A dendritic cell-recruiting, antimicrobial blood clot hydrogel for melanoma recurrence prevention and infected wound management.

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

Association of higher triglyceride-glucose index and triglyceride-to-high-density lipoprotein cholesterol ratio with early neurological deterioration after thrombolysis in acute ischemic stroke patients.

Background: Insulin resistance (IR) can predict the prognosis of patients suffering from cerebrovascular disorders. The triglyceride-glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio have been confirmed to be easy and reliable indicators of IR. However, the relationships between the TyG index or TG/HDL-C ratio and early neurological deterioration (END) after thrombolysis in patients with acute ischemic stroke (AIS) are uncertain. Methods: A retrospective analysis of 1,187 patients diagnosed with AIS who underwent intravenous thrombolysis between January 2018 and February 2024 was performed. Post-thrombolysis END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score of ≥4 within 24 h after thrombolysis. Logistic regression analysis was performed to explore the relationships of the TyG index and TG/HDL-C ratio with post-thrombolysis END. Receiver operating characteristic (ROC) analysis was used to assess the ability of the TyG index and TG/HDL-C ratio to discriminate post-thrombolysis END. Results: Among the 1,187 recruited patients, 179 (15.08%) were diagnosed with post-thrombolysis END, and 1,008 (84.92%) were diagnosed with non-END. A binary logistic regression model indicated that the TyG index (odds ratio [OR], 2.015; 95% confidence interval [CI] 1.964-2.414, p = 0.015) and TG/HDL-C ratio (OR, 1.542; 95% CI, 1.160-2.049, p = 0.004) were independent factors for post-thrombolysis END. The area under the curve (AUC) values for the TyG index, TG/HDL-C ratio, and TyG index combined with the TG/HDL-C ratio for post-thrombolysis END were 0.704, 0.674, and 0.755, respectively. Conclusion: This study indicates that the TyG index and TG/HDL-C ratio can be used as prognostic factors to predict post-thrombolysis END.

Leydig cells pyroptosis in testis mediates deoxynivalenol-induced male reproductive toxicity in mice.

Deoxynivalenol (DON) is a toxic secondary metabolite produced by Fusarium spp. It is widely distributed among various cereals and has attracted much attention as a potential health threat to humans and domestic animals. However, the effects of DON on the reproductive systems of mammals are still ambiguous. In this study, the toxic effects of DON in the male reproduction of mice were investigated. The results showed that DON caused the shedding of sperm cells at all testis levels and the presence of inflammatory cells in the testicular interstitium. The rate of living sperm was significantly reduced, and the rate of sperm deformity was increased after DON exposure. The DON exposure resulted in decreased levels of testosterone (T) and increased levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the serum. Measurements of oxidative stress markers showed that DON induced oxidative stress in mice testis. Meanwhile, DON triggered the assembly of NLRP3-ASC-Caspase-1 inflammatory complex and pyroptosis in both mice testis and TM3 cells, further causing the activation of GSDMD, promoting the leakage of inflammatory cytokines, including IL-1ß and IL-18. Notably, the inhibition of oxidative stress was found to protect pyroptosis in TM3 cells exposed to DON. We identified a novel mechanism of reproductive damage induced by DON, demonstrating the activation of the canonical Caspase-1-dependent pyroptosis pathway and clarifying the protection of antioxidation against pyroptosis damage. Our discovery provided support for the risk assessment of DON and target exploration for clinical treatment related to pyroptosis.

The promotion of cell proliferation and invasion in cutaneous squamous cell carcinomas after ARNT downregulation is associated with CXCL3.

The aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor associated with adaptive responses to cellular stress. Its role in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. The aim of this study was to investigate the role of ARNT in cSCC. Immunohistochemistry revealed downregulation of ARNT in cSCC, precancerous lesions (actinic keratosis), and cells. Knockdown of ARNT in A431 and SCL-1 cells significantly enhanced cell growth and metastasis. Microarray analysis and Ingenuity Pathway Analysis confirmed that loss of ARNT in A431 cells was highly correlated with cell growth and movement and upregulated CXCL3 expression. Cellular and xenograft experiments further confirmed that ARNT regulates cSCC proliferation and invasiveness in a CXCL3-dependent manner. ARNT may regulate CXCL3 expression through ROS-STAT3 pathway. In conclusion, this study demonstrates that ARNT plays a critical role in the development of cSCC and significantly affects the proliferation and metastatic ability of cSCC cells. It has the potential to serve as an ideal treatment target for cSCC.

Severe Neurodevelopmental Phenotype, Diagnostic and Treatment Challenges in Patients with SECISBP2 Deficiency.

PURPOSE: Defects in the gene encoding selenocysteine insertion sequence binding protein 2, SECISBP2, result in global impaired selenoprotein synthesis manifesting a complex syndrome with characteristic serum thyroid function tests due to impaired thyroid hormone metabolism. Knowledge about this multisystemic defect remains limited. METHODS: Genetic and laboratory investigations were performed in affected members from six families presenting with short stature, failure to thrive. RESULTS: Four probands presented a complex neurodevelopmental profile, including absent speech, autistic features, and seizures. Pediatric neurological evaluation prompted genetic investigations leading to the identification of SECISBP2 variants before knowing the characteristic thyroid tests in two cases. Thyroid hormone treatment improved motor development, while speech and intellectual impairments persisted. This defect poses great diagnostic and treatment challenges for clinicians, as illustrated by a case that escaped detection for 20years, as SECISBP2 was not included in the neurodevelopmental genetic panel, and his complex thyroid status prompted anti-thyroid treatment instead. CONCLUSION: This syndrome uncovers the role of selenoproteins in humans. The severe neurodevelopmental disabilities manifested in four patients with SECISBP2 deficiency highlight an additional phenotype in this multisystem disorder. Early diagnosis and treatment are required, and long-term evaluation will determine the full spectrum of manifestations and the impact of therapy.

Naphthalimide-Modified Clusters for Red-Emitting Devices with High Color Purity.

Conventional fluorescent materials frequently exhibit narrow-band emissions with a small full width at half-maximum (fwhm) due to localized-state characteristics, but electroluminescence is less efficient owing to the utilization of only singlet excitons. In this work, taking advantage of naphthalimide (NAI)-acetylide derivatives with a rigid planar structure and localized transition characteristics, we elaborately designed two mononuclear Pt(II) complexes with weak double emissions of fluorescence and phosphorescence. Taking them as synthetic precursors, we prepared three PtAu2 heteronuclear clusters and successfully attained highly efficient narrow-band red phosphorescence with the fwhm below 30 nm. Both theoretical and experimental results suggest that the phosphorescence of PtAu2 clusters mainly originates from the naphthalimide-localized 3IL (intraligand) triplet state. Solution-processed organic light-emitting diodes (OLEDs) achieved highly efficient narrow-band red electroluminescence with an external quantum efficiency (EQE) of 16.7%. The CIE coordinates of the electroluminescence (0.69, 0.31) closely match the standard red emission for ultrahigh-definition display.

Interactions between mild depressive symptoms and amyloid pathology on the trajectory of neurodegeneration, cognitive decline, and risk of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) was driven by the interplay between modifiable environmental factors and ß-amyloid (Aß) pathology. We aimed to investigate the interaction effects of mild depressive symptoms (MDS) with Aß on AD development. METHODS: Longitudinal data of 1746 non-demented adults (mean age = 73 years, female = 53 %, maximum = 10 years) were derived from the Alzheimer's Disease Neuroimaging Initiative cohort. MDS was separately defined by the baseline status, longitudinal latent class, and average intensity during follow-up. Amyloid-positive (A+) status was determined based on cerebrospinal fluid levels of ß-amyloid. Regression models were employed to analyze the interactive effects of MDS with A+ on cognitive decline, neurodegeneration, and AD incidence. RESULTS: Individuals with both A+ status and MDS at baseline experienced the fastest neurodegeneration (p < 0.01), cognitive decline (p < 0.05), and a higher risk of developing AD (HR = 5.23, p < 0.001). Furthermore, A+ participants with the trajectory of increasing depressive symptoms demonstrated more pronounced neurodegeneration (p < 0.001), cognitive decline (p < 0.01), and elevated risk of AD (HR = 10.45, p < 0.001). Finally, A+ status in combination with a higher average intensity of depressive symptoms was associated with faster brain atrophy (p < 0.01) and brain metabolism decline (p < 0.05), cognitive decline (p < 0.05), and higher AD risk (HR = 13.99, p < 0.001). CONCLUSION: These findings emphasized that the MDS-Aß interaction relationship should be considered in risk stratification, prediction, and early management of neurodegeneration and cognitive decline in the pre-dementia stage.

Effects of Social Group Housing on the Behavioral and Physiological Responses of Captive Sub-Adult Giant Pandas.

Wild giant pandas are inherently solitary creatures, however, the ex-situ conservation efforts significantly alter the living circumstances of their captive counterparts. Following the breeding period, giant pandas in captivity may be maintained in social groups. Currently, there is a lack of research on the effects of group housing on the physiology, behavior, and gut microbiota of captive giant pandas. This study divided six captive giant pandas into two groups following the breeding period. By comparing the behavior, physiology, and microorganisms of the two groups, we aim to investigate the behavioral responses and physiological adaptation mechanisms exhibited by captive giant pandas in a "group living" state. Our findings indicate that sub-adult giant pandas housed in group settings exhibit a significantly longer duration of playing behavior (including interactive and non-interactive play) compared to their counterparts housed separately (p < 0.001) while also demonstrating a significantly lower duration of stereotyped behavior than their separately housed counterparts. Additionally, an analysis of urine cortisol and heart rate variability between the two groups revealed no significant differences. Simultaneously, the group housing strategy markedly elevated the ß diversity of gut microbiota in sub-adult giant pandas. In conclusion, the group-rearing model during the sub-adult stage has been shown to significantly alter the behavioral patterns of captive giant pandas. In conclusion, within the present captive setting, the group-rearing approach during the sub-adult stage proved to be less distressing for adult captive giant pandas.

An improved tetracycline-inducible expression system for fission yeast.

The ability to manipulate gene expression is valuable for elucidating gene function. In the fission yeast Schizosaccharomyces pombe, the most widely used regulatable expression system is the nmt1 promoter and its two attenuated variants. However, these promoters have limitations, including a long lag, incompatibility with rich media, and unsuitability for non-dividing cells. Here, we present a tetracycline-inducible system free of these shortcomings. Our system features the enotetS promoter, which achieves a similar induced level and a higher induction ratio compared to the nmt1 promoter, without exhibiting a lag. Additionally, our system includes four weakened enotetS variants, offering an expression range similar to the nmt1 series promoters but with more intermediate levels. To enhance usability, each promoter is combined with a Tet-repressor-expressing cassette in an integration plasmid. Importantly, our system can be used in non-dividing cells, enabling the development of a synchronous meiosis induction method with high spore viability. Moreover, our system allows for the shutdown of gene expression and the generation of conditional loss-of-function mutants. This system provides a versatile and powerful tool for manipulating gene expression in fission yeast.

Electroacupuncture promotes angiogenesis by regulating miR-142-5p and activating ADAMTS1/PI3K/AKT pathway in ischemic stroke rats. / 电针调控miR-142-5p和ADAMTS1/PI3K/AKTé€šè·¯ä¿ƒè¿›ç¼ºè¡€æ€§è„‘å’ä¸­å¤§é¼ è¡€ç®¡æ–°ç”Ÿçš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of electroacupuncture on miR-142-5p and ADAMTS1/PI3K/AKT pathway in rats with ischemic stroke, so as to explore the regulatory mechanism of electroacupuncture on angiogenesis after ischemic stroke. METHODS: This study was divided into two parts. The first part of the experiment：SD rats were randomly divided into sham operation group, model group and electroacupuncture group. There were 20 rats in each group. The middle cerebral artery occlusion (MCAO) rat model was prepared using a modified Longa's method. In the electroacupuncture group, "Shuigou" (GV26) was selected for electroacupuncture intervention (4 Hz/20 Hz) for 30 min each time. The rats in the electroacupuncture group were given electroacupuncture immediately after successful modeling, once a day for 4 times. Hunter score and TTC staining were used to observe the neurological deficits and infarct volumes respectively；HE staining was used to observe the cortical pathological changes；immunohistochemistry was used to determine the changes of cerebral microvascular density. Real-time quantitative PCR and Western blot were used to observe the miR-142-5p expression, mRNA and protein expression levels of ADAMTS1, VEGF, PI3K, AKT, eNOS in ischemic cortex. The second part of the experiment：The rats were randomly divided into electroacupuncture+control group and electroacupuncture+miR-142-5p Antagomir group with 8 rats in each group. MCAO model was established after injection. Electroacupuncture+control group was given 0.9% sodium chloride solution injected into the right ventricle.The rats in the electroacupuncture+miR-142-5p Antagomir group were injected with miR-142-5p inhibitor into the right ventricle 30 min before modeling. Rats in electroacupuncture+control group and electroacupuncture+miR-142-5p Antagomir group were all given the same electroacupuncture treatment. Real-time fluorescence quantitative PCR was used to observe the effect of miR-142-5p Antagomir on the expression of miR-142-5p and ADAMTS1 mRNA. The effect of miR-142-5p Antagomir on ADAMTS1 protein was observed by Western blot. RESULTS: In the first part of the experiment, compared with the sham operation group, the Hunter score in the model group was significantly increased (P<0.01)；the volume of cerebral infarction in the model group was significantly increased (P<0.01)；the degree of brain edema and neuronal necrosis and the density of cerebral microvessels was increased；the cerebral microvascular density was significantly increased (P<0.01)；the expression levels of miR-142-5p and the mRNA expression levels of VEGF, AKT and eNOS were significantly decreased (P<0.01, P<0.05), and the protein expression levels of VEGF, p-AKT and eNOS were significantly down-regulated (P<0.01), while the mRNA expression levels of ADAMTS1 and PI3K, and the protein expression levels of ADAMTS1 and p-PI3K were all up-regulated (P<0.01, P<0.05) in the model group. Compared with the model group, after intervention, the Hunter score in the electroacupuncture group was decreased (P<0.01), the volume of cerebral infarction was significantly decreased (P<0.01)；the degree of brain edema and neuronal necrosis were alleviated；the cerebral microvascular density was significantly increased (P<0.01)；the expression of miR-142-5p and the mRNA expression of VEGF, PI3K, AKT and eNOS were increased (P<0.01), the protein expressions of VEGF, p-PI3K, p-AKT and eNOS were increased (P<0.01, P<0.05), while the mRNA and protein expression of ADAMTS1 were decreased (P<0.05, P<0.01). After injection of miR-142-5p inhibitor, compared with electroacupuncture+control group, the expression of miR-142-5p in electroacupuncture+miR-142-5p Antagomir group was decreased(P<0.05), while the mRNA and protein expression of ADAMTS1 were increased (P<0.01, P<0.05). CONCLUSIONS: Electroacupuncture at GV26 can improve the neurological damage of ischemic stroke rats, reduce the volume of cerebral infarction and promote angiogenesis. The mechanism may be associated with the function of electroacupuncture in promoting the expression of miR-142-5p, so as to inhibit the expression of its target gene ADAMTS1, mediate the up-regulation of VEGF expression, activate PI3K/AKT pathway, promote the release of eNOS, and participate in promoting angiogenesis in ischemic stroke rats.

Progression prediction of coronary artery lesions by echocardiography-based ultrasomics analysis in Kawasaki disease.

BACKGROUND: Echocardiography-based ultrasomics analysis aids Kawasaki disease (KD) diagnosis but its role in predicting coronary artery lesions (CALs) progression remains unknown. We aimed to develop and validate a predictive model combining echocardiogram-based ultrasomics with clinical parameters for CALs progression in KD. METHODS: Total 371 KD patients with CALs at baseline were enrolled from a retrospective cohort (cohort 1, n = 316) and a prospective cohort (cohort 2, n = 55). CALs progression was defined by increased Z scores in any coronary artery branch at the 1-month follow-up. Patients in cohort 1 were split randomly into training and validation set 1 at the ratio of 6:4, while cohort 2 comprised validation set 2. Clinical parameters and ultrasomics features at baseline were analyzed and selected for models construction. Model performance was evaluated by area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC) and decision curve analysis (DCA) in the training and two validation sets. RESULTS: At the 1-month follow-ups, 65 patients presented with CALs progression. Three clinical parameters and six ultrasomics features were selected to construct the model. The clinical-ultrasomics model exhibited a good predictive capability in the training, validation set 1 and set 2, achieving AUROCs of 0.83 (95% CI, 0.75-0.90), 0.84 (95% CI, 0.74-0.94), and 0.73 (95% CI, 0.40-0.86), respectively. Moreover, the AUPRC values and DCA of three model demonstrated that the clinical-ultrasomics model consistently outperformed both the clinical model and the ultrasomics model across all three sets, including the training set and the two validation sets. CONCLUSIONS: Our study demonstrated the effective predictive capacity of a prediction model combining echocardiogram-based ultrasomics features and clinical parameters in predicting CALs progression in KD.

[Cloning and functional verification of farnesyl pyrophosphate synthase gene(AvFPS) from Aconitum vilmorinianum].

Aconitum vilmorinianum is an authentic and superior medicinal herbal in Yunnan, which is rich in yunaconitine and other diterpene alkaloids. Diterpene alkaloids are its main active components. Farnesyl pyrophosphate synthase(FPS) is a key enzyme in the terpene biosynthetic pathway and plays an important role in diterpene alkaloid biosynthesis. Functional studies of FPS help to reveal the molecular mechanism of diterpene alkaloid biosynthesis. In this study, one FPS gene(AvFPS) was selected based on the transcriptome data of A. vilmorinianum. Its full-length sequence was cloned, and bioinformatic analysis, functional verification, and gene expression analysis were performed. The open reading frame(ORF) of AvFPS was 1 056 bp, encoding 351 amino acids. Its molecular weight was 41 kDa. AvFPS had two typical conserved functional domains of isopentenyl transferase, " DDIMD" and " DDYXD". The recombinant protein of AvFPS was expressed in Escherichia coli, and purified recombinant protein was used for in vitro enzymatic reaction. The results revealed that AvFPS was able to catalyze the synthesis of farnesyl pyrophosphate(FPP). The results of qRT-PCR analysis showed that AvFPS was expressed in the roots, stems, leaves, and flowers of A. vilmorinianum, with the highest expression level in the roots. The expression level of AvFPS was significantly up-regulated by MeJA induction. This study clarified the catalytic function of AvFPS, revealed the expression pattern of AvFPS in different tissue, as well as at different time induced by MeJA, and provided a reference for a deeper understanding of the function of FPS in the biosynthesis of diterpenoid components.

Liquid-liquid phase separation-related genes associated with prognosis, tumor microenvironment characteristics, and tumor cell features in bladder cancer.

OBJECTIVE: This study aimed to explore the Liquid-liquid phase separation (LLPS)-related genes associated with the prognosis of bladder cancer (BCa) and assess the potential application of LLPS-related prognostic signature for predicting prognosis in BCa patients. METHODS: Clinical information and transcriptome data of BCa patients were extracted from the Cancer Genome Atlas-BLCA (TCGA-BLCA) database and the GSE13507 database. Furthermore, 108 BCa patients who received treatment at our institution were subjected to a retrospective analysis. The least absolute shrinkage and selection operator (LASSO) analysis was performed to develop an LLPS-related prognostic signature for BCa. The CCK8, wound healing and Transwell assays were performed. RESULTS: Based on 62 differentially expressed LLPS-related genes (DELRGs), three DELRGs were screened by LASSO analysis including kallikrein-related peptidase 5 (KLK5), monoacylglycerol O-acyltransferase 2 (MOGAT2) and S100 calcium-binding protein A7 (S100A7). Based on three DELRGs, a novel LLPS-related prognostic signature was constructed for individualized prognosis assessment. Kaplan-Meier curve analyses showed that LLPS-related prognostic signature was significantly correlated with overall survival (OS) of BCa. ROC analyses demonstrated the LLPS-related prognostic signature performed well in predicting the prognosis of BCa patients in the training group (the area under the curve (AUC) = 0.733), which was externally verified in the validation cohort 1 (AUC = 0.794) and validation cohort 2 (AUC = 0.766). Further experiments demonstrated that inhibiting KLK5 could affect the proliferation, migration, and invasion of BCa cells. CONCLUSIONS: In this study, a novel LLPS-related prognostic signature was successfully developed and validated, demonstrating strong performance in predicting the prognosis of BCa patients.

Increased circulating LOX-1+ neutrophils activate T cells and demonstrate a pro-inflammatory role in allergic rhinitis.

Background: Low-density neutrophils are heterogeneous immune cells with immunosuppressive (such as polymorphonuclear myeloid-derived suppressor cells [PMN-MDSC]) or pro-inflammatory (such as low-density granulocytes [LDG]) properties that have been well described in multiple cancers and immune diseases. However, its role in allergic rhinitis (AR) is still unclear. Methods: In the present study, we defined low-density neutrophils as CD14-CD11B+CD15+LOX-1+ (LOX-1+ neutrophils), and their levels in the peripheral blood (PB) were evaluated and compared between patients with AR and healthy donors using flow cytometric analysis. LOX-1 expression on polymorphonuclear neutrophils was identified. Carboxyfluorescein succinimidyl ester (CFSE)-stained CD3+ T cells were cultured alone or with LOX-1+ neutrophils, T cell proliferation was assessed using flow cytometry, and pro-inflammatory cytokines in the supernatants were detected using enzyme-linked immunosorbent assay (ELISA). Clinicopathological analyses were performed to gain a thorough understanding of LOX-1+ neutrophils. Results: We determined that LOX-1+ neutrophils were significantly increased in the PB of patients with AR, and LOX-1 expression in neutrophils from patients with AR was elevated. Interestingly, LOX-1+ neutrophils derived from patients with AR, unlike PMN-MDSC, promoted T cell proliferation and pro-inflammatory cytokine production. Moreover, clinicopathological analysis revealed that there was no any relation between circulating LOX-1+ neutrophil levels and the levels of IgE, age and sex. Conclusion: These findings indicate that elevated circulating LOX-1+ neutrophils play a pro-inflammatory role in AR.

Evaluating renal injury characteristics in different rat models of hyperuricemia and elucidating pathological molecular mechanisms via serum metabolomics.

Hyperuricemia has emerged as a significant global health concern, closely associated with various metabolic disorders. The adverse effects frequently observed with current pharmacological treatments for hyperuricemia highlight the urgent need for reliable animal models to elucidate the disease's pathophysiological mechanisms, thereby facilitating the development of safer and more effective therapies. In this study, we established three rat models of hyperuricemia using potassium oxonate, either alone or in combination with fructose and adenine. Each model exhibited distinct pathological changes, with the combination of potassium oxonate, fructose, and adenine causing significantly more severe damage to liver and kidney functions than potassium oxonate alone. Serum metabolomics analyses revealed profound dysregulation in the metabolic pathways of purine, pyrimidines, and glutathione, underscoring the pivotal role of oxidative stress in the progression of hyperuricemia. We identified key biomarkers such as orotidine, ureidosuccinic acid, uracil, and pseudouridine, which are associated with uric acid-induced damage to hepatic and renal systems. MetOrigin tracing analysis further revealed that differential metabolites related to hyperuricemia are primarily involved in host-microbiome co-metabolic pathways, particularly in purine metabolism, with bacterial phyla such as Pseudomonadota, Actinomycetota, and Ascomycota being closely linked to the critical metabolic processes of uric acid production. These findings not only enhance our understanding of the pathogenic mechanisms underlying hyperuricemia but also provide a robust experimental model foundation for the development of innovative treatment strategies.

Activation of ß3-AR by mirabegron prevents aortic dissection/aneurysm by promoting lymphangiogenesis in perivascular adipose tissue.

AIMS: ß3-AR (ß3-adrenergic receptor) is essential for cardiovascular homeostasis through regulating adipose tissue function. Perivascular adipose tissue (PVAT) has been implicated in the pathogenesis of aortic dissection and aneurysm (AD/AA). Here, we aim to investigate ß3-AR activation-mediated PVAT function in AD/AA. METHODS AND RESULTS: Aortas from patients with thoracic aortic dissection (TAD) were collected to detect ß3-AR expression in PVAT. ApoE-/- and ß-aminopropionitrile monofumarate (BAPN)-treated C57BL/6 mice were induced with Angiotensin II (AngII) to simulate AD/AA, and subsequently received either placebo or mirabegron, a ß3-AR agonist. The results demonstrated an up-regulation of ß3-AR in PVAT of TAD patients and AD/AA mice. Moreover, activation of ß3-AR by mirabegron significantly prevented AngII-induced AD/AA formation in mice. RNA-sequencing analysis of adipocytes from PVAT revealed a notable increase of the lymphangiogenic factor VEGF-C in mirabegron-treated mice. Consistently, enhanced lymphangiogenesis was found in PVAT with mirabegron treatment. Mechanistically, the number of CD4+/CD8+ T cells and CD11c+ cells was reduced in PVAT but increased in adjacent draining lymph nodes (LNs) of mirabegron-treated mice, indicating the improved draining and clearance of inflammatory cells in PVAT by lymphangiogenesis. Importantly, adipocyte-specific VEGF-C knockdown by the adeno-associated virus system restrained lymphangiogenesis and exacerbated inflammatory cell infiltration in PVAT, which ultimately abolished the protection of mirabegron on AD/AA. In addition, the conditional medium derived from mirabegron-treated adipocytes activated the proliferation and tube formation of lymphatic endothelial cells (LECs), which was abrogated by the silencing of VEGF-C in adipocytes. CONCLUSIONS: Our findings illustrated the therapeutic potential of ß3-AR activation by mirabegron on AD/AA, which promoted lymphangiogenesis by increasing adipocyte-derived VEGF-C and, therefore, ameliorated PVAT inflammation.

Hematopoietic stem cell transplantation activity in China 2022-2023. The proportions of peripheral blood for stem cell source continue to grow: a report from the Chinese Blood and Marrow Transplantation Registry Group.

Over past two years, a total of 39,918 hematopoietic stem cell transplantation (HSCT) cases were reported, with 18,194 and 21,714 transplants performed in 2022 and 2023, respectively. Autologous HSCT accounted for 6562 cases (31%) in 2022, while allogeneic HSCT comprised 12,632 cases (69%). In 2023, the number of allogeneic HSCTs exceeded 15,000, maintaining a 69% share. Participation in the 2022 and 2023 surveys included 193 and 212 transplantation teams, respectively, from 27 provinces, municipalities, or autonomous regions. The leading indication of HSCT was acute leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and mixed phenotype acute leukemia, with a total of 17,421 cases. AML was the most common disease (10,339, 38%) for allogeneic HSCT, which was followed by ALL (5925 cases, 21%). Peripheral blood emerged as the primary source of stem cell grafts, utilized in 54% of matched sibling donor transplants and 77% of haploidentical donor transplants. The BuCy-based conditioning regimen was the most prevalent, used in 53% of allogeneic HSCT cases in the past two years. This survey offers a comprehensive overview of the current HSCT landscape and serves as a valuable resource for clinical practice.

Insight into the charge transfer behavior of an electrochemiluminescence sensor based on porphyrin-coumarin derivatives with a donor-acceptor configuration.

The excellent photophysical and electrochemical properties of porphyrins have inspired widespread interest in the realm of electrochemiluminescence (ECL). The aggregation-caused deficiency of ECL emission in aqueous solution, however, still severely impedes further applications. Herein, a molecule with a donor-acceptor (D-A) configuration, ATPP-Cou, consisting of monoaminoporphyrin as an electron donor and coumarin as an electron acceptor, was designed as an ECL luminophore to address the susceptibility of the porphyrin to aggregation-caused quenching (ACQ) in aqueous solution. ATPP-Cou demonstrated a three-fold enhanced ECL signal compared to pristine ATPP. Despite the acknowledged significance of intramolecular charge transfer (ICT) in generating excited states in ECL, there is a lack of quantitative descriptions. Herein, intensity-modulated photocurrent spectroscopy (IMPS) and scanning photoelectrochemical microscopy (SPECM) were utilized to validate the influence of ICT on the enhancement performance of D-A type ECL molecules. Additionally, ATPP-Cou was also developed as a probe for the successful detection of Cu2+ in aqueous solution. The present study not only enriches the repertoire of efficient porphyrin-based ECL luminophores applicable in aqueous environments but also exemplifies the successful integration of novel measurement techniques to provide more comprehensive insights into the underlying mechanisms responsible for improved ECL performance.

Selective Generation of Reactive Oxygen Species in Photocatalytic Oxidation by Tuning Porphyrin-Based COFs' Dimensionality.

Regulating the selective generation of reactive oxygen species (ROS) is a significant challenge in the field of photocatalytic oxidation, with successful approaches still being limited. Herein, we present a strategy to selectively generate singlet oxygen (1O2) and superoxide radicals (O2•-) by tuning the dimensionality of porphyrin-based covalent organic frameworks (COFs). The transformation of COFs from three-dimensional (3D) solids to two-dimensional (2D) sheets was achieved through the reversible protonation of the imine bond. Upon irradiation, both bulk and thin-layer COF-367 can transfer energy to O2 to generate 1O2. However, thin-layer COF-367 exhibited a superior performance compared to its bulk counterpart in activating O2 to form the O2•- radicals via electron transfer. After excluding the influences of the band structure, O2 adsorption energy, and frontier orbital composition attributed to the dimensionality of the COFs, it is reasonably speculated that the variance in ROS generation arises from the differential exposure ratios of the active surfaces, leading to distinct reaction pathways between the carrier and O2. This study is the first to explore the modulation mechanism of COF dimensionality on the activation of the O2 pathway, underscoring the importance of considering COF dimensionality in photocatalytic reactions.