An Organic Optoelectronic Synapse with Multilevel Memory Enabled by Gate Modulation.

Artificial synaptic devices are emerging as contenders for next-generation computing systems due to their combined advantages of self-adaptive learning mechanisms, high parallel computation capabilities, adjustable memory level, and energy efficiency. Optoelectronic devices are particularly notable for their responsiveness to both voltage inputs and light exposure, making them attractive for dynamic modulation. However, engineering devices with reconfigurable synaptic plasticity and multilevel memory within a singular configuration present a fundamental challenge. Here, we have established an organic transistor-based synaptic device that exhibits both volatile and nonvolatile memory characteristics, modulated through gate voltage together with light stimuli. Our device demonstrates a range of synaptic behaviors, including both short/long-term plasticity (STP and LTP) as well as STP-LTP transitions. Further, as an encoding unit, it delivers exceptional read current levels, achieving a program/erase current ratio exceeding 105, with excellent repeatability. Additionally, a prototype 4 × 4 matrix demonstrates potential in practical neuromorphic systems, showing capabilities in the perception, processing, and memory retention of image inputs.

Synthesis, Structures and Properties of Trioxa[9]circulene and Diepoxycyclononatrinaphthalene.

This article presents trioxa[9]circulene (3) as a novel member of hetero[n]circulenes. Its synthesis began with the synthesis of dimethoxydioxa[8]helicene (5) and used dimethoxydiepoxycyclononatrinaphthalene (4) as a key intermediate, despite the condensation reaction predominantly yielding a 1,4-addition byproduct. The structures and properties of 3-5 were extensively investigated using experimental and computational methods. Analysis of the crystal structures reveal elongation of the internal C-C bonds in the nine-membered ring of 3 compared to 4 and 5. Computational studies demonstrate the remarkable flexibility of trioxa[9]circulene's saddle-shaped polycyclic framework, while the other two compounds are rigid with large racemization barriers. Optically pure forms of 4 and 5 exhibit absorption and luminescence dissymmetry factors on the order of 10-2, with smaller values observed for compound 4. In the crystal structures, molecules of 3 stack to form columns with remarkable π-π overlap, and the π-π interactions of 4 exhibit short intermolecular C-to-C contacts. Consequently, the solution-processed film of 4 functioned as a p-type organic semiconductor in field effect transistors.

A new armchair carbon nanobelt synthesized by tuning the regioselectivity of the Scholl reaction of quinquephenyl.

A new armchair carbon nanobelt is successfully synthesized by tuning the regioselectivity of the Scholl reaction of 1,1':2',1'':4'',1''':2''',1''''-quinquephenyl. This nanobelt exhibits a preferential binding affinity towards C70 over C60 as found from photoluminescence titration experiments.

A novel approach to evaluation of tumor response for advanced pulmonary adenocarcinoma using the intertumoral heterogeneity response score.

Treatment response and prognosis estimation in advanced pulmonary adenocarcinoma are challenged by the significant heterogeneity of the disease. The current Response Evaluation Criteria in Solid Tumors (RECIST) criteria, despite providing a basis for solid tumor response evaluation, do not fully encompass this heterogeneity. To better represent these nuances, we introduce the intertumoral heterogeneity response score (THRscore), a measure built upon and expanding the RECIST criteria. This retrospective study included patients with 3-10 measurable advanced lung adenocarcinoma lesions who underwent first-line chemotherapy or targeted therapy. The THRscore, derived from the coefficient of variation in size for each measurable tumor before and 4-6 weeks posttreatment, unveiled a correlation with patient outcomes. Specifically, a high THRscore was associated with shorter progression-free survival, lower tumor response rate, and a higher tumor mutation burden. These associations were further validated in an external cohort, confirming THRscore's effectiveness in stratifying patients based on progression risk and treatment response, and enhancing the utility of RECIST in capturing complex tumor behaviors in lung adenocarcinoma. These findings affirm the promise of THRscore as an enhanced tool for tumor response assessment in advanced lung adenocarcinoma, extending the RECIST criteria's utility.

Chemotherapy versus personalized therapy for EGFR mutant lung adenocarcinoma resistance to EGFR-tyrosine kinase inhibitors: a retrospective dual-center study.

BACKGROUND: Advanced lung adenocarcinoma patients often develop resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), leaving uncertainties regarding subsequent treatment strategies. Although personalized therapy targeting individual acquired resistances (ARs) shows promise, its efficacy has not been systematically compared with platinum-containing doublet chemotherapy, a widely accepted treatment after EGFR-TKIs failure. METHODS: A retrospective dual-center study was conducted involving patients with advanced lung adenocarcinoma and EGFR mutations who developed resistance to EGFR-TKIs between January 2017 and December 2022. Eligible patients were adults aged 18 years or older with an Eastern Cooperative Oncology Group score of 0-1, normal organ function, and no prior chemotherapy. Patients were divided into the chemotherapy group (CG) or personalized therapy group (PG) based on the treatment received after disease progression. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). RESULTS: Of the 144 patients enrolled, there were 53 patients in the PG and 91 patients in the CG. The PG acquired resistance to EGFR-TKIs through the MET amplification (27, 50%) and small cell lung cancer transformation (16, 30%) and 18% of them reported multiple resistance mechanisms. The ORR of the PG was similar to that of the CG (34% vs. 33%, P = 1.0) and the PFS of the PG patients was not statistically different from that of their CG counterparts [4.2 months (95% CI: 3.6-4.8 months) vs. 5.3 months (95% CI: 4.6-6.0 months), P = 0.77]. CONCLUSIONS: These findings suggest that the therapeutic efficacy of chemotherapy approximates to that of personalized therapy, which signifies that chemotherapy is still a reliable choice for patients who develop resistance to EGFR-TKIs and that further research is awaited to explore the benefit of personalized treatment.

Cyclodextrin Polymer-Loaded Micro-Ceramic Balls for Solid-Phase Extraction of Triazole Pesticides from Water.

A citric acid cross-linked ß-cyclodextrin (ß-CD) polymer was synthesized and loaded on micro-ceramic balls to fabricate the solid-phase adsorbents (P-MCB) for adsorption and extraction of triazole pesticides from water. The stability of ß-CD polymer and P-MCB was investigated in solutions with different pH values at different temperatures. The adsorption properties and the influence of kinetics, sorbent amount, pesticide concentration, and temperature on the adsorption capacity were evaluated. The results showed P-MCB had favorable adsorption of 15.98 mg/g flutriafol in 3.5 h. The equilibrium data followed the Freundlich equation, and the adsorption of flutriafol and diniconazole followed the second-order kinetics. The recovery rate of P-MCB for triazole pesticides in water was satisfactory, and the recovery rate was still 80.1%, even at the 10th cycle. The P-MCB had good stability, with a degradation rate of 0.2% ± 0.08 within 10 days, which could ensure extraction and recycling.

Rechallenge of immune checkpoint inhibitors in advanced non-small cell lung cancer.

Immune checkpoint inhibitor (ICI) rechallenge in non-small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD-1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Baseline C-reactive protein predicts efficacy of the first-line immune checkpoint inhibitors plus chemotherapy in advanced lung squamous cell carcinoma: a retrospective, multicenter study.

AIMS: To investigate the predictive value of baseline C-reactive protein (CRP) levels on the efficacy of chemotherapy plus immune checkpoint inhibitors (ICI) in patients with advanced lung squamous cell carcinoma (LSCC). MATERIALS AND METHODS: In this retrospective multicenter study spanning from January 2016 to December 2020, advanced LSCC patients initially treated with chemotherapy or a combination of chemotherapy and ICI were categorized into normal and elevated CRP subgroups. The relationship between CRP levels and treatment outcomes was analyzed using multivariate Cox proportional hazards models and multivariate logistic regression, focusing primarily on the progression-free survival (PFS) endpoint, and secondarily on overall survival (OS) and objective response rate (ORR) endpoints. Survival curves were generated using the Kaplan-Meier method, with the log-rank test used for comparison between groups. RESULTS: Of the 245 patients evaluated, the 105 who received a combination of chemotherapy and ICI with elevated baseline CRP levels exhibited a significant reduction in PFS (median 6.5 months vs. 11.8 months, HR, 1.78; 95% CI: 1.12-2.81; p = 0.013) compared to those with normal CRP levels. Elevated CRP was identified as an independent risk factor for poor PFS through multivariate-adjusted analysis. However, among the 140 patients receiving chemotherapy alone, baseline CRP levels did not significantly influence PFS. Furthermore, within the combination therapy group, there was a notable decrease in the ORR (51% vs. 71%, p = 0.035), coupled with a significantly shorter OS (median 20.9 months vs. 31.5 months, HR, 2.24; 95% CI: 1.13-4.44; p = 0.033). CONCLUSION: In patients with advanced LSCC, elevated baseline CRP levels were identified as an independent predictive factor for the efficacy of combination therapy with chemotherapy and ICI, but not in chemotherapy alone. This suggests that CRP may be a valuable biomarker for guiding treatment strategies.

Cerebrospinal fluid circulating tumor DNA contributes to the detection and characterization of leptomeningeal metastasis in non-small cell lung cancer.

PURPOSE: Cerebrospinal fluid (CSF) has revealed the unique genetic characteristics of leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC). However, the research in this area is still very limited. METHODS: Patients with LM from NSCLC (n = 80) were retrospectively analyzed. Circulating tumor DNA (ctDNA) in CSF was tested by next-generation sequencing (NGS), with paired extracranial tissue or plasma samples included for comparison. An independent non-LM cohort (n = 100) was also analyzed for comparative purposes. Clinical outcomes were compared with Kaplan-Meier log-rank test and Cox proportional hazards methodologies. RESULTS: An overwhelming 93.8% of patients carried druggable mutations in NSCLC LM, with EGFR (78.8%) being the most prevalent. Notably, 4 patients who tested negative for driver genes in extracranial samples surprisingly showed EGFR mutations in their CSF and subsequently benefited from targeted therapy. There was a clear difference in genetic profiles between CSF and extracranial samples, with CSF showing more driver gene detections, increased Copy Number Variations (CNVs), and varied resistance mechanisms among individuals. Abnormalities in cell-cycle regulatory molecules were highly enriched in LM (50.9% vs 31.0%, p = 0.017), and CDKN2A/2B deletions were identified as an independent poor prognostic factor for LM patients, with a significant reduction in median OS (p = 0.013), supported by multivariate analysis (HR 2.63, 95% CI 1.32-5.26, p = 0.006). CONCLUSIONS: CSF-based ctDNA analysis is crucial for detecting and characterizing genetic alterations in NSCLC LM. The distinct genetic profiles in CSF and extracranial tissues emphasize the need for personalized treatment approaches.

Effects of intrathecal pemetrexed on the survival of patients with leptomeningeal metastasis from lung adenocarcinoma: a propensity score matching analysis.

PURPOSE: To explore the impact of intrathecal pemetrexed (IP) on the survival of lung adenocarcinoma (LUAC) patients with leptomeningeal metastasis (LM). METHODS: We analyzed patients with LUAC and LM who received systemic therapy after LM diagnosis at the Fujian Cancer Hospital between July 2018 and March 2022. Patients who underwent IP were assigned to the IP group; those without IP treatment were designated as the non-IP group. Propensity score matching (PSM) was performed between the two groups. RESULTS: 165 patients were enrolled: 83 and 82 in the IP and non-IP groups, respectively. After 1:1 PSM, we included 114 patients in the matched cohort. Median overall survival (OS) was 13.2 months (95% CI 10.8-15.6 months) in the IP group versus 10.1 months (95% CI 5.3-14.9 months) in the non-IP group (P = 0.488). Only Eastern Cooperative Oncology Group Performance Status (ECOG PS) was confirmed as an independent predictor for OS in the matched cohort (hazard ratio (HR) 2.03; P = 0.023). Multivariate competing-risks analysis showed that IP significantly correlated with central nervous system-related death (HR 0.31; P = 0.046). When stratified by ECOG PS, IP improved survival in patients with poor ECOG PS (PS = 2) (14.3 months vs. 1.6 months; P = 0.003). CONCLUSIONS: Intrathecal pemetrexed did not enhance OS for the entire LUAC patient with LM compared to non-intrathecal chemotherapy. However, it exhibited the potential to reduce the risk of central nervous system-related mortality and improve survival in patients with poor ECOG PS.

Clinical definition of secondary resistance to immunotherapy in non-small cell lung cancer.

Immune checkpoint inhibitors (PD-1/PD-L1 and CTLA-4 blockade) have revolutionized the treatment landscape in non-small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO-IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Synthesis, Molecular Packing and Semiconductor Properties of V-Shaped N-Heteroacene Dimers.

This article presents two groups of V-shaped π-scaffolds that consist of two N-heteroacene units fused with either a rigid or flexible eight-membered ring. These rigid and flexible N-heteroacene dimers were synthesized through the condensation of tetraphenylenetetraone with the corresponding diamine and the Pd-catalyzed cross-coupling of tetrabromodibenzo[a,e]cyclooctatetraene with the corresponding diamine, respectively. A comparison of electronic structures and properties of the two groups of V-shaped N-heteroacene dimers shows subtle difference between the rigid and flexible eight-membered ring linkers in forming extended π-systems. X-ray crystallography of these V-shaped molecules has revealed interesting π-π interaction modes, which are dependent on the central connecting units and substituting groups. These π-π interactions between the V-shaped π-scaffolds have enabled the molecules to function as organic semiconductors in solution-processed field effect transistors.

Microparticles of Sericin-Dextran Conjugate for Improving the Solubility of Antiviral Drug.

A novel sericin-dextran conjugate (SDC) and self-assembled microparticles has been prepared for improving solubility of atazanavir. Microparticles of SDC were assembled by the reprecipitation method. The size and morphology of SDC microparticles could be adjusted by the concentration and solvents. Low concentration was conducive to the preparation of microspheres. Heterogeneous microspheres could be prepared in ethanol with the range of 85-390 nm, and hollow mesoporous microspheres in propanol with an average particle size of 2.5-22 µm. The aqueous solubility of atazanavir was improved to 2.22 mg/mL in buffer solutions at pH 2.0 and 1.65 mg/mL at pH 7.4 by SDC microspheres. In vitro release of atazanavir from hollow microspheres of SDC exhibited a slower release, had the lowest linear cumulative release in basic buffer (pH 8.0), and the most rapid double exponential diphase kinetic cumulative release in acid buffer (pH 2.0).

Genomic characterisation of de novo EGFR copy number gain and its impact on the efficacy of first-line EGFR-tyrosine kinase inhibitors for EGFR mutated non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation generally respond well to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). However, genomic characterisation of de novo EGFR copy number gain (CNG) and its impact on the efficacy of first-line EGFR-TKIs remains unclear. METHODS: This multicenter, retrospective and real-world study included two cohorts that enroled EGFR mutant NSCLC patients. EGFR CNG was tested by next-generation sequencing of untreated tissue specimens. Cohort 1 detected the impact of EGFR CNG on first-line EGFR-TKIs treatment, and cohort 2 explored the genomic characterisation. RESULTS: Cohort 1 enroled 355 patients from four cancer centres between January 2013 and March 2022. The patients were divided into three groups, included the EGFR non-CNG, EGFR CNG, and EGFR uncertain-CNG. No significant difference in progression-free survival (PFS) was found between the three groups (10.0 months vs. 10.8 months vs. 9.9 months, respectively, p = 0.384). Furthermore, the overall response rate was not statistically significant in the EGFR CNG group compared to the EGFR non-CNG or uncertain arm (70.3% vs. 63.2% vs. 54.5%, respectively, p = 0.154). Cohort 2 included 7876 NSCLC patients with 16.4% showing EGFR CNG. Gene mutations such as TP53, IKZF1, RAC1, MYC, MET, CDKN2A/B and alterations of the metabolic-related and ERK signalling pathway were significantly associated with patients with EGFR CNG compared to those without. CONCLUSIONS: De novo EGFR CNG had no effect on the efficacy of first-line EGFR-TKI treatment in EGFR mutant NSCLC patients, and tumours with EGFR CNG had more complex genomic profiles than those without.

[Carbon Sequestration Characteristics Under Natural Vegetation Restoration in Ziwuling Area of the Loess Plateau].

The aim of this study was to analyze the carbon sink effect under natural vegetation restoration and the influence of changes in vegetation community characteristics on ecosystem carbon density in ecologically fragile areas of the Loess Plateau. In this study, the changes in carbon sequestration of a vegetation-soil system under eight successional stages[slope cropland, abandoned cropland for 10 years, abandoned cropland for 20 years, Sophora davidii (Franch.) Skeels., Betula platyphylla Suk., Pinus tabulaeformis Carr., Quercus wutaishanic Mary+P. tabulaeformis Carr mixed forests, and Q. wutaishanic Mary] in Ziwuling area over 150 restoration periods were investigated using the common method of spatial and temporal substitution. This study also discussed the relationship between changes in vegetation community characteristics and vegetation-soil system carbon density. The results showed that the community coverage of the investigated vegetation fluctuated from 85% in the slope cropland stage to 100% in the arbor stage. The number of species, Margalef index, Shannon-Wiener index, Pielou index, and Simpson index initially increased rapidly, then declined slowly until becoming stable, and reached a peak in the middle of the succession (B. platyphylla Suk.). The biomass and carbon density of vegetation components (above-ground biomass, below-ground roots, and litter) increased exponentially during the succession, i.e., increased slowly before B. platyphylla Suk. but increased significantly in B. platyphylla Suk. and P. tabulaeformis Carr.(P<0.05). The biomass and carbon density reached the maximum values of 27858.08 g·m-2 and 13232.51 g·m-2, respectively, in Q. wutaishanic Mary+P. tabulaeformis Carr mixed forests and tended to be stable in the late succession stage. Soil organic carbon density showed a power function relationship with vegetation restoration, with the greatest increase in the stages of abandoned cropland for 10 years and B. platyphylla, but no significant changes in the subsequent stages (P>0.05). In the early succession stage, the carbon density of the farmland ecosystem was the lowest (4395.70 g·m-2), whereas the other seven stages increased by 55.54%, 40.37%, 69.96%, 202.48%, 326.35%, 357.43%, and 351.07%, respectively, compared with the farmland ecosystem. Community coverage, Margalef index, Shannon-Wiener index, above-ground biomass, root biomass, and litter biomass were significantly positively correlated with vegetation-soil system carbon density (P<0.05). The carbon sink effect of long-term natural restoration in Ziwuling Region was significant, and the carbon density of the vegetation-soil system under interspecific competition tended to be stable in the late succession stage. Dynamic changes in the vegetation community structure and plant diversity during the succession process increased vegetation carbon density and soil carbon density. This study helps to clarify the carbon sink effect of natural vegetation restoration in ecologically fragile areas of the Loess Plateau and provides a theoretical basis for promoting natural forest conservation and achieving carbon neutrality.

Oxanorbornene-Fused Phenazine-Pyrene Scaffolds with Different Configurations.

New molecular scaffolds of C-, Z- and box-shaped configurations are constructed by fusing phenazine and pyrene units with oxanorbornene. As revealed by X-ray crystallography, the C-shaped molecules exhibit two interesting π-π stacking modes of phenazine depending on the substituting groups, and the box-shaped molecule accommodates two chloroform molecules in the cavity and forms H-bonds with another four molecules of chloroform. The C- and Z-shaped molecules as a pair of diastereomers exhibit almost the same charge transfer absorption and emission including positive solvatochromism, indicating that the intramolecular charge transfer between pyrene (π-donor) and phenazine (π-acceptor) is not dependent on the overall molecular geometry.

Association of THBS3 with Glycoprotein D Promotes Pseudorabies Virus Attachment, Fusion, and Entry.

Pseudorabies virus (PRV) is a neurotropic virus causing obvious neurological disorders and reproductive failure in pigs. PRV entry into target cells is a complex multistep process initiated by interacting viral envelope glycoproteins with cellular receptors. In the current study, we found that thrombospondin 3 (THBS3) plays an important role in PRV entry into target cells, indicating that THBS3 is a new PRV coreceptor. To confirm this hypothesis, the knockdown of THBS3 in several permissive cells inhibited PRV primary infection, and overexpression of THBS3 in PK15 cells promoted PRV infection. CRISPR-Cas9 knockout markedly reduced PRV infection in PK15 cells. Antibodies against THBS3 blocked PRV infection in naturally permissive target cells. Moreover, soluble THBS3 protein neutralized the infectivity of PRV. Mechanistically, THBS3 interacted with the PRV gD via its N and C termini to facilitate PRV binding in permissive and nonpermissive cells. Also, in the absence of Nectin-1, THBS3 promoted cell-to-cell fusion mediated by virus glycoproteins. While THBS3 alone could not increase virus entry, overexpression of it in the presence of Nectin-1 promoted virus entry into CHO-K1 cells. Our results have identified THBS3 as a critical player in PRV binding and subsequent membrane fusion and entry. IMPORTANCE Herpesvirus entry occurs through a cascade of virus-cell interactions, and multiple surface glycoproteins play a role in virus binding and entry during the virus invasion process. Early studies showed that attachment to cells by PRV, as well as other alphaherpesviruses, is mediated by interactions between the viral glycoprotein gC and cell membrane proteoglycans carrying heparan sulfate chains (HSPGs). However, gD may also be involved in virus binding in an HSPG-independent manner. To date, the respective cellular receptors are still unknown. In this report, we identified a host molecule, THBS3, involved in gD-mediated PRV binding and subsequent membrane fusion and entry, which increases our understanding of the initial events in alpha herpesvirus infections.

Interfacial engineering of heterostructured Fe-Ni3S2/Ni(OH)2 nanosheets with tailored d-band center for enhanced oxygen evolution catalysis.

Hydrogen production by electrochemical water splitting suffers from high kinetic barriers in the anodic oxygen evolution reaction (OER), which limits the overall efficiency. Herein, we report a structural and electronic engineering strategy by integrating self-standing Fe-doped Ni3S2 (denoted by Fe-Ni3S2) nanosheet arrays with Ni(OH)2 subunits to form heterostructured Fe-Ni3S2/Ni(OH)2 on a Ni Foam substrate. The strong electronic interaction between the Fe-Ni3S2 and Ni(OH)2 constituents contributes abundant catalytic sites and ensures high electron transfer. Moreover, the combined experimental and theoretical study revealed that the coupling of Ni(OH)2 onto the Fe-Ni3S2 is favorable for lowering the activation energy of water oxidation for favorable OER kinetics and upshifting the Ni d-band center to facilitate the adsorption of O-containing intermediates. Consequently, the optimized Fe-Ni3S2/Ni(OH)2 hybrid catalyst exhibits excellent OER performance in alkaline electrolytes with an ultralow overpotential of 202 mV at 10 mA cm-2, a small Tafel slope of 50.6 mV dec-1, and long-term durability under high current density (0.25 A cm-2) for up to 60 h without significant deactivation. Moreover, a two-electrode Fe-Ni3S2/Ni(OH)2||Pt/C electrolyzer requires only a low voltage of 1.54 V at 10 mA cm-2 for overall water splitting. This study emphasizes the importance of interface and surface engineering in achieving highly efficient electrocatalysts.

CD8+ T cell/cancer-associated fibroblast ratio stratifies prognostic and predictive responses to immunotherapy across multiple cancer types.

Background: Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) are critical for immune suppression by restricting immune cell infiltration in the tumor stromal zones from penetrating tumor islands and changing their function status, particularly for CD8+ T cells. However, assessing and quantifying the impact of CAFs on immune cells and investigating how this impact is related to clinical outcomes, especially the efficacy of immunotherapy, remain unclear. Materials and methods: The TME was characterized using immunohistochemical (IHC) analysis using a large-scale sample size of gene expression profiles. The CD8+ T cell/CAF ratio (CFR) association with survival was investigated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) lung cancer cohorts. The correlation between CFR and immunotherapeutic efficacy was computed in five independent cohorts. The correlation between CFR and objective response rates (ORRs) following pembrolizumab monotherapy was investigated in 20 solid tumor types. To facilitate clinical translation, the IHC-detected CD8/α-SMA ratio was applied as an immunotherapeutic predictive biomarker in a real-world lung cancer cohort. Results: Compared with normal tissue, CAFs were enriched in cancer tissue, and the amount of CAFs was overwhelmingly higher than that in other immune cells. CAFs are positively correlated with the extent of immune infiltration. A higher CFR was strongly associated with improved survival in lung cancer, melanoma, and urothelial cancer immunotherapy cohorts. Within most cohorts, there was no clear evidence for an association between CFR and programmed death-ligand 1 (PD-L1) or tumor mutational burden (TMB). Compared with TMB and PD-L1, a higher correlation coefficient was observed between CFR and the ORR following pembrolizumab monotherapy in 20 solid tumor types (Spearman's r = 0.69 vs. 0.44 and 0.21). In a real-world cohort, patients with a high CFR detected by IHC benefited considerably from immunotherapy as compared with those with a low CFR (hazard ratio, 0.37; 95% confidence interval, 0.19-0.75; p < 0.001). Conclusions: CFR is a newly found and simple parameter that can be used for identifying patients unlikely to benefit from immunotherapy. Future studies are needed to confirm this finding.

[Development and Application of the First Carbon Ion Therapy System in China].

At present, heavy ion is an ideal radiation for cancer treatment, and carbon ion is used in the treatment of many kinds of cancer due to its higher relative biological effect value. In 2019, Wuwei heavy ion center built the first medical heavy ion accelerator-carbon ion radiotherapy system in China, and obtained the registration license from the National Medical Products Administration, and officially received cancer patients in March 2020. This study introduced the development and application of the first carbon ion radiotherapy system in China.