Effects of different substrates on the growth and yield of Amorphophallus muelleri.

Seven different substrates were prepared by mixing red soil, humus and river sand in different volume ratios and the growth and yield of Amorphophallus muelleri bulbils in different substrates was investigated. The growth of A. muelleri seedlings were tracked during the reproductive period, with measurements taken of indicators such as petiole length, petiole basal diameter and leaf size during the late period of leaf expansion. Number of surviving plants, weights and sizes of corms, and leaf bulbils were recorded after lodging. The results showed that there were differences in the physical and chemical properties of the seven substrates, but all met the growth requirements of A. muelleri. T1 (river sand), T2 (river sand: humus 1:1), T3 (humus), and T7 (river sand: humus: red soil 1:1:1) had higher emergence rates, reaching 95 %. T4 (humus: red soil 1:1) and T7 had better growth, with larger petiole and leaf sizes than other substrates. T3, T4, and T7 had higher yields, with a bulbil yield of 0.30 t hm-2 and a corm yield of 22.06 t hm-2. Compared to the use of a single substrate, whether river sand, humus, or red soil, the proportional mixture of the three test materials improved the physical structure and chemical composition of the substrate, contributing to the growth of A. muelleri. T7 (river sand: humus: red soil 1:1:1) was was found to be the best nursery substrate for A. muelleri.

Turning foes to friends: Advanced "in situ nanovaccine" with dual immunoregulation for enhanced immunotherapy of metastatic triple-negative breast cancer.

As a "cold tumor", triple-negative breast cancer (TNBC) exhibits limited responsiveness to current immunotherapy. How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a formidable challenge. Herein, an "in situ nanovaccine" Au/CuNDs-R848 was designed for imaging-guided photothermal therapy (PTT)/chemodynamic therapy (CDT) synergistic therapy to trigger dual immunoregulatory effects on TNBC. On the one hand, Au/CuNDs-R848 served as a promising photothermal agent and nanozyme, achieving PTT and photothermal-enhanced CDT against the primary tumor of TNBC. Meanwhile, the released antigens and damage-associated molecular patterns (DAMPs) promoted the maturation of dendritic cells (DCs) and facilitated the infiltration of T lymphocytes. Thus, Au/CuNDs-R848 played a role as an "in situ nanovaccine" to enhance the immunogenicity of TNBC by inducing immunogenic cell death (ICD). On the other hand, the nanovaccine suppressed the myeloid-derived suppressor cells (MDSCs), thereby reversing the immunosuppressive microenvironment. Through the dual immunoregulation, "cold tumor" was transformed into a "hot tumor", not only implementing a "turning foes to friends" therapeutic strategy but also enhancing immunotherapy against metastatic TNBC. Furthermore, Au/CuNDs-R848 acted as an excellent nanoprobe, enabling high-resolution near-infrared fluorescence and computed tomography imaging for precise visualization of TNBC. This feature offers potential applications in clinical cancer detection and surgical guidance. Collectively, this work provides an effective strategy for enhancing immune response and offers novel insights into the potential clinical applications for tumor immunotherapy.

RBS and ABS Coordinated Control Strategy Based on Explicit Model Predictive Control.

During the braking process of electric vehicles, both the regenerative braking system (RBS) and anti-lock braking system (ABS) modulate the hydraulic braking force, leading to control conflict that impacts the effectiveness and real-time capability of coordinated control. Aiming to enhance the coordinated control effectiveness of RBS and ABS within the electro-hydraulic composite braking system, this paper proposes a coordinated control strategy based on explicit model predictive control (eMPC-CCS). Initially, a comprehensive braking control framework is established, combining offline adaptive control law generation, online optimized control law application, and state compensation to effectively coordinate braking force through the electro-hydraulic system. During offline processing, eMPC generates a real-time-oriented state feedback control law based on real-world micro trip segments, improving the adaptiveness of the braking strategy across different driving conditions. In the online implementation, the developed three-dimensional eMPC control laws, corresponding to current driving conditions, are invoked, thereby enhancing the potential for real-time braking strategy implementation. Moreover, the state error compensator is integrated into eMPC-CCS, yielding a state gain matrix that optimizes the vehicle braking status and ensures robustness across diverse braking conditions. Lastly, simulation evaluation and hardware-in-the-loop (HIL) testing manifest that the proposed eMPC-CCS effectively coordinates the regenerative and hydraulic braking systems, outperforming other CCSs in terms of braking energy recovery and real-time capability.

Intelligent Vehicle Path Planning Based on Optimized A* Algorithm.

With the rapid development of the intelligent driving technology, achieving accurate path planning for unmanned vehicles has become increasingly crucial. However, path planning algorithms face challenges when dealing with complex and ever-changing road conditions. In this paper, aiming at improving the accuracy and robustness of the generated path, a global programming algorithm based on optimization is proposed, while maintaining the efficiency of the traditional A* algorithm. Firstly, turning penalty function and obstacle raster coefficient are integrated into the search cost function to increase the adaptability and directionality of the search path to the map. Secondly, an efficient search strategy is proposed to solve the problem that trajectories will pass through sparse obstacles while reducing spatial complexity. Thirdly, a redundant node elimination strategy based on discrete smoothing optimization effectively reduces the total length of control points and paths, and greatly reduces the difficulty of subsequent trajectory optimization. Finally, the simulation results, based on real map rasterization, highlight the advanced performance of the path planning and the comparison among the baselines and the proposed strategy showcases that the optimized A* algorithm significantly enhances the security and rationality of the planned path. Notably, it reduces the number of traversed nodes by 84%, the total turning angle by 39%, and shortens the overall path length to a certain extent.

Exploring the potential relationship between short sleep risks and cognitive function from the perspective of inflammatory biomarkers and cellular pathways: Insights from population-based and mice studies.

AIMS: The molecular mechanism of short-sleep conditions on cognition remains largely unknown. This research aimed to investigate associations between short sleep, inflammatory biomarkers and cognitive function in the US population (NHANES data 2011-2014) and explore cellular mechanisms in mice. METHODS: Systemic immune-inflammation index (SII) was calculated using blood-cell based biomarkers. Further, we employed integrated bioinformatics and single-cell transcriptomics (GSE137665) to examine how short sleep exposure influenced the molecular pathways associated with inflammation in the brain. To explore the signaling pathways and biological processes of sleep deprivation, we carried out enrichment analyses utilizing the GO and KEGG databases. RESULTS: Population results showed that, compared with normal sleep group, severe short sleep was associated with lower cognitive ability in all the four tests. Moreover, a higher SII level was correlated with lower scores of cognitive tests. In mice study, elevated activation of the inflammatory pathway was observed in cell subgroups of neurons within the sleep deprivation and recovery sleep cohorts. Additionally, heightened expression of oxidative stress and integrated stress response pathways was noted in GABAergic neurons during sleep deprivation. CONCLUSION: This study contributed to the understanding of the influence of short sleep on cognitive function and its cellular mechanisms.

Development of interpenetrating network hydrogels: Enhancing the release and bioaccessibility of green tea polyphenols.

Green Tea polyphenols (GTP) are important bioactive compounds with excellent physiological regulation functions. However, they are easily destroyed by the gastric environment during digestion. In this work, a sodium alginate (SA)-gellan gum (GG) interpenetrating network (IPN) hydrogel was synthesized to protect and delivery GTP. The ratio of SA/GG significantly affects the network structure of IPN hydrogels and the performance of delivering GTP. The hydrogel formed by interpenetrating 20 % GG with 80 % SA as the main network had the highest water uptake (55 g/g), holding capacity (950 mg/g), and freeze-thaw stability, with springiness reaching 0.933 and hardness reaching 1300 g, which due to the filling effect and non-covalent interaction. Rheological tests showed that the crosslink density of IPN hydrogel in SA-dominated network was improved by the addition of GG to make it better bound to GTP, and the higher water uptake meant that the system could absorb more GTP-containing solution. This IPN hydrogel maintained 917.3 mg/g encapsulation efficiency at the highest loading capacity (1080 mg/g) in tests as delivery system. In in vitro digestion simulations, owing to the pH responsiveness, the IPN hydrogel reduced the loss of GTP in gastric fluid, achieving a bioaccessibility of 71.6 % in the intestinal tract.

The role of dietary intake of live microbes in the association between leisure-time physical activity and depressive symptoms: a population-based study.

Current research has shown promising associations between factors such as diet, total physical activity, and mental health outcomes, acknowledging the intricate interplay between these variables. However, the role of dietary intake of live microbes, coupled with leisure-time physical activity (LTPA), in their relationship to depressive symptoms necessitates further exploration. The present study examined a cohort of 25 747 individuals who participated in the National Health and Nutrition Examination Survey between the years 2007 and 2018. Patient's Health Questionnaire (PHQ-9) was employed, whereby individuals scoring ≥ 10 were classified as exhibiting symptoms of depression. LTPA status was reported by the Global Physical Activity Questionnaire and calculated by metabolic equivalent-minutes/week. Foods consumed by participants were evaluated by live microbes per gram, which were categorized into three groups: low, medium, and high. After controlling for all covariates, findings indicated that LTPA was negatively associated with depressive symptoms (OR (95% confidence interval (CI): 0.983 (0.976, 0.990), p < 0.001). Participating in more LTPA was positively correlated with consuming all three levels of dietary live microbes (low, ß (95% CI): 0.086 (0.063, 0.109); medium, ß (95% CI): 0.009 (0.007, 0.012); high, ß (95% CI): 0.002 (0.001, 0.002)). Moreover, taking more foods with medium live microbes was associated with lower depressive likelihood (OR (95% CI): 0.931(0.882, 0.982), p = 0.010). Intake of medium and high levels of live microbes mediated the association between LTPA and depressive symptoms by 4.15% and 0.83%, respectively. Dietary intake of foods containing medium and high levels of live microbes may be a mediator of LTPA's negative association with depressive symptoms.

The effects of adding various starches on the structures of restructured potato-based dough and the oil uptake of potato chips.

BACKGROUND: The material composition significantly influences the oil absorption and quality characteristics of fried food products. The oil absorption of restructured potato chips is highly dependent on the structural properties of the restructured potato-based dough produced prior to frying. In this study, three types of starch were added to modify the structure of restructured potato-based dough, allowing the production of potato chips with less oil absorption. RESULTS: Distinct differences were observed among the three types of starch in terms of amylose content, chain length distribution, swelling power, solubility, crystalline structure and pasting properties. The addition of wheat starch, corn starch and tapioca starch changed the rheological properties, water distribution and strength of the restructured dough. Importantly, adding wheat starch and corn starch significantly lowered the oil content of potato chips by 7.94% and 13.06%, respectively. The reduction in oil absorption by potato chips was attributed to the increased strength of the starchy gel network of the dough, a slower rate of water evaporation and a limitation of dough expansion during frying. CONCLUSION: Adding wheat starch or corn starch to restructured potato-based dough resulted in a decrease in the oil absorption of potato chips by creating a stronger starchy gel network in the dough. This study could guide the development of suitable material compositions, which are important for producing fried food products with lower oil content. © 2024 Society of Chemical Industry.

Lewis Acid-Catalyzed Tandem Reaction Strategy for the Synthesis of Dihydrophenalene-Fused Lactones.

A Lewis acid-catalyzed tandem reaction strategy for the construction of a dihydrophenalene-lactone tetracyclic skeleton has been disclosed. Starting with 2-naphthol-tethered ketones and active methylene esters, the tandem reaction catalyzed by Sc(OTf)3 proceeded well to afford an array of dihydrophenalene-fused lactones with moderate to high efficiency and diastereoselectivity. Moreover, the synthetic utility of this protocol was demonstrated by easy gram-scale preparation and diverse product transformations.

Effect of starch granule size on the properties of dough and the oil absorption of fried potato crisps.

Starch is a key element in fried potato crisps, however, the effect of starch granule size on oil absorption of the product have yet to be fully investigated. The study explored the impact of starch granule size on both the dough characteristics and oil absorption in potato crisps. The dough composed of small-sized potato granules showed more compact and uniform network system. Additionally, X-ray Microscope analysis showed that potato crisps prepared with small-sized potato granules had limited matrix expansion and fewer pores, cracks, and voids. The small-sized potato and small-sized wheat starches granule addition crisps displayed a significantly greater average cell thickness (52.05 and 53.44 µm) than other samples, while exhibiting notably lower average porosity (61.37 % and 60.28 %) compared to other samples. Results revealed that potato crisps with medium and small potato granules had 12.91 % and 21.92 % lower oil content than those containing large potato starch. Potato crisps with B-type wheat starch showed 16.36 % less oil absorption than those with A-type wheat starch. Small-sized starches significantly influence the dough structure and contribute to the reduction of oil absorption in fried products. The generated insights may provide monitoring indexes for cultivating potato varieties with low oil absorption.

The effect of magnesium ions synergistic with mineralized collagen on osteogenesis/angiogenesis properties by modulating macrophage polarizationin vitroandin vivo.

In bone tissue engineering, the bone immunomodulatory properties of biomaterials are critical for bone regeneration, which is a synergistic process involving physiological activities like immune response, osteogenesis, and angiogenesis. The effect of the macrophage immune microenvironment on the osteogenesis and angiogenesis of various material extracts was examined in this experiment using Mg2+and Nano-hydroxyapatite/collagen (nHAC) in both a single application and a combined form. This studyin vitrorevealed that the two compounds combined significantly inhibited the NF-κB signaling pathway and reduced the release of inflammatory factors from macrophages when compared with the extraction phase alone. Additionally, by contributing to the polarization of macrophages towards the M2 type, the combined effects of the two materials can significantly improve osteogenesis/angiogenesis. The results ofin vivoexperiments confirmed that Mg2+/nHAC significantly promoted bone regeneration and angiogenesis. This study offers a promising method for enhancing bone graft material osseointegration.

Stabilization of all-natural water-in-oil high internal phase pickering emulsion by using diosgenin/soybean phosphatidylethanolamine complex: Characterization and application in 3D printing.

This study aimed to prepare an all-natural water-in-oil high internal phase Pickering emulsion (W/O-HIPPE) using diosgenin/soybean phosphatidylethanolamine complex (DGSP) and investigate the 3D printing performance. Results suggested that the self-assembly of diosgenin crystal was modified by SP in DGSP (diosgenin-SP ratios at 3:1 and 1:1), revealing a variation from large-size outward radiating needle-like to small-size granular-like shape, which facilitated closely packing at the interface. Hydrophilicity of DGSP was also increased (contact angle varying from 133.3 o to 106.4 o), ensuring more adequate interfacial adsorption to reduce interfacial tension more largely (6.5 mN/m). Thus, the W/O-HIPPE made by DGSP with diosgenin-SP = 1:1, exhibited smaller droplets and better freeze/thawing stability. The W/O-HIPPE was also measured improved rheological properties for 3D printing: satisfied shear-thinning behavior, higher recovery and self-supporting (viscoelasticity and deformation resistance). Consequently, the W/O-HIPPE allowed for printing more delicate patterns. This work provided guidance to prepare W/O-HIPPE for 3D printing.

Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer's disease: insights from GWAS and single-cell transcriptomics.

Background: Aging is an important factor in the development of Alzheimer's disease (AD). The senescent cells can be recognized and removed by NK cells. However, NK cell function is gradually inactivated with age. Therefore, this study used senescence as an entry point to investigate how NK cells affect AD. Methods: The study validated the correlation between cognition and aging through a prospective cohort of the National Health and Nutrition Examination Survey database. A cellular trajectory analysis of the aging population was performed using single-cell nuclear transcriptome sequencing data from patients with AD and different ages. The genome-wide association study (GWAS) cohort of AD patients was used as the outcome event, and the expression quantitative trait locus was used as an instrumental variable. Causal associations between genes and AD were analyzed by bidirectional Mendelian randomization (MR) and co-localization. Finally, clinical cohorts were constructed to validate the expression of key genes. Results: A correlation between cognition and aging was demonstrated using 2,171 older adults over 60 years of age. Gene regulation analysis revealed that most of the highly active transcription factors were concentrated in the NK cell subpopulation of AD. NK cell trajectories were constructed for different age populations. MR and co-localization analyses revealed that CHD6 may be one of the factors influencing AD. Conclusion: We explored different levels of AD and aging from population cohorts, single-cell data, and GWAS cohorts and found that there may be some correlations of NK cells between aging and AD. It also provides some basis for potential causation.

Recent Progress in Droplet Structure Machining for Advanced Optics.

The development of optical and photonic applications using soft-matter droplets holds great scientific and application importance. The machining of droplet structures is expected to drive breakthroughs in advancing frontier applications. This review highlights recent advancements in micro-nanofabrication techniques for soft-matter droplets, encompassing microfluidics, laser injection, and microfluidic 3D printing. The principles, advantages, and weaknesses of these technologies are thoroughly discussed. The review introduces the utilization of a phase separation strategy in microfluidics to assemble complex emulsion droplets and control droplet geometries by adjusting interfacial tension. Additionally, laser injection can take full advantage of the self-assembly properties of soft matter to control the spontaneous organization of internal substructures within droplets, thus providing the possibility of high-precision customized assembly of droplets. Microfluidic 3D printing demonstrates a 3D printing-based method for machining droplet structures. Its programmable nature holds promise for developing device-level applications utilizing droplet arrays. Finally, the review presents novel applications of soft-matter droplets in optics and photonics. The integration of processing concepts from microfluidics, laser micro-nano-machining, and 3D printing into droplet processing, combined with the self-assembly properties of soft materials, may offer novel opportunities for processing and application development.

Microglial uptake of hADSCs-Exo mitigates neuroinflammation in ICH.

Intracerebral hemorrhage (ICH) is associated with secondary neuroinflammation, leading to severe central nervous system damage. Exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs-Exo) have shown potential therapeutic effects in regulating inflammatory responses in ICH. This study aims to investigate the role of hADSCs-Exo in ICH and its underlying mechanism involving miRNA-mediated regulation of formyl peptide receptor 1 (FPR1). Flow cytometry was used to identify hADSCs and extract exosomes. Transmission electron microscopy and Western blot were performed to confirm the characteristics of the exosomes. In vitro experiments were conducted to explore the uptake of hADSCs-Exo by microglia cells and their impact on inflammatory responses. In vivo, an ICH mouse model was established, and the therapeutic effects of hADSCs-Exo were evaluated through neurological function scoring, histological staining, and immunofluorescence. Bioinformatics tools and experimental validation were employed to identify miRNAs targeting FPR1. hADSCs-Exo were efficiently taken up by microglia cells and exhibited anti-inflammatory effects by suppressing the release of inflammatory factors and promoting M1 to M2 transition. In the ICH mouse model, hADSCs-Exo significantly improved neurological function, reduced hemorrhage volume, decreased neuronal apoptosis, and regulated microglia polarization. miR-342-3p was identified as a potential regulator of FPR1 involved in the neuroprotective effects of hADSCs-Exo in ICH. hADSCs-Exo alleviate neuroinflammation in ICH through miR-342-3p-dependent targeting of FPR1, providing a new therapeutic strategy for ICH.

Immunogenicity of Tetravalent Protein Vaccine SCTV01E-2 against SARS-CoV-2 EG.5 Subvaraint: A Phase 2 Trial.

The Omicron EG.5 lineage of SARS-CoV-2 is currently on a trajectory to become the dominant strain. This phase 2 study aims to evaluate the immunogenicity of SCTV01E-2, a tetravalent protein vaccine, with a specific emphasis on its immunogenicity against Omicron EG.5, comparing it with its progenitor vaccine, SCTV01E (NCT05933512). As of 12 September 2023, 429 participants aged ≥18 years were randomized into the groups SCTV01E (N = 215) and SCTV01E-2 (N = 214). Both vaccines showed increases in neutralizing antibody (nAb) against Omicron EG.5, with a 5.7-fold increase and a 9.0-fold increase in the SCTV01E and SCTV01E-2 groups 14 days post-vaccination, respectively. The predetermined statistical endpoints were achieved, showing that the geometric mean titer (GMT) of nAb and the seroresponse rate (SRR) against Omicron EG.5 were significantly higher in the SCTV01E-2 group than in the SCTV01E group. Additionally, SCTV01E and SCTV01E-2 induced a 5.5-fold and a 5.9-fold increase in nAb against XBB.1, respectively. Reactogenicity was generally mild and transient. No vaccine-related serious adverse events (SAEs), adverse events of special interest (AESIs), or deaths were reported. In summary, SCTV01E-2 elicited robust neutralizing responses against Omicron EG.5 and XBB.1 without raising safety concerns, highlighting its potential as a versatile COVID-19 vaccine against SARS-CoV-2 variants.

Intelligence detection of oil absorption in French fries by surface profiles.

Surface profiles are important evaluation indices for oil absorption behavior of fried foods. This research established two intelligent models of partial least-squares regression (PLSR) and back propagation artificial neural network (BP-ANN) for monitoring the oil absorption behavior of French fries based on the surface characteristics. Surface morphology and texture of French fries by rapeseed oil (RO) and high-oleic peanut oil (HOPO) at different temperatures were investigated. Results showed that oil content of samples increased with frying temperature, accounting for 37.7% and 41.4% of samples fried by RO and HOPO respectively. The increase of crust ratio, roughness and texture parameters (Fm, Nwr, fwr, Wc) and the decrease of uniformity were observed with the frying temperature. Coefficients of prediction set of PLSR and BP-ANN models were more than 0.93, which indicated that surface features combined with chemometrics were rapid and precise methods for determining the oil content of French fries.

Predicting the 90-day prognosis of stereotactic brain hemorrhage patients by multiple machine learning using radiomic features combined with clinical features.

Hypertensive Intracerebral Hemorrhage (HICH) is one of the most common types of cerebral hemorrhage with a high mortality and disability rate. Currently, preoperative non-contrast computed tomography (NCCT) scanning-guided stereotactic hematoma removal has achieved good results in treating HICH, but some patients still have poor prognoses. This study collected relevant clinical and radiomic data by retrospectively collecting and analyzing 432 patients who underwent stereotactic hematoma removal for HICH from January 2017 to December 2020 at the Liuzhou Workers Hospital. The prognosis of patients after 90 days was judged by the modified Rankin Scale (mRS) scale and divided into the good prognosis group (mRS ≤ 3) and the poor prognosis group (mRS > 3). The 268 patients were randomly divided into training and test sets in the ratio of 8:2, with 214 patients in the training set and 54 patients in the test set. The least absolute shrinkage and selection operator (Lasso) was used to screen radiomics features. They were combining clinical features and radiomic features to build a joint prediction model of the nomogram. The AUCs of the clinical model for predicting different prognoses of patients undergoing stereotactic HICH were 0.957 and 0.922 in the training and test sets, respectively, while the AUCs of the radiomics model were 0.932 and 0.770, respectively, and the AUCs of the combined prediction model for building a nomogram were 0.987 and 0.932, respectively. Compared with a single clinical or radiological model, the nomogram constructed by fusing clinical variables and radiomic features could better identify the prognosis of HICH patients undergoing stereotactic hematoma removal after 90 days.

Glycogen metabolism-mediated intercellular communication in the tumor microenvironment influences liver cancer prognosis.

Glycogen metabolism plays a key role in the development of hepatocellular carcinoma (HCC), but the function of glycogen metabolism genes in the tumor microenvironment (TME) is still to be elucidated. Single-cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells, and 65 glycogen metabolism genes were analyzed by a nonnegative matrix factorization (NMF). The prognosis and immune response of new glycogen TME cell clusters were predicted by using HCC and immunotherapy cohorts from public databases. HCC single-cell analysis was divided into fibroblasts, NT T cells, macrophages, endothelial cells, and B cells, which were separately divided into new cell clusters by glycogen metabolism gene annotation. Pseudo-temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell clusters. Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell-related subtypes and different glycogen subtype cell clusters. SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism. In addition, TME cell clusters of glycogen metabolism were found to be enriched in expression in CAF subtypes, CD8 depleted, M1, and M2 types. Bulk-seq analysis showed the prognostic significance of glycogen metabolism-mediated TME cell clusters in HCC, while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade (ICB), especially for CAFs, T cells, and macrophages. In summary, our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell clusters.

Peripheral blood lymphocyte subsets predict the efficacy of TACE with or without PD-1 inhibitors in patients with hepatocellular carcinoma: a prospective clinical study.

Background: Although peripheral blood lymphocyte subsets, particularly PD-1+ T cells, are promising prognostic indicators for patients with cancer. However, their clinical significance remains unclear. Methods: We prospectively enrolled 157 patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization combined with or without PD-1 inhibitors. Twenty peripheral lymphocyte subsets and cytokines were analyzed. We analyzed the differences in PD-1+ T cells between patients treated with and without PD-1 inhibitors and their associations with tumor response, survival prognosis, and clinical features. Results: We found that the baseline CD8+PD-1+ and CD4+PD-1+ T-cell frequencies in patients who had received PD-1 inhibitors were lower than those in patients who had not received PD-1 inhibitors (p < 0.001). In the former patients, there were no differences in PD-1+ T-cell frequencies between the responder and non-responder subgroups (p > 0.05), whereas in the latter patients, the levels of CD8+PD-1+ T cells, CD4+PD-1+ T cells, and CD8+PD-1+/CD4+PD-1+ ratio did not predict tumor response, progression-free survival (PFS), or overall survival (OS) (p>0.05). Furthermore, in multivariate analysis of patients treated with or without PD-1 inhibitors revealed that the levels of CD8+CD38+ T cells (OR = 2.806, p = 0.006) were associated with tumor response, whereas those of CD8+CD28+ T cells (p = 0.038, p = 0.001) and natural killer (NK) cells (p = 0.001, p = 0.027) were associated with PFS and OS. Although, these independent prognostic factors were associated with progressive tumor characteristics (p<0.05), with the exception of CD8+CD28+ T cells, changes in these factors before and after treatment were unassociated with tumor response (p > 0.05). Conclusion: Circulating CD8+CD38+ T cells, CD8+CD28+ T cells, and NK cells were identified as potential prognostic factors for tumor response and survival in patients with HCC. Contrastingly, although PD-1 inhibitors can effectively block the T cell PD-1 receptor, the baseline PD-1+ T-cell frequencies and changes in the frequency of these cells have limited prognostic value.