Effects of adipose tissues on the relationship between type 2 diabetes mellitus and reduced heart rate variability: mediation analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with decreased heart rate variability (HRV) with an unclear intermediate mechanism. This study aimed to conduct mediation analysis to explore the impact of various adipose tissues on the relationship between T2DM and HRV. METHODS: A total of 380 participants were enrolled for analysis, including 249 patients with T2DM and 131 non-diabetic controls. The thicknesses of four adipose tissues (subcutaneous, extraperitoneal, intraperitoneal, and epicardial) were measured by abdominal ultrasound or echocardiography respectively. HRV was assessed by 24-hour Holter for monitoring both frequency domain indices (LF, HF, and LF/HF) and time domain indices (SDNN, SDANN, SDNN index, rMSSD and pNN50). Mediation analysis was used toexamine whether adipose tissues mediated the relationship between T2DM and each index of HRV. Then, a latent variable - HRV burden - was constructed by structural equation model with selected HRV indices to comprehensively assess the whole HRV. RESULTS: Compared to non-diabetic controls, patients with T2DM exhibited a significant reduction in indices of HRV, and a remarkable increase in the thicknesses of extraperitoneal, intraperitoneal, and epicardial adipose tissues. Mediation analysis found significant indirect effects of T2DM on six indices of HRV, including HF, SDNN, SDANN, SDNN index, rMSSD, and pNN50, which was mediated by epicardial adipose tissue rather than other adipose tissues, with the mediation proportions of 64.21%, 16.38%, 68.33%, 24.34%, 24.10% and 30.51%, respectively. Additionally, epicardial adipose tissue partially mediated the relationship between T2DM and reduced HRV burden (24.26%), which composed by SDNN, SDNN index, rMSSD, and pNN50. CONCLUSION: Epicardial adipose tissue partially mediated the relationship between T2DM and reduced HRV, which reinforces the value of targeting heart-specific visceral fat to prevent cardiac autonomic neuropathy in diabetes.

KnoMol: A Knowledge-Enhanced Graph Transformer for Molecular Property Prediction.

Molecular property prediction (MPP) techniques are pivotal in reducing drug development costs by preemptively predicting bioactivity and ADMET properties. Despite the application of numerous deep learning approaches, enhancing the representational capacity of these models remains a significant challenge. This paper presents a novel knowledge-based Transformer framework, KnoMol, designed to improve the understanding of molecular structures. KnoMol integrates expert chemical knowledge into the Transformer, emulating the analytical methods of medicinal chemists. Additionally, the multiperspective attention mechanism provides a more precise way to represent ring systems. In the evaluation experiments, KnoMol achieved state-of-the-art performance on both MoleculeNet and small-scale data sets, surpassing existing models in terms of accuracy and generalization. Further research indicated that the incorporation of knowledge significantly reduces KnoMol's reliance on data volumes, offering a solution to the challenge of data scarcity. Moreover, KnoMol identified several new inhibitors of HER2 in a case study, demonstrating its value in real-world applications. Overall, this research not only provides a powerful tool for MPP but also serves as a successful precedent for embedding knowledge into Transformers, with positive implications for computer-aided drug discovery and the development of MPP algorithms.

Indolelactic acid as a potential metabolic biomarker for diagnosing gout.

Gout is a heterogeneous disease caused by the deposition of monosodium urate crystals in joints, but its pathogenesis is currently poorly understood. The discovery of novel biomarkers is necessary for the early detection and diagnosis of gout. The present study aimed to characterize the metabolic profile of patients with gout using metabolomics, and to uncover the underlying pathological mechanisms leading to gout development. Serum samples were collected from 49 healthy participants and 47 patients with gout. Using ultra-high-performance liquid chromatography Orbitrap Exploris mass spectrometer non-target metabolomics technology, with a variable importance in the projection >1 and a false discovery rate adjusted P<0.05 was used, while a biomarker panel was screened using receiver operating characteristic (ROC) analysis. The potential differentially expressed markers related to gout were identified by ROC analysis, and the erythrocyte sedimentation rate, uric acid, alanine transaminase, aspartate aminotransferase, creatinine, triglyceride, total cholesterol, high-density lipoprotein and low-density lipoprotein levels were significantly different in the group of patients with gout compared with those in healthy individuals. A total of 186 differentially expressed metabolites were identified, with 156 differential metabolites upregulated and 30 downregulated in the patients with gout compared with healthy individuals. Pathway analysis demonstrated that D-glutamine and D-glutamate metabolism may serve key roles in gout. Compared with healthy people, the indolelactic acid (ILA) level of patients with gout was significantly higher. ILA may serve as a potential biomarker for the diagnosis of gout and could be used to detect or predict gout progression in the future.

Efficacy and safety of vunakizumab in moderate-to-severe chronic plaque psoriasis: a randomized, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Vunakizumab, a novel anti-IL-17A antibody, has showed promising efficacy for moderate-to-severe plaque psoriasis in a phase 2 trial. OBJECTIVE: We conducted a double-blind, randomized phase 3 trial (NCT04839016) to further evaluate vunakizumab in this population. METHODS: 690 subjects were randomized (2:1) to receive vunakizumab 240 mg or placebo at weeks 0, 2, 4 and 8. At week 12, subjects on placebo were switched to vunakizumab 240 mg (weeks 12, 14, 16 and q4w thereafter). The co-primary endpoints were ≥90% improvement from baseline in the psoriasis area-and-severity index score (PASI 90) and a static Physicians Global Assessment score of 0/1 (sPGA 0/1) at week 12. RESULTS: At week 12, the vunakizumab group showed higher PASI 90 (76.8% vs 0.9%) and sPGA 0/1 (71.8% vs 0.4%) response rates, as well as higher PASI 75 (93.6% vs 4.0%), PASI 100 (36.6% vs 0.0%) and sPGA 0 (38.2% vs 0.0%) response rates (all two-sided P<0.0001 vs placebo). Efficacy was maintained through week 52 with continuous vunakizumab. Possible treatment-related serious adverse events occurred in 0.9% of vunakizumab-treated subjects. LIMITATIONS: Chinese subjects only; no active comparator. CONCLUSION: Vunakizumab demonstrated robust clinical response at week 12 and through week 52, with good tolerability in moderate-to-severe plaque psoriasis.

Serum dsDNA is environmentally contingent.

Psoriasis is a recurrent autoimmune disease characterized by seasonal and latitudinal variations. Double-stranded DNA (dsDNA) is a crucial component of nucleic acids and nucleosomes that provoke innate immune responses. Given the potential influence of climate on immunity and the development of autoimmune diseases, a comprehensive quantitative analysis of dsDNA levels in the population is warranted. In this case-control study conducted from 2016 to 2020, 10,110 psoriasis patients and matched controls from 12 regions in China were included. This study examined variations in serum dsDNA levels based on season and latitude. The results revealed significant associations between geographical location, climatic conditions, and season with serum dsDNA concentration. Individuals residing in Northern China exhibited significantly higher serum dsDNA levels compared to those in the South (1.00 vs. 0.96 ng/ml), and those in medium latitude regions had higher levels than their counterparts in areas with extreme latitudes (0.98 vs. 0.96 ng/ml). Furthermore, individuals in regions with low to medium ultraviolet exposure demonstrated higher serum dsDNA concentrations than those in areas with high ultraviolet levels (1.03 vs. 0.93 ng/ml), and individuals in winter showed higher levels than those in summer (1.03 vs. 0.92 ng/ml). Factors such as sex, UV index, humidity, and sunshine duration were inversely related to serum dsDNA levels, while age and daylight hours showed a positive association. These findings suggest that meteorological and climatic factors play a role in influencing serum dsDNA levels.

Comprehensive understanding of impacts of steam explosion on facilitated extraction and transformation of flavonoids from Astragali Radix.

Recalcitrant structure of cell walls restricts the extraction of bioactive components from edible plants. In this study, the impacts of steam explosion (SE) on the release and transformation of flavonoids in Astragali Radix (AR) were evaluated. Results revealed that SE destroyed the compact structure of cell walls. Furthermore, the porous network was reformed due to the degradation of hemicelluloses and water-soluble components. The maximum extraction contents of ethanol-soluble and water-soluble flavonoids of 6.34 and 1.48 mg/g were obtained from the pretreated AR (1.5 MPa, 5 min), which were 5.22 and 2.88 times higher than those obtained from the untreated AR, respectively. SE not only released bound flavonoids from cell walls by cleaving glycoside or ester bonds, but also transformed some flavonoid glycosides into aglycones through deglycosylation. In conclusion, SE can reduce mass transfer hindrance and facilitate flavonoid transformation, thus providing a green and facile processing method for traditional edible plants.

Microencapsulation of total saponins from stem and leaf of Panax notoginseng by freeze and spray drying: Process optimization, physicochemical properties, structure, antioxidant activity, and stability.

Ginsenosides are the primary active substance in ginseng plants and have a variety of benefits. However, its light and heat stability are weak and easy to decompose. This study used gum arabic (GA) and maltodextrin (MD) as wall materials, and 1% Tween 80 was used as emulsifier. Response surface methodology was used to optimize the preparation process of total saponins in the stems-leaves of Panax notoginseng (SLPNs) (SSLP) microcapsules by spray drying and freeze drying techniques. Under optimal process conditions, the two microcapsules have better solubility and lower moisture content (MC). The color of spray-dried SSLP microcapsules was greener and bluer, and the color was brighter. In morphology, the spray-dried SSLP microcapsules were spherical with a slightly shrunk surface, whereas the freeze-dried ones were lamellar and porous. The two microcapsules have strong stability under different storage conditions and in vitro gastrointestinal digestion simulation. In addition, both microcapsules and free SSLP contained multiple ginsenosides. At the same time, both microcapsules had good free radical scavenging ability. These results indicate that the microencapsulation technology could improve the stability and bioavailability of SSLP, which is expected to provide a reference for the intensive processing of the SLPN. PRACTICAL APPLICATION: After microencapsulation, the stem and leaf extract of Panax notoginseng improved its stability and taste, which laid a foundation for making more nutritious and better tasting food of the stem and leaf of P. notoginseng.

Gold Nanowire Sponge Electrochemistry for Permeable Wearable Sweat Analysis Comfortably and Wirelessly.

Electrochemistry-based wearable and wireless sweat analysis is emerging as a promising noninvasive method for real-time health monitoring by tracking chemical and biological markers without the need for invasive blood sampling. It offers the potential to remotely monitor human sweat conditions in relation to metabolic health, stress, and electrolyte balance, which have implications for athletes, patients with chronic conditions, and individuals for the early detection and management of health issues. The state-of-the-art mainstream technology is dominated by the concept of a wearable microfluidic chip, typically based on elastomeric PDMS. While outstanding sensing performance can be realized, the design suffers from the poor permeability of PDMS, which could cause skin redness or irritation. Here, we introduce an omnidirectionally permeable, deformable, and wearable sweat analysis system based on gold nanowire sponges. We demonstrate the concept of all-in-one soft sponge electrochemistry, where the working, reference, and counter electrodes and electrolytes are all integrated within the sponge matrix. The intrinsic porosity of sponge in conjunction with vertically aligned gold nanowire electrodes gives rise to a high electrochemically active surface area of ∼67 cm2. Remarkably, this all-in-one sponge-based electrochemical system exhibited stable performance under a pressure of 10 kPa and 300% omnidirectional strain. The gold sponge biosensing electrodes could be sandwiched between two biocompatible sweat pads, which can serve as natural sweat collection and outflow layers. This naturally biocompatible and permeable platform can be integrated with wireless communication circuits, leading to a wireless sweat analysis system for the real-time monitoring of glucose, lactate, and pH during exercise.

Detecting anomalous anatomic regions in spatial transcriptomics with STANDS.

Detection and Dissection of Anomalous Tissue Domains (DDATD) from multi-sample spatial transcriptomics (ST) data provides unprecedented opportunities to characterize anomalous tissue domains (ATDs), revealing both population-level and individual-specific pathogenic factors for understanding pathogenic heterogeneities behind diseases. However, no current methods can perform de novo DDATD from ST data, especially in the multi-sample context. Here, we introduce STANDS, an innovative framework based on Generative Adversarial Networks which integrates three core tasks in multi-sample DDATD: detecting, aligning, and subtyping ATDs. STANDS incorporates multimodal-learning, transfer-learning, and style-transfer techniques to effectively address major challenges in multi-sample DDATD, including complications caused by unalignable ATDs, under-utilization of multimodal information, and scarcity of normal ST datasets necessary for comparative analysis. Extensive benchmarks from diverse datasets demonstrate STAND's superiority in identifying both common and individual-specific ATDs and further dissecting them into biologically distinct subdomains. STANDS also provides clues to developing ATDs visually indistinguishable from surrounding normal tissues.

Role of naringin in the treatment of atherosclerosis.

Atherosclerosis (AS) is a major pathological basis of coronary heart disease. However, the currently available medications are unable to effectively reduce the incidence of cardiovascular events in the majority of patients with AS. Therefore, naringin has been attracting considerable attention owing to its anti-AS effects. Naringin can inhibit the growth, proliferation, invasion, and migration of vascular smooth muscle cells, ameliorate endothelial cell inflammation and apoptosis, lower blood pressure, halt the cell cycle at the G1 phase, and impede growth via its antioxidant and free radical scavenging effects. These activities suggest the potential anti-AS effects of naringin. In this review article, we comprehensively summarized the latest findings on the anti-AS effects of naringin and their underlying mechanisms, providing a crucial reference for future research on the anti-AS potential of this agent.

Connexin43 overexpression promoted ferroptosis and increased myocardial vulnerability to ischemia-reperfusion injury in type 1 diabetic mice.

Enhancement of Connexin43 (Cx43) and ferroptosis are respectively associated with the exacerbation of myocardial ischemia-reperfusion injury (MIRI) in diabetes. Myocardial vulnerability to ischemic insult has been shown to vary during early and later phases of diabetes in experimental settings. Whether or not Connexin43 (Cx43) and ferroptosis interplay during MIRI in diabetes is unknown. We, thus, aimed to investigate whether or not the content of myocardial Cx43 may be attributable to myocardial vulnerability to MIRI at different stages of diabetes and also to explore the potential interplay between Cx43 and ferroptosis in this pathology. Age-matched control and subgroups of Streptozotocin-induced diabetic mice were subjected to MIRI induced by 30 minutes coronary artery occlusion and 2 hours reperfusion respectively at 1, 2 and 5 weeks of diabetes. Rat cardiac H9C2 cells were exposed to high glucose (HG) for 48h in the absence or presence of Cx43 gene knockdown followed by hypoxia/reoxygenation (HR) respectively for 6 and 12 hours. Post-ischemic myocardial infarct size was reduced in 1 and 2 weeks DM mice concomitant with enhanced GPX4 and reduced cardiac Cx43 and ferroptosis as compared to control. By contrast, cardiac GPX4 was significantly reduced while Cx43 increased at DM 5 weeks (D5w) which was correspondent to significant increases in ferroptosis and myocardial infarction. Post-ischemic cardiac function was improved in 1 and 2 weeks but worsened in 5w DM mice as compared with non-diabetic control. GAP19 (Cx43 inhibitor) significantly attenuated ferroptosis and reduced myocardial infarction in D5w mice. Erastin (ferroptosis activator) reversed the cardioprotective effect of GAP19. In vitro, HR significantly reduced cell viability accompanied with reduced GPX4 but elevated Cx43 expression, MDA production and ferroptosis. Cx43 gene knockdown in H9C2 resulted in a significant increase in GPX4, reduction in MDA and ferroptosis, and subsequently reduced post-hypoxic cell viability. The beneficial effects of Cx43 gene knock-down was minified or eliminated by Erastin. It is concluded that Cx43 overexpression exacerbates MIRI under diabetic conditions via promoting ferroptosis, while its down-regulation at early state of diabetes is attributable to enhanced myocardial tolerance to MIRI.

Whole-genome sequencing of the invasive golden apple snail Pomacea canaliculata from Asia reveals rapid expansion and adaptive evolution.

Pomacea canaliculata, an invasive species native to South America, is recognized for its broad geographic distribution and adaptability to a variety of ecological conditions. The details concerning the evolution and adaptation of P. canaliculate remain unclear due to a lack of whole-genome resequencing data. We examined 173 P. canaliculata genomes representing 17 geographic populations in East and Southeast Asia. Interestingly, P. canaliculata showed a higher level of genetic diversity than other mollusks, and our analysis suggested that the dispersal of P. canaliculata could have been driven by climate changes and human activities. Notably, we identified a set of genes associated with low temperature adaptation, including Csde1, a cold shock protein coding gene. Further RNA sequencing analysis and reverse transcription quantitative polymerase chain reaction experiments demonstrated the gene's dynamic pattern and biological functions during cold exposure. Moreover, both positive selection and balancing selection are likely to have contributed to the rapid environmental adaptation of P. canaliculata populations. In particular, genes associated with energy metabolism and stress response were undergoing positive selection, while a large number of immune-related genes showed strong signatures of balancing selection. Our study has advanced our understanding of the evolution of P. canaliculata and has provided a valuable resource concerning an invasive species.

Effects of plastic aging on biodegradation of polystyrene by Tenebrio molitor larvae: Insights into gut microbiome and bacterial metabolism.

Plastics aging reduces resistance to microbial degradation. Plastivore Tenebrio molitor rapidly biodegrades polystyrene (PS, size: < 80 µm), but the effects of aging on PS biodegradation by T. molitor remain uncharacterized. This study examined PS biodegradation over 24 days following three pre-treatments: freezing with UV exposure (PS1), UV exposure (PS2), and freezing (PS3), compared to pristine PS (PSv) microplastic. The pretreatments deteriorated PS polymers, resulting in slightly higher specific PS consumption (602.8, 586.1, 566.7, and 563.9 mg PS·100 larvae-1·d-1, respectively) and mass reduction rates (49.6 %, 49.5 %, 49.2 %, and 48.7 %, respectively) in PS1, PS2, and PS3 compared to PSv. Improved biodegradation correlated with reduced molecular weights and the formation of oxidized functional groups. Larvae fed more aged PS exhibited greater gut microbial diversity, with microbial community and metabolic pathways shaped by PS aging, as supported by co-occurrence network analysis. These findings indicated that the aging treatments enhanced PS biodegradation by only limited extent but impacted greater on gut microbiome and bacterial metabolic genes, indicating that the T. molitor host have highly predominant capability to digest PS plastics and alters gut microbiome to adapt the PS polymers fed to them.

Improvement of MASLD and MASH by suppression of hepatic N-acetyltransferase 10.

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are characterized by excessive triglyceride accumulation in the liver. However, due to an incomplete understanding of its pathogenesis, more efforts are needed to identify specific and effective treatments. N4-acetylcytidine (ac4C) is a newly discovered RNA modification to regulate mRNA. N-acetyltransferase 10 (NAT10) has not been fully explored in MASLD and MASH. METHODS: The clinical relevance of NAT10 was evaluated based on its expression in various mouse and human models of MASLD and MASH. Acetylated RNA immunoprecipitation sequencing and mRNA stability assays were used to explore the role of NAT10 in regulating ac4C modification and expression of target genes. Genetically engineered mice were employed to investigate the role of NAT10 in MASLD and MASH progression. RESULTS: Hepatic NAT10 expression was significantly increased in multiple mice and humans of MASLD and MASH. Genetic knockout of NAT10 protected mice from diet-induced hepatic steatosis and steatohepatitis, whereas overexpression of NAT10 exacerbated high-fat-diet-induced liver steatosis. Mechanistically, NAT10 binds to Srebp-1c mRNA, promoting its stability and expression, thereby upregulating lipogenic enzymes. Treatment with Remodelin, a NAT10-specific inhibitor, effectively ameliorates liver steatosis and dyslipidemia in a preclinical mouse model. CONCLUSIONS: Our findings indicate that NAT10 could regulate lipid metabolism in MASLD and MASH by stabilizing Srebp-1c mRNA and upregulating lipogenic enzymes. This study highlights the role of NAT10 and RNA acetylation in the pathogenesis of MASLD and MASH. Thus, our findings suggest a promising new therapeutic approach, such as the use of NAT10 inhibitor, for treating metabolic liver disease.

Intranasal dantrolene nanoparticles inhibit lipopolysaccharide-induced depression and anxiety behavior in mice.

This study investigates the therapeutic effectiveness of intranasal dantrolene nanoparticles in the Ryanodex formulation (DNRF) pretreatment to inhibit lipopolysaccharide (LPS)-induced depressive and anxiety behavior in mice. Both wild-type (WT) B6SJLF1/J and 5XFAD adult mice were pretreated with intranasal DNRF (5mg/kg), daily, Monday to Friday, 5 days per week, for 4 weeks. Then, mice were treated with intraperitoneal injection of LPS (5mg/kg) for one time. Behavioral tests for depression and anxiety were performed 24 hours after a one-time LPS injection. Biomarkers for inflammation (IL-1ß and IL-18) in blood were measured using enzyme-linked immunosorbent assay (ELISA). In both types of mice, intranasal DNRF significantly inhibited LPS-induced pathological elevation of IL-1ß and IL-18 in the blood. Intranasal DNRF abolished LPS-induced depression and anxiety behaviors behavior in both WT and 5XFAD mice, without obvious side effects, which was associated with its significant inhibition of pathological elevation of pyroptosis related cytokines in blood.

Efficacy and Safety of General Anesthesia Induction with Ciprofol in Hip Fracture Surgery of Elderly Patients: A Randomized Controlled Trial.

Background: Ciprofol is a new intravenous sedative / anesthetic drug. In recent years, many clinical studies have also confirmed the sedative effect of ciprofol. However, more clinical research is still needed on its clinical application characteristics in special populations. Objective: The aim of this study was to compare the clinical effects of ciprofol and propofol in general anesthesia induction of elderly patients. Methods: 60 elderly (aged ≥ 75 years) patients underwent hip fracture surgery were randomly into two groups of a 1:1 ratio. Group C (ciprofol group): 0.3mg/kg ciprofol was infused. Group P (propofol group): 1.5mg/kg propofol was infused. The observation period was from the infusion of test drug to 5 min after endotracheal intubation. The primary outcomes included the incidence of severe hypotension and hypotension during the observation period. The secondary outcomes were as follows: the success rate of general anesthesia induction, the number of additional sedation, the time of loss of consciousness (LOC), Δ MAP, Δ HR, adverse events and the frequency of vasoactive drugs used. Results: Finally, 60 subjects completed the study. Compared with Group P, the incidence of severe hypotension in Group C was lower (26.7% vs 53.3%, P = 0.035), the incidence of hypotension was also lower (36.7% vs 63.3%, P = 0.037), Δ MAP in Group C was significantly lower (31.4 ± 11.4 vs 39.6 ± 15.7, P = 0.025), the frequency of ephedrine used and the incidence of injection pain in Group C were also significantly lower. Conclusion: Ciprofol showed similar efficacy to propofol when used for general anesthesia induction in elderly patients underwent hip fracture surgery and could maintain more stable blood pressure.

Perirenal Fat Thickness Is Associated With Contrast-Induced Nephropathy in Type 2 Diabetic Patients Undergoing Coronary Catheterization.

Background: Deposition of adipose tissue may have a promoting role in the development of diabetic complications. This study is aimed at investigating the relationship between adipose tissue thickness and risk of contrast-induced nephropathy (CIN) in patients with Type 2 diabetes mellitus (T2DM). Methods: A total of 603 T2DM patients undergoing percutaneous coronary angiography or angioplasty with suspicious or confirmed stable coronary artery disease were enrolled in this study. The thicknesses of perirenal fat (PRF), subcutaneous fat (SCF), intraperitoneal fat (IPF), and epicardial fat (ECF) were measured by color Doppler ultrasound, respectively. The association of various adipose tissues with CIN was analyzed. Results: Seventy-seven patients (12.8%) developed CIN in this cohort. Patients who developed CIN had significantly thicker PRF (13.7 ± 4.0 mm vs. 8.9 ± 3.6 mm, p < 0.001), slightly thicker IPF (p = 0.046), and similar thicknesses of SCF (p = 0.782) and ECF (p = 0.749) compared to those who did not develop CIN. Correlation analysis showed that only PRF was positively associated with postoperation maximal serum creatinine (sCr) (r = 0.18, p = 0.012), maximal absolute change in sCr (r = 0.33, p < 0.001), and maximal percentage of change in sCr (r = 0.36, p < 0.001). In receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of PRF (0.809) for CIN was significantly higher than those of SCF (0.490), IPF (0.594), and ECF (0.512). Multivariate logistic regression analysis further confirmed that thickness of PRF, rather than other adipose tissues, was independently associated with the development of CIN after adjusted for confounding factors (odds ratio (OR) = 1.53, 95% CI: 1.38-1.71, p < 0.001). Conclusions: PRF is independently associated with the development of CIN in T2DM patients undergoing coronary catheterization.

CD19 CAR-T treatment shows limited efficacy in r/r DLBCL with double expression and TP53 alterations.

OBJECT: Autologous CD19 chimeric antigen receptor T-cell therapy (CAR-T) significantly modifies the natural course of chemorefractory diffuse large B-cell lymphoma (DLBCL). However, 25% to 50% of patients with relapsed/refractory DLBCL still do not achieve remission. Therefore, investigating new molecular prognostic indicators that affect the effectiveness of CAR-T for DLBCL and developing novel combination therapies are crucial. METHODS: Data from 73 DLBCL patients who received CD19 CAR-T (Axi-cel or Relma-cel) were retrospectively collected from Shanghai Tongji Hospital of Tongji University, The Second Affiliated Hospital Zhejiang University School of Medicine, and The Affiliated People's Hospital of Ningbo University. Prior to CD19 CAR-T-cell transfusions, the patients received fludarabine and cyclophosphamide chemotherapy regimen. RESULTS: Our study revealed that relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) patients with both Double-expression (MYC > 40% and BCL2 > 50%) and TP53 alterations tend to have a poorer clinical prognosis after CAR-T therapy, even when CAR-T therapy is used in combination with other therapies. However, CAR-T therapy was found to be effective in patients with only TP53 alterations or DE status, suggesting that their prognosis is in line with that of patients without TP53 alterations or DE status. CONCLUSIONS: Our study suggests that r/r DLBCL patients with both DE status and TP53 alterations treated with CAR-T therapy are more likely to have a poorer clinical prognosis. However, CAR-T therapy has the potential to improve the prognosis of patients with only TP53 alterations or DE status to be similar to that of patients without these abnormalities.

Electrically tunable planar liquid-crystal singlets for simultaneous spectrometry and imaging.

Conventional hyperspectral cameras cascade lenses and spectrometers to acquire the spectral datacube, which forms the fundamental framework for hyperspectral imaging. However, this cascading framework involves tradeoffs among spectral and imaging performances when the system is driven toward miniaturization. Here, we propose a spectral singlet lens that unifies optical imaging and computational spectrometry functions, enabling the creation of minimalist, miniaturized and high-performance hyperspectral cameras. As a paradigm, we capitalize on planar liquid crystal optics to implement the proposed framework, with each liquid-crystal unit cell acting as both phase modulator and electrically tunable spectral filter. Experiments with various targets show that the resulting millimeter-scale hyperspectral camera exhibits both high spectral fidelity ( > 95%) and high spatial resolutions ( ~1.7 times the diffraction limit). The proposed "two-in-one" framework can resolve the conflicts between spectral and imaging resolutions, which paves a practical pathway for advancing hyperspectral imaging systems toward miniaturization and portable applications.

Elevated Serum IL-17A in Kawasaki Disease Patients Predicts Responsiveness to Intravenous Immunoglobulin Therapy.

INTRODUCTION: This study aimed to investigate the correlation between serum interleukin (IL)-17A levels and responsiveness to intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD) patients. METHODS: A retrospective analysis on data from 192 KD patients admitted to the Anqing Municipal Hospital between January 2021 and January 2024 was conducted. Patients were categorized into IVIG-nonresponsive and IVIG-sensitive groups as per the treatment outcomes. Outcome measures included serum IL-17A levels, left coronary artery (LCA) Z scores, and relevant laboratory parameters. Logistic regression analysis was performed to identify predictive factors for IVIG responsiveness, and diagnostic performance was assessed using receiver operating characteristic (ROC) curves and calculation of the area under the curve (AUC). RESULTS: A total of 40 IVIG-nonresponsive cases and 152 IVIG-sensitive cases were included. Prior to intervention, IVIG-nonresponsive patients had significantly higher serum IL-17A levels compared to IVIG-sensitive patients, with a statistically significant difference. After intervention, serum IL-17A levels significantly decreased in IVIG-sensitive patients while remaining elevated in IVIG-nonresponsive patients. IVIG-nonresponsive patients exhibited significantly higher levels of C-reactive protein (CRP), white blood cell count (WBC), NE, and ALT compared to IVIG-sensitive patients, whereas no significant differences in LCA Z scores between the two groups existed. Multivariable logistic regression analysis identified pre-IL-17A, CRP, WBC, and ALT as independent predictors of IVIG-nonresponsiveness in KD. When pre-IL-17A was ≥39.96 pg/mL, the specificity and sensitivity for predicting IVIG-nonresponsive KD were 63.9% and 71.9%, respectively, with an AUC of 0.637. The combined diagnosis of IL-17A, CRP, WBC, and ALT yielded an AUC of 0.780. CONCLUSION: Serum IL-17A levels were remarkably elevated in IVIG-nonresponsive KD patients both before and after intervention. A serum IL-17A level (≥39.96 pg/mL) demonstrated good predictive profile for IVIG-nonresponsive KD, and combining IL-17A with CRP, WBC, and ALT improved diagnostic performance.