Mapping the susceptibility to freeze-thaw deterioration and regionalization of freeze-thaw environments of earthen sites in China: A preliminary study.

Earthen sites in China are widely exposed to freeze-thaw environments. There is a lack of knowledge about the spatial distribution patterns of freeze-thaw deterioration and environments, as well as preventive conservation strategies and subsequent refined research on the freeze-thaw deterioration of earthen sites. In this study, the freeze-thaw deterioration process of earthen sites was divided into two periods. Thirteen relevant factors were selected, and using the GIS-FAHP method, a susceptibility map for freeze-thaw deterioration of earthen sites in China was created. The Jenks Natural Breaks method was then employed to categorize the areas into five susceptibility levels: very low (24.6 %), low (18.2 %), moderate (24.2 %), high (18.2 %) and very high (14.8 %). Based on the susceptibility map, the three-level regionalization scheme for freeze-thaw environments of earthen sites in China was systematically developed, taking into account the differences in freeze-thaw deterioration susceptibility and natural landscape within the geomorphological units, and the environmental codes were assigned to third level small-regions. The freeze-thaw environments of earthen sites in China were finally divided into 5 major-regions, 20 sub-regions and 42 small-regions. The results showed that in the area east of the Heihe-Tengchong line, the susceptibility to freeze-thaw deterioration showed latitudinal correlation, and the susceptibility gradually increased from south to north; in the area west of the Heihe-Tengchong line, the susceptibility to freeze-thaw deterioration exhibited strong zonal characteristics. Among the provincial administrative units, Gansu Province and Xinjiang Uighur Autonomous Region have the most complex freeze-thaw environments, while Qinghai, Tibet, Sichuan and Heilongjiang Provinces have the harshest freeze-thaw environments. This study can support regional management and prevention of freeze-thaw deterioration and deterioration studies of earthen sites in China.

Thoracolumbar Sagittal Morphology and Segmental Inclination: A Cross-sectional Cohort Study of Asymptomatic Adult Volunteers.

STUDY DESIGN: A cross-sectional cohort study. OBJECTIVE: To present a normative value reference of spinal segmental inclination stratified by age and pelvic incidence (PI), and to clarify the impact of segmental inclination on spinal sagittal morphology. SUMMARY OF BACKGROUND DATA: Thoracolumbar segmental inclination has been shown to correlate with the clinical outcomes of adult spinal deformity surgery. However, there currently exists no normative value reference in a large sample of asymptomatic population. METHODS: Asymptomatic adult volunteers were enrolled from the community. All volunteers underwent a standing full-spine anteroposterior and lateral radiograph. Lumbar tilt (LT) and thoracic tilt (TT) were measured to quantify the segmental inclination of the lumbar and thoracic spine. Regional curvature, global balance and thoracolumbar apex were analyzed across different age and PI groups. The correlation between sagittal parameters and age was analyzed using Pearson correlation tests. RESULTS: A total of 618 volunteers were included with a mean age of 38.7 ± 17.1 years (range 18 to 82 y). As age increased, the LT and TT significantly increased (P<0.001). The LT was significantly correlated with PI (r=0.410, P<0.001), with the low PI group exhibiting a greater negative LT. The TT remained constant across different PI groups. Compared to the young and middle-age groups, the thoracic apex and lumbar apex were located more caudally in the elderly group (P<0.001). Subjects with a more caudal lumbar apex exhibited a greater negative LT, and those with a more caudal thoracic apex exhibited a greater positive TT. CONCLUSION: The thoracic spine naturally adapts to a relatively neutral position, yet it tends to tilt forward with aging. The physiological lumbar inclination is predominantly determined by the PI value with a slight backward tilt, and tends to counteract the anterior truncal inclination with advanced age. Physiological segmental inclination should be considered in spinal surgical planning.

Machine learning-assisted amidase-catalytic enantioselectivity prediction and rational design of variants for improving enantioselectivity.

Biocatalysis is an attractive approach for the synthesis of chiral pharmaceuticals and fine chemicals, but assessing and/or improving the enantioselectivity of biocatalyst towards target substrates is often time and resource intensive. Although machine learning has been used to reveal the underlying relationship between protein sequences and biocatalytic enantioselectivity, the establishment of substrate fitness space is usually disregarded by chemists and is still a challenge. Using 240 datasets collected in our previous works, we adopt chemistry and geometry descriptors and build random forest classification models for predicting the enantioselectivity of amidase towards new substrates. We further propose a heuristic strategy based on these models, by which the rational protein engineering can be efficiently performed to synthesize chiral compounds with higher ee values, and the optimized variant results in a 53-fold higher E-value comparing to the wild-type amidase. This data-driven methodology is expected to broaden the application of machine learning in biocatalysis research.

Household fuel use and the regression from prehypertension to normotension among Chinese middle-aged and older adults: a cohort study.

To examine the association of household fuel use with prehypertension regression among middle-aged and older people based on the China Health and Retirement Longitudinal Study (CHARLS), we included a total of 3501 participants with prehypertension at baseline, and they were followed up from 2011-2012 to 2015-2016 with information on blood pressure and household solid fuel use (heating and cooking fuels). Cox proportional hazards regression models were used to explore the hazard ratio (HR) and 95% confidence interval (CI) between fuel use and prehypertension regression. Additionally, we investigated the impact of switching fuels (2011-2013) on the regression to normotension during the 4-year follow-up. Linear regression was used to examine the effect of household fuel use on changes in blood pressure. Compared to solid fuel users, those who used clean fuel for heating at baseline had a positive effect on the regression of prehypertension (HR: 1.28, 95% CI: 1.08-1.53). Participants who used clean fuels for both heating and cooking had increased odds for the regression of prehypertension (HR: 1.32, 95% CI: 1.09-1.60). Compared to consistent solid fuel users, those who consistently used clean fuel for heating had a higher likelihood of transitioning from prehypertension to normotension (HR: 1.36, 95% CI: 1.06-1.73) and exhibited 2.45 mmHg lower systolic blood pressure. In conclusion, household clean fuel use for heating was positively associated with the regression of prehypertension to normotension. Furthermore, switching from solid fuel to clean fuel for heating could reduce the risk of prehypertension in Chinese middle-aged and older adults.

Anion Recognition-Directed Supramolecular Catalysis with Functional Macrocycles and Molecular Cages.

ConspectusThe development of supramolecular chemistry has provided a variety of host molecules and noncovalent tools for boosting catalytic processes, stimulating the emergence and advance of supramolecular catalysis, among which macrocyclic and cage-like compounds have attracted great attention due to their possession of an enzyme-mimetic cavity and recognition ability. While the privileged scaffolds such as crown ethers, cyclodextrins, cucurbiturils, calixarenes, and metal-coordinated cages have been widely used, their skeletons usually do not contain a directional binding site; binding and activation mainly rely on cation-associated interactions or hydrophobic effects. In this context, the recent advance of anion supramolecular chemistry has drawn our attention to developing an anion recognition-directed approach by using tailor-made functionalized macrocycles and cages. Anions are important widely existing species in both biological and chemical systems and play an important role in regulating the structure and function of enzymes. We envisioned that by taking advantage of anions, including their rich variety, diverse geometry, and multiple interaction sites, the sophisticated cooperation of multiple noncovalent interactions can be manipulated in a confined cavity for directing efficient and selective catalysis.Following this concept, we initiated our study by introducing typical thiourea H-bonding groups to design and synthesize a series of bis-thiourea macrocycles, especially chiral macrocycles, by incorporating chiral linkers. Taking advantage of the obtained strong, cooperative anion binding, a macrocycle-enabled counteranion trapping strategy was developed, which afforded greatly enhanced catalytic efficiency and excellent stereocontrol in acid-catalyzing reactions. Furthermore, inspired by sulfate-induced macrocyclic dimerization assembly, we built a substrate-induced assembly system, enabling an induced-fit cooperative activation network for efficient and enantioselective catalysis. In addition, anion recognition-driven chirality gearing with a more sophisticated trithiourea cage was revealed, which could provide a basis for implementing anion-triggered allosteric catalysis within the induced helical space. Not limited to hydrogen bonding, the emerging anion-π interactions were largely exploited. A series of triazine-based prism cages containing three V-shaped electron-deficient π-cavities were constructed, and their anion-π binding properties were studied. Based on this system, cooperative anion-π activation was established for driving highly efficient and selective catalysis, which paved a way to push anion-π interactions toward more practical and useful catalyst design.These results demonstrated that the anion-recognition direction can serve as a powerful, versatile approach for boosting highly efficient and selective supramolecular catalysis. It is feasible not only for employing exogenous anions (e.g., counteranion) as a handle but also for recognition and regulation of anionic active intermediates/transition states, from use in conventional H-bonding to emerging anion-π recognition.

A nomogram model for early recurrence of HBV-related hepatocellular carcinomas after radical hepatectomy.

Background: To identify the risk factors and construct a predictive model for early recurrence of hepatitis B virus(HBV-)- related hepatocellular carcinomas(HCCs) after radical resection. Data and methods: A total of 465 HBV-related HCC patients underwent radical resections between January 1, 2012 and August 31, 2018.Their data were collected through the inpatient information management system of the First Affiliated Hospital of University of Science and Technology of China. Survival and subgroup analyses of early recurrence among male and female patients were performed using Kaplan-Meier curves. The independent risk factors associated with early postoperative tumor recurrence were analyzed using multivariate Cox proportional hazards regression model. Based on these independent risk factors, a risk function model for early recurrence was fitted, and a column chart for the prediction model was drawn for internal and external validation. Results: A total of 181 patients developed early recurrences, including 156 males and 25 females. There was no difference in the early recurrence rates between males and females. Tumor diameters>5cm, microvascular invasion and albumin level<35 g/L were independent risk factors for early recurrence. A nomogram for the early recurrence prediction model was drawn; the areas under the curve for the model and for external verification were 0.638 and 0.655, respectively. Conclusion: Tumor diameter>5 cm, microvascular invasion, and albumin level<35 g/L were independent risk factors for early recurrence. The prediction model based on three clinical indicators could predict early recurrence, with good discrimination, calibration, and extrapolation.

Association of changes and cumulative measures of triglyceride-glucose index-body mass index with hypertension risk: a prospective cohort study.

BACKGROUND: To investigate the relationships of the dynamic changes in triglyceride glucose index-body mass index (TyG­BMI) and cumulative TyG-BMI with the risk of hypertension among middle-aged and elderly Chinese. METHODS: Data were used from the China Health and Retirement Longitudinal Study (CHARLS). Participants who participated in the baseline study (2011-2012) and in subsequent surveys (2015-2018) were included in this study. The primary exposures were changes in TyG-BMI and cumulative TyG-BMI from 2012 to 2015. Changes in TyG-BMI were categorized using k-means clustering methods, while cumulative TyG-BMI was categorized into quartiles. Cox proportional hazards regression models were performed to examine the association between changes in TyG-BMI and cumulative TyG-BMI with the incidence of hypertension. Linear regression analyzes were performed to examine the association between changes in TyG-BMI and cumulative TyG-BMI with cumulative systolic blood pressure (SBP) and cumulative diastolic blood pressure (DBP). RESULTS: Of a total of 2,561 participants aged 56.93 ± 8.08 years old at baseline, 253 individuals (9.9%) developed hypertension during the 7-year follow-up period. The hazard ratios (HR) and 95% confidence interval (CI) for hypertension were 1.50 (1.10-2.03) for class 2 (persistently medium class) and 2.35 (1.61-3.42) for class 3 (persistently high class), compared to class 1 (persistently low class). Additionally, class 2 showed increases of 7.70 mmHg (95% CI: 5.18-10.21) in cumulative SBP and 6.53 mmHg (95% CI: 4.68-8.38) in cumulative DBP, while class 3 exhibited increases of 14.10 mmHg (95% CI: 10.56-17.64) in cumulative SBP and 12.64 mmHg (95% CI: 10.03-15.25) in cumulative DBP, compared with class 1. Regarding cumulative TyG-BMI, the HR for hypertension were 1.75 (95% CI: 1.18-2.59) for quartile 3 and 2.15 (95% CI: 1.43-3.23) for quartile 4, compared with quartile 1. In quartile 2, cumulative SBP increased by 3.99 mmHg (95% CI: 0.88-7.11) and cumulative DBP by 2.74 mmHg (95% CI: 0.45-5.02). Quartile 3 showed increases of 8.32 mmHg (95% CI: 5.09-11.54) in cumulative SBP and 7.13 mmHg (95% CI: 4.76-9.49) in cumulative DBP. Quartile 4 exhibited the highest increases, with cumulative SBP rising by 13.15 mmHg (95% CI: 9.70-16.60) and cumulative DBP by 12.20 mmHg (95% CI: 9.67-14.74). Furthermore, a linear relationship was observed between cumulative TyG-BMI and the risk of hypertension. CONCLUSIONS: Changes in TyG-BMI and cumulative TyG-BMI were associated with an increased risk of hypertension, as well as higher cumulative SBP and DBP in Chinese middle-aged and elderly population.

Spontaneous Transition between Multiple Conductance States and Rectifying Behaviors in an Artificial Single-Molecule Funnel.

It has long been an aspirational goal to create artificial channel structures that replicate the feat achieved by ion channel proteins. Biological ion channels occasionally demonstrate multiple conductance states (known as subconductance), remaining a challenging property to achieve in artificial channel molecules. We report a funnel-shaped single-molecule channel constructed by an electron-deficient macrocycle and two electron-deficient aromatic imide arms. Planar lipid bilayer measurements reveal distinct current recordings, including a closed state, two conducting states, and spontaneous transitions between the three states, resembling the events seen in biological ion channels. The transitions result from conformational changes induced by chloride transport in the channel molecule. Both opening states show a non-linear and rectifying I-V relationship, indicating voltage-dependent transport due to the asymmetrical channel structure. This work could enhance our understanding of ion permeation and channel opening mechanism.

Posterior Thoracic Antidisplacement and Fusion Surgery for a Special Type of Ossification of the Posterior Longitudinal Ligament in the Thoracic Spine: Indications and Preliminary Clinical Results of 2-Year Follow-Up.

OBJECTIVE: To describe a novel technique, posterior thoracic antidisplacement and fusion (PTAF), for a special type of ossification of the posterior longitudinal ligament in the thoracic spine (T-OPLL), and to evaluate its safety and efficacy. METHODS: From July to December 2020, 5 consecutive patients with beak-type T-OPLL located at the thoracic vertebral body level underwent PTAF surgery. Their demographic data, radiological parameters, perioperative complications, and surgery-related findings were recorded and analyzed. The surgical outcomes were assessed using a modified Japanese Orthopedic Association scale, and the recovery rate was calculated using the Hirabayashi's method. RESULTS: All patients were followed up for at least two years. The mean thickness of OPLL was 9.4 ± 1.0 mm, and the OPLL spinal canal occupying ratio was 67.7% ± 8.5%. Postoperatively, the mean antidisplacement distance of OPLL was 8.1 ± 1.8 mm, and the average shortened distance of the spinal column was 6.0 ± 1.13 mm. The mean operation time and blood loss were 158.2 ± 26.3 minutes and 460 ± 89.4 mL, respectively. Perioperative complications were cerebrospinal fluid leakage and instrument failure, 2 cases each. The mean modified Japanese Orthopedic Association score was increased from 3.6 ± 2.9 before surgery to 9.4 ± 3.0 at the last follow-up, and the average recovery rate was 84.2 ± 30.5%. CONCLUSIONS: The preliminary clinical outcomes indicate that PTAF is a safe and effective method for the treatment of beak-type T-OPLL, which has its apex located at the vertebral body level and has a high spinal canal occupation ratio.

Anion-Carbonyl Interactions.

Presented herein is the exploration of a novel non-covalent anion-carbonyl (X-···C═O) interaction using aromatic imides as receptors and halides as lone pair donors. Combined theoretical calculations and experimental methods including 13C NMR, IR, and crystallographic analyses were performed to provide the physical origin and experimental evidence of anion-carbonyl interactions. The EDA analysis (energy decomposition analysis) based on DFT calculation indicates that electrostatic terms are the dominant contributions for the binding energy while electron delocalization also significantly contributes alongside the electrostatic attraction. Orbital interaction (n → π*) involving the delocalization of halide lone pairs on the carbonyl antibonding orbitals was visualized with NBO (Natural Bond Orbital) analysis. 13C NMR and IR spectra demonstrated upfield chemical shifts and red-shift frequency of hosts upon the addition of halides, reflecting the effect of orbital overlap between the halide lone pairs and π* of carbonyl (n → π* contribution). The anion-carbonyl interactions were directly revealed by X-ray structural analysis of anion and benzene triimide complexes.

The transition of eldercare responsibility and traditional filial piety concepts and its urban-rural differences in China: an age-period-cohort analysis from 2006 to 2017.

BACKGROUND: With rapid urbanization, massive migration, and non-family-based eldercare involvement, Chinese concepts of eldercare responsibility and filial piety are shifting. We performed age-period-cohort (APC) analyses to assess the transition of old-age pension coverage, eldercare responsibility, and filial piety concepts and its urban-rural differences among Chinese adults using data from the China General Social Survey (2006-2017). METHODS: Old-age pension coverage (yes/no) and primary eldercare responsibility (government/offspring/self/sharing) were investigated in 2010, 2012, 2013, 2015, and 2017. Filial piety was evaluated using customized questionnaires in 2006 and 2017. The APC effects were estimated using mixed effects and generalized additive models. RESULTS: Among 66,182 eligible participants (mean age: 48.8 years, females: 51.7%) in the six waves, APC analyses indicated that old-age pension coverage increased with aging and over time. Across cohort groups, it grew as the cohort was younger in urban residents but decreased in rural residents. The concept of offspring-based (> 50%) and government/self/offspring-shared eldercare (> 30%) predominated. APC analyses revealed that the offspring-based concept declined with aging (OR = 0.81, 95% CI: 0.79-0.84), whereas the government-based (OR = 1.37, 95% CI: 1.33-1.41) and self-based (OR = 1.55, 95% CI: 1.47-1.63) concepts increased with aging. People born around the 1940s have a comparatively higher possibility to perceive that the primary eldercare responsibility should be undertaken by the government and elder parents. In contrast, people born in the younger cohort were more likely to perceive that adult children are responsible for their parents' primary eldercare. Filial piety score slightly increased with aging (ß = 0.18, SD: 0.05) but decreased as the birth cohort was younger. In addition, rural participants were more likely to perceive offspring-based eldercare and maintain filial piety, and the related urban-rural difference was intensified by aging. CONCLUSIONS: The traditional concept that eldercare solely relies on offspring has changed to relying on multiple entities, including the government and self-reliance. Diluted filial piety in people born in the young cohort requires reinforcement. Moreover, future healthy aging policies need to focus more on urban-rural disparities to promote equity in social well-being.

The combined effect of handgrip strength and obesity phenotype on the risk of stroke in Chinese middle-aged and elderly: A cohort study.

OBJECTIVE: The aim of this study was to investigate the combined effect of handgrip strength (HGS) and obesity phenotype on the risk of stroke in Chinese middle-aged and elderly people. METHODS: The data was used from the China Health and Retirement Longitudinal Study (CHARLS). Middle-aged and older adults who participated in surveys between 2011 and 2018 were included in the study. They were divided into 4 different types of obesity phenotypes based on obesity and metabolic status: metabolically healthy non-overweight/obesity (MHNO), metabolically healthy overweight/obesity (MHO), metabolically abnormal non-overweight/obesity (MANO), and metabolically abnormal overweight/obesity (MAO). The HGS level was divided into low and high groups according to the median values. Cox proportional risk regression model was used to analyze the joint effect of HGS and obesity phenotype on the risk of stroke among participants. RESULTS: A total of 7904 participants aged 58.89±9.08 years were included in this study. After adjusting for potential confounders, high HGS&MHO (HR=1.86, 95 % CI=1.12-3.09), high HGS&MANO (HR=2.01, 95 %CI=1.42-2.86), high HGS&MAO (HR=2.01, 95 % CI=1.37-2.93), low HGS&MHNO (HR=1.57, 95 % CI=1.00-2.46), low HGS&MHO (HR=2.09, 95 % CI=1.29-3.38), low HGS&MANO (HR=2.02, 95 % CI=1.35-3.03), and low HGS&MAO (HR=2.48, 95 % CI=1.72-3.58) group had significantly higher risks of stroke than the high HGS&MHNO group. CONCLUSION: The coexistence of metabolically unhealthy and low HGS can synergistically increase the risk of stroke in Chinese middle-aged and elderly people.

Regulation of π-π interactions between single aromatic molecules by bias voltage.

π-stacking interaction, as a fundamental type of intermolecular interaction, plays a crucial role in generating new functional molecules, altering the optoelectronic properties of materials, and maintaining protein structural stability. However, regulating intermolecular π-π interactions at the single-molecule level without altering the molecular conformation as well as the chemical properties remains a significant challenge. To this end, via conductance measurement with thousands of single molecular junctions employing a series of aromatic molecules, we demonstrate that the π-π coupling between neighboring aromatic molecules with rigid structures in a circuit can be greatly enhanced by increasing the bias voltage. We further reveal that this universal regulating effect of bias voltage without molecular conformational variation originates from the increases of the molecular dipole upon an applied electric field. These findings not only supply a non-destructive method to regulate the intermolecular interactions offering an approach to modulate the electron transport through a single molecular junction, but also deepen the understanding of the mechanism of π-π interactions.

Identification of lung adenocarcinoma subtypes and a prognostic signature based on activity changes of the hallmark and immunologic gene sets.

Background: Lung adenocarcinoma (LUAD) has a complex tumor heterogeneity. Our research attempts to clearness LUAD subtypes and build a reliable prognostic signature according to the activity changes of the hallmark and immunologic gene sets. Methods: According to The Cancer Genome Atlas (TCGA) - LUAD dataset, changes in marker and immune gene activity were analyzed, followed by identification of prognosis-related differential gene sets (DGSs) and their related LUAD subtypes. Survival analysis, correlation with clinical characteristics, and immune microenvironment assessment for subtypes were performed. Moreover, the differentially expressed genes (DEGs) between different subtypes were identified, followed by the construction of a prognostic risk score (RS) model and nomogram model. The tumor mutation burden (TMB) and tumor immune dysfunction and exclusion (TIDE) of different risk groups were compared. Results: Two LUAD subtypes were determined according to the activity changes of the hallmark and immunologic gene sets. Cluster 2 had worse prognosis, more advanced tumor and clinical stages than cluster 1. Moreover, a prognostic RS signature was established using two LUAD subtype-related DEGs, which could stratify patients at different risk levels. Nomogram model incorporated RS and clinical stage exerted good prognostic performance in LUAD patients. A shorter survival time and higher TMB were observed in the high-risk patients. Conclusions: Our findings revealed that our constructed prognostic signature could exactly predict the survival status of LUAD cases, which was helpful in predicting the prognosis and guiding personalized therapeutic strategies for LUAD.

Enhancing the thermopower of single-molecule junctions by edge substitution effects.

Heteroatom substitution and anchoring groups have an important impact on the thermoelectric properties of single-molecule junctions. Herein, thermoelectric properties of several anthracene derivative based single-molecule junctions are studied by means of first-principles calculations. In particular, we pay great attention to the edge substitution effects and find that edge substitution with nitrogen can induce a transmission peak near the Fermi energy, leading to large transmission coefficients and electrical conductance at the Fermi energy. Additionally, the steep shape of the transmission function gives rise to a high Seebeck coefficient. Therefore, an enhanced power factor can be expected. The robustness of this edge substitution effect has been examined by altering the electrode distance and introducing heteroatoms at different positions. The enhancement of the power factor due to edge substitution makes the studied single-molecule junction a promising candidate for efficient thermoelectric devices.

Chiral Bis-phosphate Macrocycles for Catalytic, Efficient, and Enantioselective Electrophilic Fluorination.

Incorporation of privileged catalytic scaffolds into a macrocyclic skeleton represents an attractive strategy to furnish supramolecular catalysis systems with enzyme-mimetic cavity and multi-site cooperation. Herein we reported the synthesis, structure, binding properties and catalytic application of a series of chiral bis-phosphate macrocycles toward the challenging asymmetric electrophilic fluorination. With a large, integrated chiral cavity and two cooperative phosphate sites, these macrocycles exhibited good inclusion toward 1,4-diazabicyclo[2.2.2]octane (DABCO) dicationic ammoniums through complementary ion-pair and C-H⋅⋅⋅O interactions, as confirmed by crystallographic and solution binding studies. In fluorocyclization of tryptamines with Selectfluor reagent which has a similar DABCO-based dicationic structure, only 2 mol% macrocycle catalyst afforded the desired pyrroloindoline products in moderate yields and up to 91 % ee. For comparison, the acyclic mono-phosphate analogue gave obviously lower reactivity and enantioselectivity (<20 % ee), suggesting a remarkable macrocyclic effect. The high catalytic efficiency and superior stereocontrol were ascribed to the tight ion-pair binding and cavity-directed noncovalent interaction cooperation.

Benzoylaconitine: A promising ACE2-targeted agonist for enhancing cardiac function in heart failure.

Benzoylaconitine is a natural product in the treatment of cardiovascular disease. However, its pharmacological effect, direct target protein, and molecular mechanisms for the treatment of heart failure are unclear. In this study, benzoylaconitine inhibited Ang II-induced cell hypertrophy and fibrosis in rat primary cardiomyocytes and rat fibroblasts, while attenuating cardiac function and cardiac remodeling in TAC mice. Using the limited proteolysis-mass spectrometry (LiP-MS) method, the angiotensin-converting enzyme 2 (ACE2) was confirmed as a direct binding target of benzoylaconitine for the treatment of heart failure. In ACE2-knockdown cells and ACE2-/- mice, benzoylaconitine failed to ameliorate cardiomyocyte hypertrophy, fibrosis, and heart failure. Online RNA-sequence analysis indicated p38/ERK-mediated mitochondrial reactive oxygen species (ROS) and nuclear factor kappa B (NF-κB) activation are the possible downstream molecular mechanisms for the effect of BAC-ACE2 interaction. Further studies in ACE2-knockdown cells and ACE2-/- mice suggested that benzoylaconitine targeted ACE2 to suppress p38/ERK-mediated mitochondrial ROS and NF-κB pathway activation. Our findings suggest that benzoylaconitine is a promising ACE2 agonist in regulating mitochondrial ROS release and inflammation activation to improve cardiac function in the treatment of heart failure.

Mimicking the Shape and Function of the ClC Chloride Channel Selective Pore by Combining a Molecular Hourglass Shape with Anion-π Interactions.

ClC is the main family of natural chloride channel proteins that transport Cl- across the cell membrane with high selectivity. The chloride transport and selectivity are determined by the hourglass-shaped pore and the filter located in the central and narrow region of the pore. Artificial unimolecular channel that mimics both the shape and function of the ClC selective pore is attractive, because it could provide simple molecular model to probe the intriguing mechanism and structure-function relevance of ClC. Here we elaborated upon the concept of molecular hourglass plus anion-π interactions for this purpose. The concept was validated by experimental results of molecular hourglasses using shape-persistent 1,3-alternate tetraoxacalix[2]arene[2]triazine as the central macrocyclic skeleton to control the conductance and selectivity, and anion-π interactions as the driving force to facilitate the chloride dehydration and movement along the channel.

Breastfeeding and the Longitudinal Changes of Body Mass Index in Childhood and Adulthood: A Systematic Review.

Mounting evidence supports the beneficial role of breastfeeding in lowering obesity risk, but the enduring impact of breastfeeding on longitudinal changes in body mass index (BMI) (i.e., BMI trajectories) remains unclear. This systematic review summarized evidence on how breastfeeding influenced the longitudinal trajectories of BMI later in life. Literature searches were conducted in Medline, Embase, Web of Science, and ScienceDirect to identify studies that assessed how breastfeeding (versus other feeding types or duration) was associated with longitudinal trajectories of BMI or BMI z-score. Three randomized controlled trials (RCTs) and 24 longitudinal cohort studies were included. Two-thirds (18/27) of studies were rated as acceptable or high quality. Most cohort studies (9/11) showed that children who continued to breastfeed at 3 to 12 mo of age had a lower BMI trajectory or lower odds of following a high BMI trajectory than those who were formula-fed or mixed-fed. The BMI differences between breastfeeding and other feeding groups were evident from age 7 mo and remained up to 8 y, and the magnitude of between-group BMI differences increased with age. For breastfeeding duration, 12 out of 15 cohort studies found that longer breastfeeding duration was associated with lower BMI trajectories up to age 18 y. Moreover, beneficial associations were observed for both exclusive and any breastfeeding with BMI trajectory. In contrast, mixed findings were reported from 3 RCTs that compared BMI trajectories from birth to ages 12 to 24 mo between breastfeeding promotion versus control or breastfeeding versus formula-feeding groups. The current review provides further longitudinal evidence from cohort studies that breastfeeding versus formula/mixed feeding or longer breastfeeding duration was associated with lower BMI trajectories. Such associations initiated in early childhood became more apparent with age and were sustained into early adulthood. The existing evidence substantiates the importance of breastfeeding promotion and continuation to support obesity prevention.

Chiral Benzene Triimide (BTI) Radical Anions for Probing the Interplay of Unpaired Electron Spin and Chirality.

Herein a series of chiral BTI radical anions bearing different chiral substituents were efficiently prepared by chemical reduction. X-ray crystallography revealed finely-tuned packing and helix assemblies of the radicals by the size of chiral substituents in crystalline state. In accordance with the crystalline-state packing, the powder ESR spectra indicate that 4 a- ⋅CoCp2 + and 4 c- ⋅CoCp2 + π-dimers exhibit thermally excited triplet states arising from strong spin-spin interactions, while discrete 4 b- ⋅CoCp2 + shows a broad doublet-state signal reflecting weak spin-spin interactions. The interplay between the unpaired electron spin and chiral substituents was studied by UV-Vis-NIR spectra, electronic circular dichroism (ECD) and TD DFT calculations. Different NIR absorptions of the radicals attributing to isolated SOMO→LUMO+1 (~889 nm) transitions were recorded. The emergence of Cotton effects (CEs) at the NIR region for 4 c- ⋅CoCp2 + radical enantiomers suggest the interplay between chirality and unpaired electron spin. The origin of the different circularly polarized light absorptions regarding SOMO derived transitions (around 880 nm) was attributed to chiral substitutes regulated electric and magnetic transition dipole moments of the unpaired electron participated transition.