Toward Ultrahigh-Rate Energy Storage of 3000 mV s-1 in Hollow Carbon: From Methodology to Surface-to-Bulk Synergy Insights.

Despite great efforts on economical and functionalized carbon materials, their scalable applications are still restricted by the unsatisfying energy storage capability under high-rate conditions. Herein, theoretical and methodological insights for surface-to-bulk engineering of multi-heteroatom-doped hollow porous carbon (HDPC), with subtly designed Zn(OH)F nanoarrays as the template are presented. This fine-tuned HDPC delivers an ultrahigh-rate energy storage capability even at a scan rate of 3000 mV s-1 (fully charged within 0.34 s). It preserves a superior capacitance of 234 F g-1 at a super-large current density of 100 A g-1 and showcases an ultralong cycling life without capacitance decay after 50 000 cycles. Through dynamic and theoretical analysis, the key role of in situ surface-modified heteroatoms and defects in decreasing the K+-adsorption/diffusion energy barrier is clarified, which cooperates with the porous conductive highways toward enhanced surface-to-bulk activity and kinetics. In situ Raman aids in visualizing the reversibly dynamic adsorption/releasing of the electrolyte ions on the tailored carbon structure during the charge/discharge process. The potential of the design concept is further evidenced by the enhanced performances in water-in-salt electrolytes. This surface-to-bulk nanotechnology opens the path for developing high-performance energy materials to better meet the practical requirements in the future.

Reconfiguration, Welding, Reprogramming, and Complex Shape Transformation of An Optical Shape Memory Polymer Network Enabled by Patterned Secondary Crosslinking.

Stimuli-triggered generation of complicated 3D shapes from 2D strips or plates without using sophisticated molds is desirable and achieving such 2D-to-3D shape transformation in combination with shape reconfiguration, welding, and reprogramming on a single material is very challenging. Here, a convenient and facile strategy using the solution of a disulfide-containing diamine for patterned secondary crosslinking of an optical shape-memory polymer network is developed to integrate the above performances. The dangling thiolectones attached to the backbones react with the diamine in the solution-deposited region so that the secondary crosslinking may not only weld individual strips into assembled 3D shapes but also suppress the relaxation of the deformed polymer chains to different extents for shape reconfiguration or heating-induced complex 3D deformations. In addition, as the dynamic disulfide bonds can be thermally activated to erase the initial programming information and the excessive thiolectones are available for subsequent patterned crosslinking, the material also allows shape reprogramming. Combining welding with patterning treatment, it is further demonstrated that a gripper can be assembled and photothermally controlled to readily grasp an object.

Effect of Crystal Transformation on the Intrinsic Defects and the Microwave Absorption Performance of Mo2 TiC2 Tx /RGO Microspheres.

The nitrides and carbides of transition metals are highly favored due to their excellent physical and chemical properties, among which MXene is a hot research topic for microwave absorption. Herein, the controlled preparation of 3D Mo2 TiC2 Tx -based microspheres toward microwave absorption is reported for the first time. With the merits of the performances of both reduced graphite oxide (RGO) and MXene sufficiently considered, the influence of carbonization temperature on the internal crystal structure and the effective microwave-material interaction surface of the prepared Mo2 TiC2 Tx /RGO is systematically investigated. The structure-activity relationships relating the apparent morphology and crystal structure to the microwave absorption performance are deeply explored, and the wave absorption mechanism is put forward as well. The results show that the Mo2 TiC2 Tx /RGO-700 product obtained after heating treatment at 700 °C exhibits excellent microwave absorption performance, with the RLmin being up to -55.1 dB@2.1 mm@13.8 GHz, and the corresponding effective absorption bandwidth covering 5.7 GHz. The outstanding microwave absorption characteristics are attributed to the appropriate impedance matching, high specific surface area, rich intrinsic defects, desirable conductivity, and strong multipolarization capabilities. This work enriches the types of MXene-based composite absorbers and provides a new strategy for controlled preparation of high-performance 3D composite absorbers.

New Insight into the Electronic Effect for Cu Porphyrin Catalysts in Electrocatalytic of CO2 into CH4.

Perturbation of the copper (Cu) active site by electron manipulation is a crucial factor in determining the activity and selectivity of electrochemical carbon dioxide (CO2 ) reduction reaction (e-CO2 RR) in Cu-based molecular catalysts. However, much ambiguity is present concerning their electronic structure-function relationships. Here, three molecular Cu-based porphyrin catalysts with different electron densities at the Cu active site, Cu tetrakis(4-methoxyphenyl)porphyrin (Cu─T(OMe)PP), Cu tetraphenylporphyrin (Cu─THPP), and Cu tetrakis(4-bromophenyl)porphyrin (Cu─TBrPP), are prepared. Although all three catalysts exhibit e-CO2 RR activity and the same reaction pathway, their performance is significantly affected by the electronic structure of the Cu site. Theoretical and experimental investigations verify that the conjugated effect of ─OCH3 and ─Br groups lowers the highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbitals (LUMO) gap of Cu─T(OMe)PP and Cu─TBrPP, promoting faster electron transfer between Cu and CO2 , thereby improving their e-CO2 RR activity. Moreover, the high inductive effect of ─Br group reduces the electron density of Cu active site of Cu─TBrPP, facilitating the hydrolysis of the bound H2 O and thus creating a preferable local microenvironment, further enhancing the catalytic performance. This work provides new insights into the relationships between the substituent group characteristics with e-CO2 RR performance and is highly instructive for the design of efficient Cu-based e-CO2 RR electrocatalysts.

ELAVL4 promotes the tumorigenesis of small cell lung cancer by stabilizing LncRNA LYPLAL1-DT and enhancing profilin 2 activation.

Small cell lung cancer (SCLC) is one of the most malignant tumors that has an extremely poor prognosis. RNA-binding protein (RBP) and long noncoding RNA (lncRNA) have been shown to be key regulators during tumorigenesis as well as lung tumor progression. However, the role of RBP ELAVL4 and lncRNA LYPLAL1-DT in SCLC remains unclear. In this study, we verified that lncRNA LYPLAL1-DT acts as an SCLC oncogenic lncRNA and was confirmed in vitro and in vivo. Mechanistically, LYPLAL1-DT negatively regulates the expression of miR-204-5p, leading to the upregulation of PFN2, thus, promoting SCLC cell proliferation, migration, and invasion. ELAVL4 has been shown to enhance the stability of LYPLAL1-DT and PFN2 mRNA. Our study reveals a regulatory pathway, where ELAVL4 stabilizes PFN2 and LYPLAL1-DT with the latter further increasing PFN2 expression by blocking the action of miR-204-5p. Upregulated PFN2 ultimately promotes tumorigenesis and invasion in SCLC. These findings provide novel prognostic indicators as well as promising new therapeutic targets for SCLC.

Access to 2,4-Disubstituted Pyrrole-Based Polymer with Long-Wavelength and Stimuli-Responsive Properties via Copper-Catalyzed [3+2] Polycycloaddition.

Pyrrole-based polymers (PBPs), a type of fascinating functional polymers, play a crucial role in materials science. However, efficient synthetic strategies of PBPs with diverse structures are mainly focused on conjugated polypyrroles and still remain challenging. Herein, an atom and step economy protocol is described to access various 2,4-disubstituted PBPs by in situ formation of pyrrole core structure via copper-catalyzed [3+2] polycycloaddition of dialkynones and diisocyanoacetates. A series of PBPs is prepared with high molecular weight (Mw up to 18 200 Da) and moderate to good yield (up to 87%), which possesses a fluorescent emission located in the green to yellow light region. Blending the PBPs with polyvinyl alcohol, the stretchable composite films exhibit a significant strengthening of the mechanical properties (tensile stress up to 59 MPa, elongation at break >400%) and an unprecedented stress-responsive luminescence enhancement that over fourfold fluorescent emission intensity is maintained upon stretching up to 100%. On the basis of computational studies, the unique photophysical and mechanical properties are attributed to the substitution of carbonyl chromophores on the pyrrole unit.

Top-down influence of areas 21a and 7 differently affects the surround suppression of V1 neurons in cats.

Surround suppression (SS) is a phenomenon whereby a neuron's response to stimuli in its central receptive field (cRF) is suppressed by stimuli extending to its surround receptive field (sRF). Recent evidence show that top-down influence contributed to SS in the primary visual cortex (V1). However, how the top-down influence from different high-level cortical areas affects SS in V1 has not been comparatively observed. The present study applied transcranial direct current stimulation (tDCS) to modulate the neural activity in area 21a (A21a) and area 7 (A7) of cats and examined the changes in the cRF and sRF of V1 neurons. We found that anode-tDCS at A21a reduced V1 neurons' cRF size and increased their response to visual stimuli in cRF, causing an improved SS strength. By contrast, anode-tDCS at A7 increased V1 neurons' sRF size and response to stimuli in cRF, also enhancing the SS. Modeling analysis based on DoG function indicated that the increased SS of V1 neurons after anode-tDCS at A21a could be explained by a center-only mechanism, whereas the improved SS after anode-tDCS at A7 might be mediated through a combined center and surround mechanism. In conclusion, A21a and A7 may affect the SS of V1 neurons through different mechanisms.

Constructing mesoporous biochar derived from waste carton: Improving multi-site adsorption of dye wastewater and investigating mechanism.

The development of cost-efficient biochar adsorbent with a simple preparation method is essential to constructing efficient wastewater treatment system. Here, a low-cost waste carton biochar (WCB) prepared by a simple two-step carbonization was applied in efficiently removing Rhodamine B (RhB) in aqueous environment. The maximum ability of WCB for RhB adsorption was 222 mg/g, 6 and 10 times higher than both of rice straw biochar (RSB) and broadbean shell biochar (BSB), respectively. It was mainly ascribed to the mesopore structure (3.0-20.4 nm) of WCB possessing more spatial sites compared to RSB (2.2 nm) and BSB (2.4 nm) for RhB (1.4 nm✕1.1 nm✕0.6 nm) adsorption. Furthermore, external mass transfer (EMT) controlled mass transfer resistance (MTR) of the RhB sorption process by WCB which was fitted with the Langmuir model well. Meanwhile, the adsorption process was dominated by physisorption through van der Waals forces and π-π interactions. A mixture of three dyes in river water was well removed by using WCB. This work provides a straightforward method of preparing mesoporous biochar derived from waste carton with high-adsorption capacity for dye wastewater treatment.

Monitoring soil moisture in winter wheat with crop water stress index based on canopy-air temperature time lag effect.

Crop water stress index (CWSI) has been widely used in soil moisture monitoring. However, the influence of the time lag effect between canopy temperature and air temperature on the accuracy of soil moisture monitoring with different CWSI models has not been further investigated. Therefore, based on the continuous record of canopy temperature and air temperature, this study explored the influence of canopy-air temperature hysteresis on the diagnosis of soil moisture with three CWSI models (CWSIT-theoretical, CWSIE-empirical, CWSIH-hybrid). The results show (1) the peak time of canopy temperature was ahead of that of air temperature, and the lag time varied under different soil moisture conditions. When the soil moisture was seriously deficient, the lag time decreased. However, from jointing-heading period to filling-ripening period, the lag time became longer. (2) The values of CWSIT, CWSIE, and CWSIH decreased when the time lag effect was considered. In jointing-heading period, heading-filling period, and filling-ripening period, CWSIT had the highest accuracy in soil moisture monitoring without the consideration of the time lag effect. When the time lag effect was considered, the monitoring accuracy of CWSIE and CWSIH was greatly improved and higher than that of CWSIT, while that of CWSIT was reduced. The findings provided a basis for further improving the accuracy of soil moisture monitoring with CWSI models.

Nanoenzyme-Reinforced Multifunctional Scaffold Based on Ti3C2Tx MXene Nanosheets for Promoting Structure-Functional Skeletal Muscle Regeneration via Electroactivity and Microenvironment Management.

The completed volumetric muscle loss (VML) regeneration remains a challenge due to the limited myogenic differentiation as well as the oxidative, inflammatory, and hypoxic microenvironment. Herein, a 2D Ti3C2Tx MXene@MnO2 nanocomposite with conductivity and microenvironment remodeling was fabricated and applied in developing a multifunctional hydrogel (FME) scaffold to simultaneously conquer these hurdles. Among them, Ti3C2Tx MXene with electroconductive ability remarkably promotes myogenic differentiation via enhancing the myotube formation and upregulating the relative expression of the myosin heavy chain (MHC) protein and myogenic genes (MyoD and MyoG) in myogenesis. The MnO2 nanoenzyme-reinforced Ti3C2Tx MXene significantly reshapes the hostile microenvironment by eliminating reactive oxygen species (ROS), regulating macrophage polarization from M1 to M2 and continuously supplying O2. Together, the FME hydrogel as a bioactive multifunctional scaffold significantly accelerates structure-functional VML regeneration in vivo and represents a multipronged strategy for the VML regeneration via electroactivity and microenvironment management.

Bridging Nickel-MOF and Copper Single Atoms/Clusters with H-Substituted Graphdiyne for the Tandem Catalysis of Nitrate to Ammonia.

Interfacial engineering of synergistic catalysts is one of the keys to achieving multiple proton-coupled electron transfer processes in nitrate-to-ammonia conversion. Herein, by joining ultrathin nickel-based metal-organic framework (denoted Ni-MOF) nanosheets with few-layered hydrogen-substituted graphdiyne-supported copper single atoms and clusters (denoted HsGDY@Cu), a tandem catalyst of Ni-MOFs@HsGDY@Cu with dual-active interfaces was developed for the concerted catalysis of nitrate-to-ammonia. In such a system, the sandwiched HsGDY layer could serve as a bridge to connect the coordinated unsaturated Ni2+ sites with Cu single atoms/clusters in a limited range of 0 to 3.6 nm. From Ni2+ to Cu, via the hydrogen spillover process, the hydrogen radicals (H⋅) generated at the unsaturated Ni2+ sites could migrate across HsGDY to the Cu sites to participate in the transformation of *HNO3 to NH3. From Cu to Ni2+, bypassing the higher reaction energy for *HNO3 formation on the Ni2+ sites, the NO2 - detached from the Cu sites could diffuse onto the unsaturated Ni2+ sites to form NH3 as well. The combined results make this hybrid a tandem catalyst with dual active sites for the catalysis of nitrate-to-ammonia conversion with improved Faradaic efficiency at lower overpotentials.

Placenta-derived exosomal miR-135a-5p promotes gestational diabetes mellitus pathogenesis by activating PI3K/AKT signalling pathway via SIRT1.

Most people are aware of gestational diabetes mellitus (GDM), a dangerous pregnancy complication in which pregnant women who have never been diagnosed with diabetes develop chronic hyperglycaemia. Exosomal microRNA (miRNA) dysregulation has been shown to be a key player in the pathophysiology of GDM. In this study, we looked into how placental exosomes and their miRNAs may contribute to GDM. When compared to exosomes from healthy pregnant women, it was discovered that miR-135a-5p was elevated in placenta-derived exosomes that were isolated from the maternal peripheral plasma of GDM women. Additionally, we discovered that miR-135a-5p encouraged HTR-8/SVneo cell growth, invasion and migration. Further research revealed that miR-135a-5p activates HTR-8/SVneo cells' proliferation, invasion and migration by promoting PI3K/AKT pathway activity via Sirtuin 1 (SIRT1). The transfer of exosomal miR-135a-5p generated from the placenta could be viewed as a promising agent for targeting genes and pertinent pathways involved in GDM, according to our findings.

The loss of B7-H4 expression in breast cancer cells escaping from T cell cytotoxicity contributes to epithelial-to-mesenchymal transition.

BACKGROUND: B7 homology 4 (B7-H4), a potential target for cancer therapy, has been demonstrated to inhibit T cell cytotoxicity in the early stages of breast cancer. However, B7-H4 manipulating breast tumor immune microenvironment (TIME) in the tumor progression remains unknown. METHODS: We engineered T cells with B7-H4-specific chimeric antigen receptors (CARs) and performed a T cell co-culture assay to characterize B7-H4 expression level in breast cancer cells escaping from T cell cytotoxicity. We generated B7-H4 knockout (KO) and overexpression (OE) breast cancer cells to determine the epithelial-to-mesenchymal transition (EMT) and stemness characteristics in vitro and in vivo, including tumor proliferation, migration, metastasis and chemoresistance. The Cancer Genome Atlas breast cancer database was accessed to investigate the correlation between B7-H4 expression levels and EMT characteristics in patients with breast cancer. RESULTS: Our result found that B7-H4 expression level was significantly reduced in a subset of breast cancer cells that escaped from the cytotoxicity of B7-H4 CAR-T cells. Compared with wild type cells, B7-H4 KO cells prompt EMT and stemness characteristics, including migration, invasion and metastasis, and OE cells vice versa. The increase in H3K27me3 in KO cells confirmed the epigenetic reprogramming of cancer stem cells. The IC50 of doxorubicin or oxaliplatin significantly increased in KO cells, which was in agreement with a decrease in OE cells. Moreover, a trend of downregulated B7-H4 from stage I to stage II breast cancer patients indicates that the low-expressing B7-H4 breast cancer cells escaping from TIME have spread to nearby breast lymph nodes in the cancer progression. CONCLUSIONS: Our study illuminates the novel role of renouncing B7-H4 in breast cancer cells through immune escape, which contributes to EMT processes and provides new insights for breast cancer treatments.

Interaction of glioma-associated microglia/macrophages and anti-PD1 immunotherapy.

Anti-PD-1-based therapy has resulted in a minimal clinical response in malignant gliomas. Gliomas contain numerous glioma-associated microglia/macrophages (GAMs), reported to contribute to an immunosuppressive microenvironment and promote glioma progression. However, whether and how GAMs affect anti-PD-1 immunotherapy in glioma remains unclear. Here, we demonstrated that M1-like GAMs contribute to the anti-PD-1 therapeutic response, while the accumulation of M2-like GAMs is associated with therapeutic resistance. Furthermore, we found that PD-L1 ablation reverses GAMs M2-like phenotype and is beneficial to anti-PD-1 therapy. We also demonstrated that tumor-induced impairment of the antigen-presenting function of GAMs could limit the antitumor immunity of CD4+ T cells in anti-PD-1 therapy. Our study highlights the impact of GAMs activation on anti-PD-1 treatment and provides new insights into the role of GAMs in regulating anti-PD-1 therapy in gliomas.

Toward Ultrahigh-Rate Energy Storage of 3000 mV s-1 in Hollow Carbon: From Methodology to Surface-to-Bulk Synergy Insights.

Despite great efforts on economical and functionalized carbon materials, their scalable applications are still restricted by the unsatisfying energy storage capability under high-rate conditions. Herein, theoretical and methodological insights for surface-to-bulk engineering of multi-heteroatom-doped hollow porous carbon (HDPC) is presented, with subtly designed Zn(OH)F nanoarrays as the template. This fine-tuned HDPC delivers an ultrahigh-rate energy storage capability even at a scan rate of 3000 mV s-1 (fully charged within 0.34 s). It preserves a superior capacitance of 234 F g-1 at a super-large current density of 100 A g-1 and showcases an ultralong cycling life without capacitance decay after 50 000 cycles. Through dynamic and theoretical analysis, the key role of in situ surface-modified heteroatoms and defects in decreasing the K+ -adsorption/diffusion energy barrier is clarified, which cooperates with the porous conductive highways toward enhanced surface-to-bulk activity and kinetics. In situ Raman further aids in visualizing the reversibly dynamic adsorption/releasing of the electrolyte ions on the tailored carbon structure during the charge/discharge process. The potential of the design concept is further evidenced by the enhanced performances in water-in-salt electrolytes. This surface-to-bulk nanotechnology opens the path for developing high-performance energy materials to better meet the practical requirements in future.

Sequentially Controlled Recognition of Different Proteins Using Programmable Protein Imprinted Nanospheres.

Although protein imprinted materials with multiple templates are developed to selectively separate different proteins, it is difficult to achieve the programmed adsorption and separation of different proteins using one material, because the available protein imprinted materials are constructed through irreversible crosslinking and their structures are unprogrammable and non-reconstructive. Herein, a novel nanosphere (MS@PTL-g-PNIPAM) is designed, which not only is temperature and pH responsive but also can dynamically reversibly crosslink/de-crosslink under ultraviolet light of different wavelengths. With the help of the dynamically reversible photo-crosslinking, the nanospheres can be repeatedly programmed into protein imprinted nanospheres toward different target proteins. Moreover, the prepared imprinted nanospheres can easily achieve the controlled rebinding and release of target proteins, benefiting from the introduced temperature- and pH-responsive moieties. As a consequence, this study realizes the specific separation of different target proteins from protein mixture and the real bovine blood sequentially by programming one material. It is resource saving, time saving, recyclable, and it will provide convenience for protein imprinted materials to use in the blood purification, drug delivery, and virus detection.

Fabrication of Graphdiyne/Graphene Composite Microsphere with Wrinkled Surface via Ultrasonic Spray Compounding and its Microwave Absorption Properties.

Advanced carbon materials are constantly being used in the field of microwave absorption. Herein, in order to enrich the variety and expand the application fields of graphdiyne (GDY), the wrinkled graphene (RGO) nanosheet coated and embedded with GDY porous microspheres (RGO/GDY) are prepared by GDY synthesis, ultrasonic spray, and pyrolysis. The study finds that RGO and GDY have effective synergistic effects. The suitable pores and composition, conductive network formed by overlapping 0D and 2D materials, special surface and internal morphology design, and high-temperature activation process make RGO/GDY exhibit excellent impedance matching and attenuation capabilities. Under the best amount of GDY (20 mg), the particle sizes of the microspheres (≈6 µm), and filler content (27.5%), the minimum reflection loss (RLmin ) is -58 dB@8.3 GHz, and the corresponding matching thickness is 2.7 mm. The effective absorption bandwidth is 4.3 GHz as the thickness is 1.9 mm. By adjusting the thickness, the absorber can completely absorb microwaves of all the C, X, and Ku bands. The microwave absorbing mechanisms are elucidated. GDY materials are first applied to the field of microwave absorption, enhancing the absorption performance of RGO/GDY. It provides a new way to manufacture electromagnetic wave absorbers with satisfactory performance.

Optimization of optical and structural properties of Al2O3/TiO2 nano-laminates deposited by atomic layer deposition for optical coating.

Optimizing the atomic layer deposition (ALD) process of films is particularly important in preparing multilayer interference films. In this work, a series of Al2O3/TiO2 nano-laminates with a fixed growth cycle ratio of 1:10 were deposited on Si and fused quartz substrates at 300 °C by ALD. The optical properties, crystallization behavior, surface appearance and microstructures of those laminated layers were systematically investigated by spectroscopic ellipsometry, spectrophotometry, X-ray diffraction, atomic force microscope and transmission electron microscopy. By inserting Al2O3 interlayers into TiO2 layers, the crystallization of the TiO2 is reduced and the surface roughness becomes smaller. The TEM images show that excessively dense distribution of Al2O3 intercalation leads to the appearance of TiO2 nodules, which in turn leads to increased roughness. The Al2O3/TiO2 nano-laminate with a cycle ratio 40:400 has relatively small surface roughness. Additionally, oxygen-deficient defects exist at the interface of Al2O3 and TiO2, leading to evident absorption. Using O3 as an oxidant instead of H2O for depositing Al2O3 interlayers was verified to be effective in reducing absorption during broadband antireflective coating experiments.

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.