Combined Strategy Research Articles

Two-step modification strategy enhances carbon fiber/old corrugated container fiber flexible conductive film

Carbon fiber (CF) possesses inherent properties of low density, high strength, and environmental stability. Its high aspect ratio and knittability enable the formation of flexible conductive networks. Old corrugated container (OCC) is rich in cellulose and hemicellulose, rendering them flexible and exhibiting a low coefficient of thermal expansion. In this paper, CF/OCC/PVA flexible conductive films were prepared using polyvinyl alcohol (PVA) as the matrix, CF as the conductive filler and OCC as the flexible support material. Firstly, the coupling agent was grafted on the surface of CF to enhance their surface activity, improve the dispersion of CF in solution and the chemical bonding of CF to the matrix. Subsequently, sizing nanoparticles were applied to increase the roughness of the CF surface. This served to increase the volume of the conductive network and enhance the mechanical interlocking between CF and PVA. The results show that the two-step combined modification strategy have a significant positive impact on the interfacial chemical activity, contact angle, and roughness of CF. Moreover, it leads to notable improvements in various properties of the conductive film materials. This finding is relevant for the preparation of CF reinforced other matrix materials as well as for expanding the special properties and application value of CF conductive thin film materials.

The efficacy and safety of dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor, in patients with advanced head and neck mucosal melanoma harboring CDK4 amplification

BackgroundMucosal melanoma (MM) is a rare but devastating subtype of melanoma. Our previous studies have demonstrated robust anti-tumor effects of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors in head and neck MM (HNMM) patient-derived xenograft models with CDK4 amplification. Herein, we aimed to investigate the efficacy and safety of dalpiciclib (SHR6390), a CDK4/6 inhibitor, in HNMM patients harboring CDK4 amplification.MethodsThe anti-tumor efficacy of dalpiciclib was assessed by HNMM patient-derived xenograft (PDX) models and patient-derived tumor cells (PDC) in vivo and in vitro. Immunohistochemical analyses and western blot were then performed to assess the markers of cell proliferation and CDK4/6 signaling pathway. For the clinical trial, advanced recurrent and/or metastatic HNMM patients with CDK4 amplification were treated with dalpiciclib 125 mg once daily for 21 consecutive days in 28-day cycles. The primary endpoint was disease control rate (DCR). Secondary endpoints included safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).ResultsDalpiciclib profoundly suppressed growth of HNMM-PDX and PDC with CDK4 amplification, whereas it showed relatively weak suppression in those with CDK4 wild type compared with vehicle. And dalpiciclib resulted in a remarkable reduction in the expression levels of Ki-67 and phosphorylated Rb compared with control group. In the clinical trial, a total of 17 patients were enrolled, and 16 patients were evaluable. The ORR was 6.3%, and the DCR was 81.3%. The estimated median PFS was 9.9 months (95% CI, 4.8-NA), and the median OS was not reached. The rate of OS at 12 months and 24 months was 68.8% (95% CI, 0.494–0.957) and 51.6% (95% CI, 0.307–0.866), respectively. The most frequent adverse events were neutrophil count decrease, white blood cell count decrease, and fatigue.ConclusionsDalpiciclib was well-tolerated and displayed a durable benefit for HNMM patients with CDK4 amplification in this study. Further studies on CDK4 inhibitors and its combination strategy for MM are worth further exploration.Trial registrationChiCTR2000031608.

Advancements and challenges in triple-negative breast cancer: a comprehensive review of therapeutic and diagnostic strategies

Triple-negative breast cancer (TNBC) poses significant challenges in oncology due to its aggressive nature, limited treatment options, and poorer prognosis compared to other breast cancer subtypes. This comprehensive review examines the therapeutic and diagnostic landscape of TNBC, highlighting current strategies, emerging therapies, and future directions. Targeted therapies, including PARP inhibitors, immune checkpoint inhibitors, and EGFR inhibitors, hold promise for personalized treatment approaches. Challenges in identifying novel targets, exploring combination therapies, and developing predictive biomarkers must be addressed to optimize targeted therapy in TNBC. Immunotherapy represents a transformative approach in TNBC treatment, yet challenges in biomarker identification, combination strategies, and overcoming resistance persist. Precision medicine approaches offer opportunities for tailored treatment based on tumor biology, but integration of multi-omics data and clinical implementation present challenges requiring innovative solutions. Despite these challenges, ongoing research efforts and collaborative initiatives offer hope for improving outcomes and advancing treatment strategies in TNBC. By addressing the complexities of TNBC biology and developing effective therapeutic approaches, personalized treatments can be realized, ultimately enhancing the lives of TNBC patients. Continued research, clinical trials, and interdisciplinary collaborations are essential for realizing this vision and making meaningful progress in TNBC management.

A field trial for remediation of multi-metal contaminated soils using the combination of fly ash stabilization and Zanthoxylumbungeanum- Lolium perenne intercropping system

Insitu stabilization and phytoextraction are considered as two convenient and effective technologies for the remediation of toxic elements (TEs) in soils. However, the effectiveness of these two remediation technologies together on the bioavailability and phytoextraction of TEs in field trials has not been explored yet. Specifically, the remediation potential of fly ash (FA; as stabilizing agent) and ryegrass (as a TE accumulator) intercropped with a target crop for soil polluted with multiple TEs has not been investigated yet, particularly in long-term field trials. Therefore, in this study, a six-month combined remediation field experiment of FA stabilization and/or ryegrass intercropping (IR) was carried out on the farmland soils contaminated with As, Cd, Cr, Cu, Hg, Ni, Pb and Zn where Zanthoxylumbungeanum (ZB) trees as native crops were grown for years. The treatments include soil cultivated alone with ZB untreated- (control) and treated-with FA (FA), produced by burning lignite in Shaanxi Datong power plant, China, soil cultivated with ZB and ryegrass untreated- (IR) and treated-with FA (FA + IR). This was underpinned by a large-scale survey in Daiziying (China), which showed that the topsoils were polluted by Cd, Cu, Hg and Pb, and that Hg and Pb contents in the Zanthoxylumbungeanum fruits exceeded their allowable limits. The TEs contents in the studied FA were lower than their total element contents in the soil. The DTPA-extractable TEs contents of the remediation modes were as follows: FA < FA + IR < IR < control. Notably, TEs contents in the ZB fruits were lowest under the FA + IR treatment, which were decreased by 27.6% for As, 42.3% for Cd, 16.7% for Cr, 30.5% for Cu, 23.1% for Hg, 15.5% for Ni, 33.2% for Pb and 38.1% for Zn compared with the control treatment. Whereas the FA + IR treatment enhanced TEs contents in ryegrass shoots and roots, and the TEs contents in ryegrass shoots were below their regulatory limits for fodder crops. The findings confirmed that the combined remediation strategy, i.e., FA (with low content of TEs) stabilization effect and intercropping of ZB (target crop) and ryegrass (accumulating plant) could provide a prospective approach to produce target plants within safe TEs thresholds with greater economic benefits, while remediating soils polluted with multiple TEs and mitigating the potential ecological and human health risk. Those results are of great applicable concern.

Apoptosis, a Metabolic “Head-to-Head” between Tumor and T Cells: Implications for Immunotherapy

Induction of apoptosis represents a promising therapeutic approach to drive tumor cells to death. However, this poses challenges due to the intricate nature of cancer biology and the mechanisms employed by cancer cells to survive and escape immune surveillance. Furthermore, molecules released from apoptotic cells and phagocytes in the tumor microenvironment (TME) can facilitate cancer progression and immune evasion. Apoptosis is also a pivotal mechanism in modulating the strength and duration of anti-tumor T-cell responses. Combined strategies including molecular targeting of apoptosis, promoting immunogenic cell death, modulating immunosuppressive cells, and affecting energy pathways can potentially overcome resistance and enhance therapeutic outcomes. Thus, an effective approach for targeting apoptosis within the TME should delicately balance the selective induction of apoptosis in tumor cells, while safeguarding survival, metabolic changes, and functionality of T cells targeting crucial molecular pathways involved in T-cell apoptosis regulation. Enhancing the persistence and effectiveness of T cells may bolster a more resilient and enduring anti-tumor immune response, ultimately advancing therapeutic outcomes in cancer treatment. This review delves into the pivotal topics of this multifaceted issue and suggests drugs and druggable targets for possible combined therapies.

Use of Different Anti-PD-1 Checkpoint Combination Strategies for First-Line Advanced NSCLC Treatment—The Experience of Ion Chiricuță Oncology Institute

Use of Different Anti-PD-1 Checkpoint Combination Strategies for First-Line Advanced NSCLC Treatment—The Experience of Ion Chiricuță Oncology Institute

Use of cardiac MRI and wearable defibrillator to identify patients at low risk for arrhythmic events: single center experience

Abstract Introduction In our Center, patients (pts) with newly diagnosed HF and reduced LVEF underwent MRI to determine the presence and extension of delayed enhancement (DE) or scar areas. These patients were discharged with a wearable cardioverter defibrillator (WCD) as monitoring and temporary antiarrhythmic therapy until a three-month follow-up (FU). Subsequent FU was performed at 6 and 12 months. Methods From May 2016 to July 2023, 120 consecutive pts (97 M; mean age 65.3y±9.7y) with reduced EF (28.5%±8.5%) on OMT, were discharged with WCD and included in clinical FU. Coronary anatomy was acquired in 119 pts: absence of coronary atherosclerosis (ats) (44 pts); not significant ats(39 pts); Significant ats(36 pts). 1 pt did not perform angiography due to thyrotoxicosis. MRI was performed in 95 pts (EDV 181.9 ± 48.7 ml/m2; Mass 96.9± 23.4 g/m2, LVEF MRI 26.8% ±9.2). FU was performed at 3 months in all patients; at 6 months in 111pts and at 12 months in 107pts. WCD is still present in 4 pts. LGE score was used to quantify myocardial fibrosis by defining reduced extension as LGE score &amp;lt;5. Results MRI identified 57 pts with a delayed enhancement(DE) midwall pattern and in 13 of these there was a regional ischemic pattern also; 27 pts with regional scar; 18 pts without DE. During follow-up, 87 patients (75%) recovered LVEF function at 3 months (LVEF 44.3±6.3%) and were no longer indicated for ICD. 29 pts were implanted with ICD (25%). These patients had higher absolute and indexed volumes on MRI (p 0.053; p 0.042) and a greater presence of ischemic pattern (p 0.05). The LGE score was low in 76 pts (&amp;lt;5). A low LGE score is linked to the recovery of LVEF (p 0.04). Patients who undergo ICD had greater DE extension (p 0.01). 1 pt with a high LGE score (36.6) refused ICD and underwent SCD at 6 months. In pts with LGE score &amp;lt;5, 1 major arrhythmic event occurred (1 SVT in pt with ICD). In pts with LGE score &amp;gt;5, 3 major events occurred (1 shock on VF, 1 ATP on SVT, 1 SCD). 1 pt with extensive anterior akinesia who refused MRI presented 1 shock on VF at 6 months. 1 pt with partial recovery of LVEF and extensive anterior akinesia refused MRI and presented cardiac arrest for VF at 6 months. Conclusions MRI has become essential for risk stratification in patients with reduced LVEF. It is useful for identifying pts with severe impairment LVEF and low risk of events. The absence of DE and/or the presence of a low LGE score are linked to a low risk of arrhythmic events at 6 and 12 months and to a higher probability of recovery LVEF regardless of the etiology. The volumetric dimensions found on MRI are inversely linked to the recovery of LVEF. The WCD represents additional safety with excellent compliance in pts who still do not have clear indications for a definitive ICD. The combined MRI and WCD strategy can help to reduce the need for definitive ICD and therefore healthcare costs. The size of the sample does not allow definitive conclusions.

Unlocking hope: talquetamab in multiple myeloma treatment: a bispecific breakthrough targeting CD3 and GPRC5D

Multiple myeloma (MM) presents a significant global health burden, with disparities in incidence and outcomes reflecting challenges in recognition and treatment. Talquetamab, a bispecific CD3 T-cell engager targeting G-protein coupled receptor family C group 5 member D (GPRC5D), has emerged as a promising immunotherapy for relapsed/refractory MM (RRMM). In August 2023, talquetamab received accelerated approval from the US FDA for RRMM treatment, followed by conditional marketing authorization from the EMA. Clinical trials demonstrated talquetamab's efficacy, with overall response rates (ORR) of 69% and 76% in heavily pretreated RRMM patients. The phase I monumenTAL-1 trial showcased talquetamab's effectiveness, particularly in high-risk MM and extramedullary disease, with ORRs around 71-74%. Subsequent phase 2 results reaffirmed its efficacy, even in patients with prior T-cell redirection therapies. Combination therapy with daratumumab further enhanced talquetamab's efficacy, addressing concerns of T cell exhaustion. Pharmacokinetic studies revealed sustained responses and manageable adverse events with subcutaneous administration, facilitating convenient dosing regimens. However, talquetamab carries risks of cytokine release syndrome (CRS) and neurologic toxicity, necessitating close monitoring and prompt management. Common adverse events included fever, CRS, musculoskeletal pain, and infections, although severe events were infrequent. Vigilant management strategies, including prophylactic measures and supportive care, mitigate these risks. In conclusion, talquetamab represents a significant advancement in RRMM treatment, offering a promising avenue for T-cell redirection therapy. Ongoing research aims to optimize treatment sequencing and combination strategies, fostering improved outcomes for MM patients. Continued investigation will refine the strategic integration of talquetamab and other immunotherapies, paving the way for enhanced treatment efficacy and patient care in RRMM.

Targeting tumor-associated macrophages to reverse antitumor drug resistance.

Currently, antitumor drugs show limited clinical outcomes, mainly due to adaptive resistance. Clinical evidence has highlighted the importance of the tumor microenvironment (TME) and tumor-associated macrophages (TAMs) in tumor response to conventional antitumor drugs. Preclinical studies show that TAMs following antitumor agent can be reprogrammed to an immunosuppressive phenotype and proangiogenic activities through different mechanisms, mediating drug resistance and poor prognosis. Potential extrinsic inhibitors targeting TAMs repolarize to an M1-like phenotype or downregulate proangiogenic function, enhancing therapeutic efficacy of anti-tumor therapy. Moreover, pharmacological modulation of macrophages that restore the immune stimulatory characteristics is useful to reshaping the tumor microenvironment, thus further limiting tumor growth. This review aims to introduce macrophage response in tumor therapy and provide a potential therapeutic combination strategy of TAM-targeting immunomodulation with conventional antitumor drugs.

Enhancing IgA-mediated neutrophil cytotoxicity against neuroblastoma by CD47 blockade

BackgroundApproximately half of the neuroblastoma patients develop high-risk neuroblastoma. Current treatment involves a multimodal strategy, including immunotherapy with dinutuximab (IgG ch14.18) targeting GD2. Despite achieving promising results, the recurrence rate...

Coordination-Driven Self-Assembly of Metal Ion-Antisense Oligonucleotide Nanohybrids for Chronic Bacterial Infection Therapy.

Bacterial infection poses a significant challenge to wound healing and skin regeneration, leading to substantial economic burdens on patients and society. Therefore, it is crucial to promptly explore and develop effective methodologies for bacterial infections. Herein, we propose a novel approach for synthesizing nanostructures based on antisense oligonucleotides (ASOs) through the coordination-driven self-assembly of Zn2+ with ASO molecules. This approach aims to provide effective synergistic therapy for chronic wound infections caused by Staphylococcus aureus (S. aureus). The resulting hybrid nanoparticles successfully preserve the structural integrity and biological functionalities of ASOs, demonstrating excellent ASO encapsulation efficiency and bioaccessibility. In vitro antibacterial experiments reveal that Zn-ASO NPs exhibit antimicrobial properties against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. This antibacterial ability is attributed to the high concentration of metal zinc ions and the generation of high levels of reactive oxygen species. Additionally, the ftsZ-ASO effectively inhibits the expression of the ftsZ gene, further enhancing the antimicrobial effect. In vivo antibacterial assays demonstrate that the Zn-ASO NPs promote optimal skin wound healing and exhibit favorable biocompatibility against S. aureus infections, resulting in a residual infected area of less than 8%. This combined antibacterial strategy, which integrates antisense gene therapy and metal-coordination-directed self-assembly, not only achieves synergistic and augmented antibacterial outcomes but also expands the horizons of ASO coordination chemistry. Moreover, it addresses the gap in the antimicrobial application of metal-coordination ASO self-assembly, thereby advancing the field of ASO-based therapeutic approaches.

GPR Mapping of Cavities in Complex Scenarios with a Combined Time-Depth Conversion.

The paper deals with a combined time-depth conversion strategy able to improve the reconstruction of voids embedded in an opaque medium, such as cavities, caves, empty hypogeal rooms, and similar targets. The combined time-depth conversion accounts for the propagation velocity of the electromagnetic waves both in free space and in the embedding medium, and it allows better imaging and interpretation of the underground scenario. To assess the strategy's effectiveness, ground penetrating radar (GPR) data referred to as an experimental test in controlled conditions are accounted for and processed by two different approaches to achieve focused images of the scenario under test. The first approach is based on a classical migration algorithm, while the second one faces the imaging as a linear inverse scattering approach. The results corroborate that the combined time-depth conversion improves the imaging in both cases.

Combination of betulinic acid and EGFR-TKIs exerts synergistic anti-tumor effects against wild-type EGFR NSCLC by inducing autophagy-related cell death via EGFR signaling pathway

BackgroundEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of lung cancer patients with mutated EGFR. However, the efficacy of EGFR-TKIs in wild-type EGFR tumors has been shown to be marginal. Methods that can sensitize EGFR-TKIs to EGFR wild-type NSCLC remain rare. Hence, we determined whether combination treatment can maximize the therapeutic efficacy of EGFR-TKIs.MethodsWe established a focused drug screening system to investigate candidates for overcoming the intrinsic resistance of wild-type EGFR NSCLC to EGFR-TKIs. Molecular docking assays and western blotting were used to identify the binding mode and blocking effect of the candidate compounds. Proliferation assays, analyses of drug interactions, colony formation assays, flow cytometry and nude mice xenograft models were used to determine the effects and investigate the molecular mechanism of the combination treatment.ResultsBetulinic acid (BA) is effective at targeting EGFR and synergizes with EGFR-TKIs (gefitinib and osimertinib) preferentially against wild-type EGFR. BA showed inhibitory activity due to its interaction with the ATP-binding pocket of EGFR and dramatically enhanced the suppressive effects of EGFR-TKIs by blocking EGFR and modulating the EGFR-ATK-mTOR axis. Mechanistic studies revealed that the combination strategy activated EGFR-induced autophagic cell death and that the EGFR-AKT-mTOR signaling pathway was essential for completing autophagy and cell cycle arrest. Activation of the mTOR pathway or blockade of autophagy by specific chemical agents markedly attenuated the effect of cell cycle arrest. In vivo administration of the combination treatment caused marked tumor regression in the A549 xenografts.ConclusionsBA is a potential wild-type EGFR inhibitor that plays a critical role in sensitizing EGFR-TKI activity. BA combined with an EGFR-TKI effectively suppressed the proliferation and survival of intrinsically resistant lung cancer cells via the inhibition of EGFR as well as the induction of autophagy-related cell death, indicating that BA combined with an EGFR-TKI may be a potential therapeutic strategy for overcoming the primary resistance of wild-type EGFR-positive lung cancers.Graphical abstract

Green synthesized silver nanoparticles in two stages: Box Behnken Design to machine learning

In order to solve the modeling issues due to data scarcity problems in the disciplines utilizing statistical approximations, a novel two-stage idea is proposed. As a use case, nanoparticle biosynthesis was selected, for which an environmentally friendly process is of vital importance. First, Box Behnken Design was used for experimental setup, quadratic model formulation and data generation. The second stage consists of Machine Learning, in which the data generated in the previous stage were fed into a Neural Network to determine the relationship between the parameters. Obtained results showed that the proposed combined strategy provided better nanoparticle size estimations than the statistical approach alone. In the absence of publicly available databases, data generation using experimental design and machine learning, as proposed here, could be a faster, lower-cost, and greener solution. Our proposed method can be applied to a wide range of biotechnology and bioengineering applications with significant advanced knowledge.

Update on Renal Cell Carcinoma Diagnosis with Novel Imaging Approaches.

This review highlights recent advances in renal cell carcinoma (RCC) imaging. It begins with dual-energy computed tomography (DECT), which has demonstrated a high diagnostic accuracy in the evaluation of renal masses. Several studies have suggested the potential benefits of iodine quantification, particularly for distinguishing low-attenuation, true enhancing solid masses from hyperdense cysts. By determining whether or not a renal mass is present, DECT could avoid the need for additional imaging studies, thereby reducing healthcare costs. DECT can also provide virtual unenhanced images, helping to reduce radiation exposure. The review then provides an update focusing on the advantages of multiparametric magnetic resonance (MR) imaging performance in the histological subtyping of RCC and in the differentiation of benign from malignant renal masses. A proposed standardized stepwise reading of images helps to identify clear cell RCC and papillary RCC with a high accuracy. Contrast-enhanced ultrasound may represent a promising diagnostic tool for the characterization of solid and cystic renal masses. Several combined pharmaceutical imaging strategies using both sestamibi and PSMA offer new opportunities in the diagnosis and staging of RCC, but their role in risk stratification needs to be evaluated. Although radiomics and tumor texture analysis are hampered by poor reproducibility and need standardization, they show promise in identifying new biomarkers for predicting tumor histology, clinical outcomes, overall survival, and the response to therapy. They have a wide range of potential applications but are still in the research phase. Artificial intelligence (AI) has shown encouraging results in tumor classification, grade, and prognosis. It is expected to play an important role in assessing the treatment response and advancing personalized medicine. The review then focuses on recently updated algorithms and guidelines. The Bosniak classification version 2019 incorporates MRI, precisely defines previously vague imaging terms, and allows a greater proportion of masses to be placed in lower-risk classes. Recent studies have reported an improved specificity of the higher-risk categories and better inter-reader agreement. The clear cell likelihood score, which adds standardization to the characterization of solid renal masses on MRI, has been validated in recent studies with high interobserver agreement. Finally, the review discusses the key imaging implications of the 2017 AUA guidelines for renal masses and localized renal cancer.

Enhanced Osteosarcoma Immunotherapy via CaCO3 Nanoparticles: Remodelling Tumour Acidic and Immune Microenvironment for Photodynamic Therapy.

Osteosarcoma (OS) is a "cold" tumour enriched in noninflammatory M2 phenotype tumour-associated macrophages (TAMs), which limits the efficacy of immunotherapy. The acidic tumour microenvironment (TME), generated by factors such as excess hydrogen (H+) ions and high lactate levels, activates immunosuppressive cells (e.g., M2 phenotype TAMs), further promoting a suppressive tumour immune microenvironment (TIME). Therefore, a multitarget synergistic combination strategy that neutralizes the acidic TME and reprograms TAMs can be beneficial for OS therapy. Here, a calcium carbonate (CaCO3)/polydopamine (PDA)-based nanosystem (A-NPs@(SHK+Ce6)) was developed for the targeted codelivery of the photosensitizer Ce6 and shikonin (SHK) to OS tumours via the bone-targeting ability of alendronate sodium (ALN). CaCO3 nanoparticles were used to neutralize H+ ions and alleviate the suppressive TIME, and the loaded SHK not only synergized with photodynamic therapy (PDT) by promoting reactive oxygen species (ROS) generation and enhancing immunogenic cell death (ICD) but also inhibited lactate production, further reversing the acidic TME and repolarizing TAMs to consequently lead to enhanced PDT-induced tumour suppression and comprehensive beneficial effects on antitumour immune responses, including the promotion of CD8+ T-cell infiltration and regulatory T-cell (Treg) suppression. Importantly, A-NPs@(SHK+Ce6), in combination with programmed cell death protein 1 (PD-1) checkpoint blockade, showed a remarkable ability to eliminate distant tumours and promote long-term immune memory function to protect against rechallenged tumours. This work presents a novel multiple-component combination strategy that coregulates the acidic TME and TAM polarization to reprogram the TIME. This article is protected by copyright. All rights reserved.

Exploring and Analyzing a Hybrid PAPR Reduction Method for OFDM Optimization

Orthogonal Frequency Division Multiplexing (OFDM) is a effective modulation technique widely used in modern communication systems, including 5G and wireless networks because of its high spectral efficiency and robustness towards multipath fading. However, OFDM signals are characterized by a high Peak-to-Average Power Ratio (PAPR), which can severely impact the power efficiency and operational cost of these systems. This research investigates and analyse effectiveness of two conventional PAPR reduction methods that is Selective Mapping (SLM), and Partial Transmit Sequence (PTS) with incorporating their approach of PAPR reduction to develop a hybrid variant: SLM-PTS. This study utilized MATLAB simulations to implement and test each PAPR reduction technique on a standard OFDM system model. Parameters such as the number of subcarriers, oversampling factor, and modulation types were systematically varied to analyze the impact on PAPR, BER, and computational complexity. The effectiveness of each technique was measured using the Complementary Cumulative Distribution Function (CCDF) of PAPR values and BER performance under different channel conditions. Key findings reveal that hybrid techniques, particularly SLM &amp; PTS, offer significant improvements in PAPR reduction compared to traditional methods alone, without a corresponding increase in BER or computational overhead. The research underscores the potential of hybrid PAPR reduction techniques to significantly enhance the efficiency and reliability of OFDM systems. These findings have important implications for the design and optimization of next-generation wireless communication systems, suggesting that hybrid approaches can provide a balanced solution to the longstanding issue of PAPR in OFDM transmissions. This study contributes valuable insights into the practical application of combined PAPR reduction strategies, offering a pathway toward more power-efficient and robust OFDM technologies. Keywords : OFDM, PAPR, CCDF, SLM and PTS

Immunomodulatory Precision: A Narrative Review Exploring the Critical Role of Immune Checkpoint Inhibitors in Cancer Treatment

An immune checkpoint is a signaling pathway that regulates the recognition of antigens by T-cell receptors (TCRs) during an immune response. These checkpoints play a pivotal role in suppressing excessive immune responses and maintaining immune homeostasis against viral or microbial infections. There are several FDA-approved immune checkpoint inhibitors (ICIs), including ipilimumab, pembrolizumab, and avelumab. These ICIs target cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PD-L1). Furthermore, ongoing efforts are focused on developing new ICIs with emerging potential. In comparison to conventional treatments, ICIs offer the advantages of reduced side effects and durable responses. There is growing interest in the potential of combining different ICIs with chemotherapy, radiation therapy, or targeted therapies. This article comprehensively reviews the classification, mechanism of action, application, and combination strategies of ICIs in various cancers and discusses their current limitations. Our objective is to contribute to the future development of more effective anticancer drugs targeting immune checkpoints.

Optimal Sizing and Management of Hybrid Wind Turbine-Diesel-Battery System for Reverse Osmosis Seawater Desalination in NEOM City

Optimal sizing and management of hybrid wind turbine-diesel-battery system for reverse osmosis seawater desalination in NEOM city is the objective of the paper. Therefore, the paper explored the different factors to optimize and introduce a technoeconomic evaluation and energy management of a stand-alone wind turbine (WT) system, diesel generator (DG), and battery storage (BS). The suggested WT/DG/BS system is implemented to feed seawater reverse osmosis (SWRO) unit in NEOM. The necessitated desalinated water per day is 100 m3. To determine the optimal size of WT/DG/BS corresponding to the minimum cost of energy (COE) and net present cost, two different ratings of the SWRO units (SWRO-100 and SWRO-150), three control dispatch strategies (load following, cycle charging, and combined dispatch), and five types of batteries are considered. HOMER software is performed to simulate and optimize the WT/DG/BS. The optimization results indicated that the best battery storage is the Trojan SAGM battery. In this case, the COE ranged between $0.337/kWh and $0.564/kWh. The lowest COE of $0.377/kWh is obtained when using a combined control strategy and SWRO-100 unit, whereas the worst COE of $0.564/kWh is obtained when using load following control strategy and SWRO-150 unit. The best option of the WT/DG/BS system to supply the SWRO unit is option number 26. This system includes one wind turbine of 90 kW, DG of 25 kW, 47 Trojan SAGM batteries, a 23.8 kW converter, a SWRO-100 unit, and a combined control strategy. The net present cost and the initial cost are $950,725 and $221,495, respectively. The annual operating cost and annual consumed fuel are $56,409 and 36,396 L, respectively. Compared with using only a 25 kW diesel generator, the COE reduced from $0.373/kWh (using only DG/BS) to $0.337/kWh (using the best option) by around 9.65%. Under this condition, the values for the internal rate of return, return on investment, and simple payback are 11%, 7.8%, and 8.3 years, respectively.

Interleukin-12 in multimodal tumor therapies for induction of anti-tumor immunity.

Interleukin-12 (IL-12) can be used as an immunomodulator in cancer immunotherapy. And it has demonstrated enormous potential in inhibiting tumor growth and improving the tumor microenvironment (TME) by several preclinical models. However, some disappointing results have showed in the early clinical trials when IL-12 used as a single agent for systemic cancer therapy. Combination therapy is an effective way to significantly fulfill the great potential of IL-12 as an immunomodulator. Here, we discuss the effects of IL-12 combined with traditional methods (chemotherapy, radiotherapy and surgery), targeted therapy or immunotherapy in the preclinical and clinical studies. Moreover, we summarized the potential mechanism underlying the anti-tumor effect of IL-12 in the combination strategies. And we also discussed the delivery methods and tumor-targeted modification of IL-12 and outlines future prospects for IL-12 as an immunomodulator.