Non-small cell lung cancer (NSCLC) is known to carry heavy mutation load. Besides smoking, cytidine deaminase APOBEC3B plays a key role in the mutation process of NSCLC. APOBEC3B is also reported to ...be upregulated and predicts bad prognosis in NSCLC. However, targeting APOBEC3B high NSCLC is still a big challenge. Here we show that APOBEC3B upregulation is significantly associated with immune gene expression, and APOBEC3B expression positively correlates with known immunotherapy response biomarkers, including: PD-L1 expression and T-cell infiltration in NSCLC. Importantly, APOBEC mutational signature is specifically enriched in NSCLC patients with durable clinical benefit after immunotherapy and APOBEC mutation count can be better than total mutation in predicting immunotherapy response. In together, this work provides evidence that APOBEC3B upregulation and APOBEC mutation count can be used as novel predictive markers in guiding NSCLC checkpoint blockade immunotherapy.
In this paper, a wideband directional coupler is proposed for high‐power applications, which is composed of a transformer and lumped elements. The introduction of the transformer greatly improves the ...directivity of the coupler. The measurement results demonstrate that the proposed design has an excellent return loss (>17 dB), small insertion loss (<0.4 dB), and high directivity (>22) over a wide frequency band (10–350 MHz). Meanwhile, it can achieve a flat coupling level of 32 dB with the imbalance less than 0.5 dB.
A wideband directional coupler is proposed for high‐power applications, which is composed of a transformer and lumped elements. The introduction of the transformer greatly improves the directivity of the coupler.
Immunotherapy, represented by immune checkpoint inhibitors (ICI), is transforming the treatment of cancer. However, only a fraction of patients show response to ICI, and there is an unmet need for ...biomarkers that will identify patients more likely to respond to ICI. Here we report that the ICI response prediction biomarker tumor mutational burden (TMB) shows significant sex differences. TMB's predictive power is significantly better for female than for male lung cancer patients. Receiver operating characteristic curve analysis was performed and the area under the curve (AUC) was reported to evaluate the predictive power of TMB in lung cancer ICI response. Hazard ratios (HR) of TMB‐high vs. TMB‐low patients were compared between male and female patients. Both AUC and HR differences between female and male are significant in all available independent lung cancer datasets. However, the AUC of programmed death ligand 1 (PD‐L1) expression does not show a difference between female and male, suggesting TMB, but not PD‐L1 expression has a better predictive power for female than for male lung cancer patients. Our study suggests significant sex differences in the performance of TMB in ICI response prediction. Future development of ICI biomarker should consider sex differences and special efforts should be paid to improve the performance of ICI predictive biomarkers for male lung cancer patients.
What's new?
Only a fraction of cancer patients show response to immune checkpoint inhibitors (ICI), and there remains an unmet need for biomarkers to select patients most likely to benefit. Inherent sex differences in immune response could potentially influence the performance of predictive biomarkers. Here, the authors report that the emerging biomarker tumor mutational burden (TMB) shows significant sex differences, with TMB's predictive power being significantly better for female than for male lung cancer patients. Future development of predictive biomarkers for ICI response should consider sex differences, and the performance of biomarkers for male lung cancer patients should also be improved.
Sex differences in innate and adaptive immune responses are known, and women generally mount a stronger immune response than men. Cancer immunotherapy, represented by immune checkpoint inhibitors ...(ICIs), has revolutionized the treatment of cancer, and sex differences in cancer immunotherapy are just starting to be revealed. Here, we summarize recent research progress concerning sex differences in cancer immunotherapy efficacy. On their own, ICIs tend to be more effective in male cancer patients compared with female patients, while ICIs combined with chemotherapy tend to be more effective in female patients than male patients. Male tumors are usually more antigenic than female tumors, and this is reflected by their increased number of tumor mutations and cancer germline antigens. The biomarker tumor mutational burden (TMB), which reflects tumor antigenicity, is more effective at predicting immunotherapy response for female lung cancer patients than for male patients. In this review, we propose different therapeutic strategies for the different sexes: For male cancer patients, the immune environment should be enhanced, whereas for female cancer patients, tumor antigenicity should be enhanced.
Designing antibacterial surfaces has become extremely important to minimize Healthcare Associated Infections which are a major cause of mortality worldwide. A previous biocide-releasing approach is ...based on leaching of encapsulated biocides such as silver and triclosan which exerts negative impacts on the environment and potentially contributes to the development of bacterial resistance. This drawback of leachable compounds led to the shift of interest towards a more sustainable and environmentally friendly approach: contact-killing surfaces. Biocides that can be bound onto surfaces to give the substrates contact-active antibacterial activity include quaternary ammonium compounds (QACs), quaternary phosphoniums (QPs), carbon nanotubes, antibacterial peptides, and N-chloramines. Among the above, QACs and N-chloramines are the most researched contact-active biocides. We review the engineering of contact-active surfaces using QACs or N-chloramines, the modes of actions as well as the test methods. The charge-density threshold of cationic surfaces for desired antibacterial efficacy and attempts to combine various biocides for the generation of new contact-active surfaces are discussed in detail. Surface positive charge density is identified as a key parameter to define antibacterial efficacy. We expect that this research field will continue to attract more research interest in view of the potential impact of self-disinfective surfaces on healthcare-associated infections, food safety and corrosion/fouling resistance required on industrial surfaces such as oil pipes and ship hulls.
Genome alteration signatures reflect recurring patterns caused by distinct endogenous or exogenous mutational events during the evolution of cancer. Signatures of single base substitution (SBS) have ...been extensively studied in different types of cancer. Copy number alterations are important drivers for the progression of multiple cancer. However, practical tools for studying the signatures of copy number alterations are still lacking. Here, a user-friendly open source bioinformatics tool "sigminer" has been constructed for copy number signature extraction, analysis and visualization. This tool has been applied in prostate cancer (PC), which is particularly driven by complex genome alterations. Five copy number signatures are identified from human PC genome with this tool. The underlying mutational processes for each copy number signature have been illustrated. Sample clustering based on copy number signature exposure reveals considerable heterogeneity of PC, and copy number signatures show improved PC clinical outcome association when compared with SBS signatures. This copy number signature analysis in PC provides distinct insight into the etiology of PC, and potential biomarkers for PC stratification and prognosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nitrogen‐doped carbon materials are proposed as promising electrocatalysts for the carbon dioxide reduction reaction (CRR), which is essential for renewable energy conversion and environmental ...remediation. Unfortunately, the unclear cognition on the CRR active site (or sites) hinders further development of high‐performance electrocatalysts. Herein, a series of 3D nitrogen‐doped graphene nanoribbon networks (N‐GRW) with tunable nitrogen dopants are designed to unravel the site‐dependent CRR activity/selectivity. The N‐GRW catalyst exhibits superior CO2 electrochemical reduction activity, reaching a specific current of 15.4 A gcatalyst−1 with CO Faradaic efficiency of 87.6% at a mild overpotential of 0.49 V. Based on X‐ray photoelectron spectroscopy measurements, it is experimentally demonstrated that the pyridinic N site in N‐GRW serves as the active site for CRR. In addition, the Gibbs free energy calculated by density functional theory further illustrates the pyridinic N as a more favorable site for the CO2 adsorption, *COOH formation, and *CO removal in CO2 reduction.
A 3D nitrogen‐doped graphene nanoribbon network is constructed by the chemical pyrolysis with high CO2 electrochemical reduction performance. The pyridinic N site is proved to be the active site by experimental and density functional theory calculations.
In recent years, the optimization of eight-link pressure mechanism using ant colony algorithm is a research hotspot, but given the limitations of traditional ant colony algorithm, this paper improves ...the ant colony algorithm based on the SSA-IACO algorithm and develops the application and analysis of eight-link pressure mechanism and its dynamic simulation. Through the study of parameter settings before and after optimization, simulation analysis and other aspects, it is concluded that: the efficiency of the new scheme optimized by the improved ant colony algorithm is 88.86% higher than the original scheme. The stator power is reduced by 4.10% and the power factor is increased by 14.67% on average over the original scheme. The maximum magnitude of the free end torsion angle of the crankshaft system is 0.16 degrees, and the increased resonance speed is about 1800 rpm. The maximum torsion angle of the main harmonic (6th harmonic) is reduced from 0.54 to 0.16, and the damping effect is noticeable. When 0.7 ≤
0.8, and ρ is close to 0.7, the algorithm performs better. When 0.15 ≤
0.2, and the value of θ is more comparable to 0.15, the algorithm obtains the optimal solution and the execution time is shorter than the 0.7,0.2 combination.
Immunotherapy, represented by immune checkpoint inhibitors (ICI), is transforming the treatment of cancer. However, only a small percentage of patients show response to ICI, and there is an unmet ...need for biomarkers that will identify patients who are more likely to respond to immunotherapy. The fundamental basis for ICI response is the immunogenicity of a tumor, which is primarily determined by tumor antigenicity and antigen presentation efficiency. Here, we propose a method to measure tumor immunogenicity score (TIGS), which combines tumor mutational burden (TMB) and an expression signature of the antigen processing and presenting machinery (APM). In both correlation with pan-cancer ICI objective response rates (ORR) and ICI clinical response prediction for individual patients, TIGS consistently showed improved performance compared to TMB and other known prediction biomarkers for ICI response. This study suggests that TIGS is an effective tumor-inherent biomarker for ICI-response prediction.
Abstract
Photocatalytic CO
2
reduction (PCR) is able to convert solar energy into chemicals, fuels, and feedstocks, but limited by the deficiencies of photocatalysts in steering photon-to-electron ...conversion and activating CO
2
, especially in pure water. Here we report an efficient, pure water CO
2
-to-CO conversion photocatalyzed by sub-3-nm-thick BiOCl nanosheets with van der Waals gaps (VDWGs) on the two-dimensional facets, a graphene-analog motif distinct from the majority of previously reported nanosheets usually bearing VDWGs on the lateral facets. Compared with bulk BiOCl, the VDWGs-rich atomic layers possess a weaker excitonic confinement power to decrease exciton binding energy from 137 to 36 meV, consequently yielding a 50-fold enhancement in the bulk charge separation efficiency. Moreover, the VDWGs facilitate the formation of VDWG-Bi-V
O
••
-Bi defect, a highly active site to accelerate the CO
2
-to-CO transformation via the synchronous optimization of CO
2
activation, *COOH splitting, and *CO desorption. The improvements in both exciton-to-electron and CO
2
-to-CO conversions result in a visible light PCR rate of 188.2 μmol g
−1
h
−1
in pure water without any co-catalysts, hole scavengers, or organic solvents. These results suggest that increasing VDWG exposure is a way for designing high-performance solar-fuel generation systems.
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