Toxic and essential metals: metabolic interactions with the gut microbiota and health implications.

Human exposure to heavy metals, which encompasses both essential and toxic varieties, is widespread. The intestine functions as a critical organ for absorption and metabolism of heavy metals. Gut microbiota plays a crucial role in heavy metal absorption, metabolism, and related processes. Toxic heavy metals (THMs), such as arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd), can cause damage to multiple organs even at low levels of exposure, and it is crucial to emphasize their potential high toxicity. Nevertheless, certain essential trace elements, including iron (Fe), copper (Cu), and manganese (Mn), play vital roles in the biochemical and physiological functions of organisms at low concentrations but can exert toxic effects on the gut microbiota at higher levels. Some potentially essential micronutrients, such as chromium (Cr), silicon (Si), and nickel (Ni), which were considered to be intermediate in terms of their essentiality and toxicity, had different effects on the gut microbiota and their metabolites. Bidirectional relationships between heavy metals and gut microbiota have been found. Heavy metal exposure disrupts gut microbiota and influences its metabolism and physiological functions, potentially contributing to metabolic and other disorders. Furthermore, gut microbiota influences the absorption and metabolism of heavy metals by serving as a physical barrier against heavy metal absorption and modulating the pH, oxidative balance, and concentrations of detoxification enzymes or proteins involved in heavy metal metabolism. The interactions between heavy metals and gut microbiota might be positive or negative according to different valence states, concentrations, and forms of the same heavy metal. This paper reviews the metabolic interactions of 10 common heavy metals with the gut microbiota and their health implications. This collated information could provide novel insights into the disruption of the intestinal microbiota caused by heavy metals as a potential contributing factor to human diseases.

Expansion of Structure Property in Cascade Nazarov Cyclization and Cycloexpansion Reaction to Diverse Angular Tricycles and Total Synthesis of Nominal Madreporanone.

A cascade Nazarov cyclization/dicycloexpansions reaction was developed for the precise synthesis of the angularly fused M/5/N (M = 5, 6; N = 4-9, 13) tricyclic skeletons. The prioritized expansion of the first ring played a critical role in the transformations, due to the release of ring strain, and the nature of the substituents present on the substrate is another influencing factor. This pioneering cascade reaction features broad substrates scope (33 examples), short reaction time, exceptional yields (up to 95%), and remarkable regioselectivities (> 20:1). Exploiting the synthetic application of this cascade reaction, we successfully executed a succinct total synthesis of nominal madreporanone for the first time.

[Study on fatigue resistance of mechanical nickel-titanium files by phase-locked infrared flaw detection method].

PURPOSE: The fatigue resistance of mechanical nickel-titanium files was tested by phase-locked infrared flaw detection method, in order to timely detect instrument wear, providing reference for clinical safe use and timely abandonment of nickel-titanium files. METHODS: Twenty sets of mechanical nickel-titanium files were selected from Reciproc-Blue(RB), MTWO and S3 respectively, and resin simulated root canals with 60° and 90° bending were prepared, which were divided into 6 subgroups. The fatigue value after use, the number of uses before breaking and the length of fracture of file 25# of each group of files were recorded and compared with SPSS 26.0 software package. RESULTS: With the increase of the times of use, the fatigue value of the three kinds of files increased gradually. Among the two types of curved root canals, the number of uses before fracture in RB group was significantly increased compared with that in MTWO group and S3 group (P＜0.05). The number of uses of the three kinds of files in the 90° curved root canal were significantly less than in the corresponding groups in the 60° curved root canal(P＜0.05). There was no significant difference in the length of fracture among the three kinds of files(P＞0.05). CONCLUSIONS: Phase-locked infrared flaw detection method can be used for non-destructive testing and quantitative analysis of the fatigue degree of nickel-titanium files.

A repeated strike loading organ culture model for studying compression-associated chronic disc degeneration.

Mechanical stress has been viewed as one of the key risk factors in accelerating the intervertebral disc degeneration process. The goal of the present study was to employ a repeated strike loading bovine caudal disc system to elucidate the pathophysiological impacts of cumulative mechanical stress on the disc. The discs in the model groups were subjected to two different mechanical stresses: one strike loading or repeated strike loading. The following indices were analyzed: histological morphology, glycosaminoglycan release, disc height, cell viability, apoptosis-related protein expression, and catabolism-related gene expression. Both mechanical stress modes induced degenerative changes in the discs by day 11, such as clefts and delamination of the annulus fibrosus; they increased glycosaminoglycan release. Cell viability was significantly decreased and catabolic gene expression was significantly up-regulated in the degenerative loading group and repeated strike loading group by day 9. These alterations remained evident in the annulus fibrosus tissue of the repeated strike loading group on day 11. Our data suggests that the repeated strike loading model adopted in this study could lead to degenerative changes in the disc organ model. Annulus fibrosus cells displayed a more noticeable response to mechanical stress damage and a slower recovery process, suggesting that the annulus fibrosus serves as a pivotal factor in disc degeneration due to mechanical stress injuries. The study also indicates that due to the gradual self-repair of intervertebral disc cells after injury, it is necessary to apply repeated strike loading on the disc at specific intervals when researching the repair of chronic disc injuries.

A viroid-derived small interfering RNA targets bHLH transcription factor MdPIF1 to regulate anthocyanin biosynthesis in Malus domestica.

Fruit colour is a critical determinant for the appearance quality and commercial value of apple fruits. Viroid-induced dapple symptom severely affects the fruit coloration, however, the underlying mechanism remains unknown. In this study, we identified an apple dimple fruit viroid (ADFVd)-derived small interfering RNA, named vsiR693, which targeted the mRNA coding for a bHLH transcription factor MdPIF1 (PHYTOCHROME-INTERACTING FACTOR 1) to regulate anthocyanin biosynthesis in apple. 5' RLM-RACE and artificial microRNA transient expression system proved that vsiR693 directly targeted the mRNA of MdPIF1 for cleavage. MdPIF1 positively regulated anthocyanin biosynthesis in both apple calli and fruits, and it directly bound to G-box element in the promoter of MdPAL and MdF3H, two anthocyanin biosynthetic genes, to promote their transcription. Expression of vsiR693 negatively regulated anthocyanin biosynthesis in both apple calli and fruits. Furthermore, co-expression of vsiR693 and MdPIF1 suppressed MdPIF1-promoted anthocyanin biosynthesis in apple fruits. Infiltration of ADFVd infectious clone suppressed coloration surrounding the injection sites in apple fruits, while a mutated version of ADFVd, in which the vsiR693 producing region was mutated, failed to repress fruit coloration around the injection sites. These data provide evidence that a viroid-derived small interfering RNA targets host transcription factor to regulate anthocyanin biosynthesis in apple.

Progress in the Use of Echocardiography in Patients with Tumors.

Advances in cancer treatment have increased patient survival rates, shifting clinical focus towards minimizing treatment-related morbidity, including cardiovascular issues. Since echocardiography allows for a comprehensive non-invasive assessment at all cancer stages, it is well suited to monitor cardiovascular disease secondary to oncology treatment. This has earned it significant attention in the study of cardiac tumors and treatment-induced cardiac alterations. Ultrasound methods-ranging from transthoracic and transesophageal echocardiography to ultrasound diagnostic techniques including myocardial strain imaging, myocardial work indices, three-dimensional cardiac imaging-offer a holistic view of both the tumor and its treatment impact cardiac function. Stress echocardiography, myocardial contrast echocardiography, and myocardial acoustic angiography further augment this capability. Together, these echocardiographic techniques provide clinicians with early detection opportunities for cardiac damage, enabling timely interventions. As such, echocardiography continues to be instrumental in monitoring and managing the cardiovascular health of oncology patients, complementing efforts to optimize their overall treatment and survival outcomes.

Long-Term Efficacy and Safety of Stapokibart in Adults with Moderate-to-Severe Atopic Dermatitis: An Open-Label Extension, Nonrandomized Clinical Trial.

BACKGROUND: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials. OBJECTIVE: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis. METHODS: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale. RESULTS: In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events. CONCLUSIONS: Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021).

The preface: Toward higher-T c superconductivity under lower pressure-from binary to ternary superhydrides.

This is the Preface to Special Topic: Challenges to Achieving Room-Temperature Superconductivity in Superhydrides under Pressure.

Tunable even- and odd-denominator fractional quantum Hall states in trilayer graphene.

Fractional quantum Hall (FQH) states are exotic quantum many-body phases whose elementary charged excitations are anyons obeying fractional braiding statistics. While most FQH states are believed to have Abelian anyons, the Moore-Read type states with even denominators - appearing at half filling of a Landau level (LL) - are predicted to possess non-Abelian excitations with appealing potential in topological quantum computation. These states, however, depend sensitively on the orbital contents of the single-particle LL wavefunctions and the LL mixing. Here we report magnetotransport measurements on Bernal-stacked trilayer graphene, whose multiband structure facilitates interlaced LL mixing, which can be controlled by external magnetic and displacement fields. We observe robust FQH states including even-denominator ones at filling factors ν = - 9/2, - 3/2, 3/2 and 9/2. In addition, we fine-tune the LL mixing and crossings to drive quantum phase transitions of these half-filling states and neighbouring odd-denominator ones, exhibiting related emerging and waning behaviour.

Development of a mouse model of chronic ventral spinal cord compression: Neurobehavioral, radiological, and pathological changes.

Objectives: The main objective of this study was to establish a mouse model of spinal ligament ossification to simulate the chronic spinal cord compression observed in patients with ossification of the posterior longitudinal ligament (OPLL). The study also aimed to examine the mice's neurobiological, radiological, and pathological changes. Methods: In the previous study, a genetically modified mouse strain was created using Crispr-Cas9 technology, namely, Enpp1 flox/flox /EIIa-Cre (C57/B6 background), to establish the OPLL model. Wild-type (WT) mice without compression were used as controls. Functional deficits were evaluated through motor score assessment, inclined plate testing, and gait analysis. The extent of compression was determined using CT imaging. Hematoxylin and eosin staining, luxol fast blue staining, TUNEL assay, immunofluorescence staining, qPCR, and Western blotting were performed to evaluate levels of apoptosis, inflammation, vascularization, and demyelination in the study. Results: The results demonstrated a gradual deterioration of compression in the Enpp1 flox/flox /EIIa-Cre mice group as they aged. The progression rate was more rapid between 12 and 20 weeks, followed by a gradual stabilization between 20 and 28 weeks. The scores for spinal cord function and strength, assessed using the Basso Mouse Scale and inclined plate test, showed a significant decline. Gait analysis revealed a noticeable reduction in fore and hind stride lengths, stride width, and toe spread. Chronic spinal cord compression resulted in neuronal damage and activated astrocytes and microglia in the gray matter and anterior horn. Progressive posterior cervical compression impeded blood supply, leading to inflammation and Fas-mediated neuronal apoptosis. The activation of Bcl2 and Caspase 3 was associated with the development of progressive neurological deficits (p < 0.05). Conclusions: The study presents a validated model of chronic spinal cord compression, enabling researchers to explore clinically relevant therapeutic approaches for OPLL.

Skinned Motion Retargeting with Preservation of Body Part Relationships.

Motion retargeting is an active research area in computer graphics and animation, allowing for the transfer of motion from one character to another, thereby creating diverse animated character data. While this technology has numerous applications in animation, games, and movies, current methods often produce unnatural or semantically inconsistent motion when applied to characters with different shapes or joint counts. This is primarily due to a lack of consideration for the geometric and spatial relationships between the body parts of the source and target characters. To tackle this challenge, we introduce a novel spatially-preserving Skinned Motion Retargeting Network (SMRNet) capable of handling motion retargeting for characters with varying shapes and skeletal structures while maintaining semantic consistency. By learning a hybrid representation of the character's skeleton and shape in a rest pose, SMRNet transfers the rotation and root joint position of the source character's motion to the target character through embedded rest pose feature alignment. Additionally, it incorporates a differentiable loss function to further preserve the spatial consistency of body parts between the source and target. Comprehensive quantitative and qualitative evaluations demonstrate the superiority of our approach over existing alternatives, particularly in preserving spatial relationships more effectively.

Accelerated Charge Transfer through Interface Chemical Bonds in MoS2/TiO2 for Photocatalytic Conversion of Lignocellulosic Biomass to H2.

Solar photocatalytic H2 production from lignocellulosic biomass has attracted great interest, but it suffers from low photocatalytic efficiency owing to the absence of highly efficient photocatalysts. Herein, we designed and constructed ultrathin MoS2-modified porous TiO2 microspheres (MT) with abundant interface Ti-S bonds as photocatalysts for photocatalytic H2 generation from lignocellulosic biomass. Owing to the accelerated charge transfer related to Ti-S bonds, as well as the abundant active sites for both H2 and ●OH generation, respectively, related to the high exposed edge of MoS2 and the large specific surface area of TiO2, MT photocatalysts demonstrate good performance in the photocatalytic conversion of α-cellulose and lignocellulosic biomass to H2. The highest H2 generation rate of 849 µmol·g-1·h-1 and apparent quantum yield of 4.45% at 380 nm was achieved in α-cellulose aqueous solution for the optimized MT photocatalyst. More importantly, lignocellulosic biomass of corncob, rice hull, bamboo, polar wood chip, and wheat straw were successfully converted to H2 over MT photocatalysts with H2 generation rate of 10, 19, 36, 29, and 8 µmol·g-1·h-1, respectively. This work provides a guiding design approach to develop highly active photocatalysts via interface engineering for solar H2 production from lignocellulosic biomass.

Conversion and fate of waste Li-ion battery electrolyte in a two-stage thermal treatment process.

Disposal of electrolytes from waste lithium-ion batteries (LIBs) has gained much more attention with the growing application of LIBs, yet handling spent electrolyte is challengeable due to its high toxicity and the lack of established methods. In this study, a novel two-stage thermal process was developed for treating residual electrolytes resulted from spent lithium-ion batteries. The conversion of fluorophosphate and organic matter in oily electrolyte during low-temperature rotation distillation was investigated. The distribution and migration of the concentrated electrolytes were studied and the corresponding reaction mechanisms were elucidated. Additionally, the influence of alkali on the fixation of fluorine and phosphate was further examined. The results indicated that hydrolyzed carbonate esters and lithium in the electrolyte could combine to form Li2CO3 and the hydrolysable hexafluorophosphate was proven to be stable in the concentrated electrolyte (45 rpm/85 °C, 30 min). It was found that CO2, CO, CH4, and H2 were the primary pyrolysis gases, while the pyrolysis oil consisted of extremely flammable substances formed by the dissociation and recombination of chemical bonds in the electrolyte solvent. After pyrolysis at 300 °C, fluorine and phosphate were present in the form of sodium fluoride and sodium phosphate. The stability of the residue was enhanced, and the environmental risk was reduced. By adding alkali (KOH/Ca(OH)2, 20 %), hexafluorophosphate in the electrolyte was transformed into fluoride and phosphate in the residue, thereby reducing the device's corrosion from fluorine-containing gas. This study provides a viable approach for managing the residual electrolyte in the waste lithium battery recovery process.

Special stent for draining the abdominal abscess respectively from colon and duodenum: A case report.

BACKGROUND: Postoperative abdominal infections are an important and heterogeneous health challenge. Many samll abdominal abscesses are resolved with antibiotics, but larger or symptomatic abscesses may require procedural management. CASE SUMMARY: A 65-year-old male patient who suffered operation for the left hepatocellular carcinoma eight months ago, came to our hospital with recurrent abdominal pain, vomit, and fever for one month. Abdominal computed tomography showed that a big low-density dumbbell-shaped mass among the liver and intestine. Colonoscopy showed a submucosal mass with a fistula at colon of liver region. Gastroscopy showed a big rupture on the submucosal mass at the descending duodenum and a fistula at the duodenal bulb. Under colonoscopy, the brown liquid and pus were drained from the mass with "special stent device". Under gastroscopy, we closed the rupture of the mass with a loop and six clips for purse stitching at the descending duodenum, and the same method as colonoscopy was used to drain the brown liquid and pus from the mass. The symptom of abdominal pain, vomit and fever were relieved after the treatment. CONCLUSION: The special stent device could be effectively for draining the abdominal abscess respectively from colon and duodenum.

Notopterygium Incisum Extract Promotes Apoptosis by Preventing the Degradation of BIM in Colorectal Cancer.

OBJECTIVE: Colorectal cancer (CRC), a prevalent malignancy worldwide, has prompted extensive research into anticancer drugs. Traditional Chinese medicinal materials offer promising avenues for cancer management due to their diverse pharmacological activities. This study investigated the effects of Notopterygium incisum, a traditional Chinese medicine named Qianghuo (QH), on CRC cells and the underlying mechanism. METHODS: The sulforhodamine B assay and colony formation assay were employed to assess the effect of QH extract on the proliferation of CRC cell lines HCT116 and Caco-2. Propidium iodide (PI) staining was utilized to detect cell cycle progression, and PE Annexin V staining to detect apoptosis. Western blotting was conducted to examine the levels of apoptotic proteins, including B-cell lymphoma 2-interacting mediator of cell death (BIM), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (BAX) and cleaved caspase-3, as well as BIM stability after treatment with the protein synthesis inhibitor cycloheximide. The expression of BAX was suppressed using lentivirus-mediated shRNA to validate the involvement of the BIM/BAX axis in QH-induced apoptosis. The in vivo effects of QH extract on tumor growth were observed using a xenograft model. Lastly, APCMin+ mice were used to study the effects of QH extract on primary intestinal tumors. RESULTS: QH extract exhibited significant in vitro anti-CRC activities evidenced by the inhibition of cell proliferation, perturbation of cell cycle progression, and induction of apoptosis. Mechanistically, QH extract significantly increased the stability of BIM proteins, which undergo rapid degradation under unstressed conditions. Knockdown of BAX, the downstream effector of BIM, significantly rescued QH-induced apoptosis. Furthermore, the in vitro effect of QH extract was recapitulated in vivo. QH extract significantly inhibited the tumor growth of HCT116 xenografts in nude mice and decreased the number of intestinal polyps in the APCMin+ mice. CONCLUSION: QH extract promotes the apoptosis of CRC cells by preventing the degradation of BIM.

Assessing the diagnostic value of left ventricular synchrony indices derived from phase analysis by D-SPECT in identifying obstructive coronary artery disease.

This study aimed to assess the diagnostic efficacy of left ventricular synchrony (LVS) for detecting coronary artery disease (CAD). We explored whether the LVS index derived from phase analysis of D-SPECT provides superior diagnostic value compared to conventional perfusion analysis in identifying obstructive CAD. Patients with suspected or confirmed CAD underwent drug-stress/rest gated D-SPECT myocardial perfusion imaging (MPI) and coronary angiography (CAG). A 50% stenosis was set as the threshold for obstructive CAD. 110 participants were enrolled in this analysis. There were significant differences in phase standard deviation (PSD), phase histogram bandwidth (PHB) and entropy among the four groups. Patients without cardiac disease and those with mild-moderate stenosis exhibited no noticeable contraction asynchrony. However, LVS indices demonstrated a gradual increase with the progression of coronary stenosis when compared to NC (P < 0.001). Obstructive CAD was identified in 43 out of 110 participants (39%). Optimal cutoff values for diagnosing obstructive CAD during stress were determined as 7.6° for PSD, 24° for PHB, and 37% for entropy, respectively. Notably, PSD, PHB, and entropy indices exhibited higher sensitivity compared to MPI. The integration of the stress-induced LVS indices into routine MPI analysis resulted in a significantly greater area under the curve (AUC), leading to improved diagnostic performance and enhanced differential capacity. Stress-induced LVS indices increase with the severity of coronary artery stenosis by D-SPECT phase analysis. Further, the indices-derived phase analysis exhibits superior sensitivity and discriminatory ability compared to MPI in detecting obstructive CAD.

Fetal movement during delivery can lead to damage to the umbilical vessels and endanger the life of the fetus.

INTRODUCTION: Fetal umbilical cord hematoma has a low incidence but high mortality, and its cause during delivery is often unclear. We report an autopsy case in which it was concluded that umbilical cord hematoma resulted from fetal movements during childbirth. CASE PRESENTATION AND AUTOPSY FINDINGS: A 27-year-old primigravida at 39 + 2 weeks gestation with normal antenatal visits suffered a fetal heart rate decrease during active labor. Bedside ultrasound revealed fetal death in utero 22 min later. Forensic pathologists found that the umbilical vessels were torn and bleeding on almost the same plane, and the hematoma compressed both umbilical arteries, which is the cause of fetal stillness in utero. A total of 32 cases were reported, including 6 umbilical cord ruptures and 26 umbilical cord hematomas. The cause of hematoma was unknown in 77 % of cases, while dysplasia was present in 56.25 % of umbilical cords. DISCUSSION: This case indicates that fetal movements may cause umbilical cord vessel injury, particularly when oxytocin is used to induce labor. When fetal heart sounds decrease for no apparent reason, the possibility of cord injury should be considered, and cesarean delivery should be performed as soon as possible. Therefore, rigorous fetal heart tracing during active delivery is necessary.

A homologous membrane-camouflaged self-assembled nanodrug for synergistic antitumor therapy.

Limited success has been achieved in ferroptosis-induced cancer treatment due to the challenges related to low production of toxic reactive oxygen species (ROS) and inherent ROS resistance in cancer cells. To address this issue, a self-assembled nanodrug have been investigated that enhances ferroptosis therapy by increasing ROS production and reducing ROS inhibition. The nanodrug is constructed by allowing doxorubicin (DOX) to interact with Fe2+ through coordination interactions, forming a stable DOX-Fe2+ chelate, and this chelate further interacts with sorafenib (SRF), resulting in a stable and uniform nanoparticle. In tumor cells, overexpressed glutathione (GSH) triggers the disassembly of nanodrug, thereby activating the drug release. Interestingly, the released DOX not only activates nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) to produce abundant H2O2 production for enhanced ROS production, but also acts as a chemotherapeutics agent, synergizing with ferroptosis. To enhance tumor selectivity and improve the blood clearance, the nanodrug is coated with a related cancer cell membrane, which enhances the selective inhibition of tumor growth and metastasis in a B16F10 mice model. Our findings provide valuable insights into the rational design of self-assembled nanodrug for enhanced ferroptosis therapy in cancer treatment. STATEMENT OF SIGNIFICANCE: Ferroptosis is a non-apoptotic form of cell death induced by the iron-regulated lipid peroxides (LPOs), offering a promising potential for effective and safe anti-cancer treatment. However, two significant challenges hinder its clinical application: 1) The easily oxidized nature of Fe2+ and the low concentration of H2O2 leads to a low efficiency of intracellular Fenton reaction, resulting in poor therapeutic efficacy; 2) The instinctive ROS resistance of cancer cells induce drug resistance. Therefore, we developed a simple and high-efficiency nanodrug composed of self-assembling by Fe2+ sources, H2O2 inducer and ROS resistance inhibitors. This nanodrug can effectively deliver the Fe2+ sources into tumor tissue, enhance intracellular concentration of H2O2, and reduce ROS resistance, achieving a high-efficiency, precise and safe ferroptosis therapy.

Enhancing hepatocellular carcinoma management: prognostic value of integrated CCL17, CCR4, CD73, and HHLA2 expression analysis.

PURPOSE: Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the chemokine ligand 17 (CCL17) and its receptor CCR4 as pivotal players in the tumor microenvironment (TME) of various cancers. This investigation aims to delineate the roles of CCL17 and CCR4 in modulating the tumor's immune landscape, assessing their potential as therapeutic interventions and prognostic markers in HCC. METHODS: 873 HCC patients post-radical surgery from 2008 to 2012 at Zhongshan Hospital, Fudan University were retrospectively examined. These individuals were stratified into a training cohort (n = 354) and a validation cohort (n = 519). Through immunohistochemical analysis on HCC tissue arrays, the expressions of CCL17, CCR4, CD73, CD47, HHLA2, and PD-L1 were quantified. Survival metrics were analyzed using the Cox model, and a prognostic nomogram was devised via R software. RESULTS: The investigation confirmed the presence of CCL17 and CCR4 within the cancerous and stromal compartments of HCC tissues, associating their heightened expression with adverse clinical markers and survival outcomes. Notably, the interplay between CD73 and CCR4 expression in tumor stroma highlighted a novel cellular entity, CCR4 + CD73 + stromal cells, impacting overall and relapse-free survival. A prognostic nomogram amalgamating these immunological markers and clinical variables was established, offering refined prognostic insights and aiding in the management of HCC. The findings suggest that reduced CCR4 and CCR4 + CD73 + cell prevalence may forecast improved outcomes post-TACE. CONCLUSION: This comprehensive evaluation of CCR4, CCL17, and associated markers introduces a nuanced understanding of the HCC immunological milieu, proposing CCR4 + CD73 + stromal cells as critical to HCC pathogenesis and patient stratification.