IGFBP2/ITGA5 promotes gefitinib resistance via activating STAT3/CXCL1 axis in non-small cell lung cancer.

There is a paucity of comprehensive knowledge pertaining to the underlying mechanisms leading to gefitinib resistance in individuals diagnosed NSCLC harboring EGFR-sensitive mutations who inevitably develop resistance to gefitinib treatment within six months to one year. In our preceding investigations, we have noted a marked upregulation of IGFBP2 in the neoplastic tissues of NSCLC, predominantly in the periphery of the tissue, implying its plausible significance in NSCLC. Consequently, in the current research, we delved into the matter and ascertained the molecular mechanisms that underlie the participation of IGFBP2 in the emergence of gefitinib resistance in NSCLC cells. Firstly, the expression of IGFBP2 in the bronchoalveolar lavage fluid and lung cancer tissues of 20 NSCLC patients with gefitinib tolerance was found to be significantly higher than that of non-tolerant patients. Furthermore, in vitro and in vivo experiments demonstrated that IGFBP2 plays a significant role in the acquisition of gefitinib resistance. Mechanistically, IGFBP2 can activate STAT3 to enhance the transcriptional activity of CXCL1, thereby increasing the intracellular expression level of CXCL1, which contributes to the survival of lung cancer cells in the gefitinib environment. Additionally, we identified ITGA5 as a key player in IGFBP2-mediated gefitinib resistance, but it does not function as a membrane receptor in the process of linking IGFBP2 to intracellular signaling transduction. In conclusion, this study demonstrates the promoting role and mechanism of IGFBP2 in acquired gefitinib resistance caused by non-EGFR secondary mutations, suggesting the potential of IGFBP2 as a biomarker for gefitinib resistance and a potential intervention target.

Prognostic value and immunological function of cuproptosis-related genes in lung adenocarcinoma.

Background: Lung cancer is one of the malignant tumors with the highest morbidity and fatality rates worldwide. The overall survival (OS) of lung adenocarcinoma (LUAD) is poor. Cuproptosis is a copper-triggered modality of mitochondrial cell death, however, its contribution to the emergence of lung cancer is unknown. The clinical implication and immunological function of cuproptosis-related genes (CRGs) in LUAD has yet to be established. Methods: TCGA, HPA, GEPIA, Kaplan-Meier, TIMER and CancerSEA database were used to explore the prognostic value and biological function of CRGs in LUAD. Results: CRGs are primarily involved in copper ion transport, the citrate cycle (TCA cycle) and central carbon metabolism in LUAD. The mRNA expression of COA6, UBE2D1, DLAT, SLC25A3, and DBH was significantly increased. The expression of COA6, DLAT, SLC25A3, DBH, and LOXL2 were all strongly associated with the clinicopathological stages in LUAD. Moreover, high expression of COA6, UBE2D1, DLAT, SLC25A3 and LOXL2 was related to poor OS. The expression of SLC25A3 and LOXL2 showed different association with immune cell infiltration. The single cell sequencing demonstrated that CRGs play important roles in the regulation of DNA damage response, inflammation and metastasis in LUAD. Conclusions: In summary, this study comprehensively uncovered that CRGs could be identified as potential prognostic and immunological biomarkers in LUAD. Our current research could provide a solid theoretical basis for LUAD survival research and clinical decision-making.

More enhanced non-growing season methane exchanges under warming on the Qinghai-Tibetan Plateau.

Uncertainty in methane (CH4) exchanges across wetlands and grasslands in the Qinghai-Tibetan Plateau (QTP) is projected to increase due to continuous permafrost degradation and asymmetrical seasonal warming. Temperature plays a vital role in regulating CH4 exchange, yet the seasonal patterns of temperature dependencies for CH4 fluxes over the wetlands and grasslands on the QTP remain poorly understood. Here, we demonstrated a stronger warming response of CH4 exchanges during the non-growing season compared to the growing season on the QTP. Analyzing 9745 daily observations and employing four methods -regression fitting of temperature-CH4 flux, temperature dependence calculations, field-based and model-based control experiments-we found that warming intensified CH4 emissions in wetlands and uptakes in grasslands. Specifically, the average reaction intensity in the non-growing season surpasses that in the growing season by 1.89 and 4.80 times, respectively. This stronger warming response of CH4 exchanges during the non-growing season significantly increases the regional CH4 exchange on the QTP. Our research reveals that CH4 exchanges in the QTP have a higher warming sensitivity in non-growing seasons, which meanwhile are dominated by a larger warming rate than the annual average. The combined effects of these two factors will significantly alter the CH4 source/sink on the QTP. Neglecting these impacts would lead to inaccurate estimations of CH4 source/sink over the QTP under climate warming.

LncRNA CALML3-AS1 modulated by m6A modification induces BTNL9 methylation to drive non-small-cell lung cancer progression.

Non-small cell lung cancer (NSCLC) is a common and lethal malignancy. The carcinogenic roles of lncRNA CALML3 antisense RNA 1 (CALML3-AS1) have been documented. However, the function and potential mechanisms of CALML3-AS1 in the progression of NSCLC need to be further explored. The molecule expression was assessed by qRT-PCR and Western blot. The subcellular localization of CALML3-AS1 was observed by fluorescence in situ hybridization (FISH). The malignant behaviors of NSCLC cells were evaluated by CCK-8, colony formation, EdU, wound healing and transwell assays. In vivo xenograft tumor and liver metastatic models were established. The molecular mechanisms were investigated by RIP, RNA pull-down and ChIP assays. The methylation level was detected by MSP. Herein, we found that CALML3-AS1 was upregulated, while butyrophilin-like 9 (BTNL9) was downregulated in NSCLC. Functionally, CALML3-AS1 depletion repressed NSCLC cell malignant phenotypes, in vivo tumor growth, and liver metastasis. Mechanistically, AlkB homolog 5 (ALKBH5) enhanced CALML3-AS1 stability via N6-methyladenosine (m6A) demethylation, whereas m6A reader YTH domain-containing 2 (YTHDC2) destabilized CALML3-AS1. Moreover, CALML3-AS1 inhibited BTNL9 transcription and expression through the recruitment of Zeste homolog 2 (EZH2). Rescue experiments demonstrated that BTNL9 downregulation counteracted sh-CALML3-AS1-mediated antitumor effects on NSCLC. Taken together, CALML3-AS1 modulated by ALKBH5 and YTHDC2 in an m6A modification dependent manner drives NSCLC progression via epigenetically repressing BTNL9.

Divergent impacts of VPD and SWC on ecosystem carbon-water coupling under different dryness conditions.

Ecosystem water use efficiency (WUE) is an indicator of carbon-water interactions and is defined as the ratio of gross primary productivity (GPP) to evapotranspiration (ET). However, it is currently unclear how WUE responds to atmospheric and soil drought events in terrestrial ecosystems with different dryness conditions. Additionally, the contributions of GPP and ET to the WUE response remain poorly understood. Based on measurements from 26 flux tower sites distributed worldwide, the binning method and random forest model were employed to separate the sensitivities of daily ecosystem WUE, GPP, and ET to vapor pressure deficit (VPD) and soil water content (SWC) under different dryness conditions (dryness index = potential evapotranspiration/precipitation, DI). Results showed that the sensitivity of WUE to VPD was negative at humid sites (DI < 1), while the sensitivity of WUE to SWC was positive at arid sites (DI > 2). Furthermore, the contribution of GPP to VPD-induced WUE variability was 63 % at humid sites, and the contribution of ET to SWC-induced WUE variability was 68 % when SWC was less than the 60th percentile at arid sites. Consequently, one increasing VPD-induced decrease in GPP was generally linked to a decrease in WUE at humid sites, and one drying soil moisture-caused decrease in ET was linked to a WUE increase under low SWC conditions at arid sites. Finally, VPD had a stronger effect on WUE than SWC when VPD was less than the 90th percentile or SWC was greater than the 50th percentile. Our findings underscore the importance of considering ecosystem dryness when investigating the impacts of VPD and SWC on ecosystem carbon-water coupling.

METTL14 promotes the development of diabetic kidney disease by regulating m6A modification of TUG1.

BACKGROUND: Diabetic kidney disease (DKD) is one of the most common diabetic complications. Endoplasmic reticulum stress (ERS) is an important step for renal tubular epithelial cell apoptosis during DKD progression. Herein, the role and regulatory mechanism of METTL14 in ERS during DKD progression were investigated. METHODS: DKD animal and cell models were established by streptozotocin (STZ) and high glucose (HG), respectively. HE and Masson staining were performed to analyze renal lesions in DKD mouse. Cell viability and proliferation were determined by MTT and EdU staining, respectively. HK2 cell apoptosis was analyzed by flow cytometry. TUG1 m6A level was determined by Me-RIP. The interaction between TUG1, LIN28B and MAPK1 was analyzed by RIP and RNA pull-down assays. RESULTS: HG stimulation promoted apoptosis and increased ERS marker proteins (GRP78, CHOP and caspase12) expression in HK2 cells, while these changes were reversed by METTL14 knockdown. METTL14 inhibited TUG1 stability and expression level in an m6A-dependent manner. As expected, TUG1 knockdown abrogated METTL14 knockdown's inhibition on HG-induced HK2 cell apoptosis and ERS. In addition, TUG1 inactivated MAPK1/ERK signaling by binding with LIN28B. And TUG1 overexpression's repression on HG-induced HK2 cell apoptosis and ERS was abrogated by MAPK1 signaling activation. Meanwhile, METTL14 knockdown or TUG1 overexpression protected against STZ-induced renal lesions and renal fibrosis in DKD mouse. CONCLUSION: METTL14 promoted renal tubular epithelial cell apoptosis and ERS by activating MAPK/ERK pathway through m6A modification of TUG1, thereby accelerating DKD progression.

Construction of lncRNA prognostic model related to cuproptosis in esophageal carcinoma.

Background: Esophageal carcinoma (ESCA) is one of the most prevalent malignant tumors in the world. The prognosis of patients has significantly improved with the development of surgery, targeted therapy and immunotherapy. But the 5-year survival rate of ESCA patients is still incredibly low. Cuproptosis is a type of mitochondrial cell death induced by copper. It is unclear how cuproptosis-related lncRNAs (CRLs) affect ESCA prognosis. Methods: In this study, we obtained the clinical data of ESCA patients, the transcriptome data from TCGA and identified CRLs by co-expression analysis, lasso regression, and cox regression analysis, to build a prognostic model. Then we validated the prognostic model using the Kaplan-Meier curve, cox regression analysis, and ROC, to create a nomogram based on risk score to forecast the prognosis of ESCA. Next, the immune escape of the CRLs was examined using the TIDE algorithm to assess its sensitivity to possible ESCA medications. Results: To predict the prognosis of ESCA patients, we created a predictive model using 6 CRLs (AC034199.1, AC125437.1, AC107032.2, CTBP1-DT, AL024508.1, and AC008610.1), validated by the Kaplan-Meier and ROC curves. The model has a higher diagnostic value compared to other clinical features. The 6 CRLs expressed high in TCGA and ESCA specimens. Enrichment analysis revealed CRLs largely contributed to the interaction between cytokines and their receptors as well as complement coagulation cascades. The immunity escape analysis demonstrated that immunotherapy had a worse effect in the low-risk group than in the high-risk group. Additionally, we screened out potential antineoplastic drugs according to the results of the immunoassay and obtained 5 drugs, including CP-466722, crizotinib, MS-275, KIN001-135, and CP-466722. Conclusion: The prognosis of patients with ESCA can be correctly predicted by the 6 CRLs chosen from this investigation. It lays the groundwork for more investigation into the ESCA mechanism and the identification of novel therapeutic targets.

Aberrant Dendritic Cell Subsets in Patients with Myasthenia Gravis and Related Clinical Features.

INTRODUCTION: Dendritic cells (DCs) play critical roles in the pathogenesis of myasthenia gravis (MG), and a series of DC-based experimental strategies for MG have recently been developed. However, the definite roles of different DC subsets in the mechanism of MG have scarcely been covered by previous studies. The present study aimed to investigate the levels of three main DC subsets, plasmacytoid DCs (pDCs) (CD303 positive) and two distinct subsets of conventional DCs (cDCs), namely CD1c+ cDCs and CD141+ cDCs, in MG patients and analyze related clinical features. METHODS: From January 2016 to December 2020, 160 newly diagnosed MG patients and matched healthy controls (n = 160) were included in the study, and their clinical data were collected. The blood samples from MG patients before treatment and controls were collected for flow cytometry analysis. A total of 14 MG thymoma, 24 control thymoma, and 3 thymic cysts were used to immunostain the DC subsets. RESULTS: The flow cytometry analysis showed a significantly higher frequency of circulating pDCs, CD1c+ cDCs, and CD141+ cDCs in MG patients than in healthy controls (p < 0.001 for all). Patients with early-onset MG (<50 years old) had a lower frequency of circulating pDCs but a higher frequency of circulating CD1c+ cDCs than those with late-onset MG (≥50 years old) (p = 0.014 and p = 0.025, respectively). The frequency of circulating pDCs was positively associated with the clinical severity of late-onset MG patients (r = 0.613, p < 0.001). 64.3% (9/14) of MG thymoma is of type B2 under the World Health Organization classification, which is higher than that in control thymoma (33.3%, 8/24) (p = 0.019). For type B2 thymoma, there were significantly more pDCs but fewer CD1c+ cDCs in MG thymoma than in the controls. CONCLUSION: The distribution of aberrant pDCs, CD1c+ cDCs, and CD141+ cDCs in MG patients displayed age- and thymoma-related differences, which may contribute to the impaired immune tolerance and lead to the onset of MG.

LINC00963 promotes the malignancy and metastasis of lung adenocarcinoma by stabilizing Zeb1 and exosomes-induced M2 macrophage polarization.

BACKGROUND: Long intergenic non-coding RNA 00963 (LINC00963) is an oncogenic lncRNA in human cancers. However, little is known on how it impacts the pathogenesis of lung adenocarcinoma (LUAD). METHODS: Biological effects on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were examined by CCK-8, colony formation, EdU incorporation, transwell, and immunofluorescence assays, respectively. Macrophage polarization was evaluated by flow cytometry. Ubiquitination of Zeb1 was examined by co-immunoprecipitation. The location of LINC00963 in LUAD tissues and cell lines was tested by FISH assay. The LINC00963/HNRNPA2B1/Siah1 mRNA complex interaction was verified using RNA pull-down and immunoprecipitation assays. The exact roles of LINC00963 were further validated in metastasis and xenograft models. RESULTS: Higher LINC00963 expression in LUAD patients positively correlated with shorter overall survival, higher stages, and metastasis. LINC00963 mainly localized in the cytoplasm and aggravated malignant phenotypes of LUAD cells in vitro and metastasis in vivo. Mechanistically, LINC00963 directly interacted HNRNPA2B1 protein to trigger the degradation of Siah1 mRNA, which inhibited the ubiquitination and degradation of Zeb1. Moreover, exosomal LINC00963 derived from LUAD cells induced M2 macrophage polarization and promoted LUAD growth and metastasis. CONCLUSION: By stabilizing Zeb1 in cancer cells and delivering exosomes to induce M2 macrophage polarization, LINC00963 promoted the malignancy and metastasis of LUAD. Targeting LINC00963 may become a valuable therapeutic target for LUAD.

Research on Properties of Dopamine and Silicon Carbon Black Modified Basalt Fiber Reinforced Magnetorheological Elastomer.

The basalt fibers (BF) and the basalt fibers etched by H2SO4 (BFH) were modified by polydopamine (PDA) or synergistically modified by PDA and silicon carbon black (SiCB). The effects of modified BF, BFH and SiCB on the basic mechanical properties and magnetorheological (MR) effects of natural rubber/butadiene rubber-based magnetorheological elastomer precursors (MREs) were investigated. The results show that the tensile strength, tear strength and stress at 300% strain of MREs/PDA-BFH-SiCB prepared with BFH synergistically modified by PDA and SiCB reach the maximum values, which are 9.58 MPa, 24.07 kN/m and 4.13 MPa, respectively. Additionally, its MR effect is more than three times higher than that of MREs before composite modification.

m6A methyltransferase METTL3-induced lncRNA SNHG17 promotes lung adenocarcinoma gefitinib resistance by epigenetically repressing LATS2 expression.

Gefitinib has been widely applied for the treatment of lung adenocarcinoma (LUAD). However, the long-term application of gefitinib usually leads to acquired drug resistance in tumour patients, resulting in clinical treatment failure. Small nucleolar host gene 17 (SNHG17) has been shown to play a regulatory role in LUAD progression. Nevertheless, the role of SNHG17 in LUAD gefitinib resistance remains elusive. The expression pattern of SNHG17 was examined in tissues and cell lines of gefitinib-sensitive and gefitinib-resistant LUAD, respectively. Gain- and loss-of-function experiments were employed to assess the biological functions of SNHG17 in cell proliferation and apoptosis, as well as aggressive phenotypes of LUAD cells. MeRIP-qPCR and colorimetric quantificational analysis were performed to detect m6A modifications and contents. Fluorescence in situ hybridisation (FISH) and subcellular fractionation analysis were used to reveal the distribution of SNHG17. RIP and ChIP assays were performed to further validate the SNHG17/EZH2/LATS2 regulatory axis. A xenograft tumour growth assay was conducted to evaluate the role of SNHG17 in LUAD gefitinib resistance in vivo. SNHG17 was upregulated in gefitinib-resistant LUAD tissues and cell lines. Functional assays showed that SNHG17 aggravated the malignant phenotypes of gefitinib-resistant LUAD cells. In addition, METTL3-mediated N6-methyladenosine modification could induce the upregulation of SNHG17by stabilising its RNA transcript. Mechanistically, SNHG17 epigenetically repressed the expression of LATS2 by recruiting EZH2 to the promoter region of LATS2. The regulatory role of the SNHG17/EZH2/LATS2 axis in LUAD gefitinib resistance was further supported in vivo. Collectively, our findings suggested that SNHG17 induced by METTL3 could promote LUAD gefitinib resistance by epigenetically repressing LATS2 expression.

Retrieval of total and fine mode aerosol optical depth by an improved MODIS Dark Target algorithm.

Total and fine mode aerosol optical depth (AODT and AODF), as well as the fine mode fraction (FMF = AODF/AODT), are critical variables for climate change and atmospheric environment studies. The retrievals with high accuracy from satellite observations, particularly FMF and AODF over land, remain challenging. This study aims to improve the Moderate-resolution Imaging Spectro-radiometer (MODIS) land dark target (DT) algorithm for retrieving AODT, AODF, and FMF on a global scale. Based on the fact that the underestimated surface reflectance (SR) could overestimate the AODT and underestimate the aerosol size parameter in the DT algorithm, two robust schemes were developed to improve SR determination: the first (NEW1 DT) used the top of the atmosphere reflectance instead of SR at 2.12 µm; the second (NEW2 DT) used eleven-year MODIS data to establish a monthly spectral SR relationship model (2.12-0.47 and 2.12-0.65 µm) database at pixel-by-pixel scale. Then a novel lookup table approach based on the physical process was proposed to retrieve the AODF and FMF. The new MODIS AODT, FMF, and AODF were compared to AERosol RObotic NETwork (AERONET) retrievals. Results showed that the root mean square error (RMSE) was 0.096-0.103, 0.098-0.099, and 0.167-0.180 for the new AODTs, AODFs, and FMFs, respectively, which were better than that of the Collection 6.1 (C6.1) DT (0.117, 0.235, and 0.426) in the validation by global AERONET sites. From the validation results, NEW2 DT provided better AODT and coarse mode AOD retrievals, while NEW1 DT had better AODF and FMF performances. The spatial patterns of AODF, FMF, and AODC of the new DT algorithms were comparable to those of the Polarization and Directionality of the Earth's Reflectances aerosol product. Hence, the new algorithms have the potential to provide global AODT, FMF, and AODF products over land to the scientific community with high accuracy using long-term MODIS data.

TGF-ß1/SH2B3 axis regulates anoikis resistance and EMT of lung cancer cells by modulating JAK2/STAT3 and SHP2/Grb2 signaling pathways.

The pathogenesis of lung cancer, the most common cancer, is complex and unclear, leading to limited treatment options and poor prognosis. To provide molecular insights into lung cancer development, we investigated the function and underlying mechanism of SH2B3 in the regulation of lung cancer. We indicated SH2B3 was diminished while TGF-ß1 was elevated in lung cancer tissues and cells. Low SH2B3 level was correlated with poor prognosis of lung cancer patients. SH2B3 overexpression suppressed cancer cell anoikis resistance, proliferation, migration, invasion, and EMT, while TGF-ß1 promoted those processes via reducing SH2B3. SH2B3 bound to JAK2 and SHP2 to repress JAK2/STAT3 and SHP2/Grb2/PI3K/AKT signaling pathways, respectively, resulting in reduced cancer cell anoikis resistance, proliferation, migration, invasion, and EMT. Overexpression of SH2B3 suppressed lung cancer growth and metastasis in vivo. In conclusion, SH2B3 restrained the development of anoikis resistance and EMT of lung cancer cells via suppressing JAK2/STAT3 and SHP2/Grb2/PI3K/AKT signaling cascades, leading to decreased cancer cell proliferation, migration, and invasion.

Pixel-scale historical-baseline-based ecological quality: Measuring impacts from climate change and human activities from 2000 to 2018 in China.

Widespread concern about ecological degradation has prompted development of concepts and exploration of methods to quantify ecological quality with the aim of measuring ecosystem changes to contribute to future policy-making. This paper proposes a conceptual framework for ecological quality measurement based on current ecosystem functions and biodiverse habitat, compared with pixel-scale historical baselines. The framework was applied to evaluate the changes and driving factors of ecological quality for Chinese terrestrial ecosystems through remote sensing-based and ecosystem process modeled data at 1 km spatial resolution from 2000 to 2018. The results demonstrated the ecological quality index (EQI) had a very different spatial pattern based upon vegetation distribution. An upward trend in EQI was found over most areas, and variability of 46.95% in EQI can be explained well by change in climate, with an additional 10.64% explained by changing human activities, quantified by population density. This study demonstrated a practical and objective approach for quantifying and assessing ecological quality, which has application potential in ecosystem assessments on scales from local to region and nation, yet would provide a new scientific concept and paradigm for macro ecosystems management and decision-making by governments.

svBreak: A New Approach for the Detection of Structural Variant Breakpoints Based on Convolutional Neural Network.

Structural variation (SV) is an important type of genome variation and confers susceptibility to human cancer diseases. Systematic analysis of SVs has become a crucial step for the exploration of mechanisms and precision diagnosis of cancers. The central point is how to accurately detect SV breakpoints by using next-generation sequencing (NGS) data. Due to the cooccurrence of multiple types of SVs in the human genome and the intrinsic complexity of SVs, the discrimination of SV breakpoint types is a challenging task. In this paper, we propose a convolutional neural network- (CNN-) based approach, called svBreak, for the detection and discrimination of common types of SV breakpoints. The principle of svBreak is that it extracts a set of SV-related features for each genome site from the sequencing reads aligned to the reference genome and establishes a data matrix where each row represents one site and each column represents one feature and then adopts a CNN model to analyze such data matrix for the prediction of SV breakpoints. The performance of the proposed approach is tested via simulation studies and application to a real sequencing sample. The experimental results demonstrate the merits of the proposed approach when compared with existing methods. Thus, svBreak can be expected to be a supplementary approach in the field of SV analysis in human tumor genomes.

miR-378d suppresses malignant phenotype of ESCC cells through AKT signaling.

BACKGROUND: Post-resistance progress in paclitaxel (PTX) treatment remains a major challenge in tumor treatment. A high dose of PTX was used for cell lines to analyze the changes in molecular expression. The miR-378d was sharply reduced in surviving cells, but the role of miR-378d in Esophageal squamous cell carcinoma (ESCC) remained unclear. METHODS: We analyzed the relationship between miR-378d expression and the clinicopathological features of ESCC. We constructed miR-378d silent expression cell lines to study phenotypes and molecular mechanisms. RESULTS: The miR-378d expression was associated with good prognosis in patients with ESCC. miR-378d inhibition promoted chemo-resistance, monoclonal formation, EMT, migration, invasion, stemness, and metastasis of ESCC cells. miR-378d can target downregulated AKT1. CONCLUSIONS: Therefore, miR-378d expression is a good prognostic factor of patients with ESCC and regulates the malignant phenotype of tumor cells through AKT.

Research on Recognition of Faces with Masks Based on Improved Neural Network.

Background: At present, the new crown virus is spreading around the world, causing all people in the world to wear masks to prevent the spread of the virus. Problem. People with masks have found a lot of trouble for face recognition. Finding a feasible method to recognize faces wearing masks is a problem that needs to be solved urgently. Method: This paper proposes a mask recognition algorithm based on improved YOLO-V4 neural network and the integrated SE-Net and DenseNet network and introduces deformable convolution. Conclusion: Compared with other target detection networks, the improved YOLO-V4 neural network used in this paper improves the accuracy of face recognition and detection with masks to a certain extent.

GRP78 facilitates M2 macrophage polarization and tumour progression.

This study investigated the regulation of GRP78 in tumour-associated macrophage polarization in lung cancer. First, our results showed that GRP78 was upregulated in macrophages during M2 polarization and in a conditioned medium derived from lung cancer cells. Next, we found that knocking down GRP78 in macrophages promoted M1 differentiation and suppressed M2 polarization via the Janus kinase/signal transducer and activator of transcription signalling. Moreover, conditioned medium from GRP78- or insulin-like growth factor 1-knockdown macrophages attenuated the survival, proliferation, and migration of lung cancer cells, while conditioned medium from GRP78-overexpressing macrophages had the opposite effects. Additionally, GRP78 knockdown reduced both the secretion of insulin-like growth factor 1 and the phosphorylation of the insulin-like growth factor 1 receptor. Interestingly, insulin-like growth factor 1 neutralization downregulated GRP78 and suppressed GRP78 overexpression-induced M2 polarization. Mechanistically, insulin-like growth factor 1 treatment induced the translocation of GRP78 to the plasma membrane and promoted its association with the insulin-like growth factor 1 receptor. Finally, IGF-1 blockade and knockdown as well as GRP78 knockdown in macrophages inhibited M2 macrophage-induced survival, proliferation, and migration of lung cancer cells both in vitro and in vivo.

LncRNA TUG1/miR-29c-3p/SIRT1 axis regulates endoplasmic reticulum stress-mediated renal epithelial cells injury in diabetic nephropathy model in vitro.

Long non-coding RNAs (lncRNAs) are important regulators in diabetic nephropathy. In this study, we investigated the potential role of lncRNA TUG1 in regulating endoplasmic reticulum stress (ERS)-mediated apoptosis in high glucose induced renal tubular epithelial cells. Human renal tubular epithelial cell line HK-2 was challenged with high glucose following transfection with lncRNA TUG1, miR-29c-3p mimics or inhibitor expression plasmid, either alone or in combination, for different experimental purposes. Potential binding effects between TUG1 and miR-29c-3p, as well as between miR-29c-3p and SIRT1 were verified. High glucose induced apoptosis and ERS in HK-2 cells, and significantly decreased TUG1 expression. Overexpressed TUG1 could prevent high glucose-induced apoptosis and alleviated ERS via negatively regulating miR-29c-3p. In contrast, miR-29c-3p increased HK-2 cells apoptosis and ERS upon high glucose-challenge. SIRT1 was a direct target gene of miR-29c-3p in HK-2 cells, which participated in the effects of miR-29c-3p on HK-2 cells. Mechanistically, TUG1 suppressed the expression of miR-29c-3p, thus counteracting its function in downregulating the level of SIRT1. TUG1 regulates miR-29c-3p/SIRT1 and subsequent ERS to relieve high glucose induced renal epithelial cells injury, and suggests a potential role for TUG1 as a promising diagnostic marker of diabetic nephropathy.

Environmental factors modulate the diffuse fertilization effect on gross primary productivity across Chinese ecosystems.

Diffuse radiation allocated by cloud cover and aerosols can promote vegetation photosynthesis, which is known as the diffuse fertilization effect (DFE). As an important uncertain factor regulating the DFE, understanding the role of environmental conditions in the response of terrestrial ecosystems to diffuse radiation is vital for quantitative and intensive studies. By using a light use efficiency model and statistical methods with satellite data and ChinaFLUX observation data, the optimal environmental range of DFE was estimated, the indirect role of vapor pressure deficit (VPD) and air temperature (Ta) on DFE was explored, and the relative contribution of diffuse photosynthetically active radiation (PARdif) on gross primary productivity (GPP) was analyzed across Chinese ecosystems under different sky conditions. The results showed that the DFE increased with leaf area index (LAI), but distributed a unimodal curve along with VPD and Ta, both of which had an optimum range that was lower in the forest (or cropland) and higher in the grass (or desert) ecosystem. When considering the co-effect of VPD and Ta, the strongest positive effect of DFE was found at 0-5 h Pa and 20-25 °C. Based on path analysis, PARdif promoted GPP and served as the main controlling factor in forest ecosystems predominantly through a direct pathway from half-hourly to the daily scale, while Ta and VPD occupied the dominant position at single-canopy ecosystem sites. When the aerosol optical depth (AOD) increased, the relative contribution of PARdif increased in multiple-canopy ecosystems and decreased in single-canopy ecosystems; when the sky conditions changed from sunny to cloudy, the relative contribution of PARdif was higher in the forest ecosystem and increased significantly in the grass ecosystem. These findings offer a more comprehensive understanding of the environmental effects of regulating DFE on GPP across ecosystems.