Mesoporous Co3O4@CdS nanorods as anode for high-performance lithium ion batteries with improved lithium storage capacity and cycle life.

Transition metal oxides based anodes are facing crucial problems of capacity fading at long cycles and high rates due to electrode degradations. In this prospective, an effective strategy is employed to develop advanced electrode materials for lithium-ion batteries (LIBs). In the present work, a mesoporous Co3O4@CdS hybrid sructure is developed and investigated as anode for LiBs. The hybrid structure owning porous nature and large specific surface area, provides an opportunity to boost the lithium storage capabilities of Co3O4 nanorods. The Co3O4@CdS electrode delivers an initial discharge capacity of 1292 mA h g-1 at 0.1C and a very stable reversible capacity of 760 mA h g-1 over 200 cycles with a capacity retention rate of 92.7%. In addition, the electrode exhibits excellent cyclic stability even after 800 cycles and good rate performance as compared to previously reported electrodes. Moreover, density functional theory (DFT) and electrochemical impedance spectroscopy (EIS) confirm the enhanced kinetics of the Co3O4@CdS electrode. The efficient performance of the electrode may be due to the increased surface reactivity, abundant active sites/interfaces for rapid Li+ ion diffusion and the synergy between Co3O4 and CdS NPs. This work demonstrates that Co3O4@CdS hybrid structures have great potential for high performance batteries.

NiCo2O4@SnS2nanosheets on carbon cloth as efficient bi-functional material for high performance supercapacitor and sensor applications.

Bi-functional materials provide an opportunity for the development of high-performance devices. Up till now, bi-functional performance of NiCo2O4@SnS2nanosheets is rarely investigated. In this work, NiCo2O4@SnS2nanosheets were synthesized on carbon cloth by utilizing a simple hydrothermal technique. The developed electrode (NiCo2O4@SnS2/CC) was investigated for the detection of L-Cysteine and supercapacitors applications. As a non-enzymatic sensor, the electrode proved to be highly sensitive for the detection of L-cysteine. The electrode exhibits a reproducible sensitivity of 4645.82µA mM-1cm-2in a wide linear range from 0.5 to 5 mM with a low limit of detection (0.005µM). Moreover, the electrode shows an excellent selectivity and long-time stability. The high specific surface area, enhanced kinetics, good synergy and distinct architecture of NiCo2O4@SnS2nanosheets produce a large number of active sites with substantial energy storage potential. As a supercapacitor, the electrode exhibits improve capacitance of 655.7 F g-1at a current density of 2 A g-1as compare to NiCo2O4/CC (560 F g-1). Moreover, the electrode achieves 95.3% of its preliminary capacitance after 10 000 cycles at 2 A g-1. Our results show that NiCo2O4@SnS2/CC nanosheets possess binary features could be attractive electrode material for the development of non-enzymatic biosensors as well as supercapacitors.

General Synthesis of Composition-Tunable High-Entropy Amorphous Oxides Toward High Efficiency Oxygen Evolution Reaction.

High-entropy materials have attracted much attention in the electrocatalysis field due to their unique structure, high chemical activity, and compositional tunability. However, the harsh and complex synthetic methods limit the application of such materials. Herein, a universal non-equilibrium liquid-phase synthesis strategy is reported to prepare high-entropy amorphous oxide nanoparticles (HEAO-NPs), and the composition of HEAO-NPs can be precisely controlled from tri- to ten-component. The non-equilibrium synthesis environment provided by an excessively strong reducing agent overcomes the difference in the reduction potentials of various metal ions, resulting in the formation of HEAO-NPs with a nearly equimolar ratio. The oxygen evolution reaction (OER) performance of HEAO-NPs is further improved by adjusting the composition and optimizing the electronic structure. The Fe16 Co32 Ni32 Mn10 Cu10 BOy exhibits a smaller overpotential (only 259 mV at 10 mA cm-2 ) and higher stability in OER compared with commercial RuO2 . The amorphous high-entropy structure with an optimized concentration of iron makes the binding energy of CoNi shift to a higher direction, promotes the generation of high-valence active intermediates, and accelerates the OER kinetic process. The HEAO-NPs have promising application potential in the field of catalysis, biology, and energy storage, and this work provides a general synthesis method for composition-controllable high-entropy materials.

Spontaneous redox reaction-mediated interfacial charge transfer in titanium dioxide/graphene oxide nanoanodes for rapid and durable lithium storage.

Titanium dioxide (TiO2) anodes show significant advantages in ion storage owing to their low cost, abundant sources, and small volume change during cycling. However, their intrinsic low electronic conductivity and sluggish ion diffusion coefficient restrict the application of TiO2 anodes, especially at high current densities. The construction of a covalently-bonded interface in TiO2-based composite anodes is an effective approach to solve these issues. Covalent bonds are usually formed in situ during materials synthesis processes, such as high-energy ball milling, solvothermal reactions, plasma-assisted thermal treatment, and addition of a linking agent for covalent coupling. In this study, we demonstrate that a spontaneous redox reaction between defective TiO2 powder and an oxidative graphene oxide (GO) substate can be used to form interfacial covalent bonds in composites. Different structural characterization techniques confirmed the formation of interfacial covalent bonds. Electrochemical measurements on an optimized sample showed that a specific capacity of 281.3 mA h g-1 after 200 cycles can be achieved at a current density of 1 C (1 C = 168 mA g-1). Even at a high rate of 50 C, the electrode maintained a reversible capacity of 97.0 mA h g-1. The good lithium storage performance of the electrode is a result of the uniquely designed composite electrodes with strong interfacial chemical bonds.

Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with NTRK family mutations.

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients harboring neurotrophin receptor kinase (NTRK) family mutations remains obscure. METHODS: The Zehir cohort from cBioPortal was used to analyze the mutations (MT) frequency of NTRK family in patients with NSCLC, and their correlation with clinical characteristics and patient survival. The influence of NTRK MT on ICIs efficacy was evaluated in ICIs-treated patients from Samstein cohort and further validated by use of data from OAK/POPLAR cohort. RESULTS: In the Zehir cohort, a significant difference was observed in median overall survival (mOS) between patients with NTRK MT and wild-type (WT) (mOS: 18.97 vs. 21.27 months, HR = 1.34, 95%CI 1.00-1.78; log-rank P = 0.047). In Samstein cohort, the mOS of NTRK mutant patients receiving ICIs has improved compared to WT patients (mOS: 21.00 vs. 11.00 months, log-rank P = 0.103). Notably, in subgroup analysis, ICIs significantly prolonged mOS in patients with NTRK3 MT than in WT patients (mOS: not available vs. 11.00 months, HR = 0.36, 95%CI 0.16-0.81; log-rank P = 0.009). Identical mOS between NTRK MT and WT patients receiving ICIs treatment (mOS: 13.24 vs. 13.50 months, log-rank P = 0.775) was observed in OAK/POPLAR cohort. Moreover, a similar programmed death ligand 1 (PD-L1) expression, but higher tumor mutational burden (TMB), blood TMB (bTMB) and enriched anti-tumor immunity were observed in NTRK MT compared to WT (P < 0.05). CONCLUSION: Taking high TMB or bTMB into consideration, patients with NTRK mutant NSCLC could benefit from ICIs treatment.

Thyroid dysfunction induced by immune checkpoint inhibitors and tumor progression during neoadjuvant therapy of non­small cell lung cancer: A case report and literature review.

Immune checkpoint inhibitors (ICIs) have a demonstrable treatment response in patients with resectable non-small cell lung cancer (NSCLC). However, immune-related adverse events and tumor progression in patients administered ICIs are of great concern. The present case study is of a 59-year-old male with NSCLC (squamous, stage IIIA) who received neoadjuvant immunotherapy combined with chemotherapy before surgery. The patient first developed hyperthyroidism and then hypothyroidism, indicating that ICI-related thyroid dysfunction had occurred. Furthermore, the patient suffered from tumor progression and could not undergo resection. The present case called attention to the prevention and management of irAEs, and the precaution that should be taken with regard to tumor progression. The case also suggested that the development of ICI-related thyroid dysfunction may not predict an improved response to ICI therapies, which needs further evidence to illustrate.

Enhancing potassium ions adsorption on mesoporous carbon spheres with abundant internal surface via engineering sulfur doping sites towards superior rate capability.

Mesoporous carbon spheres (MCSs) show great potential for using as high-performance anodes in potassium-ion batteries (PIBs). Design and synthesis of MCSs with suitable multiscale structures and heteroatom doping or co-doping in MCSs are successfully employed to optimize the ion and electron transportation, however, it is still a challenge to explore MCS-based anodes with satisfactory potassium storage performance. In this work, we report novel S-doped MCS samples with abundant internal surfaces for potassium storage. The S doping sites are controlled during the synthesis, and the effect of different doping sites on the potassium storage is systematically studied. It is found that S doping between the carbon layers enlarges interlayer spacing and facilitates potassium ion adsorption. Consequently, the optimized sample shows an excellent rate capability of 144 mAh/g at 5.0 A/g, and a high reversible specific capacity of 325 mAh/g after 100 cycles at 0.1 A/g with a capacity retention of 91.2%. The important role of element doping sites on ion adsorption and ion storage performance is confirmed by theoretical investigations. Controlling the doping sites in MCSs provides a new approach to designing high-performance electrodes for energy storage and conversion applications.

Predictive value of the prognostic nutritional index in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

Purpose: The prognostic nutritional index (PNI), which is derived from the albumin concentration and absolute lymphocyte number, is an effective indicator of cancer patients' nutritional and immunological status. According to multiple studies, PNI was strongly linked to the prognosis of patients with non-small cell lung cancer (NSCLC). The predictive value of PNI for survival outcomes in NSCLC patients receiving immune checkpoint inhibitors (ICIs) is still in dispute at present. This meta-analysis is devoted to fill this information gap and investigate the predictive ability of PNI in NSCLC patients treated with ICIs. Methods: The PubMed, Embase, Cochrane Library databases, and conference proceedings were searched for eligible studies without language restriction. Overall survival (OS) and progression-free survival (PFS) were included. The predictive value of PNI was estimated using hazard ratios and their 95% confidence intervals. Results: Thirteen relevant retrospective cohort studies were included and these studies included 1119 patients with stage III-IV NSCLC. Lower PNI status was found to be an independent risk factor for worse survival outcomes in patients with NSCLC (OS HR = 2.68; 95%CI: 1.76-4.06; P < 0.0001; PFS HR = 1.84; 95%CI: 1.39-2.42; P < 0.0001). According to the subgroup analysis, PNI was similarly connected to OS in most subgroups of NSCLC patients receiving ICIs, except for those receiving chemoimmunotherapy or first-line treatment, and those with a cut-off value < 45. Conclusion: Our findings indicated that lower PNI was associated with poorer prognosis in NSCLC patients undergoing ICI therapy. Further prospective research with bigger patient groups is required. Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO), identifier CRD42022327528.

Anatomical variation of sympathetic ganglia in R4+R5 sympathicotomy for primary palmar axillary hyperhidrosis.

Background: R4+R5 sympathicotomy is one of the standard surgical treatments for primary palmar axillary hyperhidrosis (PAH), but the reported outcomes vary. Anatomical variation of sympathetic ganglia is hypothesized to be a cause for this phenomenon. The sympathetic ganglia could be visualized via near-infrared (NIR) fluorescent thoracoscopy, we utilize this novel technique to observe the anatomical variation of sympathetic ganglia T3 and T4 and investigate its relationship with surgical outcomes. Methods: This is a prospective multi-center cohort study. All patients received intravenous indocyanine green (ICG) infusion 24 hours preoperatively. Anatomical variation of sympathetic ganglia T3 and T4 was observed via fluorescent thoracoscopy. Standard R4+R5 sympathicotomy was performed regardless of anatomical variation. Patients were followed up for the therapeutic outcome. Results: One hundred and sixty-two patients in total were enrolled in this study and 134 patients with bilateral clearly visualized thoracic sympathetic ganglia (TSG) were included. The success rate of fluorescent imaging of thoracic sympathetic ganglion was 82.7%. The T3 ganglion was shifted downward on 32 sides (11.9%) and no upward-shifted ganglion was identified. The T4 ganglion was shifted downward on 52 sides (19.4%) and no upward-shifted ganglion was identified. All patients underwent R4+R5 sympathicotomy and no perioperative death or severe complication occurred. The total improvement rates on palmar sweating at short-term and long-term follow-up were 98.1% and 95.1%, respectively. There were significant differences between T3 normal and T3 variation subgroups both in short-term (P=0.049) and long-term (P=0.032) follow-ups. The total improvement rates on axillary sweating at short-term and long-term follow-ups were 97.0% and 89.6%, respectively. No significant difference was found between T4 normal and T4 variation subgroups both in short-term and long-term follow-ups. No significant difference was found between normal and variation subgroups on the degree of compensatory hyperhidrosis (CH). Conclusions: NIR fluorescent thoracoscopy provides clear identification of anatomical variations of sympathetic ganglia during R4+R5 sympathicotomy. The improvement of palmar sweating was significantly affected by anatomical variation of T3 sympathetic ganglia.

Microwave solvothermal synthesis of Component-Tunable High-Entropy oxides as High-Efficient and stable electrocatalysts for oxygen evolution reaction.

Transition-metal-based high-entropy oxides (HEOs) are appealing electrocatalysts for oxygen evolution reaction (OER) due to their unique structure, variable composition and electronic structure, outstanding electrocatalytic activity and stability. Herein, we propose a scalable high-efficiency microwave solvothermal strategy to fabricate HEO nano-catalysts with five earth-abundant metal elements (Fe, Co, Ni, Cr, and Mn) and tailor the component ratio to enhance the catalytic performance. (FeCoNi2CrMn)3O4 with a double Ni content exhibits the best electrocatalytic performance for OER, namely low overpotential (260 mV@10 mA cm-2), small Tafel slope and superb long-term durability without obvious potential change after 95 h in 1 M KOH. The extraordinary performance of (FeCoNi2CrMn)3O4 can be attributed to the large active surface area profiting from the nano structure, the optimized surface electronic state with high conductivity and suitable adsorption to intermediate benefitting from ingenious multiple-element synergistic effects, and the inherent structural stability of the high-entropy system. In addition, the obvious pH value dependable character and TMA+ inhibition phenomenon reveal that the lattice oxygen mediated mechanism (LOM) work together with adsorbate evolution mechanism (AEM) in the catalytic process of OER with the HEO catalyst. This strategy provides a new approach for the rapid synthesis of high-entropy oxide and inspires more rational designs of high-efficient electrocatalysts.

Enhanced Interfacial Magnetization is Responsible for the Negative Capacity Fading of Cobalt Ditelluride Anodes for Lithium Storage.

In lithium-ion batteries (LIBs), the stabilized capacities of transition metal compound anodes usually exhibit higher values than their theoretical values due to the interfacial charge storage, the formation of reversible electrolyte-derived surface layer, or interfacial magnetization. But the effectively utilizing the mechanisms to achieve novel anodes is rarely explored. Herein, a novel nanosized cobalt ditelluride (CoTe2 ) anodes with ultra-high capacity and long term stability is reported. Electrochemical tests show that the lithium storage capacity of the best sample reaches 1194.7 mA h g-1 after 150 cycles at 0.12 A g-1 , which increases by 57.8% compared to that after 20 cycles. In addition, the sample offers capacities of 546.6 and 492.1 mA h g-1 at 0.6 and 1.8 A g-1 , respectively. During cycles, CoTe2 particles (average size 20 nm) are gradually pulverized into the smaller nanoparticles (<3 nm), making the magnetization more fully due to the larger contact area of Co/Li2 Te interface, yielding an increased capacity. The negative capacity fading is observed, and verified by ex situ structural characterizations and in situ electrochemical measurements. The proposed strategy can be further extended to obtain other high-performance ferromagnetic metal based electrodes for energy storage applications.

Recent advances in in situ and operando characterization techniques for Li7La3Zr2O12-based solid-state lithium batteries.

Li7La3Zr2O12 (LLZO)-based solid-state Li batteries (SSLBs) have emerged as one of the most promising energy storage systems due to the potential advantages of solid-state electrolytes (SSEs), such as ionic conductivity, mechanical strength, chemical stability and electrochemical stability. However, there remain several scientific and technical obstacles that need to be tackled before they can be commercialised. The main issues include the degradation and deterioration of SSEs and electrode materials, ambiguity in the Li+ migration routes in SSEs, and interface compatibility between SSEs and electrodes during the charging and discharging processes. Using conventional ex situ characterization techniques to unravel the reasons that lead to these adverse results often requires disassembly of the battery after operation. The sample may be contaminated during the disassembly process, resulting in changes in the material properties within the battery. In contrast, in situ/operando characterization techniques can capture dynamic information during cycling, enabling real-time monitoring of batteries. Therefore, in this review, we briefly illustrate the key challenges currently faced by LLZO-based SSLBs, review recent efforts to study LLZO-based SSLBs using various in situ/operando microscopy and spectroscopy techniques, and elaborate on the capabilities and limitations of these in situ/operando techniques. This review paper not only presents the current challenges but also outlines future developmental prospects for the practical implementation of LLZO-based SSLBs. By identifying and addressing the remaining challenges, this review aims to enhance the comprehensive understanding of LLZO-based SSLBs. Additionally, in situ/operando characterization techniques are highlighted as a promising avenue for future research. The findings presented here can serve as a reference for battery research and provide valuable insights for the development of different types of solid-state batteries.

Effect of LGR4/EGFR signaling on cell growth and cancer stem cell-like characteristics in liver cancer.

PURPOSE: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Leucine-rich repeat containing G-protein-coupled receptors 4 (LGR4) participates in tumor progression, invasion, and metastasis. Our study aimed to investigate the effect of LGR4 with epidermal growth factor receptor (EGFR) in HCC cells. METHODS: We employed Hep3B and Huh7 cells to conduct our research. Comprehensive biological activities were characterized by CCK8 and transwell assay. Molecular biology techniques were used to determine the expression of proteins. Hep3B was employed to conduct subcutaneous tumor in mice. The tumor growth and the expression levels of proteins were assessed. RESULTS: LGR4 overexpression could promote the cells proliferation, migration, and invasion ability, while siLGR4 and siEGFR could inhibit cells biological activities. In addition, LGR4 overexpression promoted the expression levels of RSPO2, ß-catenin, EGFR and cancer stem cells (CSCs) markers, whereas silence of LGR4 or EGFR could diminish the expression levels of ß-catenin and CSCs markers. Furthermore, knockdown of LGR4 or EGFR also inhibited tumor growth and reduced the expression levels of RSPO2, CD133, CD44, Nanog, ß-catenin in vivo. CONCLUSION: Our data suggest that LGR4 /EGFR signaling in HCC leads to induce tumor growth, which then contributes to stem cell characteristics. It maybe a new perspective for the targeted therapy of HCC treatment.

Trends in antineoplastic drug use, cost and prescribing patterns among patients with lung cancer in nine major cities of China, 2016-2020: a retrospective observational study based on inpatient and outpatient hospital data.

OBJECTIVES: It is unclear whether the use of antineoplastic drugs for patients with lung cancer in China has changed after the implementation of the national drug price negotiation in 2016 and continual update of clinical guidelines. This study aims to evaluate the trends in antineoplastic drug use, cost and prescribing patterns among patients with lung cancer in major cities of China. DESIGN: We conducted a retrospective observational study using data from January 2016 to December 2020. SETTING: This study used prescription records based on inpatient and outpatient hospital data from 97 hospitals in 9 major cities of China. PARTICIPANTS: A total of 218 325 antineoplastic drug prescriptions in patients with lung cancer were retrospectively collected from the Hospital Prescription Analysis Cooperative Project during the study period. OUTCOME MEASURES: Trends in antineoplastic drug use, cost and prescribing patterns among patients with lung cancer. RESULTS: The yearly antineoplastic prescriptions increased by 85.6% from 28 594 in 2016 to 53 063 in 2020 (Z=1.71, p=0.086). Significant increases were seen in the prescriptions for protein kinase inhibitors (PKIs) and monoclonal antibodies (mAbs), whereas significant decreases were observed in antimetabolites, plant alkaloids and platinum compounds. The yearly cost increased progressively by 145.0% from ¥113.6 million in 2016 to ¥278.3 million in 2020 (Z=2.20, p=0.027). The top three anticancer drug classes in terms of total cost were PKIs, antimetabolites and mAbs. In prescribing patterns of antineoplastic agents for lung cancer, monotherapy, and triple or more drug combinations gradually increased, while dual combinations decreased significantly from 30.8% to 19.6%. CONCLUSIONS: Prescription practices among patients with lung cancer in China underwent major changes during the study period. The observed trends can aid in understanding the present medication use status of patients with lung cancer in China and provide information for future drug management.

Pharmacovigilance-based drug repurposing: searching for putative drugs with hypohidrosis or anhidrosis adverse events for use against hyperhidrosis.

BACKGROUND: Drug repurposing refers to the application of existing drugs to new therapeutic indications. As phenotypic indicators of human drug response, drug side effects may provide direct signals and unique opportunities for drug repurposing. OBJECTIVES: We aimed to identify drugs frequently associated with hypohidrosis or anhidrosis adverse reactions (that is, the opposite condition of hyperhidrosis) from the pharmacovigilance database, which could be potential candidates as anti-hyperhidrosis treatment agents. METHODS: In this observational, retrospective, pharmacovigilance study, adverse event reports of hypohidrosis or anhidrosis in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) were assessed between January 2004 and December 2021 using reporting odds ratio (ROR) estimates and categorized by the World Health Organization Anatomical Therapeutic Chemical (ATC) classification code. The onset time of drug-associated hypohidrosis or anhidrosis was also examined. RESULTS: There were 540 reports of 192 drugs with suspected drug-associated hypohidrosis or anhidrosis in the FAERS database, of which 39 drugs were found to have statistically significant signals. Nervous system drugs were most frequently reported (187 cases, 55.82%), followed by alimentary tract and metabolism drugs (35 cases, 10.45%), genitourinary system and sex hormones (28 cases, 8.36%), and dermatologicals (22 cases, 6.57%). The top 3 drug subclasses were antiepileptics, drugs for urinary frequency and incontinence, and antidepressants. Taking disproportionality signals, pharmacological characteristics of drugs and appropriate onset time into consideration, the main putative drugs for hyperhidrosis were glycopyrronium, solifenacin, oxybutynin, and botulinum toxin type A. Other drugs, such as topiramate, zonisamide, agalsidase beta, finasteride, metformin, lamotrigine, citalopram, ciprofloxacin, bupropion, duloxetine, aripiprazole, prednisolone, and risperidone need more investigation. CONCLUSIONS: Several candidate agents among hypohidrosis or anhidrosis-related drugs were identified that may be redirected for diminishing sweat production. There are affirmative data for some candidate drugs, and the remaining proposed candidate drugs without already known sweat reduction mechanisms of action should be further explored.

Graphite-like structured conductive polymer anodes for high-capacity lithium storage with optimized voltage platform.

Graphite is a widely used anode material in commercial lithium-ion batteries (LIBs), but its low theoretical specific capacity and extremely low redox potential limit its application in high-performance lithium-ion batteries. However, developing lithium-ion battery anode with high specific capacity and suitable working potential is still challenging. At present, conductive polymers with excellent properties and graphite-like structures are widely used in the field of electrochemistry, but their Li+ storage mechanism and kinetics are still unclear and need to be further investigated. Therefore, we synthesized the conducting polymer Fe3(2, 3, 6, 7, 10, 11-hexahydroxytriphenylene)2 (Fe-CAT) by the liquid phase method, in which the d-π conjugated structure and pores facilitate electron transfer and electrolyte infiltration, improving the comprehensive electrochemical performance. The Fe-CAT electrode displays a high capacity of 950 mA h g-1 at 200 mA g-1. At the current density of 5.0 A g-1, the electrode shows a reversible capacity of 322 mA h g-1 after 1000 cycles. The average lithiation voltage plateau is âˆ¼ 0.79 V. The combination of ex-situ characterization techniques and electrochemical kinetic analysis reveals the source of the excellent electrochemical performance of Fe-CAT. During the charging/discharging process, the aromatic ring in the organic ligand is involved in the redox reaction. Such results will provide new insights for the design of next-generation high-performance electrode materials for LIBs.

ANK2 as a novel predictive biomarker for immune checkpoint inhibitors and its correlation with antitumor immunity in lung adenocarcinoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been shown to significantly improve the survival of patients with advanced lung adenocarcinoma (LUAD). However, only limited proportion of patients could benefit from ICIs. Novel biomarkers with strong predictability are needed for clinicians to maximize the efficacy of ICIs. Our study aimed to identify potential biomarkers predicting ICIs efficacy in LUAD. METHODS: The Cancer Genome Atlas (TCGA) PanCancer Atlas studies in cBioportal were used to evaluate the mutation frequency of ANK2 across multiple cancers. Clinical and mutational data for LUAD from ICIs-treated cohorts (Hellmann et al. and Rizvi et al.) were collected to explore the correlation between ANK2 mutation and clinical outcomes. In addition, the relationship between ANK2 expression and clinical outcomes was analyzed using LUAD data from TCGA and Gene Expression Omnibus. Furthermore, the impact of ANK2 mutation and expression on the tumor immune microenvironment of LUAD was analyzed using TCGA and TISIDB databases. RESULTS: Patients with ANK2 mutation benefited more from ICIs. In ICIs-treated cohort, prolonged progression-free survival (PFS) (median PFS: NR (not reached) vs. 5.42 months, HR (hazard ratio) 0.31, 95% CI 0.18-0.54; P = 0.0037), improved complete response rate (17.65% vs. 1.85%, P = 0.0402), and improved objective response rate (64.71% vs. 24.07%, P = 0.0033) were observed in LUAD patients with ANK2 mutation compared to their wild-type counterparts. Regarding ANK2 expression, it was observed that ANK2 expression was decreased in LUAD (P < 0.05) and a higher level of ANK2 expression was associated with longer overall survival (HR 0.69, 95% CI 0.52-0.92; P = 0.012) in TCGA LUAD cohort. Moreover, ANK2 mutation or higher ANK2 expression correlated with enhanced antitumor immunity and "hot" tumor microenvironment in LUAD, which could be potential mechanisms that ANK2 mutation facilitated ICIs therapy and patients with higher ANK2 expression survived longer. CONCLUSION: Our findings suggest that ANK2 mutation or increased ANK2 expression may serve as a favorable biomarker for the efficacy of ICIs in patients with LUAD.

Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis.

Background: Liver metastasis is the most common type of lung cancer metastasis, and is a significant prognostic factor in lung cancer. However, the effect of liver metastases on the efficacy of immune checkpoint inhibitors (ICIs) remains inconsistent and controversial. The aim of this study was to explore the relationship between liver metastases and ICI efficacy in patients with advanced lung cancer based on data from randomized controlled trials (RCTs) and observational studies. Methods: PubMed, EMBASE, Cochrane Library databases, conference proceedings, as well as grey literature websites were searched for eligible studies without language restrict ion. Study quality was assessed using Cochrane tools and the Newcastle-Ottawa Quality Assessment Scale (NOS). Outcomes of interest were overall survival (OS) and progression-free survival (PFS). The difference in efficacy between patients with and without liver metastases was calculated by pooling ratios of hazard ratios (HR), as calculated using the deft approach. Results: A total of 16 RCTs and 14 observational trials were included. Analyses of RCTs revealed a survival benefit for ICI treatment (i.e., ICI monotherapy, ICI + Chemotherapy, dual ICI therapy and dual ICI + Chemotherapy) versus standard therapies among non-small cell lung cancer (NSCLC) patients with liver metastases (PFS HR, 0.77; 95%CI, 0.61-0.97; OS HR, 0.78; 95%CI, 0.68-0.90). NSCLC patients with liver metastases achieved less PFS benefit and comparable OS benefit from ICI treatment compared with those without liver metastases (ratios of PFS-HRs, 1.19; 95%CI, 1.02-1.39; P=0.029; Ratios of OS-HRs, 1.10; 95%CI, 0.94-1.29; P=0.24). For patients with small cell lung cancer (SCLC), ICI treatment achieved a marginal effect on patients with liver metastases as compared with standard therapies (OS HR, 0.94; 95%CI, 0.73-1.23). SCLC patients with liver metastases benefited less from ICI treatment than patients without liver metastases (ratio of OS-HRs, 1.22; 95%CI, 1.01-1.46; P=0.036). In real-world data analysis, liver metastasis could be used as an independent prognostic risk factor, increasing the risk of death by 21% in lung cancer patients receiving ICI treatment compared with those without liver metastases (OS HR, 1.21; 95%CI, 1.17-1.27; P<0.0001). Subgroup analysis confirmed that this association was not modified by race (Asian vs. Western) or number of treatment lines. Conclusions: The presence of liver metastases does not significantly influence the OS benefit of ICIs in patients with NSCLC. However, a small amount of data shows that liver metastasis restrains the magnitude of OS benefit in patients with SCLC. Liver metastasis has potential as an independent prognostic risk factor for lung cancer patients receiving ICI treatment in clinical practice. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022306449).

Fibroblast growth factor receptor family mutations as a predictive biomarker for immune checkpoint inhibitors and its correlation with tumor immune microenvironment in melanoma.

Background: The emergence of immune checkpoint inhibitors (ICIs) has significantly improved the clinical outcomes of patients with metastatic melanoma. However, survival benefits are only observed in a subset of patients. The fibroblast growth factor receptor (FGFR) family genes are frequently mutated in melanoma, yet their impacts on the efficacy of ICIs remain unclear. Our study aimed to explore the association of FGFR mutations with ICIs efficacy in metastatic melanoma. Methods: The Cancer Genome Atlas (TCGA) data (PanCancer Atlas, skin cutaneous melanoma (SKCM), n = 448) in cBioPortal were collected as a TCGA cohort to investigate the association between FGFR mutations and prognosis of melanoma patients. To explore the impact of FGFR mutations on the efficacy of ICIs in melanoma, clinical and tumor whole-exome sequencing (WES) data of four ICI-treated studies from cBioPortal were consolidated as an ICIs-treated cohort. Moreover, the relationship between FGFR mutations and immunogenicity (tumor mutation burden (TMB), neo-antigen load (NAL), mismatch repair (MMR)-related genes and DNA damage repair (DDR)-related genes) of melanoma was evaluated utilizing data from the ICIs-treated cohort. The influence of FGFR mutations on the tumor immune microenvironment (TIME) of melanoma was also analyzed using the TCGA cohort. Results: In the TCGA cohort, survival in melanoma patients with or without FGFR mutations was nearly equivalent. In the ICIs-treated cohort, patients with FGFR mutations had better survival than those without (median overall survival: 60.00 vs. 31.00 months; hazard ratio: 0.58, 95% CI: 0.42-0.80; P = 0.0051). Besides, the objective response rate was higher for patients harboring FGFR mutations (55.56%) compared to wild-type patients (22.40%) (P = 0.0076). Mechanistically, it was revealed that FGFR mutations correlated with increased immunogenicity (e.g., TMB, NAL, MMR-related gene mutations and DDR-related gene mutations). Meanwhile, FGFR mutant melanoma tended to exhibit an enhanced antitumor TIME compared with its wild-type counterparts. Conclusions: Our study demonstrated that FGFR mutations is a promising biomarker in stratifying patients with advanced melanoma who might benefit from ICIs therapy.

Neutrophil-related genes predict prognosis and response to immune checkpoint inhibitors in bladder cancer.

Neutrophils play a key role in the occurrence and development of cancer. However, the relationship between neutrophils and cancer prognosis remains unclear due to their great plasticity and diversity. To explore the effects of neutrophils on the clinical outcome of bladder cancer, we acquired and analyzed gene expression data and clinical information of bladder cancer patients from IMvigor210 cohort and The Cancer Genome Atlas dataset (TCGA) database. We established a neutrophil-based prognostic model incorporating five neutrophil-related genes (EMR3, VNN1, FCGRT, HIST1H2BC, and MX1) and the predictive value of the model was validated in both an internal and an external validation cohort. Multivariate Cox regression analysis further proved that the model remained an independent prognostic factor for overall survival and a nomogram was constructed for clinical practice. Additionally, FCGRT was identified as the key neutrophil-related gene linked to an adverse prognosis of bladder cancer. Up-regulation of FCGRT indicated activated cancer metabolism, immunosuppressive tumor environment, and dysregulated functional status of immune cells. FCGRT overexpression was also correlated with decreased expression of PD-L1 and low levels of tumor mutation burden (TMB). FCGRT predicted a poor response to immunotherapy and had a close correlation with chemotherapy sensitivity. Taken together, a novel prognostic model was developed based on the expression level of neutrophil-related genes. FCGRT served as a promising candidate biomarker for anti-cancer drug response, which may contribute to individualized prognostic prediction and may contribute to clinical decision-making.