Potential Candidate Molecule of Photosystem II Inhibitor Herbicide-Brassicanate A Sulfoxide.

Brassicanate A sulfoxide, a secondary metabolite of broccoli, exhibited the inhibition of weed growth, but its mechanism of action on weeds remains unclear. To elucidate the mechanism by which brassicanate A sulfoxide suppresses weeds, this study explores the interaction between brassicanate A sulfoxide and the photosystem II D1 protein through molecular docking and molecular dynamics simulations. This research demonstrates that brassicanate A sulfoxide interacts with the photosystem II D1 protein by forming hydrogen bonds with Phe-261 and His-214. The successful expression of the photosystem II D1 protein in an insect cell/baculovirus system validated the molecular docking and dynamics simulations. Biolayer interferometry experiments elucidated that the affinity constant of brassicanate A sulfoxide with photosystem II was 2.69 × 10-3 M, suggesting that brassicanate A sulfoxide can stably bind to the photosystem II D1 protein. The findings of this study contribute to the understanding of the mode of action of brassicanate A sulfoxide and also aid in the development of natural-product-based photosynthesis-inhibiting herbicides.

NRF2 preserves genomic integrity by facilitating ATR activation and G2 cell cycle arrest.

Nuclear factor erythroid 2-related factor 2 (NRF2) is a well-characterized transcription factor that protects cells against oxidative and electrophilic stresses. Emerging evidence has suggested that NRF2 protects cells against DNA damage by mechanisms other than antioxidation, yet the mechanism remains poorly understood. Here, we demonstrate that knockout of NRF2 in cells results in hypersensitivity to ionizing radiation (IR) in the presence or absence of reactive oxygen species (ROS). Under ROS scavenging conditions, induction of DNA double-strand breaks (DSBs) increases the NRF2 protein level and recruits NRF2 to DNA damage sites where it interacts with ATR, resulting in activation of the ATR-CHK1-CDC2 signaling pathway. In turn, this leads to G2 cell cycle arrest and the promotion of homologous recombination repair of DSBs, thereby preserving genome stability. The inhibition of NRF2 by brusatol increased the radiosensitivity of tumor cells in xenografts by perturbing ATR and CHK1 activation. Collectively, our results reveal a novel function of NRF2 as an ATR activator in the regulation of the cellular response to DSBs. This shift in perspective should help furnish a more complete understanding of the function of NRF2 and the DNA damage response.

Macitentan Attenuates Chronic Mountain Sickness in Rats by Regulating Arginine and Purine Metabolism.

Chronic mountain sickness (CMS) is a high altitude complication with high rates of morbidity and mortality. CMS is characterized by high-altitude polycythemia (HAPC) and high-altitude pulmonary hypertension (HAPH). In this study, macitentan, a dual endothelin receptor antagonist, was used to treat CMS, and the induced metabolomics changes were studied. CMS was induced in rats in a hypobaric hypoxia chamber (simulating a 5500 m plateau) for 4 weeks. Macitentan was administered in the third and fourth weeks (30 mg·kg-1·day-1). At the end of the follow-up period, we performed echocardiography, measured hemodynamic parameters and hematocrit, and performed histological staining. Furthermore, ultraperformance liquid chromatography-mass spectrometry (UPLC-MS)-based metabolic analysis was applied to explore metabolic changes associated with hypobaric hypoxia, with or without macitentan. qRT-PCR and kits for the determination of xanthine oxidase (XO) activity were used for validation experiments. Macitentan was effective in attenuating CMS, including CMS-induced right ventricle hypertrophy, HAPC, and HAPH. The levels of 48 metabolites were significantly changed in the CMS model group compared to the control group. Of these changes, 21 were reversed by treatment with macitentan. Enrichment analysis revealed that the purine metabolism pathway, as well as the arginine/proline metabolism pathway, might be the key pathways adjusted by macitentan. Furthermore, we verified macitentan played a beneficial role by directly regulating the expression of arginine1 and arginine2 in the arginine/proline metabolic pathway, and the activity of xanthine oxidase in the purine metabolic pathway. In conclusion, this study demonstrated that macitentan significantly ameliorated CMS in rats, and the mechanism was attributed to the reversion of the disorder in purine and arginine/proline metabolism, via direct regulation of XO activity and arginine1/2 expression. These findings are expected to provide new insights into the therapeutics and mechanism of macitentan in CMS.

RMI1 contributes to DNA repair and to the tolerance to camptothecin.

Maintenance of genome integrity is critical for faithful propagation of genetic information and the prevention of the mutagenesis induced by various DNA damage events. RecQ-mediated genome instability protein 1 (RMI1), together with Bloom syndrome protein and topoisomerase IIIα, form an evolutionarily conserved complex that is critical for the maintenance of genomic stability. Herein, we report that RMI1 depletion increases cell sensitivity to camptothecin treatment, as shown by an elevation of genotoxic stress-induced DNA double-strand breaks, a stronger activation of the DNA damage response, and a greater G2/M cell cycle delay. Our findings support that, upon DNA damage, RMI1 forms nuclear foci at the damaged regions, interacts with RAD51, and facilitates the recruitment of RAD51 to initiate homologous recombination. Our data reveal the importance of RMI1 in response to DNA double-strand breaks and shed light on the molecular mechanisms by which RMI1 contributes to maintain genome stability.-Fang, L., Sun, X., Wang, Y., Du, L., Ji, K., Wang, J., He, N., Liu, Y., Wang, Q., Zhai, H., Hao, J., Xu, C., Liu, Q. RMI1 contributes to DNA repair and to the tolerance to camptothecin.

Interface Bonding Properties and Mechanism of Poplar Board-Veneered Wood Fiber/Polypropylene Composites with Chlorinated Polypropylene Films as an Intermediate Layer.

It is difficult to decorate wood plastic composites with wood veneer because their surface energy is low and there are no pores on the surface. In the present study, we developed an environmentally friendly and convenient method to decorate the wood fiber/polypropylene (WF/PP) composite board. We used chlorinated polypropylene (CPP) as an intermediate film to laminate wood veneer to WF/PP composite boards by hot-pressing at 110 °C and then cooling down. The interface bonding mechanism between the wood veneer, CPP layer, and WF/PP composite was analyzed using scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDS), surface roughness test, and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). The results indicated that CPP penetrated the wood pores and formed a firm anchor structure. SEM images showed small cracks at the interface between CPP and PP when WF/PP contained less WF. The results of SEM-EDS and ATR-FTIR showed that WF/PP composites with a higher WF content would have more fibers exposed at the surface, thus making the surface rough and providing more specific surface area. The veneered WF/PP composite with 80% WF content had the highest surface bond strength and water resistance.

Equatorin is not essential for acrosome biogenesis but is required for the acrosome reaction.

The acrosome is a specialized organelle that covers the anterior part of the sperm nucleus and plays an essential role in mammalian fertilization. However, the regulatory mechanisms controlling acrosome biogenesis and acrosome exocytosis during fertilization are largely unknown. Equatorin (Eqtn) is a membrane protein that is specifically localized to the acrosomal membrane. In the present study, the physiological functions of Eqtn were investigated using a gene knockout mouse model. We found that Eqtn(-/-) males were subfertile. Only approximately 50% of plugged females were pregnant after mating with Eqtn(-/-) males, whereas more than 90% of plugged females were pregnant after mating with control males. Sperm and acrosomes from Eqtn(-/-) mice presented normal motility and morphology. However, the fertilization and induced acrosome exocytosis rates of Eqtn-deficient sperm were dramatically reduced. Further studies revealed that the Eqtn protein might interact with Syntaxin1a and SNAP25, but loss of Eqtn did not affect the protein levels of these genes. Therefore, our study demonstrates that Eqtn is not essential for acrosome biogenesis but is required for the acrosome reaction. Eqtn is involved in the fusion of the outer acrosomal membrane and the sperm plasma membrane during the acrosome reaction, most likely via an interaction with the SNARE complex.

Inhibition of Potato Fusarium Wilt by Bacillus subtilis ZWZ-19 and Trichoderma asperellum PT-29: A Comparative Analysis of Non-Targeted Metabolomics.

Potato Fusarium Wilt is a soil-borne fungal disease that can seriously harm potatoes throughout their growth period and occurs at different degrees in major potato-producing areas in China. To reduce the use of chemical agents and improve the effect of biocontrol agents, the inhibitory effects of the fermentation broth of Bacillus subtilis ZWZ-19 (B) and Trichoderma asperellum PT-29 (T) on Fusarium oxysporum were compared under single-culture and co-culture conditions. Furthermore, metabolomic analysis of the fermentation broths was conducted. The results showed that the inhibitory effect of the co-culture fermentation broth with an inoculation ratio of 1:1 (B1T1) was better than that of the separately cultured fermentation broths and had the best control effect in a potted experiment. Using LC-MS analysis, 134 metabolites were determined and classified into different types of amino acids. Furthermore, 10 metabolic pathways had the most significant variations, and 12 were related to amino acid metabolism in the KEGG analysis. A correlation analysis of the 79 differential metabolites generated through the comprehensive comparison between B, T, and B1T1 was conducted, and the results showed that highly abundant amino acids in B1T1 were correlated with amino acids in B, but not in T.

Ruthenium ion catalytic oxidation depolymerization of lignite under ultra-low dosage of RuCl3 catalyst and separation of the organic products with inorganic salts.

Depolymerization of lignite into valuable chemicals via ruthenium ion catalytic oxidation (RICO) is a potential route for the non-energy utilization of lignite. However, the high cost of the Ru catalyst during depolymerization and the high content of inorganic salts in the product solution limit the development of this route. In this work, RICO depolymerization of lignite was conducted under an ultra-low dosage of RuCl3 catalyst to decrease the usage of the catalyst during the RICO process. Different approaches were attempted to fulfill the separation of benzene polycarboxylic acids (BPCAs) products with the inorganic salts derived from the oxidant NaIO4, including butanone extraction and desalting via crystallization under different temperatures. The results show that lignite can be efficiently depolymerized under the mass ratio of RuCl3/lignite as low as 1/1000 by prolonging the reaction time without decreasing the depolymerization degree and BPCAs yields compared to the commonly used mass ratio of 1/10. Butanone can extract ca. 91% of the total BPCAs in the product solution, and the inorganic salts content (mainly NaIO3) in the extraction solution was as low as 0.19 mg mL-1. A new strategy of first acidification of depolymerization aqueous solution by HCl and then extraction by butanone is proved to be efficient for the separation of BPCAs with inorganic salts. Salting out via crystallization under lower temperature can remove ca. half content of the salts, and the efficiency is inferior to butanone extraction. The low usage of RuCl3 can efficiently decrease the catalyst cost of the RICO process, and butanone extraction can fulfill the enrichment of BPCAs and the separation of BPCAs with inorganic salts. This work is meaningful for the potential application of RCIO depolymerization of lignite for the production of valuable chemicals.

Effect of Mortise and Tenon Structure on the Properties of Wood Flour Polyvinyl Chloride-Laminated Veneer Lumber Co-Extruded Composites.

Core-shell composites with strong weather resistance, mechanical strength and creep resistance can be prepared using co-extrusion technology. Considering the weak bonding strength between core-shell interfaces, this study started from the concept of a mortise and tenon combination; three types of conical, rectangular and trapezoidal mortise and tenon joints were prepared, and their bending properties, long-term creep properties, interfacial bonding properties, and dimensional stability properties were tested. Results showed that the mortise and tenon structure could form a mechanical interlock between the outer-shell-layer polyvinyl chloride (PVC) wood-plastic composite (WPVC) and the inner-core-layer laminated veneer lumber (LVL), which could effectively improve the interface bonding property between the two layers. Among them, the trapezoidal mortise and tenon structure had the largest interface bonding force compared with the tapered and rectangular mortise and tenon structure, where the interface bonding strength reached 1.01 MPa. Excellent interface bonding can effectively transfer and disperse stress, so the trapezoidal mortise and tenon structure had the best bending properties and creep resistance, with a bending strength of 59.54 MPa and a bending modulus of 5.56 GPa. In the long-term creep test, the deformation was also the smallest at about 0.2%, and its bending properties, creep resistance and interface bonding performance were also the best. The bending strength was 59.54 MPa and the bending modulus was 5.56 GPa; in the long-term creep test, the strain curve was the lowest, about 0.2%. In addition, the mortise and tenon structure could disperse the stress of the inner shell LVL after water absorption and expansion, thus significantly improving the dimensional stability of the co-extruded composite after water absorption.

Identification of novel urine proteomic biomarkers for high stamina in high-altitude adaptation.

Introduction: We aimed to identify urine biomarkers for screening individuals with adaptability to high-altitude hypoxia with high stamina levels. Although most non-high-altitude natives experience rapid decline in physical ability when ascending to high altitudes, some individuals with high-altitude adaptability continue to maintain high endurance levels. Methods: We divided the study population into two groups: the LC group (low change in endurance from low to high altitude) and HC group (high change in endurance from low to high altitude). We performed blood biochemistry testing for individuals at high altitudes and sea level. We used urine peptidome profiling to compare the HH (high-altitude with high stamina) and HL (high-altitude with low stamina) groups and the LC and HC groups to identify urine biomarkers. Results: Routine blood tests revealed that the concentration of white blood cells, lymphocytes and platelets were significantly higher in the HH group than in the HL group. Urine peptidome profiling showed that the proteins ITIH1, PDCD1LG2, NME1-NME2, and CSPG4 were significantly differentially expressed between the HH and HL groups, which was tested using ELISA. Urine proteomic analysis showed that LRG1, NID1, VASN, GPX3, ACP2, and PRSS8 were urine proteomic biomarkers of high stamina during high-altitude adaptation. Conclusion: This study provides a novel approach for identifying potential biomarkers for screening individuals who can adapt to high altitudes with high stamina.

RMI1 facilitates repair of ionizing radiation-induced DNA damage and maintenance of genomic stability.

Ionizing radiation (IR) causes a wide variety of DNA lesions, of which DNA double-stranded breaks (DSBs) are the most deleterious. Homologous recombination (HR) is a crucial route responsible for repairing DSBs. RecQ-mediated genome instability protein 1 (RMI1) is a member of an evolutionarily conserved Bloom syndrome complex, which prevents and resolves aberrant recombination products during HR, thereby promoting genome stability. However, little is known about the role of RMI1 in regulating the cellular response to IR. This study aimed to understand the cellular functions and molecular mechanisms by which RMI1 maintains genomic stability after IR exposure. Here, we showed IR upregulated the RMI1 protein level and induced RMI1 relocation to the DNA damage sites. We also demonstrated that the loss of RMI1 in cells resulted in enhanced levels of DNA damage, sustained cell cycle arrest, and impaired HR repair after IR, leading to reduced cell viability and elevated genome instability. Taken together, our results highlighted the direct roles of RMI1 in response to DNA damage induced by IR and implied that RMI1 might be a new genome safeguard molecule to radiation-induced damage.

The Aqueous Extract of Brassica oleracea L. Exerts Phytotoxicity by Modulating H2O2 and O2- Levels, Antioxidant Enzyme Activity and Phytohormone Levels.

Allelopathic interactions between plants serve as powerful tools for weed control. Despite the increasing understanding of the allelopathic mechanisms between different plant species, the inhibitory effects of B. oleracea on weed growth remain poorly understood. In this study, we conducted experiments to demonstrate that B. oleracea extract can suppress the germination of Panicum miliaceum L.varruderale Kit. seeds as well as of the roots, shoots and hypocotyl elongation of P. miliaceum seedlings. Furthermore, we observed that B. oleracea extract reduced the levels of hydrogen peroxide and superoxide anion in the roots while increasing the activities of catalase and ascorbate peroxidase. In the shoots, B. oleracea extract enhanced the activities of superoxide dismutase and peroxidase. Moreover, the use of the extract led to an increase in the content of phytohormones (indole-3-acetic acid, indole-3-acetaldehyde, methyl indole-3-acetate, N6-isoPentenyladenosine, dihydrozeatin-7-glucoside, abscisic acid and abscisic acid glucose ester) in P. miliaceum seedlings. Interestingly, the aqueous extract contained auxins and their analogs, which inhibited the germination and growth of P. miliaceum. This may contribute to the mechanism of the B. oleracea-extract-induced suppression of P. miliaceum growth.

Supplementation of mitochondria from endometrial mesenchymal stem cells improves oocyte quality in aged mice.

Maternal ageing is one of the major causes of reduced ovarian reserve and low oocyte quality in elderly women. Decreased oocyte quality is the main cause of age-related infertility. Mitochondria are multifunctional energy stations that determine the oocyte quality. The mitochondria in aged oocytes display functional impairments with mtDNA damage, which leads to reduced competence and developmental potential of oocytes. To improve oocyte quality, mitochondrial supplementation is carried out as a potential therapeutic approach. However, the selection of suitable cells as the source of mitochondria remains controversial. We cultivated endometrial mesenchymal stem cells (EnMSCs) from aged mice and extracted mitochondria from EnMSCs. To improve the quality of oocytes, GV oocytes were supplemented with mitochondria via microinjection. And MII oocytes from aged mice were fertilized by intracytoplasmic sperm injection (ICSI), combining EnMSCs' mitochondrial microinjection. In this study, we found that the mitochondria derived from EnMSCs could significantly improve the quality of aged oocytes. Supplementation with EnMSC mitochondria significantly increased the blastocyst ratio of MII oocytes from aged mice after ICSI. We also found that the birth rate of mitochondria-injected ageing oocytes was significantly increased after embryo transplantation. Our study demonstrates that supplementation with EnMSC-derived mitochondria can improve the quality of oocytes and promote embryo development in ageing mice, which might provide a prospective strategy for clinical treatment.

Menstrual blood-derived stem cells and its mitochondrial treatment improve the ovarian condition of aged mice.

Aging causes a decline in ovarian function and may contribute to ovarian failure and infertility. We investigated the effect of menstrual blood-derived mesenchymal stem cells (MenSCs) and their mitochondria on ovarian function in aged mice. We performed two treatment protocols: i) ovaries of recipient aged mice were treated in vivo with MenSCs 3D alginate gel; ii) ovaries were injected with mitochondria suspension and then incubated with mitochondrial 3D gel. Seven days after treatment, ovaries were harvested for histological assessment by HE staining and transcriptomic analysis by RNA-seq. Our data showed that after incubation with stem cell 3D gel, the MenSCs could be detected in the recipient mouse ovary. HE staining showed that the follicular state of aging ovary improved with both treatments. RNA-seq analysis showed that mitochondrial pathway-related genes were upregulated and significantly enriched in the ovaries treated by MenSCs or their mitochondria. Conclusions: Treatment with MenSCs or their mitochondria can enhance the expression of mitochondrial pathway-related genes and promote the recovery of ovarian function in aged mice.

A novel and highly efficient Zr-containing catalyst supported by biomass-derived sodium carboxymethyl cellulose for hydrogenation of furfural.

Functional use of biomass based on its structural properties is an efficient approach for the valuable utilization of biomass resources. In this work, carboxymethyl cellulose zirconium-based catalyst (Zr-CMC) was constructed by the coordination between the carboxylic groups in sodium carboxymethyl cellulose (CMC-Na) with transition metal Zr4+. The prepared catalyst was applied into the synthesis of furfuryl alcohol (FAL) by catalytic transfer hydrogenation of biomass-derived furfural (FF) using isopropanol as hydrogen donor. Both the preparation conditions and the reaction conditions of Zr-CMC catalyst were investigated and optimized. The results showed that Zr-CMC was efficient for the reaction with the FF conversion, FAL yield and selectivity reaching to 92.5%, 91.5 %, and 99.0%, respectively, under the mild conditions (90°C). Meanwhile, the Zr-CMC catalyst could be reused at least for five times without obvious decrease in efficiency, indicating the catalyst had excellent stability. With the advantages of sustainable raw materials, high efficiency, and excellent stability, the prepared catalyst is potential for application in the field of biomass conversion.

Recent Development of Optoelectronic Application Based on Metal Halide Perovskite Nanocrystals.

In the past years, metal halide perovskite (MHP) single crystals have become promising candidates for optoelectronic devices since they possess better optical and charge transport properties than their polycrystalline counterparts. Despite these advantages, traditional bulk growth methods do not lend MHP single crystals to device integration as readily as their polycrystalline analogues. Perovskite nanocrystals (NCs), nanometer-scale perovskite single crystals capped with surfactant molecules and dispersed in non-polar solution, are widely investigated in solar cells and light-emitting diodes (LEDs), because of the direct bandgap, tunable bandgaps, long charge diffusion length, and high carrier mobility, as well as solution-processed film fabrication and convenient substrate integration. In this review, we summarize recent developments in the optoelectronic application of perovskite nanocrystal, including solar cells, LEDs, and lasers. We highlight strategies for optimizing the device performance. This review aims to guide the future design of perovskite nanocrystals for various optoelectronic applications.

Concentrations, spatial distribution, and pollution assessment of heavy metals in surficial sediments from upstream of Yellow River, China.

Surface sediments were collected from 122 sites in the upstream of the Yellow River, China. The concentration of Fe, Mn, Cu, Ni, Zn, Cr, Pb, and Cd in sediments was investigated to explore the spatial distribution based on statistics and interpolation method. The results suggested that the concentrations of heavy metals were lower than potential effect levels (PEL). The samples above threshold effect level (TEL) for Pb and Zn were less than 10%, while almost 50% of samples for Ni exceeded PEL. Pb and Zn in sediments performed little or no adverse effects on the aquatic ecosystems. Higher concentrations of all heavy metals occurred in Qinghai and Gansu sections; the concentrations of Cu, Ni, and Zn were significantly higher than the Inner Mongolia section. Lower concentration of Fe, Mn, Cu, Ni, and Zn appeared in Qinghai section; the concentrations of Fe, Mn, Cr, and Pb manifested relatively steady and similar distributions and approximately decreasing tendency along the upstream of Yellow River.

CRISPR/Cas9 in zebrafish: An attractive model for FBN1 genetic defects in humans.

BACKGROUND: Mutations in the fibrillin-1 gene (FBN1) are associated with various heritable connective tissue disorders (HCTD). The most studied HCTD is Marfan syndrome. Ninety percent of Marfan syndrome is caused by mutations in the FBN1 gene. The zebrafish share high genetic similarity to humans, representing an ideal model for genetic research of human diseases. This study aimed to generate and characterize fbn1+/- mutant zebrafish using the CRISPR/Cas9 gene-editing technology. METHODS: CRISPR/Cas9 was applied to generate an fbn1 frameshift mutation (fbn1+/- ) in zebrafish. F1 fbn1+/- heterozygotes were crossed with transgenic fluorescent zebrafish to obtain F2 fbn1+/- zebrafish. Morphological abnormalities were assessed in F2 fbn1+/- zebrafish by comparing with the Tuebingen (TU) wild-type controls at different development stages. RESULTS: We successfully generated a transgenic line of fbn1+/- zebrafish. Compared with TU wild-type zebrafish, F2 fbn1+/- zebrafish exhibited noticeably decreased pigmentation, increased lengths, slender body shape, and abnormal cardiac blood flow from atrium to ventricle. CONCLUSION: We generated the first fbn1+/- zebrafish model using CRISPR/Cas9 gene-editing approach to mimic FBN1 genetic defects in humans, providing an attractive model of Marfan syndrome and a method to determine the pathogenicity of gene mutation sites.

A General Route of Using Lignite Depolymerized Derivatives for Catalyst Construction: Insights into the Effects of the Derivative Structures and Solvents.

Depolymerization is an emerging and promising route for the value-added utilization of low-rank coal (LRC) resources, and how to use the complex depolymerized mixtures efficiently is of great importance for this route. In this work, we designed the rational route of using depolymerized mixtures from lignite via ruthenium ion-catalyzed oxidation (RICO) depolymerization directly without complex separation to construct a Zr-based hydrogenation catalyst. The prepared catalyst was applied into the catalytic transfer hydrogenation of biomass-derived carbonyl compounds. Meanwhile, a copper-based oxidation catalyst was also constructed via a similar route to investigate the universality of the proposed route. Special insights were given into how the depolymerized components with different structures influenced the performances of the catalysts. The effects of the solvents used during the catalyst preparation (H2O and DMF) were also studied. The results showed that the proposed route using the depolymerized mixtures from lignite via RICO to construct catalysts was feasible for both Zr-based and Cu-based catalysts. The two catalysts prepared gave high efficiency for their corresponding reaction, i.e., the Zr-based catalyst for catalytic transfer hydrogenation of biomass-derived carbonyl compounds and the Cu-based catalyst for selective oxidation of alcohols into aldehydes. Different depolymerized components contributed differently to the activity of the catalyst, and the solvents during the preparation process could also influence the activity of the catalyst. The depolymerized components and the solvents influenced the activities of the Zr-based catalyst mainly via changing the Zr contents, the microenvironment of Zr4+, and the specific areas of the catalyst.

Effects of Intermittent Normoxia on Chronic Hypoxic Pulmonary Hypertension and Right Ventricular Hypertrophy in Rats.

Liu, Chunlei, Xu Chen, Ge Guo, Xiang Xu, Xin Li, Qingxia Wei, Yanying Shen, Hanlu Li, Jianxiu Hao, Ya Ping Tian, and Kunlun He. Effects of intermittent normoxia on chronic hypoxic pulmonary hypertension and right ventricular hypertrophy in rats. High Alt Med Biol. 22: 184-192, 2021. Background: Individuals with chronically low arterial oxygen tension owing to high altitude develop elevated rates of pulmonary hypertension (PH) and right ventricular (RV) hypertrophy. However, the effects of the frequency and duration of normoxic exposure on PH and RV hypertrophy have not been adequately assessed; thus, we aimed to analyze the same. Materials and Methods: PH and RV hypertrophy were induced in 60 rats using a hypobaric chamber. Of these 60 rats, every 10 were exposed to normoxic conditions for 30 minutes once (1T/D), three times (3T/D), or five times daily (5T/D), or for one 150-minute recovery daily (1LT/D). Furthermore, 10 rats were housed in a normoxic environment, and another 10 were subjected to continuous hypoxia. After 4 weeks, hemodynamic measurements were recorded, and the hearts were harvested for pathomorphological observations. Results: Average pulmonary arterial pressures (PAP) of control rats and those exposed to hypobaric hypoxia were 14.1 and 32.3 mmHg, respectively. After 30 minutes of exposure to normoxia 3T/D, 5T/D, or 1LT/D, PAP values were reduced to 27.1, 27.9, or 26.8 mmHg, respectively. Four weeks of hypoxic exposure elevated the RV/heart weight (HW) ratios, while exposure to normoxia 3T/D, 5T/D, and 1LT/D significantly reduced RV/HW. In addition, exposure to normoxia 3T/D, 5T/D, 1LT/D reduced the percentage wall thickness of the pulmonary artery as well as the hypertrophy indices of atrial natriuretic peptide, brain natriuretic peptide, and myosin heavy chain 7 (MYH-7). Conclusions: Thirty-minute exposure to normoxic conditions of 3T/D, 5T/D, or 1LT/D effectively ameliorates PH and RV thickening.