Chiral Aldehyde Catalysis-Enabled Asymmetric α-Functionalization of Activated Primary Amines.

ConspectusThe development of catalytic activation modes provides a reliable and effective platform for designing new enantioselective reactions and preparing chiral molecules with diverse structures. Chiral aldehyde catalysis is an attractive concept in asymmetric catalysis, which utilizes a chiral aldehyde catalyst to promote the asymmetric hydroamination of allylic amines, the asymmetric α-functionalization of primary amines, or the asymmetric transamination of α-keto esters. Typically, the chiral aldehyde-catalyzed asymmetric α-functionalization of primary amines provides an efficient and straightforward method for the synthesis of α-functionalized chiral amines, which does not require any additional protection or deprotection manipulations of the amine group. However, achieving catalytic stereoselective transformations with high efficiency and enantioselectivity by this strategy has remained an intractable challenge.This Account summarizes our endeavors in the development and application of chiral aldehyde catalysis. Using a chiral aldehyde as a catalyst, we reported the catalytic asymmetric α-C alkylation of 2-aminomalonate with 3-indolylmethanol in 2014, which represents the first chiral aldehyde-catalyzed asymmetric α-functionalization of an activated primary amine. Subsequently, several axially chiral aldehyde catalysts were continuously prepared by using chiral BINOL as the starting material, and their applications in asymmetric synthesis were explored. On the one hand, they were used as organocatalysts to realize the various transformations of α-amino acid esters, such as asymmetric 1,4-addition toward conjugated enones/α,ß-unsaturated diesters and cyclic 1-azadienes as well as asymmetric α-arylation/allylation and benzylation with corresponding halohydrocarbons. Notably, taking advantage of the difference in the distribution of catalytic sites between two chiral aldehyde catalysts, we disclosed chiral aldehyde-catalyzed diastereodivergent 1,6-conjugated addition and Mannich reactions. On the other hand, the potential for the cooperative catalysis of a chiral aldehyde with a transition metal has also been demonstrated. Enabled by the combination of a chiral aldehyde, a palladium complex, and a Lewis acid, the enantioselective α-allylation of amino acid esters with allyl alcohol esters was established. Moreover, the ternary catalytic system has been successfully used for the α-functionalization of amino acid esters with 1,3-dienes, allenes, allenylic alcohol esters, 1,3-disubstituted allyl alcohol esters, and arylmethanol esters as well as the asymmetric cascade Heck-alkylation reaction. The combination of a chiral aldehyde and nickel complex allows for the asymmetric α-propargylation of amino acid esters with propargylic alcohol esters and provides excellent enantioselectivities. These transformations provide a large library of optically active amines and amino acids. With those chiral amino acid esters as key building blocks, the synthesis or formal synthesis of multiple natural products and biologically significant unnatural molecules was accomplished. This includes the stereodivergent synthesis of natural pyrrolizidine alkaloid NP25302 and the formal synthesis of natural product (S)-hypoestestatin 1 and manzacidin C, clinical candidate compound (+)-AG-041R, and somatostatin mimetics. It is fully anticipated that chiral aldehyde catalysis will soon witness rapid expansion both in the development of novel asymmetric transformations and in innovative applications for constructing optically active nitrogen-containing molecules with significant values.

The association between triglyceride-glucose index and its combination with obesity indicators and cardiovascular disease: NHANES 2003-2018.

BACKGROUND: In the American population, the relationship between the triglyceride-glucose (TyG) index and TYG combined with indicators of obesity and cardiovascular disease (CVD) and its mortality has been less well studied. METHODS: This cross-sectional study included 11,937 adults from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. Cox proportional hazards model, binary logistic regression analyses, restricted cubic spline (RCS), and receiver operating characteristic (ROC) were used to analyze the relationship between TyG and its combined obesity-related indicators and CVD and its mortality. Mediation analysis explored the mediating role of glycated hemoglobin and insulin in the above relationships. RESULTS: In this study, except for no significant association between TyG and CVD mortality, TyG, TyG-WC, TyG-WHtR, and TyG-BMI were significantly and positively associated with CVD and CVD mortality. TyG-WHtR is the strongest predictor of CVD mortality (HR 1.66, 95% CI 1.21-2.29). The TyG index correlated better with the risk of coronary heart disease (OR 2.52, 95% CI 1.66-3.83). TyG-WC correlated best with total CVD (OR 2.37, 95% CI 1.77-3.17), congestive heart failure (OR 2.14, 95% CI 1.31-3.51), and angina pectoris (OR 2.38, 95% CI 1.43-3.97). TyG-WHtR correlated best with myocardial infarction (OR 2.24, 95% CI 1.45-3.44). RCS analyses showed that most of the above relationships were linear (P-overall < 0.0001, P-nonlinear > 0.05). Otherwise, ROC curves showed that TyG-WHtR and TyG-WC had more robust diagnostic efficacy than TyG. In mediation analyses, glycated hemoglobin mediated in all the above relationships and insulin-mediated in partial relationships. CONCLUSIONS: TyG-WC and TyG-WtHR enhance CVD mortality prediction, diagnostic efficacy of CVD and its mortality, and correlation with some CVD over and above the current hottest TyG. TyG-WC and TyG-WtHR are expected to become more effective metrics for identifying populations at early risk of cardiovascular disease and improve risk stratification.

Quantifying Methane Influx from Sewer into Wastewater Treatment Processes.

Wastewater treatment contributes substantially to methane (CH4) emissions, yet monitoring and tracing face challenges because the treatment processes are often treated as a "black box". Particularly, despite growing interest, the amount of CH4 carryover and influx from the sewer and its impacts on overall emissions remain unclear. This study quantified CH4 emissions from six wastewater treatment plants (WWTPs) across China, utilizing existing multizonal odor control systems, with a focus on Beijing and Guiyang WWTPs. In the Beijing WWTP, almost 90% of CH4 emissions from the wastewater treatment process were conveyed through sewer pipes, affecting emissions even in the aerobic zone of biological treatment. In the Guiyang WWTP, where most CH4 from the sewer was released at the inlet well, a 24 h online monitoring revealed CH4 fluctuations linked to neighborhood water consumption and a strong correlation to influent COD inputs. CH4 emission factors monitored in six WWTPs range from 1.5 to 13.4 gCH4/kgCODrem, higher than those observed in previous studies using A2O technology. This underscores the importance of considering CH4 influx from sewer systems to avoid underestimation. The odor control system in WWTPs demonstrates its potential as a cost-effective approach for tracing, monitoring, and mitigating CH4.

Characteristics and performance of layered two-dimensional materials under doping engineering.

In recent years, doping engineering, which is widely studied in theoretical and experimental research, is an effective means to regulate the crystal structure and physical properties of two-dimensional materials and expand their application potential. Based on different types of element dopings, different 2D materials show different properties and applications. In this paper, the characteristics and performance of rich layered 2D materials under different types of doped elements are comprehensively reviewed. Firstly, 2D materials are classified according to their crystal structures. Secondly, conventional experimental methods of charge doping and heterogeneous atom substitution doping are summarized. Finally, on the basis of various theoretical research results, the properties of several typical 2D material representatives under charge doping and different kinds of atom substitution doping as well as the inspiration and expansion of doping systems for the development of related fields are discussed. Through this review, researchers can fully understand and grasp the regulation rules of different doping engineering on the properties of layered 2D materials with different crystal structures. It provides theoretical guidance for further improving and optimizing the physical properties of 2D materials, improving and enriching the relevant experimental research and device application development.

Propionate outperforms conventional acetate as electron donors for highly-sensitive electrochemical active biofilm sensors in water biotoxicity early-warning.

With the ability to generate in situ real-time electric signals, electrochemically active biofilm (EAB) sensors have attracted wide attention as a promising water biotoxicity early-warning device. Organic matters serving as the electron donors potentially affect the electric signal's output and the sensitivity of the EAB sensor. To explore the influence of organic matters on EAB sensor's performance, this study tested six different organic matters during the sensor's inoculation. Besides the acetate, a conventional and widely used organic matter, propionate and lactate were also found capable of starting up the sensor. Moreover, the propionate-fed (PF) sensor delivered the highest sensitivity, which are respectively 1.4 times and 2.8 times of acetate-fed (AF) sensor and lactate-fed (LF) sensor. Further analysis revealed that EAB of PF sensor had more vulnerable intracellular metabolism than the others, which manifested as the most severe energy metabolic suppression and reactive oxygen species attack. Regarding the microbial function, a two-component system that was deemed as an environment awareness system was found in the EAB of PF, which also contributed to its high sensitivity. Finally, PF sensor was tested in real water environment to deliver early-warning signals.

A Prospective Self-controlled Clinical Trial of Nonactivated Low Leukocyte PRP in Female Pattern Hair Loss Patients of Childbearing Age.

BACKGROUND: Alopecia significantly affects the mental health and social relationship of women since childbearing age, highlighting the need for a safe, effective, and convenient treatment. METHODS: The authors have conducted a prospective self-controlled trial involving 15 female patients at childbearing age with alopecia. These patients received a subcutaneous scalp injection of platelet-rich plasma once every 4 weeks for 3 treatments in total. Outcome measurements were included below: changes in hair density (hair/cm2), hair follicle density (hair follicle/cm2), and overall photographic assessment (improved or not) at 4, 12, and 24 weeks right after the first treatment. RESULTS: Comparing the photographs taken before and after the intervention, 67% of patients' hair density increased from 151 ± 39.82 hairs/cm2 (preintervention) to 170.96 ± 37.14 hairs/cm2 (at 24-week follow-up), representing an approximate increase of 19 hairs/cm2. Meanwhile, hair follicle density increased by approximately 15 follicles/cm2 after 24 weeks since the first treatment, rising from 151.04 ± 41.99 follicles/cm2 to 166.72 ± 37.13 follicles/cm2. The primary adverse reactions observed were local swelling and pain due to injections. CONCLUSION: Local injection of nonactivated platelet-rich plasma with low leukocytes concentration could be an effective strategy to alleviate alopecia symptoms in female patients.

Interfacial engineering of halide perovskites and two-dimensional materials.

Recently, halide perovskites (HPs) and layered two-dimensional (2D) materials have received significant attention from industry and academia alike. HPs are emerging materials that have exciting photoelectric properties, such as a high absorption coefficient, rapid carrier mobility and high photoluminescence quantum yields, making them excellent candidates for various optoelectronic applications. 2D materials possess confined carrier mobility in 2D planes and are widely employed in nanostructures to achieve interfacial modification. HP/2D material interfaces could potentially reveal unprecedented interfacial properties, including light absorbance with desired spectral overlap, tunable carrier dynamics and modified stability, which may lead to several practical applications. In this review, we attempt to provide a comprehensive perspective on the development of interfacial engineering of HP/2D material interfaces. Specifically, we highlight the recent progress in HP/2D material interfaces considering their architectures, electronic energetics tuning and interfacial properties, discuss the potential applications of these interfaces and analyze the challenges and future research directions of interfacial engineering of HP/2D material interfaces. This review links the fields of HPs and 2D materials through interfacial engineering to provide insights into future innovations and their great potential applications in optoelectronic devices.

The informal discussion of advance care planning among Chinese older adults: Do education and social media use matter?

This study aimed to examine and compare the associations between education, social media use, and advance care planning (ACP) discussion among Chinese older adults in mainland China (Wuhan), Taiwan (Taichung), and the United States (Honolulu). Community-dwelling older adults (≥ 55) were recruited from 2017 to 2018. The ACP discussion rate in Wuhan, Taichung, and Honolulu were 15.2 %, 19.2 %, and 31.3 %, respectively. Logistic regression models revealed that education was positively associated with ACP discussion in Taichung and Honolulu. Social media use was positively associated with ACP discussions in Wuhan and Honolulu, and it attenuated the association between education and ACP discussion in Honolulu. The present study contributes to previous studies by comparing the associations between education, social media use, and ACP discussion in different settings within the same ethnicity. Policy and practice implications were also discussed.

IL-27 mediates anti-inflammatory effect in cigarette smoke induced emphysema by negatively regulating IFN-γ producing cytotoxic CD8+ T cells in mice.

Chronic airway inflammation mediated by CD8+ T lymphocytes contributes to the pathogenesis of Chronic obstructive pulmonary disease (COPD). Deciphering the fingerprint of the chronic inflammation orchestrated by CD8+ T cells may allow the development of novel approaches to COPD management. Here, the expression of IL-27 and IFN-γ+ CD8+ Tc1 cells were evaluated in patients with COPD and in cigarette smoke-exposed mice. The production of IL-27 by marrow-derived dendritic cells (mDCs) in response to cigarette smoke extract (CSE) was assessed. The role of IL-27 in IFN-γ+ CD8+ Tc1 cells was explored. We demonstrated that elevated IL-27 was accompanied by an exaggerated IFN-γ+ CD8+ Tc1 response in a smoking mouse model of emphysema. We noted that lung dendritic cells were one of the main sources of IL-27 during chronic cigarette smoke exposure. Moreover, CSE directly induced the production of IL-27 by mDCs in vitro. IL-27 negatively regulated the differentiation of IFN-γ+ CD8+ Tc1 cells isolated from cigarette smoke-exposed mice in a STAT1- and STAT3-independent manner. Systemic administration of recombinant IL-27 attenuated IFN-γ+ CD8+ Tc1 response in the late phase of cigarette smoke exposure. Our results uncovered that IL-27 negatively regulates IFN-γ+ CD8+ Tc1 response in the late stage of chronic cigarette smoke exposure, which may provide a new strategy for the anti-inflammatory treatment of smoking-related COPD/emphysema.

Consensus subtypes of hepatocellular carcinoma associated with clinical outcomes and genomic phenotypes.

BACKGROUND AND AIMS: Although many studies revealed transcriptomic subtypes of HCC, concordance of the subtypes are not fully examined. We aim to examine a consensus of transcriptomic subtypes and correlate them with clinical outcomes. APPROACH AND RESULTS: By integrating 16 previously established genomic signatures for HCC subtypes, we identified five clinically and molecularly distinct consensus subtypes. STM (STeM) is characterized by high stem cell features, vascular invasion, and poor prognosis. CIN (Chromosomal INstability) has moderate stem cell features, but high genomic instability and low immune activity. IMH (IMmune High) is characterized by high immune activity. BCM (Beta-Catenin with high Male predominance) is characterized by prominent ß-catenin activation, low miRNA expression, hypomethylation, and high sensitivity to sorafenib. DLP (Differentiated and Low Proliferation) is differentiated with high hepatocyte nuclear factor 4A activity. We also developed and validated a robust predictor of consensus subtype with 100 genes and demonstrated that five subtypes were well conserved in patient-derived xenograft models and cell lines. By analyzing serum proteomic data from the same patients, we further identified potential serum biomarkers that can stratify patients into subtypes. CONCLUSIONS: Five HCC subtypes are correlated with genomic phenotypes and clinical outcomes and highly conserved in preclinical models, providing a framework for selecting the most appropriate models for preclinical studies.

Individualized Choice of Simultaneous Cholecystectomy in Patients with Gastric Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Patients undergoing gastrectomy for gastric cancer are more likely to develop gallstones than the general population. Prophylactic cholecystectomy remains controversial. METHODS: Studies from 2000-2022 were systematically searched in the PubMed, EMBASE, and Cochrane Library databases. The search included simultaneous cholecystectomy or risk factors for gallstone formation with gastrectomy alone. Major prognostic factors included complications and mortality, and risk factor analyses included age, sex, TNM stage, gastrectomy type, lymph node dissection, diabetes, and duodenal exclusion. Random effects regression models were used to analyze risk estimates and data were presented as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS: There were no significant differences in postoperative morbidity (OR 1.12, 95% CI 0.90-1.39; p = 0.33, I2 = 11%) and mortality (OR 1.23, 95% CI 0.62-2.43; p = 0.56, I2 = 0%) between gastrectomy alone and simultaneous cholecystectomy. Older age (OR 1.48, 95% CI 1.36-1.59; p < 0.001, I2 = 59%), male sex (OR 1.38, 95% CI 1.10-1.71; p = 0.004, I2 = 77%), total gastrectomy (OR 1.50, 95% CI 1.25-1.81; p < 0.001, I2 = 72%), diabetes mellitus (OR 1.38, 95% CI 1.17-1.63; p < 0.001, I2 = 8%), and duodenal exclusion (OR 1.77, 95% CI 1.47-2.15; p < 0.001, I2 = 30%) were risk factors for cholecystolithiasis. CONCLUSIONS: Simultaneous cholecystectomy did not increase the incidence of postoperative complications or mortality. Older age, male sex, total gastrectomy, duodenal exclusion, and diabetes were risk factors for gallstone development after gastrectomy.

Exosomal miR-7002-5p derived from highglucose-induced macrophages suppresses autophagy in tubular epithelial cells by targeting Atg9b.

Macrophage infiltration plays an important role in the progression of diabetic nephropathy (DN). Previously, we demonstrated that highglucose-stimulated macrophage-derived exosomes (HG-exo) induces proliferation and extracellular matrix accumulation in glomerular mesangial cells, but its effect on tubular cells is unclear. This study aimed to explore the role of HG-exo on renal tubular injury in DN. The results show that HG-exo could induce dysfunction, autophagy inhibition, and inflammation in mouse tubular epithelial cell (mTEC) and C57 mouse kidney. Moreover, miR-7002-5p was differentially expressed in HG-exo based on miRNAs sequencing and bioinformatics analysis. A dual-luciferase reporter assay confirmed that Atg9b was the direct target gene of miR-7002-5p. Further experimentation showed that miR-7002-5p inhibition in vivo and vitro reserves HG-exo effects. These results demonstrated that HG-exo carries excessive miR-7002-5p and inhibits autophagy through targeting Atg9b; this process then induces renal tubular dysfunction and inflammation. In conclusion, our study clarifies the important role of macrophage-derived exosomes in DN and is expected to provide new insight on DN prevention and treatment.

Adjustable continence therapy (proACT) for the treatment of male stress urinary incontinence post-prostatectomy: a systematic review and meta-analysis (2023 update).

PURPOSE: Stress urinary incontinence (SUI) is a key factor for post-prostatectomy (RP) quality of life. Current international guidelines struggle to find the adequate place for each kind of surgeries. The aim of this systematic review and meta-analysis considering updated evidence is to assess the efficacy and safety of proACT in treating male patients with post-RP SUI. METHODS: A review of the literature was performed by searching the PubMed database. We narrowed included studies with adult male patients with SUI; outcomes included pads or pad weight per day and quality of life (QOL) questionnaires, as well as safety outcomes. RESULTS: 18 studies involving 1570 patients mean age of 68.8 (EC 2.1) were included. The mean follow-up reported was 34.7 months (EC 17.7; median 38.5; range 1-128 months). An average of 60.7% (EC 27) and 40.4% of patients suffered from mild-to-moderate and severe incontinence, respectively. The overall dryness rate was 55.1% (EC 19.3) while respecting the definition of 0-1 pads per day, and the mean dryness rate was 53% (EC 0.2). The mean overall complication rate was 31.2% (EC 18.3%), including an explantation rate of 26.5% (EC 15.3) and a reoperation rate of 22.7% (EC 8.7). The methodological quality of the 18 studies was very heterogeneous. CONCLUSION: Implantation of proACT adjustable balloons is a minimally invasive technique that provides medium outcomes (53%) with a strict definition of dryness (0-1 PPD) and important complication rate (31.2%). Past of irradiation is a negative predictive factor for incontinence.

Association Between Types of Loneliness and Risks of Functional Disability in Older Men and Women: A Prospective Analysis.

OBJECTIVE: To examine the association between types of loneliness (transient, incident, and chronic) and the risk of functional disability. METHODS: Data were from the Health and Retirement Study 2006/2008-2016/2018. A total of 7,148 adults aged ≥50 was included. Functional status was measured by activities of daily living (ADL) and instrumental activities of daily living (IADL). Loneliness was assessed using the 3-item UCLA Loneliness Scale. We defined loneliness as no/transient/incident/chronic loneliness based on the pattern and duration of loneliness across 2006/2008 and 2010/2012. We applied multivariate Cox proportional hazard models with the new-onset ADL/IADL disability as outcome. RESULTS: Overall, 69.3% respondents showed no loneliness; while 10.3%, 8.9%, and 11.5% showed transient, incident, and chronic loneliness, respectively. A total of 1,298 (18.16%) and 1,260 (17.63%) functionally normal respondents developed ADL and IADL disability during 36,294 person-years of follow-up, respectively. After adjusting for socio-demographic, behavioral, and health factors, chronic loneliness was associated with higher risks of ADL (hazard ratio [HR] = 1.37, 95% confidence interval [CI] = 1.16-1.63, p <0.001, χ2 = 3.60, degree of freedom [df] = 1) and IADL disability (HR = 1.25, 95% CI = 1.09-1.44, p = 0.002, χ2 = 3.17, df = 1) compared to no loneliness. By contrast, no significant associations between transient loneliness and ADL (HR = 1.17, 95% CI = 0.88-1.57, p = 0.273, χ2 = 1.10, df = 1) or IADL disability (HR = 1.16, 95% CI = 0.97-1.39, p = 0.112, χ2 = 1.59, df = 1) were found. Chronic loneliness was not associated with the risk of IADL disability in men (HR = 1.13, 95% CI = 0.91-1.40, p = 0.263, χ2 = 1.12, df = 1). CONCLUSION: Chronic loneliness, rather than transient loneliness, is an independent risk factor for functional disability in middle-aged and older adults, especially for women.

The application of "S.I.S" technique improves long-term continence after robotic radical prostatectomy.

AIMS: To propose a novel S.I.S technique during the robotic-assisted radical prostatectomy (RARP), encompassing pubourethral suspension, posterior wall intensification, and bladder neck stripping, and to present functional and oncological outcomes with a special focus on long-term continence. METHODS: From January 1, 2018, to December 31, 2019, consecutive patients who underwent RARP were retrospectively investigated and separated into the S.I.S group and the conventional group. Preoperative patient characteristics, tumor status, and perioperative parameters were collected, followed by the assessment of self-reported status on continence, using an International Consultation on Incontinence Modular Questionnaire-urinary incontinence short form (ICIQ-UI-SF). Statistical comparisons were performed on variables between the two surgery groups, and multivariate logistic regression analysis was used to determine predictive factors for postoperative incontinence severity. RESULTS: A total of 602 subjects were analyzed with a median follow-up of 24 months. There was no significant difference regarding baseline characteristics and perioperative parameters, except for a more advanced tumor stage in the S.I.S group. The application of the S.I.S technique did not jeopardize the positive surgical margin rate at the bladder neck or long-term tumor control. Notably, the patient-reported degree of incontinence was significantly reduced with the assistance of S.I.S technique, as evidenced by the diminished severe-to-very severe cases. On multivariate analysis, both preoperative body mass index and use of S.I.S modification were independent predictive factors for the long-term incontinence severity. CONCLUSIONS: The application of S.I.S technique during RARP is feasible and superior compare with the conventional approach, with a significantly alleviated long-term incontinence severity, without compromising cancer control.

Socioeconomic Status Disparities in Cognitive and Physical Functional Impairment among Older Adults: Comparison of Asians with other Major Racial/Ethnic Groups.

This study investigated to what extent socioeconomic status (SES) disparity associates with cognitive and physical impairment within older Asian Americans in comparison with other races/ethnicities. Data were from the National Health and Nutrition Examination Survey 2011-2018 that included 3,297 White, 1,755 Black, 1,708 Hispanic, and 730 Asian Americans aged ≥ 60. Physical functioning was measured by activities of daily living (ADL) or instrumental activities of daily living (IADL). Memory and language fluency were evaluated using the Alzheimer's Disease Word List Memory Task and Animal Fluency Tests, respectively. Multivariate logistic regressions were conducted to investigate the association between SES and physical and cognitive impairment within racial/ethnic groups, and seemingly unrelated regressions compared coefficients across subgroups. Asians with ≤ high school education had the highest prevalence of age- and sex-adjusted memory impairment among all races/ethnicities, while no difference was observed for those with > high school education. ADL/IADL disability odds did not differ between Asians and Whites, but Asians were more likely to exhibit impaired verbal fluency. Education disparity for ADL disability (OR, 3.40; 95% CI, 2.20-5.25) and memory impairment (OR, 11.57; 95% CI, 6.59-20.31) were largest among Asians compared to Whites, Blacks, and Hispanics. Income disparity for function impairment showed no significant difference across racial/ethnic groups (all P > 0.05). Asians experienced the highest burden of physical functioning and memory impairment due to education disparity. Efforts should focus on strengthening research infrastructure and creating targeted programs and services to improve cognitive and physical health for racially/ethnically underrepresented older adults with lower education attainment.

Design, synthesis and anti-tumor efficacy evaluation of novel 1,3-diaryl propane-based polyphenols obtained from Claisen rearrangement reaction.

Polyphenols such as resveratrol, honokiol and nordihydroguaiaretic acid are widely existing in nature products or synthetic compounds with interesting biological activities. Inspired by their structural feature, a total of 49 1,3-diaryl propane-based polyphenols were designed and synthesized through Claisen rearrangement reaction. New compounds were initially assessed for their anti-proliferative activities against various cancer cell lines (PC-3, U87MG, U251, HCT116) at a concentration of 50 µM, and the results guided the SAR of this series of compounds. Further screening of selected compounds against seven cancer cell lines (three additional colon cancer cell lines namely COLO205, HT29 and SW480 were chosen) led to the identification of two advanced leads 2t and 3t with IC50 values ranging from 8.2 ± 0.1 to 19.3 ± 1.9 µM. Both compounds also showed promising anti-proliferative activities against COLO205 in dose- and time-dependent manners. Furthermore, 2t and 3t exhibited good anti-tumor efficacy in COLO205 xenografted mice model with TGI values ranging from 38% to 58%. These results warrant the further investigation of this series of compounds.

Building up a view and understanding of the multifunctional activity of black phosphorous nanosheet modified with the metal atom.

Constructing metal-semiconductor interfaces by loading metal atoms onto two-dimensional material to build atomically dispersed single-atom catalysts (SACs) has emerged as a new frontier for improving atom utilization and designing multifunctional electrocatalysts. Nowadays, studies on black phosphorus nanosheets in electrocatalysis have received much attention and the successful preparation of metal nanoparticle/black phosphorus (BP) hybrid electrocatalysts indicates BP nanosheets can serve as a potential support platform for SACs. Herein, by using large-scale ab initio calculations, we explored a large composition space of SACs with transition metal atoms supported on BP monolayer (M-BP) and built a comprehensive picture of activity trend, stability, and electronic origin towards oxygen reduction and evolution reaction (ORR and OER) and hydrogen evolution reaction (HER). The results show that the catalytic activity can be widely tuned by reasonable regulation of metal atoms. Ni-, Pd-, and Pt-BP could effectively balance the binding strength of the target intermediates, thus achieving efficient bifunctional activity for OER and ORR. Favorable bifunctional catalytic performance for OER and HER can be realized on Rh-BP. Especially, Pt-BP exhibits promising trifunctional activity towards OER, ORR, and HER. Multiple-level corrections among overpotential, Gibbs free energy, orbital population, and d-band center reveal that the trend and origin of catalytic activity are intrinsically determined by the d-band center of metal sites. The thermodynamic and dynamic stability simulations demonstrate that the active metal centers are firmly anchored on BP substrate with intact M-P bonds. These findings provide a theoretical basis for the rational design of BP-based SACs toward promising multifunctional activity.

Beijing Children's Hospital guidelines on the design and conduction of the first standardized database for medulloblastoma.

Medulloblastoma (MB) is one of the most common malignant childhood brain tumors (WHO grade IV). Its high degree of malignancy leads to an unsatisfactory prognosis, requiring more precise and personalized treatment in the near future. Multi-omics and artificial intelligence have been playing a significant role in precise medical research, but their implementation needs a large amount of clinical information and biomaterials. For these reasons, it is urgent for current MB researchers to establish a large sample-size database of MB that contains complete clinical data and sufficient biomaterials such as blood, cerebrospinal fluid (CSF), cancer tissue, and urine. Unfortunately, there are few biobanks of pediatric central nervous system (CNS) tumors throughout the world for limited specimens, scarce funds, different standards collecting methods and et cl. Even though, China falls behind western countries in this area. The present research set up a standard workflow to construct the Beijing Children's Hospital Medulloblastoma (BCH-MB) biobank. Clinical data from children with MB and for collecting and storing biomaterials, along with regular follow-up has been collected and recorded in this database. In the future, the BCH-MB biobank could make it possible to validate the promising biomarkers already identified, discover unrevealed MB biomarkers, develop novel therapies, and establish personalized prognostic models for children with MB upon the support of its sufficient data and biomaterials, laying the foundation for individualized therapies of children with MB.

Correlation between physical activity and adolescent idiopathic scoliosis: a systematic review.

BACKGROUND: The multifactorial aetiology of scoliosis is well known. Physical activity is considered both a treatment and causative factor for idiopathic scoliosis; however, evidence for a causal relationship between physical activity levels and idiopathic scoliosis in adolescents is conflicting. Therefore, we aimed to summarise the current evidence regarding the association between adolescent idiopathic scoliosis and physical activity and further to assess whether the relationship is dose dependent. METHODS: PubMed, Cochrane, Scopus, and Web of Science databases were searched from 1991 to July 2022 using the following main keywords: adolescent idiopathic scoliosis, physical activity, and risk factors, supplemented with manual searches, secondary citations, and reference searches. The quality of the included literature was evaluated using the Scale for Reporting Observational Studies in Enhanced Epidemiology guidelines. RESULTS: Eight studies were included in this review, of which six reported an association between adolescent idiopathic scoliosis and physical activity levels and two reported no association. One British study reported reduced physical function early in life as a new risk factor for scoliosis onset. CONCLUSIONS: Physical activity is strongly associated with adolescent idiopathic scoliosis. Physical activity should be encouraged as it plays an important role in the prevention of adolescent idiopathic scoliosis. Further research is needed to determine the dose-dependent relationship between physical activity and prevention of adolescent idiopathic scoliosis.