Associations of Socioeconomic Status Inequity with Incident Age-related Macular Degeneration in Middle-Aged and Elderly Population.

Background: The relationship between socioeconomic status (SES) inequity and incident age-related macular degeneration (AMD) remains unclear. We aim to investigate whether low SES increases the risk of AMD and to explore the effect of a healthy lifestyle on this association. Methods: This prospective cohort study included 316,663 UK Biobank individuals. SES inequity was identified via latent class analysis using education, household income, and occupational status. Healthy lifestyle score was calculated based on smoking, alcohol drinking, and physical activity (PA). Incident AMD was defined according to diagnosis records. Cox proportional hazards models were used to evaluate the relationship of low SES and AMD. Interrelationships of healthy lifestyle score on SES-AMD association were explored, including modification, mediation, and joint effects. Results: During the average 12.2 years of follow-up, 6,355 AMD cases were diagnosed. Participants with medium SES (hazard ratio: 1.10 [95% confidence interval (CI) 1.01 to 1.21]) and low SES (hazard ratio: 1.22 [95% CI 1.11 to 1.34]) had an increased risk of incident AMD compared to participants with high SES. PA significantly affected this association. Moreover, the association between low SES and AMD was significantly mediated (11.3%, 95% CI: 6.56 to 23.0) by smoking. Similarly, alcohol drinking suppressed (9.59%, 95% CI: 4.00 to 23.2) the association between high SES and AMD. Besides, a significant joint effect of SES and healthy lifestyle score was found. Conclusions: We provide further evidence for the relationship of socioeconomic inequity, healthy lifestyle, and incident AMD. Future public health strategies should aim to reduce socioeconomic inequity to prevent AMD.

Effects of Carbon/Kevlar Hybrid Ply and Intercalation Sequence on Mechanical Properties and Damage Resistance of Composite Laminates under Quasi-Static Indentation.

The investigation of damage development is essential for the design and optimization of hybrid structures. This paper provides a reference for the structural design of brittle-ductile hybrid LVI-resistant laminates through analyzing the damage development mechanism of carbon/Kevlar fabric-reinforced composite laminates. The effects of Kevlar fabric hybrid ply and intercalation on the damage development of carbon/Kevlar composite laminates under low-velocity impact (LVI) were investigated using quasi-static indentation (QSI). It was found that an increase in the Kevlar hybrid ratio significantly reduced the peak load and stiffness of these laminates (the maximum decreases in strength and stiffness were 46.03% and 41.43%, respectively), while laminates with identical hybrid ratios but different plying configurations maintained a comparable stiffness under QSI, with differences of less than 5%. Interestingly, Kevlar fibers exhibited irregular fractures as the yarn was splitting, while carbon fibers presented neat breaks, which indicated material-specific failure modes. Notably, the introduction of Kevlar hybridization beyond pure Kevlar configurations (KKKK) resulted in a decrease in the percentage of fiber damage (CCCC, CCCK, CCKK, and KCCK accounted for 80%, 79.8%, 70%, and 60% of fiber damage, respectively), attributed to an increase in resin cracks and lower levels of Kevlar yarn breakage. The internal damage diameter of specimens was accurately predicted from the diameter of visible damage on the QSI surface. Compared with CCCC and CCKK setups, which are affected by resin cracks formed via the carbon surface on the loading side propagating along the yarn direction (including the yarn settling direction), KCCK demonstrated less delamination between the first and second ply.

C5AR1-induced TLR1/2 pathway activation drives proliferation and metastasis in anaplastic thyroid cancer.

This study aimed to elucidate the role and mechanisms of Complement C5a receptor 1 (C5AR1) in driving the malignant progression of anaplastic thyroid carcinoma (ATC). C5AR1 expression was assessed in ATC tissues and cell lines. Functional assays evaluated the effects of C5AR1 knockdown on the malignant features of ATC cells. The interaction between C5AR1 and miR-335-5p was confirmed using a luciferase reporter assay and Fluorescence in situ hybridization, and the impact of C5AR1 knockdown on the Toll-like receptor (TLR) 1/2 signaling pathway was examined. In vivo studies evaluated the effects of C5AR1 modulation on tumor growth and metastasis. C5AR1 levels were elevated in ATC tumor samples and associated with poor survival in ATC patients. C5AR1 knockdown impeded ATC cell proliferation, migration, and invasion in vitro. MiR-335-5p was identified as an upstream regulator of C5AR1, which negatively modulates C5AR1 expression. C5AR1 knockdown diminished TLR1, TLR2, and myeloid differentiation primary response 88 (MyD88) levels, while C5AR1 overexpression activated this pathway. Blocking TLR1/2 signaling abrogated the oncogenic effects of C5AR1 overexpression. C5AR1 silencing inhibited tumor growth and lung metastasis of ATC cells in nude mice. C5AR1 contributes to ATC tumorigenesis and metastasis by activating the TLR1/2 pathway, and is negatively regulated by miR-335-5p. Targeting the miR-335-5p/C5AR1/TLR1/2 axis represents a potential therapeutic strategy for ATC.

Tailoring and understanding the lithium storage performance of triple-doped cobalt phosphide composites.

Cobalt phosphide (CoP) with high theoretical capacity as well as ceramic-like and metal-like properties is considered as a promising anode for lithium-ion batteries (LIBs). However, the large volume change and sluggish kinetic response limit its practical application. The optimization of composition, structural control and performance regulation of CoP electrodes can be achieved by the bottom-up assembly technique of metal-organic frameworks (MOFs). Due to the effective electronic regulation and lithiophilicity brought by the multiple heteroatoms doping and the synergistic effect of the unique structure derived from MOFs, the N, O, P triple-doped carbon and CoP composites (ZCP@NOP) exhibited excellent rate capability (554.61 mAh g-1 at 2 A g-1) and cycling stability (806.7 mAh g-1 after 500 cycles at 0.5 A g-1). The essence and evolution of lithium storage mechanism in CoP electrodes are also confirmed by the ex-situ techniques. The synergistic benefits of heteroatom co-doping carbon and cobalt phosphide, such as the decrease of the diffusion energy barrier of Li-ions and the optimization of electronic structures, are highlighted in theoretical calculations. In conclusion, new thoughts and ideas for the creation of future battery anode are provided by the combination of the N, O, P co-doping and the adaptable structural adjustment technique.

Seasonal effects of fish, seaweed and abalone cultures on dissolved organic matter and carbon sequestration potential in Sansha Bay, China.

Coastal bays serve as undeniable dissolved organic matter (DOM) reactors and the role of prevalent mariculture in DOM cycling deserves investigation. This study, based on four seasonal field samplings and a laboratory incubation experiment, examined the source and seasonal dynamics of DOM and fluorescent dissolved organic matter (FDOM) in the seawater of fish (Larimichthys crocea, LC), seaweed (Gracilaria lemaneiformis, GL) and abalone (Haliotis sp., HA) culturing zones in Sansha Bay, China. Using three-dimensional fluorescence spectroscopy coupled with parallel factor analysis (EEMs-PARAFAC), three fluorescent components were identified, i.e. protein-like C1, protein-like C2, and humic-like C3. Our results showed that mariculture activities dominated the DOM pool by seasonal generating abundant DOM with lower aromaticity and humification degrees. Accounting for 40-95 % of total fluorescent components, C1 (Ex/Em = 300/340 nm) was regarded the same as D1 (Ex/Em = 300/335 nm) identified in a 180-day degradation experiments of G. lemaneiformis detritus, indicating that the cultured seaweed modulated DOM through the seasonal production of C1. In addition, the incubation experiment revealed that 0.7 % of the total carbon content of seaweed detritus could be preserved as recalcitrant dissolved organic carbon (RDOC). However, fish culture appeared to contribute to liable DOC and protein-like C2, exerting a substantial impact on DOM during winter but making a negligible contribution to carbon sequestration, while abalone culture might promote the potential export and sequestration of seaweed-derived carbon to the ocean. Our results highlight the influences of mariculture activities, especially seaweed culture, in shaping DOM pool in coastal bays. These findings can provide reference for future studies on the carbon accounting of mariculture.

Association between low lung function and the increased risk of age-related macular degeneration: A population-based prospective cohort study.

Background: Low lung function is associated with an increased risk of age-related diseases. However, the relationship between age-related macular degeneration (AMD), the leading cause of blindness, and lung function remains unclear. We aimed to investigate whether low lung function increases the risk of AMD and the potential mechanisms behind this association. Methods: We conducted a prospective cohort analysis of 409 230 UK Biobank participants with completed lung function after excluding individuals with AMD. We used Cox proportional hazards models to estimate the risk of AMD incidence and mediation models to explore potential mechanisms driven by inflammatory markers, erythrocyte-related measures, and metabolites. Results: Overall, 6477 AMD cases were diagnosed across an average of 12.4 years of follow-up. Participants with low lung function had an increased risk of developing AMD compared to those with high lung function (forced vital capacity: adjusted hazard ratio (aHR) = 1.20 (95% confidence interval (CI) = 1.07-1.34); forced expiratory volume in one second: aHR = 1.32 (95% CI = 1.18-1.47); peak expiratory flow: aHR = 1.32 (95% CI = 1.20-1.45)). Inflammatory markers and erythrocyte-related measures mediated this relationship, acting as a pathway through which low lung function influenced AMD. The interactions of body mass index (BMI), sex, and smoking were significant and the effect of lung function on AMD was higher in men, obese, and smoking populations. Conclusions: The increased risk of AMD was associated with low lung function, with inflammatory and erythrocyte-related markers mediating this relationship. This suggests that improvements in lung function could reduce the risk of AMD, thereby promoting health and longevity.

Exploring prognostic and immunological characteristics of pancreatic ductal adenocarcinoma through comprehensive genomic analysis of tertiary lymphoid structures and CD8 + T-cells.

PURPOSE: Tertiary lymphoid structures (TLSs) and CD8 + T-cells are potential prognostic indicators for pancreatic ductal adenocarcinoma (PDAC). We established a novel scoring system for evaluating the risk for PDAC based on TLS- and CD8 + T-cell-related genes. METHODS: We analyzed single-cell sequence data from PDAC patients in the Genome Sequence Archive. Bioinformatics and machine algorithms established and validated a scoring method (T-C score) based on PDAC survival-related genes highly expressed in TLSs and CD8 + T-cells. Patients were stratified into the low- and high-T-C score groups. Differences in survival, pathway enrichment, mutation status, immune cell infiltration, expression of immune checkpoint-associated genes, tumor stemness, and response to antitumor therapy were compared through computer simulation methods. RESULTS: Overall survival differed significantly between the training and validation cohorts' low- and high-T-C score groups. The low-T-C score group correlated with lower tumor mutation burden and lower levels of tumor stemness compared with the high-T-C score group. Patients with lower T-C scores exhibited advantages in immunotherapeutic responses and might be more sensitive to the chemotherapeutic regimen and multi-kinase inhibitors. CONCLUSION: The T-C score could serve as an effective model for predicting the survival and therapeutic responses of patients with PDAC.

KDM5A/B contribute to HIV-1 latent infection and survival of HIV-1 infected cells.

Combinational antiretroviral therapy (cART) suppresses human immunodeficiency virus type 1 (HIV-1) viral replication and pathogenesis in acquired immunodeficiency syndrome (AIDS) patients. However, HIV-1 remains in the latent stage of infection by suppressing viral transcription, which hinders an HIV-1 cure. One approach for an HIV-1 cure is the "shock and kill" strategy. The strategy focuses on reactivating latent HIV-1, inducing the viral cytopathic effect and facilitating the immune clearance for the elimination of latent HIV-1 reservoirs. Here, we reported that the H3K4 trimethylation (H3K4me3)-specific demethylase KDM5A/B play a role in suppressing HIV-1 Tat/LTR-mediated viral transcription in HIV-1 latent cells. Furthermore, we evaluated the potential of KDM5-specific inhibitor JQKD82 as an HIV-1 "shock and kill" agent. Our results showed that JQKD82 increases the H3K4me3 level at HIV-1 5' LTR promoter regions, HIV-1 reactivation, and the cytopathic effects in an HIV-1-latent T cell model. In addition, we identified that the combination of JQKD82 and AZD5582, a non-canonical NF-κB activator, generates a synergistic impact on inducing HIV-1 lytic reactivation and cell death in the T cell. The latency-reversing potency of the JQKD82 and AZD5582 pair was also confirmed in peripheral blood mononuclear cells (PBMCs) isolated from HIV-1 aviremic patients and in an HIV-1 latent monocyte. In latently infected microglia (HC69) of the brain, either deletion or inhibition of KDM5A/B results in a reversal of the HIV-1 latency. Overall, we concluded that KDM5A/B function as a host repressor of the HIV-1 lytic reactivation and thus promote the latency and the survival of HIV-1 infected reservoirs.

Association of exposure to ultraviolet radiation and warm-season ozone air pollution with incident age-related macular degeneration: A nationwide cohort study in China.

BACKGROUND: As the leading cause of blindness, age-related macular degeneration (AMD) performs an adverse impact on human health and disability. AMD have been reported to be associated with environmental factors; however, the association between ultraviolet (UV) radiation, warm-season ambient ozone pollution, and incident AMD remains unclear. METHODS: In this study, 19,707 participants without AMD at baseline were included from a nationwide longitudinal cohort in China. UV radiation and warm-season ozone exposure were evaluated through satellite-based models. Incident AMD was diagnosed via ophthalmological fundus images. Cox proportional hazard regression models were employed to explore the association of UV radiation and warm-season ozone with incident AMD, and the hazard ratios (HRs) and 95 % confidence intervals (CIs) were reported. RESULTS: During 312,935 person-month of follow-up, 3774 participants developed to AMD. High exposure to both UV radiation and warm-season ozone was associated with increasing risk of incident AMD, with HRs and 95 % CIs of 1.32 (1.23, 1.41) and 1.20 (1.11, 1.29) in two-exposure models, respectively. Moreover, negative interaction between UV radiation and warm-season ozone was identified, and it was found that exposure to high UV radiation and low ozone presented the highest hazard for AMD. Subgroup analyses showed that the UV-AMD association was stronger in southern China, while the ozone-AMD association was greater in northern China and rural areas. CONCLUSION: Our study provides the first epidemiological evidence that both UV radiation and warm-season ozone would elevate the risk of incident AMD, and the hazard of higher UV radiation may be attenuated by exposure to ozone. Strategies for decreasing AMD burden should jointly consider environmental exposures and geographic locations.

Toward High Quality Multi-Object Tracking and Segmentation Without Mask Supervision.

Recently studies have shown the potential of weakly supervised multi-object tracking and segmentation, but the drawbacks of coarse pseudo mask label and limited utilization of temporal information remain to be unresolved. To address these issues, we present a framework that directly uses box label to supervise the segmentation network without resorting to pseudo mask label. In addition, we propose to fully exploit the temporal information from two perspectives. Firstly, we integrate optical flow-based pairwise consistency to ensure mask consistency across frames, thereby improving mask quality for segmentation. Secondly, we propose a temporally adjacent pair-based sampling strategy to adapt instance embedding learning for data association in tracking. We combine these techniques into an end-to-end deep model, named BoxMOTS, which requires only box annotation without mask supervision. Extensive experiments demonstrate that our model surpasses current state-of-the-art by a large margin, and produces promising results on KITTI MOTS and BDD100K MOTS. The source code is available at https://github.com/Spritea/BoxMOTS.

Sensitive sensing of GLA and ISL based on highly conductivity nitrogen-doped carbon synergistic dual-template molecularly imprinted ratiometric electrochemical sensor.

A novel ratiometric Molecularly Imprinted Electrochemical sensor for the specific marker of Glycyrrhiza glabra L. was developed in this work. To achieve simultaneous detection of two analytes on one sensor, we constructed a double template molecular imprinted electrochemical sensor with glabridin (GLA) and isoliquiritin (ISL) as templates. Further, Ferrocene/ZIF-8 (Fc/ZIF-8) composites were prepared via a one-pot solvothermal reaction and coated on the surface of a glassy carbon electrode (GCE), and the oxidation of Fc was presented as the internal reference signal. Nitrogen-doped carbon (NOC) with high conductivity was further loaded on the modified GCE. Based on theoretical exploration and computer directional simulation of density functional theory (DFT), the optimal functional monomer and the best ratio of double template molecules to functional monomer were screened. Under optimal conditions, the sensor produced electrochemical curves when exposed to a solution containing GLA and ISL. As the concentration of GLA and ISL increased, the peak current intensity of GLA and ISL (IGLA and IISL) also increased, while the peak current intensity of Fc (as a reference signal) remained relatively constant. The values of IGLA/IFc and IISL/IFc showed excellent linear relationships with GLA and ISL concentrations in the range of 0.1-160 µM and 0.5-150 µM, respectively. The detection limits were 0.052 µM and 0.27 µM (S/N = 3), respectively. Due to the imprinting effect of MIP and the existence of a reference signal, the sensor exhibited excellent selectivity and anti-interference ability and was successfully applied to the quality evaluation of Glycyrrhiza glabra L.

Establishment and validation of an artificial intelligence-based model for real-time detection and classification of colorectal adenoma.

Colorectal cancer (CRC) prevention requires early detection and removal of adenomas. We aimed to develop a computational model for real-time detection and classification of colorectal adenoma. Computationally constrained background based on real-time detection, we propose an improved adaptive lightweight ensemble model for real-time detection and classification of adenomas and other polyps. Firstly, we devised an adaptive lightweight network modification and effective training strategy to diminish the computational requirements for real-time detection. Secondly, by integrating the adaptive lightweight YOLOv4 with the single shot multibox detector network, we established the adaptive small object detection ensemble (ASODE) model, which enhances the precision of detecting target polyps without significantly increasing the model's memory footprint. We conducted simulated training using clinical colonoscopy images and videos to validate the method's performance, extracting features from 1148 polyps and employing a confidence threshold of 0.5 to filter out low-confidence sample predictions. Finally, compared to state-of-the-art models, our ASODE model demonstrated superior performance. In the test set, the sensitivity of images and videos reached 87.96% and 92.31%, respectively. Additionally, the ASODE model achieved an accuracy of 92.70% for adenoma detection with a false positive rate of 8.18%. Training results indicate the effectiveness of our method in classifying small polyps. Our model exhibits remarkable performance in real-time detection of colorectal adenomas, serving as a reliable tool for assisting endoscopists.

Phase 2 study of pegylated liposomal doxorubicin plus cyclophosphamide, vincristine/vindesine, and prednisone in newly diagnosed PTCL: 8-year results.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the efficacy and safety of the PLD-containing CHOP regimen in newly diagnosed patients with aggressive peripheral T-cell lymphomas (PTCL). METHODS: Patients received PLD, cyclophosphamide, vincristine/vindesine, plus prednisone every 3 weeks for up to 6 cycles. The primary endpoint was the objective response rate at the end of treatment (EOT). RESULTS: From September 2015 to January 2017, 40 patients were treated. At the EOT, objective response was achieved by 82.5% of patients, with 62.5% complete response. As of the cutoff date (September 26, 2023), median progression-free survival (mPFS) and overall survival (mOS) were not reached (NR). The 2-year, 5-year, and 8-year PFS rates were 55.1%, 52.0%, and 52.0%. OS rate was 80.0% at 2 years, 62.5% at 5 years, and 54.3% at 8 years. Patients with progression of disease within 24 months (POD24) had worse prognosis than those without POD24, regarding mOS (41.2 months vs NR), 5-year OS (33.3% vs 94.4%), and 8-year OS (13.3% vs 94.4%). Common grade 3-4 adverse events were neutropenia (87.5%), leukopenia (80.0%), anemia (17.5%), and pneumonitis (17.5%). CONCLUSION: This combination had long-term benefits and manageable tolerability, particularly with less cardiotoxicity, for aggressive PTCL, which might provide a favorable benefit-risk balance. CLINICALTRIALS.GOV IDENTIFIER: Chinese Clinical Trial Registry, ChiCTR2100054588; IRB Approved: Ethics committee of Fudan University Shanghai Cancer Center (Date 2015.8.31/No. 1508151-13.

Association between exposure to a mixture of organochlorine pesticides and hyperuricemia in U.S. adults: A comparison of four statistical models.

The association between the exposure of organochlorine pesticides (OCPs) and serum uric acid (UA) levels remained uncertain. In this study, to investigate the combined effects of OCP mixtures on hyperuricemia, we analyzed serum OCPs and UA levels in adults from the National Health and Nutrition Examination Survey (2005-2016). Four statistical models including weighted logistic regression, weighted quantile sum (WQS), quantile g-computation (QGC), and bayesian kernel machine regression (BKMR) were used to assess the relationship between mixed chemical exposures and hyperuricemia. Subgroup analyses were conducted to explore potential modifiers. Among 6,529 participants, the prevalence of hyperuricemia was 21.15%. Logistic regression revealed a significant association between both hexachlorobenzene (HCB) and trans-nonachlor and hyperuricemia in the fifth quintile (OR: 1.54, 95% CI: 1.08-2.19; OR: 1.58, 95% CI: 1.05-2.39, respectively), utilizing the first quintile as a reference. WQS and QGC analyses showed significant overall effects of OCPs on hyperuricemia, with an OR of 1.25 (95% CI: 1.09-1.44) and 1.20 (95% CI: 1.06-1.37), respectively. BKMR indicated a positive trend between mixed OCPs and hyperuricemia, with HCB having the largest weight in all three mixture analyses. Subgroup analyses revealed that females, individuals aged 50 years and above, and those with a low income were more vulnerable to mixed OCP exposure. These results highlight the urgent need to protect vulnerable populations from OCPs and to properly evaluate the health effects of multiple exposures on hyperuricemia using mutual validation approaches.

The survival effect of neoadjuvant therapy and neoadjuvant plus adjuvant therapy on pancreatic ductal adenocarcinoma patients with different TNM stages: a propensity score matching analysis based on the SEER database.

BACKGROUND: Adjuvant therapy (AT) and neoadjuvant therapy (NAT) are standard treatments for pancreatic ductal adenocarcinoma (PDAC) depending on the status of the disease. However, whether AT improves survival after NAT and radical resection in all TNM stages remains unclear. RESEARCH DESIGN AND METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) database (2010-2019) for PDAC patients who underwent radical surgery and applied Pearson's chi-square test, multivariate and univariate Cox regression, Kaplan-Meier plot, Log-rank tests, and propensity score matching (PSM) for analysis. RESULTS: Given PSM after enrolling 13,868 PDAC patients, significant differences in survival were identified between AT and neoadjuvant therapy plus adjuvant therapy (NATAT) (p = 0.023) as well as between NAT and NATAT (p < 0.001). According to the AJCC 8th TNM stage, a survival advantage associated with NATAT was exclusively observed in stage III and IV disease, except for T4N0M0. Some stage IV patients receiving NATAT exhibited comparable survival to their counterparts without metastasis. CONCLUSIONS: In this retrospective cohort study, we demonstrated that patients harboring tumors in late TNM stages, including N2 resectable PDAC, might have better survival from NATAT, and that certain patients with M1 disease might still benefit from comprehensive systemic therapy and radical resection.

A Spinal MRI Image Segmentation Method Based on Improved Swin-UNet.

As the number of patients increases, physicians are dealing with more and more cases of degenerative spine pathologies on a daily basis. To reduce the workload of healthcare professionals, we propose a modified Swin-UNet network model. Firstly, the Swin Transformer Blocks are improved using a residual post-normalization and scaling cosine attention mechanism, which makes the training process of the model more stable and improves the accuracy. Secondly, we use the log-space continuous position biasing method instead of the bicubic interpolation position biasing method. This method solves the problem of performance loss caused by the large difference between the resolution of the pretraining image and the resolution of the spine image. Finally, we introduce a segmentation smooth module (SSM) at the decoder stage. The SSM effectively reduces redundancy, and enhances the segmentation edge processing to improve the model's segmentation accuracy. To validate the proposed method, we conducted experiments on a real dataset provided by hospitals. The average segmentation accuracy is no less than 95%. The experimental results demonstrate the superiority of the proposed method over the original model and other models of the same type in segmenting the spinous processes of the vertebrae and the posterior arch of the spine.

A Novel DNBS-based Fluorescent Probe for the Detection of H2S in Cells and on Test Strips.

Hydrogen sulfide (H2S) plays a key role in the physiology and pathology of organisms, and H2S in the environment is easily absorbed and harmful to health. It is of great significance to develop a probe with good selectivity, high sensitivity and good stability that can detect hydrogen sulfide inside and outside organisms. In this work, we designed a novel "turn-on" fluorescent probe CIM-SDB for the detection of H2S. The probe CIM-SDB used indene-carbazole as the fluorophore and 2,4-dinitrobenzenesulfonyl as the recognition site. The probe CIM-SDB exhibited high selectivity and sensitivity to H2S (detection limit as low as 123 nM). Moreover, the probe CIM-SDB was successfully applied to the detection of intracellular exogenous and endogenous H2S, and the test strips prepared by the probe CIM-SDB could realize the convenient and rapid detection of H2S.

PAD4 controls tumor immunity via restraining the MHC class II machinery in macrophages.

Tumor-associated macrophages (TAMs) shape tumor immunity and therapeutic efficacy. However, it is poorly understood whether and how post-translational modifications (PTMs) intrinsically affect the phenotype and function of TAMs. Here, we reveal that peptidylarginine deiminase 4 (PAD4) exhibits the highest expression among common PTM enzymes in TAMs and negatively correlates with the clinical response to immune checkpoint blockade. Genetic and pharmacological inhibition of PAD4 in macrophages prevents tumor progression in tumor-bearing mouse models, accompanied by an increase in macrophage major histocompatibility complex (MHC) class II expression and T cell effector function. Mechanistically, PAD4 citrullinates STAT1 at arginine 121, thereby promoting the interaction between STAT1 and protein inhibitor of activated STAT1 (PIAS1), and the loss of PAD4 abolishes this interaction, ablating the inhibitory role of PIAS1 in the expression of MHC class II machinery in macrophages and enhancing T cell activation. Thus, the PAD4-STAT1-PIAS1 axis is an immune restriction mechanism in macrophages and may serve as a cancer immunotherapy target.

Combined simultaneous transsphenoidal and transcranial regimen improves surgical outcomes in complex giant pituitary adenomas: A longitudinal retrospective cohort study.

BACKGROUND: Surgical treatment of complex giant pituitary adenomas (GPAs) presents significant challenges. The efficacy and safety of combining transsphenoidal and transcranial approaches for these tumors remain controversial. In this largest cohort of patients with complex GPAs, we compared the surgical outcomes between those undergoing a combined regimen and a non-combined regimen. We also examined the differences in risks of complications, costs, and logistics between the two groups, which might offer valuable information for the appropriate management of these patients. MATERIALS AND METHODS: This was a multicenter retrospective cohort study conducted at 13 neurosurgical centers. Consecutive patients who received a combined or non-combined regimen for complex GPAs were enrolled. The primary outcome was gross total resection, while secondary outcomes included complications, surgical duration, and relapse. A propensity score-based weighting method was used to account for differences between the groups. RESULTS: Out of 647 patients (298 [46.1%] women, mean age: 48.5 ± 14.0 years) with complex GPAs, 91 were in the combined group and 556 were in the non-combined group. Compared with the non-combined regimen, the combined regimen was associated with a higher probability of gross total resection (50.5% vs. 40.6%, odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.30-3.63, P = 0.003). The proportion of patients with life-threatening complications was lower in the combined group than in the non-combined group (4.4% vs. 11.2%, OR: 0.25, 95% CI: 0.08-0.78, P = 0.017). No marked differences were found between the groups in terms of other surgical or endocrine-related complications. However, the combined regimen exhibited a longer average surgery duration of 1.3 h (P < 0.001) and higher surgical costs of 22,000 CNY (approximate 3,000 USD, P = 0.022) compared with the non-combined approach. CONCLUSIONS: The combined regimen offered increased rates of total resection and decreased incidence of life-threatening complications, which might be recommended as the first-line choice for these patients.