Restoring bone-fat equilibrium: Baicalin's impact on P38 MAPK pathway for treating diabetic osteoporosis.

Diabetes can lead to a disorder of bone-fat balance, a significant cause of osteoporosis due to changes in environmental factors. Baicalin (Bai), an active ingredient of Scutellaria baicalensis, has been confirmed to possess antioxidant, hypoglycemic, and anti-osteoporotic effects. However, a comprehensive understanding of Bai's influence on diabetic osteoporosis (DOP), including its effects and underlying mechanisms, remains elusive. This study investigated Bai's impact on the bone-fat equilibrium in rats with DOP. The results indicated that Bai alleviated bone damage in DOP by promoting osteogenesis and inhibiting adipogenesis. Concurrently, through bioinformatics analysis, it was suggested that Bai's mechanism of action might involve the P38-MAPK pathway. In vitro, Bai was found to enhance the development of bone marrow mesenchymal stem cells (BMSCs) towards osteogenic lineages while suppressing their differentiation towards adipogenic lineages. It was discovered that Bai's promotion of BMSC osteogenic differentiation depends on the P38-MAPK pathway. Additionally, the synergistic effect mediated by Bai and P38-MAPK inhibitor suppressed BMSC adipogenic differentiation. Our research indicates that the P38-MAPK pathway play a role in Bai's effects on the osteogenic-adipogenic differentiation of BMSCs, showcasing the potential for DOP treatment. This study highlights Bai's ability to regulate the equilibrium between bone and fat, presenting a novel approach to adressing DOP.

[Characteristics of resting energy expenditure and evaluation of prediction formulas in young men with different body mass indexes].

OBJECTIVE: To compare the resting energy expenditure (REE) characteristics among young men with different body mass indexes (BMI). METHODS: Thirty young men [average age was (26.93±4.16) years] were enrolled in this study. They underwent resting metabolism tests in the Department of Sports Medicine of Peking University Third Hospital from December 2017 to June 2021. The resting metabolic rate (RMR) was measured by indirect calorimetry, the body composition was measured by bioresistance antibody component analyzer. The REE characteristics were analyzed, and 11 predictive equations were used to estimate RMR and compared with the measured value. The differences were analyzed by paired t-test and intra-class correlation coefficient (ICC). RESULTS: The RMR of the overall 30 young men was (1 960.17±463.11) kcal/d (1 kcal=4.186 8 kJ). Including (1 744.33±249.62) kcal/d in those with normal BMI, which was significantly lower than that in those who were overweight or obese [(2 104.06± 520.32) kcal/d, P < 0.01], but the weight-corrected RMR in those with normal BMI was significantly higher than that in those who were overweight or obese [(24.02±2.61) kcal/(kg·d) vs. (19.98±4.38) kcal/(kg·d), P < 0.01]. The RMR was significantly and positively correlated with body weight, adiposity, lean body mass, body surface area, and extracellular fluid in the subjects with diffe-rent BMI (all P < 0.05). The predicted values of the 11 prediction equations were not in good agreement with the measured values (all ICC < 0.75), with relatively high agreement between the predicted and measured values of the World Health Organization (WHO) equation in overweight obese young men (ICC=0.547, P < 0.01). CONCLUSION: There were significant differences in RMR among young men with different BMI, and the RMR after weight correction should be considered for those who were overweight or obese. The consistency between the predicted values of different prediction equations and the actual measured values of RMR was relatively poor, and it is recommended to accurately measure RMR by indirect calorimetry. For overweight or obese young men, the WHO prediction equation can be considered to calculate RMR, but it is necessary to establish an RMR prediction equation applicable to different BMI populations.

Palladium-catalyzed dehydrogenation of α-cyclohexene-substituted nitriles to α-aryl nitriles.

The development of a practical, inexpensive, and cyanide-free method for synthesizing α-aryl nitriles remains a challenging goal in synthetic chemistry. Here, we report an approach for synthesizing α-aryl nitriles toward achieving this goal, by which α-cyclohexenyl acetonitriles and α-cyclohexenyl alkenyl nitriles are dehydrogenated to α-aryl nitriles.

Impact of aerosol-boundary layer interactions on PM2.5 pollution during cold air pool events in a semi-arid urban basin.

Global emission reductions still must address winter fine particulate matter (PM2.5) pollution in urban basins with enclosed terrains and frequent cold air pool (CAP) events when the temperatures within the basin are colder than above it. The effects of urban basin aerosol-boundary layer interactions on PM2.5 pollution during CAP events remain unclear. Intensive boundary layer observations in January 2021 and numerical models were used to investigate this issue in the semi-arid urban Lanzhou Basin of China. The results showed that CAPs formed because of the synoptic weather system that exacerbated the warming over the basin. The CAPs in this experiment were characterized by stronger temperature inversion (TI) layers in the vertical direction and lower relative humidity, lower wind speed, and weaker turbulence at the bottom of the basin compared to other conditions. The strong TI layers below the top of the basin inhibited the vertical dispersion of pollutants in the basin and concentrated the PM2.5 within a height of 0.3 km from the bottom of the basin. During CAP events, the proportion of elemental carbon in PM2.5 increased, whereas that of secondary inorganic species decreased. Aerosol absorption increased faster than scattering during CAP events. Therefore, the mean single scattering albedo decreased from 0.85 during non-CAP periods to 0.81 during CAP events. Radiosonde-sounding observations and numerical simulations indicated that aerosols accumulating in the lower basin heated the atmosphere during the daytime and facilitated boundary layer development via the "stove effect" (absorption aerosol heats lower atmosphere to promote boundary layer development). No significant "dome effect" (absorption aerosol heats the upper boundary layer to suppress boundary layer development) occurred during the two CAP events. These findings provide a theoretical basis for scientifically-guided PM2.5 pollution control in winter in isolated urban basins.

KAT8/SIRT7-mediated Fascin-K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma.

Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Dry and wet experiments reveal diagnostic clustering and immune landscapes of cuproptosis patterns in patients with ankylosing spondylitis.

Cuproptosis is a new manner of mitochondrial cell death induced by copper. There is evidence that serum copper has a crucial impact on ankylosing spondylitis (AS) by copper-induced inflammatory response. However, the molecular mechanisms of cuproptosis modulators in AS remain unknown. We aimed to use a bioinformatics-based method to comprehensively investigate cuproptosis-related subtype identification and immune microenvironment infiltration of AS. Additionally, we further verified the results by in vitro experiments, in which peripheral blood and fibroblast cells from AS patients were used to evaluate the functions of significant cuproptosis modulators on AS. Finally, eight significant cuproptosis modulators were identified by analysis of differences between controls and AS cases from GSE73754 dataset. Eight prognostic cuproptosis modulators (LIPT1, DLD, PDHA1, PDHB, SLC31A1, ATP7A, MTF1, CDKN2A) were identified using a random forest model for prediction of AS risk. A nomogram model of the 8 prognostic cuproptosis modulators was then constructed; the model could be beneficial in clinical settings, as indicated by decision curve analysis. Consensus clustering analysis was used to divide AS patients into two cuproptosis subtypes (clusterA & B) according to significant cuproptosis modulators. The cuproptosis score of each sample was calculated by principal component analysis to quantify cuproptosis subtypes. The cuproptosis scores were higher in clusterB than in clusterA. Additionally, cases in clusterA were closely associated with the immunity of activated B cells, Activated CD4 T cell, Type17 T helper cell and Type2 T helper cell, while cases in clusterB were linked to Mast cell, Neutrophil, Plasmacytoid dendritic cell immunity, indicating that clusterB may be more correlated with AS. Notably, key cuproptosis genes including ATP7A, MTF1, SLC31A1 detected by RT-qPCR with peripheral blood exhibited significantly higher expression levels in AS cases than controls; LIPT1 showed the opposite results; High MTF1 expression is correlated with increased osteogenic capacity. In general, this study of cuproptosis patterns may provide promising biomarkers and immunotherapeutic strategies for future AS treatment.

Direct Synthesis of Esters from Alkylarenes and Carboxylic Acids: The C-H Bond Dehydroesterification.

Herein, a reaction in which the benzyl C-H bonds of alkylarenes are directly esterified by carboxylic acids to produce benzyl esters in high yields is reported. This reaction is catalyzed by Pd nanoparticles (NPs) on N-doped carbon (CN) composites based on a carbonizing Al-MIL-101(NH2) material, and no oxidants or hydrogen acceptors are required. Use of o-alkylbenzoic acids as substrates leads to phthalides, whereas with carboxylic acids and alkylarenes as the feedstock, the reaction produces the benzyl esters. These reactions that use readily available alkylarenes instead of benzyl halides or benzyl alcohols as raw materials for one-step synthesis of benzyl esters without oxidants are inherently atom- and step-efficient. The CN composites and the CN-supported Pd NP catalysts were prepared and are well characterized. The proposed mechanism involves dehydrogenation of both the carboxylic groups and the benzylic groups and the transformation of benzylic C-H bond into the C-O bond via hydrogen abstraction from the benzylic group through an organopalladium intermediate. The kinetic isotope effect (kH/kD = 2.77) indicated that C(sp3)-H bond cleavage of the alkane aromatics is the rate-determining step.

Co-Expression of Chromatin Assembly Factor 1 Subunit A and Proliferating Cell Nuclear Antigen Is a Prognostic Biomarker of Esophageal Cancer.

(1) Background: Esophageal cancer (EC) is an important global health challenge. Due to the lack of necessary biomarkers and therapeutic targets, the survival of EC patients is poor. The EC proteomic data of 124 patients recently published by our group provides a database for research in this field. (2) Methods: Bioinformatics analysis was used to identify DNA replication and repair-related proteins in EC. Proximity ligation assay, colony formation assay, DNA fiber assay, and flow cytometry were used to study the effects of related proteins on EC cells. Kaplan-Meier survival analysis was used to evaluate the relationship between gene expression and the survival time of EC patients. (3) Results: Chromatin assembly factor 1 subunit A (CHAF1A) was highly correlated with proliferating cell nuclear antigen (PCNA) expression in EC. CHAF1A and PCNA colocalized in the nucleus of EC cells. Compared with the knockdown of CHAF1A or PCNA alone, the double knockdown of CHAF1A and PCNA could significantly inhibit EC cell proliferation. Mechanistically, CHAF1A and PCNA synergistically accelerated DNA replication and promoted S-phase progression. EC patients with high expression of both CHAF1A and PCNA had a worse survival rate. (4) Conclusion: we identify CHAF1A and PCNA as key cell cycle-related proteins leading to the malignant progression of EC, and these proteins could serve as important prognostic biomarkers and targets for EC.

Bioinformatics identification and experimental validation of m6A-related diagnostic biomarkers in the subtype classification of blood monocytes from postmenopausal osteoporosis patients.

Background: Postmenopausal osteoporosis (PMOP) is a common bone disorder. Existing study has confirmed the role of exosome in regulating RNA N6-methyladenosine (m6A) methylation as therapies in osteoporosis. However, it still stays unclear on the roles of m6A modulators derived from serum exosome in PMOP. A comprehensive evaluation on the roles of m6A modulators in the diagnostic biomarkers and subtype identification of PMOP on the basis of GSE56815 and GSE2208 datasets was carried out to investigate the molecular mechanisms of m6A modulators in PMOP. Methods: We carried out a series of bioinformatics analyses including difference analysis to identify significant m6A modulators, m6A model construction of random forest, support vector machine and nomogram, m6A subtype consensus clustering, GO and KEGG enrichment analysis of differentially expressed genes (DEGs) between different m6A patterns, principal component analysis, and single sample gene set enrichment analysis (ssGSEA) for evaluation of immune cell infiltration, experimental validation of significant m6A modulators by real-time quantitative polymerase chain reaction (RT-qPCR), etc. Results: In the current study, we authenticated 7 significant m6A modulators via difference analysis between normal and PMOP patients from GSE56815 and GSE2208 datasets. In order to predict the risk of PMOP, we adopted random forest model to identify 7 diagnostic m6A modulators, including FTO, FMR1, YTHDC2, HNRNPC, RBM15, RBM15B and WTAP. Then we selected the 7 diagnostic m6A modulators to construct a nomogram model, which could provide benefit with patients according to our subsequent decision curve analysis. We classified PMOP patients into 2 m6A subtypes (clusterA and clusterB) on the basis of the significant m6A modulators via a consensus clustering approach. In addition, principal component analysis was utilized to evaluate the m6A score of each sample for quantification of the m6A subgroups. The m6A scores of patients in clusterB were higher than those of patients in clusterA. Moreover, we observed that the patients in clusterA had close correlation with immature B cell and gamma delta T cell immunity while clusterB was linked to monocyte, neutrophil, CD56dim natural killer cell, and regulatory T cell immunity, which has close connection with osteoclast differentiation. Notably, m6A modulators detected by RT-qPCR showed generally consistent expression levels with the bioinformatics results. Conclusion: In general, m6A modulators exert integral function in the pathological process of PMOP. Our study of m6A patterns may provide diagnostic biomarkers and immunotherapeutic strategies for future PMOP treatment.

A review of the technology and applications of methods for evaluating the transport of air pollutants.

A variety of methods based on air quality models, including tracer methods, the brute-force method (BFM), decoupled direct method (DDM), high-order decoupled direct method (HDDM), response surface models (RSMs) and so on forth, have been widely used to study the transport of air pollutants. These methods have good applicability for the transport of air pollutants with simple formation mechanisms. However, differences in research conclusions on secondary pollutants with obvious nonlinear characteristics have been reported. For example, the tracer method is suitable for the study of simplified scenarios, while HDDM and RSMs are more suitable for the study for nonlinear pollutants. Multiple observation techniques, including conventional air pollutant observation, lidar observation, air sounding balloons, vehicle-mounted and ship-borne technology, aerial surveys, and remote sensing observations, have been utilized to investigate air pollutant transport characteristics with time resolution as high as 1 sec. In addition, based on a multi-regional input-output model combined with emission inventories, the transfer of air pollutant emissions can be evaluated and applied to study the air pollutant transport characteristics. Observational technologies have advantages in temporal resolution and accuracy, while modeling technologies are more flexible in spatial resolution and research plan setting. In order to accurately quantify the transport characteristics of pollutants, it is necessary to develop a research method for interactive verification of observation and simulation. Quantitative evaluation of the transport of air pollutants from different angles can provide a scientific basis for regional joint prevention and control.

Insights into multidimensional transport flux from vertical observation and numerical simulation in two cities in North China.

This study represents the first quantitative evaluation of pollution transport budget within the boundary layer of typical cities in the Beijing-Tianjin-Hebei (BTH) region from the perspective of horizontal and vertical exchanges and further discusses the impact of the atmospheric boundary layer (ABL)-free troposphere (FT) exchange on concentration of fine particulate matter (PM2.5) within the ABL during heavy pollution. From the perspective of the transport flux balance relationship, differences in pollution transport characteristics between the two cities is mainly reflected in the ABL-FT exchange effect. The FT mainly flowed into the ABL in BJ, while in SJZ, the outflow from the ABL to the FT was more intense. Combined with an analysis of vertical wind profile distribution, BJ was found to be more susceptible to the influence of northwest cold high prevailing in winter, while sinking of strong cold air allowed the FT flowing into the ABL influence the vertical exchange over BJ. In addition, we selected a typical pollution event for targeted analysis to understand mechanistic details of the influence of ABL-FT exchange on the pollution event. These results showed that ABL-FT interaction played an important role in PM2.5 concentration within the ABL during heavy pollution. Especially in the early stage of heavy pollution, FT transport contributed as much as 82.74% of PM2.5 within the ABL. These findings are significant for improving our understanding of pollution transport characteristics within the boundary layer and the effect of ABL-FT exchange on air quality.

Chlorogenic acid intake guidance: Sources, health benefits, and safety.

Chlorogenic acid (CGA) is widely present in plant foods and has attracted much attention due to biological activities such as those which are antioxidant, anti-inflammatory, antibacterial, and antiviral. It plays a role in regulating glucose and lipid metabolism, improving insulin resistance, and reducing the risk of type 2 diabetes and cardiovascular diseases. The estimated dietary intake of CGA is 5 to 1000 mg/d. Based on the data from population intervention studies, daily oral doses of CGA at 13.5mg to 1200 mg can reduce fasting blood glucose (FBG), improve glucose tolerance, enable weight loss /prevent weight gain, and improve blood pressure in hypertensive patients. Daily intake of 200 mg or more may reduce FBG, with a dose-effect relationship in the range 13.5-500 mg/d. Therefore, a specific proposed level (SPL) of CGA to improve FBG could be ≥200 mg/d. Data insufficiency does not allow formulation of a tolerable upper intake level (TUIL) for CGA.

Myristic acid alleviates hippocampal aging correlated with GABAergic signaling.

Previous studies have shown that myristic acid (MA), a saturated fatty acid, could promote the proliferation and differentiation of neural stem cells in vitro. However, the effect of MA on hippocampal neurons aging has not been reported in vivo. Here we employed 22-month-old naturally aged C57BL/6 mice to evaluate the effect and mechanism of MA on hippocampal aging. First, we examined a decreased exploration and spatial memory ability in aging mice using the open field test and Morris water maze. Consistently, aging mice showed degenerative hippocampal histomorphology by H&E and Nissl staining. In terms of mechanism, imbalance of GABRB2 and GABRA2 expression in aging mice might be involved in hippocampus aging by mRNA high throughput sequencing (mRNA-seq) and immunohistochemistry (IHC) validation. Then, we revealed that MA alleviated the damage of exploration and spatial memory ability and ameliorated degeneration and aging of hippocampal neurons. Meanwhile, MA downregulated GABRB2 and upregulated GABRA2 expression, indicating MA might alleviate hippocampal aging correlated with GABAergic signaling. In conclusion, our findings revealed MA alleviated hippocampal aging correlated with GABAergic signaling, which might provide insight into the treatment of aging-associated diseases.

The post-translational modification of Fascin: impact on cell biology and its associations with inhibiting tumor metastasis.

The post-translational modifications (PTMs), which are crucial in the regulation of protein functions, have great potential as biomarkers of cancer status. Fascin (Fascin actin-bundling protein 1, FSCN1), a key protein in the formation of filopodia that is structurally based on actin filaments (F-actin), is significantly associated with tumor invasion and metastasis. Studies have revealed various regulatory mechanisms of human Fascin, including PTMs. Although a number of Fascin PTM sites have been identified, their exact functions and clinical significance are much less explored. This review explores studies on the functions of Fascin and briefly discusses the regulatory mechanisms of Fascin. Next, to review the role of Fascin PTMs in cell biology and their associations with metastatic disease, we discuss the advances in the characterization of Fascin PTMs, including phosphorylation, ubiquitination, sumoylation, and acetylation, and the main regulatory mechanisms are discussed. Fascin PTMs may be potential targets for therapy for metastatic disease.

Chronic Cold Exposure Leads to Daytime Preference in the Circadian Expression of Hepatic Metabolic Genes.

Circadian control allows organisms to anticipate and adapt to environmental changes through changes in physiology and behavior. The circadian system timing is entrained by cues, such as light, food, and temperature. An ambient temperature dramatically impacts the sleep-wake cycle and metabolic rhythmicity. As endotherms, mammals rely on tissues such as the liver to provide fuel for thermogenesis to maintain body temperature. The adaptive response of the circadian rhythm of liver metabolism to chronic cold exposure remains largely unexplored. Here, we investigated the circadian rhythm adaptation of hepatic metabolism in response to environmental cold stress using a mouse model of chronic cold exposure. We analyzed metabolites and transcripts of mouse livers at 24 h and found that long-term low-temperature exposure resulted in a synergistic and phase synchronization of transcriptional rhythms of many genes associated with metabolic pathways. Notably, transcription peaked in the early light phase when the body temperature was relatively low. Our results suggest that chronic cold does not alter the rhythmic expression of essential core clock genes in the liver, so the rewiring of clock control gene expression is another mechanism that optimizes the circadian rhythm of liver metabolism to meet the energy requirements of animal thermogenesis.

Zuo-Gui-Wan Aqueous Extract Ameliorates Glucocorticoid-Induced Spinal Osteoporosis of Rats by Regulating let-7f and Autophagy.

Objective: This study proposes to explore the protective effect of Zuo-Gui-Wan (ZGW) aqueous extract on spinal glucocorticoid-induced osteoporosis (GIOP) in vivo and in vitro, and the underlying mechanisms of ZGW in GIOP and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) were conducted. Methods: In vivo, SD rats were randomly divided into three groups: control group (CON), dexamethasone (DEXM) group, and ZGW group, which were given vehicle, DEXM injection, and ZGW intragastric administration at the same time. Vertebral bone microarchitecture, biomechanics, histomorphology, serum AKP activity, and the autophagosome of osteoblasts were examined. The mRNA expressions of let-7f, autophagy-associated genes (mTORC1, Beclin-1, ATG12, ATG5, and LC3), Runx2, and CTSK were examined. In vitro, the let-7f overexpression/silencing vector was constructed and transfected to evaluate the osteogenic differentiation of BMSCs. Western blot was employed to detect the expression of autophagy-associated proteins (ULK2, ATG5, ATG12, Beclin-1, LC3). Results: In vivo, ZGW promoted the bone quantity, quality, and strength; alleviated histological damage; increased the serum AKP activity; and reduced the autophagosome number in osteoblasts. Moreover, ZGW increased the let-7f, mTORC1, and Runx2 mRNA expressions and reduced the Beclin-1, ATG12, ATG5, LC3, and CTSK mRNA expressions. In vitro, bioinformatics prediction and dual luciferase reporter gene assay verified that let-7f targeted the binding to ULK2 and negatively regulated the ULK2 expression. Furthermore, by let-7f overexpression/silencing, ZGW may promote osteoblast differentiation of BMSCs by regulating let-7f and autophagy as evidenced by Western blot (ULK2, ATG5, ATG12, Beclin-1, LC3). Conclusions: ZGW may ameliorate GC-induced spinal osteoporosis by promoting osteoblast differentiation of BMSCs by activation of let-7f and suppression of autophagy.

Chemical characteristics and regional transport of submicron particulate matter at a suburban site near Lanzhou, China.

Lanzhou, which is a valley city on the Loess Plateau, frequently suffered from aerosol pollution in recent years, especially in winter. However, the lack of understanding of factors governing aerosol pollution limits the implementation of effective emission policies in and around Lanzhou. To help solve this problem, an intensive field campaign was conducted at the SACOL site, which is a suburban site near Lanzhou, in winter 2018. The chemical characteristics and sources of submicron particulate matter (PM1) were investigated, and the influence of the topography around Lanzhou on aerosol pollution was examined. In the present study, the average PM1 mass concentration reached 25.6 ± 12.8 µg m-3, with 41.0% organics, 16.1% sulfate, 19.7% nitrate, 10.7% ammonium, 3.1% chloride, and 9.4% black carbon (BC). Three organic aerosol (OA) factors were identified with the positive matrix factorization (PMF) algorithm, including a biomass burning OA (BBOA, 13.6%), a coal combustion OA (CCOA, 34.2%), and an oxygenated OA (OOA, 52.2%). The significant relationships between organics, BC, and chloride and wind pattern suggested that the SACOL site was strongly influenced by regionally transported aerosols. Further analysis suggested that these aerosol regional transport events were caused by topography. Due to the limitation of the valley, aerosols accumulated in the valley. These accumulated aerosols were then transported to the SACOL site along the valley by prevailing winds. Our study highlights enhanced aerosol regional transport in valleys, which provides a new perspective for future studies on aerosol pollution in basins and valleys.

White-matter microstructural alterations in patients with functional constipation: A tract-based spatial statistics study.

BACKGROUND: Highly prevalent functional constipation (FC) belongs to the category of functional gastrointestinal disorders. Neuroimaging studies have demonstrated brain functional and morphometric changes in patients with FC. However, whether FC is associated with white-matter (WM) microstructural alterations remains unclear. METHODS: Diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) were introduced to investigate WM microstructural changes as calculated by fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) in 26 FC patients and 31 healthy controls. KEY RESULTS: Patients with FC relative to healthy controls had significantly decreased FA with increased MD/RD in the genu (GCC) and body (BCC) of the corpus callosum, right cingulum (Cing), bilateral anterior corona radiata (ACR), bilateral superior corona radiata (SCR), and left posterior corona radiata (PCR) (pFWE  < 0.05). Between-group difference was only in the left SCR and PCR when regressing out anxiety and depression as covariates. CONCLUSIONS AND INFERENCES: These WM tracts are mainly responsible for sensory and emotional information communication and corresponding functional integration; thus, our findings indicate an association between FC and WM microstructural abnormalities in regions involved with visceral afferent and emotional-arousal processing. Alterations in WM microstructures including the CC, cingulum, and ACR are more related to psychological symptoms than constipation, which might have greater impact on brain structures.

Research on the Mechanism of Kaempferol for Treating Senile Osteoporosis by Network Pharmacology and Molecular Docking.

Kaempferol (KP), as a natural anti-inflammatory compound, has been reported to have curative effects on alleviating senile osteoporosis (SOP), which is an inflammation-related musculoskeletal disease, but the molecular mechanisms remain unclear due to scanty relevant studies. We predicted the targets of KP and SOP, and the common targets of them were subsequently used to carry out PPI analysis. Moreover, we adopted GO and KEGG enrichment analysis and molecular docking to explore potential mechanisms of KP against SOP. There were totally 152 KP-related targets and 978 SOP-related targets, and their overlapped targets comprised 68 intersection targets. GO enrichment analysis showed 1529 biological processes (p < 0.05), which involved regulation of inflammatory response, oxidative stress, regulation of bone resorption and remodeling, osteoblast and osteoclast differentiation, etc. Moreover, KEGG analysis revealed 146 items including 44 signaling pathways (p < 0.05), which were closely linked to TNF, IL-17, NF-kappa B, PI3K-Akt, MAPK, estrogen, p53, prolactin, VEGF, and HIF-1 signaling pathways. By means of molecular docking, we found that kaempferol is bound with the key targets' active pockets through some connections such as hydrogen bond, pi-alkyl, pi-sigma, pi-pi Stacked, pi-pi T-shaped, and van der Waals, illustrating that kaempferol has close combination with the key targets. Collectively, various targets and pathways involve in the process of kaempferol treatment against SOP through regulating inflammatory response, oxidative stress, bone homeostasis, etc. Moreover, our study first reported that kaempferol may regulate core targets' expression with involvement of inflammatory response, oxidative stress, and bone homeostasis, thus treating SOP.

AKT serine/threonine kinase 2-mediated phosphorylation of fascin threonine 403 regulates esophageal cancer progression.

Fascin is the main actin-bundling protein in filopodia and is highly expressed in metastatic tumor cells. The overexpression of Fascin has been associated with poor clinical prognosis and metastatic progression. Post-translational modifications of Fascin, such as phosphorylation, can affect the proliferation and invasion of tumor cells by regulating the actin-bundling activity of Fascin. However, the phosphorylation sites of Fascin and their corresponding kinases require further exploration. In the current study, we identified novel phosphorylation of Fascin Threonine 403 (Fascin-T403) mediated by AKT serine/threonine kinase 2 (AKT2), which was studied using mass spectrometry data from esophageal cancer tissues (iProX database: IPX0002501000). A molecular dynamics simulation revealed that Fascin-Threonine 403 phosphorylation (Fascin-T403D) had a distinct spatial structure and correlation of amino acid residues, which was different from that of the wild type (Fascin-WT). Low-speed centrifugation assay results showed that Fascin-T403D affected actin cross-linking. To investigate whether Fascin-T403D affected the function of esophageal cancer cells, either Fascin-WT or Fascin-T403D were rescued in Fascin-knockout or siRNA cell lines. We observed that Fascin-T403D could suppress the biological behavior of esophageal cancer cells, including filopodia formation, cell proliferation, and migration. Co-immunoprecipitation (Co-IP) and Duolink in situ proximity ligation assay (PLA) were performed to measure the interaction between Fascin and AKT2. Using in vitro and in vivo kinase assays, we confirmed that AKT2, but not AKT1 or AKT3, is an upstream kinase of Fascin Threonine 403. Taken together, the AKT2-catalyzed phosphorylation of Fascin Threonine 403 suppressed esophageal cancer cell behavior, actin-bundling activity, and filopodia formation.