Current views of drought research: experimental methods, adaptation mechanisms and regulatory strategies.

Drought stress is one of the most important abiotic stresses which causes many yield losses every year. This paper presents a comprehensive review of recent advances in international drought research. First, the main types of drought stress and the commonly used drought stress methods in the current experiment were introduced, and the advantages and disadvantages of each method were evaluated. Second, the response of plants to drought stress was reviewed from the aspects of morphology, physiology, biochemistry and molecular progression. Then, the potential methods to improve drought resistance and recent emerging technologies were introduced. Finally, the current research dilemma and future development direction were summarized. In summary, this review provides insights into drought stress research from different perspectives and provides a theoretical reference for scholars engaged in and about to engage in drought research.

Probing the interaction mechanism of SDBS with AtPrxQ from Arabidopsis thaliana: Insight into the molecular toxicity to plants.

As the most universally used anionic surfactant, ubiquitous existence and accumulation of sodium dodecyl benzene sulfonate (SDBS) in the environment has inevitably imposed the associated harmful impacts to plants due to producing excessive reactive oxygen species. However, the underlying hazardous mechanism of the SDBS-induced oxidative stress to plants at molecular level has never been reported. Here, the molecular interaction of AtPrxQ with SDBS was explored for the first time. The intrinsic fluorescence of AtPrxQ was quenched based on static quenching, and a single binding site of AtPrxQ towards SDBS and the potential interaction forces driven by hydrophobic interactions were predicted from thermodynamic parameters and molecular docking results. Besides, the interaction pattern of AtPrxQ and SDBS was also confirmed by the bio-layer interferometry with moderate binding affinity. Moreover, the structural changes of AtPrxQ along with the destructions of the protein framework and the hydrophobic enhancement around aromatic amino acids were observed upon binding with SDBS. At last, the toxic effects produced by SDBS on peroxidase activities and Arabidopsis seedlings growth were also characterized. Thus this work may provide insights on the molecular interactions of AtPrxQ with SDBS and assessments on the biological hazards of SDBS to plants even for the agriculture.

Anji white tea relaxes precontracted arteries, represses voltage-gated Ca2+ channels and voltage-gated K+ channels in the arterial smooth muscle cells: Comparison with green tea main component (-)-epigallocatechin gallate.

ETHNOPHARMACOLOGICAL RELEVANCE: Tea (Camellia sinensis) is a favorite drink worldwide. Tea extracts and green tea main component (-)-epigallocatechin gallate (EGCG) are recommended for various vascular diseases. Anji white tea is a very popular green tea. Its vascular effect profile, the mechanisms, and the contribution of EGCG to its integrated effect need elucidation. AIM: To characterize the vasomotion effects of Anji white tea and EGCG, and to explore possible involvement of voltage-gated Ca2+ channels (VGCCs) and voltage-gated K+ (Kv) channels in their vasomotion effects. MATERIALS AND METHODS: Anji white tea water soaking solution (AJWT) was prepared as daily tea-making process and concentrated to a concentration amounting to 200 mg/ml of dry tea leaves. The tension of rat arteries including aorta, coronary artery (RCA), cerebral basilar artery (CBA), intrarenal artery (IRA), intrapulmonary artery (IPA) and mesenteric artery (MA) was recorded with myographs. In arterial smooth muscle cells (ASMCs) freshly isolated from RCA, the levels of intracellular Ca2+ were measured with Ca2+-sensitive fluorescent probe fluo 4-AM, and Kv currents were recorded with patch clamp. The expressions of VGCCs and Kv channels were assayed with RT-qPCR and immunofluorescence staining. RESULTS: At 0.4-12.8 mg/ml of dry tea leaves, AJWT profoundly relaxed all tested arteries precontracted with various vasoconstrictors about half with a small transient potentiation on the precontractions before the relaxation. KCl-induced precontraction was less sensitive than precontractions induced by phenylephrine (PE), U46619 and serotonin (5-HT). IPA was less sensitive to the relaxation compared with other arteries. AJWT pretreatment for 1 h, 24 h and 72 h time-dependently inhibited the contractile responses of RCAs. In sharp contrast, at equivalent concentrations according to its content in AJWT, EGCG intensified the precontractions in most small arteries, except that it induced relaxation in PE-precontracted aorta and MA, U46619-precontracted aorta and CBA. EGCG pretreatment for 1 h and 24 h did not significantly affect RCA contractile responses. In RCA ASMCs, AJWT reduced, while EGCG enhanced, intracellular Ca2+ elevation induced by depolarization which activates VGCCs. Patch clamp study showed that both AJWT and EGCG reduced Kv currents. RT-qPCR and immunofluorescence staining demonstrated that both AJWT and EGCG reduced the expressions of VGCCs and Kv channels. CONCLUSION: AJWT, but not EGCG, consistently induces vasorelaxation. The vasomotion effects of either AJWT or EGCG vary with arterial beds and vasoconstrictors. Modulation of VGCCs, but not Kv channels, contributes to AJWT-induced vasorelaxation. It is suggested that Anji white tea water extract instead of EGCG may be a promising food supplement for vasospastic diseases.

Evaluation of the Two Typical Diamide Insecticide-Induced Oxidative Damages and the Molecular Mechanism Underlying Their Toxicity in Triticum aestivum.

As the typical representatives of diamide insecticides, excessive exposure to flubendiamide and chlorantraniliprole for plants may inevitably pose threats to plant growth and food safety. However, the underlying toxic mechanisms remain unclear. Here, glutathione S-transferase Phi1 from Triticum aestivum was employed as the biomarker to assess oxidative damages. First, flubendiamide displayed much stronger binding affinity with TaGSTF1 than chlorantraniliprole in consistent with molecular docking results, and flubendiamide also exerted more evident effects on the structure of TaGSTF1. Then, glutathione S-transferase activities of TaGSTF1 declined after interaction with these two insecticides, especially for flubendiamide with more hazardous influence. At last, the adverse impacts on the germination and growth of wheat seedlings were further evaluated with more apparent inhibition of flubendiamide. Hence, this study may illustrate the detailed binding mechanisms of TaGSTF1 with these two typical insecticides, evaluate the destructive impacts on plant growth, and further assess the threat to agriculture.

Dibazol-induced relaxation of ophthalmic artery in C57BL/6J mice is correlated with the potency to inhibit voltage-gated Ca2+ channels.

We aimed to explore the effect of dibazol on the ophthalmic artery (OA) and ophthalmic artery smooth muscle cells (OASMCs) of C57BL/6J mice as well as the underlying mechanisms. The OA of C57BL/6J mice was isolated under a dissecting microscope for primary OASMCs culture and myogenic tests. OASMCs were identified through morphological and immunofluorescence analyses. Morphology changes in the OASMCs were examined by staining using rhodamine-phalloidin. We performed a collagen gel contraction assay to measure the contractile and relaxant activities of the OASMCs. The molecular probe Fluo-4 AM was used to examine intracellular free Ca2+ levels ([Ca2+]in). The myogenic effects of OA were examined using wire myography. Additionally, the whole-cell patch-clamp technique was used to investigate the mechanisms underlying the relaxant effect of dibazol on L-type voltage-gated Ca2+ channels (LVGC) in isolated cells. 10-5 M dibazol significantly inhibited the contraction of OASMCs and increased the [Ca2+]in response to 30 mM KCl in a concentration-dependent manner. Dizabol had a more significant relaxant effect than 10-5 M isosorbide dinitrate (ISDN). Similarly, dibazol showed a significant dose-dependent relaxant effect on OA contraction induced by 60 mM KCl or 0.3 µM 9,11-Dideoxy-9α,11α-methanoepoxy prostaglandin F2α (U46619). The current-voltage (I-V) curve revealed that dibazol decreased Ca2+ currents in a concentration-dependent manner. In conclusion, dibazol exerted relaxant effects on the OA and OASMCs, which may involve the inhibition of the Ca2+ influx through LVGC in the cells.

Machine learning classifiers for screening nonalcoholic fatty liver disease in general adults.

Nonalcoholic fatty liver disease (NAFLD) is one of major causes of end-stage liver disease in the coming decades, but it shows few symptoms until it develops into cirrhosis. We aim to develop classification models with machine learning to screen NAFLD patients among general adults. This study included 14,439 adults who took health examination. We developed classification models to classify subjects with or without NAFLD using decision tree, random forest (RF), extreme gradient boosting (XGBoost) and support vector machine (SVM). The classifier with SVM was showed the best performance with the highest accuracy (0.801), positive predictive value (PPV) (0.795), F1 score (0.795), Kappa score (0.508) and area under the precision-recall curve (AUPRC) (0.712), and the second top of area under receiver operating characteristic curve (AUROC) (0.850). The second-best classifier was RF model, which was showed the highest AUROC (0.852) and the second top of accuracy (0.789), PPV (0.782), F1 score (0.782), Kappa score (0.478) and AUPRC (0.708). In conclusion, the classifier with SVM is the best one to screen NAFLD in general population based on the results from physical examination and blood testing, followed by the classifier with RF. Those classifiers have a potential to screen NAFLD in general population for physician and primary care doctors, which could benefit to NAFLD patients from early diagnosis.

Down-regulation of connexin 43 contributes to structure and function of pulmonary artery in nicotine-administered mice.

Dysregulated connexin signaling is implicated in the pathophysiology of pulmonary artery hypertension (PAH). Nicotine affects pulmonary vascular remodeling. However, the potential mechanistic link between connexin signaling and nicotine-induced pulmonary artery remodeling remains unclear. We aimed to investigate the role of connexin 43 (Cx43) in pulmonary artery remodeling in nicotine-administered C57BL/6 J wild-type (WT) and Cx43 heterozygous (Cx43+/-) mice. Hemodynamic parameters and right ventricle pathology were assessed in the mice. Serum biochemical indices of hepatic and renal function were measured. The RT-PCR, immunofluorescence, and western blotting were conducted to evaluate Cx43 mRNA and protein levels. We performed histological staining to identify pulmonary arteries. Wire myography was used to examine contraction and relaxation responses in the pulmonary arteries. Pulmonary vascular permeability was assessed through Evans blue staining. Compared with the WT group, the Cx43+/- group showed lower Cx43 mRNA and protein expression in the pulmonary arteries (P < 0.01). Nicotine treatment significantly increased Cx43 expression (P < 0.01) and induced morphological changes in the pulmonary arteries (P < 0.01). Our findings suggest that Cx43 plays a crucial role in pulmonary artery reactivity and permeability in mice. Furthermore, downregulation of Cx43 expression may contribute to alterations in pulmonary artery structure and function.

Scrutinizing the interaction between metribuzin with glutathione reductase 2 from Arabidopsis thaliana: insight into the molecular toxicity in agriculture.

As one of the triazine herbicides with widespread usage in agriculture, metribuzin exerted nonnegligible hazardous effects on plants via excessive accumulation of reactive oxygen species and destruction of antioxidant enzymes, but the underlying harmful mechanism of metribuzin-induced oxidative damage to plants has never been exploited. Here, Arabidopsis thaliana glutathione reductase 2 (AtGR2) was employed as the biomarker to evaluate the adverse impacts of metribuzin on plants. The fluorescence intensity of AtGR2 was decreased based on the static quenching mechanism with the prediction of a single binding site toward metribuzin, and the complex formation was presumed to be mainly impelled by hydrogen bonding and van der Waals forces from the negative ΔH and ΔS. In addition, the loosened and unfolded skeleton of AtGR2 along with the increased hydrophilicity around the tryptophan residues were investigated. Besides, the glutathione reductase activity of AtGR2 was also destroyed due to structural and conformational changes. At last, the severe inhibiting growth of Arabidopsis seedling roots was discovered under metribuzin exposure. Hence, the evaluation of the molecular interaction mechanism of AtGR2 with metribuzin will establish valuable assessments of the toxic effects of metribuzin on plants.

Ondansetron Reduces the Incidence of Hypotension after Spinal Anaesthesia: A Systematic Review and Meta-Analysis.

Hypotension induced by spinal anaesthesia is a common clinical complication associated with multiple perioperative adverse events. We conducted a systemic review and meta-analysis to confirm whether ondansetron could alleviate hypotension following spinal anaesthesia. PubMed, Embase, Web of Science, and Cochrane Library were searched to identify eligible randomised controlled trials from their respective database inception dates to 30 September 2022. The primary outcome of the meta-analysis was the incidence of hypotension after spinal anaesthesia. The risk of bias in the included studies was evaluated using the revised Cochrane risk of bias tool for randomised trials (RoB 2.0). Grading of Recommendations, Assessment, Development, and Evaluation was applied to assess the level of certainty. A total of 25 studies were included in this research. The meta-analysis revealed that ondansetron significantly decreased the incidence of hypotension (RR = 0.65, 95% CI 0.53−0.80, p < 0.01, I2 = 64%) and bradycardia. In addition, patients treated with ondansetron had a reduced need for vasopressors administration. This study suggests that ondansetron may be recommended as a prophylaxis for hypotension and bradycardia following spinal anaesthesia; the level of evidence was moderate with a high level of heterogeneity.

Hyperbaric Oxygen Therapy-Induced Molecular and Pathway Changes in a Rat Model of Spinal Cord Injury: A Proteomic Analysis.

Hyperbaric Oxygen Therapy (HBOT) has definitive therapeutic effects on spinal cord injury (SCI), but its mechanism of action is still unclear. Here, we've conducted a systemic proteomic analysis to identify differentially expressed proteins (DEPs) between SCI rats and HBOT + SCI rats. The function clustering analysis showed that the top enriched pathways of DEPs include oxygen transport activity, oxygen binding, and regulation of T cell proliferation. The results of functional and signal pathway analyses indicated that metabolic pathways, thermogenesis, LXR/RXR activation, acute phase response signaling, and the intrinsic prothrombin pathway in the SCI + HBOT group was higher than SCI group.

Connexins may play a critical role in cigarette smoke-induced pulmonary hypertension.

Pulmonary hypertension (PH) is a chronic progressive disease characterized by pulmonary vasoconstriction and remodeling. It causes a gradual increase in pulmonary vascular resistance leading to right-sided heart failure, and may be fatal. Chronic exposure to cigarette smoke (CS) is an essential risk factor for PH group 3; however, smoking continues to be prevalent and smoking cessation is reported to be difficult. A majority of smokers exhibit PH, which leads to a concomitant increase in the risk of mortality. The current treatments for PH group 3 focus on vasodilation and long-term oxygen supplementation, and fail to stop or reverse PH-associated continuous vascular remodeling. Recent studies have suggested that pulmonary vascular endothelial dysfunction induced by CS exposure may be an initial event in the natural history of PH, which in turn may be associated with abnormal alterations in connexin (Cx) expression. The relationship between Cx and CS-induced PH development has not yet been directly investigated. Therefore, this review will describe the roles of CS and Cx in the development of PH and discuss the related downstream pathways. We also discuss the possible role of Cx in CS-induced PH. It is hoped that this review may provide new perspectives for early intervention.

The pharmacological properties and corresponding mechanisms of farrerol: a comprehensive review.

CONTEXT: Farrerol, a typical natural flavanone isolated from the traditional Chinese herb 'Man-shan-hong' [Rhododendron dauricum L. (Ericaceae)] with phlegm-reducing and cough-relieving properties, is widely used in China for treating bronchitis and asthma. OBJECTIVE: To present the anti-inflammatory, antioxidant, vasoactive, antitumor, and antimicrobial effects of farrerol and its underlying molecular mechanisms. METHODS: The literature was reviewed by searching PubMed, Medline, Web of Knowledge, Scopus, and Google Scholar databases between 2011 and May 2021. The following key words were used: 'farrerol,' 'flavanone,' 'anti-inflammatory,' 'antioxidant,' 'vasoactive,' 'antitumor,' 'antimicrobial,' and 'molecular mechanisms'. RESULTS: Farrerol showed anti-inflammatory effects mainly mediated via the inhibition of interleukin (IL)-6/8, IL-1ß, tumour necrosis factor(TNF)-α, NF-κB, NO, COX-2, JNK1/2, AKT, PI3K, ERK1/2, p38, Keap-1, and TGF-1ß. Farrerol exhibited antioxidant effects by decreasing JNK, MDA, ROS, NOX4, Bax/Bcl-2, caspase-3, p-p38 MAPK, and GSK-3ß levels and enhancing Nrf2, GSH, SOD, GSH-Px, HO-1, NQO1, and p-ERK levels. The vasoactive effects of farrerol were also shown by the reduced α-SMA, NAD(P)H, p-ERK, p-Akt, mTOR, Jak2, Stat3, Bcl-2, and p38 levels, but increased OPN, occludin, ZO-1, eNOS, CaM, IP3R, and PLC levels. The antitumor effects of farrerol were evident from the reduced Bcl-2, Slug, Zeb-1, and vimentin levels but increased p27, ERK1/2, p38, caspase-9, Bax, and E-cadherin levels. Farrerol reduced α-toxin levels and increased NO production and NF-κB activity to impart antibacterial activity. CONCLUSIONS: This review article provides a theoretical basis for further studies on farrerol, with a view to develop and utilise farrerol for treating of vascular-related diseases in the future.

Lanthanide-uranyl phosphonates constructed from diethyl ((phenylsulfonyl)methyl)phosphonate.

Lanthanide-uranyl phosphonates possess intriguing crystal structures and huge application prospects, but the construction of these materials remains challenging. In this work, we demonstrate that new uranyl and lanthanide-uranyl sulfonylphosphonates with elegant crystal structures and photophysical properties can be assembled hydrothermally by employing the heterofunctional diethyl phosphonate (diethyl ((phenylsulfonyl)methyl)phosphonate, Et2L) as a precursor ligand, which provides an effective strategy for the construction of lanthanide-uranyl phosphonates.

Application of controlled low central venous pressure during hepatectomy: A systematic review and meta-analysis.

STUDY OBJECTIVE: Previous studies reported that controlled low central venous pressure (CVP) can reduce blood loss during liver resection. This systematic review and meta-analysis sought to explore the efficacy and safety of low CVP in patients undergoing hepatectomy. DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs). REVIEW METHODS: RCTs were searched in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical database, Chinese Scientific Journals Database, and Wanfang database from inception to April 30, 2021. Subgroup analyses were performed based on different surgical methods (open hepatectomy vs laparoscopic hepatectomy) and published countries (China vs other countries). The quality of evidence was assessed by Grading of Recommendations, Assessment, Development, and Evaluation. MAIN RESULTS: Eighteen RCTs containing 1285 participants (626 patients in the low CVP group and 659 patients in the control group) were included in this study. The forest plot showed that low CVP effectively reduced blood loss during liver resection compared with the control group (MD = -311.92 mL, 95% CI [-429.03, -194.81]; P < 0.001, I2 = 96%). Furthermore, blood transfusion volume (MD = -158.85 mL, 95% CI [-218.30, -99.40]; P < 0.001, I2 = 55%) and the number of patients requiring transfusion (RR 0.41, 95% CI 0.27-0.65, P < 0.001, I2 = 0%) were decreased in the low CVP group. Subgroup analyses showed similar results. Notably, the alanine transaminase level was significantly lower in the low CVP group during the first five postoperative days. However, no significant differences were observed for other postoperative liver function indicators (aspartate aminotransferase, total bilirubin, serum albumin, and prothrombin time), renal function indicators (blood urea nitrogen and serum creatinine) and perfusion parameters (heart rate, mean arterial pressure, and urine volume). The incidence of complications was similar between the two groups. CONCLUSION: The findings of this study showed that low CVP is effective and safe during hepatectomy. Therefore, this technique is recommended to reduce blood loss during hepatectomy. PROSPERO registration number: CRD42021232829.

Coronary hypercontractility to acidosis owes to the greater activity of TMEM16A/ANO1 in the arterial smooth muscle cells.

BACKGROUND: Severe acidosis deteriorates cardiac injury. Rat coronary arteries (RCAs) are unusually hypercontractive to extracellular (o) acidosis (EA). TMEM16A-encoded anoctamin 1 (ANO1), a Ca2+-activated chloride channel (CaCC), plays an important role in regulating coronary arterial tension. PURPOSE: We tested the possibility that the activation of CaCCs in the arterial smooth muscle cell (ASMC) contributes to EA-induced RCA constriction. METHODS: ANO1 expression was detected with immunofluorescence staining and Western blot. TMEM16A mRNA was assessed with quantitative Real-Time PCR. Cl- currents and membrane potentials were quantified with a patch clamp. The vascular tension was recorded with a myograph. Intracellular (i) level of Cl- and Ca2+ was measured with fluorescent molecular probes. RESULTS: ANO1 was expressed in all tested arterial myocytes, but was much more abundant in RCA ASMCs as compared with ASMCs isolated from rat cerebral basilar, intrarenal and mesenteric arteries. EA reduced [Cl-]i levels, augmented CaCC currents exclusively in RCA ASMCs and depolarized RCA ASMCs to a greater extent. Cl- deprivation, which depleted [Cl-]i by incubating the arteries or their ASMCs in Cl--free bath solution, decreased EA-induced [Cl-]i reduction, diminished EA-induced CaCC augmentation and time-dependently depressed EA-induced RCA constriction. Inhibitor studies showed that these EA-induced effects including RCA constriction, CaCC current augmentation, [Cl-]i reduction and/or [Ca2+]i elevation were depressed by various Cl- channel blockers, [Ca2+]i release inhibitors and L-type voltage-gated Ca2+ channel inhibitor nifedipine. ANO1 antibody attenuated all observed changes induced by EA in RCA ASMCs. CONCLUSION: The greater activity of RCA ASMC CaCCs complicated with an enhanced Ca2+ mobilization from both [Ca2+]i release and [Ca2+]o influx plays a pivotal role in the distinctive hypercontractility of RCAs to acidosis. Translation of these findings to human beings may lead to a new conception in our understanding and treating cardiac complications in severe acidosis.

Effect of continuous nursing combined with salcatonin on postoperative pains in elderly patients after hip replacement.

OBJECTIVE: This study was designed to explore the effect of continuous nursing combined with salcatonin on the improvements of postoperative pain in elderly patients after hip replacement. METHODS: A total of 99 elderly patients treated by hip replacement in our hospital were divided into the control group (CG, n=49, routine nursing + salcatonin) and the study group (SG, n=50, continuous nursing + salcatonin). The visual analogue scale (VAS) during rest (RVAS), VAS during initiative movement (IVAS) and VAS during passive movement = (PVAS) at 3 d, 7 d, 10 d, 14 d and 30 d after operation, the Harris hip score (HHS), Barthel index and geriatric depression scale (GDS) at 1 month after operation, and the incidences of tumble and refracture during the postoperative 6-month follow-up were compared between the two groups. RESULTS: In comparison with the CG, except for higher HHS and Barthel index at 1 month after operation (P<0.05), the SG was associated with lower RVAS, IVAS and PVAS at 7 d, 10 d, 14 d and 30 d after operation (P<0.05), lower GDS at 1 month after operation, and lower incidences of tumble and refracture during the 6 months after operation (P<0.05). CONCLUSION: The combination of continuous nursing and salcatonin has achieved marked effects not only on mitigating the pains at the early stage after a hip replacement in elderly patients, but also on improving their joint functions and reducing the incidences of tumble and refracture in a long run.

Exploring the toxic interactions between Bisphenol A and glutathione peroxidase 6 from Arabidopsis thaliana.

As primary industrial raw material, the widespread usage of bisphenol A (BPA) has resulted in sustained release and accumulation in the environment. Besides its endocrine-disrupting character, BPA was reported to generate excessive reactive oxygen species (ROS). However, the potential toxic mechanisms of the BPA-induced oxidative damage to plants were poorly understood. In this study, glutathione peroxidase 6 from Arabidopsis thaliana (AtGPX6) was regarded as biomarker to investigate the toxic effects of BPA on plants by multi-spectroscopic techniques and molecular docking method. Firstly, BPA effectively quenched the intrinsic fluorescence of AtGPX6 via static quenching mechanism, and a single binding site of AtGPX6 towards BPA was presumed. Moreover, the binding force was mainly driven by van der Waals forces and hydrogen bonding based on the negative values of ΔH0 and ΔS0, which was consistent with the molecular docking result. In addition, the conformational changes of AtGPX6 accompanied with the enhancement of the hydrophilicity around the tryptophan residues upon the combination with BPA, were evaluated through the combination of the fluorescence, UV-visible absorption and Circular dichroism (CD) spectroscopy. Finally, the inhibitory impact on the development of Arabidopsis seedling roots was observed under BPA exposure. Therefore, the exploration of the molecular mechanism of AtGPX6 with BPA would provide valuable assessments on the toxic effects of BPA on plants.

Up-regulation of nPKC contributes to proliferation of mice pulmonary artery smooth muscle cells in hypoxia-induced pulmonary hypertension.

This study is designed to investigate the role of novel protein kinases C (nPKC) in mediating pulmonary artery smooth muscle cells (PASMCs) proliferation in pulmonary hypertension (PH) and the underlying mechanisms. Mouse PASMCs was isolated using magnetic separation technology. The PASMCs were divided into 24 h group, 48 h group and 72 h group according to different hypoxia treatment time, then detected cell proliferation rate and nPKC expression level in each group. We treated PASMCs with agonists or inhibitors of PKCdelta (PKCδ) and PKCepsilon (PKCε) and exposed them to hypoxia or normoxia for 72 h, then measured the proliferation of PASMCs. We also constructed a lentiviral vector containing siRNA fragments for inhibiting PKCδ and PKCε to transfected PASMCs, then examined their proliferation. PASMCs isolated successfully by magnetic separation method and were in good condition. Hypoxia promoted the proliferation of PASMCs, and the treatment for 72 h had the most significant effect. Hypoxia upregulated the expression of PKCδ and PKCε in mouse PASMCs, leading to PASMCs proliferation. Moreover, Our study demonstrated that hypoxia induced upregulation of PKCδ and PKCε expression resulting to the proliferation of PASMCs via up-regulating the phosphorylation of AKT and ERK. Our study provides clear evidence that increased nPKC expression contributes to PASMCs proliferation and uncovers the correlation between AKT and ERK pathways and nPKC-mediated proliferation of PASMCs. These findings may provide novel targets for molecular therapy of pulmonary hypertension.

Rhomboid intercostal block combined with sub-serratus plane block versus rhomboid intercostal block for postoperative analgesia after video-assisted thoracoscopic surgery: a prospective randomized-controlled trial.

BACKGROUND: Rhomboid intercostal block (RIB) and Rhomboid intercostal block with sub-serratus plane block (RISS) are the two types of plane blocks used for postoperative analgesia after video-assisted thoracoscopic surgery (VATS). This prospective randomized controlled trial was performed to analyze the postoperative analgesic effects of ultrasound-guided RIB block and RISS block after video-assisted thoracoscopic surgery. METHODS: Ninety patients aged between 18 and 80 years, with American Society of Anesthesiologists physical status Classes I-II and scheduled for elective unilateral VATS were randomly allocated into three groups. In group C, no block intervention was performed. Patients in group RIB received ultrasound-guided RIB with 20-mL 0.375% ropivacaine and those in group RISS received ultrasound-guided RIB and serratus plane block using a total of 40-mL 0.375% ropivacaine. All patients received intravenous sufentanil patient-controlled analgesia upon arrival in the recovery room. Postoperative sufentanil consumption and pain scores were compared among the groups. RESULTS: The dosages of sufentanil consumption at 24 h after the surgery in the RIB and RISS groups were significantly lower than that in group C (p < 0.001 and p < 0.001 for all comparisons, respectively), the postoperative Numerical Rating Scale (NRS) scores in the RIB and RISS groups at 0.5, 1, 3, 6, 12, 18, and 24 h after surgery when patients were at rest or active were significantly lower than that in group C (p < 0.05 for all comparisons). The required dosage of sufentanil and time to first postoperative analgesic request in groupRISS were less than those in the group RIB at 24 h after the surgery (p < 0.001 and p < 0.001 for all comparisons, respectively). Similarly, the Numerical Rating Scale scores for group RISS at 12, 18, and 24 h after the surgery when the patients were active were significantly lower than those for group RIB (p < 0.05 for all comparisons). CONCLUSION: Both ultrasound-guided RIB block and RISS block can effectively reduce the demand for sufentanil within 24 h after VATS, and less sufentanil dosage is needed in patient with RISS block. Ultrasound-guided RIB block and RISS block can effectively relieve pain within 24 h after VATS, and RISS block is more effective.

Involvement of GPR30 in protection effect of Dexmedetomidine against myocardial ischemia/reperfusion injury in rat via AKT pathway.

Acute myocardial infarction (AMI) is a heart disease that seriously threatens human health. Dexmedetomidine (DEX) has a certain protective effect on cardiac injury. This study investigated the cardioprotective effect of DEX and its potential molecular mechanism in vivo and in vitro. The results showed that DEX could significantly increase the viability of hypoxia/reoxygenation (H/R) treated cardiomyocytes and reduce oxidative damage and apoptosis. Further molecular mechanism analysis showed that the above cardiac protective effects may be related to Akt signaling pathway. In addition, the expression of G-Protein Receptor 30 (GPR30) was promoted after H/R treatment. However, knockdown of GPR30 by shRNA significantly counteracted the cardioprotective effect of DEX. Meanwhile, we constructed a rat model of AMI to investigate the role of GPR30 in vivo. The results showed that DEX significantly reduced the infarct size, and GPR30 agonist G1 enhanced the protective effect of DEX on heart. On the contrary, protein kinase B (AKT) inhibitor LY294002 counteracted the protective effect of DEX on heart, suggesting that GPR30 enhanced the protective effect of DEX on ischemia-reperfusion induced heart injury by regulating AKT related pathways. In conclusion, our study provides a potential target for the clinical treatment of AMI.