Enrichment of Total Flavonoids and Licochalcone A from Glycyrrhiza inflata Bat. Residue Based on a Combined Membrane-Macroporous Resin Process and a Quality-Control Study.

Glycyrrhiza inflata Bat. produces a lot of licorice waste after water extraction, which also retains abundant total flavonoids (TFs) and licochalcone A. However, licorice residue is often wasted due to the lack of good utilization of resources in practical applications. This study first screened the optimal membrane pore size and resin type and then explored the mechanism and conditions of the adsorption of TFs on the resin. Then, different combinations and sequences of membrane and macroporous resin (MR) methods were investigated. It was found that using the membrane method for initial purification, followed by the MR method for further purification, yielded the best purification results. Next, response surface methodology was utilized to investigate the resin's dynamic desorption conditions for TFs. Finally, the TF purity increased from 32.9% to 78.2% (2.38-fold) after purification by a combined membrane-MR process; the purity of licochalcone A increased from 11.63 mg·g-1 to 22.70 mg·g-1 (1.95-fold). This study verified the feasibility of enriching TFs and licochalcone A from licorice residue using a membrane-MR coupling method. In addition, a quality-control method was established using a fingerprinting method on the basis of ultrahigh-performance liquid chromatography (UPLC) to ensure the stability of the enrichment process.

White Matter Hyperintensity is Associated with Malignant Cerebral Edema in Ischemic Stroke Treated with Thrombectomy.

BACKGROUND: White matter hyperintensity (WMH) burden may lead to poor clinical outcomes after endovascular thrombectomy (EVT). But the relationship between WMH burden and cerebral edema (CED) is unclear. PURPOSE: To examine the association between WMH burden and CED and functional outcome in patients treated with EVT. STUDY TYPE: Retrospective. SUBJECT: 344 patients with acute anterior circulation large-vessel occlusion stroke who received EVT at two comprehensive stroke centers. Mean age was 62.6 ± 11.6 years and 100 patients (29.1%) were female. FIELD STRENGTH/SEQUENCE: 3T, including diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) images. ASSESSMENT: The severity of WMH was evaluated using the Fazekas scale on a FLAIR sequence before EVT. The severity of CED was assessed using CED score (three for malignant cerebral edema [MCE]) and net water uptake (NWU)/time on post-EVT cranial CT. The impact of WMH burden on MCE, NWU/time, and 3-month poor outcome (modified Rankin scale >2) after EVT were assessed. STATISTICAL TESTS: Pearson's chi-squared test, Fisher exact test, 2-tailed t test, Mann-Whitney U test, multivariable logistic regression, multivariate regression analysis, Sobel test. A P value <0.05 was considered statistically significant. RESULTS: WMH burden was not significantly associated with MCE and parenchymal hemorrhage (PH) in the whole population (P = 0.072; P = 0.714). WMH burden was significantly associated with an increased risk of MCE (OR, 1.550; 95% CI, 1.128-2.129), higher NWU/time (Coefficient, 0.132; 95% CI, 0.012-0.240), and increased risk of 3-month poor outcome (OR, 1.434; 95% CI, 1.110-1.853) in the subset of patients without PH. Moreover, the connection between WMH burden and poor outcome was partly mediated by CED in patients without PH (regression coefficient changed by 29.8%). DATA CONCLUSION: WMH burden is associated with CED, especially MCE, and poor outcome in acute ischemic stroke patients treated with EVT. The association between WMH burden and poor outcome may partly be attributed to postoperative CED. TECHNICAL EFFICACY: Stage 5.

High Systemic Inflammatory Protein Index Is Associated with Clinically Ineffective Reperfusion in Acute Anterior Circulation Ischemic Stroke Patients Undergoing Endovascular Treatment.

Nearly half of the patients undergoing endovascular treatment (EVT) do not have favorable outcomes despite successful recanalization of the occluded artery, which is also known as clinically ineffective reperfusion. We proposed a novel index-the systemic inflammatory protein index (SIPI), based on albumin, globulin, and C-reaction protein (CRP). We aimed to evaluate the relationship between inflammatory biomarkers at varying time points and the 90-day functional outcomes and investigate inflammatory biomarkers' dynamic changes during hospitalization in acute ischemic stroke (AIS) patients of anterior circulation undergoing EVT. We retrospectively recruited consecutive patients diagnosed with AIS of anterior circulation and treated with EVT from January 2018 to June 2022 in Nanfang Hospital. Albumin, globulin, and CRP were recorded on admission, 1 day, 3 days, and 7 days after EVT. An unfavorable functional outcome was defined as 90-day modified Rankin Scale (mRS) of 3-6. Albumin-to-globulin ratio (AGR), C-reactive protein-to-albumin ratio (CAR), and SIPI were calculated as follows: AGR = albumin/globulin; CAR = CRP/albumin; SIPI = CRP × globulin/albumin. A total of 238 consecutive anterior circulation AIS patients with EVT were included, among which 145 (60.9%) patients had unfavorable outcomes. After adjusting for confounding factors, admission globulin, admission AGR, 1-day AGR, 3-day albumin, 3-day CRP, 3-day CAR, 3-day SIPI, 7-day albumin, 7-day CRP, 7-day CAR, and 7-day SIPI showed an independent association with 90-day functional outcome. Of them, 3-day SIPI had the most robust discriminative ability with an area under the curve of 0.719 (CI 0.630-0.808, p < 0.001). There were differences in the dynamic change of inflammatory biomarkers between the subjects with favorable and unfavorable functional outcomes. Inflammatory biomarkers, including albumin, globulin, CRP, AGR, CAR, and SIPI, are independent predictors of 90-day unfavorable outcomes in anterior circulation AIS patients with EVT. SIPI of day 3 has the highest predictive value.

White matter hyperintensity burden and functional outcomes in acute ischemic stroke patients after mechanical thrombectomy: A systematic review and meta-analysis.

BACKGROUND: The influence of white matter hyperintensity (WMH) on clinical outcomes in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT) remains controversial. We performed a systematic review and meta-analysis to examine whether WMH burden is associated with clinical outcomes in AIS patients after MT. METHODS: PubMed, Embase, and Web of Science were searched from inception to Sep 03, 2023. The registration number for PROSPERO is CRD42022340568. Studies reporting an association between the burden of WMH in AIS patients and clinical outcomes after MT were included in the meta-analysis. A random-effects model was used for meta-analysis. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Additionally, the presence of imprecise-study effects was evaluated using Egger's test and funnel plot. RESULTS: Fifteen studies with 3,456 patients were enrolled in this meta-analysis. Among AIS patients who underwent MT, moderate/severe WMH had higher odds of 90-day unfavorable functional outcomes (odds ratio [OR] 2.72, 95% confidence interval [CI] 2.14-3.44; I2 = 0.0%; 95% CI 0.0%-42.7%), 90-day mortality (OR 1.94, 95% CI 1.45-2.60; I2 = 19.5%; 95% CI 0.0%-65.2%) and futile recanalization (OR 2.99, 95% CI 1.42-6.28; I2 = 69.7%; 95% CI 0.0%-91.0%) compared with none/mild WMH. However, the two groups had no significant difference in successful recanalization, symptomatic hemorrhagic transformation, and hemorrhagic transformation. A subset analysis of patients from 3 articles showed that WMH volume was not significantly associated with these outcomes. A notable limitation is that this meta-analysis lacks direct adjustment for imbalances in important baseline covariates. CONCLUSIONS: Patients with moderate/severe WMH on baseline imaging are associated with substantially increased odds of 90-day unfavorable outcomes, futile recanalization, and 90-day mortality after MT. This association suggests that moderate/severe WMH may contribute to the prediction of clinical outcomes in AIS patients after MT.

Risk factors for perimenopausal depression in Chinese women: a meta-analysis.

Objective: To systematically evaluate the risk factors for perimenopausal depression in Chinese women and to provide a basis for screening perimenopausal women at high-risk for depression. Methods: A computer search of seven databases, including SinoMed, PubMed, Web of Science, and so on, and two clinical trial registries on the risk factors for depression in Chinese women during perimenopause was conducted for meta-analysis. The search time limit was from the establishment of the database to December 2022. The included case-control and cross-sectional studies were evaluated using the Newcastle-Ottawa scale (NOS) and criteria developed by the Agency for Healthcare Research and Quality (AHRQ). Results: A total of 15 papers with 12,168 patients and 18 risk factors were included. Meta-analysis results showed that the risk factors for depression in perimenopausal women were relationship quality [OR = 1.23, 95% confidence intervals (1.03, 1.46)], marital status [OR = 2.49, 95% CI (1.77, 3.50)], family income [OR = 1.48 95% CI (1.10, 2.00)], comorbid chronic diseases [OR = 2.39, 95% CI (1.93, 2.95)], exercise status [OR = 1.63, 95% CI (1.26, 2.11)], perimenopausal syndrome [OR = 2.36, 95% CI (2.11, 2.63)], age [OR = 1.04, 95% CI (1.01, 1.07)], and stressful events [OR = 12.14, 95% CI (6.48, 22.72)], and social support was a protective factor [OR = 0.76, 95% CI (0.63, 0.91), p < 0.05]. Conclusion: Based on the exploration of risk factors for perimenopausal depression in Chinese women, we aimed to provide guidance for the screening of risk factors for depression in perimenopausal women and thereby reduce the incidence of depression. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, CRD42023403972.

Daytime Resting Activity of Aedes Aegypti and Culex Quinquefasciatus Populations in Northern Mexico.

Aedes aegypti and Culex quinquefasciatus are disease vectors distributed throughout much of the world and are responsible for a high burden of vector-borne disease, which has increased during the last 2 decades. Most pathogens vectored by these mosquitoes do not have therapeutic remedies; thus, combating these diseases is dependent upon vector control. Improvements in vector control strategies are urgently needed, but these hinge on understanding the biology and ecology of Ae. aegypti and Cx. quinquefasciatus. Both species have been extensively investigated, but further knowledge on diel resting activity of these vectors can improve vector surveillance and control tools for targeting resting vector populations. From April to December 2021, we determined outdoor daytime resting habits of Ae. aegypti and Cx. quinquefasciatus male, female, and blood-fed female populations in Reynosa, Mexico, using large red odor-baited wooden box traps. The daytime resting activity for Ae. aegypti males, females, and blood-fed females was restricted to a period between 0900 h and 1300 h, with a peak at 0900 h, while the resting activity of Cx. quinquefasciatus male, female, and blood-fed females was between 0700 h and 1100 h, with a peak at 0700 h. A generalized additive model was developed to relate relative humidity and temperature to resting Cx. quinquefasciatus and Ae. aegypti male, female, and blood-fed populations caught in traps. This study advances the understanding of outdoor resting behavior for 2 important vector mosquito species and discusses future studies to fill additional knowledge gaps.

The Mechanisms of How Narcissistic Duality Traits Influence on College Student's Organizational Citizenship Behavior from an Impression Management Perspective.

Purpose: Although plenty of studies have examined the antecedents of organizational citizenship behavior, empirical studies exploring the role of individual narcissism in relation to college students' organizational citizenship behavior are relatively scarce. Drawing on the dual theory of narcissism and the conservation of resources theory, this study aimed to explore the relationship between narcissistic duality traits (narcissistic admiration and narcissistic rivalry) and organizational citizenship behavior of college students, and to further examine the mediating role of impression management motivation (assertive impression management motivation and defensive impression management motivation) and the moderating roles of teamwork, interpersonal relationships, and optimism. Methods: We used the questionnaire method with a sample of undergraduate and graduate students from several universities in Hubei, China. The data sample for analysis consists of 583 college students. Results: (1) Narcissistic admiration had a significant and positive effect on college students' organizational citizenship behavior, while the effect of narcissistic rivalry was significant and negative; (2) assertive impression management motivation mediated the relationship between narcissistic admiration and college student's organizational citizenship behavior, and defensive impression management motivation mediated the relationship between narcissistic rivalry and college student' s organizational citizenship behavior; and (3) teamwork, interpersonal relationships, and optimism positively moderated the relationship between narcissistic admiration and assertive impression management motivation, and these variables positively moderated the indirect effects of assertive narcissism on college student's organizational citizenship behavior through assertive impression management motivation. Conclusion: We found that college students with narcissistic admiration engaged in more organizational citizenship behaviors than those with narcissistic rivalry. In addition, narcissistic admiration had a positive effect on organizational citizenship behavior through assertive impression management motivation, and narcissistic rivalry had a negative effect on organizational citizenship behavior through defensive impression management motivation. Finally, teamwork, interpersonal relationships, and optimism significantly and positively mediated the relationship between narcissistic admiration and assertive impression management motivation, and the indirect effect of narcissistic admiration on organizational citizenship behavior through assertive impression management motivation. However, the direct effects of teamwork, interpersonal relationships, and optimism on the relationship between narcissistic rivalry and defensive impression management motivation, and the indirect effect of narcissistic rivalry on organizational citizenship behavior through defensive impression management motivation were not significant.

Spotted Fever and Typhus Group Rickettsiae in Dogs and Humans, Mexico, 2022.

We found serologic evidence of spotted fever group Rickettsia in humans and dogs and typhus group Rickettsia in dogs in Reynosa, Mexico. Our investigation revealed serologic samples reactive to spotted fever group Rickettsia in 5 community members, which highlights a potential rickettsial transmission scenario in this region.

Ubiquitous conservative interaction patterns between post-spliced introns and their mRNAs revealed by genome-wide interspecies comparison.

Introns, as important vectors of biological functions, can influence many stages of mRNA metabolism. However, in recent research, post-spliced introns are rarely considered. In this study, the optimal matched regions between introns and their mRNAs in nine model organism genomes were investigated with improved Smith-Waterman local alignment software. Our results showed that the distributions of mRNA optimal matched frequencies were highly consistent or universal. There are optimal matched frequency peaks in the UTR regions, which are obvious, especially in the 3'-UTR. The matched frequencies are relatively low in the CDS regions of the mRNA. The distributions of the optimal matched frequencies around the functional sites are also remarkably changed. The centers of the GC content distributions for different sequences are different. The matched rate distributions are highly consistent and are located mainly between 60% and 80%. The most probable value of the optimal matched segments is about 20 bp for lower eukaryotes and 30 bp for higher eukaryotes. These results show that there are abundant functional units in the introns, and these functional units are correlated structurally with all kinds of sequences of mRNA. The interaction between the post-spliced introns and their corresponding mRNAs may play a key role in gene expression.

A prediction nomogram for moderate-to-severe bronchopulmonary dysplasia in preterm infants < 32 weeks of gestation: A multicenter retrospective study.

Background: Moderate-to-severe bronchopulmonary dysplasia (msBPD) is a serious complication in preterm infants. We aimed to develop a dynamic nomogram for early prediction of msBPD using perinatal factors in preterm infants born at <32 weeks' gestation. Methods: This multicenter retrospective study conducted at three hospitals in China between January 2017 and December 2021 included data on preterm infants with gestational age (GA) < 32 weeks. All infants were randomly divided into training and validation cohorts (3:1 ratio). Variables were selected by Lasso regression. Multivariate logistic regression was used to build a dynamic nomogram to predict msBPD. The discrimination was verified by receiver operating characteristic curves. Hosmer-Lemeshow test and decision curve analysis (DCA) were used for evaluating calibration and clinical applicability. Results: A total of 2,067 preterm infants. GA, Apgar 5-min score, small for gestational age (SGA), early onset sepsis, and duration of invasive ventilation were predictors for msBPD by Lasso regression. The area under the curve was 0.894 (95% CI 0.869-0.919) and 0.893 (95% CI 0.855-0.931) in training and validation cohorts. The Hosmer-Lemeshow test calculated P value of 0.059 showing a good fit of the nomogram. The DCA demonstrated significantly clinical benefit of the model in both cohorts. A dynamic nomogram predicting msBPD by perinatal days within postnatal day 7 is available at https://sdxxbxzz.shinyapps.io/BPDpredict/. Conclusion: We assessed the perinatal predictors of msBPD in preterm infants with GA < 32 weeks and built a dynamic nomogram for early risk prediction, providing clinicians a visual tool for early identification of msBPD.

Biosensor-based active ingredient recognition system for screening TNF-α inhibitors from lotus leaves.

Erhuangquzhi granules (EQG) have been clinically proven to be effective in nonalcoholic steatohepatitis (NASH) treatment. However, the active components and molecular mechanisms remain unknown. This study aimed to screen active components targeting tumor necrosis factor α (TNF-α) in EQG for the treatment of NASH by a surface plasmon resonance (SPR) biosensor-based active ingredient recognition system (SPR-AIRS). The amine-coupling method was used to immobilize recombinant TNF-α protein on an SPR chip, the specificity of the TNF-α-immobilized chip was validated, and nine medicinal herbs in EQG were prescreened. Nuciferine (NF), lirinidine (ID), and O-nornuciferine (NNF) from lotus leaves were found and identified as TNF-α ligands by UPLC‒MS/MS, and the affinity constants of NF, ID, and NNF to TNF-α were determined by SPR experiments (Kd = 61.19, 31.02, and 20.71 µM, respectively). NF, ID, and NNF inhibited TNF-α-induced apoptosis in L929 cells, the levels of secreted IL-6 and IL-1ß were reduced, and the phosphorylation of IKKß and IκB was inhibited in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In conclusion, a class of new active small-molecule TNF-α inhibitors was discovered, which also provides a valuable reference for the material basis and mechanism of EQG action in NASH treatment.

Domestic Triatoma spp. Infections with Trypanosoma cruzi, Household Infestations, and Molecular Identification in Oaxaca, México.

In Latin America, Mexico is the country with the second highest annual estimated number of Chagas disease cases, caused by Trypanosoma cruzi, due to vector-borne transmission. The state of Oaxaca is the location of the first documented human cases of Chagas disease in Mexico and contained the highest T. cruzi seropositive rate (3.5%) from blood donors. Here, entomological surveys, from 2017 to 2019, were conducted to collect triatomines in 124 villages of 60 municipalities. Four principal domestic Triatoma spp. (Hemiptera: Triatominae), Triatoma phyllosoma, T. barberi, T. mazzotti, and T. dimidiata, of Oaxaca, Mexico were identified by morphology and molecular analysis of the barcode region of the cytochrome oxidase 1 (cox1 or COI or CO1) gene. A total of 41 out of 83 T. phyllosoma specimens examined by microscopy were positive for T. cruzi (49%), 49 out of 171 for T. barberi (28%), 31 out of 177 for T. mazzotti (17%), and none out of 10 for T. dimidiata (0%). Overall, the infestation index was 3.1% of households containing at least one triatomine; the crowding index was a mean of two Triatoma spp./household; and the colonization index was 0.38 for households based on presence of nymphs. Geographical distribution of triatomines in Oaxaca at the municipality level and endophilic behavior is also reported. Precise identification, endophilic habits, and infection rates of these triatomines are paramount for vector control programs of the Ministry of Health of Oaxaca and beyond.

Secondary Phosphine Sulfide-Enabled Iridium-Catalyzed Asymmetric Allylic Substitution.

An iridium-catalyzed asymmetric synthesis of branched allylic phosphine compounds under mild conditions is reported. Products bearing various functional groups can be synthesized with excellent stereoselectivity (up to 99.9 % ee) and regioselectivity. The employment of phosphine sulfides with relatively low deactivation capacity against metal catalysts is crucial for the success of this reaction.

Role of micronutrients in Alzheimer's disease: Review of available evidence.

Alzheimer's disease (AD) is one of the most common age-related neurodegenerative disorders that have been studied for more than 100 years. Although an increased level of amyloid precursor protein is considered a key contributor to the development of AD, the exact pathogenic mechanism remains known. Multiple factors are related to AD, such as genetic factors, aging, lifestyle, and nutrients. Both epidemiological and clinical evidence has shown that the levels of micronutrients, such as copper, zinc, and iron, are closely related to the development of AD. In this review, we summarize the roles of eight micronutrients, including copper, zinc, iron, selenium, silicon, manganese, arsenic, and vitamin D in AD based on recently published studies.

Traditional Chinese Nursing Using Fennel With Coarse Salt for Ironing and Umbilical Moxibustion for Epigastric Pain With Spleen-stomach Vacuity Cold.

Context: Spleen-stomach vacuity cold is the primary TCM pattern for epigastric pain, accounting for 75% of the patients. According to the TCM theory of treating both the tip and the root, epigastric pain requires the caregiver to dissipate cold and relieve pain, the treatments for the tip, which warm and supplement the spleen and stomach, the treatments for the root. Objective: This study aimed to explore effectiveness of traditional Chinese nursing care using fennel mixed with coarse salt for ironing,with umbilical moxibustion, for epigastric pain, with a pattern of spleen-stomach vacuity cold. Design: The research team designed a randomized control trial (RCT). Setting: The study was conducted at Ruikang Affiliated Hospital of Guangxi University of Chinese Medicine in the capital city of the Guangxi Zhuang autonomous region in the People's Republic of China. Participants: Participants were 96 patients who had been admitted to the hospital between October and November 2020 with epigastric pain resulting from the TCM spleen-stomach vacuity cold pattern, equivalent to chronic atrophic gastritis in Western medicine. Intervention: The research team randomly divided participants into an intervention group (n = 48) and a control group (n = 48) using a random digits table. The intervention group received fennel mixed with coarse salt for ironing, combined with umbilical moxibustion, whereas the control group received routine care. Outcome Measures: The study's instruments included the Traditional Chinese Medicine (TCM) Syndrome Score Scale (TCMSSS), Medical Outcome Study (MOS) Short Form 36 (SF-36), and Satisfaction with TCM Nursing Program (STCMNP). Data were collected and analyzed through descriptive statistics a Chi-square test and independent t test. A significance level of P < .05 was accepted for all statistical analyses. Results: The intervention group had mean scores that indicated significantly higher decreases in epigastric pain, and increases in quality of life and level of satisfaction with the traditional Chinese nursing care than the control group did (P < .05). Conclusions: The traditional Chinese nursing care was able to improve epigastric pain, enhance quality of life, and increase satisfaction with the traditional Chinese nursing care.

Domestic Dogs as Sentinels for West Nile Virus but not Aedes-borne Flaviviruses, Mexico.

We tested 294 domestic pet dogs in Mexico for neutralizing antibodies for mosquito-borne flaviviruses. We found high (42.6%) exposure to West Nile virus in Reynosa (northern Mexico) and low (1.2%) exposure in Tuxtla Gutierrez (southern Mexico) but very limited exposure to Aedes-borne flaviviruses. Domestic dogs may be useful sentinels for West Nile virus.

Cobalt-Catalysed Asymmetric Addition and Alkylation of Secondary Phosphine Oxides for the Synthesis of P-Stereogenic Compounds.

The catalytic asymmetric synthesis of P-chiral phosphorus compounds is an important way to construct P-chiral ligands. Herein, we report a new strategy that adopts the pyridinyl moiety as the coordinating group in the cobalt-catalysed asymmetric nucleophilic addition/alkylation of secondary phosphine oxides. A series of tertiary phosphine oxides were generated with up to 99 % yield and 99.5 % ee, and with broad functional-group tolerance. Mechanistic studies reveal that (R)-secondary phosphine oxides preferentially interact with the cobalt catalysts to produce P-stereogenic compounds.

Electric cyclist injury of the collision between right turn of truck and electric bicycle.

In order to focus on the injury mechanism of electric cyclists in the collision accident between right turn of truck and electric bicycle, Pc-Crash is used to value the injury of the electric cyclist in this paper. Through repeated tests in Pc-Crash, it was found that two dynamic response process were existed. The electric bicycle and cyclist collided with truck, and the electric bicycle and cyclist were thrown to the ground due to the impact force. Finally, they were crushed under certain conditions. The multi-rigid-body truck model is built on the theories of multi-rigid-body modeling and multi-rigid-body collision to get the value of the crushed part which the single rigid model can't calculate. After that, we analyze HIC, continuous 3 ms resultant acceleration of chest, the shear force of femur and leg, based on the electric bicycle speed, the mass of electric bicycle and cyclist, the height of cyclist's seat. We found that when the electric cyclist is not crushed by the truck, the value of each damage index is below the threshold. But when the cyclist is crushed by the truck, the damage index of the part where the cyclist is crushed exceeds the threshold, and causes fatal injury to the cyclist. So, reducing the possibility of crushing can improve the safety level of electric cyclists.

Treatment of Hypertensive Heart Disease by Targeting Smad3 Signaling in Mice.

Transforming growth factor ß (TGF-ß)/Smad3 signaling plays a central role in chronic heart disease. Here, we report that targeting Smad3 with a Smad3 inhibitor SIS3 in an established mouse model of hypertension significantly improved cardiac dysfunctions by preserving the left ventricle (LV) ejection fraction (LVEF) and LV fractional shortening (LVFS), while reducing the LV mass. In addition, SIS3 treatment also halted the progression of myocardial fibrosis by blocking α-smooth muscle actin-positive (α-SMA+) myofibroblasts and collagen matrix accumulation, and inhibited cardiac inflammation by suppressing interleukin (IL)-1ß, tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP1), intercellular cell adhesion molecule-1 (ICAM1) expression, and infiltration of CD3+ T cells and F4/80+ macrophages. Interestingly, treatment with SIS3 did not alter levels of high blood pressure, revealing a blood pressure-independent cardioprotective effect of SIS3. Mechanistically, treatment with SIS3 not only directly inactivated TGF-ß/Smad3 signaling but also protected cardiac Smad7 from Smurf2-mediated proteasomal ubiquitin degradation. Because Smad7 functions as an inhibitor for both TGF-ß/Smad and nuclear factor κB (NF-κB) signaling, increased cardiac Smad7 could be another mechanism through which SIS3 treatment blocked Smad3-mediated myocardial fibrosis and NF-κB-driven cardiac inflammation. In conclusion, SIS3 is a therapeutic agent for hypertensive heart disease. Results from this study demonstrate that targeting Smad3 signaling with SIS3 may be a novel and effective therapy for chronic heart disease.

Latching of the click beetle (Coleoptera: Elateridae) thoracic hinge enabled by the morphology and mechanics of conformal structures.

Elaterid beetles have evolved to 'click' their bodies in a unique maneuver. When this maneuver is initiated from a stationary position on a solid substrate, it results in a jump not carried out by the traditional means of jointed appendages (i.e. legs). Elaterid beetles belong to a group of organisms that amplify muscle power through morphology to produce extremely fast movements. Elaterids achieve power amplifications through a hinge situated in the thoracic region. The actuating components of the hinge are a peg and mesosternal lip, two conformal parts that latch to keep the body in a brace position until their release, the 'click', that is the fast launch maneuver. Although prior studies have identified this mechanism, they were focused on the ballistics of the launched body or limited to a single species. In this work, we identify specific morphological details of the hinges of four click beetle species - Alaus oculatus, Parallelostethus attenuatus, Lacon discoideus and Melanotus spp. - which vary in overall length from 11.3 to 38.8 mm. Measurements from environmental scanning electron microscopy (ESEM) and computerized tomography (CT) were combined to provide comparative structural information on both exterior and interior features of the peg and mesosternal lip. Specifically, ESEM and CT reveal the morphology of the peg, which is modeled as an Euler-Bernoulli beam. In the model, the externally applied force is estimated using a micromechanical experiment. The equivalent stiffness, defined as the ratio between the applied force and the peg tip deflection, is estimated for all four species. The estimated peg tip deformation indicates that, under the applied forces, the peg is able to maintain the braced position of the hinge. This work comprehensively describes the critical function of the hinge anatomy through an integration of specific anatomical architecture and engineering mechanics for the first time.