High-altitude hypoxia induces disorders of the brain- endocrine-immune network through activation of corticotropin-releasing factor and its type- 1 receptors

High-altitude hypoxia can induce physiological dysfunction and mountain sickness,but the underlying mechanism is not fully understood.Corticotrophin-releasing factor(CRF) and CRF type-1 receptors(CRFR1) are members of the CRF family and the essential controllers of the physiological activity of the hypothalamo-pituitary-adrenal(HPA) axis and modulators of endocrine and behavioral activity in response to various stressors.We have previously found that high-altitude hypoxia induces disorders of the brain-endocrine-immune network through activation of CRF and CRFR1 in the brain and periphery that include activation of the HPA axis in a time-and dose-dependent manner,impaired or improved learning and memory,and anxiety-like behavioral change.Meanwhile,hypoxia induces dysfunctions of the hypothalamo-pituitary-endocrine and immune systems,including suppression of growth and development,as well as inhibition of reproductive,metabolic and immune functions.In contrast,the small mammals that live on the Qinghai-Tibet Plateau alpine meadow display low responsiveness to extreme high-altitudehypoxia challenge,suggesting well-acclimatized genes and a physiological strategy that developed during evolution through interactions between the genes and environment.All the findings provide evidence for understanding the neuroendocrine mechanisms of hypoxia-induced physiological dysfunction.This review extends these findings.

Clinical efficacy of intradermal type Ⅰ collagen injections in treating skin photoaging in patients from high-altitude areas

BACKGROUND Photoaging,a result of chronic sun exposure,leads to skin damage and pigmentation changes.Traditional treatments may have limitations in high-altitude areas like Yunnan Province.Intradermal Col Ⅰ injections stimulate collagen production,potentially improving skin quality.This study aims to assess the efficacy and safety of this treatment for photoaging.AIM To evaluate the efficacy and safety of intradermal typeΙcollagen(ColΙ)injection for treating photoaging.METHODS This prospective,self-controlled study investigated the impact of intradermal injections of ColΙon skin photodamage in 20 patients from the Yunnan Province.Total six treatment sessions were conducted every 4 wk±3 d.Before and after each treatment,facial skin characteristics were quantified using a VISIA skin detector.Skin thickness data were assessed using the ultrasound probes of the Dermalab skin detector.The Face-Q scale was used for subjective evaluation of the treatment effect by the patients.RESULTS The skin thickness of the right cheek consistently increased after each treatment session compared with baseline.The skin thickness of the left cheek significantly increased after the third through sixth treatment sessions compared with baseline.The skin thickness of the right zygomatic region increased after the second to sixth treatment sessions,whereas that of the left zygomatic region showed a significant increase after the fourth through sixth treatment sessions.The skin thickness of both temporal regions significantly increased after the fifth and sixth treatment sessions compared with baseline(P<0.05).These findings were also supported by skin ultrasound images.The feature count for the red areas and wrinkle feature count decreased following the treatment(P<0.05).VISIA assessments also revealed a decrease in the red areas after treatment.The Face-QSatisfaction with Facial Appearance Overall and Face-Q-Satisfaction with Skin scores significantly increased after each treatment session.The overall appearance of the patients improved after treatment.CONCLUSION Intradermal ColΙinjection improves photoaging,with higher patient satisfaction and fewer adverse reactions,and could be an effective treatment method for populations residing in high-altitude areas.

Atmospheric transmission algorithm for pulsed X-rays from high-altitude nuclear detonations based on scattering correction

In high-altitude nuclear detonations,the proportion of pulsed X-ray energy can exceed 70%,making it a specific monitoring signal for such events.These pulsed X-rays can be captured using a satellite-borne X-ray detector following atmospheric transmission.To quantitatively analyze the effects of different satellite detection altitudes,burst heights,and transmission angles on the physical processes of X-ray transport and energy fluence,we developed an atmospheric transmission algorithm for pulsed X-rays from high-altitude nuclear detonations based on scattering correction.The proposed method is an improvement over the traditional analytical method that only computes direct-transmission X-rays.The traditional analytical method exhibits a maximum relative error of 67.79% compared with the Monte Carlo method.Our improved method reduces this error to within 10% under the same conditions,even reaching 1% in certain scenarios.Moreover,its computation time is 48,000 times faster than that of the Monte Carlo method.These results have important theoretical significance and engineering application value for designing satellite-borne nuclear detonation pulsed X-ray detectors,inverting nuclear detonation source terms,and assessing ionospheric effects.

Single-Arm Clinical Study of Combination Perindopril-Amlodipine Tablets in the Treatment of High-Altitude Hypertension

Objective:To evaluate the efficacy of combination perindopril/amlodipine tablets in patients with high-altitude hypertension who were previously unable to control their blood pressure with monotherapy.Methods:A total of 151 patients with high-altitude hypertension whose blood pressure remained inadequately controlled with previous monotherapy were enrolled in this study.All patients received an 8-week treatment with a combination of perindopril/amlodipine tablets,consisting of perindopril 10 mg/day and amlodipine 5 mg/day.Blood pressure measurements,including both diastolic and systolic pressures,were taken at baseline,and after 2,4,6,and 8 weeks of treatment.Results:After 8 weeks of treatment,there was a significant reduction in both average systolic and diastolic blood pressure compared to baseline(P<0.0001).Specifically,the average systolic blood pressure decreased by 24.45±13.75 mmHg,and the average diastolic blood pressure decreased by 13.37±8.40 mmHg.The overall heart rate showed no significant changes during the treatment period.Conclusion:A combination of perindopril/amlodipine tablets significantly improved blood pressure control in patients with high-altitude hypertension after 8 weeks of treatment.These results support the efficacy of combination perindopril/amlodipine as a viable treatment option for high-altitude hypertension.

EP300 contributes to high-altitude adaptation in Tibetans by regulating nitric oxide production

The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 （histone acetyltransferase p300）, we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide （NO） concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.

Over-starvation aggravates intestinal injury and promotes bacterial and endotoxin translocation under high-altitude hypoxic environment

AIM:To study whether over-starvation aggravates intestinal mucosal injury and promotes bacterial and endotoxin translocation in a high-altitude hypoxic environment.METHODS:Sprague-Dawley rats were exposed to hy-pobaric hypoxia at a simulated altitude of 7000 m for 72 h.Lanthanum nitrate was used as a tracer to detect intestinal injury.Epithelial apoptosis was observed with terminal deoxynucleotidyl transferase dUTP nick end labeling staining.Serum levels of diamino oxidase(DAO),malondialdehyde(MDA),glutamine(Gln),superoxide dismutase(SOD) and endotoxin were measured in intestinal mucosa.Bacterial translocation was detected in blood culture and intestinal homogenates.In addition,rats were given Gln intragastrically to observe its protective effect on intestinal injury.RESULTS:Apoptotic epithelial cells,exfoliated villi and inflammatory cells in intestine were increased with edema in the lamina propria accompanying effusion of red blood cells.Lanthanum particles were found in the intercellular space and intracellular compartment.Bacterial translocation to mesenteric lymph nodes(MLN) and spleen was evident.The serum endotoxin,DAO and MDA levels were significantly higher while the serum SOD,DAO and Gln levels were lower in intestine(P< 0.05).The bacterial translocation number was lower in the high altitude hypoxic group than in the high altitude starvation group(0.47±0.83 vs 2.38±1.45,P<0.05).The bacterial translocation was found in each organ,especially in MLN and spleen but not in peripheral blood.The bacterial and endotoxin translocations were both markedly improved in rats after treatment with Gln.CONCLUSION:High-altitude hypoxia and starvation cause severe intestinal mucosal injury and increase bacterial and endotoxin translocation,which can be treated with Gln.

Correlation of vascular endothelial growth factor to permeability of blood-brain barrier and brain edema during high-altitude exposure

BACKGROUND： Many studies have evaluated the role of vascular endothelial growth factor （VEGF） in traumatic brain edema and hemorrhagic brain edema. OBJECTIVE： To observe the effects of VEGF expression on permeability of the blood-brain barrier （BBB） during high-altitude and hypoxia exposure, and to investigate the correlation between VEGF expression and BBB permeability with regard to Evans blue staining and brain edema during high-altitude exposure. DESIGN, TIME AND SETTING： The randomized, controlled, animal study was performed at the Tanggula Etape, Central Laboratory of Chengdu Medical College, and Central Laboratory of General Hospital of Chengdu Military Area Command of Chinese PLA, China, from July 2003 to November 2004. MATERIALS： Quantitative RT-PCR kit （Sigma, USA）, VEGF ELISA kit （Biosource, USA）, and Evans blue （Jingchun, China） were acquired for this study. METHODS： A total of 180 Wistar rats were equally and randomly assigned to 15 groups： low-altitude （500 m）, middle-altitude （2 880 m）, high-altitude （4 200 m）, super-high-altitude （5 000 m）, 1,3, 5, 7, 9, 11, 13, 15, 17, 19, and 21 days of super high-altitude exposure. Wistar rats were exposed to various altitude gradients to establish a hypoxia model. MAIN OUTCOME MEASURES： Brain water content was calculated according to the wet-to-dry weight ratio. BBB permeability to Evans blue was determined by colorimetric method. VEGF mRNA and protein levels in brain tissues were detected using RT-PCR and double-antibody sandwich ELISA. RESULTS： Brain water content, BBB permeability to Evans blue, and VEGF mRNA and protein levels in brain tissues increased with increasing altitude and prolonged exposure to altitude. The greatest increase was determined on day 9 upon ascending 5 000 m. Simultaneously, VEGF expression positively correlated to BBB permeability of Evans blue and brain water content （r = 0.975, 0.917, P〈 0.01）. CONCLUSION： Increased VEGF protein and mRNA expression was responsible for increased BBB permeability, which may be an important mechanism underlying brain edema during high-altitude exposure.

Acute high-altitude hypoxic brain injury Identification of ten differential proteins

Hypobaric hypoxia can cause severe brain damage and mitochondrial dysfunction, and is involved in hypoxic brain injury. However, little is currently known about the mechanisms responsible for mi- tochondrial dysfunction in hypobaric hypoxic brain damage. In this study, a rat model of hypobaric hypoxic brain injury was established to investigate the molecular mechanisms associated with mi- tochondrial dysfunction. As revealed by two-dimensional electrophoresis analysis, 16, 21, and 36 differential protein spots in cerebral mitochondria were observed at 6, 12, and 24 hours post-hypobaric hypoxia, respectively. Furthermore, ten protein spots selected from each hypobaric hypoxia subgroup were similarly regulated and were identified by mass spectrometry. These de- tected proteins included dihydropyrimidinase-related protein 2, creatine kinase B-type, is- ovaleryI-CoA dehydrogenase, elongation factor Ts, ATP synthase beta-subunit, 3-mercaptopyruvate sulfurtransferase, electron transfer flavoprotein alpha-subunit, Chain A of 2-enoyI-CoA hydratase, NADH dehydrogenase iron-sulfur protein 8 and tropomyosin beta chain. These ten proteins are all involved in the electron transport chain and the function of ATP synthase. Our findings indicate that hypobaric hypoxia can induce the differential expression of several cerebral mitochondrial proteins, which are involved in the regulation of mitochondrial energy production.

Exendin-4 inhibits high-altitude cerebral edema by protecting against neurobiological dysfunction

The anti-inflammatory and antioxidant effects of exendin-4（Ex-4） have been reported previously.However,whether（Ex-4） has anti-inflammatory and antioxidant effects on high-altitude cerebral edema（HACE） remains poorly understood.In this study,two rat models of HACE were established by placing rats in a hypoxic environment with a simulated altitude of either 6000-or 7000-m above sea level（MASL） for 72 hours.An altitude of 7000 MASL with 72-hours of hypoxia was found to be the optimized experimental paradigm for establishing HACE models.Then,in rats where a model of HACE was established by introducing them to a 7000 MASL environment with 72-hours of hypoxia treatment,2,10 and,100 μg of Ex-4 was intraperitoneally administrated.The open field test and tail suspension test were used to test animal behavior.Routine methods were used to detect change in inflammatory cells.Hematoxylin-eosin staining was performed to determine pathological changes to brain tissue.Wet/dry weight ratios were used to measure brain water content.Evans blue leakage was used to determine blood-brain barrier integrity.Enzyme-linked immunosorbent assay（ELISA） was performed to measure markers of inflammation and oxidative stress including superoxide dismutase,glutathione,and malonaldehyde values,as well as interleukin-6,tumor necrosis factor-alpha,cyclic adenosine monophosphate levels in the brain tissue.Western blot analysis was performed to determine the levels of occludin,ZO-1,SOCS-3,vascular endothelial growth factor,EPAC1,nuclear factor-kappa B,and aquaporin-4.Our results demonstrate that Ex-4 preconditioning decreased brain water content,inhibited inflammation and oxidative stress,alleviated brain tissue injury,maintain blood-brain barrier integrity,and effectively improved motor function in rat models of HACE.These findings suggest that Ex-4 exhibits therapeutic potential in the treatment of HACE.

Geostructures, dynamics and risk mitigation of high-altitude and long- runout rockslides

Long-runout rockslides at high altitude could cause disaster chain in river basins and destroy towns and major infrasturctures.This paper firstly explores the initiation mechanism of high-altitude and long-runout rockslides.Two types of sliding-prone geostructure models,i.e.the fault control type in orogenic belt and the fold control type in platform area,are proposed.Then,large-scale experimental apparatus and associated numerical simulations are conducted to understanding the chain-style dynamics of rockslide-debris avalanche-debris flow.The results reveal the fragmentation effects,the rheological behaviors and the boundary layer effect of long-runout avalanche-debris flow.The dynamic character-istics of quasi-static-transition-inertia state and solid-liquid coupling in rapid movement of rockslide-debris avalanche-debris flow are investigated.Finally,the risk mitigation strategy of the non-structure and structure for resilient energy dissipation are illustrated for initiation,transition and deposition zones.The structural prevention and mitigation methods have been successfully applied to the high-altitude and long-runout rockslides in Zhouqu and Maoxian of the Wenchuan earthquake zone,as well as the other major geohazards in Qinghai-Tibet Plateau and its adjacent areas.

Comprehensive Marine Observing Experiment Based on High-Altitude Large Unmanned Aerial Vehicle(South China Sea Experiment2020 of the “Petrel Project”)

In collaboration with 12 other institutions, the Meteorological Observation Center of the China Meteorological Administration undertook a comprehensive marine observation experiment in the South China Sea using the Yilong-10 high-altitude large unmanned aerial vehicle(UAV). The Yilong-10 UAV carried a self-developed dropsonde system and a millimeter-wave cloud radar system. In addition, a solar-powered unmanned surface vessel and two drifting buoys were used. The experiment was further supported by an intelligent, reciprocating horizontal drifting radiosonde system that was deployed from the Sansha Meteorological Observing Station, with the intent of producing a stereoscopic observation over the South China Sea. Comprehensive three-dimensional observations were collected using the system from 31 July to2 August, 2020. This information was used to investigate the formation and development processes of Typhoon Sinlaku(2020). The data contain measurements of 21 oceanic and meteorological parameters acquired by the five devices, along with video footage from the UAV. The data proved very helpful in determining the actual location and intensity of Typhoon Sinlaku(2020). The experiment demonstrates the feasibility of using a high-altitude, large UAV to fill in the gaps between operational meteorological observations of marine areas and typhoons near China, and marks a milestone for the use of such data for analyzing the structure and impact of a typhoon in the South China Sea. It also demonstrates the potential for establishing operational UAV meteorological observing systems in the future, and the assimilation of such data into numerical weather prediction models.

Industrial Poverty Alleviation Model in Southwestern High-altitude Mountainous Areas of China——A Case Study of Industrial Poverty Alleviation of Xueshan Township in Luquan County of Yunnan Province through Planting Codonopsis pilosula

Due to the severe restrictions of natural conditions and ecological environment,high-altitude mountainous areas usually become the " hard bones" in the battle against poverty. Xueshan Township,Luquan Yi and Miao Autonomous County of Yunnan Province,located in the alpine valley of Jinsha River,is a major township with wide and deep poverty,and the incidence of poverty is up to 45. 00%. In recent years,Xueshan Township has insisted on the battle against poverty,made effort to develop the Codonopsis pilosula industry,and successfully developed a road to poverty alleviation through C. pilosula industry,and formed a unique industrial poverty alleviation model by the end of 2018,the incidence of poverty dropped to 0. 74%. Based on field survey and interview,this paper analyzes and summarizes the specific practices,main results,practical experience and promotion and application measures of the poverty alleviation model of C. pilosula planting industry in Xueshan Township,in the hope of providing certain reference for the targeted poverty alleviation in similar areas in Yunnan Province and other provinces of China.

Results of an Intentional Introduction of Artemia sinica in the High-Altitude Tibetan Lake Dangxiong Co:On a Base of Surveys in 2011 and 2013

1 Introduction The human population is projected to reach 9200million by 2050.A fundamental question for science is whether it is possible to increase food production to meet the demands of a human population of that magnitude.It’s possible only to increase an aquaculture production.Cultivation of fish/shrimp larvae is a bottleneck in a cultivation of the different organisms.Live food

Multiyear Observations of Deposition-Mode Ice Nucleating Particles at Two High-Altitude Stations in India

Ice nucleating particle(INP) measurements were made at two high-altitude stations in India. Aerosols collected on filter paper at Girawali Observatory, Inter University Center for Astronomy & Astrophysics(IGO), and at the Radio Astronomy Center, Ooty(RAC), were activated in deposition mode using a thermal gradient diffusion chamber to determine the INP concentrations. The measurement campaigns at IGO were conducted during 2011, 2013 and 2014, and at RAC during 2013 and 2014. When the aerosol samples were exposed to an ice supersaturation of between 5% and 23% in the temperature range-17.6?C to-22?C, the maximum INP number concentration at IGO and RAC was 1.0 L-1and 1.6 L-1, respectively.A maximum correlation coefficient of 0.76 was observed between the INP number concentration and ice supersaturation. The airmass trajectories analyzed for the measurement campaigns showed that the Arabian Desert and arid regions were the main INP contributors. Elemental analysis of particles showed the presence of Na, Cl, Si, Al, Fe, Cu, Co, Cd, S, Mn and K, as well as some rare-Earth elements like Mo, Ru, La, Ce, V and Zr. When aerosols in the size range 0.5–20 μm were considered, the fraction that acted as INPs was 1 : 104to 1 : 106at IGO, and 1 : 103to 1 : 104at RAC. The higher ratio of INPs to aerosols at RAC than IGO may be attributable to the presence of rare-Earth elements observed in the aerosol samples at RAC, which were absent at IGO.

Minimally invasive surgery vs laparotomy in patients with colon cancer residing in high-altitude areas

BACKGROUND Colon cancer is associated with a higher incidence among residents in highaltitude areas.Hypoxic environment at high altitudes inhibits the phagocytic and oxygen-dependent killing function of phagocytes,thereby increasing the inflammatory factors,inhibiting the body’s innate immunity and increasing the risk of colon cancer.AIM To examine the effect of minimally invasive surgery vs laparotomy in patients with colon cancer residing in high-altitude areas.METHODS Ninety-two patients with colon cancer in our hospital from January 2019 to February 2021 were selected and divided into the minimally invasive surgery and laparotomy groups using the random number table method,with 46 patients in each group.Minimally invasive surgery was performed in the minimally invasive group and laparotomy in the laparotomy group.Operative conditions,inflammatory index pre-and post-surgery,immune function index and complication probability were measured.RESULTS Operative duration was significantly longer and intraoperative blood loss and recovery time of gastrointestinal function were significantly less(all P<0.05)in the minimally invasive group than in the laparotomy group.The number of lymph nodes dissected was not significantly different.Before surgery,there were no significant differences in serum C-reactive protein,interleukin-6 and tumor necrosis factor-αlevels between the groups,whereas after surgery,the levels were significantly higher in the minimally invasive group(26.98±6.91 mg/L,146.38±11.23 ng/mL and 83.51±8.69 pg/mL vs 41.15±8.39 mg/L,186.79±15.36 ng/mL and 110.65±12.84 pg/mL,respectively,P<0.05).Furthermore,before surgery,there were no significant differences in CD3+,CD4+and CD4+/CD8+levels between the groups,whereas after surgery,the levels decreased in both groups,being significantly higher in the minimally invasive group(55.61%±4.39%,35.45%±3.67%and 1.30±0.35 vs 49.68%±5.33%,31.21%±3.25%and 1.13±0.30,respectively,P<0.05).Complication probability was significantly lower in the minimally invasive group(4.35%vs 17.39%,P<0.05).CONCLUSION Laparoscopic minimally invasive procedures reduce surgical trauma and alleviate the inflammatory response and immune dysfunction caused by invasive operation.It also shortens recovery time and reduces complication probability.

Small extracellular vesicles from hypoxia-preconditioned bone marrow mesenchymal stem cells attenuate spinal cord injury via miR-146a-5p-mediated regulation of macrophage polarization

Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.

Study on Query System of the Historical High-altitude Ground Weather Chart

We introduced query system of the historical high-altitude surface weather chart. Historical high-altitude surface data were converted to Grads data format. Grads as generation tool of the image, ASP was used to compile WEB page. By B/S mode, only user submitted necessary conditions for the image to server by client browser, historical high-altitude surface weather chart at corresponding time and height could be ob- tained. Without any procedures and related data, only needed client browser, user could use image conveniently to a large extent.

Immune consequences of exercise in hypoxia:A narrative review

Immune outcomes are key mediators of many health benefits of exercise and are determined by exercise type,dose(frequency/duration,intensity),and individual characteristics.Similarly,reduced availability of ambient oxygen(hypoxia)modulates immune functions depending on the hypoxic dose and the individual capacity to respond to hypoxia.How combined exercise and hypoxia(e.g.,high-altitude training)sculpts immune responses is not well understood,although such combinations are becoming increasingly popular.Therefore,in this paper,we summarize the impact on immune responses of exercise and of hypoxia,both independently and together,with a focus on specialized cells in the innate and adaptive immune system.We review the regulation of the immune system by tissue oxygen levels and the overlapping and distinct immune responses related to exercise and hypoxia,then we discuss how they may be modulated by nutritional strategies.Mitochondrial,antioxidant,and anti-inflammatory mechanisms underlie many of the adaptations that can lead to improved cellular metabolism,resilience,and overall immune functions by regulating the survival,differentiation,activation,and migration of immune cells.This review shows that exercise and hypoxia can impair or complement/synergize with each other while regulating immune system functions.Appropriate acclimatization,training,and nutritional strategies can be used to avoid risks and tap into the synergistic potentials of the poorly studied immune consequences of exercising in a hypoxic state.

Vital contribution of brassinosteroids to hypoxia-stimulated coleoptile elongation in submerged rice

The rapid elongation of rice(Oryza sativa)coleoptile is pivotal for the plant plumule to evade hypoxia stress induced by submergence,a condition often arising from overirrigation,ponding,rainstorms,or flooding.While brassinosteroids(BRs)are recognized for their diverse roles in plant growth and development,their influence on coleoptile elongation under hypoxic conditions remains largely unexplored.In this study,we demonstrate the significant requirement of BRs for coleoptile elongation in deep water.During coleoptile development,Glycogen Synthase Kinase3-Like Kinase2(GSK2),the central inhibitor of BR signaling in rice,undergoes substantial suppression in deep water but induction in air.In contrast,the dephosphorylated form of BRASSINAZOLE RESISTANT1(OsBZR1),representing the active form of the key BR signaling transcription factor,is induced in water but suppressed in air.Remarkably,the knockout of GSK3-like kinase genes significantly enhances coleoptile elongation in deep water,strongly indicating a vital contribution of BR response to hypoxia-stimulated coleoptile elongation.Transcriptome analysis uncovers both BR-associated and BR-independent hypoxia responses,implicating substance metabolism,redox reactions,abiotic stress responses,and crosstalk with other hormones in the regulation of BR-induced hypoxia responses.In summary,our findings suggest that rice plumules rapidly elongate coleoptiles through the activation of BR response in deep water,enabling them to escape from submergence-induced hypoxia stress.

Hypoxia-mediated programmed cell death is involved in the formation of wooden breast in broilers

Background Wooden breast(WB)myopathy is a common myopathy found in commercial broiler chickens worldwide.Histological examination has revealed that WB myopathy is accompanied by damage to the pectoralis major(PM)muscle.However,the underlying mechanisms responsible for the formation of WB in broilers have not been fully elucidated.This study aimed to investigate the potential role of hypoxia-mediated programmed cell death(PCD)in the formation of WB myopathy.Results Histological examination and biochemical analysis were performed on the PM muscle of the control(CON)and WB groups.A significantly increased thickness of the breast muscle in the top,middle,and bottom portions(P<0.01)was found along with pathological structure damage of myofibers in the WB group.The number of capillaries per fiber in PM muscle,and the levels of p O_(2) and s O_(2) in the blood,were significantly decreased(P<0.01),while the levels of p CO_(2) and TCO_(2) in the blood were significantly increased(P<0.05),suggesting hypoxic conditions in the PM muscle of the WB group.We further evaluated the PCD-related pathways including autophagy,apoptosis,and necroptosis to understand the consequence response to enhanced hypoxic conditions in the PM muscle of birds with WB.The ratio of LC3 II to LC3 I,and the autophagy-related factors HIF-1α,BNIP3,Beclin1,AMPKα,and ULK1 at the m RNA and protein levels,were all significantly upregulated(P<0.05),showing that autophagy occurred in the PM muscle of the WB group.The apoptotic index,as well as the expressions of Bax,Cytc,caspase 9,and caspase 3,were significantly increased(P<0.05),whereas Bcl-2 was significantly decreased(P<0.05)in the WB-affected PM muscle,indicating the occurrence of apoptosis mediated by the mitochondrial pathway.Additionally,the expressions of necroptosis-related factors RIP1,RIP3,and MLKL,as well as NF-κB and the pro-inflammatory cytokines TNF-α,IL-1β,and IL-6,were all significantly enhanced(P<0.05)in the WB-affected PM muscle.Conclusions The WB myopathy reduces blood supply and induces hypoxia in the PM muscle,which is closely related to the occurrence of PCD including apoptosis,autophagy,and necroptosis within myofibers,and finally leads to abnormal muscle damage and the development of WB in broilers.