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Background: With increased applications of rare earth elements (REEs) across various industries, evaluating the relationship between REEs exposure and potential health effects has become a public concern. In vivo experiments have established that REEs impact renal function. However, relevant epidemiological evidence on this relationship remains scarce. The objective of this study is to examine the impact of exposure to REEs on renal function., Methods: In this cross-sectional study, 1052 participants were recruited from Guangxi, China. We measured urinary concentrations of 12 REEs using an inductively coupled plasma-mass spectrometer (ICP-MS). Multiple linear regression models were developed to explore the relationship between a single REEs exposure and the estimated glomerular filtration rate (eGFR), a marker of renal function. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to examine the combined effects of REE co-exposure on eGFR., Results: In the multiple linear regression analysis, increasing the concentrations of lanthanum (La, β: 8.22, 95% CI: 5.67-10.77), cerium (Ce, β:6.61, 95% CI: 3.80-9.43), praseodymium (Pr, β: 8.46, 95% CI: 5.85-11.07), neodymium (Nd, β:8.75, 95% CI: 6.10-11.41), and dysprosium (Dy, β:7.38, 95% CI: 4.85-9.91) significantly increased the eGFR. In the WQS regression model, the WQS index was significantly associated with eGFR (β: 4.03, 95% CI: 2.46-5.60), with Pr having the strongest correlation with eGFR. Similar results were obtained in the BKMR model. Additionally, interactions between Pr and La, and Pr and Nd were observed., Conclusions: Co-exposure to REEs is positively associated with elevated eGFR. Pr is likely to have the most significant influence on increased eGFRs and this might be exacerbated when interacting with La and Nd. Mixed exposure to low doses of REEs had a protective effect on renal function, which can provide some evidence for the exposure threshold of REEs in the environment., Trial Registration: The study has been approved by the Guangxi Medical University Medical Ethics Committee (#20170206-1), and all participants provided written informed consent., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier GmbH.)

Background: This study aims to quantify the impacts of chilling at the grain filling stage on rice yield and grain quality. A factorial experiment with four levels of temperature and duration of chilling treatments at the early and late grain filling stages was conducted in 2017, 2018 and 2019., Results: Per 10 °C·day increase in the accumulated cooling degree day at the early and late grain filling stages, the rice emergence-maturity duration was delayed by 0.8% (0.6%) and rice yield decreased by 2.2% (1.7%). Chilling at the early grain filling stage decreased the rice heading rate, while chilling at the late grain filling stage increased rice amylose but decreased protein content. For chilling treatment at the early grain filling stage, rice yield and grain quality were mainly correlated with seed-setting rate, whereas for chilling treatment at the late grain filling stage the rice yield and grain quality were mainly correlated with 1000-grain weight., Conclusion: This study improved the understanding of how chilling at the grain filling stages affects rice phenology, yield and grain quality, providing a theoretical basis for maintaining rice yield while ensuring grain quality. The results could be used to guide the rice-growing community in combating chilling at grain filling stages. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The widespread use of silver nanoparticles (AgNPs) has resulted in their release into the aquatic environment, which threatens the health of aquatic ecosystems. Although the ecotoxicological effects of AgNPs have been widely reported at individual and population levels, the impact of long-term exposure to AgNPs on community structure and ecosystem function in aquatic ecosystems remains poorly understood. Herein, the present study investigated the effects of long-term exposure (28 d) to environmentally relevant concentrations (1 μg/L and 10 μg/L) of AgNPs on the community structure and function of freshwater ecosystems by artificially constructed 28 mesocosms freshwater ecosystem in experimental greenhouses, using plastic water tanks and food web manipulation. The results showed that long-term exposure to AgNPs significantly altered the community structure of zooplankton, phytoplankton, and bacterioplankton in the aquatic ecosystem. Exposure to 10 μg/L AgNPs significantly reduced the zooplankton density (70.3%, p < 0.05) and increased the phytoplankton biomass and bacterial richness and diversity via a "top-down effect." With regards to ecosystem function, AgNPs exposure significantly increased the respiration in freshwater ecosystems but did not have a significant effect on decomposition. The partial least squares path modeling (PLS-PM) further revealed that AgNPs may have a negative impact on ecosystem functions by reducing zooplankton community density and thus increasing phytoplankton biomass. This study is the first to show that long-term exposure to environmentally relevant concentrations of AgNPs leads to alterations in plankton community structure and promotes respiration in freshwater ecosystems. It emphasizes the need for assessing the environmental risk of long-term exposure to AgNPs at the ecosystem level., 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 Inc. All rights reserved.)

Corticosterone, an end product of the hypothalamic-pituitary-adrenal (HPA) axis, is a crucial stress hormone. A dysregulated HPA axis and corticosterone release play pivotal roles in the onset and persistence of symptoms of stress-related psychiatric disorders, such as anxiety. The intake of nutrients, probiotics, and prebiotic supplements decreases blood corticosterone levels. The dipeptide L-carnosine is composed of beta-alanine and L-histidine and is commercially available as a nutritional supplement for recovery from fatigue. L-carnosine is involved in stress-induced corticosterone responses and anxiety behaviors in rodents. Here, we assessed the effect of L-carnosine in CD157 knockout (KO) mice, a murine model of autism spectrum disorder (ASD). The uptake of L-carnosine suppressed the increase in plasma corticosterone levels in response to acute stress and attenuated anxiety-like behaviors in CD157 KO mice. These results suggest that L-carnosine supplementation may relieve anxiety by suppressing excessive stress responses in individuals with ASD.

Background and Aims: Leaf variegation is common in plants and confers diverse adaptive functions. However, its genetic underpinnings remain largely unresolved; this is particularly true for variegation that arises through modified leaf tissue structure that affects light reflection. White clover is naturally polymorphic for structure-based white leaf mark variegation. It therefore provides a useful system to examine the genetic basis of this phenotype, and to assess potential costs to photosynthetic efficiency resulting from modified leaf structures. This study sought to map the loci controlling the white leaf mark in white clover and evaluate the relationship between white leaf mark, leaf thickness, and photosynthetic efficiency., Methods: We generated a high-density genetic linkage map from an F3 mapping population, employing reference genome-based SNP markers. White leaf mark was quantified through detailed phenotypic evaluations alongside leaf thickness to test how tissue thickness may affect the variegation phenotype. Quantitative trait locus (QTL) mapping was performed to characterize their genetic bases. Photosynthetic efficiency measurements were used to test for physiological trade-offs between variegation and photosynthetic output., Key Results: The V locus, a major gene responsible for the white leaf mark polymorphism, was mapped to the distal end of chromosome 5, and several modifier loci were also mapped that contribute additively to variegation intensity. The presence and intensity of white leaf mark was associated with greater leaf thickness; however, increased variegation did not detectably affect photosynthetic efficiency., Conclusions: We have successfully mapped the major locus governing the white leaf mark in white clover, along with several modifier loci, revealing a complex basis for this structure-based variegation. The apparent absence of compromised photosynthesis in variegated leaves challenges the notion that variegation creates fitness trade-offs between photosynthetic efficiency and other adaptive functions. This finding suggests that other factors may maintain the white leaf mark polymorphism in white clover., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To develop preoperative nomograms using risk factors based on clinicopathological and MRI for predicting the risk of positive surgical margin (PSM) after radical prostatectomy (RP)., Patients and Methods: This study retrospectively enrolled patients who underwent prostate MRI before RP at our center between January 2015 and November 2022. Preoperative clinicopathological factors and MRI-based features were recorded for analysis. The presence of PSM (overall PSM [oPSM]) at pathology and the multifocality of PSM (mPSM) were evaluated. LASSO regression was employed for variable selection. For the final model construction, logistic regression was applied combined with the bootstrap method for internal verification. The risk probability of individual patients was visualized using a nomogram., Results: In all, 259 patients were included in this study, and 76 (29.3%) patients had PSM, including 40 patients with mPSM. Final multivariate logistic regression revealed that the independent risk factors for oPSM were tumor diameter, frank extraprostatic extension, and annual surgery volume (all p < 0.05), and the nomogram for oPSM reached an area under the curve (AUC) of 0.717 in development and 0.716 in internal verification. The independent risk factors for mPSM included the percentage of positive cores, tumor diameter, apex depth, and annual surgery volume (all p < 0.05), and the AUC of the nomogram for mPSM was 0.790 in both development and internal verification. The calibration curve analysis showed that these nomograms were well-calibrated for both oPSM and mPSM., Conclusions: The proposed nomograms showed good performance and were feasible in predicting oPSM and mPSM, which might facilitate more individualized management of prostate cancer patients who are candidates for surgery., (© 2024. The Author(s).)

Bisphenol A (BPA), an endocrine disrupter with estrogen activity, can infiltrate animal and human bodies through the food chain. Enzymatic degradation of BPA holds promise as an environmentally friendly approach while it is limited due to lower stability and recycling challenges. In this study, laccase from Bacillus pumilus TCCC 11568 was expressed in Pichia pastoris (fLAC). The optimal catalytic conditions for fLAC were at pH 6.0 and 80 °C, with a half-life T 1/2 of 120 min at 70 °C. fLAC achieved a 46 % degradation rate of BPA, and possible degradation pathways were proposed based on identified products and reported intermediates of BPA degradation. To improve its stability and degradation capacity, a whole-cell biocatalyst (WCB) was developed by displaying LAC (dLAC) on the surface of P. pastoris GS115. The functionally displayed LAC demonstrated enhanced thermostability and pH stability along with an improved BPA degradation ability, achieving a 91 % degradation rate. Additionally, dLAC maintained a degradation rate of over 50 % after the fourth successive cycles. This work provides a powerful catalyst for degrading BPA, which might decontaminate endocrine disruptor-contaminated water through nine possible pathways., 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: As one of the serious complications of sepsis in children, sepsis-associated encephalopathy (SAE) is associated with significantly poor prognosis and increased mortality. However, predictors of outcomes for pediatric SAE patients have yet to be identified. The aim of this study was to develop nomograms to predict the 14-day and 90-day mortality of children with SAE, providing early warning to take effective measures to improve prognosis and reduce mortality., Methods: In this multicenter, retrospective study, we screened 291 patients with SAE admitted to the PICU between January 2017 and September 2022 in Shandong Province. A least absolute shrinkage and selector operation (LASSO) method was used to identify the optimal prognostic factors predicting the outcomes in pediatric patients with SAE. Then, multivariable logistic regression analysis was performed based on these variables, and two nomograms were built for visualization. We used the area under the curve (AUC), calibration curves and decision curves to test the accuracy and discrimination of the nomograms in predicting outcomes., Results: There were 129 patients with SAE in the training cohort, and there were 103 and 59 patients in the two independent validation cohorts, respectively. Vasopressor use, procalcitonin (PCT), lactate and pediatric critical illness score (PCIS) were independent predictive factors for 14-day mortality, and vasopressor use, PCT, lactate, PCIS and albumin were independent predictive factors for 90-day mortality. Based on the variables, we generated two nomograms for the early identification of 14-day mortality (AUC 0.853, 95% CI 0.787-0.919, sensitivity 72.4%, specificity 84.5%) and 90-day mortality (AUC 0.857, 95% CI 0.792-0.923, sensitivity 72.3%, specificity 90.6%), respectively. The calibration plots for nomograms showed excellent agreement of mortality probabilities between the observed and predicted values in both training and validation cohorts. Decision curve analyses (DCA) indicated that nomograms conferred high clinical net benefit., Conclusion: The nomograms in this study revealed optimal prognostic factors for the mortality of pediatric patients with SAE, and individualized quantitative risk evaluation by the models would be practical for treatment management., 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 Wang, Gao, Fu, Huo, Guo, Jiang, Liu, Jiang and Liu.)

Background: To evaluate the performances of several advanced deep convolutional neural network models (AlexNet, VGG, GoogLeNet, ResNet) based on ensemble learning for recognizing chronic gingivitis from screening oral images., Methods: A total of 683 intraoral clinical images acquired from 134 volunteers were used to construct the database and evaluate the models. Four deep ConvNet models were developed using ensemble learning and outperformed a single model. The performances of the different models were evaluated by comparing the accuracy and sensitivity for recognizing the existence of gingivitis from intraoral images., Results: The ResNet model achieved an area under the curve (AUC) value of 97%, while the AUC values for the GoogLeNet, AlexNet, and VGG models were 94%, 92%, and 89%, respectively. Although the ResNet and GoogLeNet models performed best in classifying gingivitis from images, the sensitivity outcomes were not significantly different among the ResNet, GoogLeNet, and Alexnet models (p>0.05). However, the sensitivity of the VGGNet model differed significantly from those of the other models (p < 0.001)., Conclusion: The ResNet and GoogLeNet models show promise for identifying chronic gingivitis from images. These models can help doctors diagnose periodontal diseases efficiently or based on self-examination of the oral cavity by patients., (© 2024. The Author(s).)

Ovarian cancer (OC) manifests as a complex disease characterized by inter- and intra-patient heterogeneity. Despite enhanced biological and genetic insights, OC remains a recalcitrant malignancy with minimal survival improvement. Based on multi-site sampling and a multi-lineage patient-derived xenograft (PDX) establishment strategy, we present herein the establishment of a comprehensive PDX biobank from histologically and molecularly heterogeneous OC patients. Comprehensive profiling of matched PDX and patient samples demonstrates that PDXs closely recapitulate parental tumors. By leveraging multi-lineage models, we reveal that the previously reported genomic disparities of PDX could be mainly attributed to intra-patient spatial heterogeneity instead of substantial model-independent genomic evolution. Moreover, DNA damage response pathway inhibitor (DDRi) screening uncovers heterogeneous responses across models. Prolonged iterative drug exposure recapitulates acquired drug resistance in initially sensitive models. Meanwhile, interrogation of induced drug-resistant (IDR) models reveals that suppressed interferon (IFN) response and activated Wnt/β-catenin signaling contribute to acquired DDRi drug resistance., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In autonomous driving, the fusion of multiple sensors is considered essential to improve the accuracy and safety of 3D object detection. Currently, a fusion scheme combining low-cost cameras with highly robust radars can counteract the performance degradation caused by harsh environments. In this paper, we propose the IRBEVF-Q model, which mainly consists of BEV (Bird's Eye View) fusion coding module and an object decoder module.The BEV fusion coding module solves the problem of unified representation of different modal information by fusing the image and radar features through 3D spatial reference points as a medium. The query in the object decoder, as a core component, plays an important role in detection. In this paper, Heat Map-Guided Query Initialization (HGQI) and Dynamic Position Encoding (DPE) are proposed in query construction to increase the a priori information of the query. The Auxiliary Noise Query (ANQ) then helps to stabilize the matching. The experimental results demonstrate that the proposed fusion model IRBEVF-Q achieves an NDS of 0.575 and a mAP of 0.476 on the nuScenes test set. Compared to recent state-of-the-art methods, our model shows significant advantages, thus indicating that our approach contributes to improving detection accuracy.

Rice production is a primary contributor to global greenhouse gas emissions, with unclear pathways towards carbon neutrality. Here, through a comprehensive assessment of direct greenhouse gas (GHG) emission using DNDC model and indirect GHG emission using emission factor methods, we estimated the annual crop yield, GHG emission amount and intensity, and economic benefits of different cropping patterns in the climate-sensitive regions of rice production in China. Through the expansion of single-rice and cropping pattern change from the wheat-rice to wheat-rice-rice in the climate-sensitive regions of single and triple-cropping cultivations, the total grain yield increased by 4.4 % and 4.5 % compared with the current national grain production, the GHG emission would increase by 2.4 % and 5.4 % of the current national GHG emissions from rice and wheat production, the net economic benefits could increase 0.9 % and decrease 2.0 % of the national output value of rice and wheat production. The study takes the entire-life cycle of crop growth as the principal line, and could provide a valuable reference for the regulation of the cropping pattern and the formulation of carbon reduction policies in the climate-sensitive region., 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. Published by Elsevier B.V.)

Deep learning (DL) has a wide application in imaging through scattering media, however, most DL approaches lack related physical principle priors. Aiming at the limitation of DL methods that require high completeness of training set, a two-stage network is proposed to complete the transmission matrix (TM) measurement and image reconstruction. Thanks to the appropriate structure of the network, the amount of data required in the Measurement Stage is greatly reduced. The self-closed-loop constraint in the Imaging Stage also enables the imaging network to break from the dependence on the completeness of the training set, and achieve a reconstruction with an SSIM of 0.84 using only 10 pairs of training data. Besides, both the Imaging Stage and the Measurement Stage can be used as a stand-alone method in combination with conventional phase retrieval algorithms. This method can drive the development of TM-based imaging and provide an enlightening reference for the practical application in optical imaging scenes.

Background: Animal studies have shown that exposure to REEs can cause severe liver damage, but evidence from population studies is still lacking. Therefore, we investigated the relationship between REEs concentrations in urine and liver function in the population., Methods: We conducted a cross-sectional study on 1024 participants in Nanning, China. An inductively coupled plasma mass spectrometer (ICP-MS) was used to detect the concentrations of 12 REEs in urine. The relationship between individual exposure to individual REE and liver function was analyzed by multiple linear regression. Finally, the effects of co-exposure to 5 REEs on liver function were assessed by a weighted sum of quartiles (WQS) regression model and a Bayesian kernel machine regression (BKMR) model., Results: The detection rate of 5 REEs, lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), and dysprosium (Dy), is greater than 60%. After multiple factor correction, La, Ce, Pr, Nd, and Dy were positively correlated with serum ALP, Ce, Pr, and Nd were positively correlated with serum AST, while Ce was negatively correlated with serum TBIL and DBIL. Both WQS and BKMR results indicate that the co-exposure of the 5 REEs is positively correlated with serum ALP and AST, while negatively correlated with serum DBIL. There were potential interactions between La and Ce, La and Dy in the association of co-exposure of the 5 REEs with serum ALP., Conclusions: The co-exposure of the 5 REEs was positively correlated with serum ALP and AST, and negatively correlated with serum DBIL., 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 GmbH. All rights reserved.)

Objective: To investigate the diagnostic performance of MRI in detecting clinically significant prostate cancer (csPCa) and prostate cancer (PCa) in patients with prostate-specific antigen (PSA) levels of 4-10 ng/mL., Methods: A computerized search of PubMed, Embase, Cochrane Library, Medline, and Web of Science was conducted from inception until October 31, 2023. We included articles on the use of MRI to detect csPCa or PCa at 4-10 ng/mL PSA. The primary and secondary outcomes were MRI performance in csPCa and PCa detection, respectively; the estimates of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were pooled in a bivariate random-effects model., Results: Among the 19 studies (3879 patients), there were 10 (2205 patients) and 13 studies (2965 patients) that reported MRI for detecting csPCa or PCa, respectively. The pooled sensitivity and specificity for csPCa detection were 0.84 (95% confidence interval [CI], 0.79-0.88) and 0.76 (95%CI, 0.65-0.84), respectively, for PCa detection were 0.82 (95%CI, 0.75-0.87) and 0.74 (95%CI, 0.65-0.82), respectively. The pooled NPV for csPCa detection was 0.91 (0.87-0.93). Biparametric magnetic resonance imaging also showed a significantly higher sensitivity and specificity relative to multiparametric magnetic resonance imaging (both p < 0.01)., Conclusion: Prostate MRI enables the detection of csPCa and PCa with satisfactory performance in the PSA gray zone. The excellent NPV for csPCa detection indicates the possibility of biopsy decision-making in patients in the PSA gray zone, but substantial heterogeneity among the included studies should be taken into account., Clinical Relevance Statement: Prostate MRI can be considered a reliable and satisfactory tool for detecting csPCa and PCa in patients with PSA in the "gray zone", allowing for reducing unnecessary biopsy and optimizing the overall examination process., Key Points: Prostate-specific antigen (PSA) is a common screening tool for prostate cancer but risks overdiagnosis. MRI demonstrated excellent negative predictive value for prostate cancer in the PSA gray zone. MRI can influence decision-making for these patients, and biparametric MRI should be further evaluated., (© 2024. The Author(s).)

Due to the depletion of fossil energy on earth, it is crucial to develop resource rich and efficient non-precious metal electrocatalysts for oxygen evolution reaction (OER). Herein, we synthesized an efficient and economical electrocatalyst using a simple self-assembly strategy. Firstly, rod-shaped MIL-88A was synthesized by hydrothermal method. Then, the surface of MIL-88A was functionalized and encapsulated in zeolitic imidazolate framework-67 (ZIF-67) by hydrothermal method. The combination of MIL-88A and ZIF-67 resulted in a slight ion-exchange reaction between Co 2+ and the surface of MIL-88A to generate CoFe-LDH@ZIF-67 core-shell structure. Afterwards, in the presence of Mo 6+ , ZIF-67 was converted into CoMo-nanocages through ion-exchange reactions, forming a core-shell structure of MoCoFe hydr (oxy) oxide@CoMo-LDH (MoCoFe-HO@CoMo-LDH). Due to the advantages of core-shell structure and composition, this material exhibits excellent OER characteristics, with a small Tafel slope (45.11 mV dec -1 ) and low overpotential (324 mV) at 10 mA cm -2 . It exhibits good stability in alkaline media. This research work provides a novel approach for the development of efficient and economical non-precious metal electrocatalysts., 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 Inc. All rights reserved.)

In the context of climate change, the northern climate-based boundaries of the winter wheat-summer maize double cropping system (DCS) have moved northward and westward. The selection of spring maize single cropping system (SCS) or DCS in the potential DCS region in northern China directly affects the annual crop yield, resource use efficiency, and greenhouse gas (GHG) emissions. Reducing GHG emissions while improving yield and resource use efficiency is essential to green agricultural development. We used future climate data (2021-2060, SSP2-4.5 and SSP5-8.5), along with crop and soil data, to assess the applicability of the Denitrification-Decomposition Model (DNDC) for simulating crop yield and GHG emissions. Through simulation of DNDC, we identified a cropping system that prioritized high yield, resource use efficiency, and GHG emissions reduction, adapting to future climate change. Under this cropping system, we quantified the effects of various straw incorporation rates, irrigation, and nitrogen input on crop yield, resource use efficiency, and GHG emissions. We proposed optimal measures to adapt to future climate change while aiming for high yield, resource use efficiency, and GHG emissions reduction. The results show that the DNDC reliably simulated yield and GHG emissions for the (SCS) and the DCS. In counting for greenhouse gas emission intensity (GHGI) as GHG emissions normalized by crop yield, the GHGI was reduced by 86.4% and 89.2% in DCS than in SCS under the SSP2-4.5 and SSP5-8.5, respectively. In the study area, the DCS should be adopted for high yield, resource use efficiency, and GHG emissions reduction (increased by 28.4% and 34.4%) in the SSP2-4.5 and SSP5-8.5 with 1) straw incorporation rate for 100% of winter wheat and for 60% of summer maize; 2) total irrigating 240 mm for winter wheat at pre-sowing, jointing, booting, and filling stages; and 3) applying nitrogen of 168 kg·N/ha for both crops., 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: Calcitriol has the potential to counteract fibrotic diseases beyond its classical action of maintaining calcium and bone metabolism; however, its functional mechanism remains unknown. Autophagy-related gene 16-like 1 (Atg16l1) is one of the genes related to autophagy and is involved in protecting against fibrotic diseases. The present study aimed to explore the contribution of autophagy to the inhibition of calcitriol-induced hepatic fibrosis, as well as its potential molecular mechanism., Methods: Carbon tetrachloride (Ccl 4 )-treated mice were established as hepatic fibrosis models and received calcitriol treatment for 6 weeks. Quantification of Sirius red staining and measurement of key fibrotic markers (collagen-1 and α-SMA) was performed to detect hepatic fibrosis. Chloroquine (CQ) treatment was used to observe autophagic flux, and 3-methyladenine (3-MA) was used to inhibit autophagy. Furthermore, the effects of calcitriol on transforming growth factor β1 (TGFβ1)-stimulated primary hepatic stellate cells (HSCs) were detected. Downregulation of Atg16l1 or vitamin D receptor (VDR) in LX-2 cells was used to explore the mechanism of action of calcitriol in fibrosis and autophagy. Additionally, the electrophoretic mobility shift assay (EMSA) was used to investigate the interactions between VDR and ATG16L1., Results: Calcitriol increased the expression of VDR and ATG16L1, enhanced autophagy and attenuated hepatic fibrosis. 3-MA treatment and VDR silencing abolished the protective effects of calcitriol against fibrosis. Calcitriol-induced anti-fibrosis effects were blocked by ATG16L1 suppression. Furthermore, VDR bound to the ATG16L1 promoter and downregulation of VDR decreased the expression of ATG16L1 in LX-2 cells., Conclusion: Calcitriol mitigates hepatic fibrosis partly through ATG16L1-mediated autophagy., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Advances in intraoperative molecular imaging (IMI) may improve surgical outcomes when resecting tumors in the lung. A single-center trial was conducted using VGT-309, a cathepsin-targeted near-infrared imaging agent that causes lung nodules to fluoresce during surgical resection. The end point of this phase 2 study was to evaluate the frequency that IMI with VGT-309 resulted in a clinically significant event (CSE): localization of pulmonary nodules, discovery of unsuspected additional cancers, or identification of positive margins., Methods: Patients undergoing surgical resection for known or suspected cancer in the lung received VGT-309 (0.32 mg/kg) preoperatively. During the surgical procedure, localization and resection of the nodules were performed using standard surgical techniques. Near-infrared imaging was then used to localize nodules, seek occult lesions, and assess resection margins. Efficacy was measured by the frequency of CSEs., Results: Of the 40 patients who underwent pulmonary resection with VGT-309, 17 (42.5%) had at least 1 CSE. Near-infrared imaging identified lesions not found by standard surgical methods in 16 patients, additional cancers not found by preoperative imaging in 1 patient, and margins within 5 mm of the closest staple line in 2 patients. VGT-309 performance was tested across a broad range of tumor types and commercial near-infrared imaging systems. VGT-309 appeared safe, well-tolerated, with no infusion reactions, and no drug-related serious adverse events., Conclusions: This phase 2 study demonstrated the utility of IMI with VGT-309 in localizing pulmonary nodules, recognizing synchronous lesions, and identifying positive margins. A multi-institutional study will further evaluate the efficacy of VGT-309., Competing Interests: Disclosures Patrick Bou-Samra reports financial support was provided by Vergent Bioscience. Eric S. Bensen reports a relationship with Vergent Bioscience that includes: employment, equity or stocks, nonfinancial support, and travel reimbursement John T. Santini reports a relationship with Vergent Bioscience that includes: employment, equity or stocks, nonfinancial support, and travel reimbursement. The other authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

At present, there is no approved vaccine for prevention of infection by the opportunistic bacterium Klebsiella pneumoniae (Kp); success in treating these infections is increasingly challenged by the spread of antibiotic resistance. Preclinical investigation of adaptive immunity elicited by lung infection with live classical Kp may reveal host mechanisms of protection against this pathogen. Here, we utilize multiple virulent classical Kp strains to demonstrate that following lung infection, surviving wild-type mice develop protective immunity against both homologous and heterologous (heterotypic) reinfection. For Kp strains with low capacity to disseminate from the lung, this immunity is B-cell-independent. We further demonstrate that this immune protection is also effective against subsequent challenge with hypervirulent Kp if the strains share the same capsule type. Systemic inoculation fails to elicit the same protective effect as lung inoculation, revealing a lung-specific immune effector function is responsible for this protection. We therefore utilized clodronate-loaded liposomes to substantially deplete both alveolar macrophages and lung interstitial macrophages, finding that simultaneous depletion of both subsets entirely ablates protection. These findings indicate that following initial lung infection with Kp, lung macrophages mediate protection against ensuing Kp challenge., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Alternative splicing (AS) participates in tumor development and tumor microenvironment formation. However, the landscape of immune infiltrating AS events (IIASE) in pan-cancer and mechanisms of AS in lung adenocarcinoma (LUAD) have not been comprehensively characterized. We systematically profiled the IIASE landscape of pan-cancer using data from The Cancer Genome Atlas (TCGA), analyzing both commonalities and specific characteristics among different cancer types. We found that AS events tend to occur specifically in one cancer type rather than in multiple cancer types. AS events were used to classify 512 LUAD samples into two subtypes by unsupervised clustering: aberrant splicing subtype (ABS) and immune infiltrating subtype (IIS). The two subtypes showed significant differences in clinicopathology, prognosis, transcriptomics, genomics and immune microenvironment. We constructed a classification signature comprising 10 genes involved in 14 AS events using Logistic regression. The robustness of the signature was validated in three independent datasets using survival analysis. To explore AS mechanisms in LUAD, we constructed subtype-specific co-expression networks using Pearson correlation analysis. AS event of AKT3 regulated by splicing factor ENOX1 was associated with poor prognosis in LUAD. Overall, we outline AS events associated with immune infiltration in pan-cancer and this study provides insights into AS mechanisms in LUAD patient classification., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Broadening the absorption region to near-infrared (NIR) light is critical for the photocatalysis due to the larger proportion and stronger penetration of NIR light in solar energy. In the present paper, one-dimensional (1D) MWO 4 (M = Mn, Co, and Cd) materials synthesized by electrospinning technique, were studied by combining the density functional theory (DFT) with experiment results, which possessed the enhanced light absorption capability within the range of 200-2000 nm. It was proved that in the ultraviolet-visible (UV-Vis) region, the absorption bands of CoWO 4 and MnWO 4 samples were attributed to the metal-to-metal charge transfer mechanism, while the absorption of CdWO 4 sample may be referable to the ligand-to-metal charge transfer mechanism. In the near-infrared (NIR) region, the absorption of CoWO 4 and MnWO 4 primarily originated from the d-d orbital transitions of Mn 2+ and Co 2+ . The photocatalytic experimental results showed that the degradation rates for bisphenol A (BPA) over CoWO 4 , MnWO 4 , and CdWO 4 photocatalysts under UV-Vis/NIR light irradiation for 140 min/12 h were 78.8 %/75.9 %, 23.8 %/21.3 %, 12.8 %/8.7 %, respectively. This research offers the novel insights into the precise construction of tungstate catalytic systems and contributes to the advancement of UV-Vis-NIR full spectrum photocatalytic technology, and lays a foundation for a cleaner and more environmental-friendly future., 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 Inc. All rights reserved.)

As people age, their ability to resist injury and repair damage decreases significantly. Platelet-rich plasma (PRP) has demonstrated diverse therapeutic effects on tissue repair. However, the inconsistency of patient outcomes poses a challenge to the practical application of PRP in clinical practice. Furthermore, a comprehensive understanding of the specific impact of aging on PRP requires a systematic investigation. We derived PRP from 6 young volunteers and 6 elderly volunteers, respectively. Subsequently, 95% of high-abundance proteins were removed, followed by mass spectrometry analysis. Data are available via ProteomeXchange with the identifier PXD050061. We detected a total of 739 proteins and selected 311 proteins that showed significant differences, including 76 upregulated proteins in the young group and 235 upregulated proteins in the elderly group. Functional annotation and enrichment analysis unveiled upregulation of proteins associated with cell apoptosis, angiogenesis, and complement and coagulation cascades in the elderly. Conversely, IGF1 was found to be upregulated in the young group, potentially serving as the central source of enhanced cell proliferation ability. Our investigation not only provides insights into standardizing PRP preparation but also offers novel strategies for augmenting the functionality of aging cells or tissues.

Neuroinflammation has emerged as a major concern in ischemic stroke therapy because it exacebates neurological dysfunction and suppresses neurological recovery after ischemia/reperfusion. Fingolimod hydrochloride (FTY720) is an FDA-approved anti-inflammatory drug which exhibits potential neuroprotective effects in ischemic brain parenchyma. However, delivering a sufficient amount of FTY720 through the blood-brain barrier into brain lesions without inducing severe cardiovascular side effects remains challenging. Here, a neutrophil membrane-camouflaged polyprodrug nanomedicine that can migrate into ischemic brain tissues and in situ release FTY720 in response to elevated levels of reactive oxygen species. This nanomedicine delivers 15.2-fold more FTY720 into the ischemic brain and significantly reduces the risk of cardiotoxicity and infection compared with intravenously administered free drug. In addition, single-cell RNA-sequencing analysis identifies that the nanomedicine attenuates poststroke inflammation by reprogramming microglia toward anti-inflammatory phenotypes, which is realized via modulating Cebpb-regulated activation of NLRP3 inflammasomes and secretion of CXCL2 chemokine. This study offers new insights into the design and fabrication of polyprodrug nanomedicines for effective suppression of inflammation in ischemic stroke therapy., (© 2024 Wiley‐VCH GmbH.)

Background: The financial implications of central nervous system (CNS) cancers are substantial, not only for the healthcare service and payers, but also for the patients who bear the brunt of direct, indirect, and intangible costs. This study sought to investigate the impact of healthcare spending on CNS cancer survival using recent US data., Methods: This study used public data from the Disease Expenditure Project 2016 and the Global Burden of Disease Study 2019. The primary outcome was the annual healthcare spending trend from 1996 and 2016 on CNS tumors adjusted for disease prevalence, alongside morbidity and mortality. Secondary outcomes included drivers of change in healthcare expenditures for CNS cancers. Subgroup analysis was performed stratified by age group, expenditure type, and care type provided., Results: There was a significant increase in total healthcare spending on CNS cancers from $2.72 billion (95% CI: $2.47B to $2.97B) in 1996 to $6.85 billion (95% CI: $5.98B to $7.57B) in 2016. Despite the spending increase, the mortality rate per 100 000 people increased, with 5.30 ± 0.47 in 1996 and 7.02 ± 0.47 in 2016, with an average of 5.78 ± 0.47 deaths per 100 000 over the period. The subgroups with the highest expenditure included patients aged 45 to 64, those with private insurance, and those receiving inpatient care., Conclusions: This study highlights a significant rise in healthcare costs for CNS cancers without corresponding improvements in mortality rate, indicating a mismatch of healthcare spending, contemporary advances, and patient outcomes as it relates to mortality., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Exosomes derived from Adipose-Derived Stem Cells (ADSCs-Exo) have been implicated in the enhancement of wound repair in Diabetic Foot Ulcers (DFU)., Objective: The current research was designed to explore the therapeutic potential and underlying mechanisms of ADSCs-Exo modified with microRNA-125b (miR-125b) in the context of DFU., Methods: Rat models with DFU and human umbilical vein endothelial cells (HUVECs) subjected to high glucose (HG) conditions served as experimental systems and were administered miR-125b-engineered ADSCs-Exo. Then, the expressions of CD34, Ki-67, angiogenesis-related factors (VEGF and TGFβ-1), angiogenesis inhibitor DLL-4, and inflammation-related proteins (TLR-4 and IL-6) were detected., Results: MiR-125b was upregulated in ADSCs-Exo. MiR-125b-mimics transfection in ADSCs- Exo reduced inflammatory infiltration and promoted granulation formation and wound healing in wound tissues. MiR-125b-mimics-modified ADSCs-Exo injection increased the expression of CD34, Ki-67, VEGF, and TGFβ-1, whereas decreased the expression of DLL-4, TLR-4, and IL-6 in wound tissues of DFU rats. In addition, miR-125b-mimics-ADSCs-Exo injection reversed the negative effects of HG on the proliferation, migration, and angiogenesis of HUVECs, as well as the positive effects of cell apoptosis. Moreover, miR-125b-inhibitor-ADSCs-Exo injection had the opposite effects to miR-125b-mimics-ADSCs-Exo., Conclusion: ADSCs-Exo promoted wound healing of DFU rats, especially when overexpressing miR-125b., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Single-walled carbon nanotubes (SWCNTs) functionalized with sparse surface chemical groups are promising for a variety of optical applications such as quantum information and bio-imaging. However, the luminescence efficiencies and stability, two key aspects, undoubtedly govern their practical usage. Herein, we assess the surface migration of oxygen and triazine groups on as-modified SWCNT fragments by adopting transition state theory and explore the de-excitation of oxygen-functionalized SWCNT fragments by performing non-adiabatic excited-state dynamics simulations. According to the predicted moderate or even small reaction barriers, the migration of both oxygen and triazine groups is feasible from an sp 3 defect configuration forming an energetically more stable sp 2 configuration at moderate or even room temperatures. Such isomerization leads to drastically different light emission capabilities as indicated by the large or zero oscillator strengths. During the dynamics simulations, the lowest excited singlet (S 1 ) state rapidly decays in energy within 20 fs and then fluctuates until the end, providing insights into the emission mechanism of SWCNTs. This study highlights the potential intrinsic limitations of surface-functionalized SWCNTs for luminescence applications.

Biological nervous system outperforms in both dynamic and static information perception due to their capability to integrate the sensing, memory and processing functions. Reconfigurable neuromorphic transistors, which can be used to emulate different types of biological analogues in a single device, are important for creating compact and efficient neuromorphic computing networks, but their design remains challenging due to the need for opposing physical mechanisms to achieve different functions. Here we report a neuromorphic electrolyte-gated transistor that can be reconfigured to perform physical reservoir and synaptic functions. The device exhibits dynamics with tunable time-scales under optical and electrical stimuli. The nonlinear volatile property is suitable for reservoir computing, which can be used for multimodal pre-processing. The nonvolatility and programmability of the device through ion insertion/extraction achieved via electrolyte gating, which are required to realize synaptic functions, are verified. The device's superior performance in mimicking human perception of dynamic and static multisensory information based on the reconfigurable neuromorphic functions is also demonstrated. The present study provides an exciting paradigm for the realization of multimodal reconfigurable devices and opens an avenue for mimicking biological multisensory fusion., (© 2024. The Author(s).)

Histone methylation plays crucial roles in regulating chromatin structure and gene transcription in epigenetic modifications. Lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, is universally overexpressed in various diseases. LSD1 dysregulation is closely associated with cancer, viral infections, and neurodegenerative diseases, etc., making it a promising therapeutic target. Several LSD1 inhibitors and two small-molecule degraders (UM171 and BEA-17) have entered the clinical stage. LSD1 can remove methyl groups from histone 3 at lysine 4 or lysine 9 (H3K4 or H3K9), resulting in either transcription repression or activation. While the roles of LSD1 in transcriptional regulation are well-established, studies have revealed that LSD1 can also be dynamically regulated by other factors. For example, the expression or activity of LSD1 can be regulated by many proteins that form transcriptional corepressor complexes with LSD1. Moreover, some post-transcriptional modifications and cellular metabolites can also regulate LSD1 expression or its demethylase activity. Therefore, in this review, we will systematically summarize how proteins involved in the transcriptional corepressor complex, various post-translational modifications, and metabolites act as regulatory factors for LSD1 activity., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)

The clinical benefits of tumor-targeting antibodies (tAb) are modest in solid human tumors. The efficacy of many tAbs is dependent on Fc receptor (FcR)-expressing leukocytes that bind Fc fragments of tAb. Tumor-associated macrophages (TAM) and neutrophils (TAN) represent the majority of FcR+ effectors in solid tumors. A better understanding of the mechanisms by which TAMs and TANs regulate tAb response could help improve the efficacy of cancer treatments. Here, we found that myeloid effectors interacting with tAb-opsonized lung cancer cells used antibody-dependent trogocytosis (ADT) but not antibody-dependent phagocytosis. During this process, myeloid cells "nibbled off" tumor cell fragments containing tAb/targeted antigen (tAg) complexes. ADT was only tumoricidal when the tumor cells expressed high levels of tAg and the effectors were present at high effector-to-tumor ratios. If either of these conditions were not met, which is typical for solid tumors, ADT was sublethal. Sublethal ADT, mainly mediated by CD32hiCD64hi TAM, led to two outcomes: (i) removal of surface tAg/tAb complexes from the tumor that facilitated tumor cell escape from the tumoricidal effects of tAb; and (ii) acquisition of bystander tAgs by TAM with subsequent cross-presentation and stimulation of tumor-specific T-cell responses. CD89hiCD32loCD64lo peripheral blood neutrophils (PBN) and TAN stimulated tumor cell growth in the presence of the IgG1 anti-EGFR Ab cetuximab; however, IgA anti-EGFR Abs triggered the tumoricidal activity of PBN and negated the stimulatory effect of TAN. Overall, this study provides insights into the mechanisms by which myeloid effectors mediate tumor cell killing or resistance during tAb therapy., Significance: The elucidation of the conditions and mechanisms by which human FcR+ myeloid effectors mediate cancer cell resistance and killing during antibody treatment could help develop improved strategies for treating solid tumors., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Carotid occlusion often leads to the formation of a collateral network. On rare occasions, due to hemodynamic influence, aneurysms can occur. Here, the authors describe a 69-year-old male presenting with intracerebral hemorrhage secondary to a ruptured aneurysm within such a network., Observations: The patient presented to the emergency department with an altered level of consciousness. Imaging showed a left temporal lobe hemorrhage extending into the ventricle, subdural hematoma, and evidence of contrast extravasation. Digital subtraction angiography revealed an occluded left internal carotid artery with the left middle cerebral artery territory reconstituted by flow through an external carotid artery-internal carotid artery anastomosis. The latter was formed by the superficial temporal artery-superior orbital artery, as well as pial-pial collaterals from the posterior temporal artery. Notably, a 4-mm aneurysm arising from the pial-pial collateral network was identified. Surgical intervention involved a left temporal craniectomy and aneurysm excision, with special attention paid to preserving the anastomotic flow through the superficial temporal artery., Lessons: This case underscores the importance of recognizing and preserving collateral vascular pathways in cases of carotid occlusion with an associated aneurysm. It emphasizes the necessary balance between managing aneurysm risk and maintaining cerebral perfusion, highlighting the need for careful preoperative planning and intraoperative caution.

This study examined the impact of COVID-19 on 28 indicators of match technical performance (MTP) for football attacking players upon their return to play. Analyzing data from 100 players in the Big Five European football leagues, covering 1500 matches each before and after COVID-19 over 3 years (2020-2023), revealed significant differences in 76% of players' MTP indicators. Notably, 14 indicators, particularly the five indicators linked to scoring, significantly decreased post-COVID-19. On average, players needed 3.09 matches to regain pre-infection MTP levels. The impact varied across player groups, with those in the elite group showing a milder effect; they required an average of 2.64 matches for recovery, compared to the control group's 3.55 matches. We found that, with increasing age, the majority of players' MTP indicators did not exhibit significant changes, both before and after they contracted COVID-19. In conclusion, the study highlighted the negative impact of COVID-19 on football attacking players' MTP. Players in the elite group experienced fewer adverse effects than those in the control group. This insight assisted coaches and managers in evaluating the impact of COVID-19 and similar virus-induced illnesses on players' MTP, enabling them to formulate training regimens for recovery and specific match tactics upon players' return to play., (© 2024. The Author(s).)

Importance: Large language models (LLMs) like OpenAI's ChatGPT are powerful generative systems that rapidly synthesize natural language responses. Research on LLMs has revealed their potential and pitfalls, especially in clinical settings. However, the evolving landscape of LLM research in medicine has left several gaps regarding their evaluation, application, and evidence base., Objective: This scoping review aims to (1) summarize current research evidence on the accuracy and efficacy of LLMs in medical applications, (2) discuss the ethical, legal, logistical, and socioeconomic implications of LLM use in clinical settings, (3) explore barriers and facilitators to LLM implementation in healthcare, (4) propose a standardized evaluation framework for assessing LLMs' clinical utility, and (5) identify evidence gaps and propose future research directions for LLMs in clinical applications., Evidence Review: We screened 4,036 records from MEDLINE, EMBASE, CINAHL, medRxiv, bioRxiv, and arXiv from January 2023 (inception of the search) to June 26, 2023 for English-language papers and analyzed findings from 55 worldwide studies. Quality of evidence was reported based on the Oxford Centre for Evidence-based Medicine recommendations., Findings: Our results demonstrate that LLMs show promise in compiling patient notes, assisting patients in navigating the healthcare system, and to some extent, supporting clinical decision-making when combined with human oversight. However, their utilization is limited by biases in training data that may harm patients, the generation of inaccurate but convincing information, and ethical, legal, socioeconomic, and privacy concerns. We also identified a lack of standardized methods for evaluating LLMs' effectiveness and feasibility., Conclusions and Relevance: This review thus highlights potential future directions and questions to address these limitations and to further explore LLMs' potential in enhancing healthcare delivery., (© 2024. The Author(s).)

Scattering caused by suspended particles in the water severely reduces the radiance of the scene. This paper proposes an unsupervised underwater restoration method based on binocular estimation and polarization. Based on the correlation between the underwater transmission process and depth, this method combines the depth information and polarization information in the scene, uses the neural network to perform global optimization and the depth information is recalculated and updated in the network during the optimization process, and reduces the error generated by using the polarization image to calculate parameters, so that detailed parts of the image are restored. Furthermore, the method reduces the requirement for rigorous pairing of data compared to previous approaches for underwater imaging using neural networks. Experimental results show that this method can effectively reduce the noise in the original image and effectively preserve the detailed information in the scene.

Background: Sepsis is a life-threatening, systemic inflammatory disease that can lead to a variety of conditions, including septic acute kidney injury (AKI). Recently, multiple circular Rnas (circRNAs) have been implicated in the development of this disease., Methods: In this study, we aimed to elucidate the role of circ-Gatad1 in sepsis induced AKI and its potential mechanism of action. High-throughput sequencing was used to investigate abnormal expression of circRNA in AKI and healthy volunteer. Bioinformatics analysis and luciferase reporting analysis were used to clarify the interacted relationship among circRNA, miRNA and mRNA. HK2 cells were treated with lipopolysaccharide (LPS) to establish septic AKI cell model. HK2 cells were employ to analysis the ROS, inflammatory cytokines expression, proliferation and apoptosis under LPS condition., Results: The result show that the expression of circ-Gatad1 was increased in septic acute kidney patients. Downregulation circ-Gatad1 suppressed LPS-treated induced HK2 cells injury including apoptosis, proliferation ability, ROS and inflammatory cytokines level. Bioinformatics and luciferase report analysis confirmed that both miR-22-3p and TRPM7 were downstream targets of circ-Gatad1. Overexpression of TRPM7 or downregulation of miR-22-3p reversed the protective effect of si-circ-Gatad1 to HK2 after exposure to LPS (5 µg/ml) microenvironment., Conclusion: In conclusion, knockdown of circ-Gatad1 alleviates LPS induced HK2 cell injury via targeting miR-22-3p/TRPM7 axis in septic acute kidney., (© 2024. The Author(s).)

Objective: Ischemic stroke (IS) is one of the major diseases threatening human health and survival and a leading cause of acquired mortality and disability in adults. The aim of this study was to screen diagnostic features of IS and to explore the characteristics of immune cell infiltration in IS pathogenesis., Methods: The microarray data of IS (GSE16561, GSE58294, GSE37587, and GSE124026) in the GEO database were merged after removing the batch effect. Then integrated bioinformatic analysis and machine-learning strategies were adopted to analyze the functional correlation and select diagnostic signatures. The WGCNA was used to identify the co-expression modules related to IS. The CIBERSORT algorithm was performed to assess the inflammatory state of IS and to investigate the correlation between diagnostic signatures and infiltrating immune cells., Results: Functional analysis of dysregulated genes showed that immune response-regulating signaling pathway and pattern recognition receptor activity were enriched in the pathophysiology of IS. The turquoise module was identified as the significant module with IS. By using Lasso and SVM-RFE learning methods, we finally obtained four diagnostic genes, including LAMP2, CR1, CLEC4E, and F5. The corresponding results of AUC of ROC prediction model in training and validation cohort were 0.954 and 0.862, respectively. The immune cell infiltration analysis suggested that plasma cells, resting and activated NK cells, activated dendritic cells, memory B cells, CD8 + T cells, naïve CD4 + T cells, and resting mast cells may be involved in the development of IS. Additionally, these diagnostic signatures might be correlated with multiple immune cells in varying degrees., Conclusion: We identified four biologically relevant genes (LAMP2, CR1, CLEC4E, and F5) with diagnostic effects for IS, our results further provide novel insights regarding molecular mechanisms associated with various immune cells that related to IS for future investigations., Competing Interests: Declaration of competing interest 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. Published by Elsevier Inc.)

Pink1 (PTEN-induced putative kinase 1) is a protein associated with maintaining mitochondrial function and integrity and has been reported to mediate neurodegeneration and neuroinflammation. While the role of Pink1 in intracerebral hemorrhage (ICH)-related neurological deficits and inflammatory responses is not deciphered. Congenic blood was transfused into the left corpus striatum to construct the ICH model in C57/BL6 wild-type (WT) and Pink1 -/- mice. The relative expression of Pink1, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, Cd86, nitric oxide synthase 2 (Nos2), Cd206, arginase 1 (Arg-1), and IL-10 was detected with qRT-PCR, Western blotting, or ELISA. Mouse neurological deficit scores (mNSS) and water content were detected, and an open-field test was performed to assay anxiety-like behavior. Remarkably decreased Pink1 expression and increased MIP-2, IL-1β, MCP-1, and TNF-α expression were observed after 12 ​h, 24 ​h, 48 ​h, 72 ​h, and 7 ​d post-ICH induction in the ipsilateral injury hemispheres. Pink1 deficiency could further up-regulate mNSS scores, brain water content, MIP-2, MCP-1, IL-1β, and TNF-α in the ipsilateral injury hemispheres. On the other hand, Pink1 deficiency could decrease the number of center cross, the velocity, and the total distance traveled in open field test. Pink1 deficiency could further up-regulate the mRNA levels of pro-inflammatory (M1) molecules (Cd86, Nos2), and down-regulate the relative expression of anti-inflammatory (M2) molecules (Cd206, Arg-1, and IL-10). Pink1 deficiency deteriorates neurological deficits and inflammatory responses after ICH, which can be considered as a treatment target., 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.)

The abnormal activation of Cullin RING E3 Ligases (CRLs) is closely associated with the occurrence and development of various cancers. Targeting the neddylation pathway represents an effective approach for cancer treatment. In this work, we reported that WS-299, structurally featuring a coumarin moiety attached to the triazolopyrimidine, exhibited excellent anti-proliferative activity in MGC-803 and HGC-27 cells. WS-299 exerted potent anticancer effects by inhibiting clone formation, EdU incorporation and inducing cell cycle arrest. WS-299 inhibited CUL3/5 neddylation and caused an obvious accumulation of Nrf2 and NOXA, substrates of CRL3 and CRL5, respectively. Biochemical studies showed that WS-299 inhibited CUL3 neddylation by inhibiting RBX1-UBE2M interaction. The anti-proliferative effect of WS-299 was mainly induced by NOXA-mediated apoptosis. Of note, Nrf2 attenuated WS-299-induced reactive oxygen species (ROS) levels. Furthermore, Nrf2 accumulation also had an antagonistic effect on NOXA-induced apoptosis. Therefore, WS-299 and siNrf2 synergistically increased ROS levels, apoptotic cells and suppressed tumor growth in vivo. Taken together, our research clarified the anti-cancer mechanisms of WS-299 through targeting the RBX1-UBE2M protein-protein interaction and inhibiting the neddylation modification of CUL3 and CUL5. More importantly, our studies also demonstrated that combination of WS-299 with shNrf2 could be an effective strategy for treating gastric cancers., 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 Inc. All rights reserved.)

Dental fear and anxiety are highly prevalent among children and have been shown to lead to irregular use of dental services. Previous research has suggested that while touch can alleviate the patient's stress and help in accomplishing dental procedures, it can also be a source of stress or used to restrain the patient. In this study, we explore the emergence and intertwine of controlling and comforting touch in pediatric dental clinic settings in which patients show signs of resistance, distress, or fear. We use microanalysis of video-recorded interactions to unveil how the adults in the room-any combination of the dentist, dental assistant, hygienist, and caregiver(s)-deploy various types of touch on the child patient to perform the dental procedure while simultaneously comforting the child. Our data set covers video-recordings of naturally occurring dental clinic visits of 3- to 12-year-old child patients from four cultural contexts: Finland, China, Iraq, and the United States. Drawing on Merleau-Ponty's writings on intercorporeality and the interaffectivity of bodies, the study proposes that touch in pediatric dentistry unfolds as complex intercorporeal formations where the interaffectivity emerges not only through touch but also via vocal resonance. In contrast to clear boundaries between comforting and controlling touch, our analysis indicates that the line between comforting and controlling touch can be blurred. We suggest that touching a pediatric patient showing resistance toward a dental procedure requires careful affective attention to the patient's subtle and moment-by-moment bodily expressions and reactions to the touch., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Patients with sepsis-associated encephalopathy (SAE) have higher mortality rates and longer ICU stays. Predictors of SAE are yet to be identified. We aimed to establish an effective and simple-to-use nomogram for the individual prediction of SAE in patients with sepsis admitted to pediatric intensive care unit (PICU) in order to prevent early onset of SAE., Methods: In this retrospective multicenter study, we screened 790 patients with sepsis admitted to the PICU of three hospitals in Shandong, China. Least absolute shrinkage and selection operator regression was used for variable selection and regularization in the training cohort. The selected variables were used to construct a nomogram to predict the risk of SAE in patients with sepsis in the PICU. The nomogram performance was assessed using discrimination and calibration., Results: From January 2017 to May 2022, 613 patients with sepsis from three centers were eligible for inclusion in the final study. The training cohort consisted of 251 patients, and the two independent validation cohorts consisted of 193 and 169 patients. Overall, 237 (38.7%) patients developed SAE. The morbidity of SAE in patients with sepsis is associated with the respiratory rate, blood urea nitrogen, activated partial thromboplastin time, arterial partial pressure of carbon dioxide, and pediatric critical illness score. We generated a nomogram for the early identification of SAE in the training cohort (area under curve [AUC] 0.82, 95% confidence interval [CI] 0.76-0.88, sensitivity 65.6%, specificity 88.8%) and validation cohort (validation cohort 1: AUC 0.80, 95% CI 0.74-0.86, sensitivity 75.0%, specificity 74.3%; validation cohort 2: AUC 0.81, 95% CI 0.73-0.88, sensitivity 69.1%, specificity 83.3%). Calibration plots for the nomogram showed excellent agreement between SAE probabilities of the observed and predicted values. Decision curve analysis indicated that the nomogram conferred a high net clinical benefit., Conclusions: The novel nomogram and online calculator showed performance in predicting the morbidity of SAE in patients with sepsis admitted to the PICU, thereby potentially assisting clinicians in the early detection and intervention of SAE., (© 2024. The Author(s).)

Mg alloys with excellent high-temperature mechanical properties are urgently desired to meet the design requirements of new-generation aircraft. Herein, novel cast Mg-10Gd-2Y-0.4Zn-0.2Ca-0.5Zr-xAg alloys were designed and prepared according to the advantages of multi-component alloying. The SEM and XRD results revealed that the as-cast microstructures contained α -Mg grains, β , and Zr-containing phase. As Ag rose from 0 wt.% to 2.0 wt.%, the grain size was refined from 40.7 μm to 33.5 μm, and the β phase significantly increased. The TEM observations revealed that the nano-scaled γ ' phase could be induced to precipitate in the α -Mg matrix by the addition of Ag. The stacking sequence of lamellar γ ' phases is ABCA. The multiple strengthening phases, including β phase, γ ' phases, and Zr-containing particles, were effectively tailored through alloying and synergistically enhanced the mechanical properties. The ultimate tensile strength increased from 154.0 ± 3.5 MPa to 231.0 ± 4.0 MPa at 548 K when Ag was added from 0 to 2.0 wt.%. Compared to the Ag-free alloy, the as-cast alloy containing 2.0 wt.% Ag exhibited a minor reduction in ultimate tensile strength (7.0 ± 4.0 MPa) from 498 K to 548 K. The excellent high-temperature performance of the newly developed Mg-RE-Ag alloy has great value in promoting the use of Mg alloys in aviation industries.

Particle engulfment plays a vital role in the application of particulate reinforced metal matrix composites fabricated by ingot metallurgy. During solidification, particles are nevertheless pushed by an advancing front. As a model system, TiB 2p /Al composites were used to investigate the particle engulfment facilitated by acoustic cavitation. The implosion of bubbles drives the particles plunging towards the solid/liquid interface, which increases the engulfment probability. The secondary dendrite arms are refined from 271.2 μm to 98.0 μm as a result of the forced movements of TiB 2 particles. Owing to the particle engulfment and dendrite refinement, the composite with ultrasound vibration treatment shows a more rapid work-hardening rate and higher strength., 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 B.V. All rights reserved.)

GaN's outstanding physical characteristics allow for a wide range of applications in numerous industries. Although individual GaN-based ultraviolet (UV) photodetectors are the subject of in-depth research in recent decades, the demand for photodetectors array is rising as a result of advances in optoelectronic integration technology. However, as a prerequisite for constructing GaN-based photodetectors array, large-area, patterned synthesis of GaN thin films remains a certain challenge. This work presents a facile technique for pattern growing high-quality GaN thin films for the assembly of an array of high-performance UV photodetectors. This technique uses UV lithography, which is not only very compatible with common semiconductor manufacturing techniques, but also enables precise patterning modification. A typical detector has impressive photo-response performance under 365 nm irradiation, with an extremely low dark current of 40 pA, a high I light /I dark ratio over 10 5 , a high responsivity of 4.23 AW -1 , and a decent specific detectivity of 1.76 × 10 12 Jones. Additional optoelectronic studies demonstrate the strong homogeneity and repeatability of the photodetectors array, enabling it to serve as a reliable UV image sensor with enough spatial resolution. These outcomes highlight the proposed patterning technique's enormous potential., (© 2023 Wiley-VCH GmbH.)

Objective: To establish a machine learning radiomics model that can accurately predict MRI enhancement patterns of glioma based on T2 fluid attenuated inversion recovery (T2-FLAIR) images for optimizing the workflow of magnetic resonance imaging (MRI) examinations of glioma patients., Methods: We retrospectively collected preoperative MR T2-FLAIR images from 385 patients with pathologically confirmed glioma, who were divided into enhancing and non-enhancing groups according to the enhancement pattern. Predictive radiomics models were established using Gaussian Process, Linear Regression, Linear Regression-Least absolute shrinkage and selection operator, Support Vector Machine, Linear Discriminant Analysis or Naive Bayes as the classifiers in the training cohort ( n =201)and tested both in the internal ( n =85) and external validation cohorts ( n =99). The receiver-operating characteristic curve was used to assess the predictive performance of the models., Results: The predictive model constructed based on 15 radiomics features using Gaussian Process as the classifier had the best predictive performance in both the training cohort and the internal validation cohort, with areas under the curve (AUC) of 0.88 (95% CI : 0.81-0.94) and 0.80 (95% CI : 0.71-0.88), respectively. In the external validation cohort, the model showed an AUC of 0.81 (95% CI : 0.71-0.90) with sensitivity, specificity, positive predictive value and negative predictive value of 0.98, 0.61, 0.76 and 0.96, respectively., Conclusion: The T2-FLAIR-based machine learning radiomics model can accurately predict the enhancement pattern of gliomas on MRI.

Background: The systematic review of clinical research papers is a labor-intensive and time-consuming process that often involves the screening of thousands of titles and abstracts. The accuracy and efficiency of this process are critical for the quality of the review and subsequent health care decisions. Traditional methods rely heavily on human reviewers, often requiring a significant investment of time and resources., Objective: This study aims to assess the performance of the OpenAI generative pretrained transformer (GPT) and GPT-4 application programming interfaces (APIs) in accurately and efficiently identifying relevant titles and abstracts from real-world clinical review data sets and comparing their performance against ground truth labeling by 2 independent human reviewers., Methods: We introduce a novel workflow using the Chat GPT and GPT-4 APIs for screening titles and abstracts in clinical reviews. A Python script was created to make calls to the API with the screening criteria in natural language and a corpus of title and abstract data sets filtered by a minimum of 2 human reviewers. We compared the performance of our model against human-reviewed papers across 6 review papers, screening over 24,000 titles and abstracts., Results: Our results show an accuracy of 0.91, a macro F 1 -score of 0.60, a sensitivity of excluded papers of 0.91, and a sensitivity of included papers of 0.76. The interrater variability between 2 independent human screeners was κ=0.46, and the prevalence and bias-adjusted κ between our proposed methods and the consensus-based human decisions was κ=0.96. On a randomly selected subset of papers, the GPT models demonstrated the ability to provide reasoning for their decisions and corrected their initial decisions upon being asked to explain their reasoning for incorrect classifications., Conclusions: Large language models have the potential to streamline the clinical review process, save valuable time and effort for researchers, and contribute to the overall quality of clinical reviews. By prioritizing the workflow and acting as an aid rather than a replacement for researchers and reviewers, models such as GPT-4 can enhance efficiency and lead to more accurate and reliable conclusions in medical research., (©Eddie Guo, Mehul Gupta, Jiawen Deng, Ye-Jean Park, Michael Paget, Christopher Naugler. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 12.01.2024.)

Objectives: Intraoperative molecular imaging (IMI) uses cancer-targeted fluorescent probe to locate nodules. Pafolacianine is a Food and Drug Administration-approved fluorescent probe for lung cancer. However, it has a 8-12% false negative rate for localization. Our goal is to define preoperative predictors of tumour localization by IMI., Methods: We performed a retrospective review of patients who underwent IMI using pafolacianine for lung lesions from June 2015 to August 2019. Candidate predictors including sex, age, body mass index, smoking history, tumour size, distance of tumour from surface, use of neoadjuvant therapy and positron emission tomography avidity were included. The outcome was fluorescence in vivo and comprehensively included those who were true or false positives negatives. Multiple imputation was used to handle the missing data. The final model was evaluated using the area under the receiver operating characteristic curve., Results: Three hundred nine patients were included in our study. The mean age was 64 (standard deviation 13) and 68% had a smoking history. The mean distance of the tumours from the pleural surface was 0.4 cm (standard deviation 0.6). Smoking in pack-years and distance from pleura had an odds ratio of 0.99 [95% confidence interval: 0.98-0.99; P = 0.03] and 0.46 [95% confidence interval: 0.27-0.78; P = 0.004], respectively. The final model had an area under the receiver operating characteristic curve of 0.68 and was used to create a nomogram that gives a probability of fluorescence in vivo., Conclusions: Primary tumours that are deeper from the pleural surface, especially in patients with a higher pack-years, are associated with a decreased likelihood of intraoperative localization. We identified a nomogram to predict the likelihood of tumour localization with IMI with pafolacianine., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

It has been recognized that depth of invasion (DOI) is closely associated with patient survival for most types of cancer. The purpose of this study was to determine the DOI optimal cutoff value and its prognostic value in laryngeal squamous carcinoma (LSCC). Most importantly, we evaluated the prognostic performance of five candidate modified T-classification models in patients with LSCC. LSCC patients from Harbin Medical University Cancer Hospital and Chinese Academy of Medical Sciences Cancer Hospital were divided into training group (n = 412) and validation group (n = 147). The primary outcomes were overall survival (OS) and relapse-free survival (RFS), and the effect of DOI on prognosis was analyzed using a multivariable regression model. We identified the optimal model based on its simplicity, goodness of fit and Harrell's consistency index. Further independent testing was performed on the external validation queue. The nomograms was constructed to predict an individual's OS rate at one, three, and five years. In multivariate analysis, we found significant associations between DOI and OS (Depth of Medium-risk invasion HR, 2.631; P < .001. Depth of high-risk invasion: HR, 5.287; P < .001) and RFS (Depth of high-risk invasion: HR, 1.937; P = .016). Model 4 outperformed the American Joint Committee on Cancer (AJCC) staging system based on a low Akaike information criterion score, improvement in the concordance index, and Kaplan-Meier curves. Inclusion of DOI in the current AJCC staging system can improve the differentiation of T classification in LSCC patients.