Cuproptosis Depicts Immunophenotype and Predicts Immunotherapy Response in Lung Adenocarcinoma.

BACKGROUND: Although significant progress has been made in immunotherapy for lung adenocarcinoma (LUAD), there is an urgent need to identify effective indicators to screen patients who are suitable for immunotherapy. Systematically investigating the cuproptosis-related genes (CRGs) in LUAD may provide new ideas for patients' immunotherapy stratification. METHOD: We comprehensively analyzed the landscape of 12 CRGs in a merged TCGA and GEO LUAD cohort. We investigated the associations between tumor microenvironment and immunophenotypes. We utilized a risk score to predict the prognosis and immunotherapy response for an individual patient. Additionally, we conducted CCK-8 experiments to evaluate the impact of DLGAP5 knockdown on A549 cell proliferation. RESULT: We utilized an integrative approach to analyze 12 CRGs and differentially expressed genes (DEGs) in LUAD samples, resulting in the identification of two distinct CRG clusters and two gene clusters. Based on these clusters, we generated immunophenotypes and observed that the inflamed phenotype had the most abundant immune infiltrations, while the desert phenotype showed the poorest immune infiltrations. We then developed a risk score model for individual patient prognosis and immunotherapy response prediction. Patients in the low-risk group had higher immune scores and ESTIMATE scores, indicating an active immune state with richer immune cell infiltrations and higher expression of immune checkpoint genes. Moreover, the low-risk group exhibited better immunotherapy response according to IPS, TIDE scores, and Imvigor210 cohort validation results. In addition, our in vitro wet experiments demonstrated that DLGAP5 knockdown could suppress the cell proliferation of A549. CONCLUSION: Novel cuproptosis molecular patterns reflected the distinct immunophenotypes in LUAD patients. The risk model might pave the way to stratify patients suitable for immunotherapy and predict immunotherapy response.

An artificial intelligence network-guided signature for predicting outcome and immunotherapy response in lung adenocarcinoma patients based on 26 machine learning algorithms.

The immune cells play an increasingly vital role in influencing the proliferation, progression, and metastasis of lung adenocarcinoma (LUAD) cells. However, the potential of immune cells' specific genes-based model remains largely unknown. In the current study, by analysing single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing data, the tumour-infiltrating immune cell (TIIC) associated signature was developed based on a total of 26 machine learning (ML) algorithms. As a result, the TIIC signature score could predict survival outcomes of LUAD patients across five independent datasets. The TIIC signature score showed superior performance to 168 previously established signatures in LUAD. Moreover, the TIIC signature score developed by the immunofluorescence staining of the tissue array of LUAD patients showed a prognostic value. Our research revealed a solid connection between TIIC signature score and tumour immunity as well as metabolism. Additionally, it has been discovered that the TIIC signature score can forecast genomic change, chemotherapeutic drug susceptibility, and-most significantly-immunotherapeutic response. As a newly demonstrated biomarker, the TIIC signature score facilitated the selection of the LUAD population who would benefit from future clinical stratification.

Bioinformatics construction and experimental validation of a cuproptosis-related lncRNA prognostic model in lung adenocarcinoma for immunotherapy response prediction.

Cuproptosis is a newly form of cell death. Cuproptosis related lncRNA in lung adenocarcinoma (LUAD) has also not been fully elucidated. In the present study, we aimed to construct a prognostic signature based on cuproptosis-related lncRNA in LUAD and investigate its association with immunotherapy response. The RNA-sequencing data, clinical information and simple nucleotide variation of LUAD patients were obtained from TCGA database. The LASSO Cox regression was used to construct a prognostic signature. The CIBERSORT, ESTIMATE and ssGSEA algorithms were applied to assess the association between risk score and TME. TIDE score was applied to reflect the efficiency of immunotherapy response. The influence of overexpression of lncRNA TMPO-AS1 on A549 cell was also assessed by in vitro experiments. The lncRNA prognostic signature included AL606834.1, AL138778.1, AP000302.1, AC007384.1, AL161431.1, TMPO-AS1 and KIAA1671-AS1. Low-risk group exhibited much higher immune score, stromal score and ESTIMATE score, but lower tumor purity compared with high-risk groups. Also, low-risk group was associated with a much higher score of immune cells and immune related function sets, indicating an immune activation state. Low-risk patients had relative higher TIDE score and lower TMB. External validation using IMvigor210 immunotherapy cohort demonstrated that low-risk group had a better prognosis and might more easily benefit from immunotherapy. Overexpression of lncRNA TMPO-AS1 promoted the proliferation, migration and invasion of A549 cell line. The novel cuproptosis-related lncRNA signature could predict the prognosis of LUAD patients, and helped clinicians stratify patients appropriate for immunotherapy and determine individual therapeutic strategies.

Integrative bioinformatic analysis identified IFIT3 as a novel regulatory factor in psoriasis.

Psoriasis is an autoimmune skin disease with poor prognosis. Currently, there is no cure for psoriasis and the pathogenic mechanism of psoriasis remains unclear. Our study aims to explore key regulators underlying psoriasis and potential targets for psoriasis treatment. RNA-seq data of psoriasis and normal tissues were extracted from Gene Expression Omnibus database to screen differentially expressed genes (DEGs). Weighted correlation network analysis (WGCNA) was conducted to identify key gene modules correlated with psoriasis. Enrichment analysis was used to characterize identified genes. The expression of identified genes was verified in a data set with various types of psoriasis lesion tissues and six psoriasis and healthy control tissues by quantitative polymerase chain reaction and immunohistochemistry assays. And the biological functions of IFIT3 in keratinocytes were determined by colony formation assays, Cell Counting Kit-8, and enzyme-linked immunosorbent assays. A total of 594 overlapped genes (370 upregulated and 224 downregulated) were selected as DEGs between psoriasis and normal tissues in three independent data sets. These genes were enriched in interferon-related pathway and cytokine-related pathway. Weighted correlation network analysis identified several gene modules that were associated with psoriasis. Overlapped genes between gene modules and DEGs were associated with interferon-related pathway and T cell activities. Among these genes, OAS1, USP18, and IFIT3 had higher expression levels in psoriasis vulgaris (PV) and nonpustular palmoplantar psoriasis (NPPP) tissues but not Palmoplantar Pustular Psoriasis (PPPP). Meanwhile, these results were confirmed in our independent psoriasis tissue cohort. And results of in vitro experiments showed that inhibition of IFIT3 significantly impaired the proliferation capacity and CXCL1, CCL20, IL-1ß, and IL-6 secretion of keratinocytes. Our study identified key genes and pathways underlying the pathogenesis of psoriasis through the conduct of integrated analysis. OAS1, USP18, and IFIT3 could be potential targets for the treatment of psoriasis. IFIT3 can promote the proliferation and immune activation of keratinocytes and facilitates the development of psoriasis.

Geological Characteristics of Lower Paleozoic Shale Gas Accumulation in the Yuxi Region, Southern Sichuan Basin: In View of High-Density Methane Inclusions.

Twelve shale fracture veins and forty-nine fluid inclusion assemblages within the veins of 3800-4200 m in three wells located in different tectonic zones in the Yuxi Region, southern Sichuan Basin were selected in this study. The burial and thermal histories of single wells were reconstructed, and time-temperature-pressure of oil and gas filling were clarified using microscopy observation, Raman microprobe analyses, geochemical tests, and fluid inclusion microtemperature measurement. The shale fracture veins of the Wufeng-Longmaxi Formation in the Yuxi Region are mainly formed vertically and horizontally, where the vein-forming fluids are derived from endogenous fluids. A large number of methane inclusions, bituminous inclusions, and methane-bearing bituminous inclusions within the veins confirm the process of oil cracking gas and kerogen cracking gas. The homogeneous temperature (Th) of the aqueous inclusions contemporaneous with the bituminous inclusions ranges from 109.3 to 174.1 °C, which were trapped during 220 to 250 Ma. The homogeneous temperature of the aqueous inclusions contemporaneous with the methane inclusions ranges from 137.3 to 226.8 °C, which were trapped during 160 to 195 Ma and 51 to 56 Ma. The trapped pressure calculated by high-density methane inclusions (0.246-0.293 g/cm3) is between 82.9 and 140.1 MPa, with a pressure coefficient between 1.64 and 2.07. The formation pressure coefficient is nearly two, indicating that the current overpressure is inherited from the overpressure at the maximum burial depth. The earlier the fracture vein opening, the less the damage to the shale gas accumulation, and the more opening-closing phases, the lower the homogeneous temperature of the gas-liquid two-phase aqueous inclusions coeval with the high-density methane inclusions and the greater the degree of damage to the shale gas accumulation. The results provide a basis for further study on the genesis of overpressure and the migration of shale gas.

Cell-free fat extract protects septic lethality via restraining NLRP3 inflammasome activation.

BACKGROUND: Sepsis is a dysregulated host response to infection with high mortality and current management cannot reach optimal remission. Previous studies have shown that cell-free fat extract (CEFFE) is a kind of bioactive extraction from adipose tissues and exhibits a potent anti-inflammatory effect on wound healing and inflammatory diseases. However, the potential role of CEFFE in sepsis remains unclear. METHODS: CEFFE was extracted from healthy donors and was intraperitoneally injected into septic mice. The septic mice models were constructed using lipopolysaccharide (LPS), E. coli, and cecal ligation and puncture (CLP). The survival of septic mice was detected for 96 h and Kaplan-Meier analysis was used to analyze the differences of survival rates. Lung tissues that were collected from septic mice were subjected to HE staining to evaluate the extent of lung injury, and the mice serum was obtained for inflammasome-related cytokines detection. Moreover, peritoneal macrophages were extracted from C57 mice and treated with CEFFE and/or inflammasome activators. The level of IL-1ß, IL-18, IL-6, and TNF-α was detected by ELISA, and the activation of NLRP3 were evaluated by Western Blot. Total mtDNA and mitochondrial permeability transition pore were determined to explore the mitochondrial dysfunction in the activation of NLRP3 inflammasome with or without CEFEE. Coimmunoprecipitation (Co-IP) assays were performed to confirm the mechanism of NLRP3 activation induced by CEFFE. RESULTS: CEFFE significantly improved the survival of sepsis mice and alleviate sepsis-induced lung injury. Moreover, CEFFE significantly decreased the level of inflammasome-cytokines (IL-1ß and IL-18) but not the pro-inflammatory cytokines such as IL-6 and TNF-α. Moreover, CEFFE markedly suppressed the canonical activation of NLRP3 inflammasome without affecting inflammasomes NLRC4 and AIM2. Additionally, the non-canonical activation of NLRP3 inflammasome was significantly inhibited by CEFFE. CEFFE treatment attenuated the mtDNA outflow and the increase of mitochondrial permeability induced by both canonical and non-canonical pathway of NLRP3 inflammasome activation. The results of Co-IP assays revealed that CEFFE remarkably attenuated the oligomerization of ASC and inhibited the association between NLRP3 and ASC. CONCLUSION: Our study revealed that CEFFE could significantly alleviate sepsis-related injuries possibly by suppressing NLRP3 inflammasome activation. CEFFE was a promising approach for sepsis treatment.

Improving the catalytic and mechanical performance of alginate catalyst through functionalization by aminopolycarboxylic acids.

Biomass-based aerogel catalysts have attracted extensive attention due to their high surface aera, continuous porous and environmental friendliness. However, their catalytic activity and mechanical strength are not satisfied for industrial applications. In this work, to solve the above two issues, a new kind of graphene oxide enhancediminodiacetic acid-functionalized Cu-cross-linked alginate (GO-Cu-SA-IDA) aerogel composites were prepared. The physicochemical property of the prepared alginate aerogel composites was characterized systematically, and their catalytic activities were studied in the hydroxylation of phenol. Results illustrated that compared with Cu-SA aerogels (∼16 %), the amount of loaded copper ion which played as the active sites in GO-Cu-SA-IDA aerogel composite was increased by 2 times (32.2 %). In addition, the mechanical strength of GO-Cu-SA-IDA was increased by 10 times. After functionalization, both the catalytic activity and mechanical strength of prepared alginate aerogel composites were enhanced successfully. In addition, the catalyst had been recycled five times with only 5.8 % loss of its catalytic activity, which provided a desirable material for next generation of catalysts.

Reprogramming Macrophage Metabolism and its Effect on NLRP3 Inflammasome Activation in Sepsis.

Sepsis, the most common life-threatening multi-organ dysfunction syndrome secondary to infection, lacks specific therapeutic strategy due to the limited understanding of underlying mechanisms. It is currently believed that inflammasomes play critical roles in the development of sepsis, among which NLRP3 inflammasome is involved to most extent. Recent studies have revealed that dramatic reprogramming of macrophage metabolism is commonly occurred in sepsis, and this dysregulation is closely related with the activation of NLRP3 inflammasome. In view of the fact that increasing evidence demonstrates the mechanism of metabolism reprogramming regulating NLRP3 activation in macrophages, the key enzymes and metabolites participated in this regulation should be clearer for better interpreting the relationship of NLRP3 inflammasome and sepsis. In this review, we thus summarized the detail mechanism of the metabolic reprogramming process and its important role in the NLRP3 inflammasome activation of macrophages in sepsis. This mechanism summarization will reveal the applicational potential of metabolic regulatory molecules in the treatment of sepsis.

The Comprehensive Analysis Identified an Autophagy Signature for the Prognosis and the Immunotherapy Efficiency Prediction in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a fatal malignancy in the world. Growing evidence demonstrated that autophagy-related genes regulated the immune cell infiltration and correlated with the prognosis of LUAD. However, the autophagy-based signature that can predict the prognosis and the efficiency of checkpoint immunotherapy in LUAD patients is yet to be discovered. Methods: We used conventional autophagy-related genes to screen candidates for signature construction in TCGA cohort and 9 GEO datasets (tumor samples, n=2181; normal samples, n=419). An autophagy-based signature was constructed, its correlation with the prognosis and the immune infiltration of LUAD patients was explored. The prognostic value of the autophagy-based signature was validated in an independent cohort with 70 LUAD patients. Single-cell sequencing data was used to further characterize the various immunological patterns in tumors with different signature levels. Moreover, the predictive value of autophagy-based signature in PD-1 immunotherapy was explored in the IMvigor210 dataset. At last, the protective role of DRAM1 in LUAD was validated by in vitro experiments. Results: After screening autophagy-related gene candidates, a signature composed by CCR2, ITGB1, and DRAM1 was established with the ATscore in each sample. Further analyses showed that the ATscore was significantly associated with immune cell infiltration and low ATscore indicated poor prognosis. Meanwhile, the prognostic value of ATscore was validated in our independent LUAD cohort. GSEA analyses and single-cell sequencing analyses revealed that ATscore was associated with the immunological status of LUAD tumors, and ATscore could predict the efficacy of PD-1 immunotherapy. Moreover, in vitro experiments demonstrated that the inhibition of DRAM1 suppressed the proliferation and migration capacity of LUAD cells. Conclusion: Our study identified a new autophagy-based signature that can predict the prognosis of LUAD patients, and this ATscore has potential applicative value in the checkpoint therapy efficiency prediction.

Study on the Pore Structure and Fractal Characteristics of Different Lithofacies of Wufeng-Longmaxi Formation Shale in Southern Sichuan Basin, China.

Gas content and flow characteristics are closely related to shale lithofacies, and significant differences exist in the pore structure and fractal characteristics among lithofacies. In this study, X-ray diffractometer (XRD), field-emission scanning electron microscopy (FE-SEM), gas adsorption (N2 and CO2), and fractal theory were employed to systematically characterize the pore attributes of the marine Wufeng-Longmaxi formation shales. The information of various pores and microfractures among lithofacies was extracted and quantified via high-resolution FE-SEM image stitching technology. Shales were classified into four types based on mineral compositions, and siliceous shales possess the largest SEM-based surface porosity (2.84%) and the largest pore volume (PV) (average 0.0243 cm3/g) as well as specific surface area (SSA) (average 28.06 m2/g). The effect of lithofacies variation on the PV of shale is minor. In contrast, the lithofacies variation has a significant impact on the SSA, and the SSA of siliceous shale is 39.11% higher than that of argillaceous shale. PV and SSA show strong positive correlation with the total organic carbon (TOC) content but negative correlation with clay minerals. Siliceous shales have the greatest fractal dimension D1 (pore surface roughness) (average 2.6821), which is contributed by abundant organic matter pores with more complicated boundaries. The largest fractal dimension D2 (pore structure complexity) (average 2.8263) is found in mixed shales, which is attributed to well-developed intraparticle (intraP) pores associated with carbonate mineral dissolution. This indicates that siliceous shales have the highest methane adsorption capacity and that shale gas desorption, diffusion, and seepage are more difficult in mixed shales.

Development of pH-responsive nanocomposites with remarkably synergistic antibiofilm activities based on ultrasmall silver nanoparticles in combination with aminoglycoside antibiotics.

Bacterial biofilms are responsible for many chronic infections because antibacterial agents exhibit poor penetration into the dense matrix barrier and cannot easily reach the internal bacteria. Herein, we reported pH-responsive nanocomposites (PDA@Kana-AgNPs) that could penetrate and disperse biofilms, which were synthesized by the combination of ultrasmall silver nanoparticles (AgNPs) and kanamycin, and then coating with polydopamine. Confocal fluorescence imaging indicated that PDA@Kana-AgNPs could respond to the acidic microenvironment of biofilms, leading to biofilm-triggered on- demand drug release in situ. The zone of inhibition test and Resazurin assay showed that the combination of kanamycin and AgNPs had greater antimicrobial activity against test strains (Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Escherichia coli BL21) than when applied separately. The crystal violet staining test demonstrated that biofilms were effectively dispersed by the proposed nanocomposites. Biocompatibility was also evaluated, which showed that PDA@Kana-AgNPs were non-toxic to mammalian cells. Therefore, the proposed pH-responsive nanocomposites held great potential for efficient antibiotics delivery and showed synergistic antibacterial and antibiofilm activities. This strategy could also be used to encapsulate a variety of antibiotics in combination with other drugs or materials, thereby showing therapeutic potential in preventing biofilm-related infections and realizing fluorescence imaging in situ.

CD74 Correlated With Malignancies and Immune Microenvironment in Gliomas.

Background: Cluster of differentiation 74 (CD74) is found to be highly involved in the development of various types of cancers and could affect the activities of infiltrated cells in the tumor microenvironment. However, these studies only focus on a few types of immune cells. Our study aims to comprehensively explore the role of CD74 in glioma prognosis and immune microenvironment. Methods: A total of 40 glioma specimens were collected in this study. We extracted data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene-Expression Omnibus (GEO) databases to explore the expression pattern of CD74 in gliomas. gene sets enrichment analysis and gene set variation analysis analyses were conducted to characterize the immune features of CD74. ESTIMATE, ssGSEA, Tumor IMmune Estimation Resource, and CIBERSORT algorithms were applied to assess the immune infiltration. Kaplan-Meier analysis was used for survival analysis. Receiver operating characteristic analysis was used to evaluate the predictive accuracy of CD74 in glioma diagnosis and prognosis. Results: A total of 2,399 glioma patients were included in our study. CD74 was highly expressed in glioma tissue compared to normal brain tissue and its expression was significantly higher in the high-grade glioma compared to the lower grade glioma at transcriptional and translational levels. Besides, CD74 was positively associated with immune checkpoints and inflammatory cytokines as well as immune processes including cytokine secretion and leukocyte activation. The high expression of CD74 indicated a high infiltration of immune cells such as macrophages, dendritic cells, and neutrophils. Moreover, patients with high expression of CD74 had poor prognoses. CD74 had moderate predictive accuracy in the diagnosis of glioblastoma and prediction of survival. Conclusions: In conclusion, our study revealed that the high expression of CD74 was associated with poor prognosis and high immune infiltration. CD74 could be used as a potential target for glioma treatment and as a biomarker to predict the prognosis of glioma patients.

tRNA-derived small RNAs: novel regulators of cancer hallmarks and targets of clinical application.

tRNAs are a group of conventional noncoding RNAs (ncRNAs) with critical roles in the biological synthesis of proteins. Recently, tRNA-derived small RNAs (tsRNAs) were found to have important biological functions in the development of human diseases including carcinomas, rather than just being considered pure degradation material. tsRNAs not only are abnormally expressed in the cancer tissues and serum of cancer patients, but also have been suggested to regulate various vital cancer hallmarks. On the other hand, the application of tsRNAs as biomarkers and therapeutic targets is promising. In this review, we focused on the basic characteristics of tsRNAs, and their biological functions known thus far, and explored the regulatory roles of tsRNAs in cancer hallmarks including proliferation, apoptosis, metastasis, tumor microenvironment, drug resistance, cancer stem cell phenotype, and cancer cell metabolism. In addition, we also discussed the research progress on the application of tsRNAs as tumor biomarkers and therapeutic targets.

XBP1- IGFBP3 Signaling Pathway Promotes NSCLC Invasion and Metastasis.

Lung cancer is the most frequently diagnosed cancer and the main cause of cancer death in the world. X-box binding protein 1 (XBP1), which is an important transcription factor involved in regulating the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress, might act as a potent oncogenic protein in the processes of tumorigenesis, tumor proliferation and metastasis in various cancers. However, the clinical significance and pathological role of XBP1 in non-small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the expression of XBP1s protein in the 104 NSCLC tumor tissues and matched adjacent normal lung tissues (ANLT) by Immunohistochemical (IHC), and we found overexpressed XBP1s protein was associated with NSCLC TNM stages, lymph node metastasis and poor prognosis. The further gain-and loss-of-function experiments indicated overexpression of XBP1s protein promoted cell invasion, migration and metastasis both in vitro and in vivo. Further study showed XBP1s protein could upregulate insulin-like growth factor binding protein-3 (IGFBP3) expression, and regulated NSCLC cells invasion and metastasis by regulating IGFBP3. Taken together, XBP1s protein is markedly overexpressed in NSCLC and serves as an oncogene that play a critical role in NSCLC tumorigenesis and development. Importantly, XBP1s protein might not only be a potential biomarker for metastasis and prognosis but also a potential therapeutic target in NSCLC.

Microscopic imbibition characterization of sandstone reservoirs and theoretical model optimization.

Traditional porous media imbibition models deviate from the actual imbibition process in oil and gas reservoirs. Experimental studies on gas-water imbibition in reservoirs were carried out to describe the dynamic profile variation process of wet phase saturation in reservoirs and to further reveal the variation of the imbibition front and the imbibition amount. Optimization and correction methods were established, and experimental verifications were performed. Studies have shown the following: (1) Unlike homogeneous porous media, the water phase imbibition process in oil and gas reservoirs is more complicated, and it is impossible for the maximum saturation of imbibition to reach 100%. (2) Contrary to the theoretical hypothesis, the imbibition of water is not piston-like, and there is a clear transition zone at the imbibition front. This transition zone is the main cause of water saturation variations in the imbibition zone; with the expansion of the imbibition zone, the influence of the transition zone on water saturation weakens. (3) Traditional theoretical models predict a positive correlation between the imbibition amount and the measurements; however, there is a large deviation in the numerical values, which must be corrected. (4) The L-W model was optimized and the parameter group fluid factor F and the reservoir factor R were proposed to characterize the properties of the fluid and the reservoir, respectively. These two parameters have a clear physical significance and are easy to accurately test. After experimental correction, the optimized model is favourably suitable for oil and gas reservoirs.

Array-based microbial identification upon extracellular aminoglycoside residue sensing.

Sensitive and rapid identification of pathogenic microorganisms is of great importance for clinical diagnosis and treatment. In this study, we developed an ultrasensitive colorimetric sensor array (CSA) based on the interactions between aminoglycoside antibiotics (AMGs) and Ag nanoparticles decorated with ß-cyclodextrin (AgNPs@ß-CD) to discriminate microorganisms quickly and accurately. Microorganisms can absorb different amounts of AMGs after incubation. Upon the addition of AgNPs@ß-CD, the corresponding extracellular AMG residues will bind to AgNPs@ß-CD, leading to color changes due to the modifications in localized surface plasmon resonance. The array was developed using 4 AMGs as sensing elements and AgNPs@ß-CD as the colorimetric probe to generate a unique colorimetric response pattern for each microorganism. Standard chemometric methods indicated excellent discrimination among 20 microorganisms at low concentrations of 2 × 106 CFU/mL. Therefore, this ultrasensitive CSA can be used for microbial discrimination portably and efficiently. Importantly, the concentration of microbial discrimination by our array is much lower than that of prior CSAs. This method of extracellular residue sensing also provided a new strategy to improve the sensitivity of conventional CSA in the discrimination of microorganisms, to measure the amount of intercellular uptake of AMGs by microorganisms, and to screen drugs that can easily be accumulated by the pathogenic microorganisms.

Physical simulation for water invasion and water control optimization in water drive gas reservoirs.

The development of water drive gas reservoirs (WDGRs) with fractures or strong heterogeneity is severely influenced by water invasion. Accurately simulating the rules of water invasion and drainage gas recovery countermeasures in fractured WDGRs, thereby revealing the mechanism of water invasion and an appropriate development strategy, is important for formulating water management measures and enhancing the recovery of gas reservoirs. In this work, physical simulation methods were proposed to gain a better understanding of water invasion and to optimize the water control of fractured WDGRs. Five groups of experiments were designed and conducted to probe the impacts of the distance between the fractures and the gas well, the drainage position, the drainage timing and the aquifer size on the water invasion and production performance of a gas reservoir. The gas and water production and the internal pressure drop were monitored in real time during the experiments. Based on the above experimental works, a theoretical analysis was conducted to quantitatively evaluate the performance of the gas reservoir recovery via the gas well production performance, water invasion, dynamic pressure drop and residual gas and water distribution analysis. The results show that when the fracture scale was appropriate, a gas well drilled close to a fracture (Experiment 1-3) or a high-permeability formation could also produce gas and achieve drainage efficiently. The recovery factor of Experiment 1-3 reached 62.5%, which was 24.6% and 21.1% higher than those of Experiments 1-1 and 1-2, respectively, which had wells drilled in low-permeability areas. Draining water near an aquifer can effectively inhibit water invasion during the early stage of gas recovery. The setup in Experiment 2-1 effectively inhibited water invasion and avoided the formation of water-sealed volumes of gas to recover 30% more gas than recovered with that of Experiment 1-1 without drainage wells. A shorter distance between the drainage well and the aquifer increased the drainage capacity and decreased the gas production capacity, respectively (Well 2 at Point A vs Point B). A larger aquifer had a lower gas recovery, which reduced the economic benefit. For example, due to an infinitely large aquifer, the reserves in Experiment 4-1 were developed by a single well, the gas recovery was only 33.4%. These research results are expected to be beneficial for the preparation of development plans and the optimization of water control measures for WDGRs.

Factors and potential treatments of cough after pulmonary resection: A systematic review.

Cough is a common complication following pulmonary resection. Persistent and severe cough after pulmonary resection can cause significant impairments in quality of life among postoperative patients. Complications of cough can be life-threatening. To improve patients' probability and quality of life, factors that induce cough after pulmonary resection (CAP) and potential treatments should be explored and summarized. Previous studies have identified various factors related to CAP. However, those factors have not been categorized and analyzed in a sensible manner. Here, we summarized the different factors and classified them into four groups. Potential therapies might be developed to selectively target different factors that affect CAP. However, the exact mechanism underlying CAP remains unknown, making it difficult to treat and manage CAP. In this review, we summarized the latest studies in our understanding of the factors related to CAP and potential treatments targeting those factors. This review can help understand the mechanism of CAP and develop efficient therapies and management.

CCL13 is upregulated in alopecia areata lesions and is correlated with disease severity.

Alopecia areata (AA) is a multi-factors disease characterized by non-scarring hair loss. AA could be classified into three main clinical phenotypes including patchy type AA (AAP), alopecia totalis (AT) and alopecia universalis (AU) based on the severity and areas of hair loss. Recent studies suggested immunological factor was critical in AA, but the precise aetiology and pathogenesis of AA still need exploration. In the work, we screened two gene expression profiles (GSE45512 and GSE68801) from Gene Expression Omnibus (GEO). Based on the two data sets, 10 upregulated genes and 107 downregulated genes in AA skin biopsies were identified. CCL13, as one of the remarkably upregulated genes, was found to have potential biological functions in aberrant immune response of AA according to the GO and KEGG analyses. The PPI network showed CCL13 was associated with multiple immune-related genes. The expression of CCL13 was increased depending on the severity of disease in AA patients. Cytotoxic lymphocytes, T cells and myeloid dendritic cells accumulated remarkably in scalp tissue depending on the severity of AA, and CCL13 was significantly correlated to cytotoxic lymphocytes, T cells and myeloid dendritic cells in AA patients. Our RT-PCR and ELISA results found CCL13 was upregulated in skin biopsy and serum of AA patients, and the immunohistochemistry (IHC) detection showed CCL13 was expressed by both the hair follicle epithelium and infiltrating immune cells. In conclusion, the upregulated of CCL13 and subsequent immune cell infiltration was related to AA, which could be a promising target for diagnosis and therapy in AA patients.

CHIP-mediated CIB1 ubiquitination regulated epithelial-mesenchymal transition and tumor metastasis in lung adenocarcinoma.

CIB1 is a homolog of calmodulin that regulates cell adhesion, migration, and differentiation. It has been considered as an oncogene in many tumor cells; however, its role in lung adenocarcinoma (LAC) has not been studied. In this study, the expression levels of CIB1 in LAC tissues and adjacent normal tissues were examined by immunohistochemistry, and the relationship between CIB1 expression and patient clinicopathological characteristics was analyzed. The effects of CIB1 on epithelial-mesenchymal transition (EMT), migration, and metastasis of LAC cells were determined in vitro and vivo. Proteins interacting with CIB1 were identified using electrospray mass spectrometry (LS-MS), and CHIP was selected in the following assays. Carboxyl-terminus of Hsp70-interacting protein (CHIP) is a ubiquitin E3 ligase. We show that CHIP can degrade CIB1 via promoting polyubiquitination of CIB1 and its subsequent proteasomal degradation. Besides, lysine residue 10 and 65 of CIB1 is the ubiquitinated site of CIB1. Furthermore, CHIP-mediated CIB1 downregulation is critical for the suppression of metastasis and migration of LAC. These results indicated that CHIP-mediated CIB1 ubiquitination could regulate epithelial-mesenchymal and tumor metastasis in LAC.