Chirality-Mediated 1D-to-2D Phase Transition in Hybrid Lead Halide Perovskites.

Dimensionality engineering plays a pivotal role in optimizing the performance, ensuring long-term stability, and expanding the versatile applications of lead halide perovskites (LHPs). Currently, the manipulation of LHP dimensions primarily occurs during the synthesis stage, a procedure hampered by constraints, including synthetic complexity and irreversibility. This investigation successfully achieved a transition from one-dimensional (1D) to two-dimensional (2D) structures in chiral LHPs by applying hydrostatic pressure. Remarkably, this pressure-induced transition in dimensionality is absent in the racemic analogue due to the staggered arrangement of inorganic chains and the elevated steric hindrance posed by the organic cations. Notably, the hydrogen bonding between organic cations and the inorganic framework adopts a symmetrical arrangement in the racemic system but a helical configuration along the 1D chain direction in the chiral counterparts. This distinct helical arrangement induces a consequential distortion in the inorganic moiety, resulting in the emergence of a spin-polarized Rashba-Dresselhaus texture that explains the chirality's electronic spin origin. Furthermore, both experimental and density functional theory calculation results demonstrate that the 1D-to-2D phase transition in chiral halide perovskites can induce significant modifications in the electronic structures and associated optical emissions. In summary, the findings unveil novel avenues for manipulating optoelectronic properties in chiral perovskites through dimensionality engineering.

Response Mechanism of Extracellular Polymeric Substances Synthesized by Alternaria sp. on Drought Stress in Alfalfa (Medicago sativa L.).

This study investigates how extracellular polymeric substances (EPS) synthesized by dark septate endophytic (DSE) improve alfalfa's drought resistance. Drought stress was simulated in hydroponic culture, and roots were treated with different EPS concentrations to determine their effects on drought tolerance and applicable concentrations. Hydroponic solutions with 0.25 and 0.50% EPS concentrations alleviated leaf wilting and increased total plant fresh weight by 35.8 and 57.7%, respectively. SEM shows that EPS attached to the roots and may have served to protect the root system. EPS treatment significantly depressed the MDA contents of the roots, stems, and leaves. Roots responded to drought stress by increasing soluble sugar contents and antioxidant enzyme activities, while mitigating stem and leaf stress by synthesizing lipid compounds, amino acids, and organic acid metabolites. Five metabolites in the stem have been reported to be associated with plant stress tolerance and growth, namely 3-O-methyl 5-O-(2-methyl propyl) (4S)-2,6-dimethyl-4-(2-nitrophenyl)-3,4-dihydropyridine-3,5-dicarboxylate, malic acid, PA (20:1(11Z)/15:0), N-methyl-4,6,7-trihydroxy-1,2,3,4-tetrahydroisoquinoline, and 2-(S-glutathionyl) acetyl glutathione. In summary, EPS treatment induced oxidative stress and altered plant metabolism, and this in turn increased plant antioxidant capacity. The results provide a theoretical basis for the application of EPS in commercial products that increase plant resistance and ecological restoration.

Preparation and study of a capillary electrochromatographic column prepared by conjugating ß-CD COFs and gold-poly glycidyl methacrylate nanoparticles.

A new enantioselective open-tubular capillary electrochromatography (OT-CEC) was developed employing ß-cyclodextrin covalent organic frameworks (ß-CD COFs) conjugated gold-poly glycidyl methacrylate nanoparticles (Au-PGMA NPs) as a stationary phase. The resulting coating layer on the inner wall of the fabricated capillary column was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), energy dispersive spectroscopy (EDS), and electroosmotic flow (EOF) experiments. The performance of the fabricated capillary column was evaluated by CEC using enantiomers of seven model analytes, including two proton pump inhibitors (PPIs, omeprazole and tenatoprazole), three amino acids (AAs, tyrosine, phenylalanine, and tryptophan), and two fluoroquinolones (FQs, gatifloxacin and sparfloxacin). The influences of coating time, buffer concentration, buffer pH, and applied voltage on enantioseparation were investigated to obtain satisfactory enantioselectivity. In the optimum conditions, the enantiomers of seven analytes were fully resolved within 10 min with high resolutions of 3.03 to 5.25. The inter- to intra-day and column-to-column repeatabilities of the fabricated capillary column were lower than 4.26% RSD. Furthermore, molecular docking studies were performed based on the chiral fabricated column and as ligand isomers of analytes using Auto Dock Tools. The binding energies and interactions acquired from docking results of analytes supported the experimental data.

A high-affinity, cis-on photoswitchable beta blocker to optically control ß2-adrenergic receptors in vitro and in vivo.

This study introduces (S)-Opto-prop-2, a second-generation photoswitchable ligand designed for precise modulation of ß2-adrenoceptor (ß2AR). Synthesised by incorporating an azobenzene moiety with propranolol, (S)-Opto-prop-2 exhibited a high PSScis (photostationary state for cis isomer) percentage (∼90 %) and a favourable half-life (>10 days), facilitating diverse bioassay measurements. In vitro, the cis-isomer displayed substantially higher ß2AR binding affinity than the trans-isomer (1000-fold), making (S)-Opto-prop-2 one of the best photoswitchable GPCR (G protein-coupled receptor) ligands reported so far. Molecular docking of (S)-Opto-prop-2 in the X-ray structure of propranolol-bound ß2AR followed by site-directed mutagenesis studies, identified D1133.32, N3127.39 and F2896.51 as crucial residues that contribute to ligand-receptor interactions at the molecular level. In vivo efficacy was assessed using a rabbit ocular hypertension model, revealing that the cis isomer mimicked propranolol's effects in reducing intraocular pressure, while the trans isomer was inactive. Dynamic optical modulation of ß2AR by (S)-Opto-prop-2 was demonstrated in two different cAMP bioassays and using live-cell confocal imaging, indicating reversible and dynamic control of ß2AR activity using the new photopharmacology tool. In conclusion, (S)-Opto-prop-2 emerges as a promising photoswitchable ligand for precise and reversible ß2AR modulation with light. The new tool shows superior cis-on binding affinity, one of the largest reported differences in affinity (1000-fold) between its two configurations, in vivo efficacy, and dynamic modulation. This study contributes valuable insights into the evolving field of photopharmacology, offering a potential avenue for targeted therapy in ß2AR-associated pathologies.

Broadband Emission Induced by Band-Edge Carrier Reconfiguration in 2D Hybrid Lead Halide Perovskites.

Broadband emission in hybrid lead halide perovskites (LHPs) has gained significant attention due to its potential applications in optoelectronic devices. The origin of this broadband emission is primarily attributed to the interactions between electrons and phonons. Most investigations have focused on the impact of structural characteristics of LHPs on broadband emission, while neglecting the role of electronic mobility. In this work, the study investigates the electronic origins of broadband emission in a family of 2D LHPs. Through spectroscopic experiments and density functional theory calculations, the study unveils that the electronic states of the organic ligands with conjugate effect in LHPs can extend to the band edges. These band-edge carriers are no longer localized only within the inorganic layers, leading to electronic coupling with molecular states in the barrier and giving rise to additional interactions with phonon modes, thereby resulting in broadband emission. The high-pressure photoluminescence measurements and theoretical calculations reveal that hydrostatic pressure can induce the reconfiguration of band-edge states of charge carriers, leading to different types of band alignment and achieving macroscopic control of carrier dynamics. The findings can provide valuable guidance for targeted synthesis of LHPs with broadband emission and corresponding design of state-of-the-art optoelectronic devices.

Structural basis of ligand recognition and design of antihistamines targeting histamine H4 receptor.

The histamine H4 receptor (H4R) plays key role in immune cell function and is a highly valued target for treating allergic and inflammatory diseases. However, structural information of H4R remains elusive. Here, we report four cryo-EM structures of H4R/Gi complexes, with either histamine or synthetic agonists clobenpropit, VUF6884 and clozapine bound. Combined with mutagenesis, ligand binding and functional assays, the structural data reveal a distinct ligand binding mode where D943.32 and a π-π network determine the orientation of the positively charged group of ligands, while E1825.46, located at the opposite end of the ligand binding pocket, plays a key role in regulating receptor activity. The structural insight into H4R ligand binding allows us to identify mutants at E1825.46 for which the agonist clobenpropit acts as an inverse agonist and to correctly predict inverse agonism of a closely related analog with nanomolar potency. Together with the findings regarding receptor activation and Gi engagement, we establish a framework for understanding H4R signaling and provide a rational basis for designing novel antihistamines targeting H4R.

Nitrogen Deficiency Enhances Eggplant Defense against Western Flower Thrips via the Induction of the Jasmonate Pathway.

Plant nutrition is connected to defense against insect herbivores, but the exact mechanism underlying the effect of the nitrogen (N) supply on the anti-herbivore capacity of eggplants (Solanum melongena) has not been studied in detail. Therefore, we examined the impact of low (LN, 0.5 mM) and high (HN, 5 mM) nitrate levels on eggplant resistance against the western flower thrips Frankliniella occidentalis (WFT), a major destructive eggplant pest. Our results showed that LN plants displayed enhanced defense responses to WFT compared to HN plants. This included increased transcript levels of key genes in the jasmonic acid (JA) pathway, the accumulation of JA-amido conjugates (jasmonoyl-isoleucine, jasmonoyl-phenylalanine, and jasmonoyl-valine), JA precursor (12-oxophytodienoic acid), and methyl jasmonate, higher transcript levels of defense marker genes (MPK3, MPK7, and WRKY53), and increased activities of polyphenol oxidase and peroxidase upon a WFT attack. Our findings suggest that N deficiency can prime JA-mediated defense responses in eggplants, resulting in increased anti-herbivore resistance.

Meteorological influence on persistent O3 pollution events in Wuxi in the Yangtze River Delta, China.

The number of O3 pollution days indicates an overall increasing trend over 2014-2021 in Wuxi in the Yangtze River Delta, with the pollution concentrations of MDA8-O3 between 186 and 200 µg·m-3. Specifically, a total of 62 POPEs (persistent O3 pollution events), defined as episodes with 3 or more continuous O3 pollution days, were observed for the 8 years. Using a multi-linear regression model, we find that the meteorology can explain approximately 56.5 % of the O3 variations for the 8 years in Wuxi, with temperature being the most crucial meteorological factor, followed by relative humidity (RH) and wind speeds. High temperature, low RH, low wind speeds and downward airflows significantly correlate with POPE-O3 changes. Three types of synoptic circulations are further identified during the POPEs from 2014 to 2021 by the T-mode (T-PCA) classification method. The primary circulation patterns governing the interannual changes of POPEs are characterized by the largest positive anomalies of temperature and planetary boundary layer (PBL) height; moreover, a distinct vertical mixing process is observed with uplifting airflows in the convective PBL during the afternoon and sinking airflows in the stable PBL at night, which is incredibly conducive to the downward transport of O3 after its upward delivery during daytime and substantially contributes to midnight O3 at the surface. The other two circulation types are associated with uniform descending flows in the PBL; as a result, surface O3 accumulates only near the ground and decreases significantly at night due to the titration effect. This study systematically highlights the influence of critical meteorological factors regulated by different synoptic circulations on the POPE in Wuxi, which provides a scientific basis for pollution control and prediction.

Gut microbial metabolite facilitates colorectal cancer development via ferroptosis inhibition.

The gut microbiota play a pivotal role in human health. Emerging evidence indicates that gut microbes participate in the progression of tumorigenesis through the generation of carcinogenic metabolites. However, the underlying molecular mechanism is largely unknown. In the present study we show that a tryptophan metabolite derived from Peptostreptococcus anaerobius, trans-3-indoleacrylic acid (IDA), facilitates colorectal carcinogenesis. Mechanistically, IDA acts as an endogenous ligand of an aryl hydrocarbon receptor (AHR) to transcriptionally upregulate the expression of ALDH1A3 (aldehyde dehydrogenase 1 family member A3), which utilizes retinal as a substrate to generate NADH, essential for ferroptosis-suppressor protein 1(FSP1)-mediated synthesis of reduced coenzyme Q10. Loss of AHR or ALDH1A3 largely abrogates IDA-promoted tumour development both in vitro and in vivo. It is interesting that P. anaerobius is significantly enriched in patients with colorectal cancer (CRC). IDA treatment or implantation of P. anaerobius promotes CRC progression in both xenograft model and ApcMin/+ mice. Together, our findings demonstrate that targeting the IDA-AHR-ALDH1A3 axis should be promising for ferroptosis-related CRC treatment.

Association of depression with hypertensive left ventricular hypertrophy in age, sex, and education level-specific differences.

Previous studies have shown that hypertension and depression are associated with worse cardiovascular outcomes and reduced quality of life. Left ventricular hypertrophy (LVH) is strongly linked to increased mortality and cardiovascular disease, and depression may be one of the key factors contributing to hypertensive LVH. The authors consecutively enrolled 353 patients with uncomplicated hypertension between November 2017 and May 2021. All participants completed the Hamilton Depression Scale (HAM-D) to assess their depression status, with depression defined as a HAM-D score of 20 or higher. Linear regression analysis revealed a positive association between HAM-D and LVMI (adjusted ß, 1.51, 95% CI, 1.19-1.83, p < .001). Logistic regression models showed that individuals with hypertension and depression had a higher risk of LVH than those with hypertension alone (adjusted OR, 2.51, 95% CI, 1.14-5.52, p = .022). The association between depression and LVH significantly interacted with age, sex, education levels, but not BMI and household income. Following age, sex, and education levels stratification, an independent association of depression and LVH was observed only in age <60 years (age <60 years: OR, 7.36, 95% CI, 2.25-24.13, p < .001), male (male: OR, 16.16, 95% CI, 3.80-68.73, p < .001), and higher education levels (high school and above: OR, 11.09, 95% CI, 2.91-42.22, p < .001). Our findings suggest that depression is a significant risk factor for LVH in hypertensive patients, particularly in those who are under 60 years of age, male, and have higher education levels.

Curing Mechanisms of Polymeric Nano-Copolymer Subgrade.

The mechanical properties of the subgrade have a significant impact on the service life and pavement performance of the superstructure of pavement. By adding admixtures and via other means to strengthen the adhesion between soil particles, the strength and stiffness of the soil can be improved to ensure the long-term stability of pavement structures. In this study, a mixture of polymer particles and nanomaterials was used as a curing agent to examine the curing mechanism and mechanical properties of subgrade soil. Using microscopic experiments, the strengthening mechanism of solidified soil was analyzed with scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), Fourier infrared spectroscopy (FTIR), and X-ray diffraction (XDR). The results showed that with the addition of the curing agent, small cementing substances on the surface of soil minerals filled the pores between minerals. At the same time, with an increase in the curing age, the colloidal particles in the soil increased, and some of them formed large aggregate structures that gradually covered the surface of the soil particles and minerals. By enhancing the cohesiveness and integrity between different particles, the overall structure of the soil became denser. Through pH tests, it was found that the age had a certain effect on the pH of solidified soil, but the effect was not obvious. Through the comparative analysis of elements in plain soil and solidified soil, it was found that no new chemical elements were produced in the solidified soil, indicating that the curing agent does not have negative impacts on the environment.

Composite Indices of the Color-Picture Version of Boston Naming Test Have Better Discriminatory Power: Reliability and Validity in a Chinese Sample with Diverse Neurodegenerative Diseases.

BACKGROUND: The Boston Naming Test (BNT) is the most widely used measure to assess anomia. However, it has been criticized for failing to differentiate the underlying cognitive process of anomia. OBJECTIVE: We validated the color-picture version of BNT (CP-BNT) in a sample with diverse neurodegenerative dementia diseases (NDDs). We also verified the differential ability of the composite indices of CP-BNT across NDDs groups. METHODS: The present study included Alzheimer's disease (n = 132), semantic variant primary progressive aphasia (svPPA, n = 53), non-svPPA (n = 33), posterior cortical atrophy (PCA, n = 35), and normal controls (n = 110). We evaluated psychometric properties of CP-BNT for the spontaneous naming (SN), the percentage of correct responses on semantic cuing and word recognition cuing (% SC, % WR). Receiver operating characteristic analysis was used to examine the discriminatory power of SN alone and the composite indices (SN, % SC, and % WR). RESULTS: The CP-BNT had sufficient internal consistency, good convergent, divergent validity, and criterion validity. Different indices of CP-BNT demonstrated distinct cognitive underpinnings. Category fluency was the strongest predictor of SN (ß= 0.46, p < 0.001). Auditory comprehension tests highly associated with % WR (Sentence comprehension: ß= 0.22, p = 0.001; Word comprehension: ß= 0.20, p = 0.001), whereas a lower visuospatial score predicted % SC (ß= -0.2, p = 0.001). Composite indices had better predictability than the SN alone when differentiating between NDDs, especially for PCA versus non-svPPA (area under the curve increased from 63.9% to 81.2%). CONCLUSION: The CP-BNT is a highly linguistically relevant test with sufficient reliability and validity. Composite indices could provide more differential information beyond SN and should be used in clinical practice.

Preparation of ß-cyclodextrin covalent organic framework-immobilized poly(glycidyl methacrylate) nanoparticle-coated open tubular capillary electrochromatography column for chiral separation.

A new enantioselective open-tubular capillary electrochromatography was developed employing poly(glycidyl methacrylate) nanoparticles/ß-cyclodextrin covalent organic frameworks chemically immobilized on the inner wall of the capillary as a stationary phase. A pretreated silica-fused capillary reacted with 3-aminopropyl-trimethoxysilane followed by poly(glycidyl methacrylate) nanoparticles and ß-cyclodextrin covalent organic frameworks through a ring-opening reaction. The resulting coating layer on the capillary was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The electroosmotic flow was studied to evaluate the variation of the immobilized columns. The chiral separation performance of the fabricated capillary columns was validated by the analysis of the four racemic proton pump inhibitors including lansoprazole, pantoprazole, tenatoprazole, and omeprazole. The influences of bonding concentration, bonding time, bonding temperature, buffer type and concentration, buffer pH, and applied voltage on the enantioseparation of four proton pump inhibitors were investigated. Good enantioseparation efficiencies were achieved for all enantiomers. In the optimum conditions, the enantiomers of four proton pump inhibitors were fully resolved within 10 min with high resolutions of 9.5-13.9. The column-to-column and inter- to intra-day repeatability of the fabricated capillary columns through relative standard deviation were found better than 9.54%, exhibiting satisfactory stability and repeatability of the fabricated capillary columns.

[Characteristics and Source Apportionment of Black Carbon Over the Eastern Tibetan Plateau].

As the most important absorbing aerosol, black carbon (BC) can affect radiation, clouds, and surface snow cover over the Tibetan Plateau. In this study, the BC mass concentrations were measured using a seven-channel aethalometer (AE-33) in Litang County over the eastern Tibetan Plateau from July 5 to September 5, 2017. The aethalometer model, potential source contribution function (PSCF), and concentration-weighted trajectory (CWT) models were used to analyze the variation characteristics, potential sources, and affecting areas of BC. The results showed that the mass concentration of ρ(BC) in Litang ranged from 0.4 to 4699.8 ng·m-3, with an average value of 816.4 ng·m-3, accounting for 5.96% of PM2.5. The average mass concentrations of ρ(BCliquid) and ρ(BCsolid) in Litang were 486.1 ng·m-3 and 398.5 ng·m-3, respectively, with a C of 0.51. The ρ(BC) mass concentration was mainly distributed from 0-2000 ng·m-3, which accounted for 92.5% of the total observation period. The diurnal variation in BC, BCliquid, and BCsolid showed a bimodal distribution, with the peaks appearing at 08:00 and 20:00, respectively. The first peak was mainly related to traffic sources and incomplete combustion of carbonaceous materials, whereas the second peak was mainly related to incomplete combustion of carbonaceous materials. The potential sources and affecting areas of PM2.5 and BC were different. Imports from abroad had a greater impact on the concentrations of PM2.5 and BC in Litang, and the affecting areas were mainly transmitted to the northeast in China. The high-value centers were mainly concentrated in the surrounding areas of Litang.

System analysis based on the migration- and invasion-related gene sets identifies the infiltration-related genes of glioma.

The current database has no information on the infiltration of glioma samples. Here, we assessed the glioma samples' infiltration in The Cancer Gene Atlas (TCGA) through the single-sample Gene Set Enrichment Analysis (ssGSEA) with migration and invasion gene sets. The Weighted Gene Co-expression Network Analysis (WGCNA) and the differentially expressed genes (DEGs) were used to identify the genes most associated with infiltration. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the major biological processes and pathways. Protein-protein interaction (PPI) network analysis and the least absolute shrinkage and selection operator (LASSO) were used to screen the key genes. Furthermore, the nomograms and receiver operating characteristic (ROC) curve were used to evaluate the prognostic and predictive accuracy of this clinical model in patients in TCGA and the Chinese Glioma Genome Atlas (CGGA). The results showed that turquoise was selected as the hub module, and with the intersection of DEGs, we screened 104 common genes. Through LASSO regression, TIMP1, EMP3, IGFBP2, and the other nine genes were screened mostly in correlation with infiltration and prognosis. EMP3 was selected to be verified in vitro. These findings could help researchers better understand the infiltration of gliomas and provide novel therapeutic targets for the treatment of gliomas.

Sex difference in biological change and mechanism of Alzheimer's disease: From macro- to micro-landscape.

Alzheimer's disease (AD) is the most common form of dementia and numerous studies reported a higher prevalence and incidence of AD among women. Although women have longer lifetime, longevity does not wholly explain the higher frequency and lifetime risk in women. It is important to understand sex differences in AD pathophysiology and pathogenesis, which could provide foundation for future clinical AD research. Here, we reviewed the most recent and relevant literature on sex differences in biological change of AD from macroscopical neuroimaging to microscopical pathologic change (neuronal degeneration, synaptic dysfunction, amyloid-beta and tau accumulation). We also discussed sex differences in cellular mechanisms related to AD (neuroinflammation, mitochondria dysfunction, oxygen stress, apoptosis, autophagy, blood-brain-barrier dysfunction, gut microbiome alteration, bulk and single cell/nucleus omics) and possible causes underlying these differences including sex-chromosome, sex hormone and hypothalamic-pituitary- adrenal (HPA) axis effects.

Association of perfluoroalkyl substances with pulmonary function in adolescents (NHANES 2007-2012).

Perfluoroalkyl substances (PFASs) constitute an environmentally persistent and widespread class of anthropogenic chemicals that have been used in industrial and commercial applications in the USA and around the world. Animal studies suggested its toxic impact on lung development, but the adverse effect of PFAS exposure on childhood pulmonary function has not been clearly determined. We investigated the potential cross-sectional association of environmental PFAS exposures with pulmonary function in 765 adolescents aged 12-19 years from the US National Health and Nutrition Examination Survey (NHANES) 2007-2012. Exposure to PFASs was estimated by measuring serum concentrations, and pulmonary function was assessed by spirometry. Linear regression and weighted quantile sum (WQS) regression were performed to estimate the associations of individual chemicals and chemical mixtures with pulmonary function. Median concentrations of PFOA, PFOS, PFNA, and PFHxS (detection frequencies > 90%) were 2.70, 6.40, 0.98, and 1.51 ng/mL, respectively. No associations were found between the four individual congeners and Σ4PFASs and the pulmonary function measures in total adolescents. Sensitive analyses were further conducted stratified by age (12-15 and 16-19 years) and sex (boys and girls). In adolescents aged 12-15 years, PFNA was negatively associated with FEV1:FVC (p-trend = 0.007) and FEF25-75% (p-trend = 0.03) among girls, while PFNA was positively associated with FEV1: FVC (p-trend = 0.018) among boys. No associations were found among adolescents aged 16-19 years, either boys or girls. The aforementioned associations were confirmed when further applying WQS models, and PFNA was identified to be the most heavily weighing chemical. Our results suggested that environmental exposure to PFNA may affect pulmonary function among adolescents aged 12-15 years. Given the cross-sectional analysis and less consistent results, further replications of the association in large prospective cohort studies are warranted.

Advanced glycation end products induce skeletal muscle atrophy and insulin resistance via activating ROS-mediated ER stress PERK/FOXO1 signaling.

Skeletal muscle atrophy is often found in patients with type 2 diabetes mellitus (T2DM), which is characterized by insulin resistance. As the largest tissue in the body, skeletal muscle plays important roles in insulin resistance. Advanced glycation end products (AGEs) are a type of toxic metabolite that are representative of multiple pathophysiological changes associated with T2DM. Mice were exposed to AGEs. Forkhead box O1 (FOXO1) was silenced by using a constructed viral vector carrying siRNA. Skeletal muscle atrophy was evaluated by using hematoxylin-eosin (H&E), oil red O, myosin skeletal heavy chain (MHC), and laminin immunofluorescent stains. Reactive oxygen species (ROS) generation was assessed by using the dihydroethidium (DHE) stain. Western blotting was used to evaluate protein expression and phosphorylation. Insulin resistance was monitored via the insulin tolerance test and the glucose infusion rate (GIR). Mice exposed to AGEs showed insulin resistance, which was evidenced by reduced insulin tolerance and GIR. H&E and MHC immunofluorescent stains suggested reduced cross-sectional muscle fiber area. Laminin immunofluorescent and oil red O stains indicated increased intramuscular fibrosis and lipid deposits, respectively. Exposure to AGEs induced ROS generation, increased phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and FOXO1, facilitated FOXO1 nuclear translocation, and elevated expression of muscle atrophy F-box (MAFbx) in gastrocnemius muscle. foxo1 silencing significantly suppressed skeletal muscle atrophy and insulin resistance without affecting ROS production. AGEs exacerbated skeletal muscle atrophy and insulin resistance by activating the PERK/FOXO1 signaling pathway in skeletal muscle.NEW & NOTEWORTHY In this study, we proposed a molecular mechanism underlying the skeletal muscle atrophy-associated insulin resistance in type 2 diabetes mellitus (T2DM). Our investigation suggests that exposure to AGEs, which are characteristic metabolites of T2DM pathology, induces the activation of reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress, leading to the upregulation of the protein kinase RNA-like ER kinase (PERK)/forkhead box O1 (FOXO1)/muscle atrophy F-box pathway and subsequent skeletal muscle atrophy, ultimately resulting in insulin resistance.

Expressions and Prognostic Values of Notch3 and DLL4 in Human Breast Cancer.

Background: Notch signaling played a critical role in promoting breast tumorigenesis and progression. However, the role and prognostic value of Notch3 combined with DLL4 expression in breast carcinoma had not been explored. Methods: The retrospective study enrolled 90 breast cancer tissues and 60 noncancerous tissues from (conceal). The expression and prognostic value of Notch3 and DLL4 in patients with breast carcinoma were investigated using Oncomine and UALCAN database. Notch3 and DLL4 expression levels were detected by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. We analyzed the correlation between both proteins expression and clinicopathological parameters and survival data, respectively. Results: The expressions of Notch3 and DLL4 were increased, and Notch3 expression was significantly positively associated with DLL4 in breast carcinoma. The 2 proteins dramatically correlated with advanced stage, high grade and negative Her2 status. The overexpressing of single or both Notch3 and DLL4 resulted in shortened survival of breast cancer patients. And Notch3 overexpression was one of independent risk predictors to poor prognosis. Conclusion: The interaction of Notch3 receptor and DLL4 ligand accelerates oncogenesis, progression, and poor prognosis of breast cancer patients. Notch3 protein may serve as one of biomarker to independently predict prognosis of patients.

[Vertical Distribution Characteristics of Boundary Layer Volatile Organic Compounds in Autumn in the Mixed Industrial and Rural Areas over the Northern Suburb of Nanjing].

Based on the sounding data of VOCs in the lower troposphere (0-1000 m) in the northern suburb of Nanjing in the autumn of 2020, the vertical profile distribution, diurnal variation, and photochemical reactivity of VOCs in this area were analyzed. The results showed that the volume fraction of VOCs decreased with the increase in height (72.1×10-9±28.1×10-9-56.4×10-9±24.8×10-9). Alkanes at all heights accounted for the largest proportion (68%-75%), followed by aromatics (10%-12%), halohydrocarbons (10%-11%), alkenes (3%-7%), and acetylene (2%). The diurnal variation of the boundary layer had a great influence on the VOCs profile. The lower boundary layer in the morning and evening caused the volume fraction of VOCs to accumulate near the ground and lower in the upper layer. The vertical distribution of VOCs was more uniform in the afternoon. In the morning, the volume fraction proportion of alkenes (alkanes) with strong (weak) photochemical reactivity decreased (increased) with the increase in height, indicating that the photochemical aging of VOCs in the upper layer was significant. In the afternoon, the vertical distribution of VOCs volume fraction and OFP in the lower troposphere were more uniform. Affected by the surrounding air masses with different sources, the volume fraction and component proportion of VOCs at each height were significantly different. The alkanes in rural air masses were vertically evenly distributed, and the proportion increased gradually with the height. The vertical negative gradient of VOCs volume fraction in the urban air mass was the largest, the volume fraction of VOCs near the ground was high, and it was rich in aromatics. The proportion of aromatics increased with the increase in VOCs volume fraction between 200-400 m height of industrial air mass. The near-surface VOCs volume fraction of the highway traffic air mass was high, and alkanes accounted for the largest proportion.