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Abstract: Myelofibrosis (MF) in the chronic phase is a challenging disease to treat, and conventional treatment options are geared toward symptom palliation. In this prospective, multicenter, phase 2 trial, 21 patients with MF (18 chronic phase, 2 accelerated phase, and 1 blast phase) were treated with a 10-day schedule of subcutaneous decitabine at 0.3 mg/kg per day. The overall response rate was 33% (95% confidence interval, 15-57), primarily manifested as an improvement in cytopenias. The median duration of response was 7 months (range, 3-44). A high International Prognostic Scoring System risk score, high baseline fetal hemoglobin level, and sustained decrease in circulating CD34+ cell counts were associated with response to decitabine. All patients experienced at least 1 grade 3/4 cytopenia. Nonhematologic toxicities were less frequent, with fatigue, anorexia, and hypocalcemia being the most common. Given the lack of effective therapies in MF with severe cytopenias, this study supports further investigation into the use of hypomethylating agents as single agents or in combination therapies. This trial was registered at www.ClinicalTrials.gov as #NCT00095784., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Abnormal alkaline phosphatase (ALP) levels have been linked to breast cancer, prostate cancer, bone damage, gingivitis and abnormal liver function. Monitoring ALP levels is important for better diagnosis and treatment of these diseases. Detection of ALP by colorimetric methods is very portable in terms of signal reading, but still suffers from low sensitivity. SERS can achieve high sensitivity detection, but cannot be separated from large precision instruments. Therefore, researchers have worked to optimize various aspects of the sensor, such as sensitivity, detection time, and operating procedures, to enable portable and rapid ALP detection. Isothermal amplification using simple system components meets the current demand for rapid, portable assays. We have developed a novel one-pot high-efficiency ALP assay strategy called IHP-GT. IHP-GT performs a one-step cascade amplification using only one probe (IGHP) as a template. The phosphorylated primer P binds to IGHP, forming a P/IGHP structure. At this point, the G-quadruplex closes and no signal is generated. In the presence of ALP, primer P is dephosphorylated to remove the restriction and then amplified in a cascade using IGHP as a template to release the full G-quadruplex structure. The single-stranded G-quadruplex will bend to form a secondary structure, facilitating secondary amplification starting with primer AT to produce PrG and P'. The PrG structure will trigger triple amplification, enabling cascade amplification. The G-quadruplex structure produced by cascade amplification has the dual role of promoting amplification of primer AT and binding to ThT to produce a fluorescent signal. The IHP-GT method provides a highly sensitive detection of ALP in less than 90 min and has been successfully used to analyze ALP in human serum samples. In addition, IHP-GT can be used to screen for ALP inhibitors. Importantly, we lyophilized the IHP-GT reaction components into powder form for user-friendly poc testing., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The rapid classification of crude baijiu is pivotal for its industrialization and automated development. In this study, a colorimetric sensor array employing peroxidase nanase (Por-CoMoO 4 ) was developed to detect reducing substances and crude baijiu. The peroxidase-like activity of CoMoO 4 was significantly enhanced by porphyrin (Por), exhibiting a K m value of 0.044 mM and V max of 19.37 × 10 -8 for TMB substrate. Peroxidase activity varies at different pH levels. Organic and crude baijiu scavenge free radicals, thereby inhibiting oxTMB formation and yielding distinctive fingerprint profiles. Using linear discriminant analysis, 14 types of small molecules and 16 varieties of Luzhou-flavor crude baijiu were identified within specific concentration ranges. The method achieved 100% accuracy in distinguishing baijiu samples sourced from different distilleries, offering a straightforward, rapid, and effective approach to differentiate crude baijiu during alcoholic beverage production.

Cellular senescence is involved in the progression of neurodegenerative diseases. Motor neurons exhibit senescence-like alterations in ALS. BRD7, identified as a regulatory factor associated with cellular senescence, its function in ALS remains unclear. This study aims to investigate the potential role and mechanisms of BRD7 in ALS. We analyzed RNA levels using qRT-PCR, protein levels through immunofluorescence and western blot, and apoptosis via TUNEL staining. Cell transfection was conducted for in vitro experiments. The level of β-galactosidase was measured by β-galactosidase activity detection kit. ALS motor neurons exhibited senescence-like alterations, characterized by increased activity of p53, p21, and β-galactosidase, as well as reduced lamin B1 staining. Additionally, the expression of BRD7 was upregulated and induced cellular senescence and apoptosis. Downregulation of BRD7 alleviates the cellular senescence by inhibiting p21 rather than p53. Knockdown of BRD7 inhibited p53 mitochondrial translocation, leading to reduced apoptosis. Our results suggest that BRD7 plays an important role in the survival of ALS motor neurons. BRD7 knockdown can reduce cellular senescence and apoptosis by inhibiting p21 and p53 mitochondrial translocation., 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 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

To investigate the changing patterns of respiratory viral infections within the context of COVID-19 pandemic. The etiological surveillance data of eight respiratory viral pathogens among patients with ARIs in Shanghai between 2013 and 2023 were analyzed to evaluate the dynamic patterns of respiratory viral infections in Shanghai compared to global other regions during pre-pandemic (period 1), pandemic (period 2), and post-pandemic (period 3) periods of COVID-19. In Shanghai and various other global regions, there was a delay of 2‒4 months in the peak positive rate of IFV and a reverse seasonality for RSV, HMPV, and HBoV was observed following the relaxation of NPIs. The proportion of patients infected with any of these eight viruses experiencing fever or high fever notably increased. During the entire study period, IFV was consistently identified as the most prevalent virus, with IFV-B as the predominant stain during period 2, and IFV-A regained its dominance following the lifting of NPIs. The proportion of RSV among children significantly increased during period 2 compared to period 1. With the relaxation of NPIs, there has been a resurgence of certain viral pathogens, accompanied by notable alterations in seasonal patterns and the spectrum of viral pathogens., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Hypertrophic scar (HS) formation is a cutaneous fibroproliferative disease that occurs after skin injuries and results in severe functional and esthetic disability. To date, few drugs have shown satisfactory outcomes for the treatment of HS formation. Transforming growth factor-beta (TGF-β)/Notch interaction via small mothers against decapentaplegic 3 (Smad3) could facilitate HS formation; therefore, targeting TGF-β/ Notch interaction via Smad3 is a potential therapeutic strategy to attenuate HS formation. In addition, optic atrophy 1 (OPA1)-mediated mitochondrial fusion contributes to fibroblast proliferation, and TGF-β/Smad3 axis and the Notch1 pathway facilitate OPA1-mediated mitochondrial fusion. Thus, the aim of this study was to investigate whether drugs targeting TGF-β/Notch interaction via Smad3 suppressed fibroblast proliferation to attenuate HS formation through OPA1-mediated mitochondrial fusion. We found that the TGF-β pathway, Notch pathway, and TGF-β/Notch interaction via Smad3 were inhibited by pirfenidone, the gamma- secretase inhibitor DAPT, and SIS3 in human keloid fibroblasts (HKF) and an HS rat model, respectively. Protein interaction was detected by co-immunoprecipitation, and mitochondrial morphology was determined by electron microscopy. Our results indicated that pirfenidone, DAPT, and SIS3 suppressed the proliferation of HKFs and attenuated HS formation in the HS rat model by inhibiting TGF-β/Notch interaction via Smad3. Moreover, pirfenidone, DAPT, and SIS3 hindered OPA1-mediated mitochondrial fusion through inhibiting TGF-β/Notch interaction, thereby suppressing the proliferation of HS fibroblasts and HS formation. In summary, these findings investigating the effects of drugs targeting TGF-β/Notch interaction on HS formation might lead to novel drugs for the treatment of HS formation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hydrolytic enzymes are essential components in second-generation biofuel technology and food fermentation processes. Nanozymes show promise for large-scale industrial applications as replacements for natural enzymes due to their distinct advantages. However, there remains a research gap concerning glycosidase nanozymes. In this study, a Zn-based single-atom nanozyme (ZnN 4 -900) is developed for efficient glycosidic bond hydrolysis in an aqueous solution. The planar structure of the class-porphyrin N 4 material approximatively mimicked the catalytic centers of natural enzymes, facilitating oxidase-like (OXD-like) activity and promoting glycosidic bond cleavage. Theoretical calculations show that the Zn site can act as Lewis acids, attacking the C─O bond in glycosidic bonds. Additionally, ZnN 4 -900 has the ability to degrade starch and produce reducing sugars that increased yeast cell biomass by 32.86% and ethanol production by 14.56%. This catalyst held promising potential for enhancing processes in ethanol brewing and starch degradation industries., (© 2024 Wiley‐VCH GmbH.)

Background: For patients with breast cancer undergoing neoadjuvant chemotherapy (NACT), most of the existing prediction models of pathologic complete response (pCR) using clinicopathological features were based on standard statistical models like logistic regression, while models based on machine learning mostly utilized imaging data and/or gene expression data. This study aims to develop a robust and accessible machine learning model to predict pCR using clinicopathological features alone, which can be used to facilitate clinical decision-making in diverse settings., Methods: The model was developed and validated within the National Cancer Data Base (NCDB, 2018-2020) and an external cohort at the University of Chicago (2010-2020). We compared logistic regression and machine learning models, and examined whether incorporating quantitative clinicopathological features improved model performance. Decision curve analysis was conducted to assess the model's clinical utility., Results: We identified 56,209 NCDB patients receiving NACT (pCR rate: 34.0%). The machine learning model incorporating quantitative clinicopathological features showed the best discrimination performance among all the fitted models [area under the receiver operating characteristic curve (AUC): 0.785, 95% confidence interval (CI): 0.778-0.792], along with outstanding calibration performance. The model performed best among patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer (AUC: 0.817, 95% CI: 0.802-0.832); and by adopting a 7% prediction threshold, the model achieved 90.5% sensitivity and 48.8% specificity, with decision curve analysis finding a 23.1% net reduction in chemotherapy use. In the external testing set of 584 patients (pCR rate: 33.4%), the model maintained robust performance both overall (AUC: 0.711, 95% CI: 0.668-0.753) and in the HR+/HER2- subgroup (AUC: 0.810, 95% CI: 0.742-0.878)., Conclusions: The study developed a machine learning model ( https://huolab.cri.uchicago.edu/sample-apps/pcrmodel ) to predict pCR in breast cancer patients undergoing NACT that demonstrated robust discrimination and calibration performance. The model performed particularly well among patients with HR+/HER2- breast cancer, having the potential to identify patients who are less likely to achieve pCR and can consider alternative treatment strategies over chemotherapy. The model can also serve as a robust baseline model that can be integrated with smaller datasets containing additional granular features in future research., (© 2024. The Author(s).)

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The discovery of new effective therapeutic drugs is always a priority. Magnesium lithospermate B (MLB), a native polyphenol acid, is the major component of the aqueous extracts from Danshen, a traditional Chinese medicine derived from the dry root and rhizome of Salvia miltiorrhiza . MLB has been reported to have antioxidant, anti-inflammatory, and ion channel-regulating activities in several diseases, including cardiovascular, renal, and neuronal diseases. However, the effect of MLB on cancer progression has not been reported. In this study, a series of cellular and molecular experiments were conducted on two CRC cell lines (HCT116 and SW480) to investigate the effects of. The results demonstrated that MLB exerted inhibitory effects on cell proliferation, migration, and invasion. The administration of 50 mg/kg MLB inhibited tumor growth in HCT116 cells in xenografted models. Importantly, we found that MLB treatment inhibited the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway, and activation of JAK2-STAT3 signaling with interleukin 6 or overexpression STAT3 significantly suppressed the inhibitory effect of MLB. These findings provide evidence that MLB could inhibit CRC cell progression in vitro and might serve as a potential therapeutic drug for the treatment of CRC.

This study aimed to investigate the clinical outcomes of local muscle or myocutaneous flap transfer for emergent repair of Gustilo IIIB open tibiofibular fractures. This retrospective case series study included patients with Gustilo IIIB open tibiofibular fractures treated by local muscle or myocutaneous flap transfer in Weifang People's Hospital between May 2016 and April 2021. Fifteenpatients (11 males aged 19-72 years) were included. The follow-up ranged from 8 to 24 months. The ranges of bone healing time and wound healing time were 6-17 months and 1-3 weeks, respectively. The length of hospital stay was 26 days (11-50 days). All patients reported acceptable functional recovery and satisfactory leg appearance, with Johner-Wruhs scores of excellent, good, and fair in 10, four, and one patients, respectively. The excellent-good rate was 93.3%. The complications included one case of infection and one case of nonunion. In conclusion, local muscle or myocutaneous flap transfer for emergent repair of Gustilo IIIB open tibiofibular fractures may be useful in providing adequate soft tissue coverage and fracture healing with low complication and infection rates., (© 2024. The Author(s).)

Given the significant and potential fatal implications of glyphosate (GLY) residues on human health and the integrity of ecosystems, their presence has garnered substantial global concern and scrutiny. Herein, we introduced a pioneering colorimetric sensing platform, the first of its kind, based on ternary metal-organic frameworks (ZnCo-ZIFs@MIL-101(Fe)). This innovative platform enabled ultra-sensitive, affordable, portable and rapid on-site detection of GLY. This platform achieved a wider linear range for GLY of 0.02-40 μg/mL with an exhibiting remarkable detection limit of 1 ng/mL, which was attributed to the electronic hybridization of the Fe 3+ , Co 2+ , and Zn 2+ metal centers of ZnCo-ZIFs@MIL-101(Fe), significantly enhancing the composite's catalytic performance. The assay was successfully employed to detect GLY in food and herb samples. Moreover, to meet the demand of in-field detection for GLY, a smartphone detection method based on ZnCo-ZIFs@MIL-101(Fe) with visual, intelligent, and portable features was fabricated. This detection concentration range of GLY was 0-1 μg/mL, and the limit of smartphone detection was 23 ng/mL. Furthermore, this sensor seamlessly integrated with smartphones and paper-based microfluidic chips (μPADs), which constructed a portable test strips-smartphone sensing platform for facilitating real-time and on-site visual quantitative detection of GLY. The detection concentration range was 0-1 μg/mL, and the limit was calculated as low as 75 ng/mL. The assay was highly adaptable in practical applications. In summary, our study paved a novel pathway for the design and utilization of multi-metal MOF nanozymes in on-site pesticide monitoring., 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: Lynch syndrome (LS) is an autosomal-dominant, hereditary cancer predisposition syndrome caused by pathogenic variants (PVs) in one of the mismatch-repair genes MLH1, MSH2/EPCAM, MSH6, or PMS2. Individuals who have MLH1 PVs have high lifetime risks of colorectal cancer (CRC) and endometrial cancer (EC). There is controversy regarding whether a younger age at diagnosis (or anticipation) occurs in MLH1-associated LS. The objective of this study was to assess anticipation in families with MLH1-associated LS by using statistical models while controlling for potential confounders., Methods: Data from 31 families with MLH1 PVs were obtained from an academic registry. Wilcoxon signed-rank tests on parent-child-pairs as well as parametric Weibull and semiparametric Cox proportional hazards and Cox mixed-effects models were used to calculate hazard ratios or to compare mean ages at CRC/EC diagnosis by generation. Models were also corrected for ascertainment bias and birth-cohort effects., Results: A trend toward younger ages at diagnosis of CRC/EC in successive generations, ranging from 3.2 to 15.7 years, was observed in MLH1 PV carrier families. A greater hazard for cancer in younger generations was not precluded by the inclusion of birth cohorts in the model. Individuals who had MLH1 variants with no Mlh1 activity were at a 78% greater hazard for CRC/EC than those who retained Mlh1 activity., Conclusions: The current results demonstrated evidence in support of anticipation in families with MLH1-associated LS across all statistical models. Mutational effects on Mlh1 activity influenced the hazard for CRC/EC. Screening based on the youngest age of cancer diagnosis in MLH1-LS families is recommended., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

The correct classification of strong-flavored crude baijiu affects its quality and overall standard and is crucial for the intelligent development of the baijiu industry. In this work, we developed a novel optical sensing array using lanthanum-doped carbon dots (La-CDs). Using La-CDs with three metal complex dyes-chromium black T, alizarin red, and dimethylphenol orange-we were able to detect organic acids and tannic acid (TA) in crude baijiu in a way that was both colorimetric and fluorescent for the first time. Based on the indicator displacement (IDA) principle, organic acids competitively replace the dyes' binding sites on La 3+ , causing the dye colors to change to varying degrees. TA quenches the fluorescence of quantum dots through an internal filtering effect. We analyzed the data using pattern recognition algorithms such as HCA, PCA, and LDA, successfully classifying and identifying 16 types of strong-flavored crude baijiu, which included 10 types of carboxylic acids and various grades. In blind tests of 32 crude baijiu samples, the colorimetric method achieved a 94 % accuracy rate, while the fluorescence method achieved 100 %. The sensor demonstrates significant advantages in response speed., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background and Aims: Vascular smooth muscle cell (VSMC) senescence is crucial for the development of atherosclerosis, characterized by metabolic abnormalities. Tumour necrosis factor receptor-associated protein 1 (TRAP1), a metabolic regulator associated with ageing, might be implicated in atherosclerosis. As the role of TRAP1 in atherosclerosis remains elusive, this study aimed to examine the function of TRAP1 in VSMC senescence and atherosclerosis., Methods: TRAP1 expression was measured in the aortic tissues of patients and mice with atherosclerosis using western blot and RT-qPCR. Senescent VSMC models were established by oncogenic Ras, and cellular senescence was evaluated by measuring senescence-associated β-galactosidase expression and other senescence markers. Chromatin immunoprecipitation (ChIP) analysis was performed to explore the potential role of TRAP1 in atherosclerosis., Results: VSMC-specific TRAP1 deficiency mitigated VSMC senescence and atherosclerosis via metabolic reprogramming. Mechanistically, TRAP1 significantly increased aerobic glycolysis, leading to elevated lactate production. Accumulated lactate promoted histone H4 lysine 12 lactylation (H4K12la) by down-regulating the unique histone lysine delactylase HDAC3. H4K12la was enriched in the senescence-associated secretory phenotype (SASP) promoter, activating SASP transcription and exacerbating VSMC senescence. In VSMC-specific Trap1 knockout ApoeKO mice (ApoeKOTrap1SMCKO), the plaque area, senescence markers, H4K12la, and SASP were reduced. Additionally, pharmacological inhibition and proteolysis-targeting chimera (PROTAC)-mediated TRAP1 degradation effectively attenuated atherosclerosis in vivo., Conclusions: This study reveals a novel mechanism by which mitonuclear communication orchestrates gene expression in VSMC senescence and atherosclerosis. TRAP1-mediated metabolic reprogramming increases lactate-dependent H4K12la via HDAC3, promoting SASP expression and offering a new therapeutic direction for VSMC senescence and atherosclerosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. 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.)

Sea cucumbers are predominant deposit feeders in benthic ecosystems, providing protective benefits to coral reefs by reducing disease prevalence. However, how they receive sufficient nutrition from seabed sediments remains poorly understood. Here, we investigate Holothuria leucospilota, an ecologically significant tropical sea cucumber, to elucidate digestive mechanisms underlying marine deposit-feeding. Genomic analysis reveals intriguing evolutionary adaptation characterized by an expansion of digestive carbohydrase genes and a contraction of digestive protease genes, suggesting specialization in digesting microalgae. Developmentally, two pivotal dietary shifts, namely, from endogenous nutrition to planktonic feeding, and from planktonic feeding to deposit feeding, induce changes in digestive tract enzyme profiles, with adults mainly expressing carbohydrases and lipases. A nuanced symbiotic relationship exists between gut microbiota and the host, namely, specific resident bacteria supply crucial enzymes for food digestion, while other bacteria are digested and provide assimilable nutrients. Our study further identifies Holothuroidea lineage-specific lysozymes that are restrictedly expressed in the intestines to support bacterial digestion. Overall, this work advances our knowledge of the evolutionary innovations in the sea cucumber digestive system which enable them to efficiently utilize nutrients from seabed sediments and promote food recycling within marine ecosystems., (© 2024. The Author(s).)

Objectives: The purpose of this study is to determine if a universal 120-kV ultra-high pitch and virtual monoenergetic images (VMIs) protocol on the photon-counting computed tomography (PCCT) system can provide sufficient image quality for pediatric abdominal imaging, regardless of size, compared with protocols using a size-dependent kV and dual-source flash mode on the energy-integrating CT (EICT) system., Materials and Methods: One solid water insert and 3 iodine (2, 5, 10 mg I/mL) inserts were attached or inserted into phantoms of variable sizes, simulating the abdomens of a newborn, 5-year-old, 10-year-old, and adult-sized pediatric patients. Each phantom setting was scanned on an EICT using clinical size-specific kV dual-source protocols with a pitch of 3.0. The scans were performed with fixed scanning parameters, and the CTDI vol values of full dose were 0.30, 0.71, 1.05, and 7.40 mGy for newborn to adult size, respectively. In addition, half dose scans were acquired on EICT. Each phantom was then scanned on a PCCT (Siemens Alpha) using a universal 120-kV protocol with the same full dose and half dose as determined above on the EICT scanner. All other parameters matched to EICT settings. Virtual monoenergetic images were generated from PCCT scans between 40 and 80 keV with a 5-keV interval. Image quality metrics were compared between PCCT VMIs and EICT, including image noise (measured as standard deviation of solid water), contrast-to-noise ratio (CNR) (measured at iodine inserts with solid water as background), and noise power spectrum (measured in uniform phantom regions)., Results: Noise at a PCCT VMI of 70 keV (7.0 ± 0.6 HU for newborn, 14.7 ± 1.6 HU for adult) is comparable ( P > 0.05, t test) or significantly lower ( P < 0.05, t test) compared with EICT (7.8 ± 0.8 HU for newborn, 15.3 ± 1.5 HU for adult). Iodine CNR from PCCT VMI at 50 keV (50.8 ± 8.4 for newborn, 27.3 ± 2.8 for adult) is comparable ( P > 0.05, t test) or significantly higher ( P < 0.05, t test) to the corresponding EICT measurements (57.5 ± 6.7 for newborn, 13.8 ± 1.7 for adult). The noise power spectrum curve shape of PCCT VMI is similar to EICT, despite PCCT VMI exhibiting higher noise at low keV levels., Conclusions: The universal PCCT 120 kV with ultra-high pitch and postprocessed VMIs demonstrated equivalent or improved performance in noise (70 keV) and iodine CNR (50 keV) for pediatric abdominal CT, compared with size-specific kV images on the EICT., Competing Interests: Conflicts of interest and sources of funding: None declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder distinguished by gradual depletion of motor neurons. RNA binding motif protein 5 (RBM5), an abundantly expressed RNA-binding protein, plays a critical role in the process of cellular death. However, little is known about the role of RBM5 in the pathogenesis of ALS. Here, we found that RBM5 was upregulated in ALS hSOD1 G93A -NSC34 cell models and hSOD1 G93A mice due to a reduction of miR-141-5p. The upregulation of RBM5 increased the apoptosis of motor neurons by inhibiting Rac1-mediated neuroprotection. In contrast, genetic knockdown of RBM5 rescued motor neurons from hSOD1 G93A -induced degeneration by activating Rac1 signaling. The neuroprotective effect of RBM5-knockdown was significantly inhibited by the Rac1 inhibitor, NSC23766. These findings suggest that RBM5 could potentially serve as a therapeutic target in ALS by activating the Rac1 signalling., 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.)

Quantitative microRNA (miRNA) detection is crucial for early breast cancer diagnosis and prognosis. However, quick and stable fluorescence sensing for miRNA identification is still challenging. This work developed a novel label-free detection method based on AuNPs etching for quantitatively detecting miRNA-155. A layer of AuNPs was grown on the surface of mesoporous silica nanoparticles (MSN) loaded with Rhodamine 6G (R6G) using seed-mediated growth, followed by probe attachment. In the presence of miRNA-155, the MSN@R6G@AuNP surface loses the protection of the attached probe, rendering AuNPs susceptible to etching by hydrochloric acid. This results in a significant fluorescent signal being released in the free space. The encapsulation with AuNPs effectively reduces signal leakage, while the rapid etching process shortens detection time. This strategy enables sensitive and fast detection with a detection range of 100 fM to 100 nM, a detection limit of 2.18 fM, and a detection time of 30 min. The recovery rate in normal human serum ranges from 99.02 % to 106.34 %. This work presents a simple biosensing strategy with significant potential for application in tumor diagnosis., 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.)

The development of point-of-care testing (POCT) for circulating tumor DNA (ctDNA) is meaningful for the non-invasive cancers screening and diagnosis, particularly in resource-limited settings. The microfluidic paper-based analytical device (μPAD) provides an ideal platform, its application in ctDNA assays remains underexplored. In this work, a multifunctional μPAD was manufactured, which can enhance the efficiency and reduce the cost of ctDNA sensing. Additionally, a smartphone-based application analysis was fabricated for convenient, portable detection and colorimetric signal readout. Moreover, the novel oxidase-like MnB 2 nanozyme was introduced in the sandwiches sensing strategy, utilizing its catalytic properties to effectively generate a colorimetric signal. The use of MnB 2 nanozyme in sensing application is relatively novel, and its catalytic performance and mechanism was thoroughly evaluated via experiment and density functional theory (DFT) calculations. After optimizing the detection conditions, the proposed biosensor exhibited satisfactory results. Furthermore, the method was successfully used to detect ctDNA in tumor cell lysates and peripheral blood samples from tumor-bearing mice. The results were consistent with standard qPCR method, affirming the reliability of our POCT analysis device in ctDNA detection. Thus, this work not only provides a paper-based POCT device and intelligent analysis tool for portable cancers diagnosis, but it also paves a new application path for MnB 2 nanozyme in the sensing filed., Competing Interests: Declaration of Competing interest The author(s) declared no potential conflicts of interest with respect to the research, author-ship, and/or publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fast, sensitive, and portable detection of genetic modification contributes to agricultural security and food safety. Here, we developed RPA-CRISPR/Cas12a-G-quadruplex colorimetric assays that can combine with intelligent recognition by deep learning algorithms to achieve sensitive, rapid, and portable detection of the CaMV35S promoter. When the crRNA-Cas12a complex recognizes the RPA amplification product, Cas12 cleaves the G-quadruplex, causing the G4-Hemin complex to lose its peroxide mimetic enzyme function and be unable to catalyze the conversion of ABTS 2- to ABTS, allowing CaMV35S concentration to be determined based on ABTS absorbance. By utilizing the RPA-CRISPR/Cas12a-G4 assay, we achieved a CaMV35S limit of detection down to 10 aM and a 0.01 % genetic modification sample in 45 min. Deep learning algorithms are designed for highly accurate classification of color results. Yolov5 objective finding and Resnet classification algorithms have been trained to identify trace (0.01 %) CaMV35S more accurately than naked eye colorimetry. We also coupled deep learning algorithms with a smartphone app to achieve portable and rapid photo identification. Overall, our findings enable low cost ($0.43), high accuracy, and intelligent detection of the CaMV35S promoter., 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: During the 2022-2023 influenza season, the influenza activities in most regions of China were postponed, including Beijing. The unusually delayed influenza epidemic posed a challenge to the effectiveness of the influenza vaccine., Methods: Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022-2023 influenza season against influenza A-associated outpatient and emergency-department-attended influenza-like illness (ILI) in Beijing, China, from 9 January to 30 April 2023., Results: The analysis included 8301 medically attended ILI patients, of which 1342 (46.2%) had influenza A(H1N1)pdm09, 1554 (53.4%) had influenza A(H3N2), and 11 (0.4%) had co-infection of the two viruses. VE against influenza A-associated ILI patients was 23.2% (95% CI: -6.5% to 44.6%) overall, and 23.1%, 9.9%, and 33.8% among children aged 6 months to 17 years, adults aged 18-59 years, and adults aged ≥60 years, respectively. VE against influenza A(H1N1)pdm09 and against influenza A(H3N2) were 36.2% (95% CI: -1.9% to 60.1%) and 9.5% (95% CI: -34.1% to 39.0%), respectively. VE of the group with vaccination intervals of 14-90 days (70.1%, 95% CI: -145.4 to 96.4) was higher than that of the groups with a vaccination interval of 90-149 days (18.7%, 95% CI: -42.4% to 53.6%) and ≥150 days (21.2%, 95% CI: -18.8% to 47.7%)., Conclusions: A moderate VE against influenza A(H1N1)pdm09 and a low VE against influenza A(H3N2) were observed in Beijing during the 2022-2023 influenza season, a season characterized with a delayed and high-intensity influenza epidemic. VE appears to be better within three months after vaccination. Our findings indicate a potential need for the optimization of vaccination policies and underscore the importance of continuous monitoring of influenza to enhance vaccines and optimizing vaccination timing.

Camellia oleifera is an important woody oil tree in China, in which the flowers and fruits appear during the same period. The endogenous hormone changes and transcription expression levels in different parts of the flower tissue (sepals, petals, stamens, and pistils), flower buds, leaves, and seeds of Changlin 23 high-yield (H), Changlin low-yield (L), and control (CK) C. oleifera groups were studied. The abscisic acid (ABA) content in the petals and stamens in the L group was significantly higher than that in the H and CK groups, which may be related to flower and fruit drops. The high N6-isopentenyladenine (iP) and indole acetic acid (IAA) contents in the flower buds may be associated with a high yield. Comparative transcriptome analysis showed that the protein phosphatase 2C (PP2C), jasmonate-zim-domain protein (JAZ), and WRKY-related differentially expressed genes (DEGs) may play an important role in determining leaf color. Gene set enrichment analysis (GSEA) comparison showed that jasmonic acid (JA) and cytokinin play an important role in determining the pistil of the H group. In this study, endogenous hormone and transcriptome analyses were carried out to identify the factors influencing the large yield difference in C. oleifera in the same year, which provides a theoretical basis for C. oleifera in the future., (© 2024. The Author(s).)

This study investigates the impact of Hashimoto's thyroiditis (HT), an autoimmune disorder, on the papillary thyroid cancer (PTC) microenvironment using a dataset of 140,456 cells from 11 patients. By comparing PTC cases with and without HT, we identify HT-specific cell populations (HASCs) and their role in creating a TSH-suppressive environment via mTE3, nTE0, and nTE2 thyroid cells. These cells facilitate intricate immune-stromal communication through the MIF-(CD74+CXCR4) axis, emphasizing immune regulation in the TSH context. In the realm of personalized medicine, our HASC-focused analysis within the TCGA-THCA dataset validates the utility of HASC profiling for guiding tailored therapies. Moreover, we introduce a novel, objective method to determine K-means clustering coefficients in copy number variation inference from bulk RNA-seq data, mitigating the arbitrariness in conventional coefficient selection. Collectively, our research presents a detailed single-cell atlas illustrating HT-PTC interactions, deepening our understanding of HT's modulatory effects on PTC microenvironments. It contributes to our understanding of autoimmunity-carcinogenesis dynamics and charts a course for discovering new therapeutic targets in PTC, advancing cancer genomics and immunotherapy research., 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 Ma, Li, Huo, Su, Jin, Lu, Sun, Zhang and Chen.)

Introduction: Infectious diseases pose a significant global health and economic burden, underscoring the critical need for precise predictive models. The Baidu index provides enhanced real-time surveillance capabilities that augment traditional systems., Methods: Baidu search engine data on the keyword "fever" were extracted from 255 cities in China from November 2022 to January 2023. Onset and peak dates for influenza epidemics were identified by testing various criteria that combined thresholds and consecutive days., Results: The most effective scenario for indicating epidemic commencement involved a 90th percentile threshold exceeded for seven consecutive days, minimizing false starts. Peak detection was optimized using a 7-day moving average, balancing stability and precision., Discussion: The use of internet search data, such as the Baidu index, significantly improves the timeliness and accuracy of disease surveillance models. This innovative approach supports faster public health interventions and demonstrates its potential for enhancing epidemic monitoring and response efforts., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2024.)

Brain organoids are widely used to model brain development and diseases. However, a major challenge in their application is the insufficient supply of oxygen and nutrients to the core region, restricting the size and maturation of the organoids. In order to vascularize brain organoids and enhance the nutritional supply to their core areas, two-photon polymerization (TPP) 3D printing is employed to fabricate high-resolution meshed vessels in this study. These vessels made of photoresist with densely distributed micropores with a diameter of 20 μm on the sidewall, are cocultured with brain organoids to facilitate the diffusion of culture medium into the organoids. The vascularized organoids exhibit dimensional breaking growth and enhanced proliferation, reduced hypoxia and apoptosis, suggesting that the 3D-printed meshed vessels partially mimic vascular function to promote the culture of organoids. Furthermore, cortical, striatal and medial ganglionic eminence (MGE) organoids are respectively differentiated to generate Cortico-Striatal-MGE assembloids by 3D-printed vessels. The enhanced migration, projection and excitatory signaling transduction are observed between different brain regional organoids in the assembloids. This study presents an approach using TPP 3D printing to construct vascularized brain organoids and assembloids for enhancing the development and assembly, offering a research model and platform for neurological diseases.

Tunnel widening is a frequent problem following arthroscopic ligament reconstruction surgery that may primarily arise from a graft-tunnel mismatch caused by errors in surgical instruments and methods. The present study aimed to observe the influence of current surgical instruments and methods on graft-tunnel matching. We established an in vitro model using porcine Achilles tendons and tibias, and compared traditional surgical instruments (control group) with custom instruments (experimental group). Graft measurements, bone-tunnel creation, and measurements of the maximum pullout force of the graft from the bone tunnel were performed. Results indicated that the measuring gauge developed by our research group (capable of accurate measurement of graft diameters) may mitigate errors arising from graft-diameter measurement using traditional measuring cylinders. Therefore, errors caused by current surgical instruments and surgical methods led to an increase in graft-tunnel mismatches. The degree of mismatch was greater at the tibial end than at the femoral end., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Microorganisms are crucial components of the aquatic ecosystem due to their immense diversity and abundance. They are vital in sustaining ecological services, especially in maintaining essential biogeochemical cycles. Recent years have seen a substantial increase in surplus nitrogenous pollutants in aquatic ecosystems due to the heightened occurrence of anthropogenic activities. Elevated levels of free ammonia (FA, NH 3 ), stemming from the discharge of excess nitrogenous pollutants, have caused notable fluctuations in aquatic ecosystems, leading to water eutrophication and various ecological challenges. The impact of these oscillations on microbial communities in aquatic ecosystems has not been extensively studied. This study employed 16S rRNA gene amplicon sequencing to systematically investigate the dynamics, co-occurrence networks, and assembly processes of microbial communities and their subcommunities (abundant, moderate, and rare) in the Luanhe River Diversion Project in China. Our findings indicate that NH 3 concentration significantly influences the dynamics of microbial communities, with a notable decrease in community Richness and Phylogenetic Distance alongside increased community dissimilarity under higher NH 3 conditions. The analysis revealed that certain microbial groups, particularly Actinobacteriaota, were notably more prevalent in environments with elevated NH 3 levels, suggesting their potential resilience or adaptive responses to NH 3 stress. Additionally, through co-occurrence network analysis, we observed dynamic changes in network topology and increased connectedness under NH 3 stress. Key nodes, identified as connectors and module hubs, played crucial roles in maintaining network structure, particularly Cyanobacteria and Actinobacteriaota. Furthermore, stochastic processes, particularly drift and dispersal limitation, predominantly shaped the microbial communities. Within the three subcommunities, the impact of drift became more pronounced as the effect of dispersal limitation diminished. Overall, elucidating the dynamics of microbial communities in aquatic ecosystems exposed to NH 3 can enhance our comprehension of the ecological mechanisms of microbial communities and provide new insights into the conservation of microbial community diversity and ecological functions., Importance: The research presented in this paper explores how varying concentrations of free ammonia impact microbial communities in aquatic ecosystems. By employing advanced gene sequencing techniques, the study reveals significant changes in microbial diversity and network structures in response to increased ammonia levels. Key findings indicate that high ammonia concentrations lead to a decrease in microbial richness and diversity while increasing community dissimilarity. Notably, certain microbial groups, like Actinobacteria, show resilience to ammonia stress. This research enhances our understanding of how pollution affects microbial ecosystems and underscores the importance of maintaining balanced ammonia levels to preserve microbial diversity and ecosystem health., Competing Interests: The authors declare no conflict of interest.

Objective: To assess the effects of in-bed cycling (IBC) combined with high flow nasal cannula (HFNC) on arterial oxygen and respiratory dynamics in patients with severe respiratory failure (RF)., Methods: We retrospectively collected clinical data of 103 patients with severe RF, admitted to the intensive care unit (ICU) of The Second Affiliated Hospital of Harbin Medical University from March 2021 to March 2023. Among them, 50 patients had HFNC alone (control group), and 53 patients did IBC in addition to HFNC (observation group). We compared arterial oxygen index, lung function, respiratory dynamics, and clinical efficacy between the two groups., Results: There was no significant difference in the basic data between the two groups ( P >0.05). After the treatment, the improvement of the partial pressure of oxygen (PaO 2 ), PaO 2 /fraction of inspired oxygen (FiO 2 ), arterial oxygen saturation (SaO 2 ), and oxygen delivery (DO 2 ) in the observation group was significantly better than that in the control group ( P <0.05). After the treatment, the improvement of lung function in the observation group was better than that in the control group ( P <0.05). After the treatment, the end expiratory pulmonary pressure (P tp-ee ) and driving pressure (△P tp ) levels in the observation group were significantly higher, and the duration of ICU hospitalization and the incidence of ICU-acquired weakness(ICU-AW) were significantly lower than those in the control group ( P <0.05)., Conclusions: IBC combined with HFNC can significantly improve arterial oxygen levels, lung function, and respiratory dynamics in patients with severe RF. IBC in combination with HFNC is associated with shorter stay time in the ICU, reduced of ICU-acquired weakness, and better physical recovery of patients., (Copyright: © Pakistan Journal of Medical Sciences.)

Purpose: We aimed to update the trend of hypofractionated whole-breast irradiation (HF-WBI) use over time in the US and examine factors associated with lack of HF-WBI adoption for patients with early-stage invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) undergoing a lumpectomy., Methods and Materials: Among patients who underwent a lumpectomy, we identified 928,034 patients with early-stage IBC and 330,964 patients with DCIS in the 2004 to 2020 National Cancer Database. We defined HF-WBI as 2.5-3.33 Gy/fraction to the breast and conventionally fractionated WBI as 1.8-2.0 Gy/fraction. We evaluated the trend of HF-WBI utilization using a generalized linear model with the log link and binomial distribution. Factors associated with HF-WBI utilization were assessed using multivariable logistic regression in patients diagnosed between 2018 and 2020., Results: Among patients with IBC, HF-WBI use has significantly increased from 0.7% in 2004 to 63.9% in 2020. Similarly, HF-WBI usage among patients with DCIS has also increased significantly from 0.4% in 2004 to 56.6% in 2020. Black patients with IBC were less likely than White patients to receive HF-WBI (adjusted odds ratio [AOR] 0.81; 95% CI, 0.77-0.85). Community cancer programs were less likely to administer HF-WBI to patients with IBC (AOR, 0.80; 95% CI, 0.77-0.84) and to those with DCIS (AOR, 0.87; 95% CI, 0.79-0.96) than academic/research programs. Younger age, positive nodes, larger tumor size, low volume programs, and facility location were also associated with lack of HF-WBI adoption in both patient cohorts., Conclusions: HF-WBI utilization among postlumpectomy patients has significantly increased from 2004 to 2020 and can finally be considered standard of care in the US. We found substantial disparities in adoption within patient and facility subgroups. Reducing disparities in HF-WBI adoption has the potential to further alleviate health care costs while improving patients' quality of life., Competing Interests: Disclosures None., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Integrative medicine (IM) has received the American Society of Clinical Oncology's endorsement for managing cancer treatment-related side effects. Little is known about racial differences in familiarity, interest, and use of IM among patients with breast cancer., Methods: Patients with breast cancer enrolled in the Chicago Multiethnic Epidemiologic Breast Cancer Cohort were surveyed regarding familiarity, interest, and use of acupuncture, massage, meditation, music therapy, and yoga. Familiarity and interest, measured by a 5-point Likert scale, was modeled using proportional odds. Use was self-reported, and modeled using binary logistic regression., Results: Of 1,300 respondents (71.4% White and 21.9% Black), Black patients were less likely than White patients to be familiar with acupuncture (aOR 0.60, 95% CI 0.41-0.87); there were no racial differences in familiarity with massage, meditation, music therapy, and yoga. While there were no differences in interest in acupuncture between Black and White patients (aOR 1.12, 95% CI 0.76-1.65), Black patients were more interested in massage (aOR 1.86, 95% CI 1.25-2.77), meditation (aOR 2.03, 95% CI 1.37-3.00), music therapy (aOR 2.68, 95% CI 1.80-3.99), and yoga (aOR 2.10, 95% CI 1.41-3.12). Black patients were less likely than White patients to have used acupuncture (aOR 0.49, 95% CI 0.29-0.84); but there were no racial differences in use of massage, meditation, music therapy, and yoga., Conclusion: Black patients expressed more interest in IM than their White counterparts; there were no racial differences in IM use, except lower acupuncture use among Black patients. A breast program focused on equity should provide access to these services for patients with breast cancer., (© 2024. The Author(s).)

Discrimination of segmented Baijiu contributes to stabilizing the quality of products, improving revenue-generating effects. A fluorescence sensor array is constructed based on four fluorescence characteristic peaks of terbium@lanthanum metal-organic framework (Tb@La-MOF). Its fluorescence signal is specifically quenched, when Tb@La-MOF encounters acetaldehyde. Acetaldehyde may inhibit the absorption of energy by the organic ligands in MOF, or/and hydrogen bonding with -COOH on the organic ligand, resulting in energy transfer to Tb(Ⅲ). According to this, the quantitative detection of acetaldehyde is completed with a range of 10-300 μM and the detection limit of 5.5 μM. At the same time, it has been successfully applied to the discrimination of segmented Baijiu. Fifteen segmented from three wine cellars are 100 % discriminated with the combined processing of sensor arrays and analytical methods. Accuracy, simplicity, and low-cost are highlights of this fluorescence sensor array, which has considerable potential for application in detection, production, and food field., 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.)

In this era of precision medicine, incorporating quantitative measures of estrogen receptor (ER)/progesterone receptor (PR)/Ki-67 expressions and genomic assays could more precisely identify neoadjuvant systemic therapy with the highest likelihood of response and tumor downstaging. In our recent study, we quantified the likelihood of achieving breast-conserving surgery (BCS vs. mastectomy) after neoadjuvant chemotherapy or endocrine therapy as a function of demographics, quantitative ER/PR/Ki-67 expressions, 21-gene recurrence scores, or 70-gene risk scores in early-stage, hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Using the 2010-2020 National Cancer Database, we found that the BCS rate after neoadjuvant chemotherapy was higher among patients with high 21-gene recurrence scores, lower ER/PR expression, or higher Ki-67 expression. Most patients who received neoadjuvant endocrine therapy underwent BCS, which was mostly dependent on ER expression. Asian women were less likely than white women to undergo BCS after neoadjuvant treatments. Lack of health insurance was associated with lower odds of BCS in both neoadjuvant settings. Although our study provides insight into the associations of BCS with quantitative biomarkers at a single time point, several questions remain unanswered. With the evolving landscape of neoadjuvant therapies in development for HR-positive/HER2-negative breast cancer, ongoing work using quantitative biomarkers and genomic assay scores is needed to select the right neoadjuvant systemic therapy for the right patient. Given the increasing amount of data available at the time of breast cancer diagnosis, novel computational approaches are needed to integrate patient demographic and tumor-specific factors to predict the optimal treatment strategy and likelihood of BCS., (© 2024. Society of Surgical Oncology.)

Background: Given increased neoadjuvant therapy use in early-stage, hormone receptor (HR)-positive/HER2-negative breast cancer, we sought to quantify likelihood of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) or endocrine therapy (NET) as a function of ER%/PR%/Ki-67%, 21-gene recurrence scores (RS), or 70-gene risk groups., Methods: We analyzed the 2010-2020 National Cancer Database. Surgery was categorized as "mastectomy/BCS." Logistic regression was performed. Adjusted odds ratios (AOR) were per 10-unit increase in ER%/PR%/Ki-67%., Results: Overall, 42.3% underwent BCS after NACT, whereas 64.0% did after NET. Increasing ER% (AOR = 0.96, 95% confidence interval [CI] 0.94-0.97) or PR% (AOR=0.98, 95% CI 0.96-0.99) was associated with lower odds of BCS after NACT. Increasing Ki-67% was associated with greater odds of BCS (AOR = 1.07, 95% CI 1.04-1.10). Breast-conserving surgery rates increased by ~20 percentage points, with Ki-67% ≥15 or RS >20. Patients with a low (43.0%, AOR = 0.50, 95% CI 0.29-0.88) or intermediate (46.4%, AOR = 0.58, 95% CI 0.41-0.81) RS were less likely than patients with a high RS (65.0%) to undergo BCS after NACT. Increasing ER% was associated with higher odds of BCS after NET (AOR = 1.09, 95% CI 1.01-1.17). Breast-conserving surgery rates increased by ~20 percentage points between ER <50% and >80%. In both cohorts, the odds of BCS were similar between 70-gene low-risk and high-risk groups. Asian or uninsured patients had lower odds of BCS., Conclusions: Neoadjuvant chemotherapy is unlikely to downstage tumors with a low-intermediate RS, higher ER%/PR%, or lower Ki-67%. Breast-conserving surgery after NET was most dependent on ER%. Findings could facilitate treatment decision-making based on tumor biology and racial/socioeconomic disparities and improve patient counseling on the likelihood of successful BCS., (© 2024. The Author(s).)

This study aimed at using α-L-arabinofuranosidase CcABF to improve the clarity and active substances in fermented ginkgo kernel juice by artificial neural network (ANN) modeling and genetic algorithm (GA) optimization. A credible three-layer feedforward ANN model was established to predict the optimal parameters for CcABF clarification. The experiments proved the highest transmittance of 89.40% for fermented ginkgo kernel juice with this understanding, which exhibited a 25.56% increase over the unclarified group. With the clarification of CcABF, the antioxidant capacity in juice was enhanced with the increase of total phenolic and flavone contents, and the maximum DPPH and hydroxyl radical scavenging rates were increased by 89.71% and 26.65%, respectively. The contents of toxic ginkgolic acids declined markedly, while the active ingredients of ginkgetin and ginkgolide B showed a modest increase. Moreover, changes in free amino acids and volatile compounds improved the nutritive value and flavor of clarified fermented ginkgo kernel juice., 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 © 2023. Published by Elsevier Ltd.)

A novel approach for investigating the formation of solid electrolyte interphase (SEI) in Na-ion batteries (NIB) through the coupling of in situ liquid electrochemical transmission electron microscopy (ec-TEM) and gas-chromatography mass-spectrometry (GC/MS) is proposed. To optimize this coupling, experiments are conducted on the sodiation of hard carbon materials (HC) using two setups: in situ ec-TEM holder and ex situ setup. Electrolyte (NP30) is intentionally degraded using cyclic voltammetry (CV), and the recovered liquid product is analyzed using GC/MS. Solid product (µ-chip) is analyzed using TEM techniques in a post-mortem analysis. The ex situ experiments served as a reference to for insertion of Na+ ions in the HC, SEI size (389 nm), SEI composition (P, Na, F, and O), and Na plating. The in situ TEM analysis reveals a cyclability limitation, this issue appears to be caused by the plating of Na in the form of a "foam" structure, resulting from the gas release during the reaction of Na with DMC/EC electrolyte. The foam structure, subsequently transformes into a second SEI, is electrochemically inactive and reduces the cyclability of the battery. Overall, the results demonstrate the powerful synergy achieved by coupling in situ ec-TEM and GC/MS techniques., (© 2024 The Author(s). Small Methods published by Wiley‐VCH GmbH.)

The levels of uric acid (UA) and tyrosine (Tyr) in sweat reflect a person's overall health. However, simultaneously identifying several components in sweat remains challenging. Here, we achieve simultaneous detection of UA and Tyr by synthesizing CoWO 4 @CNT in a single step using a hydrothermal method. CoWO 4 's high catalytic efficacy and large CNT reaction area allow the detection of 1-1000 μM UA (LOD = 0.14 μM) and 5-1000 μM Tyr (LOD = 4.2 μM). To increase sweat collection, we developed a polydopamine-polyacrylamide (PDA-PAM) hydrogel with a sweat absorption rate of up to 226%. Finally, by monitoring sweat at various times of day, our sensors can discriminate between UA and Tyr in real sweat, and the results are consistent with the individuals' activity levels. Overall, the effective electrocatalytically active materials and PDA-PAM hydrogel improve the detection of UA and Tyr. The remarkable performance of CoWO 4 @CNT in real samples shows that it has the potential to improve health detection and real-time sweat analysis.

Purpose: The comprehensive evaluation of kV selection on photon-counting computed tomography (PCCT) has yet to be performed. The aim of the study is to evaluate and determine the optimal kV options for variable pediatric body sizes on the PCCT unit., Materials and Methods: In this study, 4 phantoms of variable sizes were utilized to represent abdomens of newborn, 5-year-old, 10-year-old, and adult-sized pediatric patients. One solid water and 4 solid iodine inserts with known concentrations (2, 5, 10, and 15 mg I/mL) were inserted into phantoms. Each phantom setting was scanned on a PCCT system (Siemens Alpha) with 4 kV options (70 and 90 kV under Quantum Mode, 120 and 140 kV under QuantumPlus Mode) and clinical dual-source (3.0 pitch) protocol. For each phantom setting, radiation dose (CTDIvol) was determined by clinical dose settings and matched for all kV acquisitions. Sixty percent clinical dose images were also acquired. Reconstruction was matched across all acquisitions using Qr40 kernel and QIR level 3. Virtual monoenergetic images (VMIs) between 40 and 80 keV with 10 keV interval were generated on the scanner. Low-energy and high-energy images were reconstructed from each scan and subsequently used to generate an iodine map (IM) using an image-based 2-material decomposition method. Image noise of VMIs from each kV acquisition was calculated and compared between kV options. Absolute percent error (APE) of iodine CT number accuracy in VMIs was calculated and compared. Root mean square error (RMSE) and bias of iodine quantification from IMs were compared across kV options., Results: At the newborn size and 50 keV VMI, noise is lower at low kV acquisitions (70 kV: 10.5 HU, 90 kV: 10.4 HU), compared with high kV acquisitions (120 kV: 13.8 HU, 140 kV: 13.9 HU). At the newborn size and 70 keV VMI, the image noise from different kV options is comparable (9.4 HU for 70 kV, 8.9 HU for 90 kV, 9.7 HU for 120 kV, 10.2 HU for 140 kV). For APE of VMI, high kV (120 or 140 kV) performed overall better than low kV (70 or 90 kV). At the 5-year-old size, APE of 90 kV (median: 3.6%) is significantly higher (P < 0.001, Kruskal-Wallis rank sum test with Bonferroni correction) than 140 kV (median: 1.6%). At adult size, APE of 70 kV (median: 18.0%) is significantly higher (P < 0.0001, Kruskal-Wallis rank sum test with Bonferroni correction) than 120 kV (median: 1.4%) or 140 kV (median: 0.8%). The high kV also demonstrated lower RMSE and bias than the low kV across all controlled conditions. At 10-year-old size, RMSE and bias of 120 kV are 1.4 and 0.2 mg I/mL, whereas those from 70 kV are 1.9 and 0.8 mg I/mL., Conclusions: The high kV options (120 or 140 kV) on the PCCT unit demonstrated overall better performance than the low kV options (70 or 90 kV), in terms of image quality of VMIs and IMs. Our results recommend the use of high kV for general body imaging on the PCCT., Competing Interests: Conflicts of interest and sources of funding: None declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Real-time monitoring of biological markers in sweat is a valuable tool for health assessment. In this study, we have developed an innovative wearable biosensor for precise analysis of glucose in sweat during physical activities. The sensor is based on a single-atom catalyst of platinum (Pt) uniformly dispersed on tricobalt tetroxide (Co 3 O 4 ) nanorods and reduced graphene oxide (rGO), featuring a unique three-dimensional nanostructure and excellent glucose electrocatalytic performance with a wide detection range of 1-800 μM. Additionally, density functional theory calculations have revealed the synergetic role of Pt active sites in the Pt single-atom catalyst (Co 3 O 4 /rGO/Pt) in glucose adsorption and electron transfer, thereby enhancing sensor performance. To enable application in wearable devices, we designed an S-shaped microfluidic chip and a point-of-care testing (POCT) device, both of which were validated for effectiveness through actual use by volunteers. This research provides valuable insights and innovative approaches for analyzing sweat glucose using wearable devices, contributing to the advancement of personalized healthcare., 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.)

Simultaneous detection of multiple tumor markers is of great significance for an accurate diagnosis and early treatment of cancer. Electrochemical homogeneous biosensing strategies have been shown to have advantages, such as high sensitivity and no electrode modification, but they are still a challenge in the field of simultaneous detection of multiple tumor markers. The ER, PR, HER2, and Ki67 proteins are the standard biomarkers for the clinical molecular typing of breast cancer. Precise, sensitive, and simultaneous detection of these four biomarkers is of great importance in the molecular typing of breast cancer, which helps in the creation of personalized treatment plans. In the present study, we developed an electrochemical homogeneous electrochemical bioplatform based on metal ions/SiO 2 NPs/magnetic beads for detection of the four biomarkers and simultaneous diagnosis of the 10 types of breast cancer directly in human serum at one system by a single electrode. The electrochemical bioplatform has a short detection time of 140 min; however, the current clinical tissue testing time takes about 1 week. Also, the electrochemical bioplatform selectively detects HER2, ER, Ki67, and PR in a range of 0-1000 pg/mL with detection limits of 2, 1.8, 10.36, and 1.33 pg/mL, respectively.

Dollar spot is a destructive foliar disease of amenity turfgrass caused by the fungus Clarireedia spp., and mainly Clarireedia jacksonii on the northern US region's cool-season grass. Oxalic acid (OA) is an important pathogenicity factor in related fungal plant pathogens such as Sclerotinia sclerotiorum , however, the role of OA in the pathogenic development of C. jacksonii remains unclear due to its recalcitrance to genetic manipulation. To overcome these challenges, a CRISPR/Cas9-mediated homologous recombination approach was developed. Using this novel approach, the oxaloacetate acetylhydrolase ( Oah ) gene that is required for the biosynthesis of OA was deleted from C. jacksonii wild-type stain. Two independent knockout mutants, Δ Cjoah-1 and Δ Cjoah-2 , were generated and inoculated on potted creeping bentgrass along with a wild-type isolate (WT) and a genome sequenced isolate LWC-10. After 12 days, bentgrass inoculated with the mutants Δ Cjoah-1 and Δ Cjoah-2 exhibited 59.41% lower dollar spot severity compared to the WT and LWC-10 isolates. Oxalic acid production and environmental acidification were significantly reduced in both mutants when compared to the WT and LWC-10. Surprisingly, stromal formation was also severely undermined in the mutants in vitro, suggesting a critical developmental role of OA independent of plant infection. These results demonstrate that OA plays a significant role in C. jacksonii virulence and provide novel directions for future management of dollar spot.

The sea cucumber Apostichopus japonicus can expel internal organs under stress and regenerate them subsequently. However, growth is delayed during regeneration, significantly impacting the industry. Circular RNAs (circRNAs) are single-stranded circular RNA molecules produced through alternative splicing of mRNA precursors. They play crucial roles in regulating gene expression via the ceRNA mechanism. In this study, circRNA profiles of control and regenerated intestines were constructed. A total of 15,874 circRNAs were identified, with a length of 300-350 nucleotides (nt) being the most abundant. Sanger sequencing confirmed the circular structure of circRNA398. Compared with the normal intestine, 50 and 83 differentially expressed circRNAs (DE-circRNAs) were identified in the regenerated intestine at 1 and 3 days post evisceration (dpe), respectively. Gene ontology (GO) terms for signal transduction and development regulation were most significantly enriched in 1dpeVScon and 3dpeVScon treatments, respectively. The dual-luciferase assay revealed that circRNA8388 functions as a sponge for miR-2392, participating in the remodeling of the extracellular matrix (ECM). In conclusion, these findings will contribute to the enhancement of the non-coding RNA database for echinoderms and lay the groundwork for future investigations into circRNA regulation during intestinal regeneration., 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.)

Fagopyrum tataricum , an important medicinal and edible crop, possesses significant agricultural and economic value. However, the development of buckwheat varieties and yields has been hindered by the delayed breeding progress despite the abundant material resources in China. Current research indicates that quantitative trait loci (QTLs) play a crucial role in controlling plant seed type and yield. To address these limitations, this study constructed recombinant inbred lines (RILs) utilizing both cultivated species and wild buckwheat as raw materials. In total, 84,521 Single Nucleotide Polymorphism (SNP) markers were identified through Genotyping-by-Sequencing (GBS) technology, and high-resolution and high-density SNP genetic maps were developed, which had significant value for QTL mapping, gene cloning and comparative mapping of buckwheat. In this study, we successfully identified 5 QTLs related to thousand grain weight (TGW), 9 for grain length (GL), and 1 for grain width (GW) by combining seed type and TGW data from 202 RIL populations in four different environments, within which one co-located QTL for TGW were discovered on the first chromosome. Transcriptome analysis during different grain development stages revealed 59 significant expression differences between the two materials, which can serve as candidate genes for further investigation into the regulation of grain weight and yield enhancement. The mapped major loci controlling TGW, GL and GW will be valuable for gene cloning and reveal the mechanism underlying grain development and marker-assisted selection in Tartary buckwheat., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© Prof. H.S. Srivastava Foundation for Science and Society 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.)

Breast cancer includes several subtypes with distinct characteristic biological, pathologic, and clinical features. Elucidating subtype-specific genetic etiology could provide insights into the heterogeneity of breast cancer to facilitate the development of improved prevention and treatment approaches. In this study, we conducted pairwise case-case comparisons among five breast cancer subtypes by applying a case-case genome-wide association study (CC-GWAS) approach to summary statistics data of the Breast Cancer Association Consortium. The approach identified 13 statistically significant loci and eight suggestive loci, the majority of which were identified from comparisons between triple-negative breast cancer (TNBC) and luminal A breast cancer. Associations of lead variants in 12 loci remained statistically significant after accounting for previously reported breast cancer susceptibility variants, among which, two were genome-wide significant. Fine mapping implicated putative functional/causal variants and risk genes at several loci, e.g., 3q26.31/TNFSF10, 8q22.3/NACAP1/GRHL2, and 8q23.3/LINC00536/TRPS1, for TNBC as compared with luminal cancer. Functional investigation further identified rs16867605 at 8q22.3 as a SNP that modulates the enhancer activity of GRHL2. Subtype-informative polygenic risk scores (PRS) were derived, and patients with a high subtype-informative PRS had an up to two-fold increased risk of being diagnosed with TNBC instead of luminal cancers. The CC-GWAS PRS remained statistically significant after adjusting for TNBC PRS derived from traditional case-control GWAS in The Cancer Genome Atlas and the African Ancestry Breast Cancer Genetic Consortium. The CC-GWAS PRS was also associated with overall survival and disease-specific survival among patients with breast cancer. Overall, these findings have advanced our understanding of the genetic etiology of breast cancer subtypes, particularly for TNBC. Significance: The discovery of subtype-informative genetic risk variants for breast cancer advances our understanding of the etiologic heterogeneity of breast cancer, which could accelerate the identification of targets and personalized strategies for prevention and treatment., (©2024 American Association for Cancer Research.)

In recent years, there has been a growing concern regarding health issues arising from exposure to nanoplastics (Nps) in the natural environment. The Nps bioaccumulate within the body via the circulatory system and accumulate in the liver, resulting in damage. Previous studies have demonstrated that maltol, derived from red ginseng ( Panax ginseng C.A. Meyer) as a Maillard product, exhibits hepatoprotective effects by alleviating liver damage caused by carbon tetrachloride or cisplatin. In order to explore the specific mechanism of maltol in improving hepatotoxicity induced by Nps, mice exposed to 100 mg/kg Nps were given maltol at doses of 50 and 100 mg/kg, respectively. The results showed that Nps induced an increase in the levels of liver apoptotic factors BAX and cytochrome c, a decrease in the levels of the autophagy key gene LC3 II/I, and an increase in P62. It also caused oxidative stress by affecting the Nrf2/HO-1 pathway, and a decrease in GPX4 protein expression suggested the occurrence of ferroptosis. However, treatment with maltol significantly improved these changes. In addition, maltol (2, 4, and 8 μM) also protected human normal liver L02 cells from Np (400 μg/mL)-induced damage. Our data suggest that maltol could ameliorate Np-induced L02 cytotoxicity by reducing autophagy-dependent oxidative stress, exhibiting similar protective effects in vitro as in vivo . This study helps shed light on the specific molecular mechanism of Np-induced hepatotoxicity. For the first time, we studied the protective effect of maltol on Np-induced liver injury from multiple perspectives, expanding the possibility of treatment for diseases caused by environmental pollutants.

Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and Ki67 are four crucial biomarkers used in the clinical diagnosis of breast cancer. Accurate detection of these biomarkers is essential for an effective diagnosis and treatment. MOF-based micronano motors (MOFtors) are promising for various applications, including environmental remediation, targeted nanosurgery, and biomarker detection. This paper presents a clinically feasible diagnostic electrochemical micronano motor biosensor, built on a miniature swimmer, for the multiplex detection and grading of breast cancer biomarkers. We designed a biosensor, named MOFtor-MSEM, incorporating aptamers and antibodies functionalized on SiO 2 @Co-Fe-MOF, which acts as a miniature swimmer in solution. The SiO 2 @Co-Fe-MOF serves as the body, while complementary double-chain-linked antibodies function as paddles. In a homogeneous solution, when a positive voltage is applied to the working electrode, the electrostatic interaction between the neutral SiO 2 @Co-Fe-MOF and the negatively charged complementary double-linked antibody causes the antibody to move toward the electrode and then regress due to water resistance. This back-and-forth motion propels the miniature swimmer, enabling it to move the target analyte through the solution. The sensor features an automatic "sample-amplifying signal-output" process, achieving simultaneous signal amplification and output of four electrochemical signals on a single nanomaterial, a significant challenge in electrochemical sensing. The biosensor boasts a short detection time of 40 min, compared to approximately 1 week for current clinical tissue testing. Additionally, the bioplatform selectively detects HER2, ER, Ki67, and PR in the range of 0-1500 pg/mL, with detection limits of 0.01420, 0.03201, 0.01430, and 0.01229 pg/mL, respectively.

Combination therapy is a promising strategy for cancers, increasing therapeutic options and reducing drug resistance. Yet, systematic identification of efficacious drug combinations is limited by the combinatorial explosion caused by a large number of possible drug pairs and diseases. At present, machine learning techniques have been widely applied to predict drug combinations, but most studies rely on the response of drug combinations to specific cell lines and are not entirely satisfactory in terms of mechanism interpretability and model scalability. Here, we proposed a novel network propagation-based machine learning framework to predict synergistic drug combinations. Based on the topological information of a comprehensive drug-drug association network, we innovatively introduced an affinity score between drug pairs as one of the features to train machine learning models. We applied network-based strategy to evaluate their therapeutic potential to different cancer types. Finally, we identified 17 specific-, 21 general- and 40 broad-spectrum antitumor drug combinations, in which 69% drug combinations were validated by vitro cellular experiments, 83% drug combinations were validated by literature reports and 100% drug combinations were validated by biological function analyses. By quantifying the network relationships between drug targets and cancer-related driver genes in the human protein-protein interactome, we show the existence of four distinct patterns of drug-drug-disease relationships. We also revealed that 32 biological pathways were correlated with the synergistic mechanism of broad-spectrum antitumor drug combinations. Overall, our model offers a powerful scalable screening framework for cancer treatments., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Females exposed prenatally to diethylstilbestrol (DES) have an elevated risk of cervical dysplasia, breast cancer, and clear cell adenocarcinoma (CCA) of the cervix/vagina. Testicular cancer risk is increased in prenatally exposed males. Epigenetic changes may mediate the transmission of DES effects to the next ("third") generation of offspring., Methods: Using data self-reported by third-generation females, we assessed DES in relation to the risk of cancer and benign breast and reproductive tract conditions. Using data from prenatally DES-exposed and unexposed mothers, we assessed DES in relation to cancer risk in their female and male offspring. Cancer risk was assessed by standardized incidence ratios (SIR) and 95% confidence intervals (CI); the risks of benign and malignant diagnoses were assessed by hazard ratios (HR) and 95% CI., Results: In self-reported data, DES exposure was not associated with an increased risk of overall cancer (HR 0.83; CI 0.36-1.90), breast cancer, or severe cervical dysplasia. No females reported CCA. The risk of borderline ovarian cancer appeared elevated, but the HR was imprecise (3.46; CI 0.37-32.42). Based on mothers' reports, DES exposure did not increase the risk of overall cancer (HR 0.80; CI 0.49-1.32) or of other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated (HR 1.41; CI 0.70-2.86), but the CI was wide. The risk of testicular cancer was not elevated in exposed males; no cases of prostate cancer were reported., Conclusions: To date, there is little evidence that DES is associated with cancer risk in third-generation females or males, but these individuals are relatively young, and further follow-up is needed.

A CRISPR/Cas12a-coupled multiplexed strand displacement amplification (CMSDA) for the detection of miR155 has been developed. Non-specific amplification was avoided by designing a single-stranded DNA template with a hairpin structure. The detection target miR155 was used as a primer to initiate a multiple-strand displacement reaction to produce abundant ssDNA. ssDNA was recognized by the Cas12a/CrRNA binary complex, activating the trans-cleaving activity of Cas12a. The multiple-strand displacement reaction is more efficiently detected compared with a single-strand displacement reaction. The detection range is from 250 pM to 1 nM, and the limit of the detection is 6.5 pM. The proposed method showed a good applicability in complex serum environments, indicating that the method has a broad prospect for disease detection and clinical application. In addition, we designed a dual-cavity PCR tube, which realized one-tube detection of miRNA155 and avoided open-cap contamination., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)