Anthropogenic warming induced intensification of summer monsoon frontal precipitation over East Asia.

Summer monsoon frontal rainfall in East Asia (EA) is crucial for water resources and flood hazards in densely populated areas. Recent studies have documented the increasing intensity of summer frontal rainfall over recent decades. However, the extent of ongoing climate change on the intensification of the EA frontal precipitation system remains uncertain. Using an objective method for detecting frontal systems, we found a 17 ± 3% increase in observed frontal rainfall intensity during 1958 to 2015. Climate model simulations with and without greenhouse gases suggest that anthropogenic warming plays a key role in the intensification of EA summer frontal precipitation by 5.8% from 1991 to 2015. The analysis highlights that enhanced water vapor convergence and reinforced western North Pacific subtropical High collectively increased moisture transport to the region, resulting in intensified EA frontal precipitation. The results lend support to the anthropogenic warming-induced enhancement of the EA frontal precipitation and its persistence in the future.

DNA binding properties and cell viabilities of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazone.

OBJECTIVE: This study aims to investigate the CT-DNA (Calf thymus DNA) binding properties and HeLa cell viabilities of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone (H2L1) and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazone (HL2). MATERIALS AND METHODS: A series of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone (H2L1) and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazonewere (HL2) were synthesized, and their structures were characterized through FT-IR, ESI-MS, elemental analysis, molar conductivities and X-ray diffraction. DNA binding properties between CT-DNA and metal complexes were investigated by UV-Vis spectrophotometry and viscosity titration. The toxicological properties of compounds on HeLa cell were measured in vitro. RESULTS: Ligand H2L1 or HL2 exhibits a tridentate and anion ligand and uses oxygen anion, nitrogen atom and sulfur atom to coordinate with metal ions. When coordinated with metal ions, the unit O=C-NH- of each ligand has been enolized and deprotonated into -O-C=N-. The suggested chemical formulas of metal complexes are: [Co(HL1)2], [Ni(HL1)2], [Cu(HL1)2], [Co(L2)2], [Cu(L2)2], [Zn(L2)2], [ScL2(NO3)2(H2O)2], [Pr(L2)2(NO3)] and [Dy(L2)2(NO3)]. Both ligands and their metal complexes can bind strongly to CT-DNA through hydrogen bond and intercalation with Kb of 104~105 L mol-1 compared to ethidium bromide [classical DNA intercalator, Kb(EB-DNA) = 3.068 × 104 L mol-1]; however, the groove pattern cannot be excluded. The coexistence of multiple binding modes may be a common form of drug binding to DNA. HeLa cell shows lower viabilities in the presence of [Ni(HL1)2] and [Cu(HL1)2] (*p < 0.05) compared to the other compounds, with the LC50 of 2.6 µmol L-1 and 2.2 µmol L-1, respectively. CONCLUSIONS: These compounds, especially [Ni(HL1)2] and [Cu(HL1)2], will be promising for anti-tumor drugs, which should be further studied.

Occupational Health of Education Personnel-The Role of Job Crafting and Other Control Strategies on Healthy Ageing at Work.

This article looks at the strategies that influence healthy ageing at work from the motivational theory of life span development (MTD). It aims to better understand the influence of job crafting as a selective primary control, help-seeking as a compensatory primary control, positive reappraisal as a selective secondary control, and downward social comparison and downgrading expectation as a compensatory secondary control on healthy ageing at work (work engagement, health, and motivation to continue working after retirement). A total of 386 educational personnel participated in the study. This study used hierarchical regression analysis to test incremental validity, supplemented with confirmatory factor analysis and structural equation modelling as a solution to solve the potential error problems caused. The results show that job crafting is positively correlated with healthy ageing at work. Positive reappraisal and downward social comparison showed incremental validity in predicting healthy ageing at work beyond job crafting among the middle-aged group (45-65-years-old); in particular, positive reappraisal was the determinant of healthy ageing at work among the middle-aged group. However, both help-seeking and downgrading expectation did not show incremental validity. This study can contribute to the evolution of career development interventions and human resource management focused on supporting older people at work.

Collaborative Research Activities of the Arase and Van Allen Probes.

This paper presents the highlights of joint observations of the inner magnetosphere by the Arase spacecraft, the Van Allen Probes spacecraft, and ground-based experiments integrated into spacecraft programs. The concurrent operation of the two missions in 2017-2019 facilitated the separation of the spatial and temporal structures of dynamic phenomena occurring in the inner magnetosphere. Because the orbital inclination angle of Arase is larger than that of Van Allen Probes, Arase collected observations at higher L -shells up to L ∼ 10 . After March 2017, similar variations in plasma and waves were detected by Van Allen Probes and Arase. We describe plasma wave observations at longitudinally separated locations in space and geomagnetically-conjugate locations in space and on the ground. The results of instrument intercalibrations between the two missions are also presented. Arase continued its normal operation after the scientific operation of Van Allen Probes completed in October 2019. The combined Van Allen Probes (2012-2019) and Arase (2017-present) observations will cover a full solar cycle. This will be the first comprehensive long-term observation of the inner magnetosphere and radiation belts.

Changes in tree drought sensitivity provided early warning signals to the California drought and forest mortality event.

Climate warming in recent decades has negatively impacted forest health in the western United States. Here, we report on potential early warning signals (EWS) for drought-related mortality derived from measurements of tree-ring growth (ring width index; RWI) and carbon isotope discrimination (∆13 C), primarily focused on ponderosa pine (Pinus ponderosa). Sampling was conducted in the southern Sierra Nevada Mountains, near the epicenter of drought severity and mortality associated with the 2012-2015 California drought and concurrent outbreak of western pine beetle (Dendroctonus brevicomis). At this site, we found that widespread mortality was presaged by five decades of increasing sensitivity (i.e., increased explained variation) of both tree growth and ∆13 C to Palmer Drought Severity Index (PDSI). We hypothesized that increasing sensitivity of tree growth and ∆13 C to hydroclimate constitute EWS that indicate an increased likelihood of widespread forest mortality caused by direct and indirect effects of drought. We then tested these EWS in additional ponderosa pine-dominated forests that experienced varying mortality rates associated with the same California drought event. In general, drier sites showed increasing sensitivity of RWI to PDSI over the last century, as well as higher mortality following the California drought event compared to wetter sites. Two sites displayed evidence that thinning or fire events that reduced stand basal area effectively reversed the trend of increasing hydroclimate sensitivity. These comparisons indicate that reducing competition for soil water and/or decreasing bark beetle host tree density via forest management-particularly in drier regions-may buffer these forests against drought stress and associated mortality risk. EWS such as these could provide land managers more time to mitigate the extent or severity of forest mortality in advance of droughts. Substantial efforts at deploying additional dendrochronological research in concert with remote sensing and forest modeling will aid in forecasting of forest responses to continued climate warming.

MicroRNA-340-5p inhibits the malignant phenotypes of osteosarcoma by directly targeting NRF2 and deactivating the PI3K/AKT pathway.

OBJECTIVE: The aim of the study was to examine the effects and potential mechanisms of miR-340-5p in Osteosarcoma (OS) progression. PATIENTS AND METHODS: qRT-PCR was applied to detect expressions of miR-340-5p and NRF2 mRNA. MTT and transwell assay were carried out to determine the roles of miR-340-5p in OS cells viability, invasion and migration. TargetScan and Luciferase reporter assays were performed to search for the candidate target gene of miR-340-5p. The regulatory roles of miR-340-5p in OS PI3K/AKT pathway and EMT were examined by Western blot. RESULTS: MiR-340-5p expressions were decreased in OS tissues and cells. Moreover, the decreased miR-340-5p expressions in OS tissues were frequently accompanied by shorter overall survival and malignant clinicopathologic features of OS patients. MTT assay showed that miR-340-5p upregulation prominently repressed OS cell proliferation. In addition, miR-340-5p restoration could significantly suppress OS cell invasion and migration as demonstrated by transwell assays. Results also revealed that miR-340-5p could directly target NRF2 and regulate PI3K/AKT pathway and EMT, exerting prohibitory functions in OS. CONCLUSIONS: MiR-340-5p repressed the malignant phenotypes of OS via targeting NRF2 and regulating PI3K/AKT pathway and EMT. The current study provided preclinical evidence for the potential applications of miR-340-5p/NRF2 axis in OS therapies.

Clinical benefits of routine examination and synchronous repair of occult inguinal hernia during laparoscopic peritoneal dialysis catheter insertion: a single-center experience.

PURPOSE: Occult inguinal hernias (IH) predispose peritoneal dialysis (PD) patients to the symptomatic IH formation after starting PD, which may cause complications. We conducted a retrospective study to assess the benefit/risk profile of routine laparoscopic examination for occult IH (RLEOH) with a synchronous repair in patients receiving PD catheter placement. METHODS: 432 patients were enrolled in this study. Patients with an internal hernia sac at all sizes were deemed to have occult IH. We retrospectively reviewed data including demographic characteristics and operative details. We also measured incidence rates of symptomatic IH, metachronous IH repair, and catheter survival over a follow-up period after starting PD. RESULTS: These patients were classified into the RLEOH group (n = 365) and the non-RLEOH group (n = 67). The RLEOH group was subdivided into occult IH with a synchronous repair (n = 17; the subgroup A), no occult IH (n = 339; the subgroup B), and occult IH without a synchronous repair (n = 9; the subgroup C). The incidence rates of symptomatic IH developed after staring PD in subgroups A, B, and C were 0, 5.6, and 22.2%, respectively, whereas that in the non-RLEOH group was 13.4%. The RLEOH group had a reduced hazard ratio for metachronous IH repair compared with the non-RLEOH group (HR = 0.426; 95% CI 0.195-0.930, p = 0.032). None of our patients suffered from herniorrhaphy-related complications. CONCLUSION: RLEOH with a synchronous repair during PD catheter insertion confers clinical benefits in reducing the risk of developing IH after starting PD and the need for a metachronous repair. This is a safe and reasonable approach.

Expressions of SAA, CRP, and FERR in different severities of COVID-19.

OBJECTIVE: To explore the expression and significance of SAA, CRP and FERR in patients diagnosed with COVID-19. PATIENTS AND METHODS: A total of 225 patients diagnosed with COVID-19 who were admitted to the North Hospital of First Hospital in Changsha, China, from 9th February 2020 to 7th March 2020 were enrolled. Their general data, laboratory test results and levels of SAA, CRP and FERR were extracted from electronic medical records. RESULTS: Age was an important risk factor for the severity of COVID-19 in the patients. Compared with the non-severe group, the severe group showed statistical significance in the levels of total protein, albumin, ALT and AST in liver function, UA in renal function, myocardial enzyme CK-MB and LDH, and immunoglobulin IgG and IgM. The levels of SAA, CRP, and FERR were significantly increased in patients with severe COVID-19. ROC curve analysis results showed that the AUC, from small to large, was as follows: SAA+CRP+FERR, CRP + FERR, SAA + CRP, SAA + FERR, SAA, FERR, and CRP, which indicated the benefit of the combination of the three indicators. The sensitivity and specificity of the combined detection of the three indicators were higher than those of the detection of any single indicator or two combined indicators. A Spearman correlation analysis of the data showed that the initial CRP/SAA, SAA/FERR, and CRP/FERR were positively correlated. The continuous results of SAA, CRP and FERR throughout the study period showed that the values of the severe group on a given day were higher than those of the non-severe group; the values of the two groups peaked on the 5th or 7th day and then decreased, and the decreasing trend of the severe group was more evident. CONCLUSIONS: SAA, CRP and FERR are sensitive serological indicators used to evaluate the severity of COVID-19. The combined detection of serum SAA, FERR, and CRP, which are positively related to COVID-19 infection, offers guiding significance for the occurrence of COVID-19 infection and the severity of the disease. Such detection provides effective detection indicators for the progress and prognosis of COVID-19; these indicators will enable effective intervention measures to be implemented in time and the rates of severe illness and mortality to be reduced.

Abrupt shift to hotter and drier climate over inner East Asia beyond the tipping point.

Unprecedented heatwave-drought concurrences in the past two decades have been reported over inner East Asia. Tree-ring-based reconstructions of heatwaves and soil moisture for the past 260 years reveal an abrupt shift to hotter and drier climate over this region. Enhanced land-atmosphere coupling, associated with persistent soil moisture deficit, appears to intensify surface warming and anticyclonic circulation anomalies, fueling heatwaves that exacerbate soil drying. Our analysis demonstrates that the magnitude of the warm and dry anomalies compounding in the recent two decades is unprecedented over the quarter of a millennium, and this trend clearly exceeds the natural variability range. The "hockey stick"-like change warns that the warming and drying concurrence is potentially irreversible beyond a tipping point in the East Asian climate system.

Stronger influence of growth rate than severity of drought stress on mortality of large ponderosa pines during the 2012-2015 California drought.

Forests in the western United States are being subject to more frequent and severe drought events as the climate warms. The 2012-2015 California drought is a recent example, whereby drought stress was exacerbated by a landscape-scale outbreak of western pine beetle (Dendroctonus brevicomis) and resulted in widespread mortality of dominant canopy species including ponderosa pine (Pinus ponderosa). In this study, we compared pairs of large surviving and beetle-killed ponderosa pines following the California drought in the southern Sierra Nevadas to evaluate physiological characteristics related to survival. Inter-annual growth rates and tree-ring stable isotopes (∆13C and δ18O) were utilized to compare severity of drought stress and climate sensitivity in ponderosa pines that survived and those that were killed by western pine beetle. Compared to beetle-killed trees, surviving trees had higher growth rates and grew in plots with lower ponderosa pine basal area. However, there were no detectable differences in tree-ring ∆13C, δ18O, or stable isotope sensitivity to drought-related meteorological variables. These results indicate that differences in severity of drought stress had little influence on local, inter-tree differences in growth rate and survival of large ponderosa pines during this drought event. Many previous studies have shown that large trees are more likely to be attacked and killed by bark beetles compared to small trees. Our results further suggest that among large ponderosa pines, those that were more resistant to drought stress and bark beetle attacks were in the upper echelon of growth rates among trees within a stand and across the landscape.

Subseasonal prediction for bloom dates of tart cherries in Utah and Michigan, USA: merging phenological models with CFSv2 forecast.

Temperate fruit trees require chilling for rest completion, followed by sufficient heat accumulation for onset of growth and bloom. The application of phenological models to predict bloom dates has been widely used in orchard management. Examples of such application include selecting adapted cultivars less prone to early bloom, predicting needs for frost protection, and preventing damage from late spring freezes. This study merged the Utah (chill) and ASYMCUR (forcing) phenological models by combining chill units and heat units (measured in growing degree hours) to predict bloom dates of tart cherries (Prunus cerasus L.) in Utah and Michigan, the top producing states of the USA. It was found that the modified Utah model improves the estimation of chill units compared with the original one, while the original Utah model may still be suitable for use in the colder winter of Michigan (with its later bloom dates than Utah). The combined models were applied with the temperature predicted by the Climate Forecast System v2 (CFSv2) model. The prediction was applied twice a month, starting from 1 February to 1 May. The Utah-ASYMCUR model using the forecasted temperature from CFSv2 exhibits subseasonal performance in predicting the bloom dates for 6 weeks in advance. The prediction can offer growers a way to mitigate extreme climate anomalies.

The value of 18F-FDG PET/CT imaging combined with detection of CA125 and HE4 in the diagnosis of recurrence and metastasis of ovarian cancer.

OBJECTIVE: To explore the clinical application value of 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging combined with detection of serum tumor molecular markers (carbohydrate antigen 125 (CA 125) and human epididymis protein 4 (HE4)) in the diagnosis of recurrence and metastasis of ovarian cancer. PATIENTS AND METHODS: Clinical data about 18F-FDG PET/CT imaging and serum CA125 and HE4 of 69 ovarian cancer patients after the first cytoreductive surgery and chemotherapy were retrospectively analyzed, and the clinical application value of 18F-FDG PET/CT imaging combined with detection of CA125 and HE4 in the diagnosis of recurrence and metastasis of ovarian cancer was evaluated. RESULTS: The 18F-FDG PET/CT images of recurrence and metastasis of ovarian cancer showed hypermetabolism. The sensitivity, specificity, accuracy, predictive positive value, and predictive negative value of 18F-FDG PET/CT imaging for the diagnosis of recurrence and metastasis of ovarian cancer were 90.74%, 86.67%, 89.86%, 96.08%, and 72.22%, respectively; those of CA125 for the diagnosis of them were 77.78%, 86.67%, 79.71%, 95.45% and 52.00%, respectively, and those of HE4 for the diagnosis of them were 70.37%, 93.33%, 76.84%, 97.44%, and 48.39% respectively. In addition, the sensitivity and specificity of 18F-FDG PET/CT combined with detection of serum CA125 and HE4 for the diagnosis were 100.00% and 100.00%, respectively, significantly higher than those of separate 18F-FDG PET/CT imaging, detection of serum CA125, and detection of serum HE4 (c2 = 5.243, 13.500, 18.783, p = 0.022, 0.000, 0.000; c2 = 4.000, 8.525, 9.864, p = 0.046, 0.004, 0.002), and the accuracy of the combination use of them was 95.65%, also significantly higher than that of separate CA125 and HE4 (c2 = 8.118, 10.315, p = 0.004, 0.001, both p < 0.01). Furthermore, the maximum standardized uptake value (SUVmax) of 18F-FDG PET/CT imaging for recurrence and metastasis of ovarian cancer focuses was significantly positively correlated with serum CA125 and HE4 levels (r = 0.596, p = 0.000; r = 0.431, p = 0.002), and the serum CA125 level was also significantly positively correlated with serum HE4 level in patients with recurrent or metastasized ovarian cancer (r = 0.198, p = 0.043,). CONCLUSIONS: 18F-FDG PET/CT imaging combined with detection of serum CA125 and HE4 can significantly improve the diagnostic efficiency to recurrence and metastasis of ovarian cancer and is conducive to the early diagnosis of the recurrence and metastasis, which provides a basis for further clinical intervention.

Circ_001680 aggravates the malignant process of gastric carcinoma by targeting MAP2.

OBJECTIVE: This study aims to explore the expression pattern and clinical significance of circ_001680 in gastric carcinoma (GC) process. PATIENTS AND METHODS: Circ_001680 levels in 40 pairs of GC and paracancerous ones were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between circ_001680 and GC clinicopathological parameters was analyzed. AGS and SGC-7901 cells were used for constructing circ_001680 knockdown models by shRNA transfection. Proliferative and metastatic abilities in GC cells with circ_001680 knockdown were examined by cell counting kit-8 (CCK-8) and transwell assay, respectively. Dual-Luciferase reporter assay was conducted to clarify the interaction between circ_001680 and MAP2. Their co-regulation on GC process was detected through rescue experiments. RESULTS: Circ_001680 was highly expressed in GC tissues and cell lines. High level of circ_001680 predicted high incidences of lymphatic and distant metastasis, and poor prognosis in GC patients. Knockdown of circ_001680 suppressed proliferative and metastatic abilities in AGS and SGC-7901 cells. MAP2 was the target gene binding circ_001680, which was lowly expressed in GC. In addition, MAP2 was negatively correlated to circ_001680. Knockdown of MAP2 could abolish the suppressed proliferative and metastatic abilities in GC cells with circ_001680 knockdown. CONCLUSIONS: Circ_001680 is highly expressed in GC tissues and closely related to metastasis and prognosis in GC patients, which promotes the proliferative and metastatic abilities in GC cells by negatively interacting with MAP2.

LncRNA SNHG7 enhances chemoresistance in neuroblastoma through cisplatin-induced autophagy by regulating miR-329-3p/MYO10 axis.

OBJECTIVE: Neuroblastoma (NB) is a type of extracranial solid tumor that usually occurs in children. Drug resistance has become a major obstacle in NB chemotherapy. Long non-coding RNA small nucleolar RNA host gene 7 (SNHG7) is an oncogene in many cancers, including NB. This study aimed to investigate the role of SNHG7 in cisplatin sensitivity of NB and the underlying mechanism. PATIENTS AND METHODS: Cell Counting Kit-8 (CCK-8) assay was used to detect cell viability, and the IC50 of cisplatin was calculated. The protein levels of autophagy markers were measured by Western blot assay. The levels of SNHG7, miR-329-3p and myosin X (MYO10) were examined by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assay. The interaction among SNHG7, miR-329-3p and MYO10 was confirmed by Dual-Luciferase reporter assay. RESULTS: Cisplatin curbed the viability of NB cells in a dose-dependent manner and facilitated autophagy in NB cells. Silencing of SNHG7 reduced cisplatin resistance and suppressed cisplatin-induced autophagy. SNHG7 was a sponge of miR-329-3p and modulated chemosensitivity and autophagy by regulating miR-329-3p. In addition, SNHG7 upregulated MYO10 by sponging miR-329-3p. MYO10 restored the effect of miR-329-3p on cisplatin sensitivity and autophagy. Moreover, suppression of autophagy blocked SNHG7-induced cisplatin resistance. CONCLUSIONS: Depletion of SNHG7 potentiated cisplatin sensitivity through inhibition of autophagy by modulating miR-329-3p/MYO10 axis, providing a new therapeutic approach to overcome cisplatin resistance in NB chemotherapy.

Role of miR-21 in rats with proliferative diabetic retinopathy via TGF-ß signaling pathway.

OBJECTIVE: To explore the effects of miR-21 on the rats with proliferative diabetic retinopathy by regulating the transforming growth factor-beta (TGF-ß) signaling pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into the normal group (n=12), model group (n=12), and inhibitor group (TGF-ß signaling inhibitor) (n=12). No treatment was performed in the normal group, the diabetic retinopathy model was established in the model group, and the model was established in the inhibitor group after the intraperitoneal injection of the inhibitor. Then, the materials were sampled for detection. In each group, the retinal morphology was observed via hematoxylin-eosin (HE) staining, the expressions of TGF-ß1 and Smad3 were detected via immunohistochemistry, the relative protein expression levels of phosphorylated Smad3 (p-Smad3) and TGF-ß were determined via Western blotting, the expression of miR-21 was detected via quantitative Polymerase Chain Reaction (qPCR), and the hemodynamic indicators of the ocular tissues were detected using the color Doppler ultrasonography. RESULTS: The HE staining results revealed that the rats in the model group had evident retinal damage, which could be effectively improved using the inhibitor. According to the immunohistochemistry detection results, the positive expression level of TGF-ß1 was substantially raised in both model group and inhibitor group compared with that in the normal group (p<0.05), and it was notably lower in the inhibitor group than that in the model group (p<0.05). Moreover, the three groups did not differ in the positive expression level of Smad3 (p>0.05). The Western blotting results showed that the model and inhibitor groups had remarkably higher relative protein expression levels of p-Smad3 and TGF-ß1 than the normal group (p<0.05), and they were markedly lowered in the inhibitor group compared with those in the model group (p<0.05). According to the qPCR results, the expression level of miR-21 was notably elevated in both model group and inhibitor group compared with that in the normal group (p<0.05), and there was no difference in the expression level of miR-21 between the former two groups (p>0.05). Finally, based on the color Doppler ultrasonography findings, the levels of the hemodynamic indicators substantially declined in both model group and inhibitor group compared with those in the normal group (p<0.05), and they were notably higher in the inhibitor group than those in the model group. CONCLUSIONS: We found that miR-21 regulates the TGF-ß signaling pathway to affect the hemodynamics in the rats with proliferative diabetic retinopathy.

The expression of TRPM7 in serum of patients with sepsis, its influences on inflammatory factors and prognosis, and its diagnostic value.

OBJECTIVE: This study aimed to investigate the expression of TRPM7 in the serum of patients with sepsis and its influences on inflammatory factors and prognosis. PATIENTS AND METHODS: A prospective analysis was performed. 78 patients with sepsis were enrolled in the experimental group and treated from May 2015 to April 2017 in the Emergency Department of The Second Hospital of Dalian Medical University, and 75 healthy people were collected in the control group and received physical examinations during the same period. Real-time quantitative PCR was used to detect the relative expression of TRPM7, and sandwich enzyme-linked immunosorbent assay (ELISA) was applied to measure the serum expression levels of TNF-α, IL-6, and IL-10 in patients. Besides, the receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic value of TRPM7. RESULTS: The serum level of TRPM7 mRNA in the experimental group was higher than that in the control group (p<0.05). The serum levels of TNF-α, IL-6, and IL-10 in the experimental group were significantly higher than those in the control group (p<0.05). The optimal cut-off point value for the diagnosis of sepsis was 0.841; the specificity was 86%, and the sensitivity was 99%. Based on the survival data of the experimental group and the average expression level of TRPM7 which was 1.38, patients with a TRPM7 expression level less than 1.38 were divided into the low expression group, while those with a TRPM7 expression level equal or more than 1.38 were divided into the high expression group. The survival rate of the high expression group was significantly lower than that of the low expression group (p<0.05). CONCLUSIONS: In summary, TRPM7, with high expression level in the serum of patients with sepsis is expected to be a potential prognostic indicator for sepsis.

MiR-593-5p promotes the development of hypoxic-induced pulmonary hypertension via targeting PLK1.

OBJECTIVE: The aim of this study was to investigate the role of microRNA-593-5p (miR-593-5p) in hypoxia-induced pulmonary hypertension (HPH), and to explore its underlying mechanism. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were housed in a hypoxia environment 8 hours per day for consecutive 4 weeks. After the establishment of the HPH rat model, we detected the right ventricular systolic pressure (RVSP) and right heart hypertrophy index (RVHI) in HPH rats and controls. The expression levels of miR-593-5p and polo-like kinase 1 (PLK1) in rat lungs were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Subsequently, miR-593-5p mimics and inhibitor were constructed and transfected into cells. The proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) were accessed by cell counting kit-8 (CCK-8) assay and wound healing assay, respectively. The protein level of PLK1 in PASMCs after transfection with miR-593-5p mimics or inhibitor was detected by Western blot. Dual-luciferase reporter gene assay was conducted to verify the binding condition of miR-593-5p and PLK1. Finally, rescue experiments were performed to explore whether the regulatory effect of miR-593-5p on HPH development was associated with PLK1. RESULTS: RVSP and RVHI in rats of the hypoxic group were significantly higher than those of controls. MiR-593-5p was significantly downregulated while PLK1 was remarkably upregulated in lung tissues of HPH rats than those of controls. Similarly, miR-593-5p expression in PASMCs decreased gradually with the prolongation of hypoxia induction. Overexpression of miR-593-5p remarkably inhibited the proliferation and migration of PASMCs. Subsequently, dual-luciferase reporter gene verified the binding condition of miR-593-5p and PLK1. Both the mRNA and protein levels of PLK1 were negatively regulated by miR-593-5p. Also, rescue experiments demonstrated that the inhibitory effects of miR-593-5p on the proliferation and migration of PASMCs could be reversed by PLK1 overexpression. CONCLUSIONS: MiR-593-5p is lowly expressed in lung tissues of HPH rats. Meanwhile, it stimulates the proliferation and migration of PASMCs via targeting PLK1, thereby promoting HPH development.