Chemical short-range disorder in lithium oxide cathodes.

Ordered layered structures serve as essential components in lithium (Li)-ion cathodes1-3. However, on charging, the inherently delicate Li-deficient frameworks become vulnerable to lattice strain and structural and/or chemo-mechanical degradation, resulting in rapid capacity deterioration and thus short battery life2,4. Here we report an approach that addresses these issues using the integration of chemical short-range disorder (CSRD) into oxide cathodes, which involves the localized distribution of elements in a crystalline lattice over spatial dimensions, spanning a few nearest-neighbour spacings. This is guided by fundamental principles of structural chemistry and achieved through an improved ceramic synthesis process. To demonstrate its viability, we showcase how the introduction of CSRD substantially affects the crystal structure of layered Li cobalt oxide cathodes. This is manifested in the transition metal environment and its interactions with oxygen, effectively preventing detrimental sliding of crystal slabs and structural deterioration during Li removal. Meanwhile, it affects the electronic structure, leading to improved electronic conductivity. These attributes are highly beneficial for Li-ion storage capabilities, markedly improving cycle life and rate capability. Moreover, we find that CSRD can be introduced in additional layered oxide materials through improved chemical co-doping, further illustrating its potential to enhance structural and electrochemical stability. These findings open up new avenues for the design of oxide cathodes, offering insights into the effects of CSRD on the crystal and electronic structure of advanced functional materials.

Construction of a Diagnostic Model for Small Cell Lung Cancer Combining Metabolomics and Integrated Machine Learning.

BACKGROUND: To date, no study has systematically explored the potential role of serum metabolites and lipids in the diagnosis of small cell lung cancer (SCLC). Therefore, we aimed to conduct a case-cohort study that included 191 cases of SCLC, 91 patients with lung adenocarcinoma, 82 patients with squamous cell carcinoma, and 97 healthy controls. METHODS: Metabolomics and lipidomics were applied to analyze different metabolites and lipids in the serum of these patients. The SCLC diagnosis model (d-model) was constructed using an integrated machine learning technology and a training cohort (n = 323) and was validated in a testing cohort (n=138). RESULTS: Eight metabolites, including 1-mristoyl-sn-glycero-3-phosphocholine, 16b-hydroxyestradiol, 3-phosphoserine, cholesteryl sulfate, D-lyxose, dioctyl phthalate, DL-lactate and Leu-Phe, were successfully selected to distinguish SCLC from controls. The d-model was constructed based on these 8 metabolites and showed improved diagnostic performance for SCLC, with the area under curve (AUC) of 0.933 in the training cohort and 0.922 in the testing cohort. Importantly, the d-model still had an excellent diagnostic performance after adjusting the stage and related clinical variables and, combined with the progastrin-releasing peptide (ProGRP), showed the best diagnostic performance with 0.975 of AUC for limited-stage patients. CONCLUSION: This study is the first to analyze the difference between metabolomics and lipidomics and to construct a d-model to detect SCLC using integrated machine learning. This study may be of great significance for the screening and early diagnosis of SCLC patients.

Antitumor activity of dictamnine against colorectal cancer through induction of ferroptosis and inhibition of M2 macrophage polarization via the MAPK signaling.

Colorectal cancer (CRC) is an aggressive cancer type globally. Surgery and chemotherapy are often ineffective at curing CRC. Dictamnine is a natural product derived from Dictamnus dasycarpus Turcz. root bark and possesses multi-pharmacological properties, including anticancer effects. Nevertheless, the biological roles and the possible mechanism of dictamnine in CRC are still unclear. Here, we demonstrated that dictamnine blocked cell viability and proliferation in DLD-1 human colorectal adenocarcinoma cells and LoVo human colon cancer cells. Dictamnine triggered CRC cell ferroptosis, as evidenced by enhanced levels of reactive oxygen species, malondialdehyde, and Fe2+ levels, alongside downregulation of glutathione peroxidase 4 protein expression. In addition, CD163 (HPA ID: HPA046404) was highly expressed and CD68 (HPA ID: CAB000051) was lowly expressed in CRC tissues and CRC cell culture medium-cultured THP-1 monocytes-derived macrophages. The patients with CD163 low-expression lived much longer than those with CD163 high-expression, indicating that M2 polarization of macrophages was related to poor prognosis of CRC. Dictamnine markedly inhibited CD163 protein expression, transforming growth factor-ß and arginase 1 mRNA expressions and IL-10 production in macrophages with CRC cell co-culture, suggesting that dictamnine impeded M2 polarization of macrophages. Mechanistically, dictamnine repressed ERK phosphorylation in CRC cells. The treatment with the ERK activator tBHQ counteracted the effects of dictamnine on CRC cell proliferation and ferroptosis, as well as its inhibitory effect on M2 polarization of macrophages. Results of a xenograft model showed that dictamnine effectively hindered CRC tumor growth in vivo. Collectively, these data provide evidence for the clinical trials of dictamnine as a novel drug for CRC therapy.

Molecular subtyping of small-cell lung cancer based on mutational signatures with different genomic features and therapeutic strategies.

Small-cell lung cancer (SCLC) is an exceptionally lethal malignancy characterized by extremely high alteration rates and tumor heterogeneity, which limits therapeutic options. In contrast to non-small-cell lung cancer that develops rapidly with precision oncology, SCLC still remains outside the realm of precision medicine. No recurrent and actionable mutations have been detected. Additionally, a paucity of substantive tumor specimens has made it even more difficult to classify SCLC subtypes based on genetic background. We therefore carried out whole-exome sequencing (WES) on the largest available Chinese SCLC cohort. For the first time, we partitioned SCLC patients into three clusters with different genomic alteration profiles and clinical features based on their mutational signatures. We showed that these clusters presented differences in intratumor heterogeneity and genome instability. Moreover, a wide existence of mutually exclusive gene alterations, typically within similar biological functions, was detected and suggested a high SCLC intertumoral heterogeneity. Particularly, Cluster 1 presented the greatest potential to benefit from immunotherapy, and Cluster 3 constituted recalcitrant SCLC, warranting biomarker-directed drug development and targeted therapies in clinical trials. Our study would provide an in-depth insight into the genome characteristics of the Chinese SCLC cohort, defining distinct molecular subtypes as well as subtype-specific therapies and biomarkers. We propose tailoring differentiated therapies for distinct molecular subgroups, centering on a personalized precision chemotherapy strategy combined with immunization or targeted therapy for patients with SCLC.

Tumor immune microenvironment predicts the pathologic response of neoadjuvant chemoimmunotherapy in non-small-cell lung cancer.

The clinical outcome of resectable non-small-cell lung cancer (NSCLC) patients receiving neoadjuvant chemoimmunotherapy is good but varies greatly. In addition, the pathological response after neoadjuvant chemoimmunotherapy is significantly associated with survival outcomes. The aim of this retrospective study was to identify which population of patients with locally advanced and oligometastatic NSCLC has a favorable pathological response after neoadjuvant chemoimmunotherapy. NSCLC patients treated with neoadjuvant chemoimmunotherapy were enrolled between February 2018 and April 2022. Data on clinicopathological features were collected and evaluated. Multiplex immunofluorescence was performed on pre-treatment puncture specimens and surgically resected specimens. In total, 29 patients with stages III and IV locally advanced or oligometastatic NSCLC who received neoadjuvant chemoimmunotherapy and R0 resection were enrolled. The results showed that 55% (16/29) of patients had a major pathological response (MPR) and 41% (12/29) of patients had a complete pathological response (pCR). In the stroma area of the pre-treatment specimen, the higher infiltration of CD3+ PD-L1+ tumor-infiltrating lymphocytes (TILs) and the lower infiltration of CD4+ and CD4+ FOXP3+ TILs were more likely to appear in patients with pCR. However, in the tumor area, the higher infiltration of CD8+ TILs was more likely to appear in patients with non-MPR. In the post-treatment specimen, we found increased infiltration of CD3+ CD8+ , CD8+ GZMB+ , and CD8+ CD69+ TILs and decreased infiltration of PD-1+ TILs both in the stroma and tumor areas. Neoadjuvant chemoimmunotherapy achieved an MPR rate of 55% and induced greater immune infiltration. In addition, we observed that the baseline TILs and their spatial distribution correlate to the pathological response.

Outcome and Cost-Effectiveness Analysis of Long-acting G-CSF as Primary Prophylaxis of Neutropenia Induced by Chemotherapy in Breast Cancer Patients, From a Retrospective Study.

PURPOSE: This retrospective analysis aimed to evaluate the clinical outcomes and cost-effectiveness of long-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia caused by chemotherapy for breast cancer. METHODS: Patients with breast cancer who received long- or short-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia were enrolled in this study, and incidences of neutropenia were compared between two groups. A decision-analytic and a Markov model were used to compare the health benefits and costs of utilizing long- vs short-acting granulocyte-colony stimulating factor as the primary prophylaxis from the perspective of the Chinese health service system. Subsequently, one-way deterministic and probabilistic sensitivity analyses were conducted. The incremental cost-effectiveness ratios were calculated in baseline and sensitivity analyses. RESULTS: Patients receiving long-acting granulocyte-colony stimulating factor as the primary prophylaxis of chemotherapy-induced neutropenia experienced a significant lower incidence of this adverse event, compared with the short-acting one for 2 to 7 days. The outcomes of baseline analysis indicated that long-acting granulocyte-colony stimulating factor had a gain of 0.08 quality-adjusted life years and costed $149 more than the short-acting one, yielding an incremental cost-effectiveness ratio of $1792 per quality-adjusted life year. The sensitivity analysis proved the stability of our models and economic efficiency of long-acting granulocyte-colony stimulating factor. CONCLUSIONS: Patients receiving long-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia experienced lower risk of this event compared with those underusing short-acting one. The long-acting granulocyte-colony stimulating factor may be a more cost-effective strategy for primary prophylaxis of neutropenia than short-acting one, considering the Chinese willingness-to-pay threshold of $12158.6 per quality-adjusted life year.

Molecular epidemiology analysis of fowl adenovirus detected from apparently healthy birds in eastern China.

BACKGROUND: Fowl adenovirus is of major concern to the poultry industry worldwidely. In order to monitor the prevalent status of Fowl adenovirus in China, a total of 1920 clinical samples from apparently healthy birds in the 25 sites of poultry flocks, Slaughterhouse and living bird markets from 8 provinces in eastern China were collected and detected by PCR, sequencing, and phylogenetic analysis. RESULTS: The epidemiological survey showed that Fowl adenoviruses were detected in living bird markets, and circulating in a variety of fowl species, including chickens, ducks, goose and pigeons. Among the 1920 clinical samples, 166 samples (8.65%) were positive in the fowl adenovirus PCR detection. In this study, totally all the 12 serotypes (serotypes of 1, 2, 3, 4, 5, 6, 7, 8A, 8B, 9, 10 and 11) fowl adenoviruses were detected, the most prevalent serotype was serotype 1. Phylogenetic analysis indicated that 166 FAdVs of 12 serotypes were divided into 5 fowl adenovirus species (Fowl aviadenovirus A, B, C, D, E). CONCLUSIONS: In the epidemiological survey, 8.65% of the clinical samples from apparently healthy birds were positive in the fowl adenovirus PCR detection. Totally all the 12 serotypes fowl adenoviruses were detected in a variety of fowl species, which provided abundant resources for the research of fowl adenoviruses in China. The newly prevalent FAdV serotypes provides valuable information for the development of an effective control strategy for FAdV infections in fowls.

Using High-Entropy Configuration Strategy to Design Na-Ion Layered Oxide Cathodes with Superior Electrochemical Performance and Thermal Stability.

Na-ion layered oxide cathodes (NaxTMO2, TM = transition metal ion(s)), as an analogue of lithium layered oxide cathodes (such as LiCoO2, LiNixCoyMn1-x-yO2), have received growing attention with the development of Na-ion batteries. However, due to the larger Na+ radius and stronger Na+-Na+ electrostatic repulsion in NaO2 slabs, some undesired phase transitions are observed in NaxTMO2. Herein, we report a high-entropy configuration strategy for NaxTMO2 cathode materials, in which multicomponent TMO2 slabs with enlarged interlayer spacing help strengthen the whole skeleton structure of layered oxides through mitigating Jahn-Teller distortion, Na+/vacancy ordering, and lattice parameter changes. The strengthened skeleton structure with a modulated particle morphology dramatically improves the Na+ transport kinetics and suppresses intragranular fatigue cracks and TM dissolution, thus leading to highly improved performances. Furthermore, the elaborate high-entropy TMO2 slabs enhance the TM-O bonding energy to restrain oxygen release and thermal runaway, benefiting for the improvement of thermal safety.

Clarifying the Relationship between the Lithium Deposition Coverage and Microstructure in Lithium Metal Batteries.

Improving the reversibility of lithium metal batteries is one of the challenges in current battery research. This requires better fundamental understanding of the evolution of the lithium deposition morphology, which is very complex due to the various parameters involved in different systems. Here, we clarify the fundamental origins of lithium deposition coverage in achieving highly reversible and compact lithium deposits, providing a comprehensive picture in the relationship between the lithium microstructure and solid electrolyte interphase (SEI) for lithium metal batteries. Systematic variation of the salt concentration offers a framework that brings forward the different aspects that play a role in cycling reversibility. Higher nucleation densities are formed in lower concentration electrolytes, which have the advantage of higher lithium deposition coverage; however, it goes along with the formation of an organic-rich instable SEI which is unfavorable for the reversibility during (dis)charging. On the other hand, the growth of large deposits benefiting from the formation of an inorganic-rich stable SEI is observed in higher concentration electrolytes, but the initial small nucleation density prevents full coverage of the current collector, thus compromising the plated lithium metal density. Taking advantages of the paradox, a nanostructured substrate is rationally applied, which increases the nucleation density realizing a higher deposition coverage and thus more compact plating at intermediate concentration (∼1.0 M) electrolytes, leading to extended reversible cycling of batteries.

Determining the laser-induced release probability of a nanoparticle from a soft substrate.

This Letter presents a study of laser-induced nanoparticle release from a soft substrate in air under different conditions. A continuous wave (CW) laser heats a nanoparticle and causes a rapid thermal expansion of the substrate, which gives an upward momentum that releases the nanoparticle from the substrate. The release probability of different nanoparticles from different substrates under different laser intensities is studied. The effects of surface properties of substrates and surface charges of the nanoparticles on the release are also investigated. The mechanism of nanoparticle release demonstrated in this work is different from that of laser-induced forward transfer (LIFT). Owing to the simplicity of this technology and the wide availability of commercial nanoparticles, this nanoparticle release technology may find applications in nanoparticle characterization and nanomanufacturing.

[18F]AlF-NOTA-FAPI-04 PET/CT uptake in metastatic lesions on PET/CT imaging might distinguish different pathological types of lung cancer.

PURPOSE: Heterogeneity is found in the tumor microenvironment among different pathological types of tumors. Radionuclide-labeled fibroblast-activation-protein inhibitor (FAPI), as an important tracer for non-invasive imaging of the tumor microenvironment, can be used to evaluate the expression of FAP in cancer-associated fibroblasts, macrophages, and tumor cells. Our aim was to explore the ability of [18F]AlF-NOTA-FAPI-04 positron emission tomography (PET)/computed tomography (CT) to distinguish different types of lung cancer by evaluating the uptake of this tracer in primary and metastatic lesions. METHODS: We prospectively enrolled 61 patients with histopathologically proven primary lung cancer with metastases. PET/CT scanning was performed before any antitumor therapy and 1 h after injection of 235.10 ± 3.89 MBq of [18F]AlF-NOTA-FAPI-04. Maximum standard uptake values (SUVmax) were calculated for comparison among primary and metastatic lesions. Immunohistochemical staining for FAP was performed on tumor specimens. RESULTS: Sixty-one patients with adenocarcinoma (ADC, n = 30), squamous cell carcinoma (SCC, n = 17), and small cell lung cancer (SCLC, n = 14) were enrolled in this study, and 61 primary tumors and 199 metastases were evaluated. No difference in [18F]AlF-NOTA-FAPI-04 uptake was observed among primary ADC, SCC, and SCLC tumors (P = 0.198). Additionally, no difference in uptake was found between primary and metastatic lesions of lung cancer with the same pathological type (P > 0.05). However, uptake did differ among metastases of differing pathological types (P < 0.001). The SUVmax of metastatic lymph nodes was highest for SCC, followed by ADC and then SCLC (P < 0.001). The SUVmax of bone metastases also was highest for SCC, followed by ADC and SCLC (P < 0.05), but no difference was observed between ADC and SCLC. The SUVmax of metastases in other organs was higher in SCC cases than in ADC cases but did not differ between SCC and SCLC or ADC and SCLC. Bone metastases exhibited higher uptake than those of lymph nodes and other organs in SCC and ADC (P < 0.05) but not in SCLC. Positive correlations were found between FAPI uptake and FAP expression in surgical plus biopsy specimens (r = 0.439, P = 0.012) and surgical specimens (r = 0.938, P = 0.005). CONCLUSION: [18F]AlF-NOTA-FAPI-04 PET/CT imaging revealed differences in FAP expression in metastases of lung cancer, with the highest expression specifically in bone metastases, and thus, may be valuable for distinguishing different pathological types of lung cancer.

Reverse transcription recombinase-aided amplification assay for H5 subtype avian influenza virus.

BACKGROUND: The H5 subtype avian influenza virus (AIV) has caused huge economic losses to the poultry industry and is a threat to human health. A rapid and simple test is needed to confirm infection in suspected cases during disease outbreaks. METHODS: In this study, we developed a reverse transcription recombinase-aided amplification (RT-RAA) assay for the detection of H5 subtype AIV. Assays were performed at a single temperature (39 °C), and the results were obtained within 20 min. RESULTS: The assay showed no cross-detection with Newcastle disease virus or infectious bronchitis virus. The analytical sensitivity was 103 RNA copies/µL at a 95% confidence interval according to probit regression analysis, with 100% specificity. Compared with published reverse transcription quantitative real-time polymerase chain reaction assays, the κ value of the RT-RAA assay in 420 avian clinical samples was 0.983 (p < 0.001). The sensitivity for avian clinical sample detection was 97.26% (95% CI, 89.56-99.52%), and the specificity was 100% (95% CI, 98.64-100%). CONCLUSIONS: These results indicated that our RT-RAA assay may be a valuable tool for detecting H5 subtype AIV.

Dual mimic enzyme properties of Fe nanoparticles embedded in two-dimensional carbon nanosheets for colorimetric detection of biomolecules.

The development of novel nanozymes is of great importance for the efficient analysis of biomolecules such as H2O2, glucose, and antioxidants in the diagnosis of some diseases. Herein, novel nanozymes based on Fe nanoparticles (NPs) encapsulated in 2D carbon nanosheets (denoted as Fe@CNs) were constructed and employed in the field of biosensing. Notably, Fe@CNs have intrinsic dual mimic enzyme properties. The colorless colorimetric substrate 3,3',5,5'-tetramethylbenzidine (TMB) can be oxidized by Fe@CNs as oxidase- and peroxidase-like nanozymes, respectively. The generation of the oxidation state TMB (oxTMB) resulted from the presence of reactive oxygen species (ROS) which were produced by the catalytic decomposition of the dissolved oxygen or H2O2. Thus, a simple colorimetric biosensor was proposed to detect glutathione (GSH), H2O2, and glucose. In addition, the Fe@CN-based nanozymes also have excellent reusability in enzymatic catalysis. After separating from the sensing systems, Fe@CNs can be reused in other catalytic processes. This colorimetric method could be used as a universal sensing platform for the detection of antioxidants and H2O2-related bioanalysis. This work broadens the application of novel nanozymes in biosensing.

Heterogeneous Degradation in Thick Nickel-Rich Cathodes During High-Temperature Storage and Mitigation of Thermal Instability by Regulating Cationic Disordering.

The thermal instability is a major problem in high-energy nickel-rich layered cathode materials for large-scale battery application. Due to the scarce investigation of thick electrodes at the practical full-cell level, the understanding of thermal failure mechanism is still insufficient. Herein, an intrinsic origin of thermal instability in fully charged industrial pouch cells during high-temperature storage is discovered. Through the investigation from crystals to particles, and from electrodes to cells, it is shown that serious top-down heterogeneous degradation occurs along the depth direction of the thick electrode, including phase transition, cationic disordering, intergranular/intragranular cracks, and side reactions. Such degradation originates from the abundant oxygen vacancies and reduced catalytic Ni2+ at cathode surface, causing microstructural defects and directly leading to the thermal instability. Nonmagnetic elements doping and surface modification are suggested to be effective in mitigating the thermal instability through modulating cationic disordering.

KP-10/Gpr54 attenuates rheumatic arthritis through inactivating NF-κB and MAPK signaling in macrophages.

Rheumatoid arthritis (RA) is an autoimmune disease mainly characterized as chronic inflammation of joint. Both genetic and environmental factors play important roles in RA progression. G protein-coupled receptor 54 (GPR54) and Kisspeptins (KPs), the natural GRP54 ligands encoded by Kiss-1 gene are known to play important roles in immune regulation but the precise role of KP-10/GPR54 in RA remains elusive. Kiss1/Gpr54 expression was determined by immunohistochemistry on protein and real-time PCR on RNA from isolated RA-patient synovial tissue and PBMC. Collagen-induced arthritis (CIA) mouse models were used to investigate the effect of KP-10/Gpr54 on the rheumatic arthritis severity in the mice. The signaling pathway involved in KP-10/GPR54 was assessed by western blot and immunofluorescence.In the present study, we demonstrated that GPR54 upregulation in bone marrow-derived macrophages (BMDM) was associated with the severity of RA. In addition, Gpr54-/- increased the inflammatory cytokines induced by lipopolysaccharide (LPS) in BMDM and diseased severity of CIA (n = 10), while KP-10 reduced the LPS-induced inflammatory cytokines in vitro and ameliorated the CIA symptoms in vivo. Furthermore, we demonstrated that KP-10/GPR54 binds to PP2A-C to suppressed LPS induced NF-κB and MAPK signaling in BMDM. All these findings suggest that KP-10/GPR54 may be a novel therapeutic target for the diagnosis and treatment of RA.

Additive Opto-Thermomechanical Nanoprinting and Nanorepairing under Ambient Conditions.

We demonstrate an opto-thermomechanical (OTM) nanoprinting method that allows us not only to additively print nanostructures with sub-100 nm accuracy but also to correct printing errors for nanorepairing under ambient conditions. Different from other existing nanoprinting methods, this method works when a nanoparticle on the surface of a soft substrate is illuminated by a continuous-wave (cw) laser beam in a gaseous environment. The laser heats the nanoparticle and induces a rapid thermal expansion of the soft substrate. This thermal expansion can either release a nanoparticle from the soft surface for nanorepairing or transfer it additively to another surface in the presence of optical forces for nanoprinting with sub-100 nm accuracy. Details of the printing mechanism and parameters that affect the printing accuracy are investigated. This additive OTM nanoprinting technique paves the way for rapid and affordable additive manufacturing or 3D printing at the nanoscale under ambient conditions.

Revealing High Na-Content P2-Type Layered Oxides as Advanced Sodium-Ion Cathodes.

Layered Na-based oxides with the general composition of NaxTMO2 (TM: transition metal) have attracted significant attention for their high compositional diversity that provides tunable electrochemical performance for electrodes in sodium-ion batteries. The various compositions bring forward complex structural chemistry that is decisive for the layered stacking structure, Na-ion conductivity, and the redox activity, potentially promising new avenues in functional material properties. In this work, we have explored the maximum Na content in P2-type layered oxides and discovered that the high-content Na in the host enhances the structural stability; moreover, it promotes the oxidation of low-valent cations to their high oxidation states (in this case Ni2+). This can be rationalized by the increased hybridization of the O(2p)-TM(3d-eg*) states, affecting both the local TM environment as well as the interactions between the NaO2 and TMO2 layers. These properties are highly beneficial for the Na storage capabilities as required for cathode materials in sodium-ion batteries. It leads to excellent Na-ion mobility, a large storage capacity (>100 mAh g-1 between 2.0-4.0 V), yet preventing the detrimental sliding of the TMO2 layers (P2-O2 structural transition), as reflected by the ultralong cycle life (3000 (dis)charge cycles demonstrated). These findings expand the horizons of high Na-content P2-type materials, providing new insights of the electronic and structural chemistry for advanced cathode materials.

Correction to: microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11.

An amendment to this paper has been published and can be accessed via the original article.

CD44, a marker of cancer stem cells, is positively correlated with PD-L1 expression and immune cells infiltration in lung adenocarcinoma.

BACKGROUND: PD-L1 inhibitors is widely applied in lung adenocarcinoma patients. Tumor cells with high PD-L1 expression could trigger immune evasion. Cancer stem cells (CSCs) can evade from immunesurveillance due to their immunomodulating effects. However, the correlation between CSC and PD-L1 and some immune-related markers is seldom reported in patients with lung adenocarcinoma. Therefore, we aimed to ascertain their association in lung adenocarcinoma patients. METHODS: We assessed CD44 expression and its association with PD-L1 in lung adenocarcinoma, using Tumor Immune Estimation Resource (TIMER), which was further validated in our patient cohort. The immune cells infiltration was depicted by CIBERSORT using GEO database. The correlation between CD44 and immune cells was also analyzed. We further evaluated the prognostic role of CD44 in patients with lung adenocarcinoma both using Kaplan-Meier plotter and validated in our patient cohort. RESULTS: Positive association between CD44 and PD-L1 were found in lung adenocarcinoma patients. T cells CD4 memory resting cells and mast cells resting cells varied significantly between patients with CD44 high and those with CD44 low. Furthermore, positive association could be found between CD44 expression and immune cells. Arm-level depletion of CD44 was linked with B cell, CD4+ T cell, neutrophil and dendritic cell infiltration. Patients with higher CD44 levels had worsened overall survival (OS). CONCLUSIONS: In summary, these results demonstrate that CD44 was associated with PD-L1 and infiltration of immune cells, and was a negative prognostic factor for predicting worsened OS in lung adenocarcinoma.

Comprehensive analysis of multiple parameters associated with tumor immune microenvironment in ARID1A mutant cancers.

Aim: To verify the relationship between ARID1A and tumor immune microenvironment thus immune checkpoint inhibitors (ICIs) response. Material & methods: Several public databases were used to characterize the association between ARID1A gene alteration and tumor immunity. Results: The gene mutation frequency was 8.2% in all cancer types. The ARID1A-mutated cancers have higher scores of mutation count, tumor mutational burden, neoantigen load (p < 0.001) and T cell repertoire, B cell repertoire diversity (p < 0.05). The gene mutation has tight association with multiple-activated immune cells. Survival analysis suggested that patients with ARID1A mutant cancers benefit more from ICIs treatment (p = 0.013). Conclusion: The ARID1A gene mutation was correlated with higher tumor immunogenicity and activated antitumor immune microenvironment, resulting in superior cohort that respond well to ICIs.