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Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV), has been frequently occurring in the southwestern region of China over the past few years, continuously affecting the development of the swine industry. However, the genetic diversity and prevalence of PEDV strains circulating in the swine population in southwestern China in recent years have not been well studied. To address this gap, a total of 478 clinical samples were collected from 125 pig farms experiencing piglet diarrhea in 18 cities in southwestern China. The detection results revealed that 227 out of 478 samples tested positive for PEDV nucleic acid, with a positivity rate of 47.49%. Complete S gene sequences of 28 PEDV strains were obtained and classified into four subgroups, G1-a subgroup (classical strain), G1-b subgroup (S-INDEL), and two G2 subgroups (G2-a and G2-b), accounting for 17.86% (5/28), 3.57% (1/28), 35.71% (10/28), 42.86% (12/28) of the total sequenced strains, respectively. The coexistence of multiple genotypes indicates the complex genetic background and prevalence of PEDV in southwest China. Amino acid comparisons of the S proteins showed that the 28 PEDV strains sequenced in the study showed different patterns of variation in the epitope domains compared to vaccine strains belonging to different genotypes and contained many unique amino acid mutations compared to the reference strains, which might lead to immune escape of PEDV. The complex epidemiology of PEDV with multiple subgroups co-circulating in Southwest China underscores the importance of selecting appropriate vaccine strains based on locally prevalent strains and the ongoing need for epidemiological surveillance of PEDV. The emergence of new variant strains also highlights the urgency of developing updated vaccines, and effective management practices remain crucial for controlling PED outbreaks in pig farms., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: All experimental procedures were reviewed and approved by the Sichuan Agriculture University Animal Care and Use Committee (license number SCXK (Sichuan) 2013-0001). The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent was obtained from the owners for the participation of their animals in this study. No human studies are presented in the manuscript. No potentially identifiable images or data are presented in this study., (© 2024. The Author(s).)

Objectives: To elucidate the relationship between the auricular point stimulation and the activity of glutamatergic neurons in the anterior cingulate cortex (ACC) from the perspective of intrinsic excitability plasticity of neurons in mice with posttraumatic stress disorder (PTSD), so as to explore the underlying mechanisms of acupuncture at auricular points in improving emotional diseases induced by PTSD., Methods: C57BL/6J male mice were randomly divided into control, PTSD model, sham electroacupuncture (EA), and EA groups, with 5 mice in each group. The glutamatergic neurons were labelled by injection of AAV2/9-CaMKⅡα-EGFP viral fluid into the bilateral ACC. Fourteen days after the injection, the PTSD model was established by single prolonged stress (restraint stress, forced swimming, ether exposure) and plantar electrical shock. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral "Xin" points and the center of auriculae of auricular concha area for 30 min, once daily for 7 days. Mice of the sham EA group were anesthetized for 30 min per day for 7 days, but no EA treatments were given. The anxiety-like behavior of mice was evaluated by open field (OF) and elevated plus maze (EPM) tests after 2 weeks of modeling. The whole-cell patch-clamp method was used to record the intrinsic excitability level of ACC glutamatergic neurons., Results: Compared with the control group, the dwell time and locomotor distance in the central area of the OF, the dwell time and entry times percentage in the open arms of the EPM in the model group were significantly reduced ( P <0.001, P <0.01). At the same time, the intrinsic excitability of ACC glutamatergic neurons in model mice was suppressed, presenting as enhanced rheobase currents ( P <0.01) and decreased spike number ( P <0.05, P <0.01, P <0.001). Compared with the model group, the dwell time and locomotor distance in the central area of the OF, the dwell time and entry times percentage in the open arms of the elevated plus maze were significantly increased ( P <0.001, P <0.01), and the intrinsic excitability of ACC glutamatergic neurons was significantly improved, presenting as reduced rheobase currents ( P <0.05) and an increased spike number ( P <0.05) in the EA group. Compared with the sham EA group, the dwell time and locomotor distance in the central area of the OF, the dwell time and entry times percentage in the open arms of the EPM were significantly increased ( P <0.001, P <0.01) in the EA group, and the intrinsic excitability of ACC glutamatergic neurons was significantly improved, presenting as reduced rheobase currents ( P <0.01) and an increased spike number ( P <0.05)., Conclusions: EA of auricular points can effectively alleviate the anxiety-like behavior of PTSD mice and increase the intrinsic excitability level of glutamatergic neurons in ACC, which may be one of the neural mechanisms of auricular point stimulation in the treatment of emotional diseases.

Massive numbers of modified bases in mRNAs sculpt the epitranscriptome and play vital roles in RNA metabolism. The only known acetylated RNA modification, N-4-acetylcytidine (ac 4 C), is highly conserved across cell types and among species. Although the GCN5-related acetyltransferase 10 (NAT10) functions as an ac 4 C writer, the mechanism underlying the acetylation process is largely unknown. In this study, the NAT10/PCBP/TDP43 complex mediated mRNA ac 4 C formation in mammalian cells is identified. RNA-binding proteins (RBPs) are identified, affiliated with two different families, poly(rC)-binding protein 1/2 (PCBP1/2) and TAR DNA binding protein 43 (TDP43), as NAT10 adaptors for mRNA tethering and substrate selection. Knockdown of the adaptors resulted in decreased mRNA acetylation abundance in HEK293T cells and ablated cytidine-rich ac 4 C motifs. The adaptors also affect the ac 4 C sites by recruiting NAT10 to their binding sequences. The presence of the NAT10/PCBP/TDP43 complex in mouse testes highlights its potential physiological functions in vivo. These findings reveal the composition of the mRNA ac 4 C writer complex in mammalian cells and expand the knowledge of mRNA acetylation and ac 4 C site preferences., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Gastric cancer (GC) endangers the survival and prognosis of patients worldwide. Improving the prognosis of patients with early GC (EGC) is crucial to prolong their survival time., Aim: To analyze the effects of endoscopic submucosal dissection (ESD) on gastrointestinal function and nutritional status in patients with EGC., Methods: Eighty patients with EGC between January 2021 and January 2024 were divided according to different surgical protocol into following two groups: 42 patients who underwent ESD in the ESD group and 38 patients treated with endoscopic mucosal resection (EMR) in the EMR group. Two groups were compared in the operative indices, lesion resection rate, postoperative recovery of gastrointestinal function, nutritional status, and incidence of surgical complications., Results: The overall resection rate of the lesion in the ESD group was higher. The operative bleeding volume and operation time were higher and gastrointestinal ventilation time was shorter in the ESD group than those in the EMR group ( P < 0.05). The nutritional statuses of the two groups decreased after operation; however, the levels of albumin, prealbumin, hemoglobin, and transferrin were higher in the ESD group than in the EMR group ( P < 0.05). The post-operative pepsinogen (PG) I level in the ESD group was higher than that in the EMR group, and the PG II level was lower than that in the EMR group ( P < 0.05). The incidence of postoperative complications was compared between the two groups ( P > 0.05)., Conclusion: ESD can promote the immediate recovery of patient's postoperative gastrointestinal function, improve their nutritional level, and signifies its application in patients with EGC., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Previous studies have mainly focused on the effects of individual fatty acids on depressive symptoms, while the combined effect of fatty acids on the risk of depressive symptoms has not yet been extensively reported. This study evaluate the associations between individual and multiple fatty acids with depressive symptoms in U.S. adults., Methods: Data sets were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 cycles. Both males and females aged above 18 years with complete information about dietary fatty acids intake, depression symptoms, and covariates were included. Weighted linear regression models were conducted to evaluate the relationships between individual fatty acid intake and depressive symptoms, and restricted cubic spline (RCS) models were utilized to explore the corresponding dose-response relationships. Additionally, we implemented the weighted quantile sum (WQS) regression and quantile g-computation (QGC) models to estimate the mixed effects of 19 fatty acids and identify the predominant types., Results: After multivariable adjustments, an increase of one unit in Linoleic acid (LA), Alpha-Linolenic Acid (ALA), Arachidonic acid (AA), Docosapentaenoic acid(DPA), Docosahexaenoic acid(DHA), was associated with a decrease in depressive scores by -0.021 (95 % CI: -0.039,-0.003, p = 0.021),-0.028 (95 % CI: -0.045,-0.011, p = 0.002),-0.026 (95 % CI: -0.044,-0.008, p = 0.005), -0.026 (95 % CI: -0.042,-0.009, p = 0.003), and - 0.022 (95 % CI: -0.041,-0.003, p = 0.022), respectively. However, a per unit increase in Hexanoic acid and Octanoic acid was associated with an increase in depressive scores of 0.020 (95 % CI: 0.002,0.038, p = 0.029) and 0.026 (95 % CI: 0.004,0.048, p = 0.020), respectively. Meanwhile, significant dose-response relationships were supported by the RCS models. As for the mixed effects, both WQS and QGC models demonstrated that the mixture of polyunsaturated fatty acids (PUFAs) was inversely related to depressive symptoms, and ALA and DPA were the most critical contributors. DHA was negatively correlated with depressive symptoms in WQS analysis, but positively correlated with depressive symptoms in QGC analysis., Limitations: The cross-sectional design limits our ability to establish causality, and 24-hour dietary recall can lead to potential inaccuracies reflecting participants' true eating habits., Conclusion: Our study suggests that the single effects of each PUFA were inversely associated with depressive symptoms, except for octadecatetraenoic acid. Moreover, higher combined intake of dietary PUFAs is inversely associated with depressive symptoms in U.S. adults. Among the mixed effects of PUFAs, ALA and DPA may play predominant roles. However, DHA mixed with other fatty acids may have different effects on depressive symptoms, and further study is needed., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The pathogenesis of cardiovascular diseases (CVDs) is intricate, with liquid-liquid phase separation (LLPS) considered a crucial regulatory mechanism. Epigenetics is closely intertwined with cardiovascular diseases, involving mechanisms such as DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) that play pivotal roles in cardiovascular disease progression and regression. It is known that specific proteins and mRNAs associated with epigenetic modifications exhibit LLPS characteristics, influencing cardiovascular diseases. Consequently, targeting epigenetic modifications to modulate LLPS emerges as a promising strategy for cardiovascular diseases treatment. This review delves into the regulatory impact of liquid-liquid phase separation on cardiovascular diseases, with a specific focus on the epigenetic landscape. The current study sought to investigate the relationship between epigenetic landscape and phase separation in cardiovascular diseases development, as well as their therapeutic implications., 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 Masson SAS.. All rights reserved.)

High-performance piezoelectric ceramics with excellent thermal stability are crucial for high-temperature piezoelectric sensor applications. However, conventional fabrication processes offer limited enhancements in piezoelectric performance. In this study, we achieved a significant breakthrough in the piezoelectric performance of highly textured CaBi 2 Nb 2 O 9 (CBN) ceramics by incorporating rare-earth gadolinium doping and utilizing spark plasma sintering. The resulting Ca 0.97 Gd 0.03 Bi 2 Nb 2 O 9 (CBN-3Gd) ceramics exhibited superior piezoelectric properties, with a high piezoelectric constant d 33 of 26 pC/N and a high Curie temperature T C of 946 °C. We employed piezoresponse force microscopy (PFM) to observe the morphology and dimensions of the ferroelectric domains, revealing a rod-shaped 3D domain configuration. This configuration facilitated polarization rotation in the textured ceramics, as analyzed using X-ray photoelectron spectroscopy (XPS) and polarization-electric field ( P - E ) hysteresis loops. Furthermore, the textured CBN-3Gd ceramics demonstrated exceptional thermal stability and reliability. The piezoelectric constant d 33 decreased by only 11.8% over a temperature range of room temperature to 500 °C, and the DC electrical resistivity remained at 6.7 × 10 5 Ω cm at 600 °C. This work not only highlights the great potential of textured CBN-based ceramics for high-temperature piezoelectric sensors but also provides a viable strategy for enhancing the performance of piezoelectric materials with large aspect ratio micromorphology.

Background: Mechanosensitive ion channels play a key role in heart development, physiology, and disease. However, little is known about the molecular mechanisms of the mechanosensitive nonselective cationic channel Piezo family in cardiac fibrosis., Methods and Results: Mice were treated with ISO/Ang-II/TAC to induce cardiac fibrosis. AAV9 carrying POSTN promoter-driven small hairpin RNA targeting YTHDF1, and Piezo2 were administered to ISO mice to investigate their roles in cardiac fibrosis. RNA-seq, single-cell sequencing, and histological and biochemical analyses were performed to determine the mechanism by which YTHDF1 regulates Piezo2 expression in cardiac fibrosis. Piezo2 was reconstituted in YTHDF1-deficient cardiac fibroblasts and mouse hearts to study its effects on cardiac fibroblast autophagy and fibrosis. Piezo2 but not Piezo1 expression increased in experimental cardiac fibrosis and TGF-β1-induced cardiac fibroblasts. Fibroblast-specific Piezo2 deficiency ameliorated fibroblast activation and autophagy and inhibited cardiac fibrosis. Mechanistically, Piezo2 upregulation was associated with elevated m6A mRNA levels. Site-specific m6A modifications at peak&#95;26355 were crucial for regulating the binding of YTHDF1 to Piezo2 mRNA and inducing Piezo2 translation. Notably, Piezo2 epitranscriptomic repression ameliorated experimental cardiac fibrosis., Conclusions: We demonstrated a novel epitranscriptomic mechanism through which YTHDF1 recognizes Piezo2 and controls cardiac fibroblast autophagy and fibrosis through m6A-dependent modulation. Our findings provide new insights for the development of preventive measures for cardiac fibrosis., (© 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.)

Objective: To investigate the correlation between persistent atrial fibrillation (AF) recurrence and alterations in cystatin C levels pre- and post-radiofrequency catheter ablation (RFCA)., Methods: This study encompassed 114 patients diagnosed with persistent AF. Their serum cystatin C levels were assessed both prior to and 3 months after undergoing an RFCA procedure. The variance in cystatin C levels before and after RFCA is represented as ΔCystatin C. Subsequently, we compared these values between two groups: patients who did not experience a recurrence of AF (n = 79) and those who did experience a recurrence (n = 35)., Results: A significant reduction in cystatin C levels post-RFCA in both groups, with a more pronounced decrease observed in the non-recurrence group. Moreover, the recurrence group exhibited larger left atrial diameter and volume before RFCA compared to the non-recurrence group. Cox regression analysis indicated that smaller reductions in serum cystatin C levels and greater left atrial volumes before RFCA were associated with an increased risk of recurrence, after adjusting for covariates. The receiver operating characteristic curve indicated an elevated probability of clinical recurrence of AF post-RFCA in patients with a cystatin C decline < 0.08 mg/L (AUC 0.64). The Kaplan-Meier survival analysis revealed that patients with a cystatin C decline > 0.08 mg/L exhibited significantly higher rates of remaining free from recurrence following RFCA across a 24-month follow-up period (Log-rank test p = 0.003)., Conclusions: Alterations in ΔCystatin C levels pre and post-RFCA in the initial phase could independently predict the recurrence of AF., (© 2024 The Author(s). Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Substantial evidence indicates that a decline in mitochondrial health contributes to the development of Parkinson disease. Accordingly, therapeutic stimulation of mitophagy, the autophagic turnover of dysfunctional mitochondria, is a promising approach to treat Parkinson disease. An attractive target in such a setting is PINK1, a protein kinase that initiates the mitophagy cascade. Previous reports suggest that PINK1 kinase activity can be enhanced by kinetin triphosphate (KTP), an enlarged ATP analog that acts as an alternate phosphate donor for PINK1 during phosphorylation. However, the mechanism of how KTP could exert such an effect on PINK1 was unclear. In a recent study, we demonstrate that contrary to previous thinking, KTP cannot be used by PINK1. Nucleotide-bound PINK1 structures indicate that KTP would clash with the back of PINK1's ATP binding pocket, and enlarging this pocket by mutagenesis is required to enable PINK1 to use KTP. Strikingly, mutation shifts PINK1's nucleotide preference from ATP to KTP. Similar results could be demonstrated in cells with kinetin, a membrane-permeable precursor of KTP. These results overturn the previously accepted mechanism of how kinetin enhances mitophagy and indicate that kinetin and its derivatives instead function through a currently unidentified mechanism.

Wilms' tumour 1 (WT1) can function as an oncogene or a tumour suppressor. Our previous clinical cohort studies showed that low WT1 expression at diagnosis independently predicted poor outcomes in acute myeloid leukaemia (AML) with RUNX1::RUNX1T1, whereas it had an opposite role in AML with non-favourable cytogenetic risk (RUNX1::RUNX1T1-deficient). The molecular mechanism by which RUNX1::RUNX1T1 affects the prognostic significance of WT1 in AML remains unknown. In the present study, first we validated the prognostic significance of WT1 expression in AML. Then by using the established transfected cell lines and xenograft tumour model, we found that WT1 suppresses proliferation and enhances effect of cytarabine in RUNX1::RUNX1T1(+) AML but has opposite functions in AML cells without RUNX1::RUNX1T1. Furthermore, as a transcription factor, WT1 physically interacts with RUNX1::RUNX1T1 and acts as a co-factor together with RUNX1::RUNX1T1 to activate the expression of its target gene DUSP6 to dampen extracellular signal-regulated kinase (ERK) activity. When RUNX1::RUNX1T1-deficient, WT1 can activate the mitogen-activated extracellular signal-regulated kinase/ERK axis but not through targeting DUSP6. These results provide a mechanism by which WT1 together with RUNX1::RUNX1T1 suppresses cell proliferation through WT1/DUSP6/ERK axis in AML. The current study provides an explanation for the controversial prognostic significance of WT1 expression in AML patients., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Snake venom botrocetin facilitates von Willebrand factor (VWF) binding to platelet GPIbα and has been widely used for the diagnosis of von Willebrand disease and GPIb-related disorders. Botrocetin is also commonly employed for the development/characterization of antithrombotics targeting the GPIb-VWF axis., Objectives: To explore the alternative receptor(s)/mechanisms that participate in botrocetin-induced platelet aggregation., Methods: The effects of botrocetin on platelet aggregation were examined using platelets from wild-type, VWF- and fibrinogen-deficient, GPIbα-deficient, IL4Rα/GPIbα-transgenic, ITGA2B and ITGB3-deficient mice, and Bernard-Soulier syndrome and healthy human samples. Platelet-fibrinogen and platelet-VWF interaction were measured using flow cytometry. GPIbα-VWF binding was evaluated utilizing enzyme-linked immunosorbent assay. Botrocetin-α IIb β 3 and botrocetin-GPIbα interactions were measured using enzyme-linked immunosorbent assay and fluorescence anisotropy assays. Heparinized whole blood from healthy donors was examined for thrombus formation and growth in a perfusion chamber., Results: Botrocetin could induce aggregation of platelets from a Bernard-Soulier syndrome patient and GPIbα-deficient mice as well as platelets lacking the N-terminal extracellular domain of GPIbα. Botrocetin could interact with α IIb β 3 and facilitated α IIb β 3 -VWF interaction independent of GPIb. Botrocetin competitively bound to the ligand-binding domain of activated rather than resting α IIb β 3 . Although botrocetin-induced platelet aggregation requires VWF, strikingly, in the absence of VWF, botrocetin blocked fibrinogen and other ligand binding to α IIb β 3 and inhibited platelet aggregation and thrombus formation. Consistently, recombinant botrocetin defective in VWF binding inhibited α IIb β 3 - and GPIb-mediated platelet aggregation, spreading, and thrombus formation., Conclusion: Our study provides insights into avoiding the misdiagnosis of GPIb-related disorders and developing botrocetin mutants as potential new antithrombotics that may simultaneously target both α IIb β 3 and GPIbα., Competing Interests: Declaration of competing interests Integrin β(3) monoclonal antibodies are patented in the United States, Canada, and Europe (United States patent number 7731966; Canadian patent number CA2628900C; European patent number EP2025685B1). GPIbα monoclonal antibodies are patented in the United States, Canada, and Europe (United States patent number 8323652; Canadian patent number CA2689726C; European patent number EP2186829B1)., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Reducing the charging voltage is a prerequisite for improving the chargeability and energy efficiency of Zn-air batteries (ZABs). Herein, Fe 3+ pumps electrons from oxygen-bridged cobalt (Fe-O-Co) and induces the accelerated charging kinetics. For the liquid ZABs, a charging voltage of around 1.94 V at 10 mA cm -2 was displayed, which slightly increased 2% after continuous cycles for 180 h. A steady charging voltage of around 1.87 V at 10 mA cm -2 was also exhibited for quasi-solid-state ZABs. Control experiments and characterization show that the interactions between the O 2- and Fe 3+ sites are relatively weaker than those between the O 2- and Co 3+ sites. Compared with Mn 3+ , Zn 2+ , and Cu 2+ , Fe 3+ effectively pumps electrons from Co sites to generate the active species for the oxygen evolution reaction. Thus, the deprotonation behavior and *OH conversion were improved. This work demonstrates the oxygen electron bridge modulated electron transfer between dual metal sites, contributing to the improvement of low-charging-voltage ZABs.

Bacterial aromatic polyketides are compounds with multiple aromatic rings synthesized by bacterial type II polyketide synthases (PKSs), some of which have been developed into clinical drugs. Compounds containing aromatic polyketides synthesized by hybrid type I and type II PKSs are extremely rare. Here, we report the discovery of a gene cluster encoding both modular type I and type II PKSs as well as KAS III through extensive bioinformatics analysis, leading to the characterization of the hybrid polyketide, spirocycline A. The structure of spirocycline A is rare among all aromatic polyketides, featuring a unique starter unit and four spirocycles and forming a dimer. Biosynthetic studies indicate that the starter unit of this molecule is synthesized by type I PKS in collaboration with two trans -acting ketoreductase (KR) and enoylreductase (ER). It is then transferred by KAS III to the type II PKS system, which synthesizes the tricyclic aromatic polyketide backbone. The subsequent formation of the spirocycle and dimerization are carried out by four redox enzymes encoded in the gene cluster. Overall, the discovery of spirocycline A provides a new approach for identifying novel aromatic polyketides and offers potential enzymatic tools for the bioengineering of these hybrid polyketides.

Background: This study aims to assess the performance of an established an AI algorithm trained on conventional polychromatic computed tomography (CT) images (CPIs) to detect pulmonary ground-glass nodules (GGNs) on virtual monochromatic images (VMIs), and to screen the optimal virtual monochromatic energy for the clinical evaluation of GGNs., Methods: Non-enhanced chest SDCT images of patients with pulmonary GGNs in our clinic from January 2022 to December 2022 were continuously collected: adenocarcinoma in situ (AIS, n = 40); minimally invasive adenocarcinoma (MIA, n = 44) and invasive adenocarcinoma (IAC, n = 46). A commercial CAD system based on deep convolutional neural networks (DL-CAD) was used to process the CPIs, 40, 50, 60, 70, and 80 keV monochromatic images of 130 spectral CT images. AI-based histogram parameters by logistic regression analysis. The diagnostic performance was evaluated by the receiver operating characteristic (ROC) curves, and Delong's test was used to compare the CPIs group with the VMIs group., Results: When distinguishing IAC from MIA, the diagnostic efficiency of total mass was obtained at 80 keV, which was superior to those of other energy levels (P < 0.05). And Delong's test indicated that the differences between the area-under-the-curve (AUC) values of the CPIs group and the VMIs group were not statistically significant (P > 0.05)., Conclusion: The AI algorithm trained on CPIs showed consistent diagnostic performance on VMIs. When pulmonary GGNs are encountered in clinical practice, 80 keV could be the optimal virtual monochromatic energy for the identification of preoperative IAC on a non-enhanced chest CT., (© 2024. The Author(s).)

Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1st January 2024 and 1st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Sensitive and selective detection of trace aflatoxin B1 (AFB1) in foods is of great importance to guarantee food safety and quality but still challenging because of its trace amount and the interference from the complex food matrix. Here, we report the integration of aptamer (Apt) and an ordered 2D covalent organic framework (COF) to solid-state anodic aluminum oxide (AAO) nanochannels (Apt/COF/AAO) for selective and sensitive detection of trace AFB1. The high specificity of Apt for AFB1 led to a selective change in the surface charge of Apt/COF/AAO and in turn the current change of the nanochannel, permitting the selective and sensitive determination of trace AFB1 in complex food samples. The developed nanofluidic sensor gave a wide linear range (1-500 pg mL -1 ), low detection limit (0.11 pg mL -1 ), and good precision (relative standard deviation of 1.5% for 11 replicate determinations of 100 pg mL -1 ). In addition, the developed sensor was successfully used for the detection of AFB1 in food samples with the recovery of 86.9%-102.5%. The coupling of Apt-conjugated 2D COF with an AAO nanochannel provides a promising way for sensitive and selective determination of food contaminants in complex samples.

To investigate the correlation of cervical central lymph node metastasis (CLNM) in stage T1a unifocal papillary thyroid carcinoma (PTC) with the clinicopathological characteristics, ultrasonography features and the number of lymph node dissection, and to analyze the risk factors of CLNM. Data from 493 unifocal PTC patients (T1a) who underwent partial or total thyroidectomy and pCLND at the Guizhou Provincial People's Hospital were collected and retrospectively analyzed. They were divided into two groups in accordance with cervical CLNM or not. Their information, including clinical characteristics, ultrasound (US) features, pathological results, and other characteristics of the groups, was analyzed and compared using univariate and multivariate logistic regression analyses. A total of 493 patients were eligible in this study. Among them, 33.7% (166/493) of PTC patients had cervical CLNM, and 66.3% (327/493) did not. The two groups were compared using a univariate analyses, and there were no significant differences between the two groups in age, maximum tumor size, tumor location, aspect ratio, boundary, morphology, echogenicity, BRAF V600E and HT (P > 0.05), and there were significant differences between gender, capsule contact, microcalcifications, rich vascularity, and number of lymph node dissection (P < 0.05). A multivariate logistic regression analyses was performed to further clarify the correlation of these indices. However, only male (OR = 1.770, P = 0.009), microcalcifications (OR = 1.791, P = 0.004), capsule contact (OR = 1.857, P = 0.01), and number of lymph node dissection (OR = 2.274, P < 0.001) were independent predictors of cervical CLNM. In conclusion, four independent predictors of cervical CLNM, including male, microcalcifications, capsule contact, and number of lymph node dissection, were screened out. Therefore, a comprehensive assessment of these risk factors should be conducted when designing individualized treatment regimens for PTC patients., (© 2024. The Author(s).)

Phenyl polyenes comprise a small family of bacterial natural products with broad and potent bioactivities, primarily found in actinobacteria. Here we report the discovery of five new phenyl polyene metabolites, maduraflavacins A-E ( 1 - 5 ), from a rare, marine-derived actinobacteria strain Actinomadura glauciflava NA03286. The structures of these natural products were determined by NMR spectroscopy, HRESIMS, LC-MS/MS, and chemical derivatization. All of these new maduraflavacins feature methyl substitutions at the polyene side chain, and maduraflavacins A-C ( 1 - 3 ) possessed a 1- N -β-d-glucosamine-(3 → 1)- O -β-d-glucopyranosyl-(3 → 1)- O -β-d-glucopyranosyl-(6 → 1)- O -β-d-glucopyranoside tetrasaccharide moiety via an amido linkage with a phenyl polyene skeleton. Compounds 1 and 2 showed weak antibacterial activities against the Gram-positive bacteria Staphylococcus aureus Sau 16339 and Micrococcus luteus , respectively.

Obesity and related diseases pose a major health risk, yet current anti-obesity drugs inadequately addressing clinical needs. Here we show AA005, an annonaceous acetogenin mimic, resists obesity induced by high-fat diets and leptin mutations at non-toxic doses, with the alpha subunit of the mitochondrial trifunctional protein (HADHA) as a target identified through proteomics and in vitro validation. Pharmacokinetic analysis shows AA005 enriches in adipose tissue, prompting the creation of adipose-specific Hadha-deficient mice. These mice significantly mitigate diet-induced obesity, echoing AA005's anti-obesity effects. AA005 treatment and Hadha deletion in adipose tissues increase body temperature and energy expenditure in high-fat diet-fed mice. The beneficial impact of AA005 on obesity mitigation is ineffective without uncoupling protein 1 (UCP1), essential for thermogenesis regulation. Our investigation shows the interaction between AA005 and HADHA in mitochondria, activating the UCP1-mediated thermogenic pathway. This substantiates AA005 as a promising compound for obesity treatment, targeting HADHA specifically., (© 2024. The Author(s).)

Ecdysone-induced protein 93 (E93), known as the 'adult-specifier' transcription factor in insects, triggers metamorphosis in both hemimetabolous and holometabolous insects. Although E93 is conserved in ametabolous insects, its spatiotemporal expression and physiological function remain poorly understood. In this study, we first discover that, in the ametabolous firebrat Thermobia domestica, the previtellogenic ovary exhibits cyclically high E93 expression, and E93 mRNA is broadly distributed in previtellogenic ovarioles. E93 homozygous mutant females of T. domestica exhibit severe fecundity deficiency due to impaired previtellogenic development of the ovarian follicles, likely because E93 induces the expression of genes involved in ECM (extracellular matrix)-receptor interactions during previtellogenesis. Moreover, we reveal that in the hemimetabolous cockroach Blattella germanica, E93 similarly promotes previtellogenic ovarian development. In addition, E93 is also essential for vitellogenesis that is necessary to guarantee ovarian maturation and promotes the vitellogenesis-previtellogenesis switch in the fat body of adult female cockroaches. Our findings deepen the understanding of the roles of E93 in controlling reproduction in insects, and of E93 expression and functional evolution, which are proposed to have made crucial contributions to the origin of insect metamorphosis., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Abnormal differentiation of cells is a hallmark of malignancy. Induction of cancer-cell differentiation is emerging as a novel therapeutic strategy with low toxicity in hematological malignances, but whether such treatment can be used in solid tumors is not known. Here, we uncovered a novel function of acetyl coenzyme A acetyltransferase (ACAT1) in regulating the differentiation of glioblastoma (GBM) cells. Inhibition of ACAT1 promoted the differentiation of GBM cells into astrocytes but also delayed tumor growth. Mechanistically, suppression of ACAT1 restored mitochondrial function and led to metabolic "reprogramming" in GBM cells: reduction of fatty-acid oxidation and acetyl-CoA, but an increase in free fatty acids. Importantly, ACAT1 negatively regulated the choline metabolic pathway, which is crucial for the differentiation of GBM cells. Finally, we demonstrated that a naturally available substance, chlorogenic acid (CHA), could inhibit phosphorylation of ACAT1 and so delay GBM progression, CHA is a promising candidate to treat GBM because it could induce the differentiation of cancer cells., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To evaluate the diagnostic performance of fibroblast activation protein inhibitors (FAPI) PET/CT for the detection of lymph node (LN) metastases in lung cancer patients., Methods: The PubMed and Embase databases were searched to identify relevant articles published through July 2024. We included studies reporting the diagnostic accuracy of FAPI PET/CT in detecting LN metastases in lung cancer patients. A head-to-head comparison of FAPI PET/CT and fluorodeoxyglucose (FDG) PET/CT was made among available studies. The pooled sensitivity, specificity, and area under the summary receiver-operating characteristics curve (AUC) were determined by using bivariate random-effects model., Results: Seven studies with 409 patients were eligible. The pooled sensitivity, specificity, and AUC value for FAPI PET/CT in detecting LN metastases in lung cancer patients were 88% (95% CI, 78-93%), 94% (95% CI, 89-96%), and 0.97 (95% CI, 0.95-0.98), respectively. Six studies provided head-to-head comparison data, and the pooled sensitivity, specificity, and AUC value were 89% (95% CI 80-95%), 94% (95% CI 89-97%), and 0.97 (95% CI 0.95-0.98) for FAPI PET/CT versus 78% (95% CI 64-87%), 66% (95% CI 33-88%), and 0.80 (95% CI 0.76-0.83) for FDG PET/CT. Fagan nomogram indicated that when the pre-test probability was set at 26%, the negative post-test probability for a FAPI PET/CT scan could decrease to 4%., Conclusions: FAPI PET/CT shows excellent diagnostic accuracy for the detection of LN metastases in lung cancer patients, and is superior to standard-of-care FDG PET/CT. The outstanding ruling-out performance of FAPI PET/CT for LN metastases indicates that it holds the potential to reduce invasive diagnostic procedures., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

A general one-step lateral flow immunochromatographic assay (LFIA) for the quantitative detection of triadimefon (TDF) and triadimenol (TDN) in fruit and vegetable samples was developed using time-resolved fluorescence microspheres (TRFM) as labels. A specific anti-triadimefon monoclonal antibody (mAb) was conjugated with TRFM to fabricate LFIA test strips. A time-resolved fluorometer as an LFIA reader was applied to obtain quantitative results and assess risk ranges for the LFIA test strips. Under the optimized experimental conditions, the limits of detection (LODs) in buffer/cucumbers/tomatoes/oranges were 0.046 ng/mL, 0.135 µg/kg, 1.047 µg/kg, and 5.811 µg/kg, respectively, which are ca. 1000 times lower than that of colloidal gold-labeled strips. The recovery in cucumber/tomato/orange samples was 109.4-116.7%, 87.7-110.9%, and 88.0-111.9%, respectively, indicating that the test strips had good reliability. Coupled with the easily customizable pretreatment procedures for various samples, the LFIA results were obtained within 18 min without the need for professional personnel or complicated equipment. TRFM-LFIA for TDF and TDN also shows remarkable specificity and precision. The test strips were also low-cost, portable, and convenient to use. These results indicate the test strips could be utilized as a novel strategy for on-site detection of TDF and TDN, which has the potential to expand and detect other pesticide or insecticide residues in food., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Juvenile hormone (JH) is an insect-exclusive hormone involved in regulating diverse aspects of insect physiology, and the evolution of its diverse function is widely interesting. Studying embryogenesis in basal wingless insects is important to understand the functional evolution of JH; however, experimental studies in this regard are scarce. In this study, we conducted CRISPR/Cas9-mediated knockout (KO) of genes involved in JH biosynthesis and signaling cascades in the ametabolous firebrat, Thermobia domestica. Additionally, we investigated whether the primitive action of JH is conserved in the hemimetabolous cricket, Gryllus bimaculatus., Results: We observed that KO of JHAMT, CYP15A1, Met, and Kr-h1 resulted in embryonic lethality in T. domestica. Deprivation of JH or JH signaling arrested the progression of extraembryonic fluid resorption after dorsal closure and hatching, which is consistent with the gene expression pattern showing high Kr-h1 expression in the late embryos of T. domestica. The embryos deficient in JH signaling displayed wrinkled and weak legs. Comparative transcriptome analysis revealed that JH signaling promotes embryonic leg maturation through inducing energy supply and muscle activity, as validated by transmission electron microscopy (TEM). In addition, JH signaling exhibited similar embryonic effects in G. bimaculatus., Conclusions: This study reveals the indispensable role of JH signaling in facilitating the maturation of terminal tissues during late embryogenesis, as demonstrated by the regulation of leg development, in ametabolous and hemimetabolous insects. These findings further indicate that the embryonic functions of JH evolved earlier than its anti-metamorphic functions during postembryonic development., (© 2024. The Author(s).)

Preparing stable n-type flexible single-walled carbon nanotube (SWCNT)-based thermoelectric films with high thermoelectric (TE) performance is desirable for self-powering wearable electronics but remains a challenge. Here, the interface regulation and thermoelectric enhancement mechanism of ferrocene derivatives on polyethylenimine/single-walled carbon nanotube (PEI/SWCNT) composite films have been explored by doping ferrocene derivatives (f-Fc-OH) into PEI/SWCNT films. The results show that the introduction of f-Fc-OH leads to the formation of "thorn" structures on the surfaces of SWCNT bundles via hydrophilic and hydrophobic interactions, the generated energy-filtering effect improves the thermoelectric properties of the PEI/SWCNT film, and the f-Fc-OH-doped PEI/SWCNT (f-Fc-OH/PEI/SWCNT) achieves the highest room-temperature power factor of 182.22 ± 8.60 μW m -1 K -2 with a Seebeck coefficient of -64.28 ± 0.96 μV K -1 and the corresponding ZT value of 4.69 × 10 -3 . The Seebeck coefficient retention ratio of the f-Fc-OH/PEI/SWCNT nearly remained 68% after being exposed to air for 3672 h, while the PEI/SWCNT film changed from n-type to p-type after being exposed to air for about 432 h. In addition, the temperature-dependent thermoelectric properties show that the f-Fc-OH/PEI/SWCNT achieves a high power factor of 334.57 μW m -1 K -2 at 353 K. Finally, a flexible TE module consisting of seven pairs of p-n junctions is assembled using the optimum composite film, which produces an open-circuit voltage of 42 mV and a maximum output power of 4.32 μW at a temperature gradient of 60 K. Therefore, this work provides guidance for preparing stable n-type SWCNT-based composite films with enhanced thermoelectric properties, which have potential applications in flexible generators and wearable electronic devices.

To explore the characteristics of phytoplankton communities and their relationship with environmental factors in different habitats of Hedi Reservoir, the inflow rivers, estuaries, and reservoir area of Hedi Reservoir were investigated in February （recession period）, April （flood period）, July （flood period）, and December （recession period） of 2022. During the investigation, 231 species of phytoplankton that belong to seven phyla were identified, and the cell density of phytoplankton ranged from 2.94 × 10 6 - 8.04 × 10 8 cells·L -1 . Phytoplankton cell density in flood periods were higher than that in recession periods, and that was higher in estuaries and the reservoir area than that in inflow rivers. Meanwhile, the cell density of phytoplankton in the estuarine and reservoir area was dominated by Cyanobacteria throughout the year, especially Raphidiopsis raciborskii , whereas the cell density of phytoplankton in inflow rivers was dominated by Cyanophyta, Chlorophyta, and Bacillariophyta. In the inflow river area, the dominant species of cyanobacteria were Microcystis aeruginosa , Limnothrix redekei , Pseudanabaena circinalis, and Merismopedia punctata ； the dominant species of Chlorophyta were Chlorella vulgaris and Crucigenia tetrapedia ； and the dominant species of Bacillariophyta were Chlorella vulgaris and Melosira granulate . The highest biodiversity （Shannon-Wiener Index, Pielou index, and Margalef index） were observed in the inflow river area of Hedi Reservoir. The correlation analysis （Pearson） indicated that the environmental factors that were significantly correlated to phytoplankton communities included water temperature, dissolved oxygen, pH, conductivity, nitrogen, and phosphorus concentration. The RDA analysis indicated that phytoplankton communities in the inflow river area were mainly affected by pH and total nitrogen concentration, which were majorly affected by water temperature and pH in the estuarine area and chiefly affected by turbidity and pH in the reservoir. The pH affected the changes in phytoplankton communities in all three different habitats, whereas the inflow river area was significantly affected by total nitrogen concentration, and the estuarine and reservoir were significantly affected by water temperature and turbidity, respectively.

Mycotoxins are ubiquitous natural pollutants that pose a serious threat to public health. Deoxynivalenol (DON) as one of the most prominent mycotoxins has a noticeable adverse effect on intestinal barrier function, which depends on the intestinal barrier integrity. However, the potential mechanisms and effective therapeutic strategies remain unclear. Aryl hydrocarbon receptor (AHR) has been implicated in the modulation of intestinal barrier function and inflammation. The study aims to investigate the unique role of AHR in mediating DON-induced intestinal epithelial barrier function. In the current study, we revealed that DON triggered mitochondrial structural damage and functional impairment, leading to oxidative stress and apoptosis in porcine jejunal epithelial cells (IPEC-J2). DON altered the integrity of IPEC-J2 cells by disrupting the distribution and function of tight junction proteins. Additionally, DON activated TNF-α/NF-κB/MLCK signaling pathway, thereby eliciting inflammatory response. Notably, DON inhibited AHR nuclear translocation and attenuated xenobiotic response element promoter activity and its target genes. However, overexpression of AHR mitigated DON-induced disruption of intestinal epithelial barrier functions by suppressing TNF-α/NF-κB/MLCK pathway in IPEC-J2 cells. Our findings indicate that AHR regulates intestinal epithelial barrier function and therefore is a novel therapeutic molecule for intestinal disorders., 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.)

Selective and prior extraction of 99 TcO 4 - ahead of uranium and plutonium separation is a beneficial strategy for the modern nuclear fuel cycle. Herein, a novel DGA-grafting pyridine ligand BisDODGA-DAPy (L1) was tailored for the efficient separation of TcO 4 - from simulated spent nuclear fuel based on the selectivity of pyridine and synergistic effect of diglycolamide (DGA) group. Compared to the ligands BisDOSCA-DAPy (L2) and BisDODGA-MPDA (L3) with similar structure, BisDODGA-DAPy (L1) demonstrated the better separation performance including good extraction efficiency, reusability, and high loading capacity for TcO 4 - under high acidic medium. The interactions of the ligands with Tc(VII)/Re(VII) have been investigated in detail using FT-IR, 1 H NMR titration, UV-Vis spectrophotometric titration, ESI-HRMS and DFT simulations. The extraction mechanism affected by the protonation of ligand was elucidated under different acidity. BisDODGA-DAPy (L1) demonstrated the ultra-selective extraction ability for TcO 4 - from simulated spent nuclear fuel. The maximum SF Tc/U and SF Tc/Pu values were up to 1.29 × 10 4 and 5.08 × 10 3 , respectively. In the presence of 9 × 10 4 -fold excess of NO 3 - , the extraction of TcO 4 - was almost unaffected. Moreover, the good radiolytic stability further highlights the promising potential of this ligand for 99 Tc separation. DFT calculation revealed the dominant role of DAPy and DODGA in TcO 4 - extraction, providing the theoretical evidence for BisDODGA-DAPy (L1) to selectively bind TcO 4 - over NO 3 - ., 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.)

Based on rich sulfur-involving chemical transformations, a novel spokewise synthetic strategy, a subclass of the collective strategies, has been developed to concisely synthesize four erythrina alkaloids through a single-step transformation from a common synthetic precursor. Moreover, six additional erythrina alkaloids have also been synthesized by subsequent 1-2 steps chemical transformations. The current synthetic approaches provide a valuable platform for collective total syntheses of erythrina alkaloids and pseudo -natural erythrina alkaloids.

The crucial role of gut microbiota in shaping immunotherapy outcomes has prompted investigations into potential modulators. Here we show that oral administration of acarbose significantly increases the anti-tumour response to anti-PD-1 therapy in female tumour-bearing mice. Acarbose modulates the gut microbiota composition and tryptophan metabolism, thereby contributing to changes in chemokine expression and increased T cell infiltration within tumours. We identify CD8 + T cells as pivotal components determining the efficacy of the combined therapy. Further experiments reveal that acarbose promotes CD8 + T cell recruitment through the CXCL10-CXCR3 pathway. Faecal microbiota transplantation and gut microbiota depletion assays indicate that the effects of acarbose are dependent on the gut microbiota. Specifically, acarbose enhances the efficacy of anti-PD-1 therapy via the tryptophan catabolite indoleacetate, which promotes CXCL10 expression and thus facilitates CD8 + T cell recruitment, sensitizing tumours to anti-PD-1 therapy. The bacterial species Bifidobacterium infantis, which is enriched by acarbose, also improves response to anti-PD-1 therapy. Together, our study endorses the potential combination of acarbose and anti-PD-1 for cancer immunotherapy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The aim of this study is to investigate novel strategies for reducing adverse reactions caused by erdafitinib through a drug combination based on its pharmacokinetic characteristics. The spectrum and characterizations of drugs that can inhibit the metabolism of erdafitinib are examined both in vitro and in vivo. The efficacy of combination regimens are then evaluated using subcutaneous xenograft tumor models. The results demonstrated that sertraline and duloxetine, out of more than 100 screened drugs, inhibited the metabolism of erdafitinib through mixed and non-competitive inhibition, respectively. This inhibition primarily occurred via the CYP2C9 and CYP2D6 pathways. The primary alleles of CYP2C9 and CYP2D6 not only determine the metabolic characteristics of erdafitinib but also influence the strength of drug-drug interactions. Co-administration of sertraline or duloxetine with erdafitinib in rats and mice resulted in nearly a three-fold increase in the blood exposure of erdafitinib and its major metabolite M6. When sertraline or duloxetine was combined with 1/3 of the erdafitinib dosage, the anti-proliferative and pro-apoptotic effects on SNU-16 xenografts were comparable to those of the original full dose of erdafitinib. However, the combination regimen significantly mitigated hyperphosphatemia, retinal damage, intestinal villus damage, and gut microbiome dysbiosis. This study utilized pharmacokinetic methods to propose a new formulation of erdafitinib combined with sertraline or duloxetine. The findings suggest that this combination has potential for clinical co-administration based on a database analysis, thereby providing a novel strategy for anti-tumor treatment with fibroblast growth factor receptor (FGFR) inhibitors., 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 Masson SAS.. All rights reserved.)

Immune checkpoint inhibitor-based cancer immunotherapy has shown promise as a potential treatment in the clinic. It has been reported that anti-PD-L1 combined with cisplatin treatment can improve the antitumor effect. However, the therapeutic outcome is limited due to the abundance of tumor stroma in pancreatic cancer (PC), which prevented the penetration of cisplatin and anti-PD-L1 into tumor regions, thus impeding the effectiveness in the treatment of PC. In this study, a nanocarrier-mediated codelivery system of hyaluronidase and cisplatin was constructed, which can degrade the stroma and promote cisplatin and anti-PD-L1 to penetrate the tumor stroma into the deep tumor, so as to suppress PC effectively. When combined the cisplatin nanocarrier system BPEI-SS-Pt/HAase@CaP (BSP/H@CaP) with an immune checkpoint inhibitor to overcome the poor therapeutic outcome of PC, the results indicated that the therapeutic effect of BSP/H@CaP combined with anti-PD-L1 was better than that of BSP/H@CaP and single anti-PD-L1 group. Because the stroma is degrading, a higher amount of BPEI-SS-Pt and anti-PD-L1 can enter the tumor stroma and reach the inner depths of the tumor for immune stimulation, leading to a synergistically augmented chemotherapy and immunotherapy for PC. The above combination therapy is useful for clinical translation to overcome the treatment resistance of matrix-rich PC., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The increasing prevalence of obesity-related glomerulopathy (ORG) poses a significant threat to public health. Sodium-glucose cotransporter-2 (SGLT2) inhibitors effectively reduce body weight and total fat mass in individuals with obesity and halt the progression of ORG. However, the underlying mechanisms of their reno-protective effects in ORG remain unclear. We established a high-fat diet-induced ORG model using C57BL/6J mice, which were divided into three groups: normal chow diet (NCD group), high-fat diet (HFD) mice treated with placebo (ORG group), and HFD mice treated with empagliflozin (EMPA group). We conducted 16S ribosomal RNA gene sequencing of feces and analyzed metabolites from kidney, feces, liver, and serum samples. ORG mice showed increased urinary albumin creatinine ratio, cholesterol, triglyceride levels, and glomerular diameter compared with NCD mice (all P < 0.05). EMPA treatment significantly alleviated these parameters (all P < 0.05). Multitissue metabolomics analysis revealed lipid metabolic reprogramming in ORG mice, which was significantly altered by EMPA treatment. MetOrigin analysis showed a close association between EMPA-related lipid metabolic pathways and gut microbiota alterations, characterized by reduced abundances of Firmicutes and Desulfovibrio and increased abundance of Akkermansia (all P < 0.05). The metabolic homeostasis of ORG mice, especially in lipid metabolism, was disrupted and closely associated with gut microbiota alterations, contributing to the progression of ORG. EMPA treatment improved kidney function and morphology by regulating lipid metabolism through the gut-kidney axis, highlighting a novel therapeutic approach for ORG. NEW & NOTEWORTHY Our study uncovered that empagliflozin (EMPA) potentially protects renal function and morphology in obesity-related glomerulopathy (ORG) mice by regulating the gut-kidney axis. EMPA's reno-protective effects in ORG mice are associated with the lipid metabolism, especially in glycerophospholipid metabolism and the pantothenate/CoA synthesis pathways. EMPA's modulation of gut microbiota appears to be pivotal in suppressing glycerol 3-phosphate and CoA synthesis. The insights into gut microbiota-host metabolic interactions offer a novel therapeutic approach for ORG.

The widespread use of surfactants raise challenges to biological wastewater treatment. Anaerobic ammonium oxidation (anammox) process has the potential to treat wastewater containing anionic surfactants, but the response of anammox consortia at the molecular level under long-term exposure is unclear. Using high-throughput sequencing and gene quantification, combined with molecular docking, the effect of sodium dodecyl sulfonate (SDS) on anammox consortia were investigated. Levels of reactive oxygen species (ROS) might be lower than the threshold of oxidative damage, while the increase of lactate dehydrogenase (LDH) represented the cell membrane damage. Decreased abundance of functional genes (hdh, hzsA and nirS) indicated the decrease of the anammox bacterial abundance. Trace amounts of N-acyl homoserine lactone (AHL, C6-HSL, C8-HSL and C12-HSL) contained in influent could induce endogenous quorum sensing (QS), which could regulate the correlation between functional bacteria to optimize the microbial community and strengthen the resistance of anammox consortia to SDS. In addition, the proliferation of disinfectant resistance genes might increase the environmental pathogenicity of sewage discharge. This work highlights the potential response mechanism of anammox consortium to surfactants and provides a universal microbial-friendly bioenhancement strategy based on QS., 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.)

Japanese encephalitis (JE), a mosquito-borne zoonotic disease caused by the Japanese encephalitis virus (JEV), poses a serious threat to global public health. The low viremia levels typical in JEV infections make RNA detection challenging, necessitating early and rapid diagnostic methods for effective control and prevention. This study introduces a novel one-pot detection method that combines recombinant enzyme polymerase isothermal amplification (RPA) with CRISPR/EsCas13d targeting, providing visual fluorescence and lateral flow assay (LFA) results. Our portable one-pot RPA-EsCas13d platform can detect as few as two copies of JEV nucleic acid within 1 h, without cross-reactivity with other pathogens. Validation against clinical samples showed 100 % concordance with real-time PCR results, underscoring the method's simplicity, sensitivity, and specificity. This efficacy confirms the platform's suitability as a novel point-of-care testing (POCT) solution for detecting and monitoring the JE virus in clinical and vector samples, especially valuable in remote and resource-limited settings., 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.)

Objective: Maternal stress influences in utero brain development and is a modifiable risk factor for offspring psychopathologies. Reward circuitry dysfunction underlies various internalizing and externalizing psychopathologies. This study examined (1) the association between maternal stress and microstructural characteristics of the neonatal nucleus accumbens (NAcc), a major node of the reward circuitry, and (2) whether neonatal NAcc microstructure modulates individual susceptibility to maternal stress in relation to childhood behavioral problems., Method: K-means longitudinal cluster analysis was performed to determine trajectories of maternal stress measures (Perceived Stress Scale [PSS], hair cortisol) from preconception to the third trimester. Neonatal NAcc microstructural measures (orientation density index [ODI] and intracellular volume fraction [ICVF]) were compared across trajectories. We then examined the interaction between maternal stress and neonatal NAcc microstructure on child internalizing and externalizing behaviors, assessed between ages 3 and 4 years., Results: Two trajectories of maternal stress magnitude ("low"/"high") were identified for both PSS (n = 287) and hair cortisol (n = 336). Right neonatal NAcc ODI (rNAcc-ODI) was significantly lower in "low" relative to "high" PSS trajectories (n = 77, p = .04). PSS at preconception had the strongest association with rNAcc-ODI (r = 0.293, p = .029). No differences in NAcc microstructure were found between hair cortisol trajectories. A significant interaction between preconception PSS and rNAcc-ODI on externalizing behavior was observed (n = 47, p = .047)., Conclusion: Our study showed that the preconception period contributes to in utero NAcc development, and that NAcc microstructure modulates individual susceptibility to preconception maternal stress in relation to externalizing problems., Plain Language Summary: In the S-PRESTO population-based cohort study conducted in Singapore with 351 women and their children, higher levels of maternal perceived stress within the year before pregnancy were associated with increased dendritic complexity within offsprings' nucleus accumbens, indicative of a more advanced developmental profile. Variations in right nucleus accumbens microstructure significantly modulated the association between maternal perceived stress at preconception and externalizing behaviors in early childhood. Study findings suggest that maternal stress in the preconception period accelerates in-utero nucleus accumbens development, leading to differential risk to externalizing problems in later childhood., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

High-throughput synthesis and screening of chemical libraries play pivotal roles in drug discovery. Click chemistry has emerged as a powerful strategy for constructing highly modular chemical libraries. However, the development of new click reactions and unlocking new clickable building blocks remain exceedingly challenging. Herein, we describe a double-click strategy that enables the sequential ligations of widely available carboxylic acids and amines with fluorosulfuryl isocyanate (FSO 2 NCO) via a modular amidation/SuFEx (sulfur-fluoride exchange) process. This method provides facile access to chemical libraries of N-fluorosulfonyl amides (RCONHSO 2 F) and N-acylsulfamides (RCONHSO 2 NR'R'') in near-quantitative yields under simple and practical conditions. The robustness and efficiency of this double click strategy is showcased by the facile construction of chemical libraries in 96-well microtiter plates from a large number of carboxylic acids and amines. Preliminary biological activity screening reveals that some compounds exhibit high antimicrobial activities against Gram-positive bacterium S. aureus and drug-resistant MRSA (MIC up to 6.25 μg ⋅ mL -1 ). These results provide compelling evidence for the potential application of modular click chemistry library as an enabling technology in high-throughput medicinal chemistry., (© 2024 Wiley-VCH GmbH.)

Background: Presacral cysts are rare congenital lesions predominantly affecting females. Surgery is often recommended after diagnosis due to the risk of malignant transformation and complications associated with cyst enlargement. Laparoscopic excision is increasingly favored due to its enhanced visualization and precision., Aim: To assess long-term urinary, sexual function outcomes and quality of life in female patients undergoing laparoscopic resection of presacral cysts., Methods: We conducted a retrospective review of female patients who underwent laparoscopic resection of presacral cysts between August 2012 and May 2020. Patient demographics, surgical outcomes, and postoperative complications were analyzed. The urinary function was assessed using the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Module (ICIQ-FLUTS), the sexual function was evaluated using the Female Sexual Function Index (FSFI), and quality of life was assessed using the 36-item Short-Form Health Survey (SF-36)., Results: Among the 32 female patients included, 10 experienced postoperative urinary incontinence, predominantly of the mixed type. The risk factors for urinary incontinence included abdominal distension and the proximity of the cyst to the rectum. Notably, urinary incontinence significantly impacted the overall lower urinary tract symptoms and quality of life. Additionally, seven patients reported postoperative sexual dysfunction, with previous abdominal or pelvic surgery and cyst location under S3 identified as risk factors, affecting the mental health aspects of their quality of life., Conclusion: Laparoscopic cyst resection in females poses risks of urinary and sexual dysfunction, potentially impacting quality of life. Thus, tailored management approaches are crucial., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

The 24 solar terms are a significant component of traditional Chinese culture. Amid global warming climate change, research on the Solar Terms has gained increasing prominence. Identifying the geographical origins of the Solar Terms not only provides evidence for studies on the origins of Chinese agricultural civilization but also serves as a critical foundation for the innovative utilization of traditional culture in the modern era. Previous research has primarily relied on historical records, literature review, and field investigation, often challenged by the vast and complex data, the difficulty distinguishing authenticity, the time-consuming nature of the work, and the need for direct scientific evidence. The STTMD (Solar Terms Typical Meteorological Day) method was used for typifying solar term meteorological data sequences, supplemented by isothermal estimation and clustering analysis. This approach was further validated using key crop germplasm sites, phenological indicators, and phenological observation contour maps. The results derived from statistical methods are cross-referenced with historical documents to infer the geographical origins of the 24 Solar Terms. The findings indicate that: (1)On a larger spatial scale, the Solar Terms originated in the middle and lower reaches of the Yellow River; (2)On a smaller spatial scale, the "Luoyang-Zhengzhou-Anyang" triangle is the most probable origin area; (3)The core area of origin is hypothesized to be in present-day Xingyang, Henan Province, or slightly further north. These results are consistent with historical literature and phenological records of crops, offering a novel analysis and transformative insights into the knowledge of Solar Terms. The study provides valuable evidence or methodological inspiration for historical agricultural research in China and offers references for agricultural production and the environmental impacts of global warming., (© 2024. The Author(s).)

Background: The therapeutic potential of oncolytic measles virotherapy has been demonstrated across various malignancies. However, the effectiveness against human breast cancer (BC) and the underlying mechanisms of the recombinant measles virus vaccine strain Hu191 (rMeV-Hu191) remain unclear., Methods: We utilized a range of methods, including cell viability assay, Western blot, flow cytometry, immunofluorescence, SA-β-gal staining, reverse transcription quantitative real-time PCR, transcriptome sequencing, BC xenograft mouse models, and immunohistochemistry to evaluate the antitumor efficacy of rMeV-Hu191 against BC and elucidate the underlying mechanism. Additionally, we employed transcriptomics and gene set enrichment analysis to analyze the lipid metabolism status of BC cells following rMeV-Hu191 infection., Results: Our study revealed the multifaceted antitumor effects of rMeV-Hu191 against BC. rMeV-Hu191 induced apoptosis, inhibited proliferation, and promoted senescence in BC cells. Furthermore, rMeV-Hu191 was associated with changes in oxidative stress and lipid homeostasis in infected BC cells. In vivo, studies using a BC xenograft mouse model confirmed a significant reduction in tumor growth following local injection of rMeV-Hu191., Conclusions: The findings highlight the potential of rMeV-Hu191 as a promising treatment for BC and provide valuable insights into the mechanisms underlying its oncolytic effect., (© 2024. The Author(s).)

Background: N 6 -methyladenosine (m 6 A) modification of messenger RNA (mRNA) is crucial for liquid-liquid phase separation in mammals. Increasing evidence indicates that liquid-liquid phase separation in proteins and RNAs affects diabetic cardiomyopathy. However, the molecular mechanism by which m 6 A-mediated phase separation regulates diabetic cardiac fibrosis remains elusive., Methods: Leptin receptor-deficient mice (db/db), cardiac fibroblast-specific Notch1 conditional knockout (POSTN-Cre × Notch1 flox/flox ) mice, and Cre mice were used to induce diabetic cardiac fibrosis. Adeno-associated virus 9 carrying cardiac fibroblast-specific periostin (Postn) promoter-driven small hairpin RNA targeting Alkbh5, Ythdf2, or Notch1, and the phase separation inhibitor 1,6-hexanediol were administered to investigate their roles in diabetic cardiac fibrosis. Histological and biochemical analyses were performed to determine how Alkbh5 and Ythdf2 regulate Notch1 expression in diabetic cardiac fibrosis. NOTCH1 was reconstituted in ALKBH5- and YTHDF2-deficient cardiac fibroblasts and mouse hearts to study its effects on mitochondrial fission and diabetic cardiac fibrosis. Heart tissue samples from patients with diabetic cardiomyopathy were used to validate our findings., Results: In mice with diabetic cardiac fibrosis, decreased Notch1 expression was accompanied by high m 6 A mRNA levels and mitochondrial fission. Fibroblast-specific deletion of Notch1 enhanced mitochondrial fission and cardiac fibroblast proliferation and induced diabetic cardiac fibrosis in mice. Notch1 downregulation was associated with Alkbh5-mediated m 6 A demethylation in the 3'UTR of Notch1 mRNA and elevated m 6 A mRNA levels. These elevated m 6 A levels in Notch1 mRNA markedly enhanced YTHDF2 phase separation, increased the recognition of m 6 A residues in Notch1 mRNA by YTHDF2, and induced Notch1 degradation. Conversely, epitranscriptomic downregulation rescues Notch1 expression, resulting in the opposite effects. Human heart tissues from patients with diabetic cardiomyopathy were used to validate the findings in mice with diabetic cardiac fibrosis., Conclusions: We identified a novel epitranscriptomic mechanism by which m 6 A-mediated phase separation suppresses Notch1 expression, thereby promoting mitochondrial fission in diabetic cardiac fibrosis. Our findings provide new insights for the development of novel treatment approaches for patients with diabetic cardiac fibrosis., (© 2024. The Author(s).)

Background : The effect of the expression of the newly identified immune checkpoint, T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) on NK cells in core binding factor-acute myeloid leukemia (CBF-AML) remains to be investigated. Methods : Fresh bone marrow samples from a total of 39 newly diagnosed CBF-AML patients and 25 healthy donors (HDs) were collected for testing the phenotype and function state of total NK, CD56 bright , and CD56 dim NK cell subsets after in vitro stimulation. Results : The frequencies of TIGIT + cells in total NK, CD56 bright , and CD56 dim NK cell subsets had no significant difference between patients and HDs. TNF-α and INF-γ levels were uniformly lower in TIGIT + cells than the corresponding TIGIT - cells in all HDs, whereas those for TIGIT + to TIGIT - cells in patients were highly heterogenous; TIGIT expression was not related to PFP and GZMB expression in HDs, whereas it was related to higher intracellular PFP and GZMB levels in patients. Patients' TIGIT + NK cells displayed lower K562 cell-killing activity than their TIGIT - NK cells. In addition, high frequencies of TIGIT + cells in total NK and CD56 dim NK cells were associated with poor RFS. Conclusions : TIGIT expression affected the diagnostic bone marrow-sited NK cell function and had prognostic significance in CBF-AML patients.

The emission of high-order harmonics from solids under intense laser-pulse irradiation is revolutionizing our understanding of strong-field solid-light interactions, while simultaneously opening avenues towards novel, all-solid, coherent, short-wavelength table-top sources with tailored emission profiles and nanoscale light-field control. To date, broadband spectra in solids have been generated well into the extreme-ultraviolet (XUV), but the comparatively low conversion efficiency in the XUV range achieved under optimal conditions still lags behind gas-based high-harmonic generation (HHG) sources. Here, we demonstrate that two-color high-order harmonic wave mixing in a fused silica solid is more efficient than solid HHG driven by a single color. This finding has significant implications for compact XUV sources where gas-based HHG is not feasible, as solid XUV wave mixing surpasses solid-HHG in performance. Moreover, our results enable utilizing solid high-order harmonic wave mixing as a probe of structure or material dynamics of the generating solid, which will enable reducing measurement times compared to the less efficient regular solid HHG. The emission intensity scaling that follows perturbative optical wave mixing, combined with the angular separation of the emitted frequencies, makes our approach a decisive step for all-solid coherent XUV sources and for studying light-engineered materials., (© 2024. The Author(s).)

Objectives: To compare the image quality and radiation dose in coronary computed tomography angiography (CCTA) based on different acquisition time windows corresponding to the heart rate of breath-holding after free breathing., Methods: Two hundred patients who underwent CCTA with a basal heart rate between 70 and 85 beats/min were divided into groups A and B, with 100 patients in each group. Patients in groups A and B were scanned with the acquisition time window corresponding to the heart rate determined during a breath hold obtained after free breathing and the basal heart rate during free breathing, respectively. Computed tomography (CT) attenuation values of the coronary artery, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were calculated. The subjective image scores of the groups were assessed blindly by 2 experienced physicians using a 4-point system, and score consistency was compared using the κ test. The volume CT dose index and dose-length product were recorded for each patient, and the effective dose (ED) was calculated. The Kruskal-Wallis H test was performed to evaluate differences in age, heart rate, and body mass index. A χ2 test was used to evaluate sex differences. An independent-sample t test was employed to compare objective and subjective data such as dose-length product, volume CT dose index, ED, SNR, CNR, and averaged subjective assessment scores. Statistical significance was set at P < 0.05., Results: No statistically significant differences occurred in sex, age, or body mass index between patients in group A and group B (all P > 0.05). No significant differences occurred in the mean CT values, mean SNR values, mean CNR values, or mean subjective scores of CCTA images between the patients in groups A and B (P > 0.05). The ED values of the patients in group A were 52.93% lower than those in group B (P < 0.001)., Conclusion: The radiation dose in CCTA examinations can be significantly reduced while maintaining image quality by narrowing the acquisition time window for breath-holding after free breathing., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To evaluate the clinical effect of a new surgery technique (covering corneal stromal lenticule, CSL) for macular hole (MH) in pathological myopia., Methods: This was a prospective non-randomized series case study. Fourteen eyes of 14 patients whose axial length were more than 29 mm and suffered from MH and macular hole retinal detachment (MHRD) were included in this study. All cases were treated with 25-gauge pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling, covering CSL and C 3 F 8 gas tamponade. These cases were followed for 6mo, and the best-corrected visual acuity (BCVA), healing status of MH, the reattached rate of retinal detachment (RD), and reoperation rate were analyzed., Results: All cases were successfully performed the surgery and the postoperative follow-up was completed. After surgery, MHs were healed in all 14 eyes (100%, 14/14) after assessed by optical coherence tomography. The reattachment of retina was achieved in all 6 eyes (100%, 6/6) with MHRD. BCVA was improved in 12 eyes (85.71%, 12/14), and had no significant change in 2 eyes (14.29%, 2/14). The overall mean BCVA was improved from 1.80±0.77 to 0.82±0.46 logMAR ( F =10.46, P <0.01). No serious complications occurred in all cases., Conclusion: The new surgery technique (covering CSL) has high reattached rate of RD and high healing rate of MH in pathological myopia in the preliminary study. And it can effectively improve the visual function of patients. This new technique offers meaningful new ideas for treating refractory MH in pathological myopia., Competing Interests: Conflicts of Interest: Tang ZY, None; Qiao G, None; Zhang XJ, None; Xie LJ, None; Zou QX, None; He CM, None; Zhao L, None; Yang HQ, None; Quan Y, None; Cao K, None; Jiang H, None; He YK, None., (International Journal of Ophthalmology Press.)

The understanding of activated sludge microbial status and roles is imperative for improving and enhancing the performance of wastewater treatment plants (WWTPs). In this study, we conducted a deep analysis of activated sludge microbial communities across five compartments (inflow, effluent, and aerobic, anoxic, anaerobic tanks) over temporal scales, employing high-throughput sequencing of 16S rRNA amplicons and metagenome data. Clearly discernible seasonal patterns, exhibiting cyclic variations, were observed in microbial diversity, assembly, co-occurrence network, and metabolic functions. Notably, summer samples exhibited higher α-diversity and were distinctly separated from winter samples. Our analysis revealed that microbial community assembly is influenced by both stochastic processes (66%) and deterministic processes (34%), with winter samples demonstrating more random assembly compared to summer. Co-occurrence patterns were predominantly mutualistic, with over 96% positive correlations, and summer networks were more organized than those in winter. These variations were significantly correlated with temperature, total phosphorus and sludge volume index. However, no significant differences were found among microbial community across five compartments in terms of β diversity. A core community of keystone taxa was identified, playing key roles in eight nitrogen and eleven phosphorus cycling pathways. Understanding the assembly mechanisms, co-occurrence patterns, and functional roles of microbial communities is essential for the design and optimization of biotechnological treatment processes in WWTPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)