatment yielded good outcomes in patients with stenosis >50%. A decreased iliac venous FR could indicate a better response to stent implantation and could be used in the diagnosis and guiding decisions to treat iliac venous compression.

Immuno-modulation with lifestyle behaviour change to reduce SARS-CoV-2 susceptibility and COVID-19 severity: goals consistent with contemporary physiotherapy practice.

Lifestyle-related non-communicable diseases (NCDs) and their risk factors are unequivocally associated with SARS-CoV-2 susceptibility and COVID-19 severity. NCD manifestations and their lifestyle risks are associated with chronic low-grade systemic inflammation (CLGSI). This review supports that immuno-modulation with positive lifestyle change aimed at reducing SARS-CoV-2 susceptibility and COVID-19 severity, is a goal consistent with contemporary physiotherapy practice. Physiotherapists have a long tradition of managing a , thus, managing CLGSI is a logical extension. Improving patients' lifestyle practices also reduces their NCD risks and increases activity/exercise capacity, health and wellbeing - all principal goals of contemporary physiotherapy. The COVID-19 pandemic lends further support for prioritising health and lifestyle competencies including smoking cessation; whole food plant-based nutrition; healthy weight; healthy sleep practices; and stress management; in conjunction with reducing sedentariness and increasing physical activity/exercise, to augment immunity as well as function and overall health and wellbeing. To support patients' lifestyle change efforts, physiotherapists may refer patients to other health professionals. The authors conclude that immuno-modulation with lifestyle behaviour change to reduce susceptibility to viruses including SARS-CoV-2, is consistent with contemporary physiotherapy practice. Immuno-modulation needs to be reflected in health competencies taught in physiotherapy professional education curricula and taught at standards comparable to other established interventions.

Mechanistic insights into the key marine dimethylsulfoniopropionate synthesis enzyme DsyB/DSYB.

Marine algae and bacteria produce approximately eight billion tonnes of the organosulfur molecule dimethylsulfoniopropionate (DMSP) in Earth's surface oceans annually. DMSP is an antistress compound and, once released into the environment, a major nutrient, signaling molecule, and source of climate-active gases. The methionine transamination pathway for DMSP synthesis is used by most known DMSP-producing algae and bacteria. The S-directed S-adenosylmethionine (SAM)-dependent 4-methylthio-2-hydroxybutyrate (MTHB) S-methyltransferase, encoded by the dsyB/DSYB gene, is the key enzyme of this pathway, generating S-adenosylhomocysteine (SAH) and 4-dimethylsulfonio-2-hydroxybutyrate (DMSHB). DsyB/DSYB, present in most haptophyte and dinoflagellate algae with the highest known intracellular DMSP concentrations, is shown to be far more abundant and transcribed in marine environments than any other known S-methyltransferase gene in DMSP synthesis pathways. Furthermore, we demonstrate in vitro activity of the bacterial DsyB enzyme from Nisaea denitrificans and provide its crystal structure in complex with SAM and SAH-MTHB, which together provide the first important mechanistic insights into a DMSP synthesis enzyme. Structural and mutational analyses imply that DsyB adopts a proximity and desolvation mechanism for the methyl transfer reaction. Sequence analysis suggests that this mechanism may be common to all bacterial DsyB enzymes and also, importantly, eukaryotic DSYB enzymes from e.g., algae that are the major DMSP producers in Earth's surface oceans.