[Visualization method of mechanical power exposure intensity and duration in mechanical ventilation patients].

OBJECTIVE: To visualize the relationship between different combinations of mechanical power exposure intensity-duration and death risk in mechanical ventilation patients using a visualization method. METHODS: Critically ill patients receiving mechanical ventilation were selected from the Medical Information Mart for Intensive Care- IV v1.0 (MIMIC- IV v1.0) database. The patients were divided into four subgroups according to oxygenation index (PaO2/FiO2) including > 300 mmHg (1 mmHg ≈ 0.133 kPa) group, 201-300 mmHg group, 101-200 mmHg group and ≤100 mmHg group. The baseline characteristics, ventilator parameters, and prognostic indicators for different patient populations were collected. For each patient, the mechanical power thresholds from low to high (5-30 J/min, increasing at intervals of 1 J/min) were used to evaluate the different exposures of mechanical power (above the set threshold was recorded as one exposure), and the number of events with different exposure intensity-duration combinations was counted based on their corresponding durations. Based on the 28-day survival/non-survival status, the number of exposures for survivors and non-survivors in each exposure intensity-duration combination was calculated, and the survival odds ratio (OR) for different mechanical power exposure intensity-duration combinations was subsequently computed. Two-dimensional tables were generated with mechanical power exposure duration on the x-axis and exposure intensity on the y-axis, and the heatmap and its corresponding equipotential line view were used to visualize the OR value to assess the risk of death. RESULTS: A total of 5 378 patients receiving mechanical ventilation were enrolled in the study, of whom 2 069 patients in the PaO2/FiO2 > 300 mmHg group, 813 patients in the 201-300 mmHg group, 1 493 patients in the 101-200 mmHg group, and 1 003 patients in the ≤100 mmHg group. The severity scores of patients, including sequential organ failure assessment (SOFA) score and simplified acute physiology score II (SAPS II), gradually increased following the decrease in PaO2/FiO2, and the incidence of co-morbidities also gradually increased. In terms of ventilator parameters, mechanical power was increased gradually with decrease in PaO2/FiO2, measuring 10.4 (7.8, 13.9), 11.3 (8.5, 14.7), 13.6 (10.0, 18.2), and 16.7 (12.5, 22.0) J/min (P < 0.01). In terms of prognosis, 28-day mortality of patients was gradually increased with decrease in PaO2/FiO2 [29.1% (601/2 069), 26.9% (219/813), 28.1% (420/1 493), and 33.3% (334/1 003), respectively, P < 0.05]. In the heatmap, it could be observed that the 28-day death risk of mechanical ventilation patients was gradually increased with increase in mechanical power exposure intensity and long duration, showing two distinct areas: a region near the bottom left corner (representing low mechanical power exposure intensity and short duration) was blue, indicating a greater chance of survival. In contrast, another region near the top right corner (representing high mechanical power exposure intensity and long duration) was red, indicating a higher risk of death. According to the fitted lines of death risk, for the same risk of death, a shorter mechanical power exposure duration was required for higher exposure intensity, while lower mechanical power exposure intensity required a longer exposure duration. The above trend of change was similarly reflected in the overall population and different oxygenation populations. CONCLUSIONS: Cumulative mechanical power exposure to higher intensity and/or longer duration is associated with worse outcomes in mechanical ventilation patients. Considering both the mechanical power exposure intensity and duration may help to evaluate the effectiveness of lung protection in mechanical ventilation patients and guide adjustments in mechanical ventilation strategy to reduce the risk of ventilator-induced lung injury.

Response of solar-induced chlorophyll fluorescence-based spatial and temporal evolution of vegetation in Xinjiang to multiscale drought.

Climate change and human activities have increased droughts, especially overgrazing and deforestation, which seriously threaten the balance of terrestrial ecosystems. The ecological carrying capacity and vegetation cover in the arid zone of Xinjiang, China, are generally low, necessitating research on vegetation response to drought in such arid regions. In this study, we analyzed the spatial and temporal characteristics of drought in Xinjiang from 2001 to 2020 and revealed the response mechanism of SIF to multi-timescale drought in different vegetation types using standardized precipitation evapotranspiration index (SPEI), solar-induced chlorophyll fluorescence (SIF), normalized difference vegetation index (NDVI), and enhanced vegetation index (EVI) data. We employed trend analysis, standardized anomaly index (SAI), Pearson correlation, and trend prediction techniques. Our investigation focused on the correlations between GOSIF (a new SIF product based on the Global Orbital Carbon Observatory-2), NDVI, and EVI with SPEI12 for different vegetation types over the past two decades. Additionally, we examined the sensitivities of vegetation GOSIF to various scales of SPEI in a typical drought year and predicted future drought trends in Xinjiang. The results revealed that the spatial distribution characteristics of GOSIF, normalized difference vegetation index (NDVI), and enhanced vegetation index (EVI) were consistent, with mean correlations with SPEI at 0.197, 0.156, and 0.128, respectively. GOSIF exhibited the strongest correlation with SPEI, reflecting the impact of drought stress on vegetation photosynthesis. Therefore, GOSIF proves advantageous for drought monitoring purposes. Most vegetation types showed a robust response of GOSIF to SPEI at a 9-month scale during a typical drought year, with grassland GOSIF being particularly sensitive to drought. Our trend predictions indicate a decreasing trend in GOSIF vegetation in Xinjiang, coupled with an increasing trend in drought. This study found that compared with that of the traditional greenness vegetation index, GOSIF has obvious advantages in monitoring drought in the arid zone of Xinjiang. Furthermore, it makes up for the lack of research on the mechanism of vegetation GOSIF response to drought on multiple timescales in the arid zone. These results provide strong theoretical support for investigating the monitoring, assessment, and prediction of vegetation response to drought in Xinjiang, which is vital for comprehending the mechanisms of carbon and water cycles in terrestrial ecosystems.

Role of TIM-1 in the development and treatment of tumours.

T-cell immunoglobulin and mucin structural domain 1 (TIM-1, also known as hepatitis A virus cell receptor 1) is a co-stimulatory molecule that is expressed predominantly on the surface of T cells. TIM-1 promotes the activation and proliferation of T cells, cytokine secretion, and can also be overexpressed in various types of cancer. Upregulation of TIM-1 expression may be associated with the development and progression of cancer. After reviewing the literature, we propose that TIM-1 affects tumour development mainly through two pathways. In the Direct pathway: overexpression in tumours activates tumour-related signaling pathways, mediates the proliferation, apoptosis, invasion and metastasis, and directly affects tumour development directly. In the indirect pathway: In addition to changing the tumour microenvironment and influencing the growth of tumours, TIM-1 binds to ligands to encourage the activation, proliferation, and generation of cytokines by immune cells. This review examines how TIM-1 stimulates the development of tumours in direct and indirect ways, and how TIM-1 is exploited as a target for cancer therapy.

Genotype analysis of 55,281 cases of thalassemia in northern Guangxi.

OBJECTIVE: To understand the genotype and distribution of thalassemia in northern Guangxi. METHODS: The study subjects were 55,281 individuals who came to the Affiliated Hospital of Guilin Medical University for genetic diagnosis of thalassemia from January 2012 to August 2023. All of their household registration was in the precincts of Guibei District and its affiliated counties. Red blood cell parameters and hemoglobin analysis were used for thalassemia screening. Gap-PCR, PCR-reverse dot blot hybridization (PCR-RDB), and multicolor melting curve analysis (MMCA) were used to identify common thalassemia genes. Multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing, and third-generation single-molecule real-time (SMRT) sequencing were employed to identify rare thalassemia genes. RESULTS: Among the 55,281 samples, 16,442 (29.74%) were diagnosed with thalassemia. The detection rates of α, ß, and α combined ß-thalassemia were 18.57%, 9.99% and 1.18%, respectively. Among ethnical groups, allele mutation frequency of thalassemia was the highest in Zhuang (44.97%), followed by Yao (40.11%), Dong (31.33%), Han (29.85%), Miao (24.31%), and Hui (20.6%). A total of 11,659 alleles (21.09%) of 8 types of α-thalassemia were identified in 55,281 samples, primarily --SEA (53.9%), followed by -α3.7 (21.3%), including rare alleles: --THAI (0.45%) and HKαα (0.38%). A total of 6367 (11.52%) and 14 types of ß-thalassemia alleles were identified, mainly CD41-42 (50.12%), followed by CD17 (22.22%), including rare alleles: ßCD37 (0.16%) and Gγ+ (Aγδß)0/ßN (0.05%). A total of 31 genotypes were detected in 10,264 cases of α-thalassemia, and the main types were --SEA/αα (53.23%), -α3.7/αα (19.15%), and -α4.2/αα (7.21%). A total of 34 genotypes were detected in 5525 cases of ß-thalassemia, and the main types were ßCD41-42/ßN (50.53%), ßCD17/ßN (21.77%), and ßIVS-II-654/ßN (12.16%). A total of 78 gene types were detected in 653 cases of α- and ß-thalassemia, and the main types were --SEA/αα, ßCD41-42/ßN (18.68%) and -α3.7/αα, ßCD41-42/ßN (13.02%). There were 580 cases (5.65%) of HbH disease (α0/α+), and 4 cases of Hemoglobin Bart's Hydrops Foetus syndrome (--SEA/--SEA). In addition, there were 92 cases (1.67%) of intermedia or severe types of ß-thalassemia (ß0/ß0, ß0/ß+, ß+/ß+), including 23 cases of combined α-thalassemia. Among the samples screened negative for thalassemia, 3.7% of them were found to carry thalassemia genes, and 91.35% of the genotypes were αWSα/αα, -α3.7/αα, and -α4.2/αα. In addition, 40.26% of αWSα/αα, 22.89% of -α3.7/αα, and 18.51% of -α4.2/αα had no hematological phenotype. CONCLUSION: The population in northern Guangxi exhibited rich ethnic diversity, with high allelic carrying rates among the Zhuang, Yao and Dong ethnic groups. Thalassemia gene mutations are diverse, encompassing a variety of gene types, with α thalassemia predominating, notably the --SEA/αα gene type. The prevalence of intermedia or severe types of thalassemia is not low, but there are still some carriers of thalassemia in people who are initially tested negative.

Pathological complete response to neoadjuvant lorlatinib in a patient with unresectable ALK-Positive locally advanced non-small cell lung cancer: A case report.

Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have demonstrated substantial effectiveness in individuals with advanced ALK-positive non-small cell lung cancer (NSCLC). However, the controversy over using ALK-TKIs for neoadjuvant therapy in ALK-positive NSCLC has not been fully explored. This case study describes the clinical progression of a patient initially diagnosed with unresectable stage III (cT1bN2M0) lung adenocarcinoma, who was later discovered to harbor an ALK mutation through next-generation sequencing. The patient underwent surgery to achieve a radical resection of the right upper lung lesion after neoadjuvant therapy with lorlatinib and a pathological complete response (pCR) was confirmed by pathological analysis. To our knowledge, it has never been reported that neoadjuvant therapy with lorlatinib resulted in pCR for an ALK-positive patient with stage III NSCLC who was initially unresectable. Therefore, our findings indicate that utilizing ALK-TKIs as neoadjuvant therapy could be considered a viable choice for ALK-positive NSCLC patients.

Visualizing the dynamic mechanical power and time burden of mechanical ventilation patients: an analysis of the MIMIC-IV database.

BACKGROUND: Limiting driving pressure and mechanical power is associated with reduced mortality risk in both patients with and without acute respiratory distress syndrome. However, it is still poorly understood how the intensity of mechanical ventilation and its corresponding duration impact the risk of mortality. METHODS: Critically ill patients who received mechanical ventilation were identified from the Medical Information Mart for Intensive Care (MIMIC)-IV database. A visualization method was developed by calculating the odds ratio of survival for all combinations of ventilation duration and intensity to assess the relationship between the intensity and duration of mechanical ventilation and the mortality risk. RESULTS: A total of 6251 patients were included. The color-coded plot demonstrates the intuitive concept that episodes of higher dynamic mechanical power can only be tolerated for shorter durations. The three fitting contour lines represent 0%, 10%, and 20% increments in the mortality risk, respectively, and exhibit an exponential pattern: higher dynamic mechanical power is associated with an increased mortality risk with shorter exposure durations. CONCLUSIONS: Cumulative exposure to higher intensities and/or longer duration of mechanical ventilation is associated with worse outcomes. Considering both the intensity and duration of mechanical ventilation may help evaluate patient outcomes and guide adjustments in mechanical ventilation to minimize harmful exposure.

CRISPR/dCas9-Mediated Specific Molecular Assembly Facilitates Genotyping of Mutant Circulating Tumor DNA.

Breakthroughs in circulating tumor DNA (ctDNA) analysis are critical in tumor liquid biopsies but remain a technical challenge due to the double-stranded structure, extremely low abundance, and short half-life of ctDNA. Here, we report an electrochemical CRISPR/dCas9 sensor (E-dCas9) for sensitive and specific detection of ctDNA at a single-nucleotide resolution. The E-dCas9 design harnesses the specific capture and unzipping of target ctDNA by dCas9 to introduce a complementary reporter probe for specific molecular assembly and signal amplification. By efficient homogeneous assembly and interfacial click reaction, the assay demonstrates superior sensitivity (up to 2.86 fM) in detecting single-base mutant ctDNA and a broad dynamic range spanning 6 orders of magnitude. The sensor is also capable of measuring 10 fg/µL of a mutated target in excess of wild-type ones (1 ng/µL), equivalent to probing 0.001% of the mutation relative to the wild type. In addition, our sensor can monitor the dynamic expression of cellular genomic DNA and allows accurate analysis of blood samples from patients with nonsmall cell lung cancer, suggesting the potential of E-dCas9 as a promising tool in ctDNA-based cancer diagnosis.

PD-1 blockade and radiotherapy combination for advanced Epstein-Barr virus-associated intrahepatic cholangiocarcinoma: a case report and literature review.

Advanced intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor of biliary epithelial cells, known for its extremely unfavorable prognosis. In the absence of intervention, patients typically survive for less than 5 months. Current guidelines from the Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO) recommend chemotherapy-based systemic therapy as the standard treatment for advanced ICC. However, the first-line regimen, consisting of gemcitabine in combination with cisplatin, generally results in a median survival of approximately one year, which is considered suboptimal. Significant progress has been made in radiotherapy techniques, molecular diagnostics, and tumor immune microenvironments. The integration of immune and radiation therapies has revolutionized treatment strategies for cholangiocarcinoma. Moreover, combined therapeutic regimens have shown promising results in improving survival rates among patients with advanced ICC. In this study, we present a case report of a 70-year-old male patient diagnosed with stage IV ICC, featuring metastases to the retroperitoneal, left adrenal, and left supraclavicular lymph nodes. The patient exhibited a high tumor mutational load, significant microsatellite instability, and hyper-expression of PD-L1 (90%), along with positive Epstein-Barr virus-encoded RNA (EBER). Pembrolizumab, a programmed cell death 1 (PD-1) inhibitor, was administered in conjunction with radiotherapy. As a result, considerable shrinkage and inactivation of the primary foci were observed, accompanied by the disappearance of metastases. Ultimately, the patient achieved complete remission and maintained progression-free survival for 41 months following the initial treatment. To the best of our knowledge, this represents the longest case of complete remission using a combination of immunotherapy and radiotherapy as a first-line regimen for the high tumor mutational load, microsatellite instability, and PD-L1 expression (90%) subtype of Epstein-Barr virus-associated ICC (EBVaICC). These findings suggest that the combination of PD-1 inhibitors with radiotherapy may serve as a promising therapeutic strategy for treating this particular cancer subtype.

Metal-Insulator Transition of Single-Crystal V2O3 through van der Waals Interface Engineering.

Strongly correlated electron materials harbor interesting materials physics, such as high-Tc superconductivity, colossal magnetoresistance, and metal-insulator transition. These physical properties can be greatly influenced by the dimensionality and geometry of the hosting materials and their interaction strengths with underlying substrates. In a classic strongly correlated oxide vanadium sesquioxide (V2O3), the coexistence of a metal-insulator and paramagnetic-antiferromagnetic transitions at ∼150 K makes this material an excellent platform for exploring basic physics and developing future devices. So far, most studies have been focused on epitaxial thin films in which the strongly coupled substrate has a pronounced effect on V2O3, leading to the observations of intriguing phenomena and physics. In this work, we unveil the kinetics of a metal-insulator transition of V2O3 single-crystal sheets at nano and micro scales. We show the presence of triangle-like alternating metal/insulator phase patterns during phase transition, which is drastically different from the epitaxial film. The observation of single-stage metal-insulator transition in V2O3/graphene compared to the multistage in V2O3/SiO2 evidence the importance of sheet-substrate coupling. Harnessing the freestanding form of the V2O3 sheet, we show that the phase transition of V2O3 sheet can generate a large dynamic strain to monolayer MoS2 and tune its optical property based on the MoS2/V2O3 hybrid structure. The demonstration of the capability in tuning phase transition kinetics and phase patterns using designed hybrid structure of varied sheet-substrate coupling strengths suggests an effective knob in the design and operation of emerging Mott devices.

A novel lncRNA SNHG29 regulates EP300- related histone acetylation modification and inhibits FLT3-ITD AML development.

Internal tandem duplication (ITD) mutations within the FMS-like tyrosine kinase-3 (FLT3) occur in up to 25% of acute myeloid leukemia (AML) patients and indicate a very poor prognosis. The role of long noncoding RNAs (lncRNAs) in FLT3-ITD AML progression remains unexplored. We identified a novel lncRNA, SNHG29, whose expression is specifically regulated by the FLT3-STAT5 signaling pathway and is abnormally down-regulated in FLT3-ITD AML cell lines. SNHG29 functions as a tumor suppressor, significantly inhibiting FLT3-ITD AML cell proliferation and decreasing sensitivity to cytarabine in vitro and in vivo models. Mechanistically, we demonstrated that SNHG29's molecular mechanism is EP300-binding dependent and identified the EP300-interacting region of SNHG29. SNHG29 modulates genome-wide EP300 genomic binding, affecting EP300-mediated histone modification and consequently influencing the expression of varies downstream AML-associated genes. Our study uncovers a novel molecular mechanism for SNHG29 in mediating FLT3-ITD AML biological behaviors through epigenetic modification, suggesting that SNHG29 could be a potential therapeutic target for FLT3-ITD AML.

More light components and less light damage on rats' eyes: evidence for the photobiomodulation and spectral opponency.

The blue-light hazard (BLH) has raised concerns with the increasing applications of white light-emitting diodes (LEDs). Many researchers believed that the shorter wavelength or more light components generally resulted in more severe retinal damage. In this study, based on the conventional phosphor-coated white LED, we added azure (484 nm), cyan (511 nm), and red (664 nm) light to fabricate the low-hazard light source. The low-hazard light sources and conventional white LED illuminated 68 Sprague-Dawley (SD) rats for 7 days. Before and after light exposure, we measured the retinal function, thickness of retinal layers, and fundus photographs. The expression levels of autophagy-related proteins and the activities of oxidation-related biochemical indicators were also measured to investigate the mechanisms of damaging or protecting the retina. With the same correlated color temperature (CCT), the low-hazard light source results in significantly less damage on the retinal function and photoreceptors, even if it has two times illuminance and blue-light hazard-weighted irradiance ([Formula: see text]) than conventional white LED. The results illustrated that [Formula: see text] proposed by IEC 62471 could not exactly evaluate the light damage on rats' retinas. We also figured out that more light components could result in less light damage, which provided evidence for the photobiomodulation (PBM) and spectral opponency on light damage.

USP2 Inhibits Lung Cancer Pathogenesis by Reducing ARID2 Protein Degradation via Ubiquitination.

Background: Ubiquitination is an important regulator in physiological and pathological conditions. Ubiquitin-specific protease 2 (USP2), as a member of the USP family, exhibits oncogenic effects in multiple malignancies. However, the exact role of USP2 has not been well clarified in lung cancer pathogenesis and progression. Therefore, we aimed to further investigate the regulatory roles of USP2 in lung cancer in this study. Methods: Firstly, immunoprecipitation-Mass Spectrometry (IP-MS), Co-immunoprecipitation (Co-IP), combined with immunofluorescent colocalization method, was conducted for USP2 protein interaction analysis in lung cancer cell lines. qRT-PCR, Western blot, and immunohistochemistry assays explored the USP2 expression pattern and USP2/ARID2- (AT-rich interactive domain 2-) specific shRNAs and overexpression vectors. Co-IP assays were designed to validate USP2-ARID2 protein interaction. Further functional studies including CHX chase assay, transwell assay, and wound healing assay were subsequently applied to evaluate the impact of USP2 modulation on lung cancer cells. Results: USP2 suppression was characteristic in lung cancer cell line models and lung cancer samples. USP2 and ARID2 demonstrated protein-protein interaction and overlapping localization in cancer cell models. Functional experiments suggested USP2 inhibited lung cancer cell invasion and migration by reducing ARID2 protein degradation. Subsequent ubiquitination assays indicated ARID2 protein degradation via the ubiquitination was significantly reduced by USP2 interaction. Conclusions: Our study provided novel insight that USP2 might suppress lung cancer by reducing ARID2 protein degradation via ubiquitination.

Simulation of Far-Field Light Distribution of Micro-LED Based on Its Structural Parameters.

To clarify how micro-LED far-field light distributions differ from Lambertian distributions owing to small-sized-structure effects, the light distribution of a micro-LED was simulated via the ray-tracing method in this study. Specifically, considering material absorption, far-field light distribution, and light-output efficiency, we studied micro-LEDs as a function of size. We found that the light distribution is the most uniform and the efficiency is the highest when the size is the smallest under certain conditions. Under other conditions, with increasing sapphire size, the luminous efficiency first increases and then decreases. The luminous efficiency is the highest when the thickness is 30 µm. Under certain other conditions, as the diameter of the micro-sphere structure on the sapphire increases, the luminous efficiency first increases and then decreases.

A Novel Way to Fill Green Gap of GaN-Based LEDs by Pinning Defects in Nanorod Array.

Nanorod array and planar green-emission InGaN/GaN multi-quantum well (MQW) LEDs were fabricated by lithography, nano-imprinting, and top-down etching technology. The defect-pinning effect of the nanostructure was found for the first time. The ratio of the bright regions to the global area in the panchromatic CL images of green MQW samples increased from 30% to about 90% after nano-fabrication. The overall luminous performance significantly improved. Throughout temperature-dependent photoluminescence (TDPL) and time-resolved PL (TRPL) measurements, the migration and recombination of carriers in the MQWs of green LEDs were analyzed. It was proved that nanostructures can effectively prevent carriers from being captured by surrounding nonradiative recombination centers. The overall PL integral intensity can be enhanced to above 18 times. A much lower carrier lifetime (decreasing from 91.4 to 40.2 ns) and a higher internal quantum efficiency (IQE) (increasing from 16.9% to 40.7%) were achieved. Some disputes on the defect influence were also discussed and clarified.

Multi-omics analysis for potential inflammation-related genes involved in tumour immune evasion via extended application of epigenetic data.

Accumulating evidence suggests that inflammation-related genes may play key roles in tumour immune evasion. Programmed cell death ligand 1 (PD-L1) is an important immune checkpoint involved in mediating anti-tumour immunity. We performed multi-omics analysis to explore key inflammation-related genes affecting the transcriptional regulation of PD-L1 expression. The open chromatin region of the PD-L1 promoter was mapped using the assay for transposase-accessible chromatin using sequencing (ATAC-seq) profiles. Correlation analysis of epigenetic data (ATAC-seq) and transcriptome data (RNA-seq) were performed to identify inflammation-related transcription factors (TFs) whose expression levels were correlated with the chromatin accessibility of the PD-L1 promoter. Chromatin immunoprecipitation sequencing (ChIP-seq) profiles were used to confirm the physical binding of the TF STAT2 and the predicted binding regions. We also confirmed the results of the bioinformatics analysis with cell experiments. We identified chr9 : 5449463-5449962 and chr9 : 5450250-5450749 as reproducible open chromatin regions in the PD-L1 promoter. Moreover, we observed a correlation between STAT2 expression and the accessibility of the aforementioned regions. Furthermore, we confirmed its physical binding through ChIP-seq profiles and demonstrated the regulation of PD-L1 by STAT2 overexpression in vitro. Multiple databases were also used for the validation of the results. Our study identified STAT2 as a direct upstream TF regulating PD-L1 expression. The interaction of STAT2 and PD-L1 might be associated with tumour immune evasion in cancers, suggesting the potential value for tumour treatment.

Giant pyroelectricity in nanomembranes.

Pyroelectricity describes the generation of electricity by temporal temperature change in polar materials1-3. When free-standing pyroelectric materials approach the 2D crystalline limit, how pyroelectricity behaves remained largely unknown. Here, using three model pyroelectric materials whose bonding characters along the out-of-plane direction vary from van der Waals (In2Se3), quasi-van der Waals (CsBiNb2O7) to ionic/covalent (ZnO), we experimentally show the dimensionality effect on pyroelectricity and the relation between lattice dynamics and pyroelectricity. We find that, for all three materials, when the thickness of free-standing sheets becomes small, their pyroelectric coefficients increase rapidly. We show that the material with chemical bonds along the out-of-plane direction exhibits the greatest dimensionality effect. Experimental observations evidence the possible influence of changed phonon dynamics in crystals with reduced thickness on their pyroelectricity. Our findings should stimulate fundamental study on pyroelectricity in ultra-thin materials and inspire technological development for potential pyroelectric applications in thermal imaging and energy harvesting.

circRNA circRIMS Downregulates miR-505 through Methylation to Suppress Cell Proliferation in Endometrial Cancer.

It is known that the circular RNA (circRNA) molecule circRIMS is overexpressed in gastric cancer and plays an oncogenic role. However, its role in other cancers is unknown. In this study, we analyzed its role in endometrial cancer (EC). EC and paired non-tumor tissue samples were collected from a total of 63 EC patients and subjected to total RNA isolations and reverse transcription quantitative polymerase chain reaction (RT-qPCR) to analyze the differential expression of circRIMS and miR-505. Overexpression of circRIMS and miR-505 was reached in EC cells and their interaction was analyzed using RT-qPCRs. The role of circRIMS in regulating miR-505 methylation was analyzed by methylation-specific RT-qPCR. Bromodeoxyuridine (BrdU) assay was performed to analyze the roles of circRIMS and miR-505 in regulating cell proliferation. circRIMS was upregulated in EC, while miR-505 was downregulated in EC. circRIMS and miR-505 were inversely correlated across both EC and non-tumor tissues. In EC cells, circRIMS overexpression decreased miR-505 expression and increased miR-505 gene methylation. BrdU assay showed that circRIMS overexpression increased cell proliferation and reduced the inhibitory effects of miR-505 overexpression on cell proliferation. circRIMS may downregulate miR-505 through methylation to increase cell proliferation.

TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathway.

BACKGROUND: T-cell immunoglobulin mucin-1 (TIM-1) has been reported to be associated with the biological behavior of several malignant tumors; however, it is not clear whether it has a role in cervical cancer (CC). METHODS: TIM-1 expression in cervical epithelial tumor tissues and cells was detected by immunohistochemistry or real-time quantitative-PCR and western blotting. CC cells from cell lines expressing low levels of TIM-1 were infected with lentiviral vectors encoding TIM-1. Changes in the malignant behavior of CC cells were assessed by CCK-8, wound healing, Transwell migration and invasion assays, and flow cytometry in vitro; while a xenograft tumor model was established to analyze the effects of TIM-1 on tumor growth in vivo. Changes in the levels of proteins related to the cell cycle, apoptosis, and Epithelial-mesenchymal transition (EMT) were determined by western blotting. RESULTS: TIM-1 expression was higher in CC tissues, than in high grade squamous intraepithelial lesion, low grade squamous intraepithelial lesion, or normal cervical tissues, and was also expressed in three CC cell lines. In HeLa and SiHa cells overexpressing TIM-1, proliferation, invasion, and migration increased, while whereas apoptosis was inhibited. Furthermore, TIM-1 downregulated the expression of p53, BAX, and E-cadherin, and increased cyclin D1, Bcl-2, Snail1, N-cadherin, vimentin, MMP-2, and VEGF. PI3K, p-AKT, and mTOR protein levels also increased, while total AKT protein levels remained unchanged. CONCLUSIONS: Our study indicated that TIM-1 overexpression promoted cell migration and invasion, and inhibited cell apoptosis in CC through modulation of the PI3K/AKT/p53 and PI3K/AKT/mTOR signaling pathways, and may be a candidate diagnostic biomarker of this disease.