Inhibition of PCSK9 enhances the anti-hepatocellular carcinoma effects of TCR-T cells and anti-PD-1 immunotherapy.

T cells play important roles in antitumor immunity. However, given that the hepatocellular carcinoma (HCC) tumor microenvironment confers resistance to T cell-based immunotherapies, novel strategies to boost T cell-mediated antitumor efficacy are urgently needed for the treatment of HCC. Here, we show that high proprotein convertase subtilisin/kexin type9 (PCSK9) expression was negatively associated with HCC patient's overall survival and markers of CD8+ T cells. Pharmacological inhibition of PCSK9 enhanced tumor-specific killing and downregulated PD-1 expression of AFP-specific TCR-T. Inhibition of PCSK9 significantly enhances the anti-HCC efficacy of TCR-T cells and anti-PD-1 immunotherapy in vivo. Moreover, PCSK9 inhibitor suppressed HCC growth dependent on CD8+ T cells. Mechanically, pharmacological inhibition of PCSK9 promoted low-density lipoprotein receptor (LDLR)-mediated activation of mTORC1 signaling in CD8+ T cells. LDLR deficiency was shown to impair cellular mTORC1 signaling and the anti-HCC function of CD8 T cells. On the basis of our findings in this study, we propose a potential metabolic intervention strategy that could be used to enhance the antitumor effects of immunotherapy for HCC.

Polymerizable ionic liquid-derived N, S co-doped sp3/sp2 carbon as electrocatalyst for H2O2 generation.

The H2O2 generation via the green electrochemical process is of high interest. For the H2O2 electrochemical generation, the oxygen reduction reaction (ORR) is important. Unfortunately, the ORR is kinetically sluggish and catalysts are needed. However, noble metal ORR catalysts are pricy and scarcely applicable in applications. Therefore, non-precious metal catalysts are desired. Heteroatom-doped carbons show promise as metal-free ORR catalysts. The ORR catalytic activity will be enhanced by the carbon's sp2 and/or sp3 engineering. For N, S co-doped and sp2/sp3 modulated carbon, a polymerizable ionic liquid of hydrolyzed vinyl imidazolium was studied. The carbon is studied as a metal-free catalyst for the ORR via the 2e-process. It is possible to get an onset potential of 0.88 V vs. RHE with approximately 50% selectivity for the H2O2. The current study offers a simple technique for synthesizing heteroatom-doped sp2/sp3 designed carbon as catalysts for the electroreduction of O2 to produce H2O2, and a new way of tunning the sp3/sp2 carbon catalytic activity by modulating the ionic liquid.

Enhancing Reptile search algorithm with shifted distribution estimation strategy for coverage optimization in wireless sensor networks.

The rapid development of the Internet of Things (IoT) has extensively promoted the development of Wireless Sensor Networks (WSNs), an essential technology for series displaying perception and data collected from the physical world. In densely distributed areas, sensor nodes are unevenly distributed, which leads to the network coverage build-up and the consequent efficiency and effectiveness of WSNs. To address this issue, this paper proposes a new method for WSN coverage optimization based on the Reptile Search Algorithm (RSA). In the past, the Reptile Search algorithm has been used to solve optimization problems, which means it can improve different processes. However, the RSA needs to track the trajectory of optimal individuals in each iteration, which will ignore non-optimal individuals' bioeconomic characteristics. Therefore, the paper introduces a distribution estimation strategy into the RSA framework, which can fully mine all the positional information hidden in the entire population. We selected several functions as optimization test benchmark functions to evaluate the feasibility of the proposed method. This paper compares the proposed improved RSA with the standard RSA and some traditional optimization algorithms. The result has been calculated through a series of experiments on network coverage optimization, and the change of parameters also determines the effect of the RSA in the optimization of network coverage. The simulated results of the three similar network coverage optimization experiments show that the improved RSA can be used efficiently within different scenarios.

Norepinephrine or phenylephrine for the prevention of post-spinal hypotension after caesarean section: A double-blinded, randomized, controlled study of fetal heart rate and fetal cardiac output.

STUDY OBJECTIVE: Spinal anesthesia often causes hypotension, with consequent risk to the fetus. The use of vasopressor agents has been highly recommended for the prevention of spinal anesthesia-induced hypotension during caesarean delivery. Many studies have shown that norepinephrine can provide more stable maternal hemodynamics than phenylephrine. We therefore tested the hypothesis that norepinephrine preserves fetal circulation better than phenylephrine when used to treat maternal hypotension consequent to spinal anesthesia. DESIGN: Prospective, randomized, double-blinded study. SETTING: Operating room. PATIENTS: We recruited 223 parturients with uncomplicated singleton pregnancies who were scheduled for elective caesarean section under combined spinal-epidural anesthesia. INTERVENTIONS: The patients received prophylactic intravenous infusion of either 0.08 µg/kg/min norepinephrine or 0.5 µg/kg/min phenylephrine for prevention of spinal anesthesia-induced hypotension. MEASUREMENTS: Changes in fetal heart rate and fetal cardiac output before and after spinal anesthesia were measured using noninvasive Doppler ultrasound. MAIN RESULTS: 90 subjects who received norepinephrine infusion and 93 subjects who received phenylephrine infusion were ultimately analyzed in the present study. The effects of norepinephrine and phenylephrine on the change of fetal heart rate and fetal cardiac output at 3 and 6 min after spinal block were similar. Although there was a statistically significant decrease in fetal cardiac output at 6 min after subarachnoid block initiation in both the norepinephrine group (mean difference 0.02 L/min; 95% CI, 0-0.04 L/min; P = 0.03) and the phenylephrine group (mean difference 0.02 L/min; 95% CI, 0-0.04 L/min; P = 0.02), it remained within the normal range. CONCLUSIONS: Prophylactic infusion of comparable doses of phenylephrine or norepinephrine has similar effects on fetal heart rate and cardiac output changes after spinal anesthesia. Neither phenylephrine nor norepinephrine has meaningful detrimental effects on fetal circulation or neonatal outcomes.

Two novel TMEM67 variations in a Chinese family with recurrent pregnancy loss: a case report.

BACKGROUND: Recurrent pregnancy loss (RPL) is a common pregnancy complication that brings great pain to pregnant women and their families. Genetic factors are an important cause reason of RPL. However, clinical research on monogenic diseases with recurrent miscarriage is insufficient. CASE PRESENTATION: Here we reported a Chinese family with RPL and genetic analysis of the abortion and parents. A paternally inherited heterozygous missense variant c.1415T > G (p.V472G) and a maternally inherited heterozygous nonsense variant c.2314del (p.M772*) in TMEM67 gene were identified by trio-exome sequencing. c.2314del (p.M772*) generated a premature stop codon and truncated protein, was classified as "pathogenic". c.1415T > G (p.V472G) located in extra-cellular region, was classified as "likely pathogenic". Biallelic variants in TMEM67 gene cause lethal Meckel syndrome 3, consistent with the proband's prenatal phenotype. CONCLUSION: The current study of the Chinese family expands the pathogenic variant spectrum of TMEM67 and emphasizes the necessity of exome sequencing in RPL condition.

Risk factors for avascular necrosis of the femoral head after developmental hip dislocation reduction surgery and construction of Nomogram prediction model.

BACKGROUND: To analyze the risk factors for the development of avascular necrosis (AVN) of the femoral head after reduction surgery in children with developmental hip dysplasia (DDH), and to establish a prediction nomogram. METHODS: The clinical data of 134 children with DDH (169 hips) treated with closure reduction or open reduction from December 2016 to December 2019 were retrospectively analyzed. Independent risk factors for AVN after DDH reduction being combined with cast external immobilization were determined by univariate analysis and multivariate logistic regression and used to generate nomograms predicting the occurrence of AVN. RESULTS: A total of 169 hip joints in 134 children met the inclusion criteria, with a mean age at surgery of 10.7 ± 4.56 months (range: 4-22 months) and a mean follow-up duration of 38.32 ± 27.00 months (range: 12-94 months). AVN developed in 42 hip joints (24.9%); univariate analysis showed that the International Hip Dysplasia Institute (IHDI) grade, preoperative development of the femoral head ossification nucleus, cartilage acetabular index, femoral head to acetabular Y-shaped cartilage distance, residual acetabular dysplasia, acetabular abduction angle exceeding 60°, and the final follow-up acetabular index (AI) were associated with the development of AVN (P < 0.05). Multivariate logistic regression analysis showed that the preoperative IHDI grade, development of the femoral head ossification nucleus, acetabular abduction angle exceeding 60°, and the final follow-up AI were independent risk factors for AVN development (P < 0.05). Internal validation of the Nomogram prediction model showed a consistency index of 0.833. CONCLUSION: Preoperative IHDI grade, preoperative development of the femoral head ossification nucleus, final AI, and acetabular abduction angle exceeding 60° are risk factors for AVN development. This study successfully constructed a Nomogram prediction model for AVN after casting surgery for DDH that can predict the occurrence of AVN after casting surgery for DDH.

Application of MR images in radiotherapy planning for brain tumor based on deep learning.

PURPOSE: Explore the function and dose calculation accuracy of MRI images in radiotherapy planning through deep learning methods. METHODS: 131 brain tumor patients undergoing radiotherapy with previous MR and CT images were recruited for this study. A new series of MRI from the aligned MR was firstly registered to CT images strictly using MIM software and then resampled. A deep learning method (U-NET) was used to establish a MRI-to-CT conversion model, for which 105 patient images were used as the training set and 26 patient images were used as the tuning set. Data from additional 8 patients were collected as the test set, and the accuracy of the model was evaluated from a dosimetric standpoint. RESULTS: Comparing the synthetic CT images with the original CT images, the difference in dosimetric parameters D98, D95, D2 and Dmean of PTV in 8 patients was less than 0.5%. The gamma passed rates of PTV and whole body volume were: 1%/1 mm: 93.96%±6.75%, 2%/2 mm: 99.87%±0.30%, 3%/3 mm: 100.00%±0.00%; and 1%/1 mm: 99.14%±0.80%, 2%/2 mm: 99.92%±0.08%, 3%/3 mm: 99.99%±0.01%. CONCLUSION: MR images can be used both in delineation and treatment efficacy evaluation and in dose calculation. Using the deep learning way to convert MR image to CT image is a viable method and can be further used in dose calculation.

In-situ precipitation zero-valent Co on Co2VO4 to activate oxygen vacancies and enhance bimetallic ions redox for efficient detection toward Hg(II).

Despite the widespread utilization of variable valence metals in electrochemistry, it is still a formidable challenge to enhance the valence conversion efficiency to achieve excellent catalytic activity without introducing heterophase elements. Herein, the in-situ precipitation of Co particles on Co2VO4 not only enhanced the concentration of oxygen vacancies (Ov) but also generated a greater number of low-valence metals, thereby enabling efficient reduction towards Hg(II). The electroanalysis results demonstrate that the sensitivity of Co/Co2VO4 towards Hg(II) was measured at an impressive value of 1987.74 µA µM-1 cm-2, significantly surpassing previously reported results. Further research reveals that Ov acted as the main adsorption site to capture Hg(II). The redox reactions of Co2+/Co3+ and V3+/V4+ played a synergistic role in the reduction of Hg(II), accompanied by the continuous supply of electrons from zero-valent Co to expedite the valence cycle. The Co/Co2VO4/GCE presented remarkable selectivity towards Hg(II), with excellent stability, reproducibility, and anti-interference capability. The electrode also exhibited minimal sensitivity fluctuations towards Hg(II) in real water samples, underscoring its practicality for environmental applications. This study elucidates the mechanism underlying the surface redox reaction of metal oxides facilitated by zero-valent metals, providing us with new strategies for further design of efficient and practical sensors.

Emotional labour in nursing research: A bibliometric analysis.

AIM: This study aims to conduct a comprehensive bibliometric analysis to explore the trajectory and thematic developments of emotional labour research in nursing. DESIGN: Utilizing descriptive and bibliometric analysis techniques. METHODS: The data analysis and graphical presentation were conducted using the Bibliometrix Package in R software. DATA SOURCES: The Web of Science Core Collection (WoSCC) database was searched on October 20, 2023. RESULTS: From 1992 to 2023, 842 authors published relevant articles, yielding 779 author keywords. There has been a general upward trend in the number of articles published over the past 30 years, with an annual growth rate of 11.71%. Keyword co-occurrence cluster analysis revealed the main focus areas of research on emotional labour antecedents and consequences, regulatory modalities, training and education, as well as research methods and application scenarios. CONCLUSION: Emotional labour significantly influences nursing staff's well-being and patient care outcomes. Effective management and education regarding emotional labour are crucial for enhancing nursing staff performance and patient care quality. Future research should focus on long-term effects, training efficacy, regulatory strategies across clinical settings, and innovative approaches to address current challenges. IMPACT: This study provides valuable insights into the unique trajectory and thematic developments of emotional labour research in nursing. The findings underscore the importance of addressing emotional labour in nursing practice and education to improve patient care outcomes and nursing staff well-being. REPORTING METHOD: Adherence to recognized bibliometric reporting methods, following relevant EQUATOR guidelines. NO PATIENT OR PUBLIC CONTRIBUTION: This study is based solely on existing literature and did not involve patients or the public in its design, conduct, analysis, interpretation, or preparation.

A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells (TCR-T cells) against hepatocellular carcinoma.

Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma (HCC) are urgently needed. The common cytokine receptor γ chain (γc) family cytokines such as IL-2, IL-7, IL-15 and IL-21 play fundamental roles in T cell development, differentiation and effector phases. This study aims to determine the combination effects of IL-21 in T cell therapy against HCC and investigate optimized strategies to utilize the effect of IL-21 signal in T cell therapy. The antitumor function of AFP-specific T cell receptor-engineered T cells (TCR-T) was augmented by exogenous IL-21 in vitro and in vivo. IL-21 enhanced proliferation capacity, promoted memory differentiation, downregulated PD-1 expression and alleviated apoptosis in TCR-T after activation. A novel engineered IL-21 receptor was established, and TCR-T armed with the novel engineered IL-21 receptors (IL-21R-TCR-T) showed upregulated phosphorylated STAT3 expression without exogenous IL-21 ligand. IL-21R-TCR-T showed better proliferation upon activation and superior antitumor function in vitro and in vivo. IL-21R-TCR-T exhibited a less differentiated, exhausted and apoptotic phenotype than conventional TCR-T upon repetitive tumor antigen stimulation. The novel IL-21 receptor in our study programs powerful TCR-T and can avoid side effects induced by IL-21 systemic utilization. The novel IL-21 receptor creates new opportunities for next-generation TCR-T against HCC.

Synergistic effect of cannabidiol with dasatinib on lung cancer by SRC/PI3K/AKT signal pathway.

Dasatinib-related resistance frequently occurs and may lead to the failure of chemotherapy; thus, dose interruptions are necessary. Cannabidiol (CBD) has potential for integration with orthodox cancer care. In this study, we explored the combination effect of CBD and dasatinib on A549 cells. CBD in combination with dasatinib could induce significant synergistic apoptosis in vitro (ZIP > 10) and in vivo. The combination of CBD and low-dose dasatinib exhibited antiproliferative and proapoptotic effects through up-regulation of caspase-3 and Bax, and down-regulation of Bcl-2 in A549 cells. The xenograft mouse model suggested that the combination was more efficient and safer. In short, CBD and low-dose dasatinib exhibited a synergistic effect on anticancer by targeting the SRC/PI3K/AKT signaling pathway, suggesting a potential therapeutic option for the treatment of lung cancer.

Effects of Diet on the Gut Bacterial Community of Aldrichina grahami (Diptera: Calliphoridae) across Developmental Stages.

The blowfly, Aldrichina grahami (Diptera: Calliphoridae), is a well-known forensically important insect. Basic data related to A. grahami have been well documented; but despite the pivotal role of gut microbes in various facets of insect biology, little is known about its gut microbiome. To investigate the gut bacterial community of A. grahami and explore its stability, diet and developmental stage were selected as the two variables. Larvae were reared on bovine liver, swine manure, and chicken manure, and high-throughput sequencing of the 1st, 2nd, and 3rd instar larvae and the newly emerged adults was performed. According to our results, the alpha diversity of the gut bacterial community did not significantly vary among different diets and developmental stages. Principal coordinate analysis revealed that the gut microbiome of A. grahami clustered together among different diets and developmental stages. The main phyla in the gut microbial community of A. grahami were Firmicutes and Proteobacteria, and the dominant genera were Vagococcus, Providencia, Lactobacillus, and Morganella. These findings characterized the gut microbiome of A. grahami and demonstrated that the gut bacterial community is fairly stable. The dominant genera Vagococcus, Providencia, Lactobacillus, and Morganella have the potential to serve as core microbiomes within the gut microbial community of A. grahami.

Ultrasound-Base Radiomics for Discerning Lymph Node Metastasis in Thyroid Cancer: A Systematic Review and Meta-analysis.

PURPOSE: Ultrasound is the imaging modality of choice for preoperative diagnosis of lymph node metastasis (LNM) in thyroid cancer (TC), yet its efficacy remains suboptimal. As radiomics gains traction in tumor diagnosis, its integration with ultrasound for LNM differentiation in TC has emerged, but its diagnostic merit is debated. This study assesses the accuracy of ultrasound-integrated radiomics in preoperatively diagnosing LNM in TC. METHODS: Literatures were searched in PubMed, Embase, Cochrane, and Web of Science until July 11, 2023. Quality of the studies was assessed by the radiomics quality score (RQS). A meta-analysis was executed using a bivariate mixed effects model, with a subgroup analysis based on modeling variables (clinical features, radiomics features, or their combination). RESULTS: Among 27 articles (16,410 TC patients, 6356 with LNM), the average RQS was 16.5 (SD:5.47). Sensitivity of the models based on clinical features, radiomics features, and radiomics features plus clinical features were 0.64, 0.76 and 0.69. Specificities were 0.77, 0.78 and 0.82. SROC values were 0.76, 0.84 and 0.81. CONCLUSION: Ultrasound-based radiomics effectively evaluates LNM in TC preoperatively. Adding clinical features does not notably enhance the model's performance. Some radiomics studies showed high bias, possibly due to the absence of standard application guidelines.

Wheat Seed Detection and Counting Method Based on Improved YOLOv8 Model.

Wheat seed detection has important applications in calculating thousand-grain weight and crop breeding. In order to solve the problems of seed accumulation, adhesion, and occlusion that can lead to low counting accuracy, while ensuring fast detection speed with high accuracy, a wheat seed counting method is proposed to provide technical support for the development of the embedded platform of the seed counter. This study proposes a lightweight real-time wheat seed detection model, YOLOv8-HD, based on YOLOv8. Firstly, we introduce the concept of shared convolutional layers to improve the YOLOv8 detection head, reducing the number of parameters and achieving a lightweight design to improve runtime speed. Secondly, we incorporate the Vision Transformer with a Deformable Attention mechanism into the C2f module of the backbone network to enhance the network's feature extraction capability and improve detection accuracy. The results show that in the stacked scenes with impurities (severe seed adhesion), the YOLOv8-HD model achieves an average detection accuracy (mAP) of 77.6%, which is 9.1% higher than YOLOv8. In all scenes, the YOLOv8-HD model achieves an average detection accuracy (mAP) of 99.3%, which is 16.8% higher than YOLOv8. The memory size of the YOLOv8-HD model is 6.35 MB, approximately 4/5 of YOLOv8. The GFLOPs of YOLOv8-HD decrease by 16%. The inference time of YOLOv8-HD is 2.86 ms (on GPU), which is lower than YOLOv8. Finally, we conducted numerous experiments and the results showed that YOLOv8-HD outperforms other mainstream networks in terms of mAP, speed, and model size. Therefore, our YOLOv8-HD can efficiently detect wheat seeds in various scenarios, providing technical support for the development of seed counting instruments.

Multi-Interfacial Confined Assembly of Colloidal Quantum Dots Quasisuperlattice Microcavities for High-Resolution Full-Color Microlaser Arrays.

Colloidal quantum dots (CQDs) are considered a promising material for the next generation of integrated display devices due to their designable optical bandgap and low energy consumption. Owing to their dispersibility in solvents, CQD micro/nanostructures are generally fabricated by solution-processing methods. However, the random mass transfer in liquid restricts the programmable construction in macroscopy and ordered assembly in microscopy for the integration of CQD optical structures. Herein, a multi-interfacial confined assembly strategy is developed to fabricate CQDs programmable microstructure arrays with a quasisuperlattice configuration through controlling the dynamics of three-phase contact lines (TPCLs). The motion of TPCLs dominates the division of liquid film for precise positioning of CQD microstructures, while pinned TPCLs control the solvent evaporation and concentration gradient to directionally drive the mass transfer and packing of CQDs. Owing to their long-range order and adjustable structural dimensions, CQD microring arrays function as high-quality-factor (high-Q) lasing resonant cavities with low thresholds and tunable lasing emission modes. Through the further surface treatment and liquid dynamics control, the on-chip integration of red (R), green (G), and blue (B) multicomponent CQD microlaser arrays are demonstrated. The technique establishes a new route to fabricate large-area, ultrahigh-definition, and full-color CQD laser displays.

A high concentrate diet inhibits forkhead box protein A2 expression, and induces oxidative stress, mitochondrial dysfunction and mitochondrial unfolded protein response in the liver of dairy cows.

High-concentrate diet induce subacute ruminal acidosis (SARA) and cause liver damage in ruminants. It has been reported that forkhead box protein A2 (FOXA2) can enhance mitochondrial membrane potential but its function in mitochondrial dysfunction induced by high concentrate diets is still unknown. Therefore, the aim of this study was to elucidate the effect of high-concentrate (HC) diet on hepatic FOXA2 expression, mitochondrial unfolded protein response (UPRmt), mitochondrial dysfunction and oxidative stress. A total of 12 healthy mid-lactation Holstein cows were selected and randomized into 2 groups: the low concentrate (LC) diet group (concentrate:forage = 4:6) and HC diet group (concentrate:forage = 6:4). The trial lasted 21 d. The rumen fluid, blood and liver tissue were collected at the end of the experiment. The results showed that the rumen fluid pH level was reduced in the HC group and the pH was lower than 5.6 for more than 4 h/d, indicating that feeding HC diets successfully induced SARA in dairy cows. Both FOXA2 mRNA and protein abundance were significantly reduced in the liver of the HC group compared with the LC group. The activity of antioxidant enzymes (CAT, G6PDH, T-SOD, Cu/Zn SOD, Mn SOD) and mtDNA copy number in the liver tissue of the HC group decreased, while the level of H2O2 significantly increased, this increase was accompanied by a decrease in oxidative phosphorylation (OXPHOS). The balance of mitochondrial division and fusion was disrupted in the HC group, as evidenced by the decreased mRNA level of OPA1, MFN1, and MFN2 and increased mRNA level of Drp1, Fis1, and MFF. At the same time, HC diet downregulated the expression level of SIRT1, SIRT3, PGC-1α, TFAM, and Nrf 1 to inhibit mitochondrial biogenesis. The HC group induced UPRmt in liver tissue by upregulating the mRNA and protein levels of CLPP, LONP1, CHOP, Hsp10, and Hsp60. In addition, HC diet could increase the protein abundance of Bax, CytoC, Caspase 3 and Cleaved-Caspase 3, while decrease the protein abundance of Bcl-2 and the Bcl-2/Bax ratio. Overall, our study suggests that the decreased expression of FOXA2 may be related to UPRmt, mitochondrial dysfunction, oxidative stress, and apoptosis in the liver of dairy cows fed a high concentrate diet.

A new strategy to stabilize the heavy metals in carbonized MSWI-fly ash using an acid-resistant oligomeric dithiocarbamate chelator.

Fly ash (FA) derived from municipal solid waste incineration (MSWI) requires safe handling before landfilling due to its extremely high salt content and the risk of leaching heavy metals (HMs) under acidic conditions. Herein, aimed at improving the acid stability of dithiocarbamates, a cost-effective oligomeric dithiocarbamate (ODTC) was developed to stabilize HMs from carbonated MSWI-FA. Spiking of 3.6 wt% ODTC reduced the HM leaching below landfill standards in China, even across the pH range of 2.0-13.0 or 8-week exposure to the natural environment. Stabilization decreased the acid-soluble/exchangeable fractions of Cd, Pb, and Zn from 22.2%, 4.49%, and 21.9% to 0.14%, 0.11%, and 12.2%, respectively, resulting in safe levels for Pb and Cd with risk assessments. Compared to DDTC and SDD, ODTC exhibited higher stability under acidic conditions after chelation with the HMs, minimized the risk of HM leaching, and significantly reduced stabilization costs. In-depth studies proved that the stabilization mechanism involved the ability of ODTC to chelate HMs strongly and form acid-resistant ODTC-HM complexes, agglomeration of the MSWI-FA grains to encapsulate the ODTC-HM complexes, transformations of the HMs from acid-soluble species to stable oxidizable and residual species, and specifically ODTC reducing high-valent Pb to more stable Pb(II) species.

Atovaquone enhances antitumor efficacy of TCR-T therapy by augmentation of ROS-induced ferroptosis in hepatocellular carcinoma.

T-cell receptor (TCR) engineered T-cell therapy has recently emerged as a promising adoptive immunotherapy approach for tumor treatment, yet hindered by tumor immune evasion resulting in poor therapeutic efficacy. The introduction of ferroptosis-targeted inducers offers a potential solution, as they empower T cells to induce ferroptosis and exert influence over the tumor microenvironment. Atovaquone (ATO) stands as a prospective pharmaceutical candidate with the potential to target ferroptosis, effectively provoking an excessive generation and accumulation of reactive oxygen species (ROS). In this study, we evaluated the effectiveness of a combination therapy comprising ATO and TCR-T cells against hepatocellular carcinoma (HCC), both in vitro and in vivo. The results of lactate dehydrogenase and cytokine assays demonstrated that ATO enhanced cytotoxicity mediated by AFP-specific TCR-T cells and promoted the release of IFN-γ in vitro. Additionally, in an established HCC xenograft mouse model, the combined therapy with low-dose ATO and TCR-T cells exhibited heightened efficacy in suppressing tumor growth, with no apparent adverse effects, comparable to the results achieved through monotherapy. The RNA-seq data unveiled a significant activation of the ferroptosis-related pathway in the combination therapy group in comparison to the TCR-T cells group. Mechanistically, the synergy between ATO and TCR-T cells augmented the release of IFN-γ by TCR-T cells, while concurrently elevating the intracellular and mitochondrial levels of ROS, expanding the labile iron pool, and impairing the integrity of the mitochondrial membrane in HepG2 cells. This multifaceted interaction culminated in the potentiation of ferroptosis within the tumor, primarily induced by an excess of ROS. In summary, the co-administration of ATO and TCR-T cells in HCC exhibited heightened vulnerability to ferroptosis. This heightened susceptibility led to the inhibition of tumor growth and the stimulation of an anti-tumor immune response. These findings suggest that repurposing atovaquone for adoptive cell therapy combination therapy holds the potential to enhance treatment outcomes in HCC.

Phosphorus-doped synergy of phase change in heterogeneous catalysts of NiS-NiS2 for efficient electrocatalysis of Pb(II).

A fundamental understanding of the electroanalytical activity of transition metal sulfide electrocatalysts, especially the origin of the electrocatalytic reactivity on the surface sites of heterostructures with multiple crystalline phases, is essential for the design of low-cost and highly efficient nonprecious metal electrocatalysts for further scientific and technological achievements. Herein, we injected P into NiS and occupied the S sites through a doping strategy. The redistributed electronic structure induced the construction of heterostructures, which significantly improved the structure and chemical state of electrochemically inert NiS. The phase-change mechanism between NiS and NiS2 synergistically catalyzes Pb(II), while the P and S sites jointly lose electrons. Moreover, the constructed heterojunction sensor shows the a sensitivity of 83.43 µA µM-1 to Pb(II) with a theoretical limit of detection of 48 nM, as well as excellent stability, reproducibility, and anti-interference ability. The accurate detection in real water further reveals the potential of this sensor for practical applications. This study provides a guiding strategy for improving electrochemically inert materials to design highly active electrocatalytic interfaces, which has important implications for the development of highly efficient electrode-sensitive materials similar to precious metals to achieve accurate electrical analysis.

2023: A year of accomplishments for the 13 Science Citation Index Expanded- and Emerging Sources Citation Index-indexed Baishideng journals.

In 2023, Baishideng Publishing Group (Baishideng) routinely published 47 open-access journals, including 46 English-language journals and 1 Chinese-language journal. Our successes were accomplished through the collective dedicated efforts of Baishideng staffs, Editorial Board Members, and Peer Reviewers. Among these 47 Baishideng journals, 7 are included in the Science Citation Index Expanded (SCIE) and 6 in the Emerging Sources Citation Index (ESCI). With the support of Baishideng authors, company staffs, Editorial Board Members, and Peer Reviewers, the publication work of 2023 is about to be successfully completed. This editorial summarizes the 2023 activities and accomplishments of the 13 SCIE- and ESCI-indexed Baishideng journals, outlines the Baishideng publishing policy changes and additions made this year, and highlights the unique advantages of Baishideng journals.