Increased risk of preterm birth due to heat exposure during pregnancy: Exploring the mechanism of fetal physiology.

BACKGROUND: Heat exposure during pregnancy can increase the risk of preterm birth (PTB) through a range of potential mechanisms including pregnancy complications, hormone secretion and infections. However, current research mainly focuses on the effect of heat exposure on pathophysiological pathways of pregnant women, but ignore that maternal heat exposure can also cause physiological changes to the fetus, which will affect the risk of PTB. OBJECTIVE: In this study, we aimed to explore the mediating role of fetal heart rate (FHR) in the relationship between maternal heat exposure and PTB incidence. METHODS: We assigned heat exposure to a multi-center birth cohort in China during 2015-2018, which included all 162,407 singleton live births with several times FHR measurements during the second and third trimesters. We examined the associations between heat exposure, FHR and PTB in the entire pregnancy, each trimester and the last gestational month. The inverse odds ratio-weighted approach applied to the Cox regression was used to identify the mediation effect of heat exposure on PTB and its clinical subtypes via FHR. FINDINGS: Exposure to heat significantly increased the risk of PTB during the third trimester and the entire pregnancy, hazard ratios and 95 % CIs were 1.266 (1.161, 1.379) and 1.328 (1.218, 1.447). Heat exposure during the third trimester and entire pregnancy increased FHR in the third trimester by 0.24 bpm and 0.14 bpm. The proportion of heat exposure mediated by FHR elevation on PTB and its subtype ranged from 3.68 % to 24.06 %, with the significant mediation effect found for both medically indicated PTB and spontaneous PTB. CONCLUSIONS: This study suggests that heat exposure during pregnancy has an important impact on fetal health, and FHR, as a surrogate marker of fetal physiology, may mediate the increased risk of PTB caused by extreme heat. Monitoring and managing physiological changes in the fetus would constitute a promising avenue to reduce adverse birth outcomes associated with maternal heat exposure.

N6-methyladenosine levels in peripheral blood RNA: a potential diagnostic biomarker for colorectal cancer.

BACKGROUND: N6-methyladenosine (m6A) is dysregulated in various cancers, including colorectal cancer (CRC). Herein, we assess the diagnostic potential of peripheral blood (PB) m6A levels in CRC. METHODS: We collected PB from healthy controls (HCs) and patients with CRC, analyzed PB RNA m6A levels and the expression of m6A-related demethylase genes FTO and ALKBH5, cocultured CRC cells with PB mononuclear cells (PBMCs), and constructed an MC38 cancer model. RESULTS: PB RNA m6A levels were higher in the CRC than that in HCs. The area under the curve (AUC) of m6A levels (0.886) in the CRC was significantly larger compared with carbohydrate antigen 199 (CA199; 0.666) and carcinoembryonic antigen (CEA; 0.834). The combination of CEA and CA199 with PB RNA m6A led to an increase in the AUC (0.935). Compared with HCs, the expression of FTO and ALKBH5 was decreased in the CRC. After coculturing with CRC cells, the PBMCs RNA m6A were significantly increased, whereas the expression of FTO and ALKBH5 decreased. Furthermore, m6A RNA levels in the PB of MC38 cancer models were upregulated, whereas the expression of FTO and ALKBH5 decreased. CONCLUSIONS: PB RNA m6A levels are a potential diagnostic biomarker for patients with CRC.

S100A6 mediated epithelial-mesenchymal transition affects chemosensitivity of colorectal cancer to oxaliplatin.

PURPOSE: To investigate the mechanism by which S100 calcium-binding protein A6 (S100A6) affects colorectal cancer (CRC) cells to oxaliplatin (L-OHP) chemotherapy, and to explore new strategies for CRC treatment. METHODS: S100A6 expression was assessed in both parental and L-OHP-resistant CRC cells using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assays (ELISA). Lentiviral vectors were utilized to induce the knockdown of S100A6 expression, followed by comprehensive evaluations of cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT). Additionally, RNA-seq analysis was conducted to identify genes associated with the knockdown of S100A6. RESULTS: Elevated S100A6 expression in CRC tissues correlated with an adverse prognosis in patients with CRC. Higher expression of S100A6 was also observed in L-OHP-resistant CRC cells, which showed enhanced proliferation, migration, invasion, and antiapoptotic capabilities. Notably, the knockdown of S100A6 expression resulted in decreased proliferation, increased apoptosis, and suppression of EMT and tumorigenicity in L-OHP-resistant CRC cells. Transcriptome sequencing reveals a noteworthy association between S100A6 and vimentin expression. Application of the EMT agonist, transforming growth factor ß (TGF-ß), induces EMT in CRC cells. S100A6 expression positively correlates with TGF-ß expression. TGF-ß facilitated the expression of EMT-related molecules and reduced the chemosensitivity of L-OHP in S100A6-knockdown cells. CONCLUSION: In conclusion, the knockdown of S100A6 may overcome the L-OHP resistance of CRC cells by modulating EMT.

Recent advances in microfluidic technology of arterial thrombosis investigations.

Microfluidic technology has emerged as a powerful tool in studying arterial thrombosis, allowing researchers to construct artificial blood vessels and replicate the hemodynamics of blood flow. This technology has led to significant advancements in understanding thrombosis and platelet adhesion and aggregation. Microfluidic models have various types and functions, and by studying the fabrication methods and working principles of microfluidic chips, applicable methods can be selected according to specific needs. The rapid development of microfluidic integrated system and modular microfluidic system makes arterial thrombosis research more diversified and automated, but its standardization still needs to be solved urgently. One key advantage of microfluidic technology is the ability to precisely control fluid flow in microchannels and to analyze platelet behavior under different shear forces and flow rates. This allows researchers to study the physiological and pathological processes of blood flow, shedding light on the underlying mechanisms of arterial thrombosis. In conclusion, microfluidic technology has revolutionized the study of arterial thrombosis by enabling the construction of artificial blood vessels and accurately reproducing hemodynamics. In the future, microfluidics will place greater emphasis on versatility and automation, holding great promise for advancing antithrombotic therapeutic and prophylactic measures.

What is the context? To study the mechanism of arterial thrombosis, including the platelet adhesion and aggregation behavior and the coagulation process.Microfluidic technology is commonly used to study thrombosis. Microfluidic technology can simulate the real physiological environment on the microscopic scale in vitro, with high throughput, low cost, and fast speed.As an innovative experimental platform, microfluidic technology has made remarkable progress and has found applications in the fields of biology and medicine.What is new? This review summarizes the different fabrication methods of microfluidics and compares the advantages and disadvantages of these methods. Recent developments in microfluidic integrated systems and modular microfluidic systems have led to more diversified and automated microfluidic chips in the future.The different types and functions of microfluidic models are summarized. Platelet adhesion aggregation and coagulation processes, as well as arterial thrombus-related shear force changes and mechanical behaviors, were investigated by constructing artificial blood vessels and reproducing hemodynamics.Microfluidics can provide a basis for the development of personalized thrombosis treatment strategies. By analyzing the mechanism of action of existing drugs, using microfluidic technology for high-throughput screening of drugs and evaluating drug efficacy, more drug therapy possibilities can be developed.What is the impact?This review utilizes microfluidics to further advance the study of arterial thrombosis, and microfluidics is also expected to play a greater role in the biomedical field in the future.

A Comparative Analysis of Major Cell Wall Components and Associated Gene Expression in Autotetraploid and Its Donor Diploid Rice (Oryza sativa L.) under Blast and Salt Stress Conditions.

Whole-genome duplication is a significant evolutionary mechanism in plants, with polyploid plants often displaying larger organs and enhanced adaptability to unfavorable conditions compared to their diploid counterparts. The cell wall acts as a primary defense for plant cells against external stresses, playing an essential role in the plant's resistance to various stressors. In this study, we utilized both autotetraploid and its donor diploid rice (Oryza sativa L.) to analyze their phenotypic differences comparatively, the composition of key cell wall components, and the expression of related genes under normal conditions, as well as under stress from Magnaporthe oryzae (M. oryzae) and salt. Our findings indicated that autotetraploid rice exhibits significantly larger phenotypic characteristics under normal conditions than diploid rice. At the seedling stage, the lignin, cellulose, hemicellulose, and pectin levels in autotetraploid rice were markedly lower than in diploid rice. Additionally, 24 genes associated with major cell wall components showed differential expression between diploid and tetraploid rice. At the filling stage, the lignin and pectin content in autotetraploid rice were significantly higher than in diploid rice, while the levels of cellulose and hemicellulose were notably lower. Under M. oryzae stress or salt stress, autotetraploid rice showed smaller lesion areas and less wilting than diploid rice. The increased lignin content in autotetraploid rice under M. oryzae stress suggested a stronger adaptive capacity to adverse conditions. Compared to salt stress, M. oryzae stress induced more differential expression of genes related to major cell wall components. In this study, we explored the differences in the major cell wall components of diploid and homologous tetraploid rice under various treatment conditions. This study provides valuable insights into understanding the cell wall's adaptive mechanisms in autotetraploid rice when facing blast disease and salt stress, and it reveals the differential gene expression linked to these adaptive capabilities.

Therapeutic efficacy of optimal pulse technology in the treatment of chalazions.

Introduction: To evaluate the efficacy of optimized pulse technology in treating chalazia. Methods: Prospective before-after study. All patients received two sessions of optimal pulse technology (OPT) with an interval of 1 week. The first visit was before treatment and the patients underwent 2 treatment sessions with a 1-week interval. The non-invasive tear breakup time (NIBUT), corneal fluorescein staining (CFS) score, Schirmer's test I without anesthesia, conjunctival hyperemia, and meibomian gland area were compared before and after treatment, and the related factors of curative effect were analyzed. Results: 23 patients (23 eyes) with chalazia were included. All patients received two sessions of OPT treatment at 1-week intervals. Following the first OPT treatment, a reduction in the chalazion size was observed in 17 patients (73.91%). One patient was completely cured, and 1 patient had an increase in the diameter of the chalazion. The meibomian gland area increased significantly compared to before treatment (p = 0.023). Compared with baseline, the conjunctival congestion and ST decreased, NIBUT increased, and there was no statistical difference. After the second treatment, the chalazion size decreased in 21 cases, and 3 patients were cured. A significant increase in the meibomian gland area compared with the baseline area (p < 0.001). Additionally, conjunctival congestion decreased significantly. After two sessions, the Schirmer test exhibited a decrease, and NIBUT increased, although these changes did not reach statistical significance. The curative effect was unrelated to sex, age, first onset, single disease, and other factors. Conclusion: After treatment, the diameter of chalazions was reduced in 91.3% of the patients, and the area of the meibomian gland was significantly increased compared with that before treatment, which suggested that 2 OPT treatments at an interval of 1 week can improve the signs of adult patients in the non-acute infectious stage with chalazia.

Transcriptome-Wide Analysis of Core Transcription Factors Associated with Defense Responses in Autotetraploid versus Diploid Rice under Saline Stress and Recovery.

Saline stress is a major abiotic stress that inhibits plant growth and yields worldwide. The plant transcription factor (TF) family plays an important role in converting abiotic stress signals into gene expression changes. In this study, a transcriptome-based comparative analysis was performed to investigate the global gene expression of all the TFs in diploid and autotetraploid rice during the early stage of NaCl stress and recovery period. The phenotypic data indicated that the tetraploid rice exhibited a superior salt-tolerant ability compared to the diploid rice. A total of 55 TF families were co-expressed in the tetraploid and diploid rice, and the cumulative number of TF-expressed genes was relatively higher in the diploid rice than in the tetraploid rice at all time points. Unlike the diploid rice, the overall gene expression levels of the tetraploid rice were comparable to the control during recovery. The number of differentially expressed TFs (DE-TFs) in the tetraploid rice decreased after recovery, whereas it increased to a large extent in the diploid rice. GO and KEGG pathway enrichment analysis of the DE-TFs discovered the early switching of the ABA-activated signaling pathway and specific circadian rhythm in the tetraploid rice. Combining the PPI network and heatmap analysis, some core DE-TFs were found that may have potential roles to play in tetraploid salt tolerance. This study will pave the way for elucidating the complex network regulatory mechanisms of salt tolerance in tetraploid rice.

Exosomal miR-155-5p drives widespread macrophage M1 polarization in hypervirulent Klebsiella pneumoniae-induced acute lung injury via the MSK1/p38-MAPK axis.

BACKGROUND: Hypervirulent Klebsiella pneumoniae (hvKp) infection-induced sepsis-associated acute lung injury (ALI) has emerged as a significant clinical challenge. Increasing evidence suggests that activated inflammatory macrophages contribute to tissue damage in sepsis. However, the underlying causes of widespread macrophage activation remain unclear. METHODS: BALB/c mice were intravenously injected with inactivated hvKp (iHvKp) to observe lung tissue damage, inflammation, and M1 macrophage polarization. In vitro, activated RAW264.7 macrophage-derived exosomes (iHvKp-exo) were isolated and their role in ALI formation was investigated. RT-PCR was conducted to identify changes in exosomal miRNA. Bioinformatics analysis and dual-luciferase reporter assays were performed to validate MSK1 as a direct target of miR-155-5p. Further in vivo and in vitro experiments were conducted to explore the specific mechanisms involved. RESULTS: iHvKp successfully induced ALI in vivo and upregulated the expression of miR-155-5p. In vivo, injection of iHvKp-exo induced inflammatory tissue damage and macrophage M1 polarization. In vitro, iHvKp-exo was found to promote macrophage inflammatory response and M1 polarization through the activation of the p38-MAPK pathway. RT-PCR revealed exposure time-dependent increased levels of miR-155-5p in iHvKp-exo. Dual-luciferase reporter assays confirmed the functional role of miR-155-5p in mediating iHvKp-exo effects by targeting MSK1. Additionally, inhibition of miR-155-5p reduced M1 polarization of lung macrophages in vivo, resulting in decreased lung injury and inflammation induced by iHvKp-exo or iHvKp. CONCLUSIONS: The aforementioned results indicate that exosomal miR-155-5p drives widespread macrophage inflammation and M1 polarization in hvKp-induced ALI through the MSK1/p38-MAPK Axis.

Exploration of the preterm birth risk-related heat event thresholds for pregnant women: a population-based cohort study in China.

Background: Heat events increase the risk of preterm birth (PTB), and identifying the risk-related event thresholds contributes to developing early warning system for pregnant women and guiding their public health response. However, the event thresholds that cause the risk remain unclear. We aimed to investigate the effects of heat events defined with different intensities and durations on PTB throughout pregnancy, and to determine thresholds for the high-risk heat events. Methods: Using a population-based birth cohort data, we included 210,798 singleton live births in eight provinces in China during 2014-2018. Daily meteorological variables and inverse distance weighted methods were used to estimate exposures at a resolution of 1 km × 1 km. A series of cut off temperature intensities (50th-97.5th percentiles, or 18 °C-35 °C) and durations (at least 1, 2, 3, 4 or 5 consecutive days) were used to define the heat events. Cox regression models were used to estimate the effects of heat events on PTB in various gestational weeks during the entire pregnancy, and event thresholds were determined by calculating population attributable fractions. Findings: The hazard ratios of heat event exposure on PTB ranged from 1.07 (95% CI: 1.00, 1.13) to 1.43 (1.15, 1.77). Adverse effects of heat event exposure were prominently detected in gestational week 1-4, week 21-32 and the four weeks before delivery. The heat event thresholds were determined to be daily maximum temperature at the 90th percentile of the distribution or 30 °C lasting for at least one day. If pregnant women were able to avoid the heat exposures from the early warning systems triggered by these thresholds, approximately 15% or 17% of the number of total PTB cases could have been avoided. Interpretation: Exposure to heat event can increase the risk of PTB when thermal event exceeds a specific intensity and duration threshold, particularly in the first four gestational weeks, and between week 21 and the last four weeks. This study provides compelling evidence for the development of heat-health early warning systems for pregnant women that could substantially mitigate the risk of PTB. Funding: National Key R&D Program of China (No. 2018YFA0606200), National Natural Science Foundation of China (No. 42175183), Sanming Project of Medicine in Shenzhen (No. SZSM202111001).

Boronotyrosine, a Borylated Amino Acid Mimetic with Enhanced Solubility, Tumor Boron Delivery, and Retention for the Re-emerging Boron Neutron Capture Therapy Field.

Boron neutron capture therapy (BNCT) is a re-emerging binary cellular level cancer intervention that occurs through the interaction of a cancer-specific 10boron (10B) drug and neutrons. We created a new 10B drug, 3-borono-l-tyrosine (BTS), that improves on the characteristics of the main historical BNCT drug 4-borono-l-phenylalanine (BPA). BTS has up to 4 times greater uptake in vitro than BPA and increased cellular retention. Like BPA, BTS uptake is mediated by the l-type amino acid transporter-1 (LAT1) but is less sensitive to natural amino acid competition. BTS can be formulated and bolus dosed at much higher levels than BPA, resulting in 2-3 times greater boron delivery in vivo. Fast blood clearance and greater tumor boron delivery result in superior tumor-to-blood ratios. BTS boron delivery appears to correlate with LAT1 expression. BTS is a promising boron delivery drug that has the potential to improve modern BNCT interventions.

Evaluating the Differential Response of Transcription Factors in Diploid versus Autotetraploid Rice Leaves Subjected to Diverse Saline-Alkali Stresses.

Saline-alkali stress is a significant abiotic stress factor that impacts plant growth, development, and crop yield. Consistent with the notion that genome-wide replication events can enhance plant stress resistance, autotetraploid rice exhibited a higher level of tolerance to saline-alkali stress than its donor counterparts, which is reflected by differential gene expression between autotetraploid and diploid rice in response to salt, alkali, and saline-alkali stress. In this study, we investigated the expression of the transcription factors (TFs) in the leaf tissues of autotetraploid and diploid rice under different types of saline-alkali stress. Transcriptome analysis identified a total of 1040 genes from 55 TF families that were altered in response to these stresses, with a significantly higher number in autotetraploid rice compared to diploid rice. Contrarily, under these stresses, the number of expressed TF genes in autotetraploid rice was greater than that in diploid rice for all three types of stress. In addition to the different numbers, the differentially expressed TF genes were found to be from significantly distinct TF families between autotetraploid and diploid rice genotypes. The GO enrichment analysis unraveled that all the DEGs were distributed with differentially biological functions in rice, in particular those that were enriched in the pathways of phytohormones and salt resistance, signal transduction, and physiological and biochemical metabolism in autotetraploid rice compared to its diploid counterpart. This may provide useful guidance for studying the biological roles of polyploidization in plant resilience in response to saline-alkali stress.

Comparison of vasoactive-inotropic score, vasoactive-ventilation-renal score, and modified vasoactive-ventilation-renal score for predicting the poor prognosis after coronary artery bypass grafting.

BACKGROUND: Exploring reliable prediction scoring systems is valuable for the poor prognosis of patients after coronary artery bypass grafting (CABG). Herein, we explored and compared the predictive performance of vasoactive-inotropic score (VIS), vasoactive-ventilation-renal (VVR) score, and modified VVR (M-VVR) score in the poor prognosis of patients undergoing CABG. METHODS: A retrospective cohort study was performed in Affiliated Hospital of Jining Medical University, and data of 537 patients were collected from January 2019 to May 2021. The independent variables were VIS, VVR, and M-VVR. Study endpoint of interest was the poor prognosis. Association between VIS, VVR, M-VVR and poor prognosis was assessed using logistic regression analysis, and odds ratios (OR) and 95% confidence intervals (CIs) were reported. The performance of VIS, VVR, and M-VVR to predict the poor prognosis was assessed by calculating the area under the curve (AUC), and differences of the AUC of the three scoring systems were compared using DeLong test. RESULTS: After adjusting gender, BMI, hypertension, diabetes, surgery methods, and left ventricular ejection fraction (LVEF), VIS (OR: 1.09, 95%CI: 1.05-1.13) and M-VVR (OR: 1.09, 95%CI: 1.06-1.12) were associated with the increased odds of poor prognosis. The AUC of M-VVR, VVR, and VIS was 0.720 (95%CI: 0.668-0.771), 0.621 (95%CI: 0.566-0.677), and 0.685 (95%CI: 0.631-0.739), respectively. DeLong test displayed that the performance of M-VVR was better than VVR (P = 0.004) and VIS (P = 0.003). CONCLUSIONS: Our study found the good prediction performance of M-VVR for the poor prognosis of patients undergoing CABG, indicating that M-VVR may be a useful prediction index in the clinic.

Sensitive Urine Immunoassay for Visualization of Lipoarabinomannan for Noninvasive Tuberculosis Diagnosis.

Lipoarabinomannan (LAM) is a prospective noninvasive biomarker for tuberculosis (TB) diagnosis. Here, we report a visual immunoassay of high sensitivity for detecting LAM in urine samples toward TB diagnosis. This method uses a DNA-linked immunosorbent of LAM, followed by a transduction cascade into amplified visual signals using quantum dots (QDs) and calcein reaction with Cu2+ and copper nanoparticles (Cu NPs). The limit of detection (LOD) for LAM in the urine reaches 2.5 fg/mL and 25 fg/mL using a fluorometer and length readouts on strips, respectively, demonstrating an ultrahigh sensitivity. The clinical validation of the proposed assay was performed with 147 HIV-negative clinical urine specimens. The results show the sensitivity of test is 94.1% (16/17) for confirmed TB (culture-positive) and 85% (51/60) for unconfirmed TB (clinical diagnosis without positive culture results), respectively, when the test cutoff value is 40 fg/mL for TB. Its specificity is 89.2% (25/28) in non-TB and nontuberculous mycobacterial patients. The area under the curve (AUC) was 0.86 when controls were non-TB and LTBI patients, while the AUC was 0.92 when controls were only non-TB patients. This highly sensitive visual immunoassay of LAM has shown potential for noninvasive diagnosis of TB using urine samples.

MicroRNA-196a-5p targeting LRP1B modulates phenotype of thyroid carcinoma cells.

INTRODUCTION: Thyroid cancer (TC) is a common endocrine malignancy, comprising nearly one-third of all head and neck malignancies worldwide. MicroRNAs (miRNAs) have been implicated in the malignant progression of multiple cancers; however, their contribution to thyroid diseases has not been fully explored. MATERIAL AND METHODS: This study aimed to illustrate the regulatory mechanism of microRNA-196a-5p in TC progression and to investigate whether microRNA-196a-5p affects progression of TC cells by targeting low-density lipoprotein receptor-associated protein 1B (LRP1B). MicroRNA-196a-5p and LRP1B expression status in TC cells and normal human thyroid cells was detected by quantative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. Dual-luciferase reporter assay, cell counting kit-8 (CCK-8) assay, scratch healing assay, and Transwell assay were also performed. RESULTS: The results showed that microRNA-196a-5p expression was up-regulated and LRP1B expression was down regulated in TC cells. In addition, the upregulation of microRNA-196a-5p facilitated progression of TC cells. Silencing microRNA-196a-5p led to the opposite results. Dual-luciferase reporter assay offered evidence for microRNA-196a-5p targeting LRP1B in TC. MicroRNA-196a-5p could target LRP1B to facilitate proliferation, invasion, and migration of TC cells. CONCLUSION: Overall, this study revealed that microRNA-196a-5p may be a cancer-promoting microRNA that plays an important role in TC progression.

Study on the Decoupling and Interaction Effect between Industrial Structure Upgrading and Carbon Emissions under Dual Carbon Targets.

The issue of climate and environment has been paid more and more attention by countries all over the world, especially regarding carbon emissions. Many national policies and scholars' research contents have focused on this issue, which has become a hot topic in today's society. As the world's largest carbon emitter, it is vital for China to achieve green development, upgrade its industrial structure and explore the relationship between industrial structure upgrading and carbon emissions. To explore the decoupling and interactive effects of industrial structure upgrading and carbon emissions, this paper divides industrial structure upgrading into two aspects: rationalization of industrial structure and upgrading of industrial structure. Indicators related to industrial structure upgrading and carbon emissions are selected and the decoupling model of carbon emissions and industrial structure upgrading is constructed using panel data from 30 regions from 1997 to 2019. The core density function is used to analyze the decoupling distribution characteristics, and then the Gini coefficient decomposition method is used to analyze the carbon emissions decoupling index, revealing the regional differences and sources of carbon emissions decoupling index. Finally, spatial factors are included in the regression model to verify the spatial synergy effect of industrial structure upgrading on carbon emissions. The overall and local Moran indexes are used to reveal the spatial internal structure and agglomeration characteristics of industrial structure upgrading and carbon emissions, and, based on the research results, policy recommendations are put forward to promote sustainable and stable development of industrial structure upgrading in China. This provides a new perspective for understanding the relationship between industrial structure upgrading and carbon emissions and also provides a decision-making reference for promoting decoupling of industrial structure upgrading and carbon emissions under high-quality economic development and forcing low-carbon transformation of the industrial structure.

Hypomethylation-mediated overexpression of ITGA2 stimulates cell invasion and migration of thyroid carcinoma.

OBJECTIVE: To study the molecular mechanism of DNA methylation-mediated ITGA2 overexpression in thyroid carcinoma (TC). METHODS: First, 450K methylation data and mRNA expression profiles in TCGA-THCA dataset were downloaded from TCGA database. ITGA2 was identified as a methylation-driven gene by using R package "MethylMix". Afterwards, qRT-PCR, western blot and flow cytometry assay were performed to measure ITGA2 expression in TC cells. Methylation-specific PCR was utilized to measure promoter region methylation of ITGA2 in TC cells. Transwell and wound healing assays were carried out to assess cell invasive and migratory properties. RESULTS: Compared with normal cells, TC cells presented significantly increased ITGA2 expression. In addition, ITGA2 expression was controlled by DNA methylation. Hypomethylation of CpG island resulted in an increased ITGA2 expression. Hence, methylation and expression levels of ITGA2 were inversely associated. Moreover, overexpression of ITGA2 and promoter region hypomethylation facilitated cell invasive and migratory abilities in TC. CONCLUSION: These findings authenticated that promoter region hypomethylation of ITGA2 fostered ITGA2 expression as well as TC cell invasion and migration.

Establishment of duplex TaqMan RT-PCR method for detection of Entamoeba histolytica and Giardia lamblia in fecal sample / 中国热带医学

@#Abstract: Objective To establish the duplex TaqMan RT-PCR method for detection of Entamoeba histolytica and Giardia lamblia in fecal samples. Methods Primer pairs and probes for Entamoeba histolytica and Giardia lamblia were designed and duplex TaqMan RT-PCR amplification system was constructed. PCR products were inserted into the pUC57 plasmid, and the lower limit of detection of the method was determined. Clinical stool samples were tested in order to evaluated the efficacy of the method. Results The detection limits of duplex TaqMan RT-PCR were 31.6 copies/μL for Entamoeba histolytica and 32 copies/μL for Giardia lamblia, respectively. Of the total of 212 clinical stool samples tested, all 3 samples with E. histolytica-positive patients by microscopy were positive by PCR, while 1 from 209 samples with E. histolytica-negative patients by microscopy were positive by PCR, and the remaining samples were negative. For Giardia lamblia, all 8 samples positive by microscopy were positive by PCR, and 1 from 204 sample with a microscopy-negative patient was positive by PCR, and the remaining samples were negative. The amplification product sequencing and blast analysis were used to confirm that the amplified sequence in the specimen of a patient with negative microscopy but positive PCR belongs to the targeted pathogen, supported by clinical symptoms and laboratory test results. PCR results for other diarrhea-causing pathogens were negative, indicating no cross-reactivity. Conclusions The dual TaqMan RT-PCR method developed in this study can not only detect microscopy-positive samples of Entamoeba histolytica and Giardia lamblia but also can detect samples that were missed by microscopy, with higher sensitivity than the microscopy method. Further, this detection method does not cross-react with other diarrhea-causing pathogens, including cross-react with other diarrhea-causing pathogens including Iodamoeba butschlii, Blastocystis hominis, Plesiomonas, Aeromonas, Salmonella, Shigella, Sphaerozoum fuscum, and Entamoeba hartmani, thus has a good specificity.

[Advances in the study of vasoactive-inotropic score in critically ill patients].

The degree of hemodynamic support by vasoactive drugs in critically ill patients is often considered one of the markers of disease severity. The sequential organ failure assessment (SOFA), European system for cardiac operative risk evaluation II (EuroScore II), and other scores only roughly quantify the drug support of cardiovascular system. When patients need large doses of vasoactive drugs, the mortality increases accordingly. The vasoactive-inotropic score (VIS) objectively quantifies the degree of cardiovascular support using a simple formula that standardizes the dose of different agents, and it is recommended as a simple, effective, and accurate prognostic indicator. In recent years, there are more and more clinical applications and related studies at home and abroad. This paper reviews the application and progress of VIS score in critically ill patients, providing help for doctors to judge the condition and prognosis of patients and guiding the decision-making of diagnosis and treatment.