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Mei-Ling Xia,1 Wen-Xuan Lin,2 Ling-Ling Gao,3 Mao-Ling Zhang,1 Zhi-Yun Li,4 Li-Ling Zeng4 1Reproductive Centre, Guangdong Women and Children Hospital, Guangzhou, People’s Republic of China; 2Nursing Department, Guangdong Women and Children Hospital, Guangzhou, People’s Republic of China; 3School of Nursing, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Obstetric Department, Guangdong Women and Children Hospital, Guangzhou, People’s Republic of ChinaCorrespondence: Ling-Ling Gao, School of Nursing, Sun Yat-sen University, Guangzhou, People’s Republic of China, Tel +86-20-87335013, Fax +86-20-87333043, Email gaoll@mail.sysu.edu.cnPurpose: Knowledge of the readiness for hospital discharge can help health care professionals accurately determine the patients’ discharge time. However, few studies were on the readiness for discharge and its related factors among mothers with cesarean sections. Thus, this study aims to examine the readiness for hospital discharge and its associated factors among Chinese mothers with cesarean sections.Patients and Methods: A single-centre cross-sectional study was conducted from September 2020 to March 2021 in Guangzhou, China. Three hundred thirty-nine mothers with cesarean sections completed the questionnaires on demographic and obstetric characteristics, readiness for hospital discharge, quality for discharge teaching, parenting sense of competence, family function, and social support. Multiple linear regression analysis was used to identify independent factors influencing readiness for hospital discharge among mothers with cesarean sections.Results: The total score of readiness for hospital discharge was 136.47 ± 25.29. The quality of discharge teaching, parenting sense of competence, number of cesareans, family function, and attending antenatal classes were independent factors influencing the readiness for hospital discharge (P

Liu WW, Li WD, Zhang YJ, Zhang ML. Cancer Manag Res. 2021;13:439–447. Following publication of the article, the authors raised concerns over the duplication of the two bar charts in Figure 5D. In addition, concerns were also raised about the duplication of images from Figure 2 with images from an unrelated article. Specifically, The image for Figure 2C, MDA-MB-231, miR-497-5p-inhibitor, has been duplicated with the image for Figure 2d, A549, inhibit-NC, from Ge H, Wang L, Chen W, Wang L. Mechanism of miR-760 Reversing Lung Cancer Immune Escape by Downregulating IDO1 and Eliminating Regulatory T Cells Based on Mathematical Biology. Computational and Mathematical Methods in Medicine. 2022;2022: Article ID 2960773. https://doi.org/10.1155/2022/2960773. When approached for an explanation, the authors were cooperative but were unable to provide a sufficient explanation for the image duplication or provide sufficient original data for their study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Man-Li Zhang, Wei-Wei Liu, Wei-Dong Li Department of Breast Surgery, Cangzhou People’s Hospital, Cangzhou City, 061001, Hebei Province, People’s Republic of ChinaCorrespondence: Man-Li ZhangDepartment of Breast Surgery, Cangzhou People’s Hospital, Intersection of Chongqing Road and Jilin Avenue, Yunhe District, Cangzhou City, 061001, Hebei Province, People’s Republic of ChinaTel +86-15832714444Email manko8866@126.comBackground: Triple negative breast cancer (TNBC) poses a great threat to patient prognosis. LncRNA-miRNA is a molecular module formed by a long non-coding RNA (LncRNA) and a microRNA (miRNA) that mediates the metastatic potential of tumours such as TNBC, and luteolin (LU) is a natural compound with anti-TNBC activity.Objective: We aim to explore the regulatory mechanism of terminal differentiation-induced non-coding RNA (TINCR)-miR-761 molecular module in early TNBC, as well as its influence on anti-tumor activity of LU.Methods: The serum was collected from TNBC patients in early stage to detect the expression of TINCR and miR-761 using RT-PCR. Transwell method was applied for the determination of cell migration and invasion, Western blot for epithelial–mesenchymal transition (EMT), flow cytometry (FCM) for cell apoptosis, and dual luciferase reporter and RNA pull-down experiment for the verification of the targeted relationship between TINCR and miR-761.Results: Both TINCR and miR-761 were up-regulated in the serum of patients with early TNBC and the area under the curve (AUC) of the two for distinguishing TNBC from BC was not less than 0.850. In the cell function tests, down-regulation of TINCR or miR-761 notably suppressed the metastatic potentials (cell migration, invasion and EMT) of TNBC cells were remarkably inhibited, while up-regulation of TINCR or miR-761 notably promoted the metastatic potentials. We also confirmed that TINCR acts as the molecular sponge of miR-761, and has positive regulation on it. Besides, LU can significantly down-regulate TINCR and miR-761, and partially offset the anti-TNBC activity of LU when they were abnormally up-regulated, which was mainly reflected in the decrease of anti-proliferation and pro-apoptotic ability of LU against TNBC.Conclusion: There is an imbalance of TINCR-miR-761 molecular module in early TNBC, which may be a potential new therapeutic target of TNBC.Keywords: triple negative breast cancer, TINCR, miR-761, metastasis, luteolin

Wei-Wei Liu, Wei-Dong Li, Yan-Ju Zhang, Man-Li Zhang Breast Center, Cangzhou People’s Hospital, Cangzhou 061000, Hebei Province, People’s Republic of ChinaCorrespondence: Man-Li ZhangBreast Center, Cangzhou People’s Hospital, Intersection of Chongqing Road and Jilin North Road, Yunhe District, Cangzhou 061000, Hebei Province, People’s Republic of ChinaTel +86-135-6645-8334Email manko8866@126.comObjective: To explore the regulatory role of miR497-5p–CCNE1 axis in triple-negative breast cancer (TNBC) cells and its predictive value for early diagnosis.Methods: Cancer tissue and adjacent tissue samples were collected from 86 patients with TNBC.RT-PCR was used to detect the expression of miR497-5p and CCNE1 (target gene) mRNA, determined by biological prediction in tissue and TNBC cells. ROC was used to analyze the diagnostic value of miR497-5p in TNBC. MTT, invasion, and flow cytometry were used to detect the proliferation, invasion, cycle, apoptosis rate, and expression of related proteins of TNBC cells with overexpression of miR497-5p or knockdown of CCNE1.Results: RT-qPCR results showed that miR497-5p levels were significantly downregulated in TNBC tissue and cells, while CCNE1 expression was significantly upregulated, and miR497-5p expression was negatively correlated with that of CCNE1 (P< 0.001). ROC analysis showed that the AUC of miR497-5p for TNBC was > 0.9, which had better diagnostic value. The cell tests revealed that miR497-5p played a role in tumor inhibition, including inhibiting proliferation and invasion of TNBC cells, blocking the cell cycle, and promoting apoptosis. Bioinformatic prediction and subsequent experiments revealed that CCNE1 was the direct target of miR497-5p. Furthermore, after knocking down the expression of CCNE1 in TNBC cells, the proliferation and invasion of TNBC cells were significantly inhibited, the cell cycle blocked, and the apoptosis rate significantly increased (P< 0.001), and expression of the proapoptosis-related proteins Bax and caspase 3 (cleaved) were upregulated, while expression of the antiapoptosis-related protein BCL2 was downregulated (P< 0.001).Conclusion: miR497-5p inhibited the proliferation and invasion of TNBC cells by targeting CCNE1, blocked the cell cycle and promoted the apoptosis of TNBC cells, and had better diagnostic value for TNBC. miR497-5p can be used as a new potential target for the treatment of TNBC.Keywords: miR497-5p, TNBC, CCNE1, proliferation, invasion, apoptosis

We established a zebrafish model of depression-like behaviour induced by exposure to artificial light at night (ALAN) and found that nobiletin (NOB) alleviated depression-like behaviour. Subsequently, based on the results of a 24-h free movement assay, clock gene expression and brain tissue transcriptome sequencing, the glycolysis signalling pathway was identified as a potential target through which NOB exerted antidepressant effects. Using the ALAN zebrafish model, we found that supplementation with exogenous L-lactic acid alleviated depressive-like behaviour. Molecular docking and molecular dynamics simulations revealed an inter-molecular interaction between NOB and the pyruvate kinase isozyme M1/M2 (PKM2) protein. We then used compound 3 k to construct a zebrafish model in which PKM2 was inhibited. Our analysis of this model suggested that NOB alleviated depression-like behaviour via inhibition of PKM2. In summary, NOB alleviated depressive-like behaviour induced by ALAN in zebrafish via targeting of PKM2 and activation of the glycolytic signalling pathway., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. This work has not been submitted/published or being submitted to another journal., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

As donors for effective energy transfer, metal-organic frameworks (MOFs) have attracted the attention of many experts in the field of artificial light-harvesting materials. This study introduces a novel two-dimensional Zn-MOF, synthesized using flexible 1,3-phenyldiacetic acid (H 2 mpda) and rigid 1,3,5-tris(1-imidazolyl)benzene (tib) as organic ligands. Through atomic force microscopy (AFM), we have determined the monolayer thickness of this novel material to be 5 nm. Achieving two-dimensional Zn-MOF nanosheets with large BET surface area was made possible by employing ultrasonic stripping techniques. The fluorescence emission spectrum of Zn-MOF nanosheets overlaps with the UV-vis absorption spectrum of coumarin 6 (CM6), so they can be used as a donor and acceptor for fluorescence resonance energy transfer (FRET) to construct an artificial light-harvesting system (ALHS). Compared with single crystal Zn-MOF, CM6@Zn-MOF(2) has a larger BET surface area (41 m 2 /g), higher quantum yield (Φ fl , 30.56 %), narrower energy gap (E g , 2.87 eV), and the light-harvesting range extends to the visible green light area. Notably, CM6@Zn-MOF(2) demonstrates a robust photocurrent response, characterized by a photocurrent on/off ratio (I light /I dark ) of 21, and a maximum photocurrent density that surpasses that of pure Zn-MOF (2.25:1). This study successfully designed a high-performance photoelectric conversion material CM6@Zn-MOF(2), which laid a certain theoretical foundation for new artificial optical acquisition systems and electrochemical material selection., 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.)

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by intestinal inflammation and autoimmune responses. This study aimed to identify diagnostic biomarkers for UC through bioinformatics analysis and machine learning, and to validate these findings through immunofluorescence staining of clinical samples. Differential expression analysis was conducted on expression profile datasets from 4 UC samples. Key biomarkers were selected using LASSO logistic regression, SVM-RFE, and Random Forest algorithms. The diagnostic performance of these biomarkers was evaluated using receiver operating characteristic (ROC) curves. Functional enrichment analysis assessed the biological functions of these biomarkers. The CIBERSORT algorithm was used to analyze immune cell infiltration. Regulatory networks for diagnostic markers were constructed. Additionally, immunofluorescence staining was performed on clinical samples to validate the expression levels of key biomarkers. Differential analysis identified 199 significantly differentially expressed genes. SLC6A14 was selected as a key diagnostic biomarker, demonstrating excellent diagnostic performance in training and validation sets (AUC values: 0.973, 0.984, and 0.970). Immune cell infiltration analysis revealed significant increases in Neutrophils and activated Mast cells in UC samples, whereas resting Mast cells were relatively downregulated. Furthermore, SLC6A14 showed strong correlations with various immune cells. The ceRNA network identified 22 lncRNAs and 10 miRNAs associated with SLC6A14. Immunofluorescence staining of clinical samples confirmed that SLC6A14 expression is significantly higher in UC patients compared to normal intestinal mucosa, and its expression increases with UC activity. SLC6A14 has been confirmed as a key diagnostic marker for UC, validated both through bioinformatics analysis and immunofluorescence staining of clinical samples. It maintains regulatory relationships with various non-coding RNAs and plays a significant role in the pathogenesis of UC through its interactions with immune cells., Competing Interests: Declarations. Conflict of 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. Ethical Approval: The human sample protocol was approved by the Ethics Committee of Dazhou Integrated Traditional Chinese and Western Medicine Hospital, Sichuan Province. Consent for Publication: All authors have agreed to publish this manuscript., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A pyrrole-fused analogue of warped nanographene, designated as deca-nitrogen doped 'WNG' (azaWNG), was synthesized through the annular fusion of decapyrroylcorannulene. The resulting azaWNG exhibited extremely limited solubility in common organic solvents and was characterized solely by mass spectrometry. Theoretical calculations revealed that azaWNG has a sunflower-like molecular structure with electron-deficient corannulene as the core and electron-rich pyrrole as the petals, demonstrating a significantly narrower energy gap compared to all-carbon WNG. To improve its solubility and facilitate precise structural characterization, iodine monochloride was utilized for edge-perchlorination of azaWNG, enabling successful separation and purification of chlorinated azaWNG in solution phase. X-ray crystallography analysis unequivocally confirmed that edge-perchlorinated azaWNG contains 5 heptagons and 11 pentagons embedded within the warped π skeleton. Cyclic voltammetry measurements indicated that the first oxidation potential of azaWNG is -0.59 V, representing the lowest value reported for any previously studied aza-nanographene. Consequently, azaWNG can be readily oxidized by AgPF 6 or even atmospheric oxygen to yield stable oxidation states, as corroborated by UV/Visible absorption spectroscopy; this behavior is attributed to the fusion of ten pyrroles around corannulene. This work marks the first instance of nitrogen doping in WNG (C 80 H 30 ), underscoring the significant modification to electronic structure induced by such doping., (© 2025 Wiley-VCH GmbH.)

The rapid urbanization has led to the loss of natural spaces and a subsequent disconnection between humans and nature, negatively affecting residents' well-being and environmental awareness. There is a a growing interest in leveraging technology to address this gap in Human-Computer Interaction. This article introduces GoChirp, an AI-powered wearable device for enhancing nature relatedness within urban landscapes. By utilizing machine learning algorithms, GoChirp recognizes bird sounds in the environment and provides haptic feedback that mimics the bird flapping, directing users' attention to avian life and fostering a heightened awareness and connection to nature. To evaluate GoChirp, we conducted a week-long field study with 36 urban participants divided into two groups: an experimental group using GoChirp and a control group using a dummy device. We used pre- and post-study questionnaires to assess changes in participants' nature relatedness. Additional questionnaires and semi-structured interviews were employed to evaluate the device's usability and user experience. The results suggest that AI-powered wearables like GoChirp, have the potential to augment individual's sensory and cognitive capabilities, enabling a deeper connection with the natural environment. This could further enhance users' well-being and potentially foster a greater sense of responsibility towards the natural environment, leading to mutual benefits between humans and nature., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

In hepatic drug metabolism, cytochrome P450 (CYP450) enzymes, particularly CYP3A4, catalyze the majority of drug biotransformations, accounting for over 50% of the CYP450 family's metabolic capacity. This study aimed to assess the catalytic efficiency of 22 CYP3A4 allelic variants on the in vitro oxidative metabolism of methadone. We utilized a baculovirus-insect cell expression system to produce recombinant CYP3A4 variants and subsequently assessed their catalytic activity in the N-demethylation of methadone. Of the 23 tested CYP3A4 allelic variants, CYP3A4*1 represents the wild type. Compared with CYP3A4*1, 12 variants displayed significantly lower intrinsic clearance of methadone, while 3 variants showed increased intrinsic clearance of methadone. Additionally, six variants demonstrated no significant difference in intrinsic clearance of methadone compared to CYP3A4*1, and one variant showed no detectable expression. Our evaluation of the enzymatic activity of CYP3A4 gene polymorphisms on methadone can aid in the personalized clinical use of methadone and facilitate the investigation into the relationship between genetic variations and clinical phenotypes., (© 2025 John Wiley & Sons Ltd.)

Introduction: Ancillary testing on cytopathology and other small biopsy specimens is crucial for diagnosis and provides critical information to clinicians. Testing is dependent on preanalytic factors and would benefit from standardization of specimen collection protocols across laboratories. To assess institutional practices and areas of need for evidence-based standards, we surveyed current practices across cytopathology laboratories., Materials and Methods: A twelve-question electronic survey was distributed to American Society of Cytopathology (ASC) members through email, social media, and the ASC from January 8, 2024 to March 1, 2024. Survey responses were tabulated., Results: Of 294 respondents, 257 (87%) completed at least 10/12 questions. Formalin-fixed, paraffin-embedded cell blocks (CBs) are utilized for immunohistochemistry, molecular testing, and in situ hybridization by 89%, 84%, and 71% of respondents, respectively. For fine needle aspirations, no collection medium is utilized by a majority of respondents. In contrast, 61% utilize no collection medium for fluids; 64% predominantly utilize liquid-based preservatives for other exfoliative specimens. For CB preparation, 58% of respondents use coagulating agent; 67% use no fixative before formalin. The two most significant factors limiting clinical utility of ancillary testing in cytology specimens are low cellularity and lack of validation (49% and 23% of respondents, respectively)., Conclusions: There is wide variation in current practices among laboratories, reflecting lack of consensus. Although laboratories utilize different collection media for different specimen types, for CB utilization, current survey results are similar to those reported previously. ASC has convened a task force to facilitate specimen standardization and minimize variability among preanalytic factors., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Background: Acute pancreatitis is an uncommon presentation of intraductal papillary mucinous neoplasm; however, it is considered a worrisome feature in current guidelines and can be an indication for surgery. There is controversy regarding its association with malignancy, and there is little information regarding the recurrence of pancreatitis after surgical resection., Methods: We retrospectively reviewed patients who underwent resection for intraductal papillary mucinous neoplasm at a single institution between January 1990 and December 2023. Patients with and without acute pancreatitis as part of the clinical presentation were compared., Results: A total of 812 patients were reviewed. Of these, 156 patients (19.2%) had intraductal papillary mucinous neoplasms associated with acute pancreatitis, and in 92% of them pancreatitis was the symptom leading to the diagnosis. Half of the patients had a single episode of pancreatitis (n = 77, 49.4%), and 42 (26.9%) had had 3 or more episodes before diagnosis. Acute pancreatitis was significantly associated with high-grade dysplasia (odds ratio 2.07) but had a lower likelihood of invasive cancer (odds ratio 0.62). It was also significantly associated with main duct and mixed duct-type intraductal papillary mucinous neoplasm (odds ratio 1.97) and intestinal epithelial subtype (odds ratio 2.28). Median follow-up for all patients was 61 months, and the likelihood of recurrent pancreatitis after surgical resection was 9% (14 patients), whereas pancreatitis after resection in patients without prior history occurred in only 0.9% (6 patients, P < .001)., Conclusions: Almost 1 in 5 patients undergoing resection for intraductal papillary mucinous neoplasm have a history of acute pancreatitis and are twice as likely to have high-grade dysplasia, supporting its categorization as a worrisome feature. Recurrence of pancreatitis after resection was 9%., Competing Interests: Conflict of Interest/Disclosure The authors have no related conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Because ascorbic acid (AA) is one of the basic elements to maintain the normal physiological functions of human body, it is urgent to develop a material that can achieve efficient, rapid and in-situ detection for AA. A new fluorescence organic compound 4',4'''-(benzo[c][1,2,5]thiadiazole-4,7-diyl)bis([1,1'-biphenyl]-4-carboxylic acid) (H 2 BTBC) based on benzothiadiazole group has been synthesized, which can detect Fe 3+ ions by fluorescence turn-off effect with a detection limit of 0.015 μM, as well as recognize linear amines by fluorescence turn-on effect. Moreover, a highly stable Tb(III) metal-organic framework has been solvothermally prepared with H 2 BTBC, namely {[(CH 3 ) 2 NH 2 ] 2 [Tb 2 (BTBC) 4 ]∙solvents} n (JXUST-39), which can selectively detect AA among biological fluids by fluorescence enhancement effect with a detection limit of 0.077 μM. In addition, the mechanism for JXUST-39 detecting AA is possibly the cooperative effect of absorbance-caused enhancement and charge transfer between JXUST-39 and AA. Moreover, LED lamp beads, fluorescent films and fluorescent detection test paper based on JXUST-39 were prepared to achieve portable detection via fluorescence enhancement effect., 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.)

Tissue-resident memory T (T RM ) cells preferentially reside in peripheral tissues, serving as key players in tumor immunity and immunotherapy. The lack of effective approaches for expanding T RM cells and delivering these cells in vivo hinders the exploration of T RM cell-mediated cancer immunotherapy. Here, we report a nanoparticle artificial antigen-presenting cell (nano-aAPC) ex vivo expansion approach and an in vivo delivery system for T RM cells. Using the nano-aAPC platform, we expanded functional antigen-specific murine and human T RM -like CD8 + T cells ex vivo. We also developed an injectable macroporous hyaluronic acid (HA) hydrogel to deliver T RM -like cells. T RM -like cells delivered in the optimized HA hydrogel trigger robust local and systemic antitumor immunity and show synergistic effects with anti-PD-1 treatment. Our findings suggest that nano-aAPC-induced T RM -like cells, coupled with a hydrogel delivery system, offer an efficient way to advance the understanding of T RM cell-mediated cancer therapy.

Complementary label learning (CLL) requires annotators to give irrelevant labels instead of relevant labels for instances. Currently, CLL has shown its promising performance on multi-class data by estimating a transition matrix. However, current multi-class CLL techniques cannot work well on multi-labeled data since they assume each instance is associated with one label while each multi-labeled instance is relevant to multiple labels. Here, we show theoretically how the estimated transition matrix in multi-class CLL could be distorted in multi-labeled cases as they ignore co-existing relevant labels. Moreover, theoretical findings reveal that calculating a transition matrix from label correlations in multi-labeled CLL (ML-CLL) needs multi-labeled data, while this is unavailable for ML-CLL. To solve this issue, we propose a two-step method to estimate the transition matrix from candidate labels. Specifically, we first estimate an initial transition matrix by decomposing the multi-label problem into a series of binary classification problems, then the initial transition matrix is corrected by label correlations to enforce the addition of relationships among labels. We further show that the proposal is classifier-consistent, and additionally introduce an MSE-based regularizer to alleviate the tendency of BCE loss overfitting to noises. Experimental results have demonstrated the effectiveness of the proposed method.

Crohn's disease (CD) presents significant diagnostic and therapeutic challenges due to its unclear etiology, frequent relapses, and limited treatment options. Traditional monitoring often relies on invasive and costly gastrointestinal procedures. This study aimed to identify specific diagnostic markers for CD using advanced computational approaches. Four gene expression datasets from the Gene Expression Omnibus (GEO) were analyzed, identifying differentially expressed genes (DEGs) through gene set enrichment analysis in R. Key biomarkers were selected using machine learning algorithms, including LASSO logistic regression, SVM‑RFE, and Random Forest, and their accuracy was assessed using receiver operating characteristic (ROC) curves and nomogram models. Immune cell infiltration was analyzed using the CIBERSORT algorithm, which helped reveal associations between diagnostic markers and immune cell patterns in CD. From a training set of 605 CD samples and 82 normal controls, we identified eight significant biomarkers: LCN2, FOLH1, CXCL1, FPR1, S100P, IGFBP5, CHP2, and AQP9. The diagnostic model showed high predictive power (AUC=0.954) and performed well in external validation (AUC = 1). Immune cell infiltration analysis highlighted various immune cells involved in CD, with all diagnostic markers strongly linked to immune cell interactions. Our findings propose candidate hub genes and present a nomogram for CD diagnosis, providing potential diagnostic biomarkers for clinical applications in CD.

Procambarus clarkii is an economically important species in China; however, its high mortality rate due to pathogenic bacteria, particularly Vibrio parahaemolyticus, results in significant economic loss. This study aimed to understand the immune response of crayfish to bacterial infection by comparing and analyzing transcriptome data of hepatopancreatic tissue from P. clarkii challenged with V. parahaemolyticus or treated with PBS. Physiological indices (TP, Alb, ACP, and AKP) were analyzed, and tissue sections were prepared. After assembling and annotating the data, 18,756 unigenes were identified. A comparison of the expression levels of these unigenes between the control and V. parahaemolyticus groups revealed 4037 DEGs, with 2278 unigenes upregulated and 1759 downregulated in the V. parahaemolyticus group. GO (Gene Ontology) enrichment analysis shows that the DGEs are mainly enriched in cellular anatomical activity, bindinga and cellular process, enrichment analysis of KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways showed that DGEs were mainly enriched in Base excision repair, Phagosome and Longevity regulating pathway. At the same time, lysosome was also enriched. The phagosome and lysosome pathways play a crucial role in the immune defense of crayfish against V. parahaemolyticus injection that will be highlighted. In addition, the expression levels of six selected immune-related DEGs were measured using qRT-PCR, which validated the results of RNA-seq analysis. This study provides a new perspective on the immune system and defense mechanisms of P. clarkii and a valuable foundation for further investigation of the molecular immune mechanisms of this species., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Azvudine (AZV), the first Chinese oral anti-coronavirus disease 2019 (COVID-19) drug, has shown substantial clinical benefits to viral clearance and prognosis in patients with mild and common COVID-19. However, there is no evidence in severe hospitalized COVID-19 patients., Methods: In this multicenter study, we analyzed 209 severe hospitalized COVID-19 patients in four hospitals. All the clinical data and the 28-day composite outcomes were recorded. All of the patients were categorized into two groups according to drug: the dexamethasone (DXM) group and the azvudine plus dexamethasone (AZV+DXM) group., Results: There were no differences in sex, age, BMI, and underlying diseases between the two groups. The ratio of the 28-day composite outcome was lower for the AZV+DXM group than that for the DXM group (16.97% vs . 31.82%, p = 0.029). The viral clearance time was shorter in the AZV+DXM group than in the DXM group (7.32 ± 2.57 vs . 8.55 ± 2.34 days, p = 0.017). The PaO 2 /FiO 2 levels on day 5 (258.89 ± 55.22 vs . 233.12 ± 60.51, p = 0.026) and day 10 (289.48 ± 44.09 vs . 261.52 ± 37.34, p = 0.015) were higher in the AZV+DXM group than the DXM group. However, data on the hospitalization duration of the two groups were similar. Cox analysis showed the benefit of AZV+DXM in the subgroups of ≥65 years old, multiple organ dysfunction syndrome (MODS), cerebrovascular disease, C-reactive protein (CRP) ≥70mg/L, and D-dimer ≥1 µg/L., Conclusion: This study is the first to indicate that treatment with AZV+DXM might benefit severe Omicron-infected patients compared with DXM treatment alone. This finding demonstrates, at least partly, the necessity of antiviral treatment in severe patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Wei, Su, Jiang, Xu and Zeng.)

Introduction: Drug discovery research targeting SARS-CoV-2 and other emerging pathogens remains critically important. Active compounds derived from plants frequently serve as lead compounds for further drug discovery; however, numerous unrelated chemical constituents in crude extracts may obscure the effective ingredients in LC-MS analysis., Objective: The aim of this study is to construct a biolayer interferometry (BLI)-based system for recognizing active ingredients that inhibit the main protease (Mpro) of SARS-CoV-2 and to identify the active chemical components binding to Mpro from herbal medicines., Methodology: We developed a novel FRET fluorogenic probe by linking the amino acid sequences of the fluorescent proteins Lssmorange and mKate2 (Ls-mK). The interaction between traditional Chinese medicine and Mpro was analyzed using BLI. Ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was employed to analyze the composition of herbal medicines., Results: Fluorescence detection and spectroscopy confirmed the successful construction of an Mpro inhibitor screening system. Lanqin Oral Liquid (LQL) and Gardeniae fructus exhibited strong inhibitory effects on Mpro. Ten compounds were identified from G. fructus extracts; among them, deacetyl asperulosidic acid methyl ester (DAAME) and Gardoside were found to strongly bind to Mpro, with dissociation constants (KD) of 3.41 μM and 801 nM, respectively. The half-maximal inhibitory concentrations (IC50) of DAAME and Gardoside for Mpro were 27.46 and 13.7 μM, respectively., Conclusion: This study established a functional Mpro inhibitor screening system. Among the 10 components identified from G. fructus that bind to Mpro, DAAME and Gardoside displayed strong binding and inhibitory activity, indicating their potential as lead compounds for inhibiting SARS-CoV-2 viral replication., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: Early stage administration of Paxlovid has been shown to improve the prognosis of mild to moderate COVID-19 patients with high risk. However, few evidence was validated in severe COVID-19 patients with hypoxemia. It is also unclear whether delayed usage of Paxlovid affected prognosis in COVID-19 patients or not., Methods: In this multiple-centers prospective study, we collected the clinical data in hospitalized severe adult Omicron infection patients with hypoxemia. All patients were divided into two groups according to the time of Paxlovid usage after the symptom onset: early group (Paxlovid administration in 5 days after symptom onset) and delayed group (Paxlovid administration beyond 5 days after symptom onset). The 28-day composite outcomes were evaluated., Results: Totally 198 hospitalized severe omicron-infected subjects with hypoxemia were enrolled. There was no difference between the two groups about the baseline characteristics and laboratory parameters, except for leukocytes (5.29 × 10 9 vs. 7.90 × 10 9 /L, p  = 0.01) and albumin levels (35 vs. 31 g/L, p  = 0.04). The 28-day composite outcomes in early group were slightly lower than that in delayed group but with no difference (12.8% vs. 16.67%, p  = 0.602). The viral clearance ratio at Day 7 after Paxlovid treatment in early group was higher than that in delayed group (79.48% vs. 58.33%, p  = 0.029). The medium hospitalized duration in early group was shorter than that in delayed group (11.31 vs. 15.32 days, p  = 0.005). Logistic analysis showed the independent risk factors of prognosis including underlying diseases ≥ 3 kinds (ORR = 1.72), d-dimer ≥ 2.0 μg/mL (ORR = 1.35), and MODS (ORR = 14.01)., Conclusions: In Omicron-infected subjects with hypoxemia, early usage of Paxlovid received benefits in hospitalized time and viral clearance, but delayed usage did not result in a worse composite prognosis. This result might provide direct evidence of antiviral strategy in severe Omicron infection subjects with hypoxemia., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Fresh dough products lead to instability in product quality, high production costs, and more production time, which seriously affects the industrial production of the food industry. The frozen dough technology mitigates the problems of short shelf-life and easy deterioration of quality during storage and transportation. It has shown a series of advantages in large-scale industrialization, high-quality standardization, and chain operation. However, the further development of frozen dough is restricted by the deterioration of the main components (gluten, starch, and yeast) caused by freezing. This review summarizes the main production process of frozen steamed bread and buns, and the deterioration reasons for the main component of frozen dough. The improvement mechanisms of raw ingredients, processing technology, processing equipment, and additives on frozen dough quality were analyzed from the perspective of improving gluten network integrity and yeast freeze tolerance. From prefermented frozen raw to steamed products without thawing has become the preferred production process to improve production efficiency. Wheat flour mixed with other flour can maintain the gluten network continuity of frozen dough. The freeze tolerance of yeast was improved by treatment with yeast suspension, yeast cell encapsulation, screening hybridization, and genetic engineering. Process optimization and new technology-assisted fermentation and freezing effectively reduce freezing damage. Various additives improve the freeze resistance of the gluten-starch matrix by promoting protein cross-linking and inhibiting water migration. In addition, ice structural proteins and ice nucleating agents have been proven to change the growth morphology and formation temperature of ice crystals. More new technologies and additive synergies need to be further explored., (© 2024 Institute of Food Technologists®.)

Predominant instrument recognition plays a vital role in music information retrieval. This task involves identifying and categorizing the dominant instruments present in a piece of music based on their distinctive time-frequency characteristics and harmonic distribution. Existing predominant instrument recognition approaches mainly focus on learning implicit mappings (such as deep neural networks) from time-domain or frequency-domain representations of music audio to instrument labels. However, different instruments playing in polyphonic music produce local superposed time-frequency representations while most implicit models could be sensitive to such local data changes. This thus poses a challenge for these implicit methods to accurately capture the unique harmonic features of each instrument. To address this challenge, considering that the complete harmonic information of an instrument is also distributed across a wide range of frequencies, we design a label-specific time-frequency feature learning approach to convert the task of building implicit classification mappings into the process of extracting and matching features that are specific to each instrument, as a result, a new explicit learning model: label-specific time-frequency energy-based neural network (LSTN) is proposed. Unlike existing implicit models, LSTN not only extracts their commonly used local time-frequency features but also incorporates time-domain factors and frequency-domain factors in its energy function to explicitly parameterize the long-term correlation and long-frequency correlation features. Using the extracted time-frequency features and the two long correlation features as instrument label-specific features, LSTN detects whether the harmonic distribution of each instrument appears in polyphonic music on both long time-frequency scales and local time-frequency scales to mitigate the challenges posed by local superposed representations. We conduct an analysis of the complexity and the convergence of LSTN, then experiments conducted on benchmark datasets demonstrate the superiority of LSTN over other established instrument recognition algorithms.

Herein, corannulene-based quintuple [6]helicenes (Q[6]H-1 and Q[6]H-2) and [7]helicene (Q[7]H) were synthesized via penta-fold Heck and Mallory reaction. Notably, Q[7]H represents the highest reported helicene based on corannulene. X-ray crystallography reveals that Q[6]H-2 adopts a propeller-shaped conformation with a well-preserved corannulene core, while Q[6]H-1 and Q[7]H exhibit quasi-propeller-shaped conformations. Upon heating, conformer Q[6]H-1 undergoes conversion to the thermodynamically more stable conformer Q[6]H-2, whereas conformer Q[7]H remains unchanged due to larger steric congestion. Racemization of the enantiomer of Q[6]H-1 and conformational conversion were observed simultaneously at elevated temperature, with DFT studies indicating a racemization barrier of 32.06 kcal ⋅ mol -1 . In contrast, the racemization barrier for Q[6]H-2 was calculated to be 45.46 kcal ⋅ mol -1 , indicating exceptional chiral stability. Surprisingly, the bowl inversions of Q[6]H-1 and Q[6]H-2 conformers are somewhat inhibited by the helical blades, whereas this was not observed for other possible conformers of Q[6]H. These results first demonstrated that subtle conformational variations can lead to significant changes in chiral stability and bowl inversions of multiple helicenes. Due to the well-preserved corannulene core, propeller-shaped conformation and electron complementarity, Q[6]H-2 can recognize fullerenes in both solution and solid state, which is a rare instance of co-crystallization assembly between multiple helicenes and fullerenes., (© 2024 Wiley-VCH GmbH.)

Electrochemical reduction of CO 2 into high-value-added products is a potential approach to solving environmental problems but is limited by poor product selectivity and low efficiency. Metal-organic framework (MOF) materials have been considered one of the most promising catalysts, but their application is limited by complicated preparation processes, especially during the synthesis of organic ligands. In this work, a new three-dimensional Cu-MOF ( JXUST-301 ) with high porosity was constructed based on the naphthalene diimide (NDI) ligand. Furthermore, JXUST-301 with ligand defects ( JXUST-301D ) originating from the missing NDI unit was synthesized via an in situ reaction. The presence of ligand defects endows JXUST-301D with a better CO 2 RR performance with a FE C2 of 56.7% and a j C2 of -162.4 mA cm -2 . Mechanistic studies revealed that the hierarchical pore structure and amino sites are created from the absence of the NDI unit, which promotes the exposure of catalytically active sites and CO 2 enrichment. Furthermore, the electronic structure of the Cu sites is modulated to upshift the d-band center, facilitating chemical adsorption and activation of key reaction intermediates. This work provides new insight into the in situ preparation of efficient Cu-MOF catalysts by introducing defects for the CO 2 RR.

Kidney-yang deficiency syndrome (KYDS) is characterized by a metabolic disorder stemming from neuroendocrine dysregulation, often associated with hepatic dysfunction. In traditional Chinese medicine, Psoralea corylifolia Linn. (BGZ) is commonly utilized for treating KYDS. However, the specific therapeutic effects of BGZ on liver function regulation remain unclear. To evaluate the protective effects of BGZ against KYDS in rats, organ index, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and other biochemical indices were analyzed. Hematoxylin and eosin (HE) staining was utilized to assess liver histopathology. Additionally, transcriptomic and metabolomic analyses were conducted to identify potential biomarkers. BGZ treatment led to a significant reduction in ALT and AST levels, accompanied by improvements in liver histopathology in rats with KYDS. Moreover, BGZ induced significant alterations in 92 differentially expressed genes (DEGs) and 20 metabolites in the KYDS rat model. The comprehensive examination of metabolites and DEGs identified potential mechanisms underlying the therapeutic effects of BGZ, highlighting the neuroactive ligand-receptor interaction, cAMP signaling pathway, calcium signaling pathway, and cytokine-cytokine receptor interaction as key mechanisms. Validation of key targets within the cAMP pathway was substantiated through enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. The cAMP pathway emerges as a plausible mechanism through which BGZ exerts protective effects against KYDS. The findings of this study contribute to an improved understanding of the therapeutic actions of BGZ and establish a groundwork for further research into the complex pathways involved, as well as the potential for drug-targeted therapies for KYDS., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jin-Fa Tang reports was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Cottonseed meal (CSM) and cottonseed protein concentrate (CPC) serve as protein alternatives to fish meal and soybean meal in the feed industry. However, the presence of gossypol residue in CSM and CPC can potentially trigger severe intestinal inflammation, thereby restricting the widespread utilization of these two protein sources. Probiotics are widely used to prevent or alleviate intestinal inflammation, but their efficacy in protecting fish against gossypol-induced enteritis remains uncertain. Here, the protective effect of Pediococcus pentosaceus, a strain isolated from the gut of Nile tilapia (Oreochromis niloticus), was evaluated. Three diets, control diet (CON), gossypol diet (GOS) and GOS supplemented with P. pentosaceus YC diet (GP), were used to feed Nile tilapia for 10 weeks. After the feeding trial, P. pentosaceus YC reduced the activity of myeloperoxidase (MPO) in the proximal intestine (PI) and distal intestine (DI). Following a 7-day exposure to Aeromonas hydrophila, the addition of P. pentosaceus YC was found to increase the survival rate of the fish. P. pentosaceus YC significantly inhibited the oxidative stress caused by gossypol, which was evidenced by lower reactive oxygen species (ROS) and malondialdehyde (MDA), as well as higher activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in PI and DI. Addition of P. pentosaceus YC significantly inhibited enteritis, with the lower expression of pro-inflammatory cytokines (il-1β, il-6, il-8) and higher expression of anti-inflammatory cytokines tgf-β. RNA-seq analysis indicated that P. pentosaceus YC supplementation significantly inhibited nlrc3 and promoted nf-κb expression in PI and DI, and the siRNA interference experiment in vivo demonstrated that intestinal inflammation was mediated by NLRC3/NF-κB/IL-1β signaling pathway. Fecal bacteria transplantation experiment demonstrated that gut microbiota mediated the protective effect of P. pentosaceus YC. These findings offer valuable insights into the application of P. pentosaceus YC for alleviating gossypol-induced intestinal inflammation in fish., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Jilin Province is an important ecological security barrier in Northeast China as it is located at the junction of the Northeast forest belts and the northern sand prevention belts. In recent years, Jilin Province has actively carried out ecological protection and restoration projects, resulting in a continuous improvement trend for the overall ecological environment. However, the evolution patterns and mechanisms of habitat quality are largely unkown. We applied the InVEST model and geographic detector method to analyze the changes in habitat quality and evaluate the main driving factors from 2000 to 2020. The results showed that the average habitat quality in Jilin Province showed a slight downward trend, and that the spatial heterogeneity characteristics of habitat quality in east and west gradually increased. The degree of habitat degradation presented a single nuclear radiation pattern centered on Changchun City. Vegetation factors and terrain factors were the first and secondary causes of spatial heterogeneity of habitat quality, respectively. The average habitat quality within the eco-redline of Jilin Province was showing an increasing trend year by year, which was consistent with the overall distribution of regions with extremely high habitat quality levels. There was a local spatial dislocation (the phenomenon of extremely high habitat quality levels not within the eco-redline) in the eastern part of Jilin Province. Our results could provide reference basis for ecosystem protection and the spatial pattern optimization.

Multiclass classification problems are often addressed by decomposing them into a set of binary classification tasks. A critical step in this approach is the effective aggregation of predictions from each decomposed binary classifier to yield the final multiclass prediction, a process known as decoding. Existing studies have ignored the varying generalization ability of each binary classifier across different samples during decoding, potentially leading to suboptimal performance. In this article, we propose an instance-specific loss-weighted (ILW) decoding strategy that gauges the generalization ability of each binary classifier for one specific sample based on its neighboring samples. This estimated generalization ability is then used to adjust the importance of the binary classifier in determining the sample's final prediction. Experimental results validate the effectiveness of the ILW decoding strategy. Furthermore, we demonstrate that softmax regression can be reinterpreted as a one-versus-rest (OvR) decomposition-based multiclass classification algorithm, enabling the application of our decoding strategy to enhance its performance. Comparative studies clearly demonstrate the superiority of the improved softmax regression over its traditional counterpart.

Background: Grade 3 neuroendocrine tumor (G3 PanNET) and poorly differentiated neuroendocrine carcinoma (PanNEC) of the pancreas are considered distinct entities from a biological and prognostic perspective but may have overlapping features complicating a definitive diagnosis., Case Presentation: A 52-year-old female presented with a pancreatic body mass and liver lesions. Initial biopsies showed variable lower- and higher-grade morphologies and modestly elevated Ki67 proliferation index up to 30%, leading to a diagnosis of G3 PanNET. The patient underwent everolimus treatment followed by surgical resection, revealing a complex tumor with features of both G3 PanNET and PanNEC, including admixed well- and poorly differentiated morphologies, modestly elevated hotspot Ki67 of 28%, retained ATRX/DAXX expression, and loss of RB expression. The final diagnosis rendered was "high-grade neuroendocrine neoplasm" with discussion of both entities in the differential. Post-operatively, the patient remains alive with stable metastases., Conclusions: This case highlights the diagnostic complexities of distinguishing G3 PanNET and PanNEC even with the support of ancillary immunohistochemical and molecular studies. In addition, such cases raise the possibility that G3 PanNET and PanNEC may lie on a spectrum of disease with potential biological overlap., (© 2024. The Author(s).)

Partial label learning (PLL) is a form of weakly supervised learning, where each training example is linked to a set of candidate labels, among which only one label is correct. Most existing PLL approaches assume that the incorrect labels in each training example are randomly picked as the candidate labels. However, in practice, this assumption may not hold true, as the candidate labels are often instance-dependent. In this paper, we address the instance-dependent PLL problem and assume that each example is associated with a latent label distribution where the incorrect label with a high degree is more likely to be annotated as a candidate label. Motivated by this consideration, we propose two methods VALEN and MILEN, which train the predictive model via utilizing the latent label distributions recovered by the label enhancement process. Specifically, VALEN recovers the latent label distributions via inferring the variational posterior density parameterized by an inference model with the deduced evidence lower bound. MILEN recovers the latent label distribution by adopting the variational approximation to bound the mutual information among the latent label distribution, observed labels and augmented instances. Experiments on benchmark and real-world datasets validate the effectiveness of the proposed methods.

The mitochondrial citrate shuttle, which relies on the solute carrier family 25 member 1 (SLC25A1), plays a pivotal role in transporting citrate from the mitochondria to the cytoplasm. This shuttle supports glycolysis, lipid biosynthesis, and protein acetylation. Previous research has primarily focused on SLC25A1 in pathological models, particularly high-fat diet (HFD)-induced obesity. However, the impact of SLC25A1 inhibition on nutrient metabolism under HFD remains unclear. To address this gap, we used zebrafish ( Danio rerio ) and Nile tilapia ( Oreochromis niloticus ) to evaluate the effects of inhibiting Slc25a1. In zebrafish, we administered Slc25a1-specific inhibitors (CTPI-2) for 4 wk, whereas Nile tilapia received intraperitoneal injections of dsRNA to knock down slc25a1b for 7 days. Inhibition of the mitochondrial citrate shuttle effectively protected zebrafish from HFD-induced obesity, hepatic steatosis, and insulin resistance. Of note, glucose tolerance was unaffected. Inhibition of Slc25a1 altered hepatic protein acetylation patterns, with decreased cytoplasmic acetylation and increased mitochondrial acetylation. Under HFD conditions, Slc25a1 inhibition promoted fatty acid oxidation and reduced hepatic triglyceride (TAG) accumulation by deacetylating carnitine palmitoyltransferase 1a (Cpt1a). In addition, Slc25a1 inhibition triggered acetylation-induced inactivation of Pdhe1α, leading to a reduction in glucose oxidative catabolism. This was accompanied by enhanced glucose uptake and storage in zebrafish livers. Furthermore, Slc25a1 inhibition under HFD conditions activated the SIRT1/PGC1α pathway, promoting mitochondrial proliferation and enhancing oxidative phosphorylation for energy production. Our findings provide new insights into the role of nonhistone protein acetylation via the mitochondrial citrate shuttle in the development of hepatic lipid deposition and hyperglycemia caused by HFD. NEW & NOTEWORTHY The mitochondrial citrate shuttle is a crucial physiological process for maintaining metabolic homeostasis. In the present study, we found that inhibition of mitochondrial citrate shuttle (Slc25a1) could alleviate metabolic syndromes induced by high-fat diet (HFD) through remodeling hepatic protein acetylation modification. Briefly, Slc25a1 inhibition reduces hepatic triglyceride deposition by deacetylating Cpt1a and reduces glucose oxidative catabolism by acetylating Pdhe1α. Our study provides new insights into the treatment of diet-induced metabolic syndromes.

Introduction: Congo red staining of fat pad fine needle aspiration specimens is a method utilized for evaluation of amyloid deposition. However, these specimens can pose diagnostic challenges for cytopathologists. As part of ongoing internal quality improvement measures, the objective of this study was to evaluate the intradepartmental interobserver agreement of these specimens and to identify factors that affect the variability of the interpretations., Materials and Methods: There were 7 participants, which included 3 trainees, 3 cytopathologists, and 1 cytotechnologist. Each participant reviewed 50 Congo red stained fat pad fine needle aspiration slides. The interpretations were categorized into 3 groups: negative, indeterminate/suspicious, and positive. The participants also noted any interpretation challenges they encountered for each case., Results: There was only slight interobserver agreement among all participants (κ = 0.133). Stratified by participant group, the interobserver agreement among the trainees was slight bordering on poor (κ = 0.028) and among cytopathologists was fair (κ = 0.249). The highest agreement between 2 observers was between 2 cytopathologists and the level of agreement was moderate bordering on fair (κ = 0.426). There were only 3 cases (6.0%) with full agreement among observers, while in 25 cases (50.0%), there were 2 category differences in interpretations. The primary diagnostic challenge reported by participants was when weak or focal birefringence was encountered as well as cases complicated by poor stain quality and overstaining., Conclusions: We found only slight interobserver agreement among all study participants. A major area of challenge was cases with weak birefringence resulting in high variance of interpretation among participants., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors have no conflicts of interest to declare.

The solute carrier family 25 member 1 (Slc25a1)-dependent mitochondrial citrate shuttle is responsible for exporting citrate from the mitochondria to the cytoplasm for supporting lipid biosynthesis and protein acetylation. Previous studies on Slc25a1 concentrated on pathological models. However, the importance of Slc25a1 in maintaining metabolic homeostasis under normal nutritional conditions remains poorly understood. Here, we investigated the mechanism of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis in male Nile tilapia (Oreochromis niloticus). To achieve the objective, we blocked the mitochondrial citrate shuttle by inhibiting Slc25a1 under normal nutritional conditions. Slc25a1 inhibition was established by feeding Nile tilapia with 250 mg/kg 1,2,3-benzenetricarboxylic acid hydrate for 6 weeks or intraperitoneal injecting them with dsRNA to knockdown slc25a1b for 7 days. The Nile tilapia with Slc25a1 inhibition exhibited an obesity-like phenotype accompanied by fat deposition, liver damage and hyperglycemia. Moreover, Slc25a1 inhibition decreased hepatic citrate-derived acetyl-CoA, but increased hepatic triglyceride levels. Furthermore, Slc25a1 inhibition replenished cytoplasmic acetyl-CoA through enhanced acetate pathway, which led to hepatic triglycerides accumulation. However, acetate-derived acetyl-CoA caused by hepatic Slc25a1 inhibition did not activate de novo lipogenesis, but rather modified protein acetylation. In addition, hepatic Slc25a1 inhibition enhanced fatty acids esterification through acetate-derived acetyl-CoA, which increased Lipin1 acetylation and its protein stability. Collectively, our results illustrate that inhibiting mitochondrial citrate shuttle triggers lipid anabolic remodeling and results in lipid accumulation, indicating the importance of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pancreatic lesions can be solid or cystic and comprise a wide range of benign, premalignant, and malignant entities. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the current primary sampling method for the preoperative diagnosis of pancreatic lesions. Optimal handling of cytology/small tissue specimens is critical to ensure that the often-scant diagnostic material is appropriately utilized for ancillary and/or molecular studies when appropriate. Ultimately, evaluation of EUS-FNA cytology and small biopsy material can provide accurate and timely diagnoses to guide patient management and triage them to surveillance or surgical intervention., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Several studies have explored the relationship between socially constructed neighbourhood boundaries (henceforth social boundaries) and ethnic tensions. To measure these relationships, studies have used area-level demographic data to predict the location of social boundaries and their characteristics. The most common approach uses areal wombling to locate neighbouring areas with large differences in residential characteristics. Areas with large differences (or higher boundary values) are used as a proxy for well-defined social boundaries. However, to date, the results of these predictions have never been empirically validated. This article presents results from a simple discrete choice experiment designed to test whether the areal wombling approach to boundary detection produces social boundaries that are recognisable to local residents and experts as such. We conducted a small feasibility trial with residents and experts in Rotherham, England. Our results shows that participants were more likely to recognise boundaries with higher boundary values as local community borders. We end with a discussion on the scalability of the design and suggest future improvements., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: This research was done in collaboration with Rotherham United Community Sports Trust (RUCUST); ZR works as a community manager at RUCUST., (Copyright: © 2024 Zhang 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.)

Aim: To investigate the effects of fibrillin-1 (FBN1) deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions., Methods: Streptozotocin (STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy (DR) patients, and FBN1 expression was detected in retinas from STZ-diabetic mice and controls. In the Gene Expression Omnibus (GEO) database, the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR patients. Using lentivirus to knock down FBN1 levels, vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay, fluorescein fundus angiography (FFA) and immunofluorescence labeled with tight junction marker in vivo . High glucose-induced monkey retinal vascular endothelial cells (RF/6A) were used to investigate effects of FBN1 on the cells in vitro . The vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance (TEER) assay and flow cytometry, respectively., Results: FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients (GSE60436 datasets) using RNA-seq approach. Besides, knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA detection. Expressions of tight junction markers in STZ-DR mouse retinas were lower than those in the control group, and knocking down of FBN1 increased the tight junction levels. In vitro , 30 mmol/L glucose could significantly inhibit viability of RF/6A cells, and FBN1 mRNA expression was increased under 30 mmol/L glucose stimulation. Down-regulation of FBN1 reduced high glucose (HG)-stimulated retinal microvascular endothelial cell permeability, increased TEER, and inhibited RF/6A cell apoptosis in vitro ., Conclusion: The expression level of FBN1 increases in retinas and vascular endothelial cells under diabetic conditions. Down-regulation of FBN1 protects the retina of early diabetic rats from retina-blood barrier damage, reduce vascular leakage, cell apoptosis, and maintain vascular endothelial cell barrier function., Competing Interests: Conflicts of Interest: Zhang Y, None; Liu XJ, None; Zhai XR, None; Yao Y, None; Shao B, None; Zhen YH, None; Zhang X, None; Xiao Z, None; Wang LF, None; Zhang ML, None; Chen ZM, None., (International Journal of Ophthalmology Press.)

Objectives: An increasing number of studies have shown that third (CB3)- and fourth-generation cryoballoons (CB4) have been used to treat various types of atrial fibrillation (AF), but previous research regarding the safety and efficacy of CB3 or CB4 ablation remains controversial. Therefore, a meta-analysis was performed to further evaluate the safety and efficacy of pulmonary vein isolation (PVI) using the CB3 and CB4 in the treatment of AF., Methods: We searched PubMed, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, and Clinicaltrials.gov up to December 2023 for qualified trials and data extraction according to inclusion and exclusion criteria. All analyses were carried out using Review Manager 5.3 software., Results: The meta-analysis included 13 observational studies consisting of 3,281 subjects and did not include a randomized controlled trial. Overall analyses indicated that the CB3 significantly reduced total procedure time [weighted mean difference (WMD) = -8.69 min, 95% confidence interval (CI) = -15.45 to -1.94 min, I 2  = 93%], increased the PVI recording [relative risk (RR) = 1.24, 95% CI = 1.03-1.49, I 2  = 90%], and increased the mean nadir temperature of overall PVs (WMD = 2.80°C, 95% CI = 1.08-4.51°C, I 2  = 89%) compared with the CB2. Moreover, the CB4 significantly reduced the total procedure time (WMD = -14.50 min, 95% CI = -20.89 to -8.11 min, I 2  = 95%), reduced the fluoroscopy time (WMD = -2.37 min, 95% CI = -4.28 to -0.46 min, I 2  = 95%), increased the PVI recording (RR = 1.40, 95% CI = 1.15-1.71, I 2  = 90%) compared with the CB2. Time-to-isolation, the success rate of PVI, AF recurrence, and complications in the CB3 and CB4 were not significantly different compared with the CB2., Conclusion: These findings demonstrated that the CB3 and CB4 tended to be more effective than the CB2 in the treatment of AF, with shorter procedure times, more PVI recording, and similar safety endpoints., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Zhang, Zhang, Peng, Xing, Guo, Wei, Zhang, Ma and Chen.)

Aims: Small invasive carcinomas arising in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can present as multiple, small foci. In such cases, there is no clear optimal measurement method for determining the invasive size for tumour staging and prognostication., Methods: In all, 117 small invasive IPMNs (size of largest invasive component ≤2 cm) from seven institutions (2000-2016) were reviewed, and all individual foci of invasive carcinoma were measured. T stages (AJCC 8th edition) based on the largest single focus size (LS), average size of all foci (AS), and total sum of all foci (TS) were examined in association with clinicopathologic parameters and patient outcomes., Results: The cohort comprised IPMNs with invasive tubular-type (n = 82, 70%) and colloid-type (n = 35, 30%) carcinomas. The mean LS, AS, and TS were 0.86, 0.71, and 1.32 cm, respectively. Based on the LS, AS, and TS, respectively, 48, 65, and 39 cases were classified as pT1a; 22, 18, and 11 cases as pT1b; and 47, 34, and 50 cases as pT1c. Higher pT stages based on all measurements were significantly associated with small vessel, large vessel, and perineural invasion (P < 0.05). LS-, AS-, and TS-based pT stages were not significantly associated with recurrence-free survival (RFS) or overall survival (OS) by univariate or multivariate analyses. However, among tubular-type carcinomas, higher LS-, AS-, and TS-based pT stages trended with lower RFS (based on 1-, 3-, and 5-year survival rates). All microscopic measurement methods were most predictive of RFS and OS using a 1.5-cm cutoff, with LS significantly associated with both RFS and OS by univariate and multivariate analysis., Conclusions: For invasive tubular-type carcinomas arising in IPMN, microscopic size-based AJCC pT stages were not significant predictors of patient outcomes. However, for LS, a size threshold of 1.5 cm was optimal for stratifying both RFS and OS. The AJCC 8th ed. may not be applicable for stratifying small invasive IPMNs with colloid-type histology that generally portend a more favourable prognosis., (© 2024 John Wiley & Sons Ltd.)

Background: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine)., Methods: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log 10 plaque forming units (PFU; low-dose v7D group), 3·9 log 10 PFU (medium-dose v7D group), and 4·2 log 10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434., Findings: On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related., Interpretation: The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future., Funding: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests J-ZJ, J-LH, and X-ZY are employees of and have stock options in Beijing Wantai. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Altitude illness has serious effects on individuals who are not adequately acclimatized to high-altitude areas and may even lead to death. However, the individualized mechanisms of onset and preventive measures are not fully elucidated at present, especially the relationship between altitude illness and elements, which requires further in-depth research., Methods: Fresh serum samples were collected from individuals who underwent health examinations at the two hospitals in Xining and Sanya between November 2021 and December 2021. The blood zinc (Zn), iron (Fe), and calcium (Ca) concentrations, as well as hypoxia-inducible factor 1-alpha (HIF-1α) concentrations, were measured. This study conducted effective sample size estimation, repeated experiments, and used GraphPad Prism 9.0 and IBM SPSS version 19.0 software for comparative analysis of differences in the expression of elements and HIF-1α among different ethnic groups, altitudes, and concentration groups. Linear regression and multiple linear regression were employed to explore the relationships among elements and their correlation with HIF-1α., Results: This study included a total of 400 participants. The results from the repeated measurements indicated that the consistency of the laboratory test results was satisfactory. In terms of altitude differences, except for Fe ( p  = 0.767), which did not show significant variance between low and high altitude regions, Zn, Ca, and HIF-1α elements all exhibited notable differences between these areas ( p  < 0.0001, p  = 0.004, and p  < 0.0001). When grouping by the concentrations of elements and HIF-1α, the results revealed significant variations in the distribution of zinc among different levels of iron and HIF-1α ( p  < 0.05). The outcomes of the linear regression analysis demonstrated that calcium and zinc, iron and HIF-1α, calcium and HIF-1α, and zinc and HIF-1α displayed substantial overall explanatory power across different subgroups ( p  < 0.05). Finally, the results of the multiple linear regression analysis indicated that within the high-altitude population, the Li ethnic group in Sanya, and the Han ethnic group in Sanya, the multiple linear regression model with HIF-1αas the dependent variable and elements as the independent variables exhibited noteworthy overall explanatory power ( p  < 0.05)., Conclusion: The levels of typical elements and HIF-1α in the blood differ among various altitudes and ethnic groups, and these distinctions may be linked to the occurrence and progression of high-altitude illness., 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 Guo, Lu, Zhang, Zhang, Liu, Chen and Zhang.)

Abstract: Recent advances in molecular pathology and an improved understanding of the etiology of neuroendocrine neoplasms (NENs) have given rise to an updated World Health Organization classification. Since gastroenteropancreatic NENs (GEP-NENs) are the most common forms of NENs and their incidence has been increasing constantly, they will be the focus of our attention. Here, we review the findings at the foundation of the new classification system, discuss how it impacts imaging research and radiological practice, and illustrate typical and atypical imaging and pathological findings. Gastroenteropancreatic NENs have a highly variable clinical course, which existing classification schemes based on proliferation rate were unable to fully capture. While well- and poorly differentiated NENs both express neuroendocrine markers, they are fundamentally different diseases, which may show similar proliferation rates. Genetic alterations specific to well-differentiated neuroendocrine tumors graded 1 to 3 and poorly differentiated neuroendocrine cancers of small cell and large-cell subtype have been identified. The new tumor classification places new demands and creates opportunities for radiologists to continue providing the clinically most relevant report and on researchers to design projects, which continue to be clinically applicable., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)