Anemoside B4, a new pyruvate carboxylase inhibitor, alleviates colitis by reprogramming macrophage function.

OBJECTIVES: Colitis is a global disease usually accompanied by intestinal epithelial damage and intestinal inflammation, and an increasing number of studies have found natural products to be highly effective in treating colitis. Anemoside B4 (AB4), an abundant saponin isolated from Pulsatilla chinensis (Bunge), which was found to have strong anti-inflammatory activity. However, the exact molecular mechanisms and direct targets of AB4 in the treatment of colitis remain to be discovered. METHODS: The anti-inflammatory activities of AB4 were verified in LPS-induced cell models and 2, 4, 6-trinitrobenzene sulfonic (TNBS) or dextran sulfate sodium (DSS)-induced colitis mice and rat models. The molecular target of AB4 was identified by affinity chromatography analysis using chemical probes derived from AB4. Experiments including proteomics, molecular docking, biotin pull-down, surface plasmon resonance (SPR), and cellular thermal shift assay (CETSA) were used to confirm the binding of AB4 to its molecular target. Overexpression of pyruvate carboxylase (PC) and PC agonist were used to study the effects of PC on the anti-inflammatory and metabolic regulation of AB4 in vitro and in vivo. RESULTS: AB4 not only significantly inhibited LPS-induced NF-κB activation and increased ROS levels in THP-1 cells, but also suppressed TNBS/DSS-induced colonic inflammation in mice and rats. The molecular target of AB4 was identified as PC, a key enzyme related to fatty acid, amino acid and tricarboxylic acid (TCA) cycle. We next demonstrated that AB4 specifically bound to the His879 site of PC and altered the protein's spatial conformation, thereby affecting the enzymatic activity of PC. LPS activated NF-κB pathway and increased PC activity, which caused metabolic reprogramming, while AB4 reversed this phenomenon by inhibiting the PC activity. In vivo studies showed that diisopropylamine dichloroacetate (DADA), a PC agonist, eliminated the therapeutic effects of AB4 by changing the metabolic rearrangement of intestinal tissues in colitis mice. CONCLUSION: We identified PC as a direct cellular target of AB4 in the modulation of inflammation, especially colitis. Moreover, PC/pyruvate metabolism/NF-κB is crucial for LPS-driven inflammation and oxidative stress. These findings shed more light on the possibilities of PC as a potential new target for treating colitis.

Race-based outcomes of thoracic aortic aneurysms and dissections in the Global Registry for Endovascular Aortic Treatment.

OBJECTIVE: This study characterizes racial differences in presentation, as well as short- and long-term outcomes after endovascular treatment of thoracic aortic aneurysm (TAA) and type B aortic dissection (TBAD). METHODS: We queried the Gore Global Registry for Endovascular Aortic Treatment for thoracic endovascular aortic repairs (TEVARs) performed between 2010 and 2016 and followed through 2022. Pathologies represented were descending TAA, complicated TBAD, and uncomplicated TBAD. Using standard statistical tests, we compared overall and pathology-specific demographics, procedural factors, and outcomes among Black and White patients undergoing TEVAR. RESULTS: We identified 438 TEVAR cases, including 236 descending TAA, 121 complicated TBAD, and 74 uncomplicated TBAD. Overall, Black patients were younger and had a higher incidence of renal insufficiency (P = .001), whereas White patients had more chronic obstructive pulmonary disease (P = .003) and cardiac arrhythmias (P = .037). In patients treated for descending TAA, Black patients had increased device- and procedure-related complications (34.3% vs 17.4%; P = .014), conversion to open repair (2.9% vs 0%; P = .011) and type II endoleak (5.7% vs 1.0%; P = .040), but no differences in mortality, length of hospital stay, or major adverse cardiovascular events. Whereas outcomes of TEVAR for uncomplicated TBAD were comparable, Black patients more frequently presented with complicated TBAD than White patients (Black, 40.5% vs White, 24.8%; P = .008) and had subsequently greater reintervention rates (28.1% vs 12.4%; P = .012), all-cause mortality (hazard ratio, 4.28; 95% confidence interval, 1.74-10.5; P = .002) and aortic-related mortality (hazard ratio, 16.7; 95% confidence interval, 1.49-186; P = .022). CONCLUSIONS: Despite increased device- and procedure-related complications, similar short- and long-term outcomes are achieved in Black and White patients undergoing TEVAR for descending TAA and uncomplicated TBAD. However, Black patients are more likely to present with, require reintervention for, and suffer mortality from complicated TBAD.

Recent Advances and Perspectives on Supported Catalysts for Heterogeneous Hydrogen Production from Ammonia Borane.

Ammonia borane (AB), a liquid hydrogen storage material, has attracted increasing attention for hydrogen utilization because of its high hydrogen content. However, the slow kinetics of AB hydrolysis and the indefinite catalytic mechanism remain significant problems for its large-scale practical application. Thus, the development of efficient AB hydrolysis catalysts and the determination of their catalytic mechanisms are significant and urgent. A summary of the preparation process and structural characteristics of various supported catalysts is presented in this paper, including graphite, metal-organic frameworks (MOFs), metal oxides, carbon nitride (CN), molybdenum carbide (MoC), carbon nanotubes (CNTs), boron nitride (h-BN), zeolites, carbon dots (CDs), and metal carbide and nitride (MXene). In addition, the relationship between the electronic structure and catalytic performance is discussed to ascertain the actual active sites in the catalytic process. The mechanism of AB hydrolysis catalysis is systematically discussed, and possible catalytic paths are summarized to provide theoretical considerations for the designing of efficient AB hydrolysis catalysts. Furthermore, three methods for stimulating AB from dehydrogenation by-products and the design of possible hydrogen product-regeneration systems are summarized. Finally, the remaining challenges and future research directions for the effective development of AB catalysts are discussed.

Effect of Body Mass Index on Early Outcomes of Endovascular Abdominal Aortic Aneurysm Repair.

BACKGROUND: This study compares the presentation, management, and outcomes of patients undergoing endovascular abdominal aortic aneurysm repair (EVAR), based on their weight status as defined by their body mass index (BMI). METHODS: Patients with primary EVAR for ruptured and intact abdominal aortic aneurysm (AAA) were identified in the National Surgical Quality Improvement Program database (2016-2019). Patients were categorized by weight status (underweight: BMI < 18.5 kg/m2, normal weight: 18.5-24.9 kg/m2, overweight: 25-29.9 kg/m2, Obese I: 30-34.9 kg/m2, Obese II: 35-39.9 kg/m2, Obese III: > 40 kg/m2). Preoperative characteristics and 30-day outcomes were compared. RESULTS: Of 3,941 patients, 4.8% were underweight, 24.1% normal weight, 37.6% overweight, and 22.5% with Obese I, 7.8% Obese II, and 3.3% Obese III status. Underweight patients presented with larger (6.0 [5.4-7.2] cm) and more frequently ruptured (25.0%) aneurysms than normal weight patients (5.5 [5.1-6.2] cm and 4.3%, P < 0.001 for both). Pooled 30-day mortality was worse for underweight (8.5%) compared to all other weight status (1.1-3.0%, P < 0.001), but risk-adjusted analysis demonstrated that aneurysm rupture (odds ratio [OR] 15.9, 95% confidence interval [CI] 8.98-28.0) and not underweight status (OR 1.75, 95% CI 0.73-4.18) accounted for increased mortality in this population. Obese III status was associated with prolonged operative time and respiratory complications after ruptured AAA, but not 30-day mortality (OR 0.82, 95% CI 0.25-2.62). CONCLUSIONS: Patients at either extreme of the BMI range had the worst outcomes after EVAR. Underweight patients represented only 4.8% of all EVARs, but 21% of mortalities, largely attributed to higher incidence of ruptured AAA at presentation. Severe obesity, on the other hand, was associated with prolonged operative time and respiratory complications after EVAR for ruptured AAA. BMI, as an independent factor, was however not predictive of mortality for EVAR.

Utility of Closed Suction Drains in Groin Incisions after Femoral Artery Exposure.

BACKGROUND: Surgical groin wounds are at risk of delayed healing and infection, leading to costly and prolonged postoperative recoveries. This study assesses the use of closed suction drains (CSDs) as a wound care adjunct in groin incisions to prevent surgical site infections (SSI). METHODS: A single-center retrospective review was performed on 210 consecutive patients after vascular surgery with common femoral artery exposure from 2016 to 2021. The cohort was divided into 2 groups, groins with and without CSD, looking for surgical site complications. A subgroup analysis comparing postoperative outcomes between complicated and uncomplicated groin incisions within both groups was also performed. RESULTS: Of 293 surgical groins, 20% (n = 59) had drains. Overall, the CSD group had higher SSI rates (14% vs. 5.6%), but also had higher proportion of smokers (92% vs. 83%; P = 0.019), diabetes (56% vs. 36%; P = 0.005), coronary artery disease (69% vs. 46%; P = 0.001), hyperlipidemia (69% vs. 51%; P = 0.01), and previous groin surgery (54% vs. 17%; P < 0.001). The higher risk of SSI was not significant after adjustment of these confounders. A separate analysis within each group showed SSI groins with CSD had lower reintervention rates (37.5%) than those without CSD (69%), as well as shorter length of hospital stay (7 [5-11] vs. 22 [7-25] days). CONCLUSIONS: Our study suggests that CSDs can be a beneficial adjunct for groin wounds after common femoral artery exposure in patients with comorbidities cited above. CSDs decrease the risk of reintervention and length of hospital stay.

Penetrating aortic ulcer and aortic intramural hematoma: Treatment strategy.

OBJECTIVES: The indication, timing, and choice of the treatment modality for penetrating aortic ulcers (PAUs) and intramural hematoma (IMH) are frequently challenging. This article reviews these pathologies and their relation to aortic dissection and proposes a diagnostic and treatment algorithm. METHODS: A review of literature on diagnosis and treatment of PAU and IMH was conducted. The PubMed database was searched using the terms "penetrating aortic ulcer" and "aortic intramural hematoma". Articles were reviewed and the studies involving diagnosis and management of PAU and IMH were included. We subsequently proposed a management algorithm for PAU and IMH based on available evidence. RESULTS: PAU and IMH are distinct entities from aortic dissection, although they carry a significant risk of progression into dissection, aneurysm, and rupture. PAU and IMH originating in zone 0 of the aorta generally require surgical treatment. When the origin is beyond zone 0, a trial of medical therapy is recommended. Progression of disease on imaging studies, persistent uncontrolled pain, and certain high-risk features warrant surgery. High-risk features signaling risk of disease progression include PAU with IMH, PAU depth more than 10 mm, PAU diameter more than 20 mm, IMH thickness more than 10 mm, and maximum initial aortic diameter more than 40 mm. CONCLUSIONS: High-quality evidence regarding the treatment of PAU and IMH is lacking. These entities can have a malignant course when they are present with associated symptoms and/or when they have associated high-risk features on imaging. An aggressive surgical approach is necessary in that group of patients.

Racial disparities in presentation and outcomes for endovascular abdominal aortic aneurysm repair.

OBJECTIVE: In the present study, we used a national database to identify racial differences in the presentation and outcomes for patients undergoing endovascular abdominal aortic aneurysm (AAA) repair (EVAR) and identified areas for improving their care. METHODS: We queried the EVAR-targeted National Surgical Quality Improvement Program database (2016-2019) to identify patients who had undergone EVAR for both ruptured and nonruptured AAAs. The patients were categorized according to race (White, Black, and Asian). Patients with a history of abdominal aortic surgery or an indication other than AAAs were excluded. The data was analyzed using the χ2 and Kruskal-Wallis tests, presented as frequencies and percentages or median and interquartile range (IQR) for categorical and continuous variables, respectively. RESULTS: We identified 3629 patients (16.6% female), including 3312 White (91.3%), 248 Black (6.8%), and 69 Asian (1.9%) patients. Black patients were more frequently women (27.0%) compared with White patients (15.9%) and were younger (median age, 71 years; IQR, 64-77 years) than White (median age, 73 years; IQR, 67-79 years) and Asian (median age, 76 years; IQR, 67-81 years) patients (P < .001 for both). The incidence of smoking, congestive heart failure, and dialysis dependency was highest for Black patients, and the incidence of obesity was lowest for Asian patients. The AAAs in Black patients extended more frequently beyond the aortic bifurcation (P = .047). In Asian patients, the internal iliac arteries were more involved (P = .040). For Black patients, 29.8% of the EVARs were performed in a nonelective setting compared with 20.2% for the White and 15.9% for the Asian patients (P < .001). The aneurysm diameter, nonruptured symptomatic rate, and rupture rate were similar across the groups (P = .807). The operative time was prolonged for Black (median, 128 minutes; IQR, 96-177 minutes) compared with White (median, 114 minutes; IQR, 84-162 minutes) patients (P < .001). Postoperatively, Black patients were more likely to require blood transfusion (16.5%) and had prolonged length of hospital stay (median, 2 days; IQR, 1-4 days) compared with White (10.0%; median, 1 day; IQR, 1-3 days) and Asian (4.3%; median, 1 day; IQR, 1-3 days) patients (P = .001 and P < .001, respectively). Black patients also had a higher 30-day readmission rate (P = .038). On multivariate analysis, Black race was an independent factor for length of stay >1 day after both elective and nonelective EVAR and 30-day readmission for elective EVAR, but not 30-day mortality after elective and nonelective EVAR. CONCLUSIONS: In the present nationwide sample of EVAR cases, Black patients were more often women and younger. Despite similar rates of symptomatic and ruptured AAAs at presentation and 30-day mortality, Black patients more often presented and were treated during the same nonelective admission; they also had associated increased length of hospital stay and readmission. These findings signal a missed opportunity to diagnose, optimize, and treat this particular group of patients in an elective setting.

COVID-19-related thrombotic complications experience before and during delta wave.

OBJECTIVE: Hypercoagulability and thrombotic complications seen in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as the associated pathophysiology, have been reported extensively. However, there is limited information regarding the factors related to this phenomenon and its association with the Coronavirus disease 2019 (COVID-19) Delta variant. METHODS: A retrospective review including patients admitted to a tertiary center with a COVID-19 positive test and at least one acute thrombotic event confirmed by imaging between June 2020 and August 2021 was performed. We compared the rates of thrombotic events in patients with COVID-19 before and during the Delta peak. We also analyzed the association of the thrombotic complications with demographic characteristics, comorbidities, anticoagulation strategies, and prothrombotic markers while describing other complications secondary to COVID-19 infection. RESULTS: Of 964 patients admitted with COVID-19 diagnosis, 26.5% (n = 256) had a thrombotic event evidenced by ultrasound or computed tomography scan. Venous thromboembolism was found in 60% (n = 153), arterial thrombosis in 23% (n = 60), and both venous and arterial thromboses in 17% (n = 17) of the study cohort. Of all patients, 94% were not vaccinated. Delta variant wave (DW) patients had thrombotic episodes in 34.7% (n = 50/144) of cases compared with 25% (n = 206/820) of non-Delta wave (NDW) patients, posing an estimated risk 1.36 times higher in patients infected with COVID-19 during the DW than NDW. Overall, DW subjects were significantly younger (P < .001) with lower body mass index (P = .021) compared with NDW patients. Statistical analyses showed African American patients were more likely to have arterial thrombosis compared with the other groups when testing positive for COVID-19 (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.04-3.05; P = .035, whereas immunosuppressed patients had less risk of arterial thrombosis (OR, 0.38; 95% CI, 0.15-0.96; P = .042). Female gender (OR, 2.15; 95% CI, 1.20-3.85; P = .009) and patients with active malignancy (OR, 5.99; 95% CI, 2.14-16.78; P = .001) had an increased risk of having multiple thrombotic events at different locations secondary to COVID-19. CONCLUSIONS: COVID-19 infection is associated with elevated rates of thrombotic complications and an especially higher risk in patients infected during the Delta variant peak. We highlight the importance of vaccination and the development of new anticoagulation strategies for patients with COVID-19 with additional hypercoagulable risk factors to prevent thrombotic complications caused by this disease.

Percutaneous endovascular abdominal aortic aneurysm repair with monitored anesthesia care decreases operative time but not pulmonary complications.

OBJECTIVES: To report our experience and compare the results of percutaneous endovascular aortic aneurysm repair (PEVAR) performed under monitored anesthesia care (MAC) to PEVAR under general anesthesia (GA). METHODS: A retrospective review of patients who underwent non-emergency endovascular abdominal aortic aneurysm repair (EVAR) was completed. Patients were excluded if they had a complex repair, including fenestrated, branched, or parallel endografting. Demographics, operative data, 30-day mortality/morbidity and postoperative outcomes were analyzed. RESULTS: A total of 159 patients were identified with a median age of 69. 115 patients had PEVAR, 45 (39.1%) PEVAR MAC and 70 (60.9%) PEVAR GA. PEVAR MAC compared to PEVAR GA had decreased operative time (106 vs. 134 min, P < 0.001), time in the operating room (163 vs. 245 min, P = 0.016), and estimated blood loss (EBL) (115 vs. 176 mL P = 0.012). There was no statistically significant difference in the hospital length of stay (LOS) (1.9 vs. 2.7 days, P = 0.133), and post-operative complications including pulmonary (2.2 vs. 2.9%, P = 0.835). Forty-four patients had EVAR with a femoral cutdown (FC), including 14 PEVAR conversions. PEVAR conversion was associated with higher EBL (543 vs. 323 mL, P = 0.03), operative time (230 vs. 178 min, P = 0.01), and operating room time (307 vs. 275 min, P = 0.01) compared to planned EVAR with FC. CONCLUSIONS: PEVAR under MAC is associated with shorter time in the operating room compared to PEVAR under GA. PEVAR under MAC does however not decrease overall morbidities, including postoperative pulmonary complications.

Establishing and maintaining a remote vascular surgery aortic program: A single-center 5-year experience at the Veterans Affairs.

OBJECTIVE: We sought to detail the process of establishing a surgical aortic telehealth program and report the outcomes of a 5-year experience. METHODS: A telehealth program was established between two regional Veterans Affairs hospitals, one of which was without a comprehensive aortic surgical program, until such a program was established at the referring institution. A retrospective review was performed of all patients who underwent aortic surgery from 2014 to 2019. The operative data, demographics, perioperative complications, and follow-up data were reviewed. RESULTS: From 2014 to 2019, 109 patients underwent aortic surgery for occlusive and aneurysmal disease. Preoperative evaluation and postoperative follow-up were done remotely via telehealth. The median age of the patients was 68 years, 107 were men (98.2%), 28 (25.7%) underwent open aortic repair, and 81 (74.3%) underwent endovascular repair. Of the 109 patients, 101 (92.7%) had a median follow-up of 24.3 months, 5 (4.6%) were lost to follow-up or were noncompliant, 2 (1.8%) were noncompliant with their follow-up imaging studies but responded to telephone interviews, and 1 (0.9%) moved to another state. At the 30-day follow-up, eight patients (7.3%) required readmission. Four complications were managed locally, and four patients (3.6%) required transfer back to the operative hospital for additional care. CONCLUSIONS: Telehealth is a great tool to provide perioperative care and long-term follow-up for patients with aortic pathologies in remote locations. Most postoperative care and complications can be managed remotely, and patient compliance for long-term follow-up is high.

Anemoside B4 inhibits enterovirus 71 propagation in mice through upregulating 14-3-3 expression and type I interferon responses.

Enterovirus 71 (EV71) is the major pathogens of human hand, foot, and mouth disease (HFMD). EV71 efficiently escapes innate immunity responses of the host to cause infection. At present, no effective antiviral drugs for EV71 are available. Anemoside B4 (B4) is a natural saponin isolated from the roots of Pulsatilla chinensis (Bunge) Regel. P. chinensis extracts that shows a wide variety of biological activities. In this study, we investigated the antiviral activities of B4 against EV71 both in cell culture and in suckling mice. We showed that B4 (12.5-200 µM) dose dependently increased the viability of EV71-infected RD cells with an IC50 value of 24.95 ± 0.05 µM against EV71. The antiviral activity of B4 was associated with enhanced interferon (IFN)-ß response, since knockdown of IFN-ß abolished its antiviral activity. We also confirmed that the enhanced IFN response was mediated via activation of retinoic acid-inducible gene I (RIG-I) like receptors (RLRs) pathway, and it was executed by upregulation of 14-3-3 protein, which disrupted the interaction between yes-associated protein (YAP) and interferon regulatory factor 3 (IRF3). By using amino acids in cell culture (SILAC)-based proteomics profiling, we identified the Hippo pathway as the top-ranking functional cluster in B4-treated EV71-infected cells. In vivo experiments were conducted in suckling mice (2-day-old) infected with EV71 and subsequently B4 (200 mg · kg-1 · d-1, i.p.) was administered for 16 days. We showed that B4 administration effectively suppressed EV71 replication and improved muscle inflammation and limb activity. Meanwhile, B4 administration regulated the expressions of HFMD biomarkers IL-10 and IFN-γ, attenuating complications of EV71 infection. Collectively, our results suggest that B4 could enhance the antiviral effect of IFN-ß by orchestrating Hippo and RLRs pathway, and B4 would be a potential lead compound for developing an anti-EV71 drug.

Rapid and efficient reduction of chromate by novel Pd/Fe@biomass derived from Enterococcus faecalis.

Efficient reduction of chromate is highly desirable for its detoxification and remediation of the contaminated environment. This study described a fusion of the concepts of precious metal biorecovery and fabrication of Pd/Fe@biomass derived from simulated wastewater. The effectiveness of Pd/Fe@biomass during reduction process of Cr(VI) was evaluated by comparing with pure nZVI, E. faecalis and Pd@biomass. Results showed that Pd(II) could be recovered by E. faecalis with Fe(II) as the electron donor, and precipitation could yield nZVI anchored onto Pd-loaded E. faecalis. The nano particles (NPs) on Pd/Fe@biomass were well-dispersed, which provided 2.70 folds specific surface area comparing with nZVI. Efficient Cr(VI) reduction could be achieved at a higher catalyst dosage, the most appropriated Pd/Fe molar ratio of 2% and a wide pH range. Typically, 0.5 mM Cr(VI) could be completely reduced in 5 min driven by Pd/Fe@biomass under the conditions of dosage of 1.0 g/L and pH 3. Moreover, the mechanisms of Cr(VI) reduction by Pd/Fe@biomass were proposed, which intimately related to nZVI electron donating capacities, Pd catalysis for hydrogenation and galvanic cell effects between Fe and Pd. Therefore, Pd/Fe@biomass could be an alternative for rapid and complete reduction of Cr(VI).

Traumatic Lower Extremity Vascular Injuries and Limb Salvage in a Civilian Urban Trauma Center.

BACKGROUND: Data on management of traumatic lower extreity arterial injuries comes largely from military experience and involves few civilian centers. This study reports on the experience of an urban trauma center and factors associated with limb loss. METHODS: A retrospective review of lower extremity arterial injuries between 2013 and 2020 at an academic urban level 1 trauma center was completed. Patients with lower extremity revascularization were included in the final data analysis. Demographics, clinical variables, operative details, type of revascularization, as well as 30-day morbidity and postoperative outcomes were analyzed. The primary outcome of interest was 30-day limb loss. Secondary outcomes included postoperative complications and functional outcomes. RESULTS: Seventy-five patients were included in our analysis. Sixty-nine were male (92%), mean age 33 ± 15 years, 50 patients had penetrating trauma (67%), mean injury severity score was 15 ± 9. Thirty-day limb loss was reported in 8 (11%). Factors associated with limb loss included female sex (P = 0.001), high body mass index (P = 0.001), blunt injury (P = 0.001), associated fractures (P = 0.005), significant soft tissue injury (P = 0.007), delayed repair after shunt placement (P = 0.003), bypass revascularization (P = 0.001), initial revascularization failure (P = 0.019), and wound complications (P < 0.001). Fifty-five patients had at least one return to the operating room (ROR), including 24 patients (32%) for complications related to their revascularization. These included delayed compartment syndrome (n = 7), revascularization failure (n = 9), bleeding (n = 3), and vascular surgical wound complications (n = 5). Mean length of hospital stay (LOS) for the cohort was 24 ± 20 days with 3 ± 3 ROR, in contrast patients who ultimately required amputation had LOS of 57 ± 21 days with 8 ± 4 ROR. Fifty-seven patients (76%) followed in clinic for a median 36 [14-110] days, with only 32 (43%) at >30 days. Twenty-three reported ambulation without assistance, 9 neuromotor deficit including 1 patient that had delayed amputation. CONCLUSION: Patients with blunt trauma and associated fracture and/or extensive soft tissue injury are at risk of limb loss. These injuries are often associated with postoperative wound complications, requiring aggressive soft tissue care that substantially increases ROR and LOS; Expectations for limb salvage in these patients should be tempered when the other associated factors with limb loss mentioned above are also present. When limb salvage is achieved, regaining full limb function remains a challenge.

Anemoside B4 ameliorates TNBS-induced colitis through S100A9/MAPK/NF-κB signaling pathway.

BACKGROUND: Despite the increased morbidity of ulcerative colitis (UC) in the developing countries, available treatments remain unsatisfactory. Therefore, it is urgent to discover more effective therapeutic strategies. Pulsatilla chinensis was widely used for the treatment of inflamed intestinal diseases including UC for thousands of years in China. Anemoside B4, the most abundant triterpenoid saponin isolated from P. chinensis, exerts anti-inflammatory and antioxidant effects and may be the most active compounds, which is responsible for the therapeutic effects. However, the mechanism how anemoside B4 executes its biological functions is still elusive. METHODS: Here, we used the 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rat model to evaluate the therapeutic effect of anemoside B4. Blood samples of colitis rats were collected for hematology analysis. The inflammation-associated factors were investigated by enzyme-linked immunosorbent assay (ELISA). Cell proliferation and apoptosis was determined with EdU cell proliferation assay and TUNEL assay. The proteins regulated by anemoside B4 were identified by label-free quantitative proteomics. The significantly down-regulated proteins were verified by Western blotting analysis. mRNA expression was analyzed by quantitative real-time RT-PCR. RESULTS: The results showed that anemoside B4 ameliorated TNBS-induced colitis symptoms, including tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine production, apoptosis and slowed proliferation in colon. Quantitative proteomic analyses discovered that 56 proteins were significantly altered by anemoside B4 in the TNBS-induced rats. These proteins mainly clustered in tricarboxylic acid (TCA) cycle and respiratory electron transport chain. Among the altered proteins, S100A9 is one of the most significantly down-regulated proteins and associated with NF-κB and MAPK signaling pathways in the pathogenesis of UC. Further experiments revealed that anemoside B4 suppressed the expression of S100A9 and its downstream genes including TLR4 and NF-κB in colon. In vitro, anemoside B4 could inhibit the NF-κB signaling pathway induced by recombinant S100A9 protein in human intestinal epithelial Caco-2 cells. Moreover, anemoside B4 inhibits neutrophils recruitment and activation in colon induced by TNBS. CONCLUSIONS: Our results demonstrate that anemoside B4 prevents TNBS-induced colitis by inhibiting the NF-κB signaling pathway through deactivating S100A9, suggesting that anemoside B4 is a promising therapeutic candidate for colitis.

Ginsenoside Rb1 is an immune-stimulatory agent with antiviral activity against enterovirus 71.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the theory of traditional Chinese medicine, the main pathogenesis of severe hand, foot and mouth disease (HFMD) is that the heat and wet poisons are deeply trapped in the viscera, which causes the deficiency of Qi and Yin in the patient's body. Ginsenoside Rb1 (Rb1) is the most abundant triterpenoid saponin in Panax quinquefolius L., which has the function of Qi-invigorating and Yin-nourishing. Enterovirus 71 (EV71) is one of the causative pathogens of HFMD, especially the form associated with some lethal complications. Therefore, the therapeutic effect of Rb1 on this disease caused by EV71 infection is worth exploring. AIM OF THE STUDY: We explored the effective antiviral activities of Rb1 against EV71 in vitro and in vivo and investigated its preliminary antiviral mechanisms. MATERIAL AND METHODS: EV71-infected two-day-old suckling mice model was employed to detect the antiviral effects of Rb1 in vivo. To detect the antiviral effects of Rb1 in vitro, cytopathic effect (CPE) reduction assay was performed in EV71-infected Rhabdomyosarcoma (RD) cells. Interferon (IFN)-ß interference experiment was employed to detect the antiviral mechanism of Rb1. RESULTS: In this paper, we first found that Rb1 exhibited strong antiviral activities in EV71-infected suckling mice when compared to those of ribavirin. Administration of Rb1 reduced the CPE of EV71-infected RD cells in a dose-dependent manner. Moreover, EV71-induced viral protein-1 (VP-1) expression was significantly reduced by Rb1 administration in vitro and in vivo. Furthermore, Rb1 treatment could induce high cellular and humoral immune responses in vivo. Meanwhile, Rb1 contributed to the enhanced Type I IFN responses and IFN-ß knockdown reversed the antiviral activity of Rb1 in vitro. CONCLUSION: In summary, our findings suggest that Rb1 is an immune-stimulatory agent and provide an insight into therapeutic potentials of Rb1 for the treatment of EV71 infection.

Visible-Light Acceleration of H2 Evolution from Aqueous Solutions of Inorganic Hydrides Catalyzed by Gold-Transition-Metal Nanoalloys.

Production of hydrogen (H2) upon hydrolysis of inorganic hydrides potentially is a key step in green energy production. We find that visible-light irradiation of aqueous solutions of ammonia-borane (AB) or NaBH4 containing "click"-dendrimer-stabilized alloyed nanocatalysts composed of nanogold and another late transition-metal nanoparticle (LTMNP) highly enhances catalytic activity for H2 generation while also inducing alloy to Au core@M shell nanocatalyst restructuration. In terms of visible-light-induced acceleration of H2 production from both AB and NaBH4, the Au1Ru1 alloy catalysts show the most significant light-boosting effect. Au-Rh and Au-PtNPs are also remarkable with total H2 release time from AB and NaBH4 down to 1.3 min at 25 °C (AuRh), 3 times less than in the dark, and Co is the best earth-abundant metal alloyed with nanogold. This boosting effect is explained by the transfer of plasmon-induced hot electron from the Au atoms to the LTMNP atoms facilitating water O-H oxidative addition on the LTMNP surface, as shown by the large primary kinetic isotope effect kH/kD upon using D2O obtained for both AB and NaBH4. The second simultaneous and progressive effect of visible-light irradiation during these reactions, alloy to Au core@M shell restructuration, enhances the catalytic activity in the recycling, because, in the resulting Au core@M shell, the surface metal (such as Ru) is much more active than the original Au-containing alloy surface in dark reactions. There is no light effect on the rate of hydrogen production for the recycled nanocatalyst because of the absence of Au on the NP surface, but it is still very efficient in hydrogen release during four cycles because of the initial light-induced restructuration, although it is slightly less efficient than the original nanoalloy in the presence of light. The dendritic triazole coordination on each LTMNP surface appears to play a key role in these remarkable light-induced processes.

Acute upper limb ischemia as the first manifestation in a patient with COVID-19.

Coronavirus disease-19 (COVID-19) first emerged in December 2019 in China and rapidly spread worldwide. Although various studies have reported that COVID-19 is associated with a hypercoagulable state and thrombotic complications in critically ill patients, there are few case reports on thrombotic events as one of the presenting symptoms. We report a case of acute upper extremity ischemia as the initial clinical presentation of a patient with COVID-19.

Hybrid Treatment of an Enlarging Hypogastric Aneurysm Previously Excluded During Abdominal Aortic Aneurysm Repair.

Hypogastric aneurysm is rare, often asymptomatic, but associated with high mortality if it ruptures. Given the deep location of the artery and proximity to critical anatomical structures (i.e., ureter, bladder, and rectum), open surgical repair carries high morbidity and mortality compared with an endovascular approach. We report a simple hybrid approach to repair an enlarging isolated hypogastric aneurysm after a previous aortic aneurysm repair during which the origin of the hypogastric artery was ligated.

Effect of reaction temperature on the protein structure and the ability to encapsulate ß-carotene of WPI-dextran conjugates.

In this paper, we studied the effect of glycosylation reaction on the molecular structure and functional properties of whey protein isolate (WPI), and studied the effect of reaction temperature (50 to 90 °C) on the molecular structure and functional properties of WPI-dextran conjugates (WPI-D). The results of the extent of glycation (EG) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed the formation of WPI-D. Circular dichroism (CD), Fourier transform infrared spectrum, and fluorescence spectroscopy indicated that the molecular structure of WPI was changed after glycosylation-the ß-sheet content was decreased and the tryptophan content was increased. The emulsifying properties and the ability to encapsulate ß-carotene of WPI-D were improved compared with WPI (P < 0.05). When the reaction temperature was 70 and 80 °C, the EG and the ability to encapsulate ß-carotene of WPI-D were better (P < 0.05), which was related to protein unfolding. However, due to the polymerization between the WPI molecules, the emulsion activity index of WPI-D and the ability to encapsulate ß-carotene were lowered at 90 °C (P < 0.05). Therefore, the glycosylation reaction can change the molecular structure and functional properties of WPI; the emulsifying properties and the ability to encapsulate ß-carotene of WPI-D can be changed by controlling the reaction temperature of glycosylation. PRACTICAL APPLICATION: The glycosylation reaction can change the molecular structure and functional properties of Whey protein isolate; the emulsifying properties and the ability to encapsulate ß-carotene of WPI-dextran conjugates can be changed by controlling the reaction temperature of glycosylation.