Spatial response of water level and quality shows more significant heterogeneity during dry seasons in large river-connected lakes.

The spatial response mechanism of hydrology and water quality of large river-connected lakes is very complicated. In this study, we developed a spatial response analysis method that couples wavelet correlation analysis (WTC) with self-organizing maps (SOM), revealing the spatial response and variation of water level and water quality in Poyang Lake, China's largest river-connected lake, over the past decade. The results show that: (1) there was significant spatial heterogeneity in water level and quality during the dry seasons (2010-2018) compared to other hydrological stages. (2) We identified a more pronounced difference in response of water level and quality between northern and southern parts of Poyang Lake. As the distance increases from the northern lake outlet, the impact of rising water levels on water quality deterioration intensified during the dry seasons. (3) The complex spatial heterogeneity of water level and quality response in the dry seasons is primarily influenced by water level fluctuations from the northern region and the cumulative pollutant entering the lake from the south, which particularly leads to the reversal of the response in the central area of Poyang Lake. The results of this study can contribute to scientific decision-making regarding water environment zoning management in large river-connected lakes amidst complex environment conditions.

Seasonal dynamics and typology of microplastic pollution in Huixian karst wetland groundwater: Implications for ecosystem health.

This study offers an insightful and detailed examination of microplastic pollution in the Huixian karst wetland's groundwater, providing novel insights into the complex interplay of microplastic characteristics and their seasonal dynamics. We meticulously quantified microplastic concentrations, observing significant seasonal variation with values ranging from 4.9 to 13.4 n·L-1 in the wet season and 0.53-49.4 n·L-1 in the dry season. Our analysis pinpoints human activities and atmospheric deposition as key contributors to this contamination. A critical finding of our research is the pronounced disparity in microplastic levels between open wells and covered artesian wells, highlighting the vulnerability of open wells to higher pollution levels. Through correlation analysis, we unearthed the crucial influence of the karst region's unique hydrogeological characteristics on microplastic migration, distinctively different from non-karst areas. The karst terrain, characterized by its caves and subterranean rivers, facilitates the downward movement of microplastics from surface to groundwater, exacerbating pollution levels. Our investigation identifies agricultural runoff and domestic wastewater as primary pollution sources. These findings not only underscore the urgent need for environmental stewardship in karst regions but also provide a crucial foundation for formulating effective strategies to mitigate microplastic pollution in karst groundwater. The implications of this study extend beyond the Huixian karst wetland, offering a template for addressing microplastic pollution in similar ecosystems globally.

Cinnamaldehyde: an effective component of Cinnamomum cassia inhibiting Helicobacter pylori.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Presl (Cinnamomum cassia) is a common traditional Chinese medicine, which can promote the secretion and digestion of gastric juice, improve the function of gastrointestinal tract. Cinnamaldehyde (CA) is a synthetic food flavoring in the Chinese Pharmacopoeia. AIM OF THE STUDY: This study aimed to search for the active ingredient (CA) of inhibiting H. pylori from Cinnamomum cassia, and elucidate mechanism of action, so as to provide the experimental basis for the treatment of H. pylori infection with Cinnamomum cassia. MATERIALS AND METHODS: It's in vitro and in vivo pharmacological properties were evaluated based on minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and an acute gastric inflammation model in mice infected with H. pylori. Drug safety was evaluated using the CCK8 method and high-dose administration in mice. The advantageous characteristics of CA in inhibiting H. pylori were confirmed using acidic conditions and in combination with the antibiotics. The mechanism underlying the action of CA on H. pylori was explored using scanning electron microscopy (SEM), adhesion experiments, biofilm inhibition tests, ATP and ROS release experiments, and drug affinity responsive target stability (DARTS) screening of target proteins. The protein function and target genes were verified by molecular docking and Real-Time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The results demonstrated that CA was found to be the main active ingredient against H. pylori in Cinnamomum cassia in-vitro tests, with a MIC of 8-16 µg/mL. Moreover, CA effectively inhibited both sensitive and resistant H. pylori strains. The dual therapy of PPI + CA exhibited remarkable in vivo efficacy in the acute gastritis mouse model, superior to the standard triple therapy. DARTS, molecular docking, and qRT-PCR results suggested that the target sites of action were closely associated with GyrA, GyrB, AtpA, and TopA, which made DNA replication and transcription impossible, then leading to inhibition of bacterial adhesion and colonization, suppression of biofilm formation, and inhibition ATP and enhancing ROS. CONCLUSIONS: This study demonstrated the suitability of CA as a promising lead drug against H. pylori, The main mechanisms can target GyrA ect, leading to reduce ATP and produce ROS, which induces the apoptosis of bacterial.

Suboptimal peak inspiratory flow rate: a noticeable risk factor for inhaler concordance in patients with chronic airway diseases.

BACKGROUND: Inhaler concordance and the peak inspiratory flow rate (PIFR) are important determinants of treatment effects in patients with chronic airway diseases. Adequate PIFR is required for driving aerosol medication into the lower respiratory tract. However, the relationship between them has not been discussed previously. This study aimed to describe the characteristics of inhaler concordance and PIFR in Chinese patients with chronic airway diseases and discuss the associated variables and the relationship between them. METHODS: In this single-centre, observational study, a total of 680 patients with chronic airway diseases were enrolled from July 2021 to April 2023. We collected data on the socio-demographic and clinical variables of inhaler concordance using the test of adherence to inhalers (TAI) and PIFR. Multivariate logistic regression was conducted to examine variables related to inhaler concordance and PIFR. RESULTS: A total of 49.4% of patients had low concordance. Patients with chronic obstructive pulmonary disease (COPD) were more concordant than patients with asthma (mean TAI score: 43.60 vs 41.20; p<0.01), while there was no difference in concordance between the asthma-COPD overlap group and the asthma or COPD group. Suboptimal PIFR (adjusted OR, 1.61; 95% CI 1.04 to 2.51) increased the risk of poor concordance among all patients, while triple therapy (adjusted OR, 0.60; 95% CI 0.35 to 0.86) reduced the risk. A total of 54.9% of patients had suboptimal PIFR. Older age, lower educational level, use of dry powder inhalers and lower forced expiratory volume in 1 s % predicted were significantly correlated with insufficient PIFR. Subgroup analysis revealed a greater proportion of patients with insufficient PIFR during exacerbation than during the stable phase (61.7% vs 43.5%, p<0.001). CONCLUSION: Inhaler concordance was low, and suboptimal PIFR was a risk factor for poor concordance among Chinese patients with chronic airway diseases. In addition, current inhalation devices may not be suitable, and PIFR reassessment should be considered for patients with COPD during exacerbation. TRIAL REGISTRATION NUMBER: The study was registered in chictr.org.cn (ChiCTR2100052527) on 31 October 2021.

Glucose regulation of adipose tissue browning by CBP/p300- and HDAC3-mediated reversible acetylation of CREBZF.

Glucose is required for generating heat during cold-induced nonshivering thermogenesis in adipose tissue, but the regulatory mechanism is largely unknown. CREBZF has emerged as a critical mechanism for metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). We investigated the roles of CREBZF in the control of thermogenesis and energy metabolism. Glucose induces CREBZF in human white adipose tissue (WAT) and inguinal WAT (iWAT) in mice. Lys208 acetylation modulated by transacetylase CREB-binding protein/p300 and deacetylase HDAC3 is required for glucose-induced reduction of proteasomal degradation and augmentation of protein stability of CREBZF. Glucose induces rectal temperature and thermogenesis in white adipose of control mice, which is further potentiated in adipose-specific CREBZF knockout (CREBZF FKO) mice. During cold exposure, CREBZF FKO mice display enhanced thermogenic gene expression, browning of iWAT, and adaptive thermogenesis. CREBZF associates with PGC-1α to repress thermogenic gene expression. Expression levels of CREBZF are negatively correlated with UCP1 in human adipose tissues and increased in WAT of obese ob/ob mice, which may underscore the potential role of CREBZF in the development of compromised thermogenic capability under hyperglycemic conditions. Our results reveal an important mechanism of glucose sensing and thermogenic inactivation through reversible acetylation.

Genome-Wide Identification of PYL/RCAR ABA Receptors and Functional Analysis of LbPYL10 in Heat Tolerance in Goji (Lycium barbarum).

The characterization of the PYL/RCAR ABA receptors in a great deal of plant species has dramatically advanced the study of ABA functions involved in key physiological processes. However, the genes in this family are still unclear in Lycium (Goji) plants, one of the well-known economically, medicinally, and ecologically valuable fruit crops. In the present work, 12 homologs of Arabidopsis PYL/RCAR ABA receptors were first identified and characterized from Lycium (L.) barbarum (LbPYLs). The quantitative real-time PCR (qRT-PCR) analysis showed that these genes had clear tissue-specific expression patterns, and most of them were transcribed in the root with the largest amount. Among the three subfamilies, while the Group I and Group III members were down-regulated by extraneous ABA, the Group II members were up-regulated. At 42 °C, most transcripts showed a rapid and violent up-regulation response to higher temperature, especially members of Group II. One of the genes in the Group II members, LbPYL10, was further functionally validated by virus-induced gene silencing (VIGS) technology. LbPYL10 positively regulates heat stress tolerance in L. barbarum by alleviating chlorophyll degradation, thus maintaining chlorophyll stability. Integrating the endogenous ABA level increase following heat stress, it may be concluded that LbPYL-mediated ABA signaling plays a vital role in the thermotolerance of L. barbarum plants. Our results highlight the strong potential of LbPYL genes in breeding genetically modified L. barbarum crops that acclimate to climate change.

Evaluating the efficacy and safety of Alzheimer's disease drugs: A meta-analysis and systematic review.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and daily living ability. Currently, there are not many drugs that can be selected to treat mild to moderate AD, and the value of drugs remains controversial. OBJECTIVE: The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) in the treatment of patients with AD. Additionally, molecular docking analysis will be used to investigate the binding affinities of donepezil, galantamine, rivastigmine, and memantine with key receptor proteins associated with AD, including beta-amyloid (Abeta), microtubule-associated protein (MAP), apolipoprotein E4 (APOE4), and Mitofusin-2 (MFN2), to further validate the results of the meta-analysis. METHODS: We obtained clinical trials characterized by randomization, placebo control, and double-blinded methodologies concerning ChEIs, memantine, and GV-971. Statistical analysis was performed using Review Manager Version 5.4 software. Molecular docking was also conducted to evaluate the results. RESULTS: All drugs improved the cognitive function, with the effect value ranging from -1.23 (95% CI -2.17 to -0.30) for 20 mg memantine to -3.29 (95% CI -4.14 to -2.45) for 32 mg galantamine. Although 32 mg galanthamine and GV-971 did not improve the clinicians' Global Impression of Change scale, other drugs showed significant results compared with placebo. On NPI, only 10 mg of donepezil and 24 mg of galantamine had improvement effects. On ADCS/ADL, only 20 mg memantine and 900 mg GV-971 had no significant difference from the placebo. Donepezil 5 mg and GV-971 900 mg did not increase the drug withdrawal rates due to various reasons or adverse reactions when compared to the placebo. Donepezil demonstrated superior binding to the protein and exhibited greater efficacy compared to other drugs. CONCLUSION: ChEIs, memantine, and GV-971 all can slow the progression of AD but have different effects on respective assessments. Donepezil and GV-971 were relatively well tolerated.

Lymph node targeting strategy using a hydrogel sustained-release system to load effector memory T cells improves the anti-tumor efficacy of anti-PD-1.

Communication between tumors and lymph nodes carries substantial significance for antitumor immunotherapy. Remodeling the immune microenvironment of tumor-draining lymph nodes (TdLN) plays a key role in enhancing the anti-tumor ability of immunotherapy. In this study, we constructed a biomimetic artificial lymph node structure composed of F127 hydrogel loading effector memory T (TEM) cells and PD-1 inhibitors (aPD-1). The biomimetic lymph nodes facilitate the delivery of TEM cells and aPD-1 to the TdLN and the tumor immune microenvironment, thus realizing effective and sustained anti-tumor immunotherapy. Exploiting their unique gel-forming and degradation properties, the cold tumors were speedily transformed into hot tumors via TEM cell supplementation. Meanwhile, the efficacy of aPD-1 was markedly elevated compared with conventional drug delivery methods. Our finding suggested that the development of F127@TEM@aPD-1 holds promising potential as a future novel clinical drug delivery technique. STATEMENT OF SIGNIFICANCE: F127@TEM@aPD-1 show unique advantages in cancer treatment. When injected subcutaneously, F127@TEM@aPD-1 can continuously supplement TEM cells and aPD-1 to tumor draining lymph nodes (TdLN) and the tumor microenvironment, not only improving the efficacy of ICB therapy through slow release, but also exhibiting dual regulatory effects on the tumor and TdLN.

The additive effect of metabolic syndrome on left ventricular impairment in patients with obstructive coronary artery disease assessed by 3.0 T cardiac magnetic resonance feature tracking.

BACKGROUND: Metabolic syndrome (MetS) can increase the risk of morbidity and mortality of cardiovascular disease and obstructive coronary artery disease (OCAD), which usually have a poor prognosis. This study aimed to explore the impact of MetS on left ventricular (LV) deformation and function in OCAD patients and investigate the independent factors of impaired LV function and deformation. MATERIALS AND METHODS: A total of 121 patients with OCAD and 52 sex- and age-matched controls who underwent cardiac magnetic resonance scanning were enrolled in the study. All OCAD patients were divided into two groups: OCAD with MetS [OCAD(MetS+), n = 83] and OCAD without MetS [OCAD(MetS-), n = 38]. LV functional and global strain parameters were measured and compared among the three groups. Multivariable linear regression analyses were constructed to investigate the independent factors of LV impairment in OCAD patients. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to test the prediction efficiency of MetS for LV impairment. RESULTS: From controls to the OCAD(MetS-) group to the OCAD(MetS+) group, LV mass (LVM) increased, and LV global function index (LVGFI) and LV global longitudinal peak strain (GLPS) decreased (all p < 0.05). Compared with the OCAD(MetS-) group, the LV GLPS declined significantly (p = 0.027), the LVM increased (p = 0.006), and the LVGFI decreased (p = 0.043) in the OCAD(MetS+) group. After adjustment for covariates in OCAD patients, MetS was an independent factor of decreased LV GLPS (ß = - 0.211, p = 0.002) and increased LVM (ß = 0.221, p = 0.003). The logistic multivariable regression analysis and ROC analysis showed that combined MetS improved the efficiency of predicting LV GLPS reduction (AUC = 0.88) and LVM (AUC = 0.89) increase. CONCLUSIONS: MetS aggravated the damage of LV deformation and function in OCAD patients and was independently associated with LV deformation and impaired LV strain. Additionally, MetS increased the prediction efficiency of increased LVM and decreased LV GLPS. Early detection and intervention of MetS in patients with OCAD is of great significance.

Homologous-magnetic dual-targeted metal-organic framework to improve the Anti-hepatocellular carcinoma efficacy of PD-1 inhibitor.

The insufficient abundance and weak activity of tumour-infiltrating lymphocytes (TILs) are two important reasons for the poor efficacy of PD-1 inhibitors in hepatocellular carcinoma (HCC) treatment. The combined administration of tanshinone IIA (TSA) and astragaloside IV (As) can up-regulate the abundance and activity of TILs by normalising tumour blood vessels and reducing the levels of immunosuppressive factors respectively. For enhancing the efficacy of PD-1 antibody, a magnetic metal-organic framework (MOF) with a homologous tumour cell membrane (Hm) coating (Hm@TSA/As-MOF) is established to co-deliver TSA&As into the HCC microenvironment. Hm@TSA/As-MOF is a spherical nanoparticle and has a high total drug-loading capacity of 16.13 wt%. The Hm coating and magnetic responsiveness of Hm@TSA/As-MOF provide a homologous-magnetic dual-targeting, which enable Hm@TSA/As-MOF to counteract the interference posed by ascites tumour cells and enhance the precision of targeting solid tumours. Hm coating also enable Hm@TSA/As-MOF to evade immune clearance by macrophages. The release of TSA&As from Hm@TSA/As-MOF can be accelerated by HCC microenvironment, thereby up-regulating the abundance and activity of TILs to synergistic PD-1 antibody against HCC. This study presents a nanoplatform to improve the efficacy of PD-1 inhibitors in HCC, providing a novel approach for anti-tumour immunotherapy in clinical practice.

Inhibition of SUV39H1 reduces tumor angiogenesis via Notch1 in oral squamous cell carcinoma.

Targeting tumor angiogenesis is an important approach in advanced tumor therapy. Here we investigated the effect of the suppressor of variegation 3-9 homolog 1 (SUV39H1) on tumor angiogenesis in oral squamous cell carcinoma (OSCC). The GEPIA database was used to analyze the expression of SUV39H1 in various cancer tissues. The expression of SUV39H1 in OSCC was detected by immunohistochemistry, and the correlation between SUV39H1 and Notch1 and microvascular density (MVD) was analyzed. The effect of SUV39H1 inhibition on OSCC was investigated in vivo by chaetocin treatment. The migration and tube formation of vascular endothelial cells by conditioned culture-medium of different treatments of oral squamous cell cells were measured. The transcriptional level of SUV39H1 is elevated in various cancer tissues. The transcription level of SUV39H1 in head and neck squamous cell carcinoma was significantly higher than that in control. Immunohistochemistry result showed increased SUV39H1 expression in OSCC, which was significantly correlated with T staging. The expression of SUV39H1 was significantly correlated with Notch1 and CD31. In vivo experiment chaetocin treatment significantly inhibit the growth of tumor, and reduce SUV39H1, Notch1, CD31 expression. The decreased expression of SUV39H1 in OSCC cells lead to the decreased expression of Notch1 and VEGF proteins, as well as the decreased migration and tube formation ability of vascular endothelial cells. Inhibition of Notch1 further enhance this effect. Our results suggest inhibition of SUV39H1 may affect angiogenesis by regulating Notch1 expression. This study provides a foundation for SUV39H1 as a potential therapeutic target for OSCC.

Carboxyl-terminal sequences in APOA5 are important for suppressing ANGPTL3/8 activity.

Apolipoprotein AV (APOA5) lowers plasma triglyceride (TG) levels by binding to the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and suppressing its capacity to inhibit lipoprotein lipase (LPL) catalytic activity and its ability to detach LPL from binding sites within capillaries. However, the sequences in APOA5 that are required for suppressing ANGPTL3/8 activity have never been defined. A clue to the identity of those sequences was the presence of severe hypertriglyceridemia in two patients harboring an APOA5 mutation that truncates APOA5 by 35 residues ("APOA5Δ35"). We found that wild-type (WT) human APOA5, but not APOA5Δ35, suppressed ANGPTL3/8's ability to inhibit LPL catalytic activity. To pursue that finding, we prepared a mutant mouse APOA5 protein lacking 40 C-terminal amino acids ("APOA5Δ40"). Mouse WT-APOA5, but not APOA5Δ40, suppressed ANGPTL3/8's capacity to inhibit LPL catalytic activity and sharply reduced plasma TG levels in mice. WT-APOA5, but not APOA5Δ40, increased intracapillary LPL levels and reduced plasma TG levels in Apoa5-/- mice (where TG levels are high and intravascular LPL levels are low). Also, WT-APOA5, but not APOA5Δ40, blocked the ability of ANGPTL3/8 to detach LPL from cultured cells. Finally, an antibody against a synthetic peptide corresponding to the last 26 amino acids of mouse APOA5 reduced intracapillary LPL levels and increased plasma TG levels in WT mice. We conclude that C-terminal sequences in APOA5 are crucial for suppressing ANGPTL3/8 activity in vitro and for regulating intracapillary LPL levels and plasma TG levels in vivo.

Weakened hydrological oscillation period increased the frequency of river algal blooms.

The evolution of riverine aquatic ecosystems typically exhibits notable characteristic with cumulative, enduring, and hysteresis. Exploring the non-linear response of riverine ecology to long-term hydrological fluctuations become a major challenge in contemporary interdisciplinary research. In response to the critical issue of frequent river algal blooms in the lower Han River, which is impacted by Asian largest inter-basin water diversion project. We identified the non-linear response of eco-hydrology across various time scales through the integration of Continuous Wavelet Transform (CWT) and Inverse Wavelet Transform (IWT). Our study revealed that: 1) Over the past half century, the hydrological regime in the lower Han river showed a significant downward trend, and existed three significant hydrological oscillation periods (HOPs), including the short-scale Intra-AC (180 days), the medium-scale AC (365 days, the first major period), and the long-scale Inter-AC (2500 days), the variation of Inter-AC changed most dramatically. 2) We further found that the Inter-AC variation of hydrology is more closely related to the formation of river algal blooms in the Han River, and when the hydrological Inter-AC shows steady state or downward trend, the frequency of algal blooms in the lower Han River increases significantly. 3) The river algal blooms in the lower Han River is a cumulative consequence to the long-term hydrological influences. Weakened hydrological Inter-AC is more likely to increase the frequency of river algal blooms, and 10-years Inter-AC cumulation increased the frequency by 60%. Therefore, the weaken of long-scale HOP will significantly increase the frequency of river algal blooms in the future. This study received a critical scientific insight and aimed at provide guidance for the optimization of ecological management within the framework of national large-scale water conservation.

Extracorporeal vs. conventional CPR for out-of-hospital cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a significant cause of mortality and morbidity worldwide. Extracorporeal cardiopulmonary resuscitation (ECPR) is a potential intervention for OHCA, but its effectiveness compared to conventional cardiopulmonary resuscitation (CCPR) needs further evaluation. METHOD: We systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and ClinicalTrials.gov for relevant studies from January 2010 to March 2023. Pooled meta-analysis was performed to investigate any potential association between ECPR and improved survival and neurological outcomes. RESULTS: This systematic review and meta-analysis included two randomized controlled trials enrolling 162 participants and 10 observational cohort studies enrolling 4507 participants. The pooled meta-analysis demonstrated that compared to CCRP, ECPR did not improve survival and neurological outcomes at 180 days following OHCA (RR: 3.39, 95% CI: 0.79 to 14.64; RR: 2.35, 95% CI: 0.97 to 5.67). While a beneficial effect of ECPR was obtained regarding 30-day survival and neurological outcomes. Furthermore, ECPR was associated with a higher risk of bleeding complications. Subgroup analysis showed that ECPR was prominently beneficial when exclusively initiated in the emergency department. Additional post-resuscitation treatments did not significantly impact the efficacy of ECPR on 180-day survival with favorable neurological outcomes. CONCLUSIONS: There is no high-quality evidence supporting the superiority of ECPR over CCPR in terms of survival and neurological outcomes in OHCA patients. However, due to the potential for bias, heterogeneity among studies, and inconsistency in practice, the non-significant results do not preclude the potential benefits of ECPR. Further high-quality research is warranted to optimize ECPR practice and provide more generalizable evidence. Clinical trial registration PROSPERO, https://www.crd.york.ac.uk/prospero/, registry number: CRD42023402211.

Cu(I)-Catalyzed Three-Component Annulation for the Synthesis of 3-Acyl Imidazo[1, 5-a]Pyridines from 2-Pyridinyl-Substituted p-Quinone Methides, Terminal Alkynes, and TsN3 Using O2 as the Oxygen Source.

Currently, most conventional methods to achieve imidazo[1,5-a]pyridines have limitations for the synthesis of 3-acyl imidazo[1,5-a]pyridines. Herein, a novel and efficient Cu(I)-catalyzed three-component annulation method for the synthesis of valuable 3-acyl imidazo[1,5-a]pyridines by the reaction of 2-pyridinyl-substituted p-QMs, terminal alkynes, and TsN3 in the presence of O2 under mild conditions have successfully been developed. The investigation indicated that molecular oxygen (O2) and TsN3, respectively, serving as oxygen and nitrogen sources, were essential for the successful completion of the reaction system.

Palladium-Catalyzed Asymmetric Decarboxylation of 5-Vinyloxazolidine-2,4-Diones Triggering the Dearomatization of Electron-Deficient Indoles for the Synthesis of Chiral Highly Functionalized Pyrroloindolines.

A catalyst system consisting of a chiral phosphoramidite ligand and Pd2(dba)3·CHCl3 causes the decarboxylation of 5-vinyloxazolidine-2,4-diones to generate amide-containing aza-π-allylpalladium 1,3-dipole intermediates, which are capable of triggering the dearomatization of 3-nitroindoles for diastereo- and enantioselective [3+2] cycloaddition, leading to the formation of a series of highly functionalized pyrroloindolines containing three contiguous stereogenic centers with excellent results (up to 99% yield, 88:12 dr, and 96% ee).

Comparative in vitro toxicological effects of water-soluble and insoluble components of atmospheric PM2.5 on human lung cells.

Fine particulates in city air significantly impact human health, but the hazardous compositional mechanisms are still unclear. Besides the toxicity of environmental PM2.5 to in vitro human lung epithelial cells (A549), the independent cytotoxicity of PM2.5-bound water-soluble (WS-PM2.5) and water-insoluble (WIS-PM2.5) fractions were also compared by cell viability, oxidative stress (reactive oxygen species, ROS), and inflammatory injury (IL-6 and TNF-α). The cytotoxicity of PM2.5 varied significantly by sampling season and place, with degrees greater in winter and spring than in summer and autumn, related to corresponding trend of air PM2.5 level, and also higher in industrial than urban site, although their PM2.5 pollution levels were comparable. The PM2.5 bound metals (Ni, Cr, Fe, and Mn) may contribute to cellular injury. Both WS-PM2.5 and WIS-PM2.5 posed significant cytotoxicity, that WS-PM2.5 was more harmful than WIS-PM2.5 in terms of decreasing cell viability and increasing inflammatory cytokines production. In particular, industrial samples were usually more toxic than urban samples, and those from summer were generally less toxic than other seasons. Hence, in order to mitigate the health risks of PM2.5 pollution, the crucial targets might be components of heavy metals and soluble fractions, and sources in industrial areas, especially during the cold seasons.

High Performance Nacre Fibers by Engineering Interfacial Entanglement.

Biological materials exhibit fascinating mechanical properties for intricate interactions at multiple interfaces to combine superb toughness with wondrous strength and stiffness. Recently, strong interlayer entanglement has emerged to replicate the powerful dissipation of natural proteins and alleviate the conflict between strength and toughness. However, designing intricate interactions in a strong entanglement network needs to be further explored. Here, we modulate interlayer entanglement by introducing multiple interactions, including hydrogen and ionic bonding, and achieve ultrahigh mechanical performance of graphene-based nacre fibers. Two essential modulating trends are directed. One is modulating dynamic hydrogen bonding to improve the strength and toughness up to 1.58 GPa and 52 MJ/m3, simultaneously. The other is tailoring ionic coordinating bonding to raise the strength and stiffness, reaching 2.3 and 253 GPa. Modulating various interactions within robust entanglement provides an effective approach to extend performance limits of bioinspired nacre and optimize multiscale interfaces in diverse composites.

MODY Probability Calculator Is Suitable for MODY Screening in China: A Population-based Study.

Context: Selecting appropriate individuals for genetic testing is essential due to the optimal treatment for maturity-onset diabetes of the young (MODY). However, how to effectively screen for MODY in China remains unclear. Objective: To validate the performance of current screening strategies in selecting patients with MODY based on a nationwide type 2 diabetes cohort. Methods: A panel of 14 MODY genes was analyzed from 1911 type 2 diabetes patients who were ages 15 to 35 years. Variants were evaluated according to the American College of Medical Genetics and Genomics guidelines. Based on this cohort, we simulated the 2 most frequently used screening strategies, including the traditional MODY criteria and the MODY probability calculator (MPC), to assess their ability to select patients with MODY. Results: From a total of 1911 participants, 42 participants harbored pathogenic/likely pathogenic variants. The performance of the traditional criteria was sensitivity: 19.0%, specificity: 72.9%, positive predictive value (PPV): 1.6%, and missing rate: 81.0%. The optimal cut-off for MPC was 40.7%. Based on this cut-off value, the performance was sensitivity: 54.8%, specificity: 81.0%, PPV: 6.1%, and missing rate: 45.2%. Moreover, hemoglobin A1c, insulin treatment, and family history of diabetes have poor discrimination between MODY and young-onset type 2 diabetes. Conclusion: The MPC is better than traditional criteria in terms of both sensitivity and PPV. To ensure more MODY patients benefit from optimal treatment, we therefore suggest that routine genetic testing be performed on all type 2 diabetes patients who are between the ages of 15 and35 years and have MPC probability value over 40.7%.