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Cadmium (Cd) is a toxic contaminant widely spread in natural and industrial environments. Adolescent exposure to Cd increases risk for obesity-related morbidity in young adults including type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). Despite this recognition, the direct impact of adolescent Cd exposure on the progression of MASLD later in life, and the mechanisms underlying these effects, remain unclear. Here, adolescent rats received control diet or diets containing 2 mg Cd 2+ /kg feed for 4 weeks, and then HFD containing 15% lard or control diet in young adult rats was selected for 6 weeks to clarify this issue. Data firstly showed that HFD-fed rats in young adulthood due to adolescent Cd exposure exhibited more severe MASLD, evidenced by increased liver damage, disordered serum and hepatic lipid levels, and activated NLRP3 inflammasome. Hepatic transcriptome analysis revealed the potential effects of mitochondrial dysfunction in aggravated MASLD due to Cd exposure. Verification data further confirmed that mitochondrial structure and function were targeted and disrupted during this process, shown by broken mitochondrial ridges, decreased mitochondrial membrane potential, imbalanced mitochondrial dynamic, insufficient ATP concentration, and enhanced mitochondrial ROS generation. However, mitophagy is inactively involved in clearance of damaged mitochondria induced by early Cd in HFD condition due to inhibited mitophagy receptor FUNDC1. In contrast, FUNDC1-dependent mitophagy activation prevents lipotoxicity aggravated by early Cd via suppressing mitochondrial ROS generation. Collectively, our data show that insufficient FUNDC1-dependent mitophagy can drive the transition from HFD-induced MASLD to MASH, and accordingly, these findings will provide a better understanding of potential mechanism of diet-induced metabolic diseases in the context of early environmental Cd exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Acute aortic dissection (AD) in pregnancy poses a lethal risk to both mother and fetus. However, well-established therapeutic guidelines are lacking. This study aimed to investigate clinical features, outcomes and optimal management strategies for pregnancy-related AD., Methods: We conducted a retrospective multicentre cohort study including 67 women with acute AD during pregnancy or within 12 weeks postpartum from three major cardiovascular centres in China between 2003 and 2021. Patient characteristics, management strategies and short-term outcomes were analysed., Results: Median age was 31 years, with AD onset at median 32 weeks gestation. Forty-six patients (68.7%) had type A AD, of which 41 underwent immediate surgery. Overall maternal mortality was 10.4% (7/67) and fetal mortality was 26.9% (18/67). Compared with immediate surgery, selective surgery was associated with higher risk of composite maternal and fetal death (adjusted RR: 12.47 (95% CI 3.26 to 47.73); p=0.0002) and fetal death (adjusted RR: 8.77 (95% CI 2.33 to 33.09); p=0.001)., Conclusions: Immediate aortic surgery should be considered for type A AD at any stage of pregnancy or postpartum. For pregnant women with AD before fetal viability, surgical treatment with the fetus in utero should be considered. Management strategies should account for dissection type, gestational age, and fetal viability., Trial Registration Number: NCT05501145., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Reports on stress-associated halitosis are scarce and have only focused on intraoral halitosis. This work aimed to study stress-associated extraoral halitosis (EOH) and further investigate its potential association with stress-induced intestinal inflammation., Methods: This retrospective study included 664 white-collar employees with self-reported stress-associated halitosis. They underwent the organoleptic score (OLS) to assess halitosis, modified Brief Job Stress Questionnaire (BJSQ) score to assess job stress, OralChroma breath test to measure volatile sulfur compounds (VSCs) in breath, and hydrogen/methane breath test (HMBT) and nitric oxide breath test (NOBT) to detect intestinal inflammation. They were classified into high-stress and low-stress groups based on their modified BJSQ score., Results: Totally, 106 eligible patients were identified as having stress-associated EOH, and 61 of them had high stress. Additionally, 70 (66.04%) and 73 (68.87%) of them tested positive for HMB and NOBT, respectively. Dimethyl sulfide (DMS) was found to be the predominant VSC in breath. High-stress patients had significantly higher positivity rates for HMBT and NOBT, OLS, and exhaled DMS levels compared to low-stress patients. HMBT-positive patients and NOBT-positive patients had significantly higher OLS and exhaled DMS levels compared to their respective negative counterparts., Conclusions: Job stress can lead to intestinal inflammation and subsequent gut-originated EOH., (© 2024 John Wiley & Sons Ltd.)

Objectives: To develop and validate a clinical diagnostic model based on optical pumped magnetometer magnetocardiography (OPM-MCG) for the detection of myocardial ischaemia in patients with borderline coronary lesions prior to invasive coronary angiography (ICA)., Design: Prospective observational cohort study., Setting: Single centre of the China National Clinical Research Centre for Cardiovascular Disease (NCCMRC)., Participants: Adults with borderline coronary lesions on ICA (n=141)., Interventions: Underwent OPM-MCG before ICA and fractional flow reserve measurement., Results: Five parameters were included in the final diagnostic model: MAg max -TT, δDt sum -PN, δAg sum -C, δAr sum -N and δAr min -N. 1000 bootstrap replications showed that the area under the receiver operating characteristic curve and 95% CI of the diagnostic model were 0.864 (0.803-0.925), with a sensitivity of 79.4%, specificity of 80.8%, positive predictive value of 79.4% and negative predictive value of 80.8%. Decision curve analysis showed a net benefit from the predictive model when the threshold probability of an ischaemic patient was >12%, suggesting the potential utility of the model in the real world., Conclusions: A nomogram based on five OPM-MCG parameters was developed to assess myocardial ischaemia in patients with borderline coronary lesions and has the potential to reduce the need for unnecessary ICA., Trial Registration Number: China Clinical Trial Registry (ChiCTR2300072382)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Carbon quantum dots (CQDs) are garnering attention for their broad applications. This study offers a detailed evaluation of the biomedical safety and health risks of carbon quantum dots (CQDs) with different surface modifications, addressing a key gap in their safe application. It focuses on three CQD types: diammonium citrate-based (CQDs-A), spermidine trihydrochloride-based (CQDs-S), and a combination (CQDs-A/S), analyzing their physicochemical properties, cytotoxicity, oxidative stress, inflammatory responses, and nephrotoxicity. While all CQDs were under 10 nm, their biological impacts varied. Positively charged CQDs-S and CQDs-A/S showed significant cytotoxicity in HEK293 cells, inducing oxidative stress but not activating NLRP3 inflammasome, indicating a limited inflammatory response. Renal integrity remained unaffected, with stable zonula occludens 2 expression and unaltered renal markers. In vivo studies in BALB/c mice further supported the safety of CQDs, showing no organ damage or kidney pathology at high doses. The findings underscore the potential for safe biomedical use of CQDs, particularly when their retention time is minimized. This research makes a novel contribution by linking CQDs' surface charge to cytotoxic effects and oxidative stress, providing key insights into their safe use in biomedicine and filling a critical gap in nanoparticle toxicity studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Colorectal cancer (CRC) is a prevalent global malignancy with substantial morbidity and mortality. Accurate prognostic evaluation is essential in CRC patient management. This study investigates the prognostic significance of red blood cell count (RBC) and Onodera's prognostic nutritional index (OPNI) in resectable CRC patients., Methods: A retrospective analysis of 210 CRC patients undergoing radical resection (January 2015-January 2017) assessed clinical and hematological factors, including RBC, albumin, hemoglobin, and OPNI. A novel comprehensive biomarker, R-OPNI, combining preoperative RBC with OPNI, was introduced. Correlations with patient survival were analyzed, and R-OPNI's independent prognostic value was assessed through univariate and multivariate Cox models. Predictive ability was compared to other factors using the receiver operating characteristic (ROC) method., Results: Higher RBC levels (≥ 3.9 × 10 12 /L) and elevated OPNI were associated with significantly improved overall survival. Lower R-OPNI scores (0 or 1) indicated notably poorer survival. Multivariate analysis confirmed R-OPNI's independent prognostic significance (HR: 0.273, 95% CI: 0.098-0.763, p  = 0.013). R-OPNI (AUC = 0.732) demonstrated superior predictive value compared to individual prognostic factors., Conclusion: R-OPNI emerges as a robust, independent prognostic predictor for resectable CRC patients, emphasizing the importance of assessing preoperative nutritional status.

Severe cytokine release syndrome (sCRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have limited the widespread use of chimeric antigen receptor T (CAR T)-cell therapy. We designed a novel anti-CD19 CAR (ssCART-19) with a small hairpin RNA (shRNA) element to silence the interleukin-6 (IL-6) gene, hypothesizing it could reduce sCRS and ICANS by alleviating monocyte activation and proinflammatory cytokine release. In a post hoc analysis of two clinical trials, we compared ssCART-19 with common CAR T-cells (cCART-19) in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Among 87 patients, 47 received ssCART-19 and 40 received cCART-19. Grade ≥3 CRS occurred in 14.89% (7/47) of the ssCART-19 group versus 37.5% (15/40) in the cCART-19 group ( p  = 0.036). ICANS occurred in 4.26% (2/47) of the ssCART-19 group (all grade 1) compared to 15% (2/40) of the cCART-19 group. Patients in the ssCART-19 group showed comparable rates of treatment response (calculated with rates of complete remission and incomplete hematological recovery) were 91.49% (43/47) for ssCART-19 and 85% (34/40) for cCART-19 ( p  = 0.999). With a median follow-up of 21.9 months, cumulative nonrelapse mortality was 10.4% for ssCART-19 and 13.6% for cCART-19 ( p  = 0.33). Median overall survival was 37.17 months for ssCART-19 and 32.93 months for cCART-19 ( p  = 0.40). Median progression-free survival was 24.17 months for ssCART-19 and 9.33 months for cCART-19 ( p  = 0.23). These data support the safety and efficacy of ssCART-19 for r/r B-ALL, suggesting its potential as a promising therapy., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)

In this study, a novel colorimetric screening method for identifying menaquinone-7 (MK-7) producing strains was established using potassium permanganate. To our knowledge, this method represents the first direct screening methodology for the identification of MK-7 producing strains. Utilizing this screening method, a new MK-7 producing strain, Bacillus subtilis GSA-184, was identified from the soil of the Tibetan Plateau. Under the optimized fermentation medium (50 g/L glycerol, 30 g/L yeast extract powder, 100 g/L soybean peptone, 1 g/L KH 2 PO 4 , and 1 g/L MnSO 4 ), the production of MK-7 was increased to 25.7 mg/L. Additionally, the maximum production of MK-7 reached 36.46 mg/L after 48 h in a 5-L fermenter., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04097-1., Competing Interests: Conflict of interestThe authors declare that they have no competing interests., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Retinal microcirculation alterations are early indicators of diabetic microvascular complications. Optical coherence tomography angiography (OCTA) is a noninvasive method to assess these changes. This study analyzes changes in retinal microcirculation in prediabetic patients during short-term increases in blood glucose using OCTA., Aim: To investigate the changes in retinal microcirculation in prediabetic patients experiencing short-term increases in blood glucose levels using OCTA., Methods: Fifty volunteers were divided into three groups: Group 1 [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)], Group 2 (both IFG and IGT), and a control group. Retinal microcirculation parameters, including vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) metrics, were measured using OCTA. Correlations between these parameters and blood glucose levels were analyzed in both the fasting and postprandial states., Results: One hour after glucose intake, the central VD ( P = 0.023), central PD ( P = 0.026), and parafoveal PD ( P < 0.001) were significantly greater in the control group than in the fasting group. In Group 1, parafoveal PD ( P < 0.001) and FAZ circularity ( P = 0.023) also increased one hour after glucose intake. However, no significant changes were observed in the retinal microcirculation parameters of Group 2 before or after glucose intake ( P > 0.05). Compared with the control group, Group 1 had a larger FAZ area ( P = 0.032) and perimeter ( P = 0.018), whereas Group 2 had no significant differences in retinal microcirculation parameters compared with the control group ( P > 0.05). Compared with Group 1, Group 2 had greater central VD ( P = 0.013) and PD ( P = 0.008) and a smaller FAZ area ( P = 0.012) and perimeter ( P = 0.010). One hour after glucose intake, Group 1 had a larger FAZ area ( P = 0.044) and perimeter ( P = 0.038) than did the control group, whereas Group 2 showed no significant differences in retinal microcirculation parameters compared with the control group ( P > 0.05). Group 2 had greater central VD ( P = 0.042) and PD ( P = 0.022) and a smaller FAZ area ( P = 0.015) and perimeter ( P = 0.016) than Group 1. At fasting, central PD was significantly positively correlated with blood glucose levels ( P = 0.044), whereas no significant correlations were found between blood glucose levels and OCTA parameters one hour after glucose intake., Conclusion: A short-term increase in blood glucose has a more pronounced effect on retinal microcirculation in prediabetic patients with either IFG or IGT., Competing Interests: Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Three major types of GABAergic interneurons, parvalbumin-, somatostatin-, and vasoactive intestinal peptide-expressing (PV, SOM, VIP) cells, play critical but distinct roles in the cortical microcircuitry. Their specific electrophysiology and connectivity shape their inhibitory functions. To study the network dynamics and signal processing specific to these cell types in the cerebral cortex, we developed a multi-layer model incorporating biologically realistic interneuron parameters from rodent somatosensory cortex. The model is fitted to in vivo data on cell-type-specific population firing rates. With a protocol of cell-type-specific stimulation, network responses when activating different neuron types are examined. The model reproduces the experimentally observed inhibitory effects of PV and SOM cells and disinhibitory effect of VIP cells on excitatory cells. We further create a version of the model incorporating cell-type-specific short-term synaptic plasticity (STP). While the ongoing activity with and without STP is similar, STP modulates the responses of Exc, SOM, and VIP cells to cell-type-specific stimulation, presumably by changing the dominant inhibitory pathways. With slight adjustments, the model also reproduces sensory responses of specific interneuron types recorded in vivo. Our model provides predictions on network dynamics involving cell-type-specific short-term plasticity and can serve to explore the computational roles of inhibitory interneurons in sensory functions., (© The Author(s) 2024. Published by Oxford University Press.)

Tilapia stands out as one of the most extensively farmed and consumed fish species globally, valued for its ease of preparation and relative affordability. Although tilapia is a valuable protein source, it can also function as a vector for foodborne pathogens. This literature review reveals that tilapia could carry a variety of contamination with various foodborne pathogens, including Plesiomonas shigelloides, diarrheagenic Escherichia coli, Vibrio parahaemolyticus, Salmonella Weltevreden, Salmonella enterica, Shigella, Staphylococcus aureus, Campylobacter jejuni, Clostridium botulinum, and Listeria monocytogenes. Although guidelines from entities, such as the Global Seafood Alliance, Aquaculture Stewardship Council, and International Organization for Standardization, have been established to ensure the microbiological safety of tilapia, the unique challenges posed by pathogens in tilapia farming call for a more nuanced and targeted approach. Recognizing that contaminants could emerge at various stages of the tilapia supply chain, there is a crucial need for enhanced detection and monitoring of pathogens associated with this fish and its culturing environment. Additionally, it is essential to acknowledge the potential impact of climate change on the safety of tilapia, which may elevate the prevalence and contamination levels of pathogens in this fish. Proactive measures are essential to understand and mitigate the effects of climate change on tilapia production, ensuring the sustainability and safety of this seafood product for both present and future generations., (© 2024 Institute of Food Technologists®.)

Although the Three Gorges Dam (TGD) is the world's largest hydroelectric dam, little is known about the spatial-temporal patterns and community assembly mechanisms of meio- and micro-eukaryotes and its two subtaxa (zooplankton and zoobenthos). This knowledge gap is particularly evident across various habitats and during different water-level periods, primarily arising from the annual regular dam regulation. To address this inquiry, we employed mitochondrial cytochrome c oxidase I (COI) gene-based environmental DNA (eDNA) metabarcoding technology to systematically analyze the biogeographic pattern of the three communities within the Three Gorges Reservoir (TGR). Our findings reveal distinct spatiotemporal characteristics and complementary patterns in the distribution of meio- and micro-eukaryotes. The three communities showed similar biogeographic patterns and assembly processes. Notably, the diversity of these three taxa gradually decreased along the river. Their communities were less shaped by stochastic processes, which gradually decreased along the longitudinal riverine-transition-lacustrine gradient. Hence, deterministic factors, such as seasonality, environmental, and spatial variables, along with species interactions, likely play a pivotal role in shaping these communities. Environmental factors primarily drive seasonal variations in these communities, while hydrological conditions, represented as spatial distance, predominantly influence spatial variations. These three communities followed the distance-decay pattern. In winter, compared to summer, both the decay and species interrelationships are more pronounced. Taken together, this study offers fresh insights into the composition and diversity patterns of meio- and micro-eukaryotes at the spatial-temporal level. It also uncovers the mechanisms behind community assembly in various environmental niches within the dam-induced river-reservoir systems. KEY POINTS: • Distribution and diversity of meio- and micro-eukaryotes exhibit distinct spatiotemporal patterns in the TGR. • Contribution of stochastic processes in community assembly gradually decreases along the river. • Deterministic factors and species interactions shape meio- and micro-eukaryotic community., (© 2024. The Author(s).)

Deep models, e.g., CNNs and Vision Transformers, have achieved impressive achievements in many vision tasks in the closed world. However, novel classes emerge from time to time in our ever-changing world, requiring a learning system to acquire new knowledge continually. Class-Incremental Learning (CIL) enables the learner to incorporate the knowledge of new classes incrementally and build a universal classifier among all seen classes. Correspondingly, when directly training the model with new class instances, a fatal problem occurs - the model tends to catastrophically forget the characteristics of former ones, and its performance drastically degrades. There have been numerous efforts to tackle catastrophic forgetting in the machine learning community. In this paper, we survey comprehensively recent advances in class-incremental learning and summarize these methods from several aspects. We also provide a rigorous and unified evaluation of 17 methods in benchmark image classification tasks to find out the characteristics of different algorithms empirically. Furthermore, we notice that the current comparison protocol ignores the influence of memory budget in model storage, which may result in unfair comparison and biased results. Hence, we advocate fair comparison by aligning the memory budget in evaluation, as well as several memory-agnostic performance measures.

Acute lung injury (ALI) is a serious adverse event in the management of acute type A aortic dissection (ATAAD). Using a large-scale cohort, we applied artificial intelligence-driven approach to stratify patients with different outcomes and treatment responses. A total of 2,499 patients from China 5A study database (2016-2022) from 10 cardiovascular centers were divided into 70% for derivation cohort and 30% for validation cohort, in which extreme gradient boosting algorithm was used to develop ALI risk model. Logistic regression was used to assess the risk under anti-inflammatory strategies in different risk probability. Eight top features of importance (leukocyte, platelet, hemoglobin, base excess, age, creatinine, glucose, and left ventricular end-diastolic dimension) were used to develop and validate an ALI risk model, with adequate discrimination ability regarding area under the receiver operating characteristic curve of 0.844 and 0.799 in the derivation and validation cohort, respectively. By the individualized treatment effect prediction, ulinastatin use was significantly associated with significantly lower risk of developing ALI (odds ratio [OR] 0.623 [95% CI 0.456, 0.851]; P = 0.003) in patients with a predicted ALI risk of 32.5-73.0%, rather than in pooled patients with a risk of <32.5 and >73.0% (OR 0.929 [0.682, 1.267], P = 0.642) (Pinteraction = 0.075). An artificial intelligence-driven risk stratification of ALI following ATAAD surgery were developed and validated, and subgroup analysis showed the heterogeneity of anti-inflammatory pharmacotherapy, which suggested individualized anti-inflammatory strategies in different risk probability of ALI., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Microplastics (MPs) and okadaic acid (OA) are known to coexist in marine organisms, potentially impacting humans through food chain. However, the combined toxicity of OA and MPs remains unknown. In this study, mice were orally administered OA at 200 μg/kg bw and MPs at 2 mg/kg bw. The co-exposure group showed a significant increase in malondialdehyde (MDA) content and significant decreases in superoxide dismutase (SOD) activity and glutathione (GSH) level compared to the control, MPs and OA groups (p < 0.05). Additionally, the co-exposure group exhibited significantly higher levels of IL-1β and IL-18 compared to other groups (p < 0.05). These results demonstrated that co-exposure to MPs and OA induces oxidative stress and exacerbates inflammation. Histological and cellular ultrastructure analyses suggested that this combined exposure may enhance gut damage and compromise barrier integrity. Consequently, the concentration of OA in the small intestine of the co-exposure group was significantly higher than that in the OA group. Furthermore, MPs were observed in the lamina propria of the gut in the co-exposure group. Transcriptomic analysis revealed that the co-exposure led to increased expression of certain genes related to the NF-κB/NLRP3 pathway compared to the OA and MPs groups. Overall, this combined exposure may disrupt the intestinal barrier, and promote inflammation through the NF-κB/NLRP3 pathway. These findings provide precious information for the understanding of health risks associated with MPs and phycotoxins., Competing Interests: Declaration of Competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the infiltration characteristics of tumour-associated macrophages (TAMs) in buccal mucosa carcinoma (BMC) and the correlation of these features with clinicopathological factors., Materials and Methods: Immunohistochemistry was used to detect the expression of TAM-related markers (CD68, CD163, CD206), CD8+ T cell markers, PD-L1, and epidermal growth factor receptor (EGFR) in 46 patients with mucosal cancer after radical surgery. In addition, the correlation between TAM infiltration and clinical characteristics, PD-L1 expression, and EGFR expression was analysed., Results: A high infiltration level of M2-polarized (CD206+) TAMs and M2-polarized (CD163+) TAMs was more common in stage T3-T4, N+, III-IV patients than in other patient groups (P < 0.05). The infiltration degree of M2-polarized (CD68+) TAMs was positively correlated with the PD-L1 TPS (P = 0.0331). The infiltration level of M2-polarized (CD206+) TAMs was higher in the EGFR high expression group than in the EGFR low expression group (P = 0.040)., Conclusion: High infiltration of M2-polarized TAMs is highly associated with advanced disease stage and higher expression of PD-L1 and EGFR in BMCs, suggesting that M2-polarized TAMs infiltration can serve as a potential therapeutic target., (© 2024. The Author(s).)

The rise of two-dimensional (2D) materials has provided a confined geometry and yielded methods for guiding electrons at the nanoscale level. 2D material-enabled electronic devices can interact and transduce the subtle charge perturbation and permit significant advancement in molecule discrimination technology with high accuracy, sensitivity, and specificity, leaving a significant impact on disease diagnosis and health monitoring. However, high-performance biosensors with scalable fabrication ability and simple protocols have yet to be fully realized due to the challenges in wafer-scale 2D film synthesis and integration with electronics. Here, we propose a molybdenum oxide (MoO x )-interdigitated electrode (IDE)-based label-free biosensing chip, which stands out for its wafer-scale dimension, tunability, ease of integration and compatibility with the complementary metal-oxide-semiconductor (CMOS) fabrication. The device surface is biofunctionalized with monoclonal anti-carcinoembryonic antigen antibodies (anti-CEA) via the linkage agent (3-aminopropyl)triethoxysilane (APTES) for carcinoembryonic antigen (CEA) detection and is characterized step-by-step to reveal the working mechanism. A wide range and real-time response of the CEA concentration from 0.1 to 100 ng mL -1 and a low limit of detection (LOD) of 0.015 ng mL -1 were achieved, meeting the clinical requirements for cancer diagnosis and prognosis in serum. The MoO x -IDE biosensor also demonstrates strong surface affinity towards molecules and high selectivity using L-cysteine (L-Cys), glycine (Gly), glucose (Glu), bovine serum albumin (BSA), and immunoglobulin G (IgG). This study showcases a simple, scalable, and low-cost strategy to create a nanoelectronic biosensing platform to achieve high-performance cancer biomarker discrimination capabilities.

Sepsis is a life-threatening condition that can progress to septic shock as the body's extreme response to pathogenesis damages its own vital organs. Staphylococcus aureus (S. aureus) accounts for 50% of nosocomial infections, which are clinically treated with antibiotics. However, methicillin-resistant strains (MRSA) have emerged and can withstand harsh antibiotic treatment. To address this problem, curcumin (CCM) is employed to prepare carbonized polymer dots (CPDs) through mild pyrolysis. Contrary to curcumin, the as-formed CCM-CPDs are highly biocompatible and soluble in aqueous solution. Most importantly, the CCM-CPDs induce the release of neutrophil extracellular traps (NETs) from the neutrophils, which entrap and eliminate microbes. In an MRSA-induced septic mouse model, it is observed that CCM-CPDs efficiently suppress bacterial colonization. Moreover, the intrinsic antioxidative, anti-inflammatory, and anticoagulation activities resulting from the preserved functional groups of the precursor molecule on the CCM-CPDs prevent progression to severe sepsis. As a result, infected mice treated with CCM-CPDs show a significant decrease in mortality even through oral administration. Histological staining indicates negligible organ damage in the MRSA-infected mice treated with CCM-CPDs. It is believed that the in vivo studies presented herein demonstrate that multifunctional therapeutic CPDs hold great potential against life-threatening infectious diseases., (© 2024 Wiley‐VCH GmbH.)

Background: Most tail-anchored (TA) membrane proteins are delivered to the endoplasmic reticulum through a conserved posttranslational pathway. Although core mechanisms underlying the targeting and insertion of TA proteins are well established in eukaryotes, their role in mediating TA protein biogenesis in plants remains unclear. We reported the crystal structures of algal arsenite transporter 1 (ArsA1), which possesses an approximately 80-kDa monomeric architecture and carries chloroplast-localized TA proteins. However, the mechanistic basis of ArsA2, a Get3 (guided entry of TA proteins 3) homolog in plants, for TA recognition remains unknown., Results: Here, for the first time, we present the crystal structures of the diatom Pt-Get3a that forms a distinct ellipsoid-shaped tetramer in the open (nucleotide-bound) state through crystal packing. Pulldown assay results revealed that only tetrameric Pt-Get3a can bind to TA proteins. The lack of the conserved zinc-coordination CXXC motif in Pt-Get3a potentially leads to the spontaneous formation of a distinct parallelogram-shaped dimeric conformation in solution, suggesting a new dimer state for subsequent tetramerization upon TA targeting. Pt-Get3a nonspecifically binds to different subsets of TA substrates due to the lower hydrophobicity of its α-helical subdomain, which is implicated in TA recognition., Conclusions: Our study provides new insights into the mechanisms underlying TA protein shielding by tetrameric Get3 during targeting to the diatom's cell membrane., (© 2024. The Author(s).)

Quercetin, a flavonoid abundantly found in onions, fruits, and vegetables, is recognized for its pharmacological potential, especially for its anticoagulant properties that work by inhibiting thrombin and coagulation factor Xa. However, its clinical application is limited due to poor water solubility and bioavailability. To address these limitations, we engineered carbonized nanogels derived from quercetin (CNGs Qur ) using controlled pyrolysis and polymerization techniques. This led to substantial improvements in its anticoagulation efficacy, water solubility, and biocompatibility. We generated a range of CNGs Qur by subjecting quercetin to varying pyrolytic temperatures and then assessed their anticoagulation capacities both in vitro and in vivo . Coagulation metrics, including thrombin clotting time (TCT), activated partial thromboplastin time (aPTT), and prothrombin time (PT), along with a rat tail bleeding assay, were utilized to gauge the efficacy. CNGs Qur showed a pronounced extension of coagulation time compared to uncarbonized quercetin. Specifically, CNGs Qur synthesized at 270 °C (CNGs Qur270 ) exhibited the most significant enhancement in TCT, with a binding affinity to thrombin exceeding 400 times that of quercetin. Moreover, variants synthesized at 310 °C (CNGs Qur310 ) and 290 °C (CNGs Qur290 ) showed the most substantial delays in PT and aPTT, respectively. Our findings indicate that the degree of carbonization significantly influences the transformation of quercetin into various CNGs Qur forms, each affecting distinct coagulation pathways. Additionally, both intravenous and oral administrations of CNGs Qur were found to extend rat tail bleeding times by up to fivefold. Our studies also demonstrate that CNGs Qur270 effectively delays and even prevents FeCl 3 -induced vascular occlusion in a dose-dependent manner in mice. Thus, controlled pyrolysis offers an innovative approach for generating quercetin-derived CNGs with enhanced anticoagulation properties and water solubility, revealing the potential for synthesizing self-functional carbonized nanomaterials from other flavonoids for diverse biomedical applications.

Background: Peripheral platelet-white blood cell ratio (PWR) integrating systemic inflammatory and coagulopathic pathways is a key residual inflammatory measurement in the management of acute DeBakey type I aortic dissection (AAD); however, trajectories of PWR in AAD is poorly defined., Methods: Two AAD cohorts were included in two cardiovascular centers (2020-2022) if patients underwent emergency total arch replacement with frozen elephant trunk implantation. PWR data were collected over time at baseline and five consecutive days after surgery. Trajectory patterns of PWR were determined using the latent class mixed modelling (LCMM). Cox regression was used to determine independent risk factors. By adding PWR Trajectory, a user-friendly nomogram was developed for predicting mortality after surgery., Results: Two hundred forty-six patients with AAD were included with a median follow-up of 26 (IRQ 20-37) months. Three trajectories of PWR were identified [cluster α 45(18.3%), β105 (42.7%), and γ 96 (39.0%)]. Cluster γ was associated with higher risk of mortality at follow-up (crude HR, 3.763; 95% CI: 1.126-12.574; P =0.031) than cluster α. By the addition of PWR trajectories, an inflammatory nomogram, composed of age, hemoglobin, estimated glomerular filtration rate, and cardiopulmonary time was developed and internally validated, with adequate discrimination [the area under the receiver-operating characteristic curve 0.765, 95% CI: 0.660-0.869)], calibration, and clinical utility., Conclusion: Based on PWR trajectories, three distinct clusters were identified with short-term outcomes, and longitudinal residual inflammatory shed some light to individualize treatment strategies for AAD., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children., Methods: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored., Results: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924-0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010-1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation., Conclusions: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. Supplementary file 2 (MP4 18937 KB)., (© 2023. The Author(s).)

Background: It remains unclear whether conservative oxygen therapy (COT) or liberal oxygen therapy (LOT) is more beneficial to the clinical outcomes of intensive care unit (ICU) patients. We systematically reviewed the efficacy and safety of conservative versus liberal oxygen therapy for ICU patients., Methods: We systematically searched PubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, MedRxiv, and BioRxiv for reports on randomized controlled trials (RCTs) that compared the effects of COT versus LOT on the clinical outcomes of ICU patients published in English before April 2024. The primary outcome was the mortality rate, secondary outcomes included ICU and hospital length of stay, days free from mechanical ventilation support (MVF), vasopressor-free time (VFT), and adverse events., Results: In all, 13 RCTs involving 10,632 patients were included in analyses. Meta-analysis showed COT did not reduce mortality at 30-day (risk ratio [RR] = 1.01, 95% confidence interval [CI] 0.94 to 1.09, I 2  = 42%, P = 0.78), 90-day (RR = 1.01, 95% CI 0.95 to 1.08, I 2  = 9%, P = 0.69), or longest follow-up (RR = 1.00, 95% CI 0.95 to 1.06, I 2  = 22%, P = 0.95) compared to LOT in ICU patients. In subgroup analyses, no significant difference was observed between the two groups in terms of the different ICU, baseline P/F, and actual PaO 2 . In addition, COT did not affect ICU length of stay, hospital length of stay, or VFT, it only affected MVF days., Conclusions: COT did not reduce all-cause mortality in ICU patients. Further RCTs are urgently needed to confirm the impact of COT strategy on specific populations., (© 2024. The Author(s).)

Objectives: This study aimed to analyze the influencing factors of hospitalization cost of hypertensive patients in TCM (traditional Chinese medicine, TCM) hospitals, which can provide a scientific basis for hospitals to control the hospitalization cost of hypertension., Methods: In this study, 3,595 hospitalized patients with a primary diagnosis of tertiary hypertension in Tianshui City Hospital of TCM, Gansu Province, China, from January 2017 to June 2022, were used as research subjects. Using univariate analysis to identify the relevant variables of hospitalization cost, followed by incorporating the statistically significant variables of univariate analysis as independent variables in multiple linear regression analysis, and establishing the path model based on the results of the multiple linear regression finally, to explore the factors influencing hospitalization cost comprehensively., Results: The results showed that hospitalization cost of hypertension patients were mainly influenced by length of stay, age, admission pathways, payment methods of medical insurance, and visit times, with length of stay being the most critical factor., Conclusion: The Chinese government should actively exert the characteristics and advantages of TCM in the treatment of chronic diseases such as hypertension, consistently optimize the treatment plans of TCM, effectively reduce the length of stay and steadily improve the health literacy level of patients, to alleviate the illnesses pain and reduce the economic burden of patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hou, Cong, Cai, Ba, Chen, Yang and Luo.)

Objectives: The diameter, area, and volume of the true lumen and false lumen (FL) have been measured in previous studies to evaluate the extent of DeBakey type I aortic dissection. However, these indicators have limitations because of the irregular shapes of the true and false lumens and the constant oscillation of intimal flap during systole and diastole. The ratio of arch lengths seems to be a more reliable indicator. FL% was defined as the ratio of the arch length of FL to the circumference of the aorta at the different levels of the aorta. The purpose of this article was to investigate whether FL% is a predictor of the severity of acute DeBakey type I aortic dissection in patients undergoing frozen elephant trunk (FET) and total arch replacement., Methods: In this retrospective observational study, we analyzed a total of 344 patients with acute DeBakey type I aortic dissection that underwent FET and total arch replacement at our center from October 2015 to October 2019. The patients were divided into two groups by cluster analysis according to the perioperative course. Binary logistic regression analyses were performed to determine whether FL% could predict the severity of acute DeBakey type I aortic dissection. The area under the receiver operating characteristic curve (AUROC) was used to assess the power of the multivariate logistic regression model for the severity of acute DeBakey type I aortic dissection., Results: The patients in the ultra-high-risk group (109 patients) had significantly more severe clinical comorbidities and complications than the patients in the high-risk group (235 patients). The ascending aortic FL% [odds ratio (OR), 11.929 (95% CI: 1.421-100.11); P  = 0.022], location of initial tear [OR, 0.68 (95% CI: 0.47-0.98); P  = 0.041], the degree of left iliac artery involvement [OR, 1.95 (95% CI: 1.15-3.30); P  = 0.013], and the degree of right coronary artery involvement [OR, 1.46 (95% CI: 1.01-2.12); P  = 0.045] on preoperative computed tomography angiography were associated with the severity of acute DeBakey type I aortic dissection. The AUROC value of this multivariate logistic regression analysis was 0.940 (95% CI: 0.914-0.967; P  < 0.001). The AUROC value of ascending aortic FL% was 0.841 (95% CI: 0.798-0.884; P  < 0.001) for the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement., Conclusions: Ascending aortic FL% was validated as an essential radiologic index for assessing the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Higher values of ascending aortic FL% were more severe., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Wang, Li, Jin, Li, Zhang, Gong, Zhang, Liu and Lai.)

Compact efficient high-power continuous-wave Nd:YVO 4 Raman lasers for selectable wavelengths within 559-603 nm are achieved by using KGW crystal for intracavity stimulated Raman scattering (SRS) and lithium triborate (LBO) crystal for intracavity sum frequency generation (SFG) and second harmonic generation (SHG). The LBO crystal with the cut angle in the XY plane for the type-I phase matching is used to perform intracavity SHG or SFG. Experimental results reveal that the participated Stokes lines include the internal vibration mode at 901 cm -1 , the external vibrational mode at 209 cm -1 , and the combination mode of the 901 cm -1 and 209 cm -1 Raman shifts. By tuning LBO temperature for attaining the maximum output power, the output spectrum reveals the triple peaks of 588.7, 595.7, and 603.1 nm with the intensity ratio of 10:4:1. Under this circumstance, the output power can reach the highest value of 10.8 W at a pump power of 40 W. Furthermore, the output spectrum can be simply concentrated on the single peaks among 588.7 (orange), 565.7 (yellow), and 559.1 nm (lime) by tuning LBO temperature to fulfill the selection of the critical phase matching. The output powers at a pump power of 40 W can be up to 8.0, 6.1, and 9.8 W for the single-peak emission at 588.7, 565.7, and 559.1 nm, respectively. Finally, a dual-peak emission of 565.7 and 572.3 nm with total output power of 5.2 W can be generated by tuning LBO temperature to match the SFG for 572.3 nm.

High-power efficient continuous-wave Nd:YVO 4 /KGW Raman lasers at 555 and 559 nm are achieved by using a double-sided dichroic coating output coupler to improve the resonance quality factor. The Np-cut potassium gadolinium tungstate (KGW) is used to generate the Stokes waves at 1159 and 1177 nm by placing the polarization of the1064 nm fundamental wave parallel to the Ng and Nm axes, respectively. The lithium triborate (LBO) crystal with the cut angle in the XY plane for the type-I phase matching is used to perform the intracavity sum frequency generation for yielding the green light at 555 nm and the lime light at 559 nm at the optimal phase matching temperature. Experimental results were systematically accomplished to comprehend the optimal cavity length for the conversion efficiency. Under the optimal cavity length, the output powers can reach 6.6 and 6.3 W at a pump power of 22 W for the wavelengths of 555 and 559 nm, respectively. The conversion efficiencies can be up to 30% and 28.6% for 555 and 559 nm, respectively.

Background: Acute DeBakey type I aortic dissection is associated with high morbidity and mortality. Little is known regarding the role of leukocyte trajectory in prognosis., Methods: We included adult acute DeBakey type I aortic dissection patients with emergency frozen elephant trunk and total arch replacement in 2 cardiovascular centers (2020-2022). We used latent class mixed model to group patients according to their leukocyte patterns from hospital admission to the first 5 days after surgery. We investigated the association of leukocyte trajectory and 30-day and latest follow-up mortality (October 31, 2023), exploratorily analyzing the effects of ulinastatin treatment on outcome., Results: Of 255 patients included, 3 distinct leukocyte trajectories were identified: 196 in group I (decreasing trajectory), 34 in group II (stable trajectory), and 25 in group III (rising trajectory). Overall, 30-day mortality was 25 (9.8%), ranging from 8.2% (16/196) in group I, 8.8% (3/34) in group II, to 24.0% (6/25) in group III ( P for trend = .036). Group III was associated with higher mortality both at 30 days (adjusted hazard ratio, 3.260; 95% CI, 1.071-9.919; P = .037) and at the last follow-up (adjusted hazard ratio, 2.840; 95% CI, 1.098-7.345; P = .031) compared with group I., Conclusions: Distinct and clinically relevant groups can be identified by analyzing leukocyte trajectories, and a rising trajectory was associated with higher short-term and midterm mortality., (© 2024 The Author(s).)

Purine nucleoside ester is one of the derivatives of purine nucleoside, which has antiviral and anticancer activities. In this work, a continuous flow synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus was successfully achieved. Various parameters including solvent, reaction temperature, reaction time/flow rate and substrate ratio were investigated. The best yields were obtained with a continuous flow microreactor for 35 min at 50 °C with the substrate ratio of 1 : 5 (nucleosides to vinyl esters) in the solvent of tert -amyl alcohol. 12 products were efficiently synthesized with yields of 78-93%. Here we reported for the first time the use of lipase TL IM from Thermomyces lanuginosus in the synthesis of purine nucleoside esters. The significant advantages of this methodology are a green solvent and mild conditions, a simple work-up procedure and the highly reusable biocatalyst. This research provides a new technique for rapid synthesis of anticancer and antiviral nucleoside drugs and is helpful for further screening of drug activity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Mythimna separata (Lepidoptera: Noctuidae) is an omnivorous pest that poses a great threat to food security. Insect antimicrobial peptides (AMPs) are small peptides that are important effector molecules of innate immunity. Here, we investigated the role of the AMP cecropin B in the growth, development, and immunity of M. separata . The gene encoding M. separata cecropin B ( MscecropinB ) was cloned. The expression of MscecropinB was determined in different developmental stages and tissues of M. separata . It was highest in the prepupal stage, followed by the pupal stage. Among larval stages, the highest expression was observed in the fourth instar. Tissue expression analysis of fourth instar larvae showed that MscecropinB was highly expressed in the fat body and haemolymph. An increase in population density led to upregulation of MscecropinB expression. MscecropinB expression was also upregulated by the infection of third and fourth instar M. separata with Beauveria bassiana or Bacillus thuringiensis ( Bt ). RNA interference (RNAi) targeting MscecropinB inhibited the emergence rate and fecundity of M. separata , and resulted in an increased sensitivity to B. bassiana and Bt . The mortality of M. separata larvae was significantly higher in pathogen plus RNAi-treated M. separata than in controls treated with pathogens only. Our findings indicate that MscecropinB functions in the eclosion and fecundity of M. separata and plays an important role in resistance to infection by B. bassiana and Bt .

Photoperiod is an important environmental factor that influences seasonal reproduction behavior in birds. Birds translate photoperiodic information into neuroendocrine signals through deep brain photoreceptors (DBPs). OPN5 has been considered candidate DBPs involved in regulating seasonal reproduction in birds. We found that OPN5 could mediate light to regulate the follicle development in ducks. In this study, we further verified the effect of OPN5 on follicular development in Shan Partridge ducks by immunizing against the extracellular domain (ECD) of OPN5. We investigated the specific regulatory mechanism of photoperiod mediated by OPN5 on the reproductive activity of ducks. The trial randomly divided 120 Shan Partridge ducks into 3 groups with different treatments: the immunization of OPN5 group was done at d0, d15, d30, and d40 with 1 mL of vaccine containing OPN5 protein (thus containing 1, 1, 0.5, and 0.5 mg of OPN5-KLH protein), and the control group (CS and CL groups) was injected at the same time with the same dose of OPN5-uncontained blank vaccine. The group of CS (900 lux), OPN5 (600 lux), and CL (600 lux) lasted for 40 d in 12 L:12 D photoperiods, respectively. Then, the groups of CS, OPN5, and CL subsequently received 12 L:12 D, 12 L:12 D, and 17 L:7 D light treatments for 33 d, respectively. The ducks were caged in 3 constant rooms with the same feeding conditions for each group, free water, and limited feeding (150 g per duck each day). Duck serum and tissue samples were collected at d 40, d 62, and d 73 (n = 12). It was found that before prolonged light, the group of immunization (group OPN5) and the group of strong light intensity (group CS) were higher than the group of CL in egg production. Subsequent to prolonged light, the group CL in egg production rose about the same as the group immunization, while the strong light group (group CS) was lower. Group OPN5 increased the ovarian index of ducks, and both the immunization of group OPN5 and group CL (extended light) increased the thickness of the granular layer and promoted the secretion of E2, P4, LH, and PRL hormones. Compared with group CS, group CL and OPN5 increased the mRNA level and protein expression of OPN5 in the hypothalamus on d 62 and d 73 (P < 0.05). The gene or protein expression patterns of GnRH, TRH, TSHβ, DIO2, THRβ, VIP, and PRL were positively correlated with OPN5, whereas the gene expression patterns of GnIH and DIO3 were negatively correlated with OPN5. The results showed that immunization against OPN5 could activate the corresponding transmembrane receptors to promote the expression of OPN5, up-regulate the expression of TSHβ and DIO2, and then regulate the HPG axis-related genes to facilitate the follicular development of Shan Partridge ducks. In addition, in this experiment, prolonging the photoperiod or enhancing the light intensity could also enhance follicle development, but the effect was not as significant as immunizing against OPN5. Our results will offer beneficial data and more supportive shreds of evidence in favor of elucidating the role of OPN5 in relation to photoperiods and reproduction., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Observational studies have suggested an association between endometriosis and glycemic traits, but causality remains unclear. We used bidirectional and multivariate Mendelian randomization (MR) to examine the causal effect of glycemic traits on endometriosis and vice versa., Methods: We obtained genome-wide association studies summary data of endometriosis and glycemic traits in our study. Inverse variance weighted (IVW), Weighted median, MR-Egger and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) were applied in bidirectional two-sample MR analyses. MVMR was implemented to estimate the causal effect for fasting insulin (FI), fasting glucose (FG), and glycosylated hemoglobin A1c (HbA1c) on endometriosis. To test the validity of our findings, a number of sensitivity analyses were conducted., Results: The risk of endometriosis was significantly increased by genetically predicted T1DM (OR = 1.02, 95% CI 1.00-1.04, p = 0.0171, q = 0.0556) and GDM (OR = 1.01, 95% CI 1.01-1.02, p = 1.34 × 10 - 8 , q = 1.74 × 10 - 7 ). Endometriosis had a suggestive association with HbA1c (Beta = 0.04, 95% CI 0.00-0.08, p = 0.0481, q = 0.1251). Using multivariate Mendelian randomization (MVMR), a significant causal effect of FI on genetically predicted endometriosis was found (OR = 2.18, 95% CI 1.16-4.09, p = 0.0154, q = 0.0547). Moreover, no causal associations between endometriosis and other glycemic traits were detected., Conclusion: Our findings supported the significant causal associations of T1DM, GDM and FI with endometriosis, respectively. Additionally, a suggestive association was found of endometriosis on HbA1c. Importantly, our study may shed light on etiology studies and clinical management of endometriosis., (© 2024. The Author(s).)

Diatoms, efficient carbon capture organisms, contribute to 20% of global carbon fixation and 40% of ocean primary productivity, garnering significant attention to their growth. Despite their significance, the synthesis mechanism of polyamines (PAs), especially spermidine (Spd), which are crucial for growth in various organisms, remains unexplored in diatoms. This study reveals the vital role of Spd, synthesized through the spermidine synthase (SDS)-based pathway, in the growth of the diatom Phaeodactylum tricornutum . PtSDS1 and PtSDS2 in the P. tricornutum genome were confirmed as SDS enzymes through enzyme-substrate selectivity assays. Their distinct activities are governed primarily by the Y79 active site. Overexpression of a singular gene revealed that PtSDS1, PtSDS2, and PtSAMDC from the SDS-based synthesis pathway are all situated in the cytoplasm, with no significant impact on PA content or diatom growth. Co-overexpression of PtSDS1 and PtSAMDC proved essential for elevating Spd levels, indicating multifactorial regulation. Elevated Spd content promotes diatom growth, providing a foundation for exploring PA functions and regulation in diatoms.

Background: There is controversy regarding sex differences in short-term mortality in acute type A aortic dissection (ATAAD)., Objectives: This study aimed to investigate the impact of sex differences on 30-day operative mortality after ATAAD surgery and to determine if other covariates modify the association., Methods: Consecutive patients (N = 5670) with surgically repaired ATAAD were identified from the multicenter China 5A study. The primary outcome was operative mortality. The age dependency was modeled using a cubic spline curve., Results: There were 1,503 females (26.5%) and 4,167 males (73.5%). Females were older and had a lower percentage of comorbidities compared with males. Females had higher mortality compared to males (10.2% vs 8.2%, P  = 0.019); however, there was no difference after propensity analyses (adjusted OR: 1.334 [95% CI: 0.918-1.938]). There was an interaction with sex and age ( P interaction  = 0.035): older age was associated with higher odds of operative mortality among females (OR: 1.045 [95% CI: 1.029-1.061]) compared with males (OR: 1.025 [95% CI: 1.016-1.035]). The risk of mortality for males and females appears to diverge at 55 years of age ( P interaction  = 0.019): females under 55 years of age had similar odds to males (OR: 0.852 [95% CI: 0.603-1.205]) but higher odds when over 55 years (OR: 1.420 [95% CI: 1.096-1.839]) compared to males., Conclusions: Under the age of 55 years, females have similar odds of operative mortality compared with males; however, over the age of 55 years females have higher odds than males. Understanding differences in risk allows for individualized treatment strategies. (Additive Anti-inflammatory Action for Aortopathy & Arteriopathy; NCT04398992)., Competing Interests: This work was supported in part by the Scientific Research Common Program of 10.13039/501100002888Beijing Municipal Commission of Education (KM202110025014), 10.13039/501100009592Beijing Municipal Science and Technology Commission (Z211100002921010), and Jiangsu Province Capability Improvement Project through Science, Technology, and Education (ZDXK202230). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Photocatalysis driven by plasmon-induced hot carriers has been gaining increasing attention. Recent studies have demonstrated that plasmon-induced hot carriers can directly participate in photocatalytic reactions, leading to great enhancement in solar energy conversion efficiency, by improving the catalytic activity or changing selectivity. Nevertheless, the utilization efficiency of hot carriers remains unsatisfactory. Therefore, how to correctly understand the generation and transfer process of hot carriers, as well as accurately differentiate between the possible mechanisms, have become a key point of attention. In this review, we overview the fundamental processes and mechanisms underlying hot carrier generation and transport, followed by highlighting the importance of hot carrier monitoring methods and related photocatalytic reactions. Furthermore, possible strategies for the further characterization of plasmon-induced hot carriers and boosting their utilization efficiency have been proposed. We hope that a comprehensive understanding of the fundamental behaviors of hot carriers can aid in designing more efficient photocatalysts for plasmon-induced photocatalytic reactions.

Pollution variation, source characteristics, and meteorological effects of water-soluble inorganic ions (WSIIs) in PM 2.5 were analyzed in Xinxiang city, Henan Province. PM 2.5 samples and their chemical components were monitored online by using URG-9000 in four seasons:winter (January, 2022), spring (April, 2022), summer (July, 2022), and fall (October, 2022). The results showed that the TWSIIs had the same seasonal fluctuations as PM 2.5 . The average seasonal concentrations of WSIIs ranged from 19.62-72.15 μg·m -3 , accounting for more than 60% of PM 2.5 , demonstrating that WSIIs were the major components of PM 2.5 . The annual concentration value of NO 3 - /SO 4 2- was 2.11, which showed an increasing trend, suggesting predominantly mobile sources for secondary inorganic aerosols (SNA). Further, the molar concentration value [NH 4 + ]/[NO 3 - ] was 1.95, demonstrating that agriculture emissions were the dominant contributors to atmospheric nitrogen. Furthermore, the backward trajectory analysis showed that the concentrations of Ca 2+ and Mg 2+ were higher when the northeasterly wind prevailed and the wind speed was high. High values of SOR and NOR were correlated with low temperatures and high relative humidity ( T < 8℃, RH > 60%), demonstrating that more gaseous precursors were converted into sulfate and nitrate. At high temperatures ( T > 24℃), there was no apparent high NOR value like that for SOR, mainly due to the decomposition of NH 4 NO 3 at high temperatures. Finally, backward trajectories associated with the PMF-resolved results were used to explore the regional transport characteristics. The results illustrated that dust sources in the study areas were mainly influenced by air trajectories originating from the northwest regions, whereas secondary sulfate, secondary nitrate, and biomass sources contributed more to WSIIs when wind speed and altitude air masses were low in the area surrounding the observation site.

Two-dimensional ferromagnetic materials with intrinsic half-metallic properties have strong application advantages in nanoscale spintronics. Herein, density functional theory calculations show that monolayer ScCl is a ferromagnetic metallic material when undoped ( n = 0), and the transition from metal to half-metal occurs with the continuous doping of holes. On the contrary, as the concentration of doped electrons increases, the system will exhibit metallic characteristics, which is particularly evident from a variation in spin polarizability. Furthermore, we have discussed how doped carriers affect the shape of the Fermi surface and the Fermi velocity of electrons. Most importantly, Monte Carlo simulations show that the ScCl monolayer is particularly regulated by carrier concentration ( n ) and magnetic field ( h ). Additionally, trends in energy and magnetic exchange coupling in different magnetic configuratio n s (AFM phase and FM phase) with different doping concentrations are presented. When n < -0.16, the material is not only a half-metallic material that easily flips the magnetic axis, but also proves to be a candidate ferromagnetic material that works stably at room temperature in terms of dynamic stability. In addition, the origin of magnetocrystalline anisotropy is analyzed, and the contribution of different orbitals to spin-orbit coupling is presented. Moreover, we note that when magnetic field is small ( h < 1 T), the change in size has a significant effect on ferromagnetic phase transition. However, when the system size is large (size >15 nm), T C is less sensitive to magnetic field. In addition, hole doping and size effect will greatly affect the hC of the system, but when the hole doping exceeds the critical value ( n = -0.16), its influence on the hysteresis loop is no longer obvious. These interesting magnetic phenomena and easily adjustable physical properties show us that monolayer ScCl will be a promising functional material.

Puerarin (Pue) is a naturally bioactive compound with many potential functions in regulating blood glucose and lipid metabolism. However, the low bioavailability and rapid elimination in vivo limit the application of Pue in diabetic treatment. Here, we developed a metal-polyphenol-functionalized microgel to effectively deliver Pue in vivo and eventually alleviate the onset of diabetes. Pue was initially encapsulated in alginate beads through electrospray technology, and further immersed in Fe 3+ and tannic acid solution from tannic acid (TA)-iron (Fe) coatings (TF). These constructed Pue@SA-TF microgels exhibited uniform spheres with an average size of 367.89 ± 18.74 µm and high encapsulation efficiency of Pue with 61.16 ± 1.39%. In vivo experiments proved that compared with free Pue and microgels without TF coatings, the biological distribution of Pue@SA-TF microgels specifically accumulated in the small intestine, prolonged the retention time of Pue, and achieved a high effectiveness in vivo. Anti-diabetic experimental results showed that Pue@SA-TF microgels significantly improved the levels of blood glucose, blood lipid, and oxidative stress in diabetic mice. Meanwhile, histopathological observations indicated that Pue@SA-TF microgels could significantly alleviate the damage to the liver, kidney, and pancreas in diabetic mice. Our study provided an effective strategy for oral delivery of Pue and achieved high anti-diabetic efficacy., (© 2023. Controlled Release Society.)

Few-shot learning (FSL) aims to generate a classifier using limited labeled examples. Many existing works take the meta-learning approach, constructing a few-shot learner (a meta-model) that can learn from few-shot examples to generate a classifier. Typically, the few-shot learner is constructed or meta-trained by sampling multiple few-shot tasks in turn and optimizing the few-shot learner's performance in generating classifiers for those tasks. The performance is measured by how well the resulting classifiers classify the test (i.e., query) examples of those tasks. In this paper, we point out two potential weaknesses of this approach. First, the sampled query examples may not provide sufficient supervision for meta-training the few-shot learner. Second, the effectiveness of meta-learning diminishes sharply with the increasing number of shots (i.e., the number of training examples per class). To resolve these issues, we propose a novel meta-training objective for the few-shot learner, which is to encourage the few-shot learner to generate classifiers that perform like strong classifiers. Concretely, we associate each sampled few-shot task with a strong classifier, which is trained with ample labeled examples. The strong classifiers can be seen as the target classifiers that we hope the few-shot learner to generate given few-shot examples, and we use the strong classifiers to supervise the few-shot learner. We present an efficient way to construct the strong classifier, making our proposed objective an easily plug-and-play term to existing meta-learning based FSL methods. We validate our approach, (Learning with A Strong Teacher for few-SHOT learning), in combinations with many representative meta-learning methods. On several benchmark datasets including miniImageNet and tieredImageNet, our approach leads to a notable improvement across a variety of tasks. More importantly, with our approach, meta-learning based FSL methods can consistently outperform non-meta-learning based methods at different numbers of shots, even in many-shot settings, greatly strengthening their applicability.

Background: Acute aortic syndrome (AAS) is a life-threatening condition. Inflammation plays a key role in the pathogenesis, development and progression of AAS, and is associated with significant mortality and morbidity. Understanding the inflammatory responses and inflammation resolutions is essential for an appropriate management of AAS., Method: Thirty Chinese cardiovascular centers have collaborated to create a multicenter observational registry (named Chinese Additive Anti-inflammatory Action for Aortopathy & Arteriopathy [5A] registry), with consecutive enrollment of adult patients who underwent surgery for AAS that was started on Jan 1, 2016 and will be ended on December 31, 2040. Specially, the impact of inflammation and anti-inflammatory strategies on the early and late adverse events are investigated. Primary outcomes are severe systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), Sequential Organ Failure Assessment (SOFA) scores at 7 days following this current surgery. Secondary outcomes are SISR, 30-day mortality, operative mortality, hospital mortality, new-onset stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit., Discussion: The analysis of this multicenter registry will allow our better knowledge of the prognostic importance of preoperative inflammation and different anti-inflammatory strategies in adverse events after surgery for AAS. This registry is expected to provide insights into novel different inflammatory resolutions in management of AAS beyond conventional surgical repair., Trial Registration: ClinicalTrials.gov Identifier: NCT04398992 (Initial Release: 05/19/2020)., (© 2024. The Author(s).)

During breast cancer progression, there is typically increased collagen deposition resulting in elevated extracellular matrix rigidity. This results in changes to cell-matrix adhesion and cell migration, impacting processes such as the epithelial-mesenchymal transition (EMT) and metastasis. We aim to investigate the roles of cell-matrix adhesion and cell migration on breast tumor growth and progression by studying the impacts of different types of extracellular matrices and their rigidities. We embedded MCF7 spheroids within three-dimensional (3D) collagen matrices and agarose matrices. MCF7 cells adhere to collagen but not agarose. Contrasting the results between these two matrices allows us to infer the role of cell-matrix adhesion. We found that MCF7 spheroids exhibited the fastest growth rate when embedded in a collagen matrix with a rigidity of 5.1 kPa (0.5 mg/mL collagen), whereas, for the agarose matrix, the rigidity for the fastest growth rate is 15 kPa (1.0% agarose) instead. This discrepancy is attributable to the presence of cell adhesion molecules in the collagen matrix, which initiates collagen matrix remodeling and facilitates cell migration from the tumor through the EMT. As breast tumors do not adhere to agarose matrices, it is suitable to simulate the cell-cell interactions during the early stage of breast tumor growth. We conducted further analysis to characterize the stresses exerted by the expanding spheroid on the agarose matrix. We identified two distinct MCF7 cell populations, namely, those that are non-dividing and those that are dividing, which exerted low and high expansion stresses on the agarose matrix, respectively. We confirmed this using Western blot which showed the upregulation of proliferating cell nuclear antigen, a proliferation marker, in spheroids grown in the 1.0% agarose (≈13 kPa). By treating the embedded MCF7 spheroids with an inhibitor or activator of myosin contractility, we showed that the optimum spheroids' growth can be increased or decreased, respectively. This finding suggests that tumor growth in the early stage, where cell-cell interaction is more prominent, is determined by actomyosin tension, which alters cell rounding pressure during cell division. However, when breast tumors begin generating collagen into the surrounding matrix, collagen remodeling triggers EMT to promote cell migration and invasion, ultimately leading to metastasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chong, Yip, Farm, Mahmoud, Zeng and Chiam.)

Recently, carbon quantum dots (CQDs) have become popular because of their simple synthesis and potential applications. Although CQDs have high biocompatibility, their biotoxicity must be verified to reduce the possible risks associated with large-scale application. In this study, the hepatotoxicity of three CQD types, namely diammonium citrate (AC)-based (CQDs-AC), spermidine trihydrochloride (Spd)-based (CQDs-Spd), and AC- and Spd-based CQDs (CQDs-AC/Spd), were evaluated in vivo and in vitro. It was observed in vivo that CQDs-Spd and CQDs-AC/Spd, but not CQDs-AC, caused histopathological damage, including liver steatosis and mild mixed inflammatory cell infiltration; however, reduced liver function was only observed in CQD-Spd-treated mice. The in vitro results revealed that only CQDs-Spd significantly decreased the number of viable HepG2 cells (NADH depletion) and induced oxidative stress (heme oxygenase-1 activation) after 24 h of exposure, which promoted inflammatory factor secretion (NF-κB activation). Additionally, decreasing zonula occludens-2 and α1-antitrypsin protein expression in HepG2 cells suggested that CQD-Spd exposure increases the risk of liver diseases. Our results revealed that CQDs-Spd had greater hepatotoxic potential than CQDs-AC and CQDs-AC/Spd, which might be attributable to their high positive surface charge. Overall, the risk of CQD-induced hepatotoxic risk must be considered when applying positively charged CQDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The shortcomings of plaster in water resistance, air permeability, skin comfort, fixed stability and weight of wearing are still to be solved. 3D printed cast can overcome the above shortcomings. At present, there is a relative lack of data on the clinical application of 3D printed cast, probably due to its complexity, relatively long operating time, and high price. We aimed to compare and evaluate the short-term effectiveness, safety and advantages of 3D printed wrist cast versus polymer orthosis in the treatment of Colles fracture., Methods: Forty patients with Colles fracture in our hospital from June to December 2022 were selected and divided into an observation group (20 patients, treated with instant 3D printed cast) and a control group (20 cases, treated with polymer orthosis). Both groups treated with manual reduction and external fixation. The visual analogue scale (VAS), immobilization effectiveness and satisfaction scores, Disability of the Arm, Shoulder and Hand (DASH) score, complications and imaging data were collected and compared before immobilization and at 2, 6 and 12 weeks after the fracture., Results: VAS at 2 weeks after the fracture was significantly lower in the observation group than in the control group ( P < 0.05). The immobilization effectiveness and satisfaction scores at 6 weeks after the fracture were significantly higher in the observation group than in the control group (all P < 0.05). The DASH scores at 2 and 6 weeks after the fracture were significantly lower in the observation group than in the control group (all P < 0.05). There wasn't rupture of the printed cast or orthosis in both groups. There were 2 cases of skin irritation in the control group, and no skin irritation occurred in the observation group. The palmar tilt angle and ulnar inclination angle at 2 weeks and 12 weeks after the fracture were significantly higher in the observation group than in the control group (all P < 0.05)., Conclusions: Both instant 3D printed cast and polymer orthosis are effective in the treatment of Colles fracture. But instant 3D printed cast is better than polymer orthosis in areas of good clinical and imaging performance, and high patient satisfaction and comfort., (© 2024. The Author(s).)

Background: Early identification of patients at high risk of operative mortality is important for acute type A aortic dissection (TAAD). We aimed to investigate whether patients with distinct risk stratifications respond differently to anti-inflammatory pharmacotherapy., Methods: From 13 cardiovascular hospitals, 3110 surgically repaired TAAD patients were randomly divided into a training set (70%) and a test set (30%) to develop and validate a risk model to predict operative mortality using extreme gradient boosting. Performance was measured by the area under the receiver operating characteristic curve (AUC). Subgroup analyses were performed by risk stratifications (low versus middle-high risk) and anti-inflammatory pharmacotherapy (absence versus presence of ulinastatin use)., Results: A simplified risk model was developed for predicting operative mortality, consisting of the top ten features of importance: platelet-leukocyte ratio, D-dimer, activated partial thromboplastin time, urea nitrogen, glucose, lactate, base excess, hemoglobin, albumin, and creatine kinase-MB, which displayed a superior discrimination ability (AUC: 0.943, 95 % CI 0.928-0.958 and 0.884, 95 % CI 0.836-0.932) in the derivation and validation cohorts, respectively. Ulinastatin use was not associated with decreased risk of operative mortality among each risk stratification, however, ulinastatin use was associated with a shorter mechanical ventilation duration among patients with middle-high risk (defined as risk probability >5.0 %) (β -1.6 h, 95 % CI [-3.1, -0.1] hours; P = 0.048)., Conclusion: This risk model reflecting inflammatory, coagulation, and metabolic pathways achieved acceptable predictive performances of operative mortality following TAAD surgery, which will contribute to individualized anti-inflammatory pharmacotherapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Community-acquired bacterial meningitis (CABM) is the main cause of morbidity and mortality in children. The epidemiology of CABM is regional and highly dynamic. To clarify the diagnostic status and epidemiological characteristics of children with CABM in this region, and pay attention to the disease burden, so as to provide evidence for the prevention and treatment of CABM. By retrospective case analysis, the clinical data of 918 CABM cases in children aged 0-14 years in Zhejiang Province from January, 2019 to December, 2020 were collected. The etiological diagnosis rate of CABM in children was 23.1%, the annual incidence rate 4.42-6.15/100,000, the annual mortality rate 0.06-0.09/100,000,the cure and improvement rate 94.4%, and the case fatality rate 1.4%. The total incidence of neuroimaging abnormalities was 20.6%. The median length of stay for CABM children was 20(16) days, with an average cost of 21,531(24,835) yuan. In addition, the incidence rate was decreased with age. Escherichia coli(E.coli) and group B Streptococcus agalactiae(GBS) were the principal pathogens in CABM infant<3 months(43.3%, 34.1%), and Streptococcus pneumoniae(S. pneumoniae) was the most common pathogen in children ≥ 3 months(33.9%). In conclusion, the annual incidence and mortality of CABM in children aged 0-14 years in Zhejiang Province are at intermediate and low level. The distribution of CABM incidence and pathogen spectrum are different in age; the incidence of abnormal neuroimaging is high; and the economic burden is heavy., (© 2023. The Author(s).)

An increasing number of studies have shown that many nicotinamide derivatives exhibited extensive biological activities, such as anti-inflammatory and antitumor activity. In this paper, a green, concise synthesis of nicotinamide derivatives in sustainable continuous-flow microreactors catalysed by Novozym® 435 from Candida antarctica has been developed. Application of an easily obtainable and reusable lipase in the synthesis of nicotinamide derivatives from methyl nicotinate and amines/benzylamines reacted for 35 min at 50 °C led to high product yields (81.6-88.5%). Environmentally friendly tert -amyl alcohol was applied as a reaction medium. Substantially shorter reaction times as well as a significant increase in the product yield were obtained as compared to the batch process. This innovative approach provides a promising green, efficient and rapid synthesis strategy for pharmaceutical synthesis and further activity research of novel nicotinamide derivatives., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: High-flow nasal cannula (HFNC) and conventional oxygen therapy (COT) are important respiratory support strategies for acute hypoxemic respiratory failure (AHRF) in coronavirus disease 2019 (COVID-19) patients. However, the results are conflicting for the risk of intubation with HFNC as compared to COT., Objectives: We systematically synthesized the outcomes of HFNC relative to COT in COVID-19 patients with AHRF and evaluated these outcomes in relevant subpopulations., Design: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Data Sources and Methods: We searched PubMed, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, medRxiv, BioRxiv, and the Cochrane Central Register of Controlled Trials for randomized controlled trials and observational studies that compared the efficacy of HFNC with COT in patients with COVID-19-related AHRF. Primary outcomes were intubation rate and mortality rate. Secondary outcomes were the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO 2 /FiO 2 ), respiratory rate, hospital length of stay, intensive care unit (ICU) length of stay, and days free from invasive mechanical ventilation., Results: In total, 20 studies with 5732 patients were included. We found a decreased risk of requiring intubation in HFNC compared to COT [odds ratio (OR) = 0.61, 95% confidence interval (CI): 0.46-0.82, p  = 0.0009, I 2  = 75%]. Similarly, we found HFNC was associated with lower risk of intubation rate compared to COT in the subgroup of patients with baseline PaO 2 /FiO 2  < 200 mmHg (OR = 0.69, 95% CI: 0.55-0.86, p  = 0.0007, I 2  = 45%), and who were in ICU settings at enrollment (OR = 0.57, 95% CI: 0.38-0.85, p  = 0.005, I 2  = 80%). HFNC was associated with an improvement of PaO 2 /FiO 2 and respiratory rate compared to COT. The use of HFNC compared to COT did not reduce the mortality rate, days free from invasive mechanical ventilation, hospital length of stay, or ICU length of stay., Conclusion: Compared to COT, HFNC may decrease the need for tracheal intubation in patients with COVID-19-related AHRF, particularly among patients with baseline PaO 2 /FiO 2  < 200 mmHg and those in ICU settings., Trial Registration: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (no. CRD42022339072).

Objective: Cabrol shunt has been introduced for surgical repair of type A aortic dissection (TAAD) without robust evidence supporting its routine preventive use., Methods: Adult patients with TAAD from China 5A study were included if surgically repaired between 2016 and 2022. Primary outcome was operative mortality according to Society of Thoracic Surgeons criterion. Overall, we compared clinical outcomes in patients with and without Cabrol shunt, and subgroup analysis were further examined between Cabrol shunt and outcome among patients with or without root replacement., Results: 3283 patients were finally identified for analysis, with median age of 51 (IQR 41-59) years, 2389 men, and 2201 treated with Cabrol shunt technique. Cabrol shunt-treated patients were more severely ill before surgery than those without Cabrol shunt. Overall, the rate of operative mortality was 6.6% (146/2201 in Cabrol shunt group and 71/1082 in non-Cabrol shunt group), with no association between Cabrol shunt and operative mortality (OR 1.012 (95% CI 0.754 to 1.357); p=0.938). Stratified by root replacement, Cabrol shunt was associated with similar risk of operative mortality either in patients without root replacement (OR 1.054 (0.747 to 1.487); p=0.764) or in patients with root replacement (OR 1.194 (0.563 to 2.536); p=0.644) (P interaction=0.765). Results were similar in multiple sensitivity analysis., Conclusion: Cabrol shunt was not associated with either a greatly lowered or an increased risk of operative mortality, regardless of aortic root replacement. Our study did not support the use of Cabrol shunt as a routine preventive strategy in the treatment of TAAD., Trial Registration Number: NCT04398992., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Purpose: To investigate the value of serum free prostate-specific antigen density (fPSAD) in the diagnosis of prostate cancer (PCa)., Methods: The data of 558 patients who underwent transrectal ultrasound-guided prostate biopsy were retrospectively analyzed. According to the pathological results, the patients were divided into a PCa group and a benign prostatic hyperplasia (BPH) group. Receiver operating characteristic curves were plotted, based on which the sensitivity, specificity, Youden index, concordance, and kappa values of free prostate-specific antigen (fPSA), the free-to-total f/tPSA, prostate-specific antigen density (PSAD), the free-to-total (f/t)/PSAD ratio, and fPSAD were compared. The patients were divided into three groups by PSA levels (PSA < 4 ng/mL, PSA = 4-10 ng/mL, and PSA > 10 ng/mL), into three groups by age (age < 60 year, age = 60-80y, and age > 80 years), and into two groups by prostate volume (PV) (PV ≤ 80 mL and PV > 80 mL) to compare the sensitivity, specificity, and concordance of indicators., Results: tPSA, PSAD, (f/t)/PSAD, and fPSAD had high accuracy in predicting PCa with AUC values of 0.820, 0.900, 0.846, and 0.867. fPSAD showed lower diagnostic sensitivity but significantly higher specificity and concordance for PCa than tPSA, f/tPSA, (f/t)/PSAD, or PSAD. Thus, fPSAD had the highest accuracy in the diagnosis of PCa. In the groups with different PSA, age, and PV stratification, the concordance of fPSAD was significantly higher (88.61%, 90.74%, and 90.38%) than that of other indicators., Conclusion: With the optimal cutoff value of 0.062, fPSAD has a higher diagnostic value for PCa than tPSA, f/tPSA, (f/t)/PSAD, and PSAD, and can well predict the risk of PCa, significantly improve the clinical diagnostic rate of PCa, and reduce unnecessary biopsy., (© 2023. The Author(s).)