Efficacy and safety of perioperative immunotherapy combinations for resectable non-small cell lung cancer: a systematic review and network meta-analysis.

INTRODUCTION: Several trials of perioperative immunotherapy for resectable non-small cell lung cancer (NSCLC) reported positive results. They were designed to adjuvant, neoadjuvant and sandwich (neoadjuvant plus adjuvant) immunotherapy with immune checkpoint inhibitors and chemotherapy (CT). The differences between neoadjuvant and sandwich modalities were unclear. METHOD: We performed a systematic review and Bayesian network meta-analysis by retrieving relevant literature from PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, WHO ICTRP and major international conferences. RESULTS: We analyzed 8 studies involving 3429 patients, including 6 neoadjuvant plus adjuvant (Neo-Adj) and 2 neoadjuvant (Neo) trials. Neo-Adj had better event-free survival (EFS) (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.45-0.71) than CT. There existed no difference between Neo-Adj and Neo in EFS (HR = 0.87, 95% CI: 0.53-1.46) and overall survival (OS) (HR = 1.04, 95% CI: 0.38-2.57). Neo might have lower incidence of treatment-related adverse events (TRAEs) (relative risk [RR] = 0.96, 95% CI: 0.87-1.12) than Neo-Adj. Subgroup analysis of PD-L1 ≥ 50% suggested that EFS of Neo-Adj (HR = 0.46, 95% CI: 0.27-0.76) and Neo (HR = 0.24, 95% CI: 0.06-0.89) was better than CT, and Neo-Adj potentially caused shorter EFS than Neo (HR = 1.92, 95% CI: 0.46-7.84). CONCLUSIONS: Our results suggest that Neo-Adj and Neo have similar EFS for patients with PD-L1 < 1% or 1-49%. However, patients with PD-L1 ≥ 50% may obtain more EFS benefit from Neo than Neo-Adj. Neo might present a more favorable assessment than Neo-Adj when evaluating OS. Moreover, adding adjuvant immunotherapy may increase toxicity.

Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment.

Non-small cell lung cancer (NSCLC) is characterized by several molecular alterations that contribute to its development and progression. These alterations include the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), human epidermal growth factor receptor 2 (HER2), and mesenchymal-epithelial transition factor (c-MET). Among these, the hepatocyte growth factor (HGF)/c-MET signaling pathway plays a crucial role in NSCLC. In spite of this, the involvement of the HGF/c-MET signaling axis in remodeling the tumor microenvironment (TME) remains relatively unexplored. This review explores the biological functions of the HGF/c-MET signaling pathway in both normal and cancerous cells, examining its multifaceted roles in the NSCLC tumor microenvironment, including tumor cell proliferation, migration and invasion, angiogenesis, and immune evasion. Furthermore, we summarize the current progress and clinical applications of MET-targeted therapies in NSCLC and discuss future research directions, such as the development of novel MET inhibitors and the potential of combination immunotherapy.

Revealing the Hidden Mechanism of Enhanced Responsivity of Doped p-i-n Perovskite Photodiodes via Coupled Opto-Electronic Model.

Organic-inorganic halide perovskites have demonstrated preeminent optoelectronic performance in recent years due to their unique material properties, and have shown great potential in the field of photodetectors. In this study, a coupled opto-electronic model is constructed to reveal the hidden mechanism of enhancing the performance of perovskite photodetectors that are suitable for both inverted and regular structure doped p-i-n perovskite photodiodes. Upon illumination, the generation rate of photogenerated carriers is calculated followed by carrier density distribution, which serves as a coupled joint to further analyze the recombination rate, electric field strength, and current density of carriers under different doping types and densities. Moreover, experiments were carried out in which the doping types and densities of the active layer were regulated by changing the precursor ratios. With optimal doping conditions, the inverted and regular perovskite photodiodes achieved an external quantum efficiency of 74.83% and 73.36%, and a responsivity of 0.417 and 0.404 A/W, respectively. The constructed coupled opto-electronic model reveals the hidden mechanism and along with the doping strategy, this study provides important guidance for further analysis and improvement of perovskite-based photodiodes.

Analyzing and modulating energy transfer in ternary-emissive system of quantum dot light-emitting diodes towards efficient emission.

The mechanisms for energy transfer including Förster resonance energy transfer (FRET) and radiative energy transfer in ternary-emissive system consists of blended-quantum dots (QDs, red-QDs blended with blue-QDs) emissive layer (EML) and blue-emissive hole-transport material that contained in quantum dot light-emitting diodes (QLEDs) are complicated. As the energy transfer could exhibit either positive or negative impact on QD's photoluminescence (PL) and electroluminescence (EL), it is important to analyze and modulate energy transfer in such ternary-emissive system to obtain high-efficiency QLEDs. In this work, we have demonstrated that proper B-QDs doping has a positive impact on R-QDs' PL and EL, where these improvements were attributed to the B-QDs' spacing effect on R-QDs which weakens homogeneous FRET among R-QDs and near 100% efficient heterogeneous FRET from B-QDs to R-QDs. With optimization based on the analysis of energy transfer, the PL quantum yield of blended-QDs (with R:B blending ratio of 90:10, in quality) film has been enhanced by 35% compared with that of unblended R-QDs film. Moreover, thanks to the spacing effect and high-efficiency FRET from B-QDs to R-QDs, the external quantum efficiency of QLEDs that integrate optimized blended-QDs (R:B=90:10) EML reaches 22.1%, which is 15% higher than that of the control sample (19.2%) with unblended R-QDs EML. This work provides a systematically analytical method to study the energy transfer in ternary-emissive system, and gives a valid reference for the analysis and development of the emerging QLEDs that with blended-QDs EML.

Factors influencing the working temperature of quantum dot light-emitting diodes.

Quantum dot light-emitting diodes (QLEDs) possess huge potential in display due to their outstanding optoelectronic performance; however, serve degradation during operation blocks their practical applications. High temperature is regarded as one of major factors causing degradation. Therefore, a systematical study on the working temperature of QLEDs is very essential and urgent for the development of high stable QLEDs. In this work, different influence factors such as the electro-optic conversion efficiency (EOCE), voltage, current density, active area, substrate size, substrate type and sample contact are discussed in detail on the working temperature of QLEDs. The research results show that the working temperature of general QLEDs under normal operation conditions is usually smaller than 75 °C when the ambient temperature is 25 °C. However, temperature of QLEDs working under extreme conditions, such as high power or small substrate size, will exceed 100 °C, resulting in irreversible damage to the devices. Moreover, some effective measures to reduce the working temperature are also proposed. The analysis and discussion of various influencing factors in this work will provide guidance for the design of stable QLEDs and help them work at a safer temperature.

Improving the modulation bandwidth of LED by CdSe/ZnS quantum dots for visible light communication.

Visible light communication (VLC) is an advanced and high-efficiency wireless communication technology. As one of the most important light sources in VLC, conventional white light emitting diode (WLED) based on Y3Al5O12:Ce3+ (YAG:Ce) phosphor limits the system transmitting rate severely due to its narrow modulation bandwidth. Considering the short fluorescent lifetime of quantum dots (QDs), QD-LEDs with wide modulation bandwidths were designed here to improve the transmitting rate of VLC. CdSe/ZnS core/shell QDs and related luminescent microspheres (LMS) were implemented as light conversion materials for the QD-LEDs. Compared with conventional phosphor WLED, the proposed QD-LED and QD-WLED reached maximum improvement on modulation bandwidth at 74.19% and 67.75% respectively. Furthermore, mathematical modeling of smearing was analyzed to establish the relationship between fluorescent lifetime and modulation bandwidth. Our findings will provide an effective solution of white LEDs for high speed VLC.

Neurological adverse events associated with oxaliplatin: A pharmacovigilance analysis based on FDA adverse event reporting system.

Objective: This study aimed to explore the neurological adverse events of oxaliplatin through the Food and Drug Administration Adverse Event Reporting System (FAERS) database and to provide reference for safe clinical drug use. Methods: The adverse events report data of oxaliplatin from the first quarter of 2019 (1 January 2019) to the third quarter of 2023 (30 September 2023) were extracted from FAERS database, and the adverse events signal intensity was determined using the reporting odds ratio, proportional reporting ratio, information component, and empirical Bayes geometric mean methods. Time-to-onset and univariate logistic regression analysis were performed to describe the characteristics and risk factors of oxaliplatin-associated neurological adverse events. Results: A total of 4,471 cases of oxaliplatin-associated neurological adverse events were identified, with 318 neurological adverse events being documented, among which 87 adverse events satisfied the thresholds of four methodologies. The median time-to-onset of oxaliplatin-associated neurological adverse events was 2 days (interquartile range 0-36 days). Among the factors significantly influencing oxaliplatin-related neurological adverse events, male sex and combination medication decreased the risk of neurological adverse events, while higher cumulative dose increased the risk. Conclusion: The real-world neurotoxicity spectrum of oxaliplatin and its characteristics and influencing factors were obtained through data mining of FAERS, providing valuable insights for healthcare professionals to effectively manage the risk of neurological adverse events associated with oxaliplatin in clinical practice.

Efficient and stable hybrid perovskite-organic light-emitting diodes with external quantum efficiency exceeding 40 per cent.

Light-emitting diodes (LEDs) based on perovskite semiconductor materials with tunable emission wavelength in visible light range as well as narrow linewidth are potential competitors among current light-emitting display technologies, but still suffer from severe instability driven by electric field. Here, we develop a stable, efficient and high-color purity hybrid LED with a tandem structure by combining the perovskite LED and the commercial organic LED technologies to accelerate the practical application of perovskites. Perovskite LED and organic LED with close photoluminescence peak are selected to maximize photon emission without photon reabsorption and to achieve the narrowed emission spectra. By designing an efficient interconnecting layer with p-type interface doping that provides good opto-electric coupling and reduces Joule heating, the resulting green emitting hybrid LED shows a narrow linewidth of around 30 nm, a peak luminance of over 176,000 cd m-2, a maximum external quantum efficiency of over 40%, and an operational half-lifetime of over 42,000 h.

Electric dipole modulation for boosting carrier recombination in green InP QLEDs under strong electron injection.

Enhanced and balanced carrier injection is essential to achieve highly efficient green indium phosphide (InP) quantum dot light-emitting diodes (QLEDs). However, due to the poor injection of holes in green InP QLEDs, the carrier injection is usually balanced by suppressing the strong electron injection, which decreases the radiation recombination rate dramatically. Here, an electric dipole layer is introduced to enhance the hole injection in the green InP QLED with a high mobility electron transport layer (ETL). The ultra-thin MoO3 electric dipole layer is demonstrated to form a positive built-in electric field at the interface of the hole injection layer (HIL) and hole transport layer (HTL) due to its deep conduction band level. Simulation and experimental results support that strong electric fields are produced for efficient hole hopping, and the carrier recombination rate is substantially increased. Consequently, the green InP QLEDs based on enhanced electron and hole injection have achieved a high luminance of 52 730 cd m-2 and 1.7 times external quantum efficiency (EQE) enhancement from 4.25% to 7.39%. This work has provided an effective approach to enhance carrier injection in green InP QLEDs and indicates the feasibility to realize highly efficient green InP QLEDs.

Green Tea Polyphenols Prevent Early Vascular Aging Induced by High-Fat Diet via Promoting Autophagy in Young Adult Rats.

OBJECTIVE: Epidemiology studies indicate that green tea polyphenols (GTP) perform a protective effect on cardiovascular diseases, but the underlying mechanisms are complex. The present study aimed to investigate the effect of GTP on high-fat diets (HFD) induced-early vascular aging. METHODS: Six-week young adult Wistar rats were fed with standard chow or HFD in the presence and absence of GTP (200 mg/kg body weight) for 18 weeks. In vitro experiment, human umbilical vascular endothelial cells (HUVECs) were treated with palmitic acid (PA) and GTP. RESULTS: The results showed that GTP alleviated the disorganized arterial wall and the increased intima-media thickness induced by HFD. In addition, the vascular oxidative injury was suppressed following GTP treatment. Furthermore, GTP elevated the ratio of LC3-II/LC3-I and suppressed expression of p62/SQSTM1, and restored SIRT3 expression in the aorta of HFD rats. Consistently, in cultured HUVECs, GTP inhibited cell senescence indicated by SA-ß-gal and promoted endothelial autophagy compared with the PA treatment group. The activity of SIRT3 was specifically inhibited by 3-TYP, and the protective effect of GTP was consequently abolished. CONCLUSION: The findings indicated that GTP protected against early vascular senescence in young HFD rats via ameliorating oxidative injury and promoting autophagy which was partially regulated by the SIRT3 pathway.

High-Performance Blue Quasi-2D Perovskite Light-Emitting Diodes via Balanced Carrier Confinement and Transfer.

Extensive investigation of the passivating agents has been performed to suppress the perovskite defects. However, very few attentions have been paid to rationally design the passivating agents for the balance of the carrier confinement and transfer in quasi-2D perovskites, which is essential to achieve high-performance perovskite LEDs (PeLEDs). In this work, tributylphosphine oxide (TBPO) with moderate carbon chain length is demonstrated as a decent passivator for the quasi-2D perovskites by strengthening the carrier confinement for massive radiative recombination within the perovskites, and more importantly providing efficient carrier transfer in the quasi-2D perovskites. Benefiting from these interesting optoelectronic properties of TBPO-incorporated perovskites, we achieve high-efficient blue PeLEDs with an external quantum efficiency up to 11.5% and operational stability as long as 41.1 min without any shift of the electroluminescence spectra. Consequently, this work contributes an effective approach to promote the carrier confinement and transfer for high-performance and stable blue PeLEDs.

Systematic evaluation during early-phase ischemia predicts outcomes in middle cerebral artery occlusion mice.

Identifying outcome predictors for ischemic stroke is beneficial for choosing correct intervention protocols. Thus, it is necessary to systemically evaluate histological outcome-associated changes such as hemodynamics, behavior, and body weight during the early phase of ischemia. Here, 50 mice were subjected to 45-min middle cerebral artery occlusion (MCAO) using Longa's method. Hemodynamic changes were monitored by Doppler laser probe, and behaviors were evaluated by scales while the tissues were visualized by staining. The results by correlation analysis demonstrated that with a probe located near the posterior boundary zone of MCA territory, the latency of anoxic depolarization, as well as the cerebral blood flow reduction during MCAO were confirmed to be predictors for the infarct volume on day 3 post-ischemia; histology showed that the risk of a space-occupying secondary hemorrhage was significantly correlated with the increase of infarct volume versus the traditional Bederson's neurological deficit scale, a renewed combined behavioral scoring method performed nicely to reflect the severity of tissue lesions. Weight loss was a valuable metric for the enlargement of both infarct volume and secondary hemorrhage. Monitoring changes during early-phase ischemia may benefit the optimization of ischemia models and the discovery of potential intervention targets.See Video Abstract, http:/links.lww.com/WNR/A601).

Universal Strategy for Improving Perovskite Photodiode Performance: Interfacial Built-In Electric Field Manipulated by Unintentional Doping.

Organic-inorganic halide perovskites have demonstrated significant light detection potential, with a performance comparable to that of commercially available photodetectors. In this study, a general design guideline, which is applicable to both inverted and regular structures, is proposed for high-performance perovskite photodiodes through an interfacial built-in electric field (E) for efficient carrier separation and transport. The interfacial E generated at the interface between the active and charge transport layers far from the incident light is critical for effective charge carrier collection. The interfacial E can be modulated by unintentional doping of the perovskite, whose doping type and density can be easily controlled by the post-annealing time and temperature. Employing the proposed design guideline, the inverted and regular perovskite photodiodes exhibit the external quantum efficiency of 83.51% and 76.5% and responsivities of 0.37 and 0.34 A W-1 , respectively. In the self-powered mode, the dark currents reach 7.95 × 10-11 and 1.47 × 10-8 A cm-2 , providing high detectivities of 7.34 × 1013 and 4.96 × 1012 Jones, for inverted and regular structures, respectively, and a long-term stability of at least 1600 h. This optimization strategy is compatible with existing materials and device structures and hence leads to substantial potential applications in perovskite-based optoelectronic devices.

Effective Surface Ligand-Concentration Tuning of Deep-Blue Luminescent FAPbBr3 Nanoplatelets with Enhanced Stability and Charge Transport.

Metal-halide perovskite-based green and red light-emitting diodes (LEDs) have witnessed a rapid development because of their facile synthesis and processability; however, the blue-band emission is constrained by their unstable chemical properties and poorly conducting emitting layers. Here, we show a trioctylphosphine oxide (TOPO)-mediated one-step approach to realize bright deep-blue luminescent FAPbBr3 nanoplatelets (NPLs) with enhanced stability and charge transport. The concentration of NPL surface ligands is shown to be progressively tuned via varying the amount of intermediate TOPO due to the acid-base equilibrium between protic acid and TOPO. By effectively optimizing the concentration of surface ligands, the structural integrity of NPL solids can be preserved in ambient air for a week, mainly because of the highly ordered and dense solid assembly and the reduced defects. The removal of excess organic ligands also enables the improvement of charge mobility by orders of magnitude. Ultimately, ultrapure deep-blue perovskite LEDs (439 nm) with a narrow emission width of 14 nm and a peak EQE of 0.14% are achieved at low driving voltage. Our finding expands the current understanding of surface ligand modulation in the development of pure bromide deep-blue perovskite optoelectronics.

Aggregation-Induced Emission Luminogens as Color Converters for Visible-Light Communication.

In this work, we report the application of the aggregation-induced emission luminogens (AIEgens) as color converters for visible light communication (VLC). In the form of pure solid powder, the AIEgens studied herein have demonstrated blue-to-red full-color emissions, large -6 dB electrical modulation bandwidths up to 279 MHz (∼56× that of commercial phosphor), and most of them can achieve high data rates of 428-493 Mbps (up to ∼49× that of commercial phosphor) at a maximum bit error rate of 3.8 × 10-3 using on-off keying. Their data communication performances strongly suggest that AIEgens are very promising candidates as color converters for VLC applications, together with their unique AIE properties that will benefit usage in high concentration. Based on the comprehensive experimental results, we further propose some insights into improving data rate of the color converter in VLC: the data rate limit is influenced by modulation bandwidth and signal-noise ratio (SNR). We have experimentally proved that the -6 dB electrical modulation bandwidth f c can be estimated from the effective lifetime τ of the color converter with the theoretical prediction of [Formula: see text] within experimental uncertainties, while theoretically derived that the SNR is proportional to its PL quantum efficiency. These observations and implications are very profound for exploring materials as color converters and improve the data transmission performance in VLC.