Recovery of organic matters by activated sludge from municipal wastewater: Performance and characterization.

Municipal wastewater treatment processes consume a significant amount of energy and generate substantial carbon emissions. However, organic matters existing in municipal wastewater hold the potential as a valuable carbon source. Activated sludge has the potential to capture and recover the organic matters, thereby enriching carbon sources and facilitating subsequent sludge anaerobic digestion as well as in line with the concept of sustainable development. Based on above, this study investigated the enrichment and recovery characteristics and mechanisms of activated sludge adsorption on carbon sources in municipal wastewater, while optimizing the recovery conditions. The results indicated that insoluble organic matters, as well as a fraction of dissolved organic matters, can be effective recovered within approximately 40 min. Specifically, 74.1% of insoluble organic matters and 25.8% of soluble organic matters were successfully captured by the activated sludge, resulting in a 5.0% increase in sludge organic matter content. Moreover, activated sludge demonstrated remarkable recovery of particulate organic matters across various particle sizes, particularly larger particles (>5 µm) with high protein content. Notably, the dissolved biodegradable organics such as tryptophan and tyrosine protein-like substances according to 3D-EEM and lipids, proteins/amino sugars, and carbohydrates according to FT-ICR MS can be effectively recovered. Finally, the study revealed that the recovery of organic matters from the wastewater by activated sludge followed the pseudo-second-order kinetics model, with surface binding, hydrogen bonding and interparticle diffusion in sludge flocs as the primary adsorption mechanisms. This approach had abroad application prospects for improving the profitability of wastewater treatment plants.

Concurrent inhibition of ALK and SRC kinases disrupts the ALK lung tumor cell proteome.

Precision oncology has revolutionized the treatment of ALK-positive lung cancer with targeted therapies. However, an unmet clinical need still to address is the treatment of refractory tumors that contain drug-induced resistant mutations in the driver oncogene or exhibit resistance through the activation of diverse mechanisms. In this study, we established mouse tumor-derived cell models representing the two most prevalent EML4-ALK variants in human lung adenocarcinomas and characterized their proteomic profiles to gain insights into the underlying resistance mechanisms. We showed that Eml4-Alk variant 3 confers a worse response to ALK inhibitors, suggesting its role in promoting resistance to targeted therapy. In addition, proteomic analysis of brigatinib-treated cells revealed the upregulation of SRC kinase, a protein frequently activated in cancer. Co-targeting of ALK and SRC showed remarkable inhibitory effects in both ALK-driven murine and ALK-patient-derived lung tumor cells. This combination induced cell death through a multifaceted mechanism characterized by profound perturbation of the (phospho)proteomic landscape and a synergistic suppressive effect on the mTOR pathway. Our study demonstrates that the simultaneous inhibition of ALK and SRC can potentially overcome resistance mechanisms and enhance clinical outcomes in ALK-positive lung cancer patients. ONE SENTENCE SUMMARY: Co-targeting ALK and SRC enhances ALK inhibitor response in lung cancer by affecting the proteomic profile, offering hope for overcoming resistance and improving clinical outcomes.

Mechanisms of transcranial direct current stimulation (tDCS) for pain in patients with fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) is a recurrent pain condition that can be challenging to treat. Transcranial direct current stimulation (tDCS) has become a promising non-invasive therapeutic option in alleviating FMS pain, but the mechanisms underlying its effectiveness are not yet fully understood. In this article, we discuss the most current research investigating the analgesic effects of tDCS on FMS and discuss the potential mechanisms. TDCS may exert its analgesic effects by influencing neuronal activity in the brain, altering cortical excitability, changing regional cerebral blood flow, modulating neurotransmission and neuroinflammation, and inducing neuroplasticity. Overall, evidence points to tDCS as a potentially safe and efficient pain relief choice for FMS by multiple underlying mechanisms. This article provides a thorough overview of our ongoing knowledge regarding the mechanisms underlying tDCS and emphasizes the possibility of further studies to improve the clinical utility of tDCS as a pain management tool.

PRMT1 Inhibition Activates the Interferon Pathway to Potentiate Antitumor Immunity and Enhance Checkpoint Blockade Efficacy in Melanoma.

Despite the immense success of immune checkpoint blockade (ICB) in cancer treatment, many tumors, including melanoma, exhibit innate or adaptive resistance. Tumor-intrinsic T-cell deficiency and T-cell dysfunction have been identified as essential factors in the emergence of ICB resistance. Here, we found that protein arginine methyltransferase 1 (PRMT1) expression was inversely correlated with the number and activity of CD8+ T cells within melanoma specimen. PRMT1 deficiency or inhibition with DCPT1061 significantly restrained refractory melanoma growth and increased intratumoral CD8+ T cells in vivo. Moreover, PRMT1 deletion in melanoma cells facilitated formation of double-stranded RNA derived from endogenous retroviral elements (ERV) and stimulated an intracellular interferon response. Mechanistically, PRMT1 deficiency repressed the expression of DNA methyltransferase 1 (DNMT1) by attenuating modification of H4R3me2a and H3K27ac at enhancer regions of Dnmt1, and DNMT1 downregulation consequently activated ERV transcription and the interferon signaling. Importantly, PRMT1 inhibition with DCPT1061 synergized with PD-1 blockade to suppress tumor progression and increase the proportion of CD8+ T cells as well as IFNγ+CD8+ T cells in vivo. Together, these results reveal an unrecognized role and mechanism of PRMT1 in regulating antitumor T-cell immunity, suggesting PRMT1 inhibition as a potent strategy to increase the efficacy of ICB. SIGNIFICANCE: Targeting PRMT1 stimulates interferon signaling by increasing expression of endogenous retroviral elements and double-stranded RNA through repression of DNMT1, which induces antitumor immunity and synergizes with immunotherapy to suppress tumor progression.

BCL3 rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases.

The t(14;19)(q32;q13) often juxtaposes BCL3 with immunoglobulin heavy chain (IGH) resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3 rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5' (n=9) and 3' (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5' breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3' breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in chronic lymphocytic leukemia (CLL) but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter four tumors transformed to a large B-cell lymphoma. We designed a novel fluorescence in situ hybridization assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively.

The changing career paths of PhDs and postdocs trained at EMBL.

Individuals with PhDs and postdoctoral experience in the life sciences can pursue a variety of career paths. Many PhD students and postdocs aspire to a permanent research position at a university or research institute, but competition for such positions has increased. Here, we report a time-resolved analysis of the career paths of 2284 researchers who completed a PhD or a postdoc at the European Molecular Biology Laboratory (EMBL) between 1997 and 2020. The most prevalent career outcome was Academia: Principal Investigator (636/2284=27.8% of alumni), followed by Academia: Other (16.8%), Science-related Non-research (15.3%), Industry Research (14.5%), Academia: Postdoc (10.7%) and Non-science-related (4%); we were unable to determine the career path of the remaining 10.9% of alumni. While positions in Academia (Principal Investigator, Postdoc and Other) remained the most common destination for more recent alumni, entry into Science-related Non-research, Industry Research and Non-science-related positions has increased over time, and entry into Academia: Principal Investigator positions has decreased. Our analysis also reveals information on a number of factors - including publication records - that correlate with the career paths followed by researchers.

Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective non-interventional SMARTrial.

Ex vivo drug response profiling is a powerful tool to study genotype-drug response associations and is being explored as a tool set for precision medicine in cancer. Here we conducted a prospective non-interventional trial to investigate feasibility of ex vivo drug response profiling for treatment guidance in hematologic malignancies (SMARTrial, NCT03488641 ). The primary endpoint to provide drug response profiling reports within 7 d was met in 91% of all study participants (N = 80). Secondary endpoint analysis revealed that ex vivo resistance to chemotherapeutic drugs predicted chemotherapy treatment failure in vivo. We confirmed the predictive value of ex vivo response to chemotherapy in a validation cohort of 95 individuals with acute myeloid leukemia treated with daunorubicin and cytarabine. Ex vivo drug response profiles improved ELN-22 risk stratification in individuals with adverse risk. We conclude that ex vivo drug response profiling is clinically feasible and has the potential to predict chemotherapy response in individuals with hematologic malignancies beyond clinically established genetic markers.

Negative feedback regulation of MAPK signaling is an important driver of chronic lymphocytic leukemia progression.

Despite available targeted treatments for the disease, drug-resistant chronic lymphocytic leukemia (CLL) poses a clinical challenge. The objective of this study is to examine whether the dual-specific phosphatases DUSP1 and DUSP6 are required to negatively regulate mitogen-activated protein kinases (MAPKs) and thus counterbalance excessive MAPK activity. We show that high expression of DUSP6 in CLL correlates with poor clinical prognosis. Importantly, genetic deletion of the inhibitory phosphatase DUSP1 or DUSP6 and blocking DUSP1/6 function using a small-molecule inhibitor reduces CLL cell survival in vitro and in vivo. Using global phospho-proteome approaches, we observe acute activation of MAPK signaling by DUSP1/6 inhibition. This promotes accumulation of mitochondrial reactive oxygen species and, thereby, DNA damage and apoptotic cell death in CLL cells. Finally, we observe that DUSP1/6 inhibition is particularly effective against treatment-resistant CLL and therefore suggest transient DUSP1/6 inhibition as a promising treatment concept to eliminate drug-resistant CLL cells.

Comparing the value of mono- vs coculture for high-throughput compound screening in hematological malignancies.

Large-scale compound screens are a powerful model system for understanding variability of treatment response and discovering druggable tumor vulnerabilities of hematological malignancies. However, as mostly performed in a monoculture of tumor cells, these assays disregard modulatory effects of the in vivo microenvironment. It is an open question whether and to what extent coculture with bone marrow stromal cells could improve the biological relevance of drug testing assays over monoculture. Here, we established a high-throughput platform to measure ex vivo sensitivity of 108 primary blood cancer samples to 50 drugs in monoculture and coculture with bone marrow stromal cells. Stromal coculture conferred resistance to 52% of compounds in chronic lymphocytic leukemia (CLL) and 36% of compounds in acute myeloid leukemia (AML), including chemotherapeutics, B-cell receptor inhibitors, proteasome inhibitors, and Bromodomain and extraterminal domain inhibitors. Only the JAK inhibitors ruxolitinib and tofacitinib exhibited increased efficacy in AML and CLL stromal coculture. We further confirmed the importance of JAK-STAT signaling for stroma-mediated resistance by showing that stromal cells induce phosphorylation of STAT3 in CLL cells. We genetically characterized the 108 cancer samples and found that drug-gene associations strongly correlated between monoculture and coculture. However, effect sizes were lower in coculture, with more drug-gene associations detected in monoculture than in coculture. Our results justify a 2-step strategy for drug perturbation testing, with large-scale screening performed in monoculture, followed by focused evaluation of potential stroma-mediated resistances in coculture.

Subgroup-specific gene expression profiles and mixed epistasis in chronic lymphocytic leukemia.

Understanding the molecular and phenotypic heterogeneity of cancer is a prerequisite for effective treatment. For chronic lymphocytic leukemia (CLL), recurrent genetic driver events have been extensively cataloged, but this does not suffice to explain the disease's diverse course. Here, we performed RNA sequencing on 184 CLL patient samples. Unsupervised analysis revealed two major, orthogonal axes of gene expression variation: the first one represented the mutational status of the immunoglobulin heavy variable (IGHV) genes, and concomitantly, the three-group stratification of CLL by global DNA methylation. The second axis aligned with trisomy 12 status and affected chemokine, MAPK and mTOR signaling. We discovered non-additive effects (epistasis) of IGHV mutation status and trisomy 12 on multiple phenotypes, including the expression of 893 genes. Multiple types of epistasis were observed, including synergy, buffering, suppression and inversion, suggesting that molecular understanding of disease heterogeneity requires studying such genetic events not only individually but in combination. We detected strong differentially expressed gene signatures associated with major gene mutations and copy number aberrations including SF3B1, BRAF and TP53, as well as del(17)(p13), del(13)(q14) and del(11)(q22.3) beyond dosage effect. Our study reveals previously underappreciated gene expression signatures for the major molecular subtypes in CLL and the presence of epistasis between them.

Trends of the Global Burden of Disease Attributable to Cannabis Use Disorder in 204 Countries and Territories, 1990-2019: Results from the Disease Burden Study 2019.

Cannabis is the fourth psychoactive substance to be legalized which are of far-reaching significance to the world. We analyzed data from the 2019 Global Burden of Disease Study (GBD) to estimate the incidence and prevalence of cannabis use disorder (CUD) and calculated the disease burden of CUD in 204 countries and territories and 21 regions over the past three decades. We reported disease burden due to CUD in terms of disability-adjusted life years (DALYs), age-standardized rate (ASR), estimated annual percentage change (EAPC), and analyzed associations between the burden of CUD and sociodemographic index (SDI) quintiles. Globally, the number of incidence cases of CUD was estimated to be increasing by 32.3% from 1990 to 2019 and males are nearly double higher than that of female. DALYs increase 38.6% from 1990. Young people aged 20-24 years old with cannabis use disorder have the highest DALYs in 2019, followed by those younger than 20 years old. India, Canada, USA, Qatar, Kenya, and high SDI quintile areas showed a high burden of disease. Nearly 200 million individuals are cannabis users worldwide, and CUD is a notable condition of GBD. The global cultivation of cannabis, rooted in different cultures, diversified access to cannabis, legalization in controversy, the promotion of medical cannabis, and many other factors promote the global cannabis industry is constantly updated and upgraded. It deserves more discussion in the future in terms of pathophysiological mechanisms, socioeconomics, law, and policy improvement. Supplementary Information: The online version contains supplementary material available at 10.1007/s11469-022-00999-4.

Association between triglyceride-glucose index and worsening renal function in the elderly.

Background: Triglyceride-glucose (TyG) index is a simple marker of insulin resistance. However, insufficient data is available on whether the TyG index is associated with worsening renal function (WRF) in the elderly. Therefore, this study was designed to explore the association between the TyG index and WRF based on a community elderly cohort. Methods: In this study, 7,822 elderly (aged ≥ 65 years) adults from southern China were enrolled and divided into four groups according to the TyG index quartiles. The primary endpoint was incident chronic kidney disease (CKD), defined as incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Additional endpoints included a decline in eGFR of 30% and 40% during the follow-up period. Results: During the median 2.04 year follow-up period, 1,541 (19.7%) participants developed CKD. After adjusting for confounding factors, multivariable Cox regression models revealed significant associations between TyG index and incident CKD (HR per SD increase, 1.21; 95% CI: 1.14-1.29), a decline in eGFR of 30% (HR per SD increase, 1.38; 95% CI: 1.26-1.50), and decline in eGFR of 40% (HR per SD increase, 1.42; 95% CI: 1.24-1.63). Furthermore, compared with those in Q1, participants in Q4 demonstrated a higher risk of developing CKD (HR, 1.59; 95% CI: 1.35-1.88). These positive associations remained consistent across different subgroup populations. Conclusion: Our study suggests a positive and independent association between the TyG index and WRF in the elderly.

Proteogenomics refines the molecular classification of chronic lymphocytic leukemia.

Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond the currently established genomic and transcriptomic-based diagnostics. The relevance of proteomics for disease classifications remains to be established in clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterize the proteome and transcriptome alongside genetic and ex-vivo drug response profiling in a clinically annotated CLL discovery cohort (n = 68). Unsupervised clustering of the proteome data reveals six subgroups. Five of these proteomic groups are associated with genetic features, while one group is only detectable at the proteome level. This new group is characterized by accelerated disease progression, high spliceosomal protein abundances associated with aberrant splicing, and low B cell receptor signaling protein abundances (ASB-CLL). Classifiers developed to identify ASB-CLL based on its characteristic proteome or splicing signature in two independent cohorts (n = 165, n = 169) confirm that ASB-CLL comprises about 20% of CLL patients. The inferior overall survival in ASB-CLL is also independent of both TP53- and IGHV mutation status. Our multi-omics analysis refines the classification of CLL and highlights the potential of proteomics to improve cancer patient stratification beyond genetic and transcriptomic profiling.

Viral transduction of primary human lymphoma B cells reveals mechanisms of NOTCH-mediated immune escape.

Hotspot mutations in the PEST-domain of NOTCH1 and NOTCH2 are recurrently identified in B cell malignancies. To address how NOTCH-mutations contribute to a dismal prognosis, we have generated isogenic primary human tumor cells from patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), differing only in their expression of the intracellular domain (ICD) of NOTCH1 or NOTCH2. Our data demonstrate that both NOTCH-paralogs facilitate immune-escape of malignant B cells by up-regulating PD-L1, partly dependent on autocrine interferon-γ signaling. In addition, NOTCH-activation causes silencing of the entire HLA-class II locus via epigenetic regulation of the transcriptional co-activator CIITA. Notably, while NOTCH1 and NOTCH2 govern similar transcriptional programs, disease-specific differences in their expression levels can favor paralog-specific selection. Importantly, NOTCH-ICD also strongly down-regulates the expression of CD19, possibly limiting the effectiveness of immune-therapies. These NOTCH-mediated immune escape mechanisms are associated with the expansion of exhausted CD8+ T cells in vivo.

A gene expression assay based on chronic lymphocytic leukemia activation in the microenvironment to predict progression.

Several gene expression profiles with a strong correlation with patient outcomes have been previously described in chronic lymphocytic leukemia (CLL), although their applicability as biomarkers in clinical practice has been particularly limited. Here we describe the training and validation of a gene expression signature for predicting early progression in patients with CLL based on the analysis of 200 genes related to microenvironment signaling on the NanoString platform. In the training cohort (n = 154), the CLL15 assay containing a 15-gene signature was associated with the time to first treatment (TtFT) (hazard ratio [HR], 2.83; 95% CI, 2.17-3.68; P < .001). The prognostic value of the CLL15 score (HR, 1.71; 95% CI, 1.15-2.52; P = .007) was further confirmed in an external independent validation cohort (n = 112). Notably, the CLL15 score improved the prognostic capacity over IGHV mutational status and the International Prognostic Score for asymptomatic early-stage (IPS-E) CLL. In multivariate analysis, the CLL15 score (HR, 1.83; 95% CI, 1.32-2.56; P < .001) and the IPS-E CLL (HR, 2.23; 95% CI, 1.59-3.12; P < .001) were independently associated with TtFT. The newly developed and validated CLL15 assay successfully translated previous gene signatures such as the microenvironment signaling into a new gene expression-based assay with prognostic implications in CLL.

Drug-microenvironment perturbations reveal resistance mechanisms and prognostic subgroups in CLL.

The tumour microenvironment and genetic alterations collectively influence drug efficacy in cancer, but current evidence is limited and systematic analyses are lacking. Using chronic lymphocytic leukaemia (CLL) as a model disease, we investigated the influence of 17 microenvironmental stimuli on 12 drugs in 192 genetically characterised patient samples. Based on microenvironmental response, we identified four subgroups with distinct clinical outcomes beyond known prognostic markers. Response to multiple microenvironmental stimuli was amplified in trisomy 12 samples. Trisomy 12 was associated with a distinct epigenetic signature. Bromodomain inhibition reversed this epigenetic profile and could be used to target microenvironmental signalling in trisomy 12 CLL. We quantified the impact of microenvironmental stimuli on drug response and their dependence on genetic alterations, identifying interleukin 4 (IL4) and Toll-like receptor (TLR) stimulation as the strongest actuators of drug resistance. IL4 and TLR signalling activity was increased in CLL-infiltrated lymph nodes compared with healthy samples. High IL4 activity correlated with faster disease progression. The publicly available dataset can facilitate the investigation of cell-extrinsic mechanisms of drug resistance and disease progression.

Inferring tumor-specific cancer dependencies through integrating ex vivo drug response assays and drug-protein profiling.

The development of cancer therapies may be improved by the discovery of tumor-specific molecular dependencies. The requisite tools include genetic and chemical perturbations, each with its strengths and limitations. Chemical perturbations can be readily applied to primary cancer samples at large scale, but mechanistic understanding of hits and further pharmaceutical development is often complicated by the fact that a chemical compound has affinities to multiple proteins. To computationally infer specific molecular dependencies of individual cancers from their ex vivo drug sensitivity profiles, we developed a mathematical model that deconvolutes these data using measurements of protein-drug affinity profiles. Through integrating a drug-kinase profiling dataset and several drug response datasets, our method, DepInfeR, correctly identified known protein kinase dependencies, including the EGFR dependence of HER2+ breast cancer cell lines, the FLT3 dependence of acute myeloid leukemia (AML) with FLT3-ITD mutations and the differential dependencies on the B-cell receptor pathway in the two major subtypes of chronic lymphocytic leukemia (CLL). Furthermore, our method uncovered new subgroup-specific dependencies, including a previously unreported dependence of high-risk CLL on Checkpoint kinase 1 (CHEK1). The method also produced a detailed map of the kinase dependencies in a heterogeneous set of 117 CLL samples. The ability to deconvolute polypharmacological phenotypes into underlying causal molecular dependencies should increase the utility of high-throughput drug response assays for functional precision oncology.

The Association Between the Frequency of Annual Health Checks Participation and the Control of Cardiovascular Risk Factors.

Background: General health checks can help in controlling cardiovascular risk factors. However, few studies have investigated whether regular participation in annual health checks could further improve the control of cardiovascular risk factors compared with intermittent participation. Therefore, our study aimed to explore the association between the frequency of annual health check participation and the control of cardiovascular risk factors. Methods: Residents aged ≥ 65 years or having chronic diseases (hypertension or diabetes) from 37 communities of Guangzhou, Guangdong, who participated in the Basic Public Health Service project between January 2015 and December 2019, were enrolled and divided into 3 groups ("Sometimes," "Usually," and "Always") according to their frequencies of annual health check participation. Multivariable linear regression models were performed to assess the association between the frequency of annual health check participation and the control of cardiovascular risk factors. A subgroup analysis stratified by gender was also conducted. Results: In total, 9,102 participants were finally included. Significant differences were identified between groups in systolic blood pressure (SBP), diastolic blood pressure (DBP), weight, fasting glucose, total cholesterol, high-density lipoprotein cholesterol, and serum creatinine. After fully adjusting for confounding factors, residents who always participated in the annual health check tended to have lower SBP (ß = -4.36, 95% CI: -5.46; -3.26, p < 0.001), fasting glucose (ß = -0.27, 95% CI: -0.38; -0.15, p < 0.001), and total cholesterol (ß = -0.19, 95% CI: -0.26; -0.13, p < 0.001), compared with those who attended sometimes. Furthermore, gender did not alter these associations. Conclusion: A higher frequency of annual health check participation was associated with lower SBP, fasting glucose, and total cholesterol.

Immunoprognostic model of lung adenocarcinoma and screening of sensitive drugs.

Screening of mRNAs and lncRNAs associated with prognosis and immunity of lung adenocarcinoma (LUAD) and used to construct a prognostic risk scoring model (PRS-model) for LUAD. To analyze the differences in tumor immune microenvironment between distinct risk groups of LUAD based on the model classification. The CMap database was also used to screen potential therapeutic compounds for LUAD based on the differential genes between distinct risk groups. he data from the Cancer Genome Atlas (TCGA) database. We divided the transcriptome data into a mRNA subset and a lncRNA subset, and use multiple methods to extract mRNAs and lncRNAs associated with immunity and prognosis. We further integrated the mRNA and lncRNA subsets and the corresponding clinical information, randomly divided them into training and test set according to the ratio of 5:5. Then, we performed the Cox risk proportional analysis and cross-validation on the training set to construct a LUAD risk scoring model. Based on the risk scoring model, patients were divided into distinct risk group. Moreover, we evaluate the prognostic performance of the model from the aspects of Area Under Curve (AUC) analysis, survival difference analysis, and independent prognostic analysis. We analyzed the differences in the expression of immune cells between the distinct risk groups, and also discuss the connection between immune cells and patient survival. Finally, we screened the potential therapeutic compounds of LUAD in the Connectivity Map (CMap) database based on differential gene expression profiles, and verified the compound activity by cytostatic assays. We extracted 26 mRNAs and 74 lncRNAs related to prognosis and immunity by using different screening methods. Two mRNAs (i.e., KLRC3 and RAET1E) and two lncRNAs (i.e., AL590226.1 and LINC00941) and their risk coefficients were finally used to construct the PRS-model. The risk score positions of the training and test set were 1.01056590 and 1.00925190, respectively. The expression of mRNAs involved in model construction differed significantly between the distinct risk population. The one-year ROC areas on the training and test sets were 0.735 and 0.681. There was a significant difference in the survival rate of the two groups of patients. The PRS-model had independent predictive capabilities in both training and test sets. Among them, in the group with low expression of M1 macrophages and resting NK cells, LUAD patients survived longer. In contrast, the monocyte expression up-regulated group survived longer. In the CMap drug screening, three LUAD therapeutic compounds, such as resveratrol, methotrexate, and phenoxybenzamine, scored the highest. In addition, these compounds had significant inhibitory effects on the LUAD A549 cell lines. The LUAD risk score model constructed using the expression of KLRC3, RAET1E, AL590226.1, LINC00941 and their risk coefficients had a good independent prognostic power. The optimal LUAD therapeutic compounds screened in the CMap database: resveratrol, methotrexate and phenoxybenzamine, all showed significant inhibitory effects on LUAD A549 cell lines.