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Kaifang Wang,1,2 Xin Ning,1 Chuanyue Qin,1 Jianlin Wang,1 Wenjie Yan,1 Xin Zhou,1 Deping Wang,1 Jimin Cao,1 Yanlin Feng1 1Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Cardiology, First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Jimin Cao; Yanlin Feng, Email caojimin@sxmu.edu.cn; feng@sxmu.edu.cnIntroduction: The wide application of copper oxide nanoparticles (CuO NPs) in industry, agriculture, environmental remediation, and biomedicine has increased the risk of human exposure to CuO NPs. Recent studies suggested that CuO NPs have genotoxic and cytotoxic effects on various cells. However, little is known about the toxicity of CuO NPs on major peripheral organs after respiratory exposure.Materials and Methods: We investigated the toxicities of CuO NPs on human bronchial epithelial (BEAS-2B) and human cardiomyocytes (AC16) cells in vitro, and on the lungs, liver, kidneys, and heart of spontaneously hypertensive rats (SHRs) at 24 and 72 h after intrabronchial instillation in vivo.Results: CuO NPs induced concentration-dependent toxicities in both BEAS-2B and AC16 cells mainly through hierarchical oxidative stress mechanisms, involving generation of reactive oxygen species (ROS), upregulation of heme oxygenase-1 (HO-1), mitochondrial dysfunction, and secretion of proinflammatory and profibrogenic cytokines. Respiratory exposure to CuO NPs induced acute multiple organ injuries in SHRs manifesting through inflammation and fibrosis. However, cardiac injury was relatively less severe than injuries in the lungs, liver, and kidneys. Upregulation of serum C-reaction protein (CRP), tumor necrosis factor α (TNF-α), intercellular adhesion molecule 1 (ICAM-1), endothelin-1 (ET-1), angiotensin converting enzyme (ACE), and von Willebrand factor (vWF) after exposure to CuO NPs indicated systematic inflammation, endothelial injury, and potential prothrombosis.Conclusion: Respiratory exposure to CuO NPs induced acute injuries in main peripheral organs, including the lungs, liver, kidneys, and heart. Individuals with existing cardiovascular diseases were susceptible to exposure to CuO NPs. This study provides a warning about the extensive toxic effects of CuO NPs, especially in the susceptible population.Keywords: CuO nanoparticle, nanotoxicology, hierarchical oxidative stress response, intratracheal instillation, spontaneously hypertensive rat

Perennial trees develop and coordinate endogenous response signaling pathways, including their crosstalk and convergence, to cope with various environmental stresses which occur simultaneously in most cases. These processes are involved in gene transcriptional regulations that depend on dynamic interactions between regulatory proteins and corresponding chromatin regions, but the mechanisms remain poorly understood in trees. In this study, we detected chromatin regulatory landscapes of poplar under abscisic acid, methyl jasmonate, salicylic acid and sodium chloride (NaCl) treatment, through integrating ATAC-seq and RNA-seq data. Our results showed that the degree of chromatin accessibility for a given gene is closely related to its expression level. However, unlike the gene expression that shows treatment-specific response patterns, changes in chromatin accessibility exhibit high similarities under these treatments. We further proposed and experimentally validated that a homologous gene copy of RESPONSIVE TO DESICCATION 26 mediates the crosstalk between jasmonic acid and NaCl signaling pathways by directly regulating the stress-responsive genes and that circadian clock-related transcription factors like REVEILLE8 play a central role in response of poplar to these treatments. Overall, our study provides a chromatin insight into the molecular mechanism of transcription regulatory networks in response to different environmental stresses and raises the key roles of the circadian clock of poplar to adapt to adverse environments.

Acute ocular hypertension (AOH) is the most important characteristic of acute glaucoma, which can lead to retinal ganglion cell (RGC) death and permanent vision loss. So far, approved effective therapy is still lacking in acute glaucoma. PANoptosis (pyroptosis, apoptosis, and necroptosis), which consists of three key modes of programmed cell death-apoptosis, necroptosis, and pyroptosis-may contribute to AOH-induced RGC death. Previous studies have demonstrated that melatonin (N-acetyl-5-methoxytryptamine) exerts a neuroprotective effect in many retinal degenerative diseases. However, whether melatonin is anti-PANoptotic and neuroprotective in the progression of acute glaucoma remains unclear. Thus, this study aimed to explore the role of melatonin in AOH retinas and its underlying mechanisms. The results showed that melatonin treatment attenuated the loss of ganglion cell complex thickness, retinal nerve fiber layer thickness, and RGC after AOH injury, and improved the amplitudes of a-wave, b-wave, and oscillatory potentials in the electroretinogram. Additionally, the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells was decreased, and the upregulation of cleaved caspase-8, cleaved caspase-3, Bax, and Bad and downregulation of Bcl-2 and p-Bad were inhibited after melatonin administration. Meanwhile, both the expression and activation of MLKL, RIP1, and RIP3, along with the number of PI-positive cells, were reduced in melatonin-treated mice, and p-RIP3 was in both RGC and microglia/macrophage after AOH injury. Furthermore, melatonin reduced the expression of NLRP3, ASC, cleaved caspase-1, gasdermin D (GSDMD), and cleaved GSDMD, and decreased the number of Iba1/interleukin-1β-positive cells. In conclusion, melatonin ameliorated retinal structure, prevented retinal dysfunction after AOH, and exerted a neuroprotective effect via inhibition of PANoptosis in AOH retinas.

Colorectal cancer (CRC) is a commonly diagnosed cancer with poor prognosis and high mortality rate. Hyperthermia (HT) is an adjunctive therapy to enhance the antitumor effects of traditional chemo- or radio- therapy. Here, we report that a cluster of essential regulator genes and speed-limit enzymes of glucose metabolism were significantly elevated under HT from a glucose metabolism PCR array analysis. Under low glucose supply or glucose metabolism inhibition, CRC cells displayed increased sensitivity to HT treatments. By transcript sequencing from the established HT resistant (HTR) colon cancer cell line LoVo HTR, we observed that IGF2BP1, an RNA-binding protein, was significantly upregulated in HTR cells compared with parental cells. Furthermore, LDHA mRNA was identified as an IGF2BP1 direct target. An RNA immunoprecipitation assay and RNA pull-down assay consistently illustrated IGF2BP1 specifically bonds to the 3′ UTR of LDHA mRNA, leading to enhanced stability of LDHA mRNA. Finally, we demonstrated that inhibiting the IGF2BP1-promoted glycolysis sensitized colon cancer cells to HT treatment via both in vitro and in vivo experiments. Our findings suggest that targeting the IGF2BP1-LDHA-glycolysis pathway might be a promising therapeutic approach to enhance the anti-cancer effects of HT treatment., Graphical Abstract, Glucose metabolism and IGF2BP1 are upregulated under HT treatment by RNA-seq analysis. IGF2BP1 promotes glucose metabolism of CRC cells via stabilization of LDHA expression by specific binding to 3′ UTR of LDHA mRNA. In vitro and in vivo experiments demonstrated inhibiting the IGF2BP1-promoted glycolysis sensitized colon cancer cells to HT.

Aims:This study aimed to unveil the functional roles of LINC00221 in hepatocellular carcinoma (HCC). Materials and methods:A discovery cohort and a validation cohort were respectively used to identify and verify the clinical value of LINC00221 in HCC. Bioinformatics analysis was performed to explore its potential mechanisms. Results: LINC00221 was upregulated in HCC tissues and serum samples. Survival analysis and receiver operating characteristic curve further revealed its prognostic and diagnostic roles. Exploration of the mechanism showed that LINC00221 might exert a pro-cancer role via the lncRNA–miRNA–mRNA network.Conclusions: Our study reveals that upregulated LINC00221 can serve as a potential diagnostic and prognostic biomarker and provides novel clues as to the role of LINC00221 in HCC.

Recent studies reported that serum anion gap could be regarded as a prognostic biomarker for patients admitted to intensive care units. However, the association between AG and mortality in cerebral infarction patients remained largely unknown.Relevant clinical data were collected from Medical Information Mart for Intensive Care III. Patients were divided into three groups according to tertiles of AG. Kaplan-Meier curve and Cox proportional hazards models were used to evaluate the association between AG levels and all-cause mortality. Subgroup analyses were performed to verify the predictive role of AG on mortality.Kaplan-Meier analysis showed that patients with higher AG had shorter survival time. Cox regression model indicated high AG as an independent risk factor of 30-day, 60-day and 180-day all-cause mortality (30-day: HR = 2.45, 95% CI = 1.21-4.97, 60-day: HR = 2.04, 95% CI = 1.07-3.89, and 180-day: HR = 1.85, 95% CI = 1.02-3.36). However, no significance was observed between AG and 365-day all-cause mortality (HR = 1.56, 95% CI = 0.87-2.78).High AG was associated with increased risk of all-cause mortality, and AG could be an independent short-term prognostic factor for cerebral infarction.

Acute lung injury (ALI) is an important cause of mortality of patients with sepsis, shock, trauma, pneumonia, multiple transfusions and pancreatitis. Physalis alkekengi L. var. franchetii (Mast.) Makino (PAF) has been extensively used in Chinese folk medicine because of a good therapeutic effect in respiratory diseases. Here, an integrated approach combining network pharmacology, proton nuclear magnetic resonance‐based metabolomics, histopathological analysis and biochemical assays was used to elucidate the mechanism of PAF against ALI induced by lipopolysaccharide (LPS) in a mouse model. We found that the compounds present in PAF interact with 32 targets to effectively improve the damage in the lung undergoing ALI. We predicted the putative signalling pathway involved by using the network pharmacology and then used the orthogonal signal correction partial least‐squares discriminant analysis to analyse the disturbances in the serum metabolome in mouse. We also used ELISA, RT‐qPCR, Western blotting, immunohistochemistry and TUNEL assay to confirm the potential signalling pathways involved. We found that PAF reduced the release of cytokines, such as TNF‐α, and the accumulation of oxidation products; decreased the levels of NF‐κB, p‐p38, ERK, JNK, p53, caspase‐3 and COX‐2; and enhanced the translocation of Nrf2 from the cytoplasm to the nucleus. Collectively, PAF significantly reduced oxidative stress injury and inflammation, at the same time correcting the energy metabolism imbalance caused by ALI, increasing the amount of antioxidant‐related metabolites and reducing the apoptosis of lung cells. These observations suggest that PAF may be an effective candidate preparation alleviating ALI.

Photothermal therapy (PTT) and chemodynamic therapy (CDT) are promising therapeutic modalities with high specificity, however, a single therapeutic modality cannot maximize therapeutic efficacy. In the present study, glucose oxidase (GOx) was decorated on N-doped carbon (NC) nanoparticles (NPs) as a biomimetic nanoenzyme (NC@GOx NPs), which could promote starvation therapy enhanced PTT and CDT against tumors. GOx could decompose to cut off the supply of energy and nutrients, inducing starvation therapy, which further lowered adenosine triphosphate (ATP) levels, inducing downregulated heat shock proteins and creating a more suitable microenvironment for improving PTT efficacy. Meanwhile, the generated endogenous hydrogen peroxide (H2O2) could be converted into hydroxyl radicals to attack cancer cells. In fact, in vitro and in vivo experiments demonstrated that NC@GOx NPs could effectively kill cancer cells and eliminate tumors. This design provides a strategy for synergistic cancer therapy by using biomimetic nanoenzymes.

Background Image reconstruction algorithm is one of the important factors affecting the quantitative parameters of PET/CT. The purpose of this study was to investigate the effects of time of flight (TOF) and point spread function (PSF) on quantitative parameters of lung lesions in 18F-FDG PET/CT. Methods This retrospective study evaluated 60 lung lesions in 39 patients who had undergone 18F-fluoro-deoxy-glucose (FDG) PET/CT. All lesions larger than 10 mm in diameter were included in the study. The PET data were reconstructed with a baseline ordered-subsets expectation–maximization (OSEM) algorithm, OSEM + PSF, OSEM + TOF and OSEM + TOF + PSF respectively. The differences of maximum standard uptake value (SUVmax), mean standard uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG)and signal to noise ratio (SNR)were compared among different reconstruction algorithms. Results Compared with OSEM reconstruction, using OSEM + TOF + PSF increased SUVmean and SUVmax by 23.73% and 22.71% respectively, and SNR increased by 70.18%, MTV decreased by 23.84% (p 15.31). The difference of TLG among various reconstruction algorithms is relatively small, the highest value is − 6.48% of OSEM + TOF + PSF, and the lowest value is 0.81% of OSEM + TOF. Conclusion TOF and PSF significantly affected the quantitative parameters of lung lesions in 18F-FDG PET/CT. OSEM + TOF + PSF can significantly increased SUVmax, SUVmean and SNR, and significantly reduce MTV, especially in small lesions and low contrast lesions. TLG can be relatively stable in different reconstruction algorithms.

AimsThis study aimed to reveal the functional role of LINC00485 in hepatocellular carcinoma (HCC).Materials & Methods210 serum samples from Zhongnan Hospital of Wuhan University were employed to evaluate clinical value of LINC00485. Bioinformatics analysis was adopted to explore its potential mechanisms.ResultsLINC00485 was confirmed to be upregulated in HCC tissues and serum samples. Survival analysis and receiver operating characteristic curve revealed its prognostic and diagnostic roles. The combination of serum LINC00485 with AFP can remarkably improve diagnostic ability of HCC. Exploration of the underlying mechanism demonstrated that LINC00485 might exert pro-oncogenic activity by LINC00485—three miRNAs—four mRNAs network.ConclusionsOur study unveiled that upregulated LINC00485 could act as a potential diagnostic and prognostic biomarker and provide a novel insight into the molecular mechanisms of LINC00485 in HCC pathogenesis.

Despite recent technological advances allowing for quantitative single-photon emission computed tomography (SPECT), quantitative SPECT has not been widely used in the clinical practice of osteoporosis. The aim of this study is to evaluate the feasibility of quantitative bone SPECT/CT for measuring lumbar standard uptake value (SUV) in patients with different bone-mineral density (BMD), and investigate the correlation between SUV measured with 99mTc-methylene diphosphonate (MDP) SPECT/CT and BMD assessment by dual-energy X-ray absorptiometry (DXA). A retrospective analysis of 62 cases 99mTc-MDP whole-body bone imaging and local lumbar SPECT/CT tomography were performed. According to the results of dual-energy X-ray bone density examination, they were divided into normal group, osteopenic group, and osteoporosis group. The raw SPECT data were reconstructed using flash3D which includes attenuation correction, scatter compensation, and collimator resolution recovery, SPECT images from this algorithm were calibrated for SUV analysis. Comparing difference of lumbar SUV in different BMD subjects, and investigating the correlation between lumbar SUV and BMD. Data were analyzed by one-way ANOVA and Pearson regression analysis using SPSS 17.0 software. The maximum SUV (SUVmax) and mean SUV (SUVmean) of L1–L4 vertebral in 62 subjects were 7.39 ± 1.84 and 4.90 ± 1.27, respectively. The average BMD was 0.85 ± 0.15 (g/cm2), and the average CT value was 145.88 ± 53.99 (HU). The SUVmax, SUVmean, BMD, and CT values of the lumbar spine were statistically significantly different among the three groups (F = 24.089, 30.501, 94.847, 30.241, all p 0.05). Lumbar SUVmax and SUVmean increased significantly with the increase of BMD (r = 0.638, 0.632, p

The development of effective nanoplatforms is extremely necessary for cancer therapy. Herein, we prepared polydopamine (PDA) and ammonium bicarbonate (NH4HCO3) coated and doxorubicin (Dox) loaded hollow cerium oxide (CeO2) NPs (PDAC NPs), which showed excellent synergistic effect for photothermal therapy, chemotherapy and chemodynamic therapy. Under near infrared laser irradiation, PDA shell could absorb the incident light and convert it into heat, which could not only kill tumor cells with hyperthermia, but also trigger the decomposition of NH4HCO3 into gaseous carbon dioxide and ammonia, leading to the destroy of PDA shell. The leakage of PDA further accelerated Dox release and exposed CeO2 surface, in which Dox could enter into cell nucleus to induce chemotherapy, and CeO2 could catalyze cellular hydrogen peroxide into hydroxyl radical to present chemodynamic therapy. In fact, PDAC NPs showed an excellent therapeutic efficacy both in vitro and in vivo. This design provides a new strategy for synergistic tumor therapy.

Aim: This study aimed to excavate the roles of BCYRN1 in hepatocellular carcinoma (HCC). Methods: A comprehensive strategy of microarray data mining, computational biology and experimental verification were adopted to assess the clinical significance of BCYRN1 and identify related pathways. Results: BCYRN1 was upregulated in HCC and its expression was positively associated with both tumor, node, metastasis and worse survival rate in patients with HCC. Through combing plasma BCYRN1 with alpha fetoprotein, the diagnosis of HCC was remarkably improved. BCYRN1 may regulate some cancer-related pathways to promote HCC initiation via an lncRNA–miRNA–mRNA network. Conclusion: Our results propose BCYRN1 as a potential diagnostic and prognostic biomarker and offer a novel perspective to explore the etiopathogenesis of HCC.

Silver nanoparticles (Ag NPs) have promising plasmonic properties, however, they are rarely used in biomedical applications because of their potent toxicity. Herein, an electron compensation effect from Au to Ag was applied to design safe Au@Ag core-shell NPs. The Ag shell thickness was precisely regulated to enable the most efficient electron enrichment in Ag shell of Au@Ag

Silver (Ag)-based nanoparticles (NPs) with a high potential of Ag+ release have been known to be capable of promoting bacteria inactivation and the wound healing process; however, keeping a steady flux of high levels of Ag+ in Ag-based NPs is still challenging. Herein, a novel strategy in terms of altering the intrinsic electronic structure of Ag NPs was attempted to facilitate Ag oxidation and boost the Ag+ flux, as results of improved antibacterial and wound healing performance of Ag NPs. Gold (Au), platinum (Pt), and palladium (Pd) were doped into Ag NPs to tune their d band centers to upshift toward the Fermi level, and the formed Pd-Ag alloy NPs showed the largest shift, followed by Pt-Ag and Au-Ag NPs, as determined by density function theory calculation and ultraviolet photoemission spectroscopy measurement. Further X-ray photoelectron spectroscopy analysis indicates that a larger upshift could induce less electron filling in the antibonding orbital and a higher Ag oxidation level, leading to the more remarkable Ag+ release as determined by inductively coupled plasma optical emission spectrometry. All these alloy Ag NPs could more efficiently inhibit bacterial growth and accelerate the wound healing process than pure Ag NPs, and their antibacterial activity and wound healing performance were progressively proportional to the upshift values of the d band center. Taken together, tuning the d band center to upshift toward the Fermi level becomes a feasible strategy for designing therapeutic Ag-based NPs with a promising antibacterial and wound healing performance.

Background Hyperthermic intraperitoneal chemotherapy (HIPEC) is widely used for clinical treatment of advanced cancers. However, the regulatory mechanism underlying precise hyperthermia treatment in advanced gastric cancer (AGC) remains unclear. MiR-409–3p is reportedly downregulated in a variety of cancers, although its role in regulating treatment of AGC by precise hyperthermia remains unclear. The underlying mechanisms of miRNA-medicated regulation have been investigated using predicted and validated miRNA-gene targets, confirming the role of miRNA in HIPEC; Methods We used quantitative real time PCR (qRT-PCR) to detect miR-409–3p expression in gastric cancer (GC), as well as adjacent normal tissues, following exposure to varying temperatures. We detected miR-409–3p targets using dual-luciferase assay, then performed cell apoptosis, western blotting, invasion, and migration assays to detect GC functions; Results MiR-409–3p was upregulated and downregulated in precise hyperthermia and AGC, respectively. Moreover, miR-409–3p upregulated the Kruppel-like-factor 17 (KLF17), which subsequently inhibited migration, invasiveness, and epithelial-mesenchymal transition (EMT) but promoted apoptosis in GC cells; Conclusions Precise hyperthermia upregulated miR-409–3p and KLF17 indirectly, thereby inhibiting invasion, migration, and EMT, and promoting apoptosis of gastric cancer cells.

The combination of MAPK-targeted therapy and immune checkpoint blockade is one of the most promising regimens for patients with advanced melanoma. However, the synergistic efficacy of the combo regimen is still controversial in clinical trials. Here, we report that MAPK inhibition induced T-cell suppression within tumor microenvironment is mediated by attenuation of HSP27/HSP70 and deficiency of neoantigen presentation. To address this problem, we designed a photothermal-responsive on-demand controlled drug release gold nano-system to carry BRAF inhibitor. The nano-system can be specifically delivered into tumor cells rather than T-cells, and effectively transformed the optical energy into heat energy upon laser irradiation. Combination of photothermal and targeted therapy significantly promoted immunogenic cell death and T-cell infiltration. On top of this regimen, systematically administration of PD-1 antibody not only suppressed local-treated tumor but also inhibited abscopal tumor by enhancing generalized immune-related antitumor response. More importantly, the triple-combo regimen could efficiently convert immune "cold" tumors into "hot" ones. In conclusion, our research proves the advantage of photothermal-targeted-immune triple combinatorial regimen in treating tumors which are clinical unresectable multifocal and lack of T-cell infiltration.

Colon cancer is one of the most prevalent malignancies that lead to high occurrence of cancer-related deaths. Currently, chemotherapies and radiotherapies remain the primary treatments for advanced colon cancer. Despite the initial effectiveness, a fraction of colon cancer patients developed cisplatin resistance, resulting in therapeutic failure. The long non-coding RNA differentiation antagonizing non-coding RNA (DANCR) has been shown to be upregulated in multiple cancers, indicating an oncogenic role of DANCR. This study aims to elucidate the roles of DANCR in regulating cisplatin (CDDP) resistance of colon cancer. We found DANCR was significantly upregulated in colon cancer tissues and cells compared with normal colon tissues and cells. DANCR was upregulated in cisplatin-resistant colon cancer cells. Moreover, overexpression of DANCR significantly desensitized colon cancer cells to cisplatin. On the other way, silencing DANCR dramatically overrode CDDP resistance of colon cancer cells. Bioinformatics prediction revealed DANCR could bind to seeding region of miR-125b-5p as a competitive endogenous RNA. This interference was further validated by luciferase assay. Moreover, we detected a negative correlation between DANCR and miR-125b-5p in colon cancer patient tissues: miR-125b-5p was clearly downregulated in colon cancer tissues and cells. Overexpression of miR-125b-5p significantly sensitized cisplatin-resistant cells. Interestingly, we observed the cisplatin-resistant cells were associated with a significantly increased glycolysis rate. We further identified glycolysis enzyme, hexokinase 2 (HK2), as a direct target of miR-125b-5p in colon cancer cells. Rescue experiments showed overexpression of miR-125b-5p suppressed cellular glycolysis rate and increased cisplatin sensitivity through direct targeting the 3′ UTR of HK2. Importantly, silencing endogenous DANCR significantly induced the miR-125b-5p/HK2 axis, resulting in suppression of the glycolysis rate and increase in cisplatin sensitivity of colon cancer cell. Expectedly, these processes could be further rescued by inhibiting miR-125b-5p in the DANCR-silenced cells. Finally, we validated the DANCR-promoted cisplatin resistance via the miR-125b-5p/HK2 axis from an in vivo xenograft mice model. In summary, our study reveals a new mechanism of the DANCR-promoted cisplatin resistance, presenting the lncRNA-DANCR–miR-125b-5p/HK2 axis as a potential target for treating chemoresistant colon cancer.

Gauge field is essential for exploring novel phenomena in modern physics. However, it has not been realized in the recent breakthrough experiment about two-leg superconducting circuits with transmon qubits [Phys. Rev. Lett. 123, 050502 (2019)]. Here we present an experimentally-feasible method to achieve the synthetic gauge field by introducing ac microwave driving in each qubit. In particular, the effective magnetic flux per plaquette achieved can be tuned independently by properly choosing the driving phases. Moreover, the ground-state chiral currents for the single- and two-qubit excitations are obtained and the Meissner-vortex phase transition is found. In the Meissner phase, the ground-state chiral current increases as the magnetic flux increases, while it decreases in the vortex phase. In addition, the chiral dynamics that depends crucially on the initial state of the system is also revealed. Finally, the possible experimental observations of the chiral current and dynamics are addressed. Therefore, our results provide a new route to explore novel many-body properties induced by the interplay of gauge field, two-leg hoppings and interaction of photons on superconducting circuits., 8 pages and 7 figures

Background: To explore the molecular mechanisms and modulatory effects of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the hyperthermia-induced gastric cancer cell death. Methods: Combined qRT-PCR and GLS activity detection of glutamine metabolism, we demonstrate the difference of expression of MALAT1 and miR-206 in normal or cancer tissue/ several cell lines and the roles of two in regulation of glutamine, respectively. The relation of MALAT1 and miR-206 was research by bioinformatical analysis and luciferase report. In addition, the molecular regulation between apoptotic effects and MALAT1-miR-206-GLS axis in gastric cancer after mild hyperthermia treatments were discovered by western blotting, luciferase report, quantitative real-time PCR (qRT-PCR), GLS activity detection of glutamine metabolism and cell viability test. Results: MALAT1 positively associated with GC by promoting glutamine metabolism under short time hyperthermia treatment, it involved in an adaptive reaction, an increased glutamine metabolism rate which could be further overridden by long time hyperthermia exposures. miR-206 could inhibit glutamine metabolism of GC and target 3’UTR of GLS which has oncogenic functions in GC directly. In addition, miR-206-suppresed glutamine metabolism was through direct targeting GLS. LncRNA MALAT1 inhibited miR-206 expression in GC by sponging it as a competing endogenous RNA. In summary, MALAT1-promoted glutamine metabolism was through the miR-206-GLS axis. Furthermore, we demonstrated effective approaches from the MALAT1-miR-206 axis for enhancing the mild hyperthermia-induced cancer death under a short time. Conclusions: Taken together, the MALAT1-miR-206-glutamine metabolism axis is a new strategy for enhancing the selectivity of hyperthermia treatments specific to GC cells

Existing work on augmenting question answering (QA) models with external knowledge (e.g., knowledge graphs) either struggle to model multi-hop relations efficiently, or lack transparency into the model's prediction rationale. In this paper, we propose a novel knowledge-aware approach that equips pre-trained language models (PTLMs) with a multi-hop relational reasoning module, named multi-hop graph relation network (MHGRN). It performs multi-hop, multi-relational reasoning over subgraphs extracted from external knowledge graphs. The proposed reasoning module unifies path-based reasoning methods and graph neural networks to achieve better interpretability and scalability. We also empirically show its effectiveness and scalability on CommonsenseQA and OpenbookQA datasets, and interpret its behaviors with case studies., Comment: Accepted to EMNLP 2020. Project page: https://github.com/INK-USC/MHGRN

Airborne fine particulate matter (PM2.5) has been known capable of causing lung inflammation and fibrosis, as a result of a series of chronic respiration diseases. Although NLRP3 inflammasome activation is essential for development of many chronic diseases, the relationship between PM2.5-induced toxicological effect and NLRP3 inflammasome activation is rarely investigated. Since PM2.5 contains a large population of nanosized materials and many types of nanomaterials can activate NLRP3 inflammasome, the NLRP3 inflammasome activation and lung fibrosis induced by PM2.5 were investigated in the present study. PM2.5 was found capable of causing weak cell death but potent IL-1β secretion in THP-1 cells, which was involved in NLRP3 inflammasome activation as evidenced by Z-YVAD-FMK inhibited IL-1β secretion and overexpressed ASC and NLRP3 protein in PM2.5 treated cells. PM2.5 could be internalized into cells through multiple endocytosis processes, such as phagocytosis and pinocytosis (macropinocytosis, clathrin- and caveolin-mediated endocytosis), and activate NLRP3 inflammasome through cathepsin B release, ROS production, and potassium efflux. After 21 days of exposure to PM2.5 through oropharyngeal aspiration, Balb/c mice showed increased IL-1β and TGF-β1 levels in the bronchoalveolar lavage fluid (BALF) of lung and significant collagen deposition around small airways of mice, suggesting potential lung inflammation and pulmonary fibrosis.

It has been shown that the short-lived halogenated hydrocarbons, such as dichloromethane (DCM), which are not regulated by the Montreal Protocol, have the potential to impact stratospheric ozone. DCM with increasing atmospheric mixing ratios in recent years, is widely used in solvent, foam-blowing and methyl fluoride production sectors in China, which is a large producer as well as consumer of DCM. This study develops a comprehensive emission inventory of anthropogenic DCM in China using a bottom-up method based on the industrial consumption of DCM in China from 2005 to 2016 and makes a projection to 2030. The inventory considered solvent use, polyurethane (PU) foam manufacturing, the chemical industry, and other end uses. Anthropogenic emissions of DCM increased from 101 (80–122) Gg/yr to 318 (254–384) Gg/yr between 2005 and 2016, a increase of 215% over the last 11 years. Solvent use and the manufacture of PU foam agents are the major contributors to total DCM emissions. Under a business as usual (BAU) scenario future Chinese emissions of DCM are predicted to increase to 708 (588–831) Gg/yr by 2030, more than twice the emission IHS, 2016. Chinese emission account for approximately 25%–37% of the 515 Gg/yr estimates by the WMO as average annual global emissions in 2008.

Bismuth sulfide (Bi2 S3 ) nanomaterials are emerging as a promising theranostic platform for computed tomography imaging and photothermal therapy of cancer. Herein, the photothermal properties of Bi2 S3 nanorods (NRs) were unveiled to intensely correlate to their intrinsic deep-level defects (DLDs) that potentially could work as electron-hole nonradiative recombination centers to promote phonon production, ultimately leading to photothermal performance. Bi2 S3 -Au heterojunction NRs were designed to hold more significant DLD properties, exhibiting more potent photothermal performance than Bi2 S3 NRs. Under 808 nm laser irradiation, Bi2 S3 -Au NRs could trigger higher cellular heat shock protein 70 expression and more apoptotic cells than Bi2 S3 NRs, and caused severe cell death and tumor growth inhibition, showing great potential for photothermal therapy of cancer guided by computed tomography imaging.

Despite recent technological advances allowing for quantitative single-photon emission computed tomography (SPECT), quantitative SPECT has not been widely used in the clinical practice of osteoporosis. The aim of this study is to evaluate the feasibility of quantitative bone SPECT/CT for measuring lumbar standard uptake value (SUV) in patients with different bone-mineral density (BMD), and investigate the correlation between SUV measured withA retrospective analysis of 62 casesThe maximum SUV (SUVThe SUV of lumbar spine in

Nitric oxide (NO) molecular messenger can reverse the multidrug resistance (MDR) effect of cancer cells through reducing P-glycoprotein (P-gp) expression, beneficial for creating a favorable microenvironment for the treatment of doxorubicin (Dox)-resistant cancer cells. Development of sophisticated nanosystems to programmably release NO and Dox becomes an efficient strategy to overcome the MDR obstacles and achieve promising therapeutic effects in Dox-resistant cancer. Herein, a NO stimulated nanosystem was designed to engineer a significant time gap between NO and Dox release, promoting MDR cancer therapy. A o-phenylenediamine-containing lipid that can hydrolyze in response to NO was embedded in the phospholipid bilayer structure of liposome to form NO-responsive liposome, which could further encapsulate l-arginine (l-Arg)/Dox-loaded gold@copper sulfide yolk-shell nanoparticls (ADAu@CuS YSNPs) to form ADLAu@CuS YSNPs. Under 808 nm laser irradiation, the unique resonant energy transfer (RET) process and reactive oxygen species (ROS) generation in the confined space of ADLAu@CuS YSNPs could effectively convert l-Arg into NO, regionally destabilizing the phospholipid bilayer structure, as a result of NO release. However, at this early stage Dox could not be released from YSNPs due to the molecular scaffold limit. As the NO release progressed, the NO-responsive liposome layer was deteriorated more severely, allowing Dox to escape. This NO and Dox sequential release of ADLAu@CuS YSNPs could significantly inhibit P-gp expression and enhance Dox accumulation in Dox-resistant MCF-7/ADR cells, leading to promising in vitro and in vivo therapeutic effects and presenting their great potential for MDR cancer therapy.