Carbon-based nanozymes: design, catalytic mechanisms, and environmental applications.

Carbon-based nanozymes are synthetic nanomaterials that are predominantly constituted of carbon-based materials, which mimic the catalytic properties of natural enzymes, boasting features such as tunable catalytic activity, robust regenerative capacity, and exceptional stability. Due to the impressive enzymatic performance similar to various enzymes such as peroxidase, superoxide dismutase, and oxidase, they are widely used for detecting and degrading pollutants in the environment. This paper presents an exhaustive review of the fundamental design principles, catalytic mechanisms, and prospective applications of carbon-based nanozymes in the environmental field. These studies not only serve to augment the comprehension on the intricate operational mechanism inherent in these synthetic nanostructures, but also provide essential guidelines and illuminating perspectives for advancing their development and practical applications. Future studies that are imperative to delve into the untapped potential of carbon-based nanozymes within the environmental domain was needed to be explored to fully harness their ability to deliver broader and more impactful environmental preservation and management outcomes.

Diagnosis of neuropsychiatric systemic lupus erythematosus by label-free serum microsphere-coupled SERS fingerprints with machine learning.

Surface-enhanced Raman spectroscopy (SERS) is a powerful optical technique for non-invasive and label-free bioanalysis of liquid biopsy, facilitating to diagnosis of potential diseases. Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the subgroups of systemic lupus erythematosus (SLE) with serious manifestations for a high mortality rate. Unfortunately, lack of well-established gold standards results in the clinical diagnosis of NPSLE being a challenge so far. Here we develop a novel Raman fingerprinting machine learning (ML-) assisted diagnostic method. The microsphere-coupled SERS (McSERS) substrates are employed to acquire Raman spectra for analysis via convolutional neural network (CNN). The McSERS substrates demonstrate better performance to distinguish the Raman spectra from serums between SLE and NPSLE, attributed to the boosted signal-to-noise ratio of Raman intensities due to the multiple optical regulation in microspheres and AuNPs. Eight statistically-significant (p-value <0.05) Raman shifts are identified, for the first time, as the characteristic spectral markers. The classification model established by CNN algorithm demonstrates 95.0% in accuracy, 95.9% in sensitivity, and 93.5% in specificity for NPSLE diagnosis. The present work paves a new way achieving clinical label-free serum diagnosis of rheumatic diseases by enhanced Raman fingerprints with machine learning.

Type I Cystatin Derived from Cysticercus pisiformis-Stefins, Suppresses LPS-Mediated Inflammatory Response in RAW264.7 Cells.

Cysticercus pisiformis is a kind of tapeworm larvae of Taenia pisiformis, which parasitizes the liver envelope, omentum, mesentery, and rectum of rodents such as rabbits. Cysteine protease inhibitors derived from helminth were immunoregulatory molecules of intermediate hosts and had an immunomodulatory function that regulates the production of inflammatory factors. Thus, in the present research, the recombinant Stefin of C. pisiformis was confirmed to have the potential to fight inflammation in LPS-Mediated RAW264.7 murine macrophages. CCK8 test showed that rCpStefin below 50 µg/mL concentration did not affect cellular viability. Moreover, the NO production level determined by the Griess test was decreased. In addition, the secretion levels of IL-1ß, IL-6, and TNF-α as measured by ELISA were decreased. Furthermore, it exerted anti-inflammatory activity by decreasing the production of proinflammatory cytokines and proinflammatory mediators, including IL-1ß, IL-6, TNF-α, iNOS, and COX-2 at the gene transcription level, as measured by qRT-PCR. Therefore, Type I cystatin derived from C. pisiformis suppresses the LPS-Mediated inflammatory response of the intermediate host and is a potential candidate for the treatment of inflammatory diseases.

A collaborative manipulation strategy to enhance the sodium ion storage capability of Prussian white cathodes.

A collaborative manipulation strategy of proper heat treatment and self-customized hydrofluoroether-based electrolyte design has been proposed for boosting the sodium-ion storage kinetics of Prussian white cathodes. Improved monoclinic phase stability and electrolyte-cathode compatibility are responsible for an impressive discharge capacity of 148.4 mA h g-1 and excellent electrode reversibility.

In Vitro Comparison of a Closed and Semi-closed Leaflet Design for Adult and Pediatric Transcatheter Heart Valves.

Transcatheter heart valve replacements (TVR) are mostly designed in a closed position (c) with leaflets coaptating. However, recent literature suggests fabricating valves in semi-closed (sc) position to minimize pinwheeling. With about 100,000 children in need of a new pulmonary valve each year worldwide, this study evaluates both geometrical approaches in adult as well as pediatric size and condition. Three valves of each geometry were fabricated in adult (30 mm) and pediatric (15 mm) size, using porcine pericardium. To evaluate performance, the mean transvalvular pressure gradient (TPG), effective orifice area (EOA), and regurgitation fraction (RF) were determined in three different annulus geometries (circular, elliptic, and tilted). For both adult-sized valve geometries, the TPG (TPGC = 2.326 ± 0.115 mmHg; TPGSC = 1.848 ± 0.175 mmHg)* and EOA (EOAC = 3.69 ± 0.255 cm2; EOASC = 3.565 ± 0.025 cm2)* showed no significant difference. Yet the RF as well as its fluctuation was significantly higher for valves with the closed geometry (RFC = 12.657 ± 7.669 %; RFSC = 8.72 ± 0.977 %)*. Recordings showed that the increased backflow was caused by pinwheeling due to a surplus of tissue material. Hydrodynamic testing of pediatric TVRs verified the semi-closed geometry being favourable. Despite the RF (RFC = 7.721 ± 0.348 cm2; RFSC = 5.172 ± 0.679 cm2), these valves also showed an improved opening behaviour ((TPGC = 20.929 ± 0.497 cm2; TPGSC = 15.972 ± 1.158 cm2); (EOAC = 0.629 ± 0.017 cm2; EOASC = 0.731 ± 0.026 cm2)). Both adult and pediatric TVR with semi-closed geometry show better fluiddynamic functionality compared to valves with a closed design due to less pinwheeling. Besides improved short-term functionality, less pinwheeling potentially prevents early valve degeneration and improves durability. *Results are representatively shown for a circular annulus geometry.

11C-CFT PET brain imaging in Parkinson's disease using a total-body PET/CT scanner.

PURPOSE: This study aimed to evaluate the feasibility of 11C-CFT PET brain imaging in Parkinson's Disease using a total-body PET/CT scanner and explore the optimal scan duration to guide the clinical practice. METHODS: Thirty-two patients with Parkinson's disease (PD) performing 11C-CFT PET/CT brain imaging using a total-body PET/CT scanner were retrospectively enrolled. The PET data acquired over a period of 900 s were reconstructed into groups of different durations: 900-s, 720-s, 600-s, 480-s, 300-s, 180-s, 120-s, 60-s, and 30-s (G900 to G30). The subjective image quality analysis was performed using 5-point scales. Semi-quantitative measurements were analyzed by SUVmean and dopamine transporter (DAT) binding of key brain regions implicated in PD, including the caudate nucleus and putamen. The full-time images (G900) were served as reference. RESULTS: The overall G900, G720, and G600 image quality scores were 5.0 ± 0.0, 5.0 ± 0.0, and 4.9 ± 0.3 points, respectively, and there was no significant difference among these groups (P > 0.05). A significant decrease in these scores at durations shorter than 600 s was observed when compared to G900 images (P < 0.05). However, all G300 image quality was clinically acceptable (≥ 3 points). As the scan duration reduced, the SUVmean and DAT binding of caudate nucleus and putamen decreased progressively, while there were no statistically significant variations in the SUVmean of the background among the different groups. Moreover, the changes in the lesion DAT binding (ΔDAT-binding) between the full-time reference G900 image and other reconstructed group G720 to G30 images generally increased along with the reduced scan time. CONCLUSION: Sufficient image quality and lesion conspicuity could be achieved at 600-s scan duration for 11C-CFT PET brain imaging in PD assessment using a total-body PET/CT scanner, while the image quality of G300 was acceptable to meet clinical diagnosis, contributing to improve patient compliance and throughput of PET brain imaging.

Enhancing Ionic Conductivity and Electrochemical Stability of Li3PS4 via Zn, F Co-Doping for All-Solid-State Li-S Batteries.

Sulfide solid-state electrolytes have garnered considerable attention owing to their notable ionic conductivity and mechanical properties. However, achieving an electrolyte characterized by both high ionic conductivity and a stable interface between the electrode and electrolyte remains challenging, impeding its widespread application. In this work, we present a novel sulfide solid-state electrolyte, Li3.04P0.96Zn0.04S3.92F0.08, prepared through a solid-phase reaction, and explore its usage in all-solid-state lithium sulfur batteries (ASSLSBs). The findings reveal that the Zn, F co-doped solid-state electrolyte exhibits an ionic conductivity of 1.23 × 10-3 S cm-1 and a low activation energy (Ea) of 9.8 kJ mol-1 at room temperature, illustrating the aliovalent co-doping's facilitation of Li-ion migration. Furthermore, benefiting from the formation of a LiF-rich interfacial layer between the electrolyte and the Li metal anode, the Li/Li3.04P0.96Zn0.04S3.92F0.08/Li symmetrical cell exhibits critical current densities (CCDs) of up to 1 mA cm-2 and maintains excellent cycling stability. Finally, the assembled ASSLSBs exhibit an initial discharge capacity of 1295.7 mAh g-1 at a rate of 0.05 C and at room temperature. The cell maintains a capacity retention of 70.5% for more than 600 cycles at a high rate of 2 C, representing a substantial improvement compared to the cell with Li3PS4. This work provides a new idea for the design of solid-state electrolytes and ASSLSBs.

A GITRL-mTORC1-GM-CSF Positive Loop Promotes Pathogenic Th17 Response in Primary Sjögren Syndrome.

OBJECTIVE: Glucocorticoid-induced tumor necrosis factor receptor superfamily-related protein (GITR), with its ligand (GITRL), plays an important role in CD4+ T cell-mediated autoimmunity. This study aimed to investigate the underlying mechanisms of GITRL in primary Sjögren syndrome (pSS). METHODS: Patients with pSS and healthy controls were recruited. Serum GITRL and Th17-related cytokines were determined. RNA sequencing was performed to decipher key signal pathways. Nonobese diabetes (NOD) mice were adopted as experimental Sjögren models and recombinant adeno-associated virus (rAAV) transduction was conducted to verify the therapeutic potentials of targeting GITRL in vivo. RESULTS: Serum GITRL was significantly higher in patients with pSS and showed a positive correlation with leukopenia, thrombocytopenia, autoantibodies, lung involvement, and disease activity. Serum GITRL was correlated with Th17-related cytokines. GITRL promoted the expansion of Th17 and Th17.1 cells. Expansion of granulocyte-macrophage colony-stimulating factor positive (GM-CSF+) CD4+ T cells induced by GITRL could be inhibited by blockade of GITRL. Moreover, GM-CSF could stimulate GITRL expression on monocytes. RNA sequencing revealed mammalian target of rapamycin complexes 1 (mTORC1) might be the key modulator. The increased phosphorylation of S6 and STAT3 and the expansion of Th17 and Th17.1 cells induced by GITRL were effectively inhibited by rapamycin, suggesting a GITRL-mTORC1-GM-CSF positive loop in pathogenic Th17 response in pSS. Administration of an rAAV vector expressing short hairpin RNA targeting GITRL alleviated disease progression in NOD mice. CONCLUSION: Our results identified the pathogenic role of GITRL in exacerbating disease activity and promoting pathogenic Th17 response in pSS through a GITRL-mTORC1-GM-CSF loop. These findings suggest GITRL might be a promising therapeutic target in the treatment of pSS.

Long-term function of a novel autologous transcatheter pulmonary heart valve implant in an adult animal model.

BACKGROUND: Current heart valve implants entail major disadvantages in the treatment for younger patients or those with congenital heart defects. AIM: Evaluation of novel transcatheter pulmonary valve implant made from autologous pericardium with natural crosslinking agent in an in vitro setup and in vivo animal model METHODS: Valves were tested in a pulse duplicator according to ISO-standard 5840. For in vivo studies computer tomography was performed to measure sheep's native pulmonary valve dimensions. Pericardium was harvested by thoracotomy, personalized implants were manufactured and deployed in pulmonary valve position of the same sheep. Every 3 months implant functionality was evaluated by intracardiac echocardiography, intracardiac pressure measurements and cardiac magnetic resonance imaging (cMRI). Implants were explanted for macroscopic and histological examination. RESULTS: In vitro experiments showed compliance with regulatory requirements in terms of valve opening and insufficiency. Five sheep successfully received an autologous valve implant. Two animals had to be euthanized due to trauma sustained in the stable. Long-term valve function was excellent in three out of four animals with median implant cMRI regurgitation fraction of 9% (n = 4) at 3 months, 8% (n = 3) at 6, 8% (n = 3) at 9, 12% (n = 3) at 13, 8% (n = 2) at 17% and 8% (n = 2) at 20.5 months after implantation. Despite good adherence to neighboring tissue and endothelization, histological assessment revealed some signs of degeneration. CONCLUSION: Transcatheter pulmonary valve implants showed promising function for up to 20.5 months encouraging research to further improve this approach.

GSTP alleviates acute lung injury by S-glutathionylation of KEAP1 and subsequent activation of NRF2 pathway.

Oxidative stress plays an important role in the pathogenesis of acute lung injury (ALI). As a typical post-translational modification triggered by oxidative stress, protein S-glutathionylation (PSSG) is regulated by redox signaling pathways and plays diverse roles in oxidative stress conditions. In this study, we found that GSTP downregulation exacerbated LPS-induced injury in human lung epithelial cells and in mice ALI models, confirming the protective effect of GSTP against ALI both in vitro and in vivo. Additionally, a positive correlation was observed between total PSSG level and GSTP expression level in cells and mice lung tissues. Further results demonstrated that GSTP inhibited KEAP1-NRF2 interaction by promoting PSSG process of KEAP1. By the integration of protein mass spectrometry, molecular docking, and site-mutation validation assays, we identified C434 in KEAP1 as the key PSSG site catalyzed by GSTP, which promoted the dissociation of KEAP1-NRF2 complex and activated the subsequent anti-oxidant genes. In vivo experiments with AAV-GSTP mice confirmed that GSTP inhibited LPS-induced lung inflammation by promoting PSSG of KEAP1 and activating the NRF2 downstream antioxidant pathways. Collectively, this study revealed the novel regulatory mechanism of GSTP in the anti-inflammatory function of lungs by modulating PSSG of KEAP1 and the subsequent KEAP1/NRF2 pathway. Targeting at manipulation of GSTP level or activity might be a promising therapeutic strategy for oxidative stress-induced ALI progression.

Deficiency of peripheral CLA+ Tregs and clinical relevance in Behcet's syndrome.

BACKGROUND: Autoimmune responses have been suggested to involvement in patients with Behcet's syndrome (BS). There has been growing attention towards the roles of cutaneous lymphocyte antigen (CLA)+ regular T cells (Tregs) in autoimmune diseases. The role of CLA+ Tregs in BS is still uncertain. This study aims to clarify the impact of CLA+ Tregs on BS. METHODS: We collected peripheral blood from a total of 107 patients with BS and 114 healthy controls (HCs). The number of CLA+ Tregs, natural killer (NK) cells, B cells, and several subtypes of CD4+ T cells were detected using flow cytometry and compared between patients and HCs. RESULTS: The absolute number and proportion of CLA+ Tregs among CD4+ T lymphocytes and CD4+ Tregs were lower in patients with BS than in HCs. CLA+ Tregs were positively related with NK cells (r = 0.500, P < 0.001) and B cells (r = 0.470, P < 0.001) and negatively related with effector T cells (r=-0.402, P < 0.001) in patients with BS. Patients with BS and arterial aneurysms had CLA+ Treg cell deficiency. A decreased proportion of CLA+ Tregs was associated with arterial aneurysms in patients with BS. The proportion of CLA+ Tregs in patients with BS increased with corticosteroids and immunosuppressants. CONCLUSION: CLA+ Tregs decrease in association with arterial aneurysm in patients with BS. CLA+ Tregs may be a predictor of response to BS treatment.

Computational drug development for membrane protein targets.

The application of computational biology in drug development for membrane protein targets has experienced a boost from recent developments in deep learning-driven structure prediction, increased speed and resolution of structure elucidation, machine learning structure-based design and the evaluation of big data. Recent protein structure predictions based on machine learning tools have delivered surprisingly reliable results for water-soluble and membrane proteins but have limitations for development of drugs that target membrane proteins. Structural transitions of membrane proteins have a central role during transmembrane signaling and are often influenced by therapeutic compounds. Resolving the structural and functional basis of dynamic transmembrane signaling networks, especially within the native membrane or cellular environment, remains a central challenge for drug development. Tackling this challenge will require an interplay between experimental and computational tools, such as super-resolution optical microscopy for quantification of the molecular interactions of cellular signaling networks and their modulation by potential drugs, cryo-electron microscopy for determination of the structural transitions of proteins in native cell membranes and entire cells, and computational tools for data analysis and prediction of the structure and function of cellular signaling networks, as well as generation of promising drug candidates.

Simultaneous detection of seven bacterial pathogens transmitted by flies using the reverse line blot hybridization assay.

BACKGROUND: Traditional methods for detecting insect-borne bacterial pathogens are time-consuming and require specialized laboratory facilities, limiting their applicability in areas without access to such resources. Consequently, rapid and efficient detection methods for insect-borne bacterial diseases have become a pressing need in disease prevention and control. METHODS: We aligned the ribosomal 16S rRNA sequences of seven bacterial species (Staphylococcus aureus, Shigella flexneri, Aeromonas caviae, Vibrio vulnificus, Salmonella enterica, Proteus vulgaris, and Yersinia enterocolitica) by DNASTAR Lasergene software. Using DNASTAR Lasergene and Primer Premier software, we designed universal primers RLB-F and RLB-R, two species-specific probes for each pathogen, and a universal probe (catch-all). The PCR products of seven standard strains were hybridized with specific oligonucleotide probes fixed on the membrane for specific experimental procedures. To evaluate the sensitivity of PCR-RLB, genomic DNA was serially diluted from an initial copy number of 1010 to 100 copies/µl in distilled water. These dilutions were utilized as templates for the PCR-RLB sensitivity analysis. Simultaneous detection of seven fly-borne bacterial pathogens from field samples by the established PCR-RLB method was conducted on a total of 1060 houseflies, collected from various environments in Lanzhou, China. RESULTS: The established PCR-RLB assay is capable of detecting bacterial strains of about 103 copies/µl for S. aureus, 103 copies/µl for S. flexneri, 105 copies/µl for A. caviae, 105 copies/µl for V. vulnificus, 100 copies/µl for S. enterica, 105 copies/µl for P. vulgaris, and 100 copies/µl for Y. enterocolitica. The results demonstrate that the detection rate of the established PCR-RLB method is higher (approximately 100 times) compared to conventional PCR. This method was applied to assess the bacterial carrier status of flies in various environments in Lanzhou, China. Among the seven bacterial pathogens carried by flies, S. enterica (34.57%), S. flexneri (32.1%), and Y. enterocolitica (20.37%) were found to be the predominant species. CONCLUSIONS: Overall, this research shows that the rapid and efficient PCR-RLB detection technology could be a useful for surveillance and therefore effective prevention and control the spread of insect-borne diseases. Meanwhile, the experimental results indicate that urban sanitation and vector transmission sources are important influencing factors for pathogen transmission.

Breaking Iron Homeostasis: Iron Capturing Nanocomposites for Combating Bacterial Biofilm.

Given the scarcity of novel antibiotics, the eradication of bacterial biofilm infections poses formidable challenges. Upon bacterial infection, the host restricts Fe ions, which are crucial for bacterial growth and maintenance. Having coevolved with the host, bacteria developed adaptive pathways like the hemin-uptake system to avoid iron deficiency. Inspired by this, we propose a novel strategy, termed iron nutritional immunity therapy (INIT), utilizing Ga-CT@P nanocomposites constructed with gallium, copper-doped tetrakis (4-carboxyphenyl) porphyrin (TCPP) metal-organic framework, and polyamine-amine polymer dots, to target bacterial iron intakes and starve them. Owing to the similarity between iron/hemin and gallium/TCPP, gallium-incorporated porphyrin potentially deceives bacteria into uptaking gallium ions and concurrently extracts iron ions from the surrounding bacteria milieu through the porphyrin ring. This strategy orchestrates a "give and take" approach for Ga3+/Fe3+ exchange. Simultaneously, polymer dots can impede bacterial iron metabolism and serve as real-time fluorescent iron-sensing probes to continuously monitor dynamic iron restriction status. INIT based on Ga-CT@P nanocomposites induced long-term iron starvation, which affected iron-sulfur cluster biogenesis and carbohydrate metabolism, ultimately facilitating biofilm eradication and tissue regeneration. Therefore, this study presents an innovative antibacterial strategy from a nutritional perspective that sheds light on refractory bacterial infection treatment and its future clinical application.

Machine Learning Deciphered Molecular Mechanistics with Accurate Kinetic and Thermodynamic Prediction.

Time-lagged independent component analysis (tICA) and the Markov state model (MSM) have been extensively employed for extracting conformational dynamics and kinetic community networks from unbiased trajectory ensembles. However, these techniques may not be the optimal choice for elucidating transition mechanisms within low-dimensional representations, especially for intricate biosystems. Unraveling the association mechanism in such complex systems always necessitates permutations of several essential independent components or collective variables, a process that is inherently obscure and may require empirical knowledge for selection. To address these challenges, we have implemented an integrated unsupervised dimension reduction model: uniform manifold approximation and projection (UMAP) with hierarchy density-based spatial clustering of applications with noise (HDBSCAN). This approach effectively generates low-dimensional configurational embeddings. The hierarchical application of this architecture, in conjunction with MSM, reveals global kinetic connectivity while identifying local conformational states. Consequently, our methodology establishes a multiscale mechanistic elucidation framework. Leveraging the benefits of the uniform sample distribution and a denoising approach, our model demonstrates robustness in preserving global and local data structures compared to traditional dimension reduction methods in the field of MD analysis area. The interpretability of hyperparameter selection and compatibility with downstream tasks are cross-validated across various simulation data sets, utilizing both computational evaluation metrics and experimental kinetic observables. Furthermore, the predicted Mcl1-BH3 association kinetics (0.76 s-1) is in close agreement with surface plasmon resonance experiments (0.12 s-1), affirming the plausibility of the identified pathway composed of representative conformations. We anticipate that the devised workflow will serve as a foundational framework for studying recognition patterns in complex biological systems. Its contributions extend to the exploration of protein functional dynamics and rational drug design, offering a potent avenue for advancing research in these domains.

Screening of low-toxic zinc oxide nanomaterials and study the apoptosis mechanism of NSC-34 cells.

With the increasing application of ZnO nanomaterials (ZnO-NMts) in the biomedical field, it is crucial to assess their potential risks to humans and the environment. Therefore, this study aimed to screen for ZnO-NMts with low toxicity and establish safe exposure limits, and investigate their mechanisms of action. The study synthesized 0D ZnO nanoparticles (ZnO NPs) and 3D ZnO nanoflowers (ZnO Nfs) with different morphologies using a hydrothermal approach for comparative research. The ZnO-NMts were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Mouse brain neuronal cells (NSC-34) were incubated with ZnO NMts for 6, 12, and 24 h, and the cell morphology was observed using TEM. The toxic effects of ZnO Nfs on NSC-34 cells were studied using CCK-8 cell viability detection, reactive oxygen species (ROS) measurement, caspase-3 activity detection, Annexin V-FITC/PI apoptosis assay, and mitochondrial membrane potential (Δφm) measurement. The results of the research showed that ZnO-NMts caused cytoplasmic vacuolization and nuclear pyknosis. After incubating cells with 12.5 µg mL-1 ZnO-NMts for 12 h, ZnO NRfs exhibited the least toxicity and ROS levels. Additionally, there was a significant increase in caspase-3 activity, depolarization of mitochondrial membrane potential (Δφm), and the highest rate of early apoptosis.This study successfully identified ZnO NRfs with the lowest toxicity and determined the safe exposure limit to be < 12.5 µg mL-1 (12 h). These findings will contribute to the clinical use of ZnO NRfs with low toxicity and provide a foundation for further research on their potential applications in brain disease treatment.

Ion channel TRPV2 is critical in enhancing B cell activation and function.

The function of transient receptor potential vanilloid (TRPV) cation channels governing B cell activation remains to be explored. We present evidence that TRPV2 is highly expressed in B cells and plays a crucial role in the formation of the B cell immunological synapse and B cell activation. Physiologically, TRPV2 expression level is positively correlated to influenza-specific antibody production and is low in newborns and seniors. Pathologically, a positive correlation is established between TRPV2 expression and the clinical manifestations of systemic lupus erythematosus (SLE) in adult and child SLE patients. Correspondingly, mice with deficient TRPV2 in B cells display impaired antibody responses following immunization. Mechanistically, the pore and N-terminal domains of TRPV2 are crucial for gating cation permeation and executing mechanosensation in B cells upon antigen stimulation. These processes synergistically contribute to membrane potential depolarization and cytoskeleton remodeling within the B cell immunological synapse, fostering efficient B cell activation. Thus, TRPV2 is critical in augmenting B cell activation and function.

H2O2-triggered controllable carbon monoxide delivery for photothermally augmented gas therapy.

Carbon monoxide (CO) gas therapy has shown great potential as a very promising approach in the ongoing fight against tumors. However, delivering unstable CO to the tumor site and safely releasing it for maximum efficacy still have unsatisfactory outcomes. In this study, we've developed nanotheranostics (IN-DPPCO NPs) based on conjugated polymer IN-DPP and carbon monoxide (CO) carrier polymer mPEG(CO) for photothermal augmented gas therapy. The IN-DPPCO NPs can release CO with the hydrogen peroxide (H2O2) overexpressed in the tumor microenvironment. Meanwhile, IN-DPPCO NPs exhibit strong absorption in the near-infrared window, showing a high photothermal conversion efficiency of up to 41.5% under 808 nm laser irradiation. In vitro and in vivo experiments demonstrate that these nanotheranostics exhibit good biocompatibility. Furthermore, the synergistic CO/photothermal therapy shows enhanced therapeutic efficacy compared to gas therapy alone. This work highlights the great promise of conjugated polymer nanoparticles as versatile nanocarriers for spatiotemporally controlled and on-demand delivery of gaseous messengers to achieve precision cancer theranostics.

Implications of Sarcopenia and Glucometabolism Parameters of Muscle Derived From Baseline and End-of-Treatment 18F-FDG PET/CT in Diffuse Large B-Cell Lymphoma.

OBJECTIVE: We previously found that the incidence of sarcopenia increased with declining glucose metabolism of muscle in patients with treatment-naïve diffuse large B-cell lymphoma (DLBCL). This study aimed to investigate the relationship between sarcopenia and muscle glucometabolism using 18F-FDG PET/CT at baseline and end-of-treatment, analyze the changes in these parameters through treatment, and assess their prognostic values. MATERIALS AND METHODS: The records of 103 patients with DLBCL (median 54 years [range, 21-76]; male:female, 50:53) were retrospectively reviewed. Skeletal muscle area at the third lumbar vertebral (L3) level was measured, and skeletal muscle index (SMI) was calculated to determine sarcopenia, defined as SMI < 44.77 cm²/m² and < 32.50 cm²/m² for male and female, respectively. Glucometabolic parameters of the psoas major muscle, including maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean), were measured at L3 as well. Their changes across treatment were also calculated as ΔSMI, ΔSUVmax, and ΔSUVmean; Δbody mass index was also calculated. Associations between SMI and the metabolic parameters were analyzed, and their associations with progression-free survival (PFS) and overall survival (OS) were identified. RESULTS: The incidence of sarcopenia was 29.1% and 36.9% before and after treatment, respectively. SMI (P = 0.004) was lower, and sarcopenia was more frequent (P = 0.011) at end-of-treatment than at baseline. The SUVmax and SUVmean of muscle were lower (P < 0.001) in sarcopenia than in non-sarcopenia at both baseline and end-of-treatment. ΔSMI was positively correlated with ΔSUVmax of muscle (P = 0.022). Multivariable Cox regression analysis showed that sarcopenia at end-of-treatment was independently negatively associated with PFS (adjusted hazard ratio [95% confidence interval], 2.469 [1.022-5.965]), while sarcopenia at baseline was independently negatively associated with OS (5.051 [1.453-17.562]). CONCLUSION: Sarcopenic patients had lower muscle glucometabolism, and the muscular and metabolic changes across treatment were positively correlated. Sarcopenia at baseline and end-of-treatment was negatively associated with the prognosis of DLBCL.