Genomic structural variation contributes to evolved changes in gene expression in high-altitude Tibetan sheep.

Tibetan sheep were introduced to the Qinghai Tibet plateau roughly 3,000 B.P., making this species a good model for investigating genetic mechanisms of high-altitude adaptation over a relatively short timescale. Here, we characterize genomic structural variants (SVs) that distinguish Tibetan sheep from closely related, low-altitude Hu sheep, and we examine associated changes in tissue-specific gene expression. We document differentiation between the two sheep breeds in frequencies of SVs associated with genes involved in cardiac function and circulation. In Tibetan sheep, we identified high-frequency SVs in a total of 462 genes, including EPAS1, PAPSS2, and PTPRD. Single-cell RNA-Seq data and luciferase reporter assays revealed that the SVs had cis-acting effects on the expression levels of these three genes in specific tissues and cell types. In Tibetan sheep, we identified a high-frequency chromosomal inversion that exhibited modified chromatin architectures relative to the noninverted allele that predominates in Hu sheep. The inversion harbors several genes with altered expression patterns related to heart protection, brown adipocyte proliferation, angiogenesis, and DNA repair. These findings indicate that SVs represent an important source of genetic variation in gene expression and may have contributed to high-altitude adaptation in Tibetan sheep.

PAIP1 binds to pre-mRNA and regulates alternative splicing of cancer pathway genes including VEGFA.

BACKGROUND: Poly (A) binding protein interacting protein 1 (PAIP1) has been shown to causally contribute to the development and progression of cancer. However, the mechanisms of the PAIP1 regulation in tumor cells remain poorly understood. RESULTS: Here, we used a recently developed UV cross-linking and RNA immunoprecipitation method (iRIP-seq) to map the direct and indirect interaction sites between PAIP1 and RNA on a transcriptome-wide level in HeLa cells. We found that PAIP1 not only binds to 3'UTRs, but also to pre-mRNAs/mRNAs with a strong bias towards the coding region and intron. PAIP1 binding sites are enriched in splicing enhancer consensus GA-rich motifs. RNA-seq analysis revealed that PAIP1 selectively modulates the alternative splicing of genes in some cancer hallmarks including cell migration, the mTOR signaling pathway and the HIF-1 signaling pathway. PAIP1-regulated alternative splicing events were strongly associated with PAIP1 binding, demonstrating that the binding may promote selection of the nearby splice sites. Deletion of a PAIP1 binding site containing seven repeats of GA motif reduced the PAIP1-mediated suppression of the exon 6 inclusion in a VEGFA mRNA isoform. Proteomic analysis of the PAIP1-interacted proteins revealed the enrichment of the spliceosome components and splicing factors. CONCLUSIONS: These findings suggest that PAIP1 is both a polyadenylation and alternative splicing regulator, that may play a large role in RNA processing via its role in alternative splicing regulation.

Continuous genetic monitoring of transient mesenchymal gene activities in distal tubule and collecting duct epithelial cells during renal fibrosis.

Epithelial cells (ECs) have been proposed to contribute to myofibroblasts or fibroblasts through epithelial-mesenchymal transition (EMT) during renal fibrosis. However, since EMT may occur dynamically, transiently, and reversibly during kidney fibrosis, conventional lineage tracing based on Cre-loxP recombination in renal ECs could hardly capture the transient EMT activity, yielding inconsistent results. Moreover, previous EMT research has primarily focused on renal proximal tubule ECs, with few reports of distal tubules and collecting ducts. Here, we generated dual recombinases-mediated genetic lineage tracing systems for continuous monitoring of transient mesenchymal gene expression in E-cadherin+ and EpCAM+ ECs of distal tubules and collecting ducts during renal fibrosis. Activation of key EMT-inducing transcription factor (EMT-TF) Zeb1 and mesenchymal markers αSMA, vimentin, and N-cadherin, were investigated following unilateral ureteral obstruction (UUO). Our data revealed that E-cadherin+ and EpCAM+ ECs did not transdifferentiate into myofibroblasts, nor transiently expressed these mesenchymal genes during renal fibrosis. In contrast, in vitro a large amount of cultured renal ECs upregulated mesenchymal genes in response to TGF-ß, a major inducer of EMT.

Identifying genes for regulating osteogenic differentiation of human periodontal ligament stem cells in inflammatory environments by bioinformatics analysis.

BACKGROUND AND OBJECTIVES: Periodontitis is an immuno-inflammatory disease caused by dental plaque biofilms and inflammations. The regeneration of bone tissue in inflammatory environment is of great significance for the treatment of periodontal disease, but the specific molecular mechanism of bone formation in periodontitis still needs further exploration. The objective of this study was to identify key osteogenesis-related genes (ORGs) in periodontitis. METHODS: We used two datasets from the Gene Expression Omnibus (GEO) database to find differentially expressed mRNAs and miRNAs, further performed Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then we predicted the downstream genes of the differentially expressed miRNAs (DEMs) by the TargetScan database and established a miRNA-mRNA regulatory network. Finally, the osteogenic mechanism of periodontitis was explored through quantitative real-time PCR (qRT-PCR) by inducing inflammatory environment and osteogenic differentiation of hPDLSCs. RESULTS: Through differential expression analysis and prediction of downstream target genes of DEMs, we created a miRNA-mRNA regulatory network consisting of 29 DEMs and 11 differentially expressed osteogenesis-related genes (DEORGs). In addition, the qRT-PCR results demonstrated that BTBD3, PLAT, AKAP12, SGK1, and GLCE expression levels were significantly upregulated, while those of TIMP3, ZCCHC14, LIN7A, DNAH6, NNT, and ITGA6 were downregulated under the dual effects of inflammatory stimulation and osteogenic induction. CONCLUSION: DEORGs might be important factors in the osteogenic phase of periodontitis, and the miRNA-mRNA network may shed light on the clarification of the role and mechanism of osteogenesis in periodontitis and contribute to the development of novel therapeutic strategies.

Quantitative phosphoproteomic analysis of the molecular substrates of sleep need.

Sleep and wake have global effects on brain physiology, from molecular changes1-4 and neuronal activities to synaptic plasticity3-7. Sleep-wake homeostasis is maintained by the generation of a sleep need that accumulates during waking and dissipates during sleep8-11. Here we investigate the molecular basis of sleep need using quantitative phosphoproteomic analysis of the sleep-deprived and Sleepy mouse models of increased sleep need. Sleep deprivation induces cumulative phosphorylation of the brain proteome, which dissipates during sleep. Sleepy mice, owing to a gain-of-function mutation in the Sik3 gene 12 , have a constitutively high sleep need despite increased sleep amount. The brain proteome of these mice exhibits hyperphosphorylation, similar to that seen in the brain of sleep-deprived mice. Comparison of the two models identifies 80 mostly synaptic sleep-need-index phosphoproteins (SNIPPs), in which phosphorylation states closely parallel changes of sleep need. SLEEPY, the mutant SIK3 protein, preferentially associates with and phosphorylates SNIPPs. Inhibition of SIK3 activity reduces phosphorylation of SNIPPs and slow wave activity during non-rapid-eye-movement sleep, the best known measurable index of sleep need, in both Sleepy mice and sleep-deprived wild-type mice. Our results suggest that phosphorylation of SNIPPs accumulates and dissipates in relation to sleep need, and therefore SNIPP phosphorylation is a molecular signature of sleep need. Whereas waking encodes memories by potentiating synapses, sleep consolidates memories and restores synaptic homeostasis by globally downscaling excitatory synapses4-6. Thus, the phosphorylation-dephosphorylation cycle of SNIPPs may represent a major regulatory mechanism that underlies both synaptic homeostasis and sleep-wake homeostasis.

Constructing a Novel Amino Acid Metabolism Signature: A New Perspective on Pheochromocytoma Diagnosis, Immune Landscape, and Immunotherapy.

Pheochromocytoma/paraganglioma (PGPG) is a rare neuroendocrine tumor. Amino acid metabolism is crucial for energy production, redox balance, and metabolic pathways in tumor cell proliferation. This study aimed to build a risk model using amino acid metabolism-related genes, enhancing PGPG diagnosis and treatment decisions. We analyzed RNA-sequencing data from the PCPG cohort in the GEO dataset as our training set and validated our findings using the TCGA dataset and an additional clinical cohort. WGCNA and LASSO were utilized to identify hub genes and develop risk prediction models. The single-sample gene set enrichment analysis, MCPCOUNTER, and ESTIMATE algorithm calculated the relationship between amino acid metabolism and immune cell infiltration in PCPG. The TIDE algorithm predicted the immunotherapy efficacy for PCPG patients. The analysis identified 292 genes with differential expression, which are involved in amino acid metabolism and immune pathways. Six genes (DDC, SYT11, GCLM, PSMB7, TYRO3, AGMAT) were identified as crucial for the risk prediction model. Patients with a high-risk profile demonstrated reduced immune infiltration but potentially higher benefits from immunotherapy. Notably, DDC and SYT11 showed strong diagnostic and prognostic potential. Validation through quantitative Real-Time Polymerase Chain Reaction and immunohistochemistry confirmed their differential expression, underscoring their significance in PCPG diagnosis and in predicting immunotherapy response. This study's integration of amino acid metabolism-related genes into a risk prediction model offers critical clinical insights for PCPG risk stratification, potential immunotherapy responses, drug development, and treatment planning, marking a significant step forward in the management of this complex condition.

Boosting Photocatalytic Performance of ZnO Nanowires via Building Heterojunction with Conjugated 2,4,6-Triaminopyrimidine-g-C3N4.

Photocatalysis is one of the most effective ways to solve environmental problems by solving pollutants. This article designed and prepared a conjugated system of 2,4,6-triaminopyrimidine-g-C3N4 (TAP-CN) to modify ZnO NWs. We systematically studied the photocatalytic performance of ZnO NWs modified with different ratios of TAP-CN. The results showed that 9 wt% TAP-CN-30/ZnO NWs had the best degradation effect on Rhodamine B dye. The degradation rate was 99.36% in 80 min. The excellent degradation performance was attributed to the TAP-CN conjugated system promoting photo-generated charge transfer. This work provided guidance for designing efficient composite catalysts for application in other renewable energy fields.

Enhancing Performance of Organic Pollutant Degradation via Building Heterojunctions with ZnO Nanowires and Na Doped Conjugated 2,4,6-Triaminopyrimidin-g-C3N4.

Organic pollutants were one of the main sources of environmental pollutants. The degradation of organic pollutants through photocatalytic technology was one of the effective solutions. By preparing zinc oxide(ZnO) nanowires modified with sodium-doped conjugated 2,4,6-triaminopyrimidin-g-C3N4 (NaTCN) heterojunction (ZnO/NaTCN), the photocatalytic performance of NaTCN modified with different ratios of ZnO was systematically studied. The photocatalytic performance was studied through the degradation performance of methyl blue (MB) dye. The results showed that 22.5 wt% ZnO/NaTCN had the best degradation effect on MB dye. The degradation rate of MB reached 98.54% in 70 min. After three cycles, it shows good cycling stability (degradation rate is 96.99%) for dye degradation. It was found that there are two types of active species: ·OH and h+, of which h+ is the main active species produced by photocatalytic degradation of dyes. The excellent degradation performance was attributed to the fact that ZnO facilitated the extraction and transport of photogenerated carriers. The doping of sodium facilitated charge transfer. The NaTCN conjugated system promoted the extraction and transfer of photogenerated carriers. It provided guidance for designing efficient composite catalysts for use in other renewable energy fields.

Z-Scheme Heterojunction of Phosphorus-Doped Carbon Nitride/Titanium Dioxide: Photocatalytic Performance.

With increasingly serious environmental pollution problems, the development of efficient photocatalytic materials has become a hotspot in current research. This study focused on phosphorus-doped carbon nitride/titanium dioxide (PCT) Z-type heterojunctions, aiming to deeply investigate their photocatalytic degradation and photosensitive antimicrobial properties. A PCT Z-type heterojunction was successfully fabricated using melamine phosphate, cyanuric acid, and titanium dioxide. The structure, morphology, and optical properties of PCT Z-type heterojunctions were explored by FTIR, XRD, XPS, BET, SEM, UV-Vis DRS, TEM, EIS, and PL. A comprehensive and in-depth analysis of the structure, morphology, and optical properties of PCT Z-type heterojunctions was carried out. The photocatalytic degradation experiments revealed that PC3T Z-type heterojunctions exhibited an excellent degradation capability for methylene blue (MB) under visible light. The effect of PC3T on the adsorption-photocatalytic degradation of MB is more than 1.5 times that of a single titanium dioxide and P-doped carbon nitride. In the photosensitive antimicrobial performance study, PC3T reduced the survival rate of E. coli to 7%, after 120 min. Through free radical trapping experiments, it was shown that the hydroxyl radicals and superoxide radicals exerted an influence on the photocatalytic process. This study offers new ideas and approaches to address environmental pollution problems and holds significant theoretical and applied value.

Functional and structural MRI based obsessive-compulsive disorder diagnosis using machine learning methods.

BACKGROUND: The success of neuroimaging in revealing neural correlates of obsessive-compulsive disorder (OCD) has raised hopes of using magnetic resonance imaging (MRI) indices to discriminate patients with OCD and the healthy. The aim of this study was to explore MRI based OCD diagnosis using machine learning methods. METHODS: Fifty patients with OCD and fifty healthy subjects were allocated into training and testing set by eight to two. Functional MRI (fMRI) indices, including amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree of centrality (DC), and structural MRI (sMRI) indices, including volume of gray matter, cortical thickness and sulcal depth, were extracted in each brain region as features. The features were reduced using least absolute shrinkage and selection operator regression on training set. Diagnosis models based on single MRI index / combined MRI indices were established on training set using support vector machine (SVM), logistic regression and random forest, and validated on testing set. RESULTS: SVM model based on combined fMRI indices, including ALFF, fALFF, ReHo and DC, achieved the optimal performance, with a cross-validation accuracy of 94%; on testing set, the area under the receiver operating characteristic curve was 0.90 and the validation accuracy was 85%. The selected features were located both within and outside the cortico-striato-thalamo-cortical (CSTC) circuit of OCD. Models based on single MRI index / combined fMRI and sMRI indices underperformed on the classification, with a largest validation accuracy of 75% from SVM model of ALFF on testing set. CONCLUSION: SVM model of combined fMRI indices has the greatest potential to discriminate patients with OCD and the healthy, suggesting a complementary effect of fMRI indices on the classification; the features were located within and outside the CSTC circuit, indicating an importance of including various brain regions in the model.

Suspension fixation of iliac bone grafts under arthroscopy is an effective method for the treatment of unstable bony Bankart disease of the shoulder joint in patients with joint relaxation.

PURPOSE: To evaluate the results of arthroscopic autologous iliac bone graft suspension fixation combined with the Remplissage procedure in the treatment of recurrent shoulder dislocation with bony Bankart lesions and joint hyperlaxity. METHODS: From 2018 to 2020, 22 patients with joint laxity underwent arthroscopic autologous iliac bone graft suspension fixation and Bankart repair combined with the Remplissage procedure due to recurrent shoulder dislocation. Clinical assessment included range of motion (forward flexion, abduction, 90° external rotation, conventional external rotation, adduction, and internal rotation), visual analog scale (VAS) score, Rowe score, University of California Los Angeles (UCLA) score, and Western Ontario Shoulder Instability Index (WOSI) score. Post-operatively, the healing of the bone graft was evaluated with computed tomography (CT) scanning. RESULTS: All 22 patients were followed up for a mean of 19.3 ± 4.1 months. CT imaging showed that the healing time of the bone graft was 6-8 weeks. The patient satisfaction rate was 100%, there were no cases of redislocation, all patients returned to their preinjury training state, and the fear test was negative. At the final follow-up, the UCLA, VAS, Rowe, and WOSI scores were 29.8 ± 2.1, 2.2 ± 0.8, 89.4 ± 4.2, and 482.3 ± 46.2, respectively (p < 0.001). CONCLUSION: Arthroscopic autologous iliac bone graft suspension fixation and Bankart repair combined with the Remplissage procedure are effective in preventing recurrent instability with joint hyperlaxity. Furthermore, no patient had redislocation. LEVEL OF EVIDENCE: IV.

Boosting Photocatalytic Performance of ZnO Nanowires via Building Heterojunction with g-C3N4.

The development of a stable and highly active photocatalyst has garnered significant attention in the field of wastewater treatment. In this study, a novel technique involving a facile stirring method was devised to fabricate an array of g-C3N4/ZnO nanowire (ZnO NW) composites. Through the introduction of g-C3N4 to augment the generation of electron-hole pairs upon exposure to light, the catalytic efficacy of these composites was found to surpass that of the pristine ZnO NWs when subjected to simulated sunlight. The photocatalytic performance of a 20 mg·L-1 methylene blue solution was found to be highest when the doping rate was 25 wt%, resulting in a degradation rate of 99.1% after 60 min. The remarkable enhancement in catalytic efficiency can be ascribed to the emergence of a captivating hetero-junction at the interface of g-C3N4 and ZnO NWs, characterized by a harmoniously aligned band structure. This alluring arrangement effectively curtailed charge carrier recombination, amplified light absorption, and augmented the distinct surface area, culminating in a notable boost to the photocatalytic prowess. These findings suggest that the strategic engineering of g-C3N4/ZnO NW heterostructures holds tremendous promise as a pioneering avenue for enhancing the efficacy of wastewater treatment methodologies.

Excellent Dark/Light Dual-Mode Photoresponsive Activities Based on g-C3N4/CMCh/PVA Nanocomposite Hydrogel Using Electron Beam Radiation Method.

Photocatalytic technology for inactivating bacteria in water has received much attention. In this study, we reported a dark-light dual-mode sterilized g-C3N4/chitosan/poly (vinyl alcohol) hydrogel (g-CP) prepared through freeze-thaw cycling and an in situ electron-beam radiation method. The structures and morphologies of g-CP were confirmed using Fourier infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), solid ultraviolet diffuse reflectance spectroscopy (UV-vis DRS), and Brunauer-Emmett-Teller (BET). Photocatalytic degradation experiments demonstrated that 1 wt% g-CP degraded rhodamine B (RhB) up to 65.92% in 60 min. At the same time, g-CP had good antimicrobial abilities for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) within 4 h. The shapes of g-CP were adjustable (such as bar, cylinder, and cube) and had good mechanical properties and biocompatibility. The tensile and compressive modulus of 2 wt% g-CP were 0.093 MPa and 1.61 MPa, respectively. The Cell Counting Kit-8 (CCK-8) test and Hoechst33342/PI double staining were used to prove that g-CP had good biocompatibility. It is expected to be applied to environmental sewage treatment and wound dressing in the future.

Efficacy of sternocleidomastoid muscle flap in reducing anastomotic mediastinal/pleural cavity leak.

BACKGROUND: Anastomotic mediastinal/pleural cavity leak (AMPCL) is a life-threatening postoperative complication after esophagectomy. The objective of this study was to find a safe and effective surgical method to reduce the incidence of AMPCL. METHODS: A total of 223 patients who underwent surgery in Fujian Medical University Union Hospital from May 2020 to October 2021 were enrolled in this study. Data for preoperative and postoperative test indices, postoperative complications, perioperative treatment were collected. After using 1:1 propensity score matching (PSM) to match two cohort (caliper = 0.1), the relationship between various factors and the incidence of AMPCL were analyzed. RESULTS: 209 patients were included for further analysis in the end. There were 95 patients in the sternocleidomastoid muscle flap embedding group (intervention group) and 114 in the routine operation group (control group). There was a significant difference in mean age between two groups. Gender, age, body mass index, diabetes, American society of anesthesiologists score, preoperative neoadjuvant therapy, pathological stage were included in performing 1:1 PSM, and there were no significant differences between two groups. Median operative time was significantly less in intervention group. Anastomotic leak (AL) did not present significant difference between two groups (8 [8.6] vs. 13 [14.0], p = 0.247), however, the AMPCL in intervention group was significantly lower than control group (0 [0] vs. 6 [6.5], p = 0.029). CONCLUSIONS: The sternocleidomastoid muscle flap embedding could significantly reduce the incidence of AMPCL. This additional procedure is safe, and effective without increase in the occurrence of postoperative complications and hospital expenses.

Electrophoresis of Phosphoproteins on a Tandem Polymerized Gel.

A substrate with n phosphorylated sites may have 2n phosphor-forms for temporal-spatial regulation of biological events. Because phosphates do not significantly change molecular masses but net charges of proteins, those isoforms cannot be separated by regular mass-based sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE). A tandem polymerized gel was developed to resolve phosphor-isoforms with different masses, charges, and posttranslational modifications. Without the usage of SDS, the electrophoresis was primarily performed on three adjacent acidic polyacrylamide gels. After being concentrated on a stacking gel, protonated proteins were then separated on the Zr4+ immobilized gel through the coordination of metal ions with phosphates followed by further charge and mass (z/m)-based electrophoretic separation on a TiO2 containing gel. The presence of TiO2 nanoparticles in the third gel is aimed for the initiation of the polymerization of acrylamide in acidic conditions upon ultraviolet irradiation. Distinct isoforms of α-S1-casein, α-S2-casein, ß-casein, and κ casein model proteins located on 11, 8, 8, and 7 different bands of the tandem gel were unambiguously identified, respectively. With the tandem polymerized gel electrophoresis, new phosphorylation events that may occur simultaneously or sequentially were discovered in not only model proteins but also complex biological samples including human saliva, chicken egg, and sprouting maize. This provides a new tool to dissect complex biological processes that are triggered by dynamic phosphorylation events.

Cell-Based Ambient Venturi Autosampling and Matrix-Assisted Laser Desorption Ionization Mass Spectrometric Imaging of Secretory Products.

A cell-based ambient Venturi autosampling device was established for the monitoring of dynamic cell secretions in response to chemical stimulations in real time with temporal resolution on the order of a second. Detection of secretory products of cells and screening of bioactive compounds are primarily performed on an ambient autosampling probe and matrix-assisted laser desorption ionization (MALDI) mass spectrometry. It takes advantage of the Venturi effect in which the fluid flowing through an inlet capillary tube is automatically fed into a parallel array of multiple outlet capillaries. Cells are incubated inside the inlet capillary tube that is connected with either a syringe pump or liquid chromatography (LC) for the transfer of single compounds or mixtures, respectively. Secretory products were continuously pushed into the outlet capillaries and then spotted into a compressed thin film of the matrix material 9-aminoacridine for MALDI mass spectrometric imaging. In physiological pH, without the use of high voltages and without the use of chemical derivatizations, this platform can be applied to the direct assay of neurotransmitters or other secretory products released from cells in response to the stimulation of individual compounds or LC-separated eluates of natural mixtures. It provides a new way to identify bioactive compounds with a detection limit down to 0.04 fmol/pixel.

Sodium Pentobarbital Suppresses Breast Cancer Cell Growth Partly via Normalizing Microcirculatory Hemodynamics and Oxygenation in Tumors.

Breast cancer remains the leading cause of cancer-related death among women worldwide. Sodium pentobarbital was found to play an inhibitory role in glioma growth in rats. In this study, we aimed to evaluate the effects of sodium pentobarbital on breast cancer growth both in vitro and in vivo, and its impacts on the microcirculatory changes on both skin and tumor surface in mice bearing subcutaneous xenograft. Cell counting assay was used to assess the antiproliferative effect of sodium pentobarbital on MDA-MB-231 breast cancer cells. Subcutaneous xenograft model was established to study the role of sodium pentobarbital on in vivo tumor growth. Speed-resolved blood perfusion, hemoglobin oxygen saturation (SO2, %), total hemoglobin tissue concentration (ctTHb, µM), and red blood cell (RBC) tissue fraction (%) were examined simultaneously by using enhanced perfusion and oxygen saturation system to investigate the effects of sodium pentobarbital on microcirculatory hemodynamics and oxygenation. Sodium pentobarbital suppressed breast tumor growth both in vitro and in vivo. Cutaneous blood flux in nutritive capillaries with low-speed flow was significantly increased in tumor-bearing mice, and high-dose sodium pentobarbital treatment cause a reduction in this low-speed blood flux, whereas sodium pentobarbital therapy caused an elevated blood flux in larger microvessels with mid and high speed in a dose-dependent manner. Different doses of sodium pentobarbital exerted different actions on SO2, ctTHb, and RBC tissue fraction. Collectively, the inhibitory effect of sodium pentobarbital on breast tumor growth was at least partly associated with its ability to normalize microcirculatory hemodynamics and oxygenation in tumors. SIGNIFICANCE STATEMENT: This study is the first to demonstrate the inhibiting effect of sodium pentobarbital on breast cancer growth both in vitro and in vivo, and such an inhibition was at least partly associated with its ability to normalize microcirculatory hemodynamics and oxygenation in tumors.

Microwave-Induced Deep Catalytic Oxidation of NO Using Molecular-Sieve-Supported Oxygen-Vacancy-Enriched Fe-Mn Bimetal Oxides.

A novel microwave (MW) catalytic oxidation denitrification method was developed, which can deeply oxidize NO into nitrate/nitrite with little NO2 yield. A molecular-sieve-supported oxygen-vacancy-enriched Fe2O3-MnO2 catalyst (Ov-Fe-Mn@MOS) was fabricated. Physicochemical properties of the catalyst were revealed by various characterization methods. MW irradiation was superior to the conventional heating method in NO oxidation (90.5 vs 70.6%), and MW empowered the catalyst with excellent low-temperature activity (100-200 °C) and good resistance to H2O and SO2. Ion chromatography analysis demonstrated that the amount of nitrate/nitrite accounted for over 90.0% of the N products, but the main product gradually varied from nitrate to nitrite as the reaction proceeded because of the switching of the main reaction path of NO removal. Mechanism analyses clarified that NO oxidation was a non-radical catalytic reaction: (i) the chemisorbed NO on ≡Mn(IV) reacted with O2* to produce nitrate and (ii) the excited NO* due to MW irradiation reacted with the active O* generated from Ov···O2 to form nitrite. Density functional theory calculations combined with electron paramagnetic resonance tests revealed the promotional effects of Fe2O3 in (i) boosting the Ov's quantity; (ii) facilitating O2 adsorption; (iii) increasing the nitrite formation; and (iv) alleviating the suppression of SO2.

Metal-organic framework on porous TiO2 thin film-coated alumina beads for fractional distillation of plant essential oils.

Fractionation of essential oils is technically challenging due to enormous scaffold diversities and structural complexities as well as difficulties in the implementation of the fractionation in the gas phase. Packing beads with multi-dimensional hierarchical nanostructures have been developed herein to pack fractional columns for atmospheric distillations. Activated alumina beads were coated with a porous TiO2 thin film. Growth of Cu-BTC (benzene-1,3,5-tricarboxylate) crystals in resultant porous surfaces leads to the generation of new nanopores and increased metal centers for differential coordination with diverse components of essential oils. The TiO2 thin film is not only an integral part of the composites but also induces the oriented growth of Cu-BTC metal organic framework (MOF) crystals through coordinative interactions. These Al2O3@TiO2@Cu-BTC MOF beads show very strong absorptive capability for major components of essential oils, except for a single cyclic ether eucalyptol with steric hindrances. The eucalyptol was fractionated by using the column packed with those modified alumina beads from raw materials of Artemisia argyi, and Rosmarinus officinalis with high purities up to 96% and 93%, respectively.

Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a chronic, progressive lung vascular disease accompanied by elevated pulmonary vascular pressure and resistance, and it is characterized by increased pulmonary artery smooth muscle cell (PASMC) proliferation. Apolipoprotein A5 (ApoA5) improves monocrotaline (MCT)-induced PAH and right heart failure; however, the underlying mechanism remains unknown. Here we speculate that ApoA5 has a protective effect in pulmonary vessels and aim to evaluate the mechanism. METHODS: ApoA5 is overexpressed in an MCT-induced PAH animal model and platelet-derived growth factor (PDGF)-BB-induced proliferating PASMCs. Lung vasculature remodeling was measured by immunostaining, and PASMC proliferation was determined by cell counting kit-8 and 5-ethynyl-2'-deoxyuridine5-ethynyl-2'-deoxyuridine incorporation assays. Coimmunoprecipitation-mass spectrometry was used to investigate the probable mechanism. Next, its role and mechanism were further verified by knockdown studies. RESULTS: ApoA5 level was decreased in MCT-induced PAH lung as well as PASMCs. Overexpression of ApoA5 could help to inhibit the remodeling of pulmonary artery smooth muscle. ApoA5 could inhibit PDGF-BB-induced PASMC proliferation and endoplasmic reticulum stress by increasing the expression of glucose-regulated protein 78 (GRP78). After knocking down GRP78, the protecting effects of ApoA5 have been blocked. CONCLUSION: ApoA5 ameliorates MCT-induced PAH by inhibiting endoplasmic reticulum stress in a GRP78 dependent mechanism.