Defining the spatial distribution of extracellular adenosine revealed a myeloid-dependent immunosuppressive microenvironment in pancreatic ductal adenocarcinoma.

BACKGROUND: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) remains extremely poor. It has been suggested that the adenosine pathway contributes to the ability of PDAC to evade the immune system and hence, its resistance to immuno-oncology therapies (IOT), by generating extracellular adenosine (eAdo). METHODS: Using genetically engineered allograft models of PDAC in syngeneic mice with defined and different immune infiltration and response to IOT and autochthonous tumors in KPC mice we investigated the impact of the adenosine pathway on the PDAC tumor microenvironment (TME). Flow cytometry and imaging mass cytometry (IMC) were used to characterize the subpopulation frequency and spatial distribution of tumor-infiltrating immune cells. Mass spectrometry imaging (MSI) was used to visualize adenosine compartmentalization in the PDAC tumors. RNA sequencing was used to evaluate the influence of the adenosine pathway on the shaping of the immune milieu and correlate our findings to published data sets in human PDAC. RESULTS: We demonstrated high expression of adenosine pathway components in tumor-infiltrating immune cells (particularly myeloid populations) in the murine models. MSI demonstrated that extracellular adenosine distribution is heterogeneous in tumors, with high concentrations in peri-necrotic, hypoxic regions, associated with rich myeloid infiltration, demonstrated using IMC. Protumorigenic M2 macrophages express high levels of the Adora2a receptor; particularly in the IOT resistant model. Blocking the in vivo formation and function of eAdo (Adoi), using a combination of anti-CD73 antibody and an Adora2a inhibitor slowed tumor growth and reduced metastatic burden. Additionally, blocking the adenosine pathway improved the efficacy of combinations of cytotoxic agents or immunotherapy. Adoi remodeled the TME, by reducing the infiltration of M2 macrophages and regulatory T cells. RNA sequencing analysis showed that genes related to immune modulation, hypoxia and tumor stroma were downregulated following Adoi and a specific adenosine signature derived from this is associated with a poorer prognosis in patients with PDAC. CONCLUSIONS: The formation of eAdo promotes the development of the immunosuppressive TME in PDAC, contributing to its resistance to conventional and novel therapies. Therefore, inhibition of the adenosine pathway may represent a strategy to modulate the PDAC immune milieu and improve therapy response in patients with PDAC.

[Expression and protective effect of chemerin in idiopathic pulmonary fibrosis].

Objective: To explore the expression and the role of chemerin in idiopathic pulmonary fibrosis (IPF). Methods: Quantitative PCR and Western blotting were used to determine the mRNA and protein levels of chemerin in lung tissues from IPF patients and the controls. Clinical serum level of chemerin was analyzed by enzyme-linked immunosorbent assay. The mouse lung fibroblasts isolated and cultured in vitro were divided into the control, TGF-ß, TGF-ß+chemerin and chemerin groups. Immunofluorescence staining was used to observe the expression of α-smooth muscle actin (α-SMA). C57BL/6 mice were randomly divided into the control, bleomycin, bleomycin+chemerin, and chemerin groups. Masson and immunohistochemical staining were performed to evaluate the severity of pulmonary fibrosis. Expression of epithelial to mesenchymal transition (EMT) markers was detected by quantitative PCR and immunohistochemical staining in the in vitro and in vivo models of pulmonary fibrosis, respectively. Results: Compared with the control group, the expression of chemerin was downregulated in both the lung tissue and the serum of IPF patients. Immunofluorescence showed that treatment of fibroblasts with TGF-ß alone resulted in a robust expression of α-SMA, whereas treatment with TGF-ß and chemerin together exhibited the similar expression levels of α-SMA as the control group. Masson staining indicated that the bleomycin-induced pulmonary fibrosis model was constructed successfully, while treatment of chemerin partially alleviated the damage of lung tissue. Immunohistochemical staining showed that the expression of chemerin in the lung tissue was significantly decreased in the bleomycin group. Quantitative PCR and immunohistochemistry showed that chemerin attenuated EMT induced by TGF-ß and bleomycin both in vitro and in vivo. Conclusions: The expression of chemerin was reduced in patients with IPF. Chemerin may play a protective role in the development of IPF by regulating EMT, providing a new idea for the clinical treatment of IPF.

Seeking Repeating Anthropogenic Seismic Sources: Implications for Seismic Velocity Monitoring at Fault Zones.

Seismic velocities in rocks are highly sensitive to changes in permanent deformation and fluid content. The temporal variation of seismic velocity during the preparation phase of earthquakes has been well documented in laboratories but rarely observed in nature. It has been recently found that some anthropogenic, high-frequency (>1 Hz) seismic sources are powerful enough to generate body waves that travel down to a few kilometers and can be used to monitor fault zones at seismogenic depth. Anthropogenic seismic sources typically have fixed spatial distribution and provide new perspectives for velocity monitoring. In this work, we propose a systematic workflow to seek such powerful seismic sources in a rapid and straightforward manner. We tackle the problem from a statistical point of view, considering that persistent, powerful seismic sources yield highly coherent correlation functions (CFs) between pairs of seismic sensors. The algorithm is tested in California and Japan. Multiple sites close to fault zones show high-frequency CFs stable for an extended period of time. These findings have great potential for monitoring fault zones, including the San Jacinto Fault and the Ridgecrest area in Southern California, Napa in Northern California, and faults in central Japan. However, extra steps, such as beamforming or polarization analysis, are required to determine the dominant seismic sources and study the source characteristics, which are crucial to interpreting the velocity monitoring results. Train tremors identified by the present approach have been successfully used for seismic velocity monitoring of the San Jacinto Fault in previous studies.

Measurement of the

The ^{18}O(α,γ)^{22}Ne reaction is critical for AGB star nucleosynthesis due to its connection to the abundances of several key isotopes, such as ^{21}Ne and ^{22}Ne. However, the ambiguous resonance energy and spin-parity of the dominant 470 keV resonance leads to substantial uncertainty in the ^{18}O(α,γ)^{22}Ne reaction rate for the temperature of interest. We have measured the resonance energies and strengths of the low-energy resonances in ^{18}O(α,γ)^{22}Ne at the Jinping Underground Nuclear Astrophysics experimental facility (JUNA) with improved precision. The key 470 keV resonance energy has been measured to be E_{α}=474.0±1.1 keV, with such high precision achieved for the first time. The spin-parity of this resonance state is determined to be 1^{-}, removing discrepancies in the resonance strengths in earlier studies. The results significantly improve the precision of the ^{18}O(α,γ)^{22}Ne reaction rates by up to about 10 times compared with the previous data at typical AGB temperatures of 0.1-0.3 GK. We demonstrate that such improvement leads to precise ^{21}Ne abundance predictions, with an impact on probing the origin of meteoritic stardust SiC grains from AGB stars.

Genome-wide identification and expression analysis of SlRR genes in response to abiotic stress in tomato.

The cytokinin two-component signal transduction system (TCS) is involved in many biological processes, including hormone signal transduction and plant growth regulation. Although cytokinin TCS has been well characterized in Arabidopsis thaliana, its role in tomato remains elusive. In this study, we characterized the diversity and function of response regulator (RR) genes, a critical component of TCS, in tomato. In total, we identified 31 RR genes in the tomato genome. These SlRR genes were classified into three subgroups (type-A, type-B and type-C). Various stress-responsive cis-elements were present in the tomato RR gene promoters. Their expression responses under pesticide treatment were evaluated by transcriptome analysis. Their expression under heat, cold, ABA, salinity and NaHCO3 treatments was further investigated by qRT-PCR and complemented with the available transcription data under these treatments. Specifically, SlRR13 expression was significantly upregulated under salinity, drought, cold and pesticide stress and was downregulated under ABA treatment. SlRR23 expression was induced under salt treatment, while the transcription level of SlRR1 was increased under cold and decreased under salt stress. We also found that GATA transcription factors played a significant role in the regulation of SlRR genes. Based on our results, tomato SlRR genes are involved in responses to abiotic stress in tomato and could be implemented in molecular breeding approaches to increase resistance of tomato to environmental stresses.

[A report of 7 cases of toxic liver disease caused by mixed gas in a shoe factory].

Trichloromethane and dichloromethane have toxic effects on the liver, and incidents of toxic liver disease caused by them have been reported from time to time. In November 2021, an occupational chemical poisoning incident occurred in a shoe factory in Huidong County, Guangdong Province. After testing the air at the scene and analyzing the clinical data of the poisoning patients, it was preliminarily determined that the poisoning was caused by a mixed gas poisoning incident dominated by trichoromethane. At admission, the liver function of 7 patients was tested for different degrees of impairment (alanine aminotransferase 145-2501 IU/L, aspartate aminotransferase 66-1286 IU/L). The volatile organic components of on-site raw and auxiliary materials were analyzed. The percentages of trichloromethane and dichloromethane detected in 103A powder glue used in the poisoning workshop site accounted for 21.11% and 6.77% respectively.

Monitoring Seismic Velocity Changes Across the San Jacinto Fault Using Train-Generated Seismic Tremors.

Microseismic noise has been used for seismic velocity monitoring. However, such signals are dominated by low-frequency surface waves that are not ideal for detecting changes associated with small tectonic processes. Here we show that it is possible to extract stable, high-frequency body waves using seismic tremors generated by freight trains. Such body waves allow us to focus on small velocity perturbations in the crust with high spatial resolution. We report on 10 years of seismic velocity temporal changes at the San Jacinto Fault. We observe and map a two-month-long episode of velocity changes with complex spatial distribution and interpret the velocity perturbation as produced by a previously undocumented slow-slip event. We verify the hypothesis through numerical simulations and locate this event along a fault segment believed to be locked. Such a slow-slip event stresses its surroundings and may trigger a major earthquake on a fault section approaching failure.

[Clinical application of a self-developed suction-irrigation device in endoscopic ear surgery for attic cholesteatoma].

Objective: To introduce a new self-developed irrigation device(SID) that does not employ a sheath or an irrigation-suction system and evaluate to its efficiency in transcanal endoscopic ear surgery (TEES) for attic cholesteatoma. Methods: 38 patients who were subjected to TEES for attic cholesteatoma between October 2019 to June 2021 were included in this study, including 17 males and 21 females with an average age of (38.6±11.9) years. SID and underwater continuous drilling were used during operation. Width of endoscope and irrigation speed were measured when SID was applied. The operating time, surgical view and complications were compared between two groups. Results: The width of the endoscope was 3.5-4.6 mm in diameter and the irrigation speed was 20-40 ml/min when SID was used. SID cleaned the lens at the tip of the endoscope and created a clear field of view during TEES. The operation time was (86.6±18.1) min. The skin of the external ear canal was found injured during operation in 3 patients, but there were no complications such as necrosis of the flap, stenosis of external ear canal, sensorineural hearing loss, facial paralysis and cerebrospinal fluid leakage. Conclusions: SID is simple and enhances the efficacy of TEES, providing a new irrigation choice in TEES for attic cholesteatoma.

[Characteristics and regulatory mechanisms of lipid metabolism remodeling after malignant transformation of glioma-associated macrophages].

Objective: To observe the lipid metabolism characteristics of tumor-associated macrophages (TAM) after malignant transformation in the glioma micro-environment, and analyze the biological phenotype changes and regulatory mechanisms after inhibiting the lipid metabolism remodeling. Methods: Twelve male Balb/c mice of 6-8 weeks were used in the study. Macrophages (Mφ) were derived from mouse bone marrow, and malignantly transformed macrophages (tMφ1 and tMφ2) were cloned from the model of glioma stem cell (GSC) through interaction with Mφ in vivo and in vitro. Intracellular lipid droplet formation and cellular cholesterol content were measured respectively in Mφ, tMφ1 and tMφ2. qRT-PCR was performed to detect the genes expression level related with lipid metabolism, including sterol regulatory element binding protein (SREBP), fatty acid synthase (FASN), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase (HMG-CoA). Simvastatin (SIM) was used to analyze the proliferation, immigration and invasiveness ability in tMφ1 and tMφ2 after inhibition of the lipid metabolism. Differential expression profiles of miRNAs after SIM treatment were constructed in t-Mφ1 and bio-informatics analysis was screened and verified for miR449a and its target gene sorting micro-tubule connectin 17 (SNX17) associated with lipid metabolism remodeling. The effect on SNX17 by up-regulated miR-449a were analyzed by qRT-PCR and Western blot, meanwhile, the biological phenotype and cholesterol content were observed after up-regulation of miR449a. Low-density lipoprotein receptor (LDLR) protein levels after SNX17 knockdown and intracellular cholesterol content after LDLR knockdown were detected respectively. Results: The numbers of intracellular lipid droplet formation in tMφ1 and tMφ2 were more than that in Mφ (P<0.001). Likewise, the relative contents of cholesterol (3.89±0.68 and 3.56±0.53), SREBP (4.78±0.60 and 2.84±0.41), FASN (4.65±0.70 and 3.01±0.45), and HMG-CoA (5.74±0.55 and 2.97±0.34) were significantly higher in tMφ1 and tMφ2 than those of Mφ (1.01 wel, 1.02 wel and 0.99 wel, respectively) (all P<0.001). The proliferation rates of tMφ1 and tMφ2 decreased from (47.06±5.88) % and (45.29±5.64)% to (23.53±4.70)% and (18.74±5.76)%, respectively after treatment with SIM (both P<0.05). The numbers of migrated cells decreased from 1 025±138 and 350±47 to 205±63 and 99±25, respectively (both P<0.001). And the numbers of invasiveness cells decreased from 919±45 and 527±34 to 220±23 and 114±21, respectively (both P<0.001). While the relative intracellular cholesterol content decreased to 0.52±0.08 and 0.58±0.07 (both P<0.05), respectively. MiR-449a was screened from tMφ1 by SIM, and the target gene was analyzed and verified to be SNX17. SNX17 expression was down-regulated, and the proliferation rate, the number of migration and invasiveness was significantly decreased after miR-449a over-expression (all P<0.05). Low-density lipoprotein receptor (LDLR) expression was down-regulated after knock-down of SNX17, while the cholesterol content was decreased after knock-down of LDLR in tMφ1 and tMφ2 (all P<0.05). Conclusions: Malignantly transformed TAMs undergo lipid metabolism remodeling characterized with enhanced lipid metabolism. MiR-449a regulates the LDLR by targeting SNX17, thereby affecting the lipid metabolism of malignantly transformed macrophages, and subsequently inhibiting its proliferation, migration, and invasion ability. Precise intervention with miR-449a/SNX17/LDLR axis could provide an experimental basis for reversing its tumor-promoting micro-environment remodeled by GSC through metabolic intervention.

Deep Underground Laboratory Measurement of

The ^{13}C(α,n)^{16}O reaction is the main neutron source for the slow-neutron-capture process in asymptotic giant branch stars and for the intermediate process. Direct measurements at astrophysical energies in above-ground laboratories are hindered by the extremely small cross sections and vast cosmic-ray-induced background. We performed the first consistent direct measurement in the range of E_{c.m.}=0.24 to 1.9 MeV using the accelerators at the China Jinping Underground Laboratory and Sichuan University. Our measurement covers almost the entire intermediate process Gamow window in which the large uncertainty of the previous experiments has been reduced from 60% down to 15%, eliminates the large systematic uncertainty in the extrapolation arising from the inconsistency of existing datasets, and provides a more reliable reaction rate for the studies of the slow-neutron-capture and intermediate processes along with the first direct determination of the alpha strength for the near-threshold state.

circRNA CRIM1 regulates the migration and invasion of bladder cancer by targeting miR182/Foxo3a axis

PurposeTo explore the molecular mechanism of circRNA CRIM1 in the regulation of bladder cancer by targeting the miR182/Foxo3a axis.Methods50 pairs of cancer tissues and para-cancerous tissues of patients with bladder cancer were collected. RT-PCR method was used to detect the expression of CRIM1 and miR-182. The association between circRNA CRIM1 and clinical data was analyzed. qPCR was used to measure the expression of circRNA CRIM1 and miR-182 in bladder cancer cell UMUC3 and endothelial cell line HUVEC. CRIM1 genes and miR-182 in UMUC3 cell lines were overexpressed and silenced, respectively, to investigate their effects on invasion and migration of bladder cancer, and to detect the changes of miR182/Foxo3a expression. The association between circRNA CRIM1 and miR182/Foxo3a was determined by bioinformatics analysis.ResultsThe results showed that there was a significant association between the expression of circRNA CRIM1 and distal migration. The expression of CRIM1 in adjacent tissues was significantly down-regulated and negatively correlated with distal migration. The overexpression of circRNA CRIM1 reduced migration and invasion processes in bladder cancer cells. After circRNA CRIM1 was overexpressed, the miR-182 was significantly down-regulated. The expression levels of Foxo3a mRNA and proteins were up-regulated after miR-182 silencing of bladder cancer cell line UMUC3. miR-182 silencing inhibited invasion and migration of cancer cells to some extent. In bladder cancer cells and tissues, CRIM1 and Foxo3a were significantly down-regulated, miR-182 was significantly up-regulated.ConclusioncircRNA CRIM1 regulated the migration and invasion of bladder cancer by targeting the miR182/Foxo3a axis.

A sensitivity study of rising compound coastal inundation over large flood plains in a changing climate.

Coastal flood hazards and damage to coastal communities are increasing steeply and nonlinearly due to the compound impact of intensifying tropical cyclones (TCs) and accelerating sea-level rise (SLR). We expand the probabilistic coastal flood hazard analysis framework to facilitate coastal adaptation by simulating the compound impact of predicted intensifying TCs and rising sea levels in the twenty-first century. We compared the characteristics of landfalling TCs in Florida (FL) and southwest Florida (SWFL) for the late twentieth and twenty-first centuries predicted by several climate models and downscaling models. TCs predicted by four climate models, one without downscaling and three with downscaling, were used by a coupled surge-wave model to predict the future flood hazard due to compound effects of TCs and SLR over a large SWFL coastal flood plain. By 2100, the coastal inundation metrics of the 1% annual chance coastal flood could become almost 3-7 folds of their current values, depending on the climate and downscaling models, Representative Concentration Pathway scenarios, Atlantic Multi-decadal Oscillation phases, TCs, SLR, precipitation, and how TCs and SLR are incorporated. By 2100, the current 1% (100-year) inundation event could become a 3-year event, and the 0.2% (500-year) inundation event could become a 5-year event.

Coastal marshes provide valuable protection for coastal communities from storm-induced wave, flood, and structural loss in a changing climate.

Wetlands such as tidal marshes and mangroves are known to buffer coastal communities from wave, flood, and structural loss during storms. Coastal communities and resource managers seek to understand the ecosystem service value of coastal wetlands for reducing storm-induced flood loss in a changing climate. A recent modeling study found that a tall and dense Phragmites-dominated Piermont Marsh reduced the flood loss in the Village of Piermont, New York, U.S.A. during Superstorm Sandy and the 1% annual chance flood and wave event by 8% and 11%, respectively. Here we used the same modeling approach to examine the marsh's buffering capacity in a changing climate (from 2020 to 2100), considering a potential marsh restoration plan (from 2020 to 2025) and potential marsh loss due to sea-level rise. Results showed that from 2020 to 2100, the 1% annual chance flood, wave, and structural loss would increase due to sea-level rise, storms, and marsh loss. However, the marsh will buffer ~ 11-12% of structural loss until 2050. Under the extreme SLR scenario of 2.89 m and a low accretion rate, Piermont Marsh is expected to lose its buffering capacity by 2080-2100 but will retain some buffering capacity with a high accretion rate of 10 mm/year and marsh growth. The marsh's buffering capacity will remain during extra-tropical storms during winter and spring unless the wind has a significant northerly component. Lessons learned from this study can be used by coastal communities and marsh managers to develop coastal resiliency and marsh restoration plan.

circRNA CRIM1 regulates the migration and invasion of bladder cancer by targeting miR182/Foxo3a axis.

PURPOSE: To explore the molecular mechanism of circRNA CRIM1 in the regulation of bladder cancer by targeting the miR182/Foxo3a axis. METHODS: 50 pairs of cancer tissues and para-cancerous tissues of patients with bladder cancer were collected. RT-PCR method was used to detect the expression of CRIM1 and miR-182. The association between circRNA CRIM1 and clinical data was analyzed. qPCR was used to measure the expression of circRNA CRIM1 and miR-182 in bladder cancer cell UMUC3 and endothelial cell line HUVEC. CRIM1 genes and miR-182 in UMUC3 cell lines were overexpressed and silenced, respectively, to investigate their effects on invasion and migration of bladder cancer, and to detect the changes of miR182/Foxo3a expression. The association between circRNA CRIM1 and miR182/Foxo3a was determined by bioinformatics analysis. RESULTS: The results showed that there was a significant association between the expression of circRNA CRIM1 and distal migration. The expression of CRIM1 in adjacent tissues was significantly down-regulated and negatively correlated with distal migration. The overexpression of circRNA CRIM1 reduced migration and invasion processes in bladder cancer cells. After circRNA CRIM1 was overexpressed, the miR-182 was significantly down-regulated. The expression levels of Foxo3a mRNA and proteins were up-regulated after miR-182 silencing of bladder cancer cell line UMUC3. miR-182 silencing inhibited invasion and migration of cancer cells to some extent. In bladder cancer cells and tissues, CRIM1 and Foxo3a were significantly down-regulated, miR-182 was significantly up-regulated. CONCLUSION: circRNA CRIM1 regulated the migration and invasion of bladder cancer by targeting the miR182/Foxo3a axis.

Effect of menopausal symptom treatment options on palpitations: a systematic review.

This systematic review provides an overview of the effects of menopausal symptom treatment options on palpitations, defined as feelings of missed or exaggerated heart beats, reported by perimenopausal and postmenopausal women. Guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searches were conducted in PubMed, CINAHL and PsycINFO to identify articles meeting pre-specified inclusion criteria. Of 670 unique articles identified, 37 were included in the review. Treatments included drug therapies and non-drug therapies. Palpitations were studied as an outcome in 89% of articles and as an adverse effect in 11%. Articles provided mostly level II/III evidence due to their design and/or small sample sizes. Based on available evidence, no therapies can be fully recommended for clinical practice. Only some hormonal agents (e.g. estradiol) can be recommended with caution based on some positive evidence for reducing palpitation prevalence or severity. However, other drug therapies (e.g. moxonidine, atenolol), dietary supplementary treatments (e.g. isoflavones, Rheum rhaponticum, sage), cognitive-behavioral intervention and auricular acupressure cannot be recommended given the existing evidence. Additional well-designed randomized controlled treatment trials focusing on palpitations during the menopause transition as an inclusion criteria and outcome are needed to advance the field.

[MicroRNA 424-5p promotes the sensitivity of hepatocellular carcinoma cells to sorafenib by targeting Kinesin family member 23].

Objective: To explore the effect of MicroRNA 424-5p/Kinesin family member 23(miR-424-5p/KIF23)axis on the malignant phenotype of hepatoma cells and its sensitivity of sorafenib. Methods: Real-time quantitative reverse PCR(qRT-PCR) and/or Western blot were used to detect the expression of miR-424-5p and KIF23 in liver cancer tissues and paracancerous tissues, human hepatocellular carcinoma(HCC) cells HepG2 and normal hepatocyte LO2. HepG2 cells transfected with miR-424-5p mimic and miR-424-5p mimic NC were respectively defined as miR-424-5p mimic group and mimic NC group, HepG2 cells transfected with KIF23 overexpression vector pcDNA3.1-KIF23 or empty vector pcDNA3.1 respectively were defined as OE-KIF23 group and Vector group, and HepG2 cells co-transfected with miR-424-5p mimic and overexpression vector pcDNA3.1-KIF23 were defined as mimic+OE-KIF23 group: The KIF23-3'UTR wild-type vector (KIF23-WT) and the mutant vector (KIF23-MT) were co-transfected with miR-424-5p micic and mimic NC, respectively, and the targeting relationship between miR-424-5p and KIF23 was verified by dual-luciferase reporting experiments. The cell counting Kit-8 (CCK-8) was used to detect HepG2 cell proliferation and sensitivity to sorafenib. Flow cytometry was used to assess apoptosis in HepG2 cells. Transwell and scratch experiments were used to detect HepG2 cell migration and invasion capabilities. Intergroup data were compared using t-tests or analysis of variance. Results: Compared with the paracancerous tissue and normal hepatocytes, miR-424-5p in the HCC tissue and hepatocellular cells was significantly down-regulated (the relative expression was 0.604±0.121, 0.585±0.064), and KIF23 was significantly up-regulated (the relative expression was 5.451±1.834, 2.482±0.545), P<0.05. miR-424-5p mimic can inhibit the proliferation, migration and invasion of HCC cells and promote apoptosis of HCC cells (P<0.05). Overexpression of KIF23 can promote the proliferation, migration and invasion of HCC cells and inhibit apoptosis of HCC cells (P<0.05). The luciferase activity of HepG2 cells in the mimic and KIF23-WT co-transfection groups was significantly reduced compared with HepG2 cells in the mimic NC and KIF23-WT co-transfection groups (the relative fluorescence intensities were 3.668±0.091 and 2.629±0.056, respectively, P<0.05),however, there was no significant comparison between the luciferase activity of cells in the mimic and KIF23-MT co-transfection groups compared with those in the mimic NC and KIF23-MT co-transfection groups. miR-424-5p mimic can reverse the role of overexpression of KIF23 in promoting the ability of HCC cells to proliferate, migrate and invade (P<0.05). The inhibition rates of sorafenib on HepG2 cells in the mimic+OE-KIF23 group and the OE-KIF23 group were 47.491%±3.863% and 36.246%±6.063% (t=3.027, P<0.05). Conclusion: miR-424-5p can inhibit the proliferation, migration and invasion of HCC cells and can increase the sensitivity of HCC cells to sorafenib by targeting the expression level of KIF23.

[Application of diffusion-weighted magnetic resonance imaging in evaluating the efficacy of radiotherapy and chemotherapy for esophageal cancer].

This study was a prospective single arm trial conducted in Zhejiang Jinhua Guangfu hospital from February 2018 to June 2020. A total of 39 patients (32 males and 7 females) with esophageal cancer, aged from 44 to 82 (69±9) years were enrolled. Diffusion weighted magnetic resonance imaging(MR-DWI) was implemented to evaluate the changes of apparent diffusion coefficient(ADC) value before and after chemoradiotherapy. The results showed that the ADC value after chemoradiotherapy was higher than that before treatment[(2.03±0.42)×10⁻³ mm 2/s vs (1.60±0.28)×10⁻³ mm2/s], and there was a positive correlation between the increase of ADC value and the prognosis of patients.

Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing.

Ageing is associated with increased vulnerability to environmental cold exposure. Previously, we identified the role of the cold-sensitive transient receptor potential (TRP) A1, M8 receptors as vascular cold sensors in mouse skin. We hypothesised that this dynamic cold-sensor system may become dysfunctional in ageing. We show that behavioural and vascular responses to skin local environmental cooling are impaired with even moderate ageing, with reduced TRPM8 gene/protein expression especially. Pharmacological blockade of the residual TRPA1/TRPM8 component substantially diminished the response in aged, compared with young mice. This implies the reliance of the already reduced cold-induced vascular response in ageing mice on remaining TRP receptor activity. Moreover, sympathetic-induced vasoconstriction was reduced with downregulation of the α2c adrenoceptor expression in ageing. The cold-induced vascular response is important for sensing cold and retaining body heat and health. These findings reveal that cold sensors, essential for this neurovascular pathway, decline as ageing onsets.