A pervasive phosphorylation cascade modulation of plant transcription factors in response to abiotic stress.

MAIN CONCLUSION: Transcriptional regulation of stress-responsive genes is a crucial step in establishing the mechanisms behind plant abiotic stress tolerance. A sensitive method of regulating transcription factors activity, stability, protein interaction, and subcellular localization is through phosphorylation. This review highlights a widespread regulation mechanism that involves phosphorylation of plant TFs in response to abiotic stress. Abiotic stress is one of the main components limiting crop yield and sustainability on a global scale. It greatly reduces the land area that is planted and lowers crop production globally. In all living organisms, transcription factors (TFs) play a crucial role in regulating gene expression. They participate in cell signaling, cell cycle, development, and plant stress response. Plant resilience to diverse abiotic stressors is largely influenced by TFs. Transcription factors modulate gene expression by binding to their target gene's cis-elements, which are impacted by genomic characteristics, DNA structure, and TF interconnections. In this review, we focus on the six major TFs implicated in abiotic stress tolerance, namely, DREB, bZIP, WRKY, ABF, MYB, and NAC, and the cruciality of phosphorylation of these transcription factors in abiotic stress signaling, as protein phosphorylation has emerged as one of the key post-translational modifications, playing a critical role in cell signaling, DNA amplification, gene expression and differentiation, and modification of other biological configurations. These TFs have been discovered after extensive study as stress-responsive transcription factors which may be major targets for crop development and important contributors to stress tolerance and crop production.

Lycium barbarum Ameliorates Neural Damage Induced by Experimental Ischemic Stroke and Radiation Exposure.

Ischemic stroke and cranial radiotherapy may induce brain inflammatory response, oxidative stress, apoptosis and neuronal loss, and impairment of neurogenesis. Lycium barbarum has anti-oxidation, anti-inflammatory, anti-tumor and anti-aging properties, may produce both neuroprotective and radioprotective effects. In this narrative review paper, we described the neuroprotective effect of Lycium barbarum in different animal models of experimental ischemic stroke and limited studies in irradiated animal models. Relevant molecular mechanisms are also summarized. It has been shown that in experimental ischemic stroke models, Lycium barbarum produces neuroprotective effects by modulating neuroinflammatory factors such as cytokines and chemokines, reactive oxygen species, and neurotransmitter and receptor systems. In irradiation animal models, Lycium barbarum prevents radiation-induced loss of hippocampal interneurons. Given its minimal side-effects, these preclinical studies suggest that Lycium barbarum may be a promising radio-neuro-protective drug that can be used as an adjunct treatment to radiotherapy for brain tumor and in the treatment of ischemic stroke. At molecular levels, Lycium barbarum may regulate PI3K/Akt/GSK-3ß, PI3K/Akt/mTOR, PKCε/Nrf2/HO-1, keap1-Nrf2/HO-1, and NR2A and NR2B receptor- related signal transduction pathways to produce neuroprotective effects.

The impact of image quality on the diagnostic performance of CT-derived fractional flow reserve / 中华放射学杂志

Objective:To explore the impact of coronary CT angiography (CCTA) image quality and related factors on the diagnostic performance of CT-derived fractional flow reserve (CT-FFR).Methods:Based on the CT-FFR CHINA trial, the prospective multicenter trial enrolled patients with suspected coronary artery disease who underwent CCTA, CT-FFR and FFR measurement. The subjective and objective assessments of CCTA image were performed on a per-vessel level. The objective assessments included the enhancement degree of coronary artery, the signal-to-noise ratio (SNR) of the aortic root. We used χ 2 test and DeLong test to compare the diagnostic performance of CT-FFR with FFR as the reference standard in different subjective groups (non-artifact vs. artifact), enhancement degree of coronary artery groups (≤400 vs. 401-500 vs.>500 HU), SNR of the aortic root groups (≤16.9 vs.>16.9), body mass index (BMI) groups (<25 kg/m 2 vs.≥25 kg/m 2) and heart rate groups (<75 bpm vs.≥75 bpm). FFR and CT-FFR values≤0.80 was identified as myocardial ischemia. Results:The study enrolled 317 patients with 366 vessels. All target vessels in CCTA images were successfully analyzed by CT-FFR. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value and AUC of the non-artifact group were 90.45%, 86.75%, 93.10%, 90.00%, 90.76% and 0.928, respectively, and those of the artifact group were 83.23%, 87.21%, 79.01%, 81.52%, 85.33% and 0.869, respectively. The differences in accuracy and specificity were statistically significant (χ 2=4.23, P=0.040; χ 2=8.55, P=0.003). The diagnostic efficacy of CT-FFR had no statistically significant differences among different objective groups (all P>0.05). Conclusions:The artifact of CCTA image has an effect on CT-FFR in the diagnosis of myocardial ischemia. The degree of vascular enhancement, SNR, BMI, and heart rate have no significant effect on the diagnostic performance of CT-FFR.

Research progress in hip-preserving modalities for early osteonecrosis of the femoral head in young and middle-aged patients / 中华创伤杂志

Osteonecrosis of the femoral head (ONFH) is one of the common and difficult-to-treat orthopedic diseases caused by a variety of factors that lead to abnormal blood flow to the femoral head, which in turn leads to deformation and collapse of the femoral head and eventually results in severe hip joint dysfunction. The key to the treatment is early diagnosis and correct treatment according to the stage classification and active prevention of further aggravation of ONFH aiming to delay or avoid hip replacement surgery in young and middle-aged patients. At present, there are various non-surgical and surgical hip-preserving modalities for early ONFH, designed to slow down the progression of the disease, prevent the femoral head from collapsing and stop the mild collapse. In recent years, with the emergence and development of bone reconstruction biomaterials, artificial bone reconstruction after scraping of ONFH lesions has shown great potential in the treatment of early ONFH. The authors review the research progress in hip-preserving modalities for early ONFH in young and middle-aged patients from non-surgical and surgical perspectives, hoping to provide a reference for clinical treatment of early ONFH.

Clinical analysis of 202 patients with drug-induced liver injury / 中国基层医药

Objective:To investigate the clinical characteristics of drug-induced liver injury and provide a theoretical basis for the prevention and treatment of drug-induced liver injury.Methods:The clinical data of 202 patients with complete information on drug-induced liver injury who received treatment in First Hospital of Shanxi Medical University from November 2018 to November 2021 were collected. The information including gender, age, type and name of drugs taken or exposed, clinical characteristics, autoantibodies, and liver function was statistically analyzed.Results:Among the 202 patients with drug-induced liver injury, 77 patients (38.1%) were male and 125 patients (61.9%) were female. Age distribution was mainly at > 40-60 years. There were 141 cases (69.8%) of hepatocellular type, 27 cases (13.4%) of cholestatic type, and 34 cases (16.8%) of mixed type. There were statistically significant differences in alanine aminotransferase, aspartate aminotransferase, γ-glutamine transferase, alkaline phosphatase, prothrombin time, international standardized ratio, and prothrombin activity between different clinical types ( H = 91.43, 58.65, 9.25, 32.69, 9.56, 8.19, 9.40, all P < 0.05). Among the 202 patients with drug-induced liver injury, severe liver injury occurred in the largest proportion of cases (40.6%). There was no significant difference in the disease severity between different clinical types ( P = 0.789). The top three types of drugs causing liver injury were traditional Chinese medicine [52.0% (105/202)], antineoplastic drugs [6.4% (13/202)], and antipsychotics [5.9% (12/202)]. The detection rate of autoantibodies in 202 patients with drug-induced liver injury was 29.7% (60/202). Conclusion:Drug-induced liver injury lacks specificity in clinical manifestations. A wide variety of drugs can cause liver injury. Clinicians should strengthen liver function monitoring in key populations. The proportion of patients with mixed-type liver failure is high, which should be taken seriously. When patients with drug-induced liver injury are positive for liver disease-related antibodies, clinicians should be vigilant about the possibility of drug-induced liver injury.

Preliminary Exploration of Integrating Narrative Medicine into General Practice Education / 中国医学伦理学

In the context of a healthy China, strengthening humanistic literacy education for general medical students reflects the demands of the times, promotes the transformation of medical models, and has important practical significance in reducing the work burnout of general practitioners in practice. Integrating narrative medicine into general practice student education is conducive to implement the patient-centered concept of general practice, provide continuous and systematic medical services, and further improve the humanistic literacy of general practitioners. Based on these, this paper proposed the relevant paths of integrating narrative medicine into student education in general medicine, including changing educational concepts and integrating educational resources, boldly carrying out curriculum reforms and innovating educational methods, fully utilizing parallel medical records and reflective writing, as well as cultivating the habit of lifelong learning.

Monoterpenes and hexenol glycosides from an aqueous extract of Monochasma savatieri / 药学学报

Twelve compounds, including 5 new monoterpenes and 7 known derivatives, were isolated from a water decoction of Monochasma savatieri by column chromatography over macroporous adsorbent resin, MCI resin, Sephadex LH-20, and HW-40C, combined with preparative TLC, reversed phase HPLC, and flash column chromatographic techniques. Their structures were elucidated by comprehensive analysis of spectroscopic data, along with enzymatic hydrolysis as well as electronic circular dichroism (ECD) and NMR calculations, the new structures named monochaside I (1) and monochairidols A-D (2-5), respectively. The known compounds 6-12 were obtained from the Monochasma plants for the first time.

Clinical Treatment Ideas of “Treatment with Combination of Diverse Methods and Prescriptions” in TheInner Canon of Yellow Emperor （《黄帝内经》） / 中医杂志

As a basic source for the theoretical system of traditonal Chinese medicine （TCM）， the Inner Canon of Yellow Emperor （《黄帝内经》） made the point of “treatment with combination of diverse methods and prescriptions”，which is one of the characteristics of TCM in treating diseases. This paper discussed the therapeutic idea of “diverse methods and prescriptions” from five dimensions， including time， population， regions， diseases， and treatments， and proposed that “combined treatment” is an effective measure to embody the idea of “diverse methods and prescriptions”. That is to say， by taking the combination of the concept of holism and syndrome differentiation and treatment as the starting point， combining pharmacological and non-pharmacological therapies， and treating both internal and external diseases through multiple ways and methods， the goal to treat the disease at the root， and keep yin at peace and yang compact can be achieved. Finally， it is suggested to guide the clinical practice with “treatment with combination of diverse methods and prescriptions”， providing new ideas for clinical diagnosis and treatment.

Triterpenoids from an aqueous extract of the Ziziphus jujuba var. spinosa seeds / 药学学报

Four new triterpenoids, together with six known analogues, were isolated from an aqueous extract of the Ziziphus jujuba var. spinosa seeds, by multiple column chromatographic separation methods using stationary phases of macroporous adsorption resin, MCI resin, normal phase silica gel, Sephadex LH-20, and Toyopearl HW-40C as well as preparative thin-layer chromatography and reversed-phase HPLC. Their structures were determined by spectroscopic data analysis, the new structures were trivially named jujubaceanothoside A (1), 23-epijujuboside A (2), and jujubosides J and K (3 and 4), while the known analogues were identified as jujubosides A-C (5-7) and II (8), alphitolic acid (9), and betulinic acid (10). The structure of 1 was confirmed by single crystal X-ray diffraction.

The Biological Connotation of the “Fire Failing to Warm Earth” Pathogenesis of Carcinoma Transformation of Colitis Based on “Metabolic-Immune Interaction” / 中医杂志

During the carcinoma transformation of colitis， the imbalance of “metabolic-immune interaction” resulted from abnormal energy and metabolic substrates flow and direction was the key process， which caused by intercellular metabolic competition. Based on traditional Chinese medicine （TCM） theory and clinical research， we found that “fire failing to warm earth” is the key pathogenesis of colon-cancer transformation. “Fire” was a synonym for TCM to understand the energy metabolism， combined modern medical research findings， we thought energy metabolism disorders was a microcosmic manifestation of the “fire decline”， while abnormal immune function was the biological basis of “earth deficiency”. The imbalance between “metabolism-immune interaction” and the “fire failing to warm earth” pathogenesis of colitis-cancer transformation demonstrated the different understanding of the same pathological mechanism between western medicine and TCM. For treatment， it could be effectivce to delay the transformation of colitis-cancer by synergistically regulated the energy metabolism - “replenish fire” and enhanced the immune function - “nourish earth”， which was called the methods of replenishing fire to nourish earth.

Effect of acute kidney injury on near-term prognosis of the recipients with idiopathic pulmonary fibrosis after lung transplantation / 中华器官移植杂志

Objective:To explore the effect of acute kidney injury(AKI)on near-term survival after lung transplantation(LT)in patients with idiopathic pulmonary fibrosis(IPF).Methods:Through consulting electronic medical records, anesthetic modes and Chinese Lung Transplant Registration System, clinical data are retrospectively reviewed for 275 IPF patients undergoing LT at Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2017 to April 2021.According to the diagnostic criteria of Kidney Disease: Improving Global Outcomes(KDIGO), they are divided into two groups of AKI(169 cases)and non-AKI(106 cases).Perioperative findings of two groups are recorded.Then univariate and multivariate Cox regression models are employed for determining whether or not inter-group differences existed in survival rates post-LT.Also AKI is staged according to the KDIGO.And the effect of stage 1/2/3 AKI on near-term postoperative prognosis is examined.Results:The differences are significantly different in recipient gender, creatinine, 6-minute walking test, forced vital capacity(FVC), lung allocation score, oxygenation index, N-terminal pro-brain natriuretic peptide(NT-Pro BNP), preoperative hormone use and volume of crystal infusion( P<0.05).After multivariate Cox regression correcting for covariates, no statistical significance exists in effect of AKI stage 1 on near-term postoperative survival rate( P<0.05).AKI stage 2/3 still has statistical significance in risk of mortality at Day 30/90/180/365 post-operation( P>0.05). Conclusions:As a common complication post-LT, AKI significantly affects near-term postoperative prognosis of transplant IPF patients.Stage 2/3 AKI impacts near-term postoperative survival while stage 1 AKI is not associated with higher mortality.

Effects of bilateral erector spinae plane block for posterior lumbar spine surgery in elderly patients / 中南大学学报(医学版)

OBJECTIVES@#With the rapid development of aging population, the number of elderly patients undergoing posterior lumbar spine surgery continues to increase. Lumbar spine surgery could cause moderate to severe postoperative pain, and the conventional opioid-based analgesia techniques have many side effects, which are barriers to the recovery after surgery of the elderly. Previous studies have demonstrated that erector spinae plane block (ESPB) could bring about favorable analgesia in spinal surgery. As far as the elderly are concerned, the analgesic and recovery effects of ESPB on posterior lumbar spine surgery are not completely clear. This study aims to observe the effects of bilateral ESPB on elderly patients undergoing posterior lumbar spine surgery, and to improve the anesthesia techniques.@*METHODS@#A total of 70 elderly patients of both sex, who were selected from May 2020 to November 2021, scheduled for elective posterior lumbar spine surgery, and in the age of 60-79 years, with American Society of Anesthesiologists class Ⅱ-Ⅲ, were divided into a ESPB group and a control (C) group using a random number table method, with 35 patients each. Before general anesthesia induction, 20 mL 0.4% ropivacaine was injected to the transverse process of L3 or L4 bilaterally in the ESPB group and only saline in the C group. The score of Numerical Rating Scale (NRS) indicating pain at rest and on movement within 48 h after operation, time of first patient control analgesia (PCA), cumulative consumptions of sufentanil within 48 hours, Leeds Sleep Evaluation Questionnaire (LSEQ) scores on the morning of day 1 and day 2 after operation, Quality of Recovery-15 (QoR-15) scores at 24 and 48 h after operation, full diet intake times, perioperative adverse reactions such as intraoperative hypotension, postoperative dizziness, nausea, vomiting, and constipation were compared between the 2 groups.@*RESULTS@#A total of 70 patients were enrolled and 62 subjects completed the study, including 32 in the ESPB group and 30 in the C group. Compared with the C group, the postoperative NRS scores at rest at 2, 4, 6, and 12 h and on movementat at 2, 4, and 6 h were lower, time of first PCA was later, sufentanil consumptions were significantly decreased during 0-12 h and 12-24 h after operation, LSEQ scores on the morning of day 1 and QoR-15 scores at 24 and 48 h after operation were higher, full diet intakes achieved earlier in the ESPB group (all P<0.05). There were no significant differences in the incidences of intraoperative hypotension, postoperative dizziness, nausea, vomiting, and constipation between the 2 groups (all P>0.05).@*CONCLUSIONS@#Providing favorable analgesic effects with reduced opioids consumption, bilateral ESPB for posterior lumbar spine surgery in the elderly patients could also improve postoperative sleep quality, promote gastrointestinal functional restoration, and enhance recovery with few adverse reactions.

Minor triterpenoid acids from an aqueous extract of Uncaria rhynchophylla / 药学学报

Seventeen minor triterpenoid acids (1-17) were isolated from an aqueous decoction of Uncaria rhynchophylla by a combinatory application of column chromatography using multiple stationary phases, including macroporous adsorbent resin, MCI resin, Sephadex LH-20, Toyopearl HW-40C, silica gel, and C18 reversed phase silica gel, combined with separation techniques of flash chromatography (FC) and high performance liquid chromatography (HPLC). Their structures were determined by analysis of HR-ESI-MS, UV, CD, and IR as well as 1D and 2D NMR spectroscopic data, of which eight new compounds (1-8) are named successively uncarinic acids Q-X, while the structures of 2 and 7 were confirmed by single crystal X-ray diffraction. In the in vitro assays, 27-hydroxyolean-12-en-28-oic acid (17) inhibited TGF-β-induced HSC-T6 cell activation at the concentration of 5 μmol·L-1.

Dimeric phthalides from an aqueous extract of the Angelica sinensis root head / 药学学报

Ten dimeric phthalide racemates (1-10) were isolated from an aqueous extract of the Angelica sinensis root head (Guitou) by separation techniques of column chromatography over macroporous adsorbent resin, MCI resin, silica gel, and Sephadex LH-20, together with preparative thin-layer chromatography and reversed phase HPLC. The racemates were further separated into (+)-/(-)-1-(+)-/(-)-10 with chiral HPLC. Their structures including absolute configurations were elucidated by comprehensive analysis of spectroscopic data, combined with electronic circular dichroism (ECD) and NMR calculations as well as single crystal X-ray diffractions. Compounds (+)-/(-)-1-(+)-/(-)-10 are either new structure or new natural product, named (+)-/(-)-angelidipthalidic acids A-H [(+)-/(-)-1-(+)-/(-)-8] and (+)-/(-)-angelidipthalidols A and B [(+)-/(-)-9 and (+)-/(-)-10], respectively. Meanwhile, dimeric phthalide mono- and bis-lactone derivatives with 3.3′a,8.6′- and 3.6′,8.3′a-coupling patterns as well as determination of their relative configurations are discussed.

Effect of donor age on short-term survival of patients with idiopathic pulmonary fibrosis after lung transplantation / 器官移植

Objective To evaluate the effect of donor age on short-term survival of patients with idiopathic pulmonary fibrosis (IPF) after lung transplantation. Methods Clinical data of 235 IPF donors and recipients of lung transplantation were retrospectively analyzed. Univariate and multivariate Cox proportional hazard regression models were employed to analyze the correlation between donor age and short-term mortality rate of IPF patients after lung transplantation. Kaplan-Meier was used to draw the survival curve. Results Univariate Cox regression analysis showed that donor age was correlated with the 1-year fatality of IPF patients after lung transplantation. The 1-year fatality of recipients after lung transplantation was increased by 0.020 times if donor age was increased by 1 year (P=0.009). Oxygenation index of the donors, preoperative oxygenation index, preoperative lung allocation score, preoperative N-terminal pro brain natriuretic peptide, pattern of transplantation, pattern of intraoperative extracorporeal membrane oxygenation and intraoperative blood transfusion volume of the recipients were correlated with 1-year fatality after lung transplantation (all P < 0.1). Multivariate Cox regression analysis demonstrated that there was no correlation between donor age and 30-, 90-, 180-d and 1-year fatality of IPF patients after lung transplantation (all P > 0.05). Sensitivity analysis showed that there was no significant difference in 30-, 90-, 180-d and 1-year fatality after lung transplantation among donors aged < 18, 18-33, 34-49 and ≥50 years (all P > 0.05). Conclusions Donor age exerts no effect upon short-term survival of IPF patients after lung transplantation. Considering the mechanical ventilation time, oxygenation index, infection and other factors of donors, the age range of lung transplant donors may be expanded.

Based on the theory of treating impotence alone with Yang Ming to explore the intervention of finger-pressing therapy on ICU-acquired weakness in critically ill children / 中国实用护理杂志

Objective:To explore the clinical feasibility of finger-pressing therapy based on the theory of treating impotence alone with Yang Ming to reduce incidence of ICU acquired weakness (ICU-AW) in critically ill children and provide a feasible nursing plan for ICU acquired asthenia in critically ill children.Methods:A quasi-experimental study was conducted. A total of 73 critically ill children were admitted to the PICU of Kunming Children′s Hospital from January 1 to April 30, 2021. According to the random number table, the subjects were divided into the observation group (37 cases) and the control group (36 cases). Children in the control group received routine PICU nursing. The children in the observation group were treated with PICU routine nursing and finger-pressing therapy based on the theory of treating impotence alone with Yang Ming. The two groups were compared in terms of limb muscle strength score (MRC-Score), incidence of ICU-AW, basic activities of life (Barthel Index, BI), limb muscle thickness.Results:After intervention, the MRC-Score of the observation group was 50 (46, 52) points, which was higher than 46 (40, 48) points of the control group, and the difference between the two groups was statistically significant ( Z=-3.70, P<0.05). The incidence of ICU-AW in the observation group was 32.43% (12/37), and the incidence of ICU-AW in the control group was 72.22% (26/36). The difference between the two groups was statistically significant ( χ2=11.58, P<0.05). The BI score of the observation group was 63 (50, 70), which was higher than 44 (40,60) of the control group, and the difference between the two groups was statistically significant ( Z=-3.94, P<0.05). The reduction degree of quadriceps femoris thickness in the observation group at D3-D1 was (-0.381 ± 0.131) cm, which was lower than (-0.762 ± 0.182) cm in the control group, and the difference between the two groups was statistically significant ( t=10.29, P<0.05). Conclusions:The application of finger-pressing therapy guided by theory of treating impotence alone with Yang Ming in the early rehabilitation of critically ill children can enhance muscle strength, prevent muscle atrophy and reduce the incidence of ICU-AW in critically ill children.

Association of hs-CRP with frailty and its components among the elderly over 65 years old in 9 longevity areas of China / 中华预防医学杂志

Objective: To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China. Methods: Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline. Results: A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the OR (95%CI) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/L. As for the components, the hs-CRP level was also positively associated with ADL disability, IADL disability, functional limitation and multimorbidity. After adjusting for confounding factors, compared with the low-level group, the OR (95%CI) values of the high-level group for the four components were 1.68 (1.25-2.27), 1.88 (1.42-2.50), 1.68 (1.31-2.14) and 1.39 (1.12-1.72), respectively. Conclusion: There is a positive association between the levels of hs-CRP and the risk of frailty among the elderly over 65 years old in 9 longevity areas of China. The higher hs-CRP level may increase the risk of frailty by elevating the risk of four physical functional disabilities, namely ADL disability, IADL disability, functional limitation and multimorbidity.

The role of Nrf2 in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated MMP9 / 中华劳动卫生职业病杂志

Objective: To investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated matrix metalloproteinase 9 (MMP9) . Methods: In October 2020, immortalized rat choroid plexus epithelial cell line (Z310) cells were used as the blood-cerebrospinal fluid barrier in vitro, and were divided into control group and 0.125, 0.25, 0.5 mmol/L lanthanum chloride (LaCl(3)) treatment group. After treating Z310 cells with different concentrations of LaCl(3) for 24 hours, the morphological changes of Z310 cells were observed under inverted microscope, the protein expression levels of MMP9, occludin and zonula occludens-1 (ZO-1) were observed by cellular immunofluorescence method, and the protein expression levels of MMP9, tissue inhibitors of metalloproteinase1 (TIMP1) , occludin, ZO-1 and Nrf2 were detected by Western blotting. The level of reactive oxygen species (ROS) in cells was detected by flow cytometry. Results: Compared with the control group, Z310 cells in the LaCl(3) treatment group were smaller in size, with fewer intercellular junctions, and more dead cells and cell fragments. The expression level of MMP9 protein in cells treated with 0.25 and 0.5 mmol/L LaCl(3) was significantly higher than that in the control group (P<0.05) , and the expression level of TIMP1 and tight junction proteins occudin and ZO-1 was significantly lower than that in the control group (P<0.05) . Compared with the control group, the ROS production level in the 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly increased (P<0.05) , and the Nrf2 protein expression level in the 0.125, 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly decreased (P<0.05) . Conclusion: Lanthanum may increase the level of ROS in cells by down regulating the expression of Nrf2, thus activating MMP9 to reduce the expression level of intercellular tight junction proteins occludin and ZO-1.

Responses of blood parameters and hemoglobin subtypes in plateau zokors and plateau pikas to different altitude habitats / 生理学报

The plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) are native species unique to the Qinghai-Tibetan Plateau with successful adaptation to the hypoxic environment. In this study, the number of red blood cells, hemoglobin concentration, mean hematocrit and mean volume of red blood cells were measured in plateau zokors and plateau pikas at different altitudes. Hemoglobin subtypes of two plateau animals were identified by mass spectrometry sequencing. The forward selection sites in two animals' hemoglobin subunits were analyzed by PAML4.8 program. Homologous modeling was used to analyze the effect of forward selection sites on the affinity of hemoglobin to oxygen. The adapting strategies of plateau zokors and plateau pikas to hypoxia at different altitudes were analyzed through comparing blood parameters between the two species. The results indicated that, with increasing altitudes, plateau zokors responded to hypoxia by increasing red blood cell count and decreasing red blood cell volume, while plateau pikas took the opposite strategies to plateau zokors. In erythrocytes of plateau pikas, both adult α2β2 and fetal α2ε2 hemoglobins were identified, while erythrocytes of plateau zokors only had adult α2β2 hemoglobin, however the affinities and the allosteric effects of the hemoglobin of plateau zokors were significantly higher than those of plateau pikas. Mechanistically, in the α and β subunits of hemoglobin of plateau zokors and pikas, the numbers and the sites of the positively selected amino acids as well as the side chain groups polarities and orientations of the amino acids differed significantly, which may result in the difference of the affinities to oxygen of hemoglobin between plateau zokors and pikas. In conclusion, the adaptive mechanisms to respond to hypoxia in blood properties of plateau zokors and plateau pikas are species-specific.