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Extracellular signal-regulated kinase 5 (ERK5), a mitogen-activated protein kinase (MAPK) family member, plays an important role in various biological processes, such as proliferation, apoptosis, differentiation, survival, and cell regulation. However, studies on the effects of ERK5 on porcine preimplantation embryos are limited. In this study, to determine the function of ERK5 during porcine embryo development, ERK5 function was inhibited by adding the ERK5 inhibitor JWG-071. The ERK5 mRNA and protein expression levels tended to decrease from the 4-cell stage compared to the 1-cell and 2-cell stages, suggesting that ERK5 is the maternal gene. During embryonic development in pigs, adding 5 μM of JWG-071 significantly reduced the phosphorylation of ERK5 and the blastocyst development rate (control: 53.44 ± 8.38 %; treatment: 26.65 ± 3.40 %). Additionally, ERK5 inhibition increased the expression of UPR-related proteins, glucose-regulated protein (GRP78), and C/EBP homologous protein (CHOP) by inducing ER stress. Compared to the control group, the expression of the autophagy-related proteins LC3 and ATG7 was significantly increased in the ERK5 inhibition group, indicating that the inhibition of ERK5 induced autophagy. In addition, ERK5 inhibition increased the expression of BAX, a pro-apoptotic gene, resulting in apoptosis. In conclusion, the results show that ERK5 inhibition during porcine embryonic development induces autophagy and apoptosis by increasing ER stress, resulting in a negative effect on embryonic development in pigs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ciprofloxacin (CIP) and gallium (Ga) are widely used in many fields and their excessive presences will pose serious threats to the environment and life health. Therefore, developing an intelligent detection method for rapidly tracking and determination of CIP and Ga 3 ⁺ concentration in environments and organisms is of great significance. In this work, a europium-doped carbon dots (Eu-CDs) with unique structure and performances was prepared by a one-pot hydrothermal method. Eu-CDs can efficiently overcome the problem of aggregation-induced fluorescence quenching in complex environments to track CIP and Ga 3⁺ with highly sensitivity. The "antenna effect" of non-radiative energy transfer is introduced to explain the pathway on fluorescence transition of Eu-CDs through DFT theoretical calculations and mechanism investigations, which provide a theoretical basis for the design and development of novel carbon dots with specific functions. Eu-CDs can successfully be applied to fluorescence imaging in organisms, moreover, it also exhibits excellent application potentials in the field of anti-tumor and antibacterial. In addition, a portable intelligent detection platform based on Eu-CDs-hydrogel device have been developed, which provides a new strategy for rapidly detection of CIP and Ga 3⁺ in real samples., 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.)

Chemical investigation on the 80% EtOH extract of the air dried aerial parts of Hypericum sampsonii resulted in the isolation of two new polycyclic polyprenylated derivatives, hypersampines A and B ( 1 and 2 ). The structures of the new compounds were elucidated by spectroscopic data (NMR, IR, and UV) and high resolution mass analysis. The two isolated polyprenylated acylphloroglucinols were tested in vitro for cytotoxic activities against 6 pancreatic cell lines. As a result, compounds 1 and 2 possessed modest cytotoxic activities against all the tested tumor cell lines with IC 50 values less than 40 μM.

The anterior cingulate cortex (ACC) is recognized as a pivotal cortical region involved in the perception of pain. The retrosplenial cortex (RSC), located posterior to the ACC, is known to play a significant role in navigation and memory processes. Although the projections from the RSC to the ACC have been found, the specifics of the synaptic connections and the functional implications of the RSC-ACC projections remain less understood. In this study, we employed a combination of whole-brain imaging, in vitro electrophysiology, and two-photon calcium imaging techniques to confirm the presence of direct excitatory glutamatergic projections from the RSC to the ACC in mice. This excitatory transmission is predominantly mediated by the postsynaptic AMPA receptors. Furthermore, the activation of the RSC-ACC projections through opto-/chemogenetics significantly facilitated the behavioral responses to both mechanical and thermal nociceptive stimuli in adult mice. Notably, this activation did not influence spinal nociceptive responses in the tail-flick test, nor did it affect anxiety-like or aversive behaviors. These findings indicate that the RSC-ACC glutamatergic pathway modulates nociceptive perception primarily at the supraspinal cortical level. We have identified a novel cortico-cortical facilitatory pathway that contributes to nociceptive processing in the cingulate cortex. The RSC-ACC pathway probably serves to integrate memory engrams with pain perception in both humans and animals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Hao 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.)

Background: Pulmonary arterial hypertension (PAH) is an incurable disease initiated by endothelial dysfunction, secondary to vascular inflammation and occlusive pulmonary arterial vascular remodeling, resulting in elevated pulmonary arterial pressure and right heart failure. Previous research has reported that dysfunction of type 2 bone morphogenetic protein receptor (BMPR2) signaling pathway in endothelium is inclined to prompt inflammation in PAH models, but the underlying mechanism of BMPR2 deficiency-mediated inflammation needs further investigation. This study was designed to investigate whether BMPR2 deficiency contributes to pulmonary arterial hypertension via the NLRP3 (NOD-like receptor family protein 3)/GSDME (gasdermin E)-mediated pyroptosis pathway., Methods and Results: NLRP3 knockout or short hairpin RNA interference of GSDME was performed in PAH animal models to investigate its effect on PAH progression. In addition, the effects of BMPR2 deficiency and restoration of BMPR2 by BMP9 (bone morphogenetic protein 9) or FK506 on pyroptosis were explored both in animal and cell models. Knockout of NLRP3 or short hairpin RNA interference of GSDME in animal models can alleviate the development of pyroptosis, accompanied with improved endothelial integrity, vascular remodeling, and right ventricular systolic pressure. Blocking BMPR2 is sufficient to induce NLRP3 upregulation and release of inflammatory factor IL-1β (interleukin-1β) in pulmonary arterial endothelial cells. Moreover, BMPR2 deficiency can induce GSDME-mediated pyroptosis through NLRP3 activation in 2 animal models, whereas activation of BMPR2 signaling by FK506 or BMP9 can reverse these phenotypes., Conclusions: These findings provide evidence that loss of BMPR2 signaling promotes endothelial cell pyroptosis by enhancing NLRP3/GSDME signaling in PAH. Our findings may provide new insights to explore the inflammatory mechanism of PAH treatment.

Objective: To investigate the relationship between the grip strength (GS) and stress urinary incontinence (SUI) after endoscopic enucleation of the prostate (EEP)., Methods: We retrospectively collected 87 patients who underwent EEP at our center from January to December 2023. The associations between GS and post-surgical SUI at immediate, 1, 4, 12 and 24 weeks were analyzed. The cohort was then divided into the SUI and non-SUI group based on the presence of the SUI at 4-week postoperatively., Results: Of overall 87 patients, 49 (56.3%), 40 (46.0%), 33 (37.9%), 20 (23.0%), and 9 (10.3%) patients presented SUI at immediate, 1, 4, 12 and 24 weeks postoperatively. Significant negative correlations were consistently observed between the GS and SUI till 12 weeks postoperatively, with patients requiring more daily pads presenting lower GS. Compared to the non-SUI group, the SUI group had significantly higher average age (76.0 ± 8.4 vs. 70.1 ± 6.3, P = 0.001), BMI (25.1 ± 2.9 vs. 23.8 ± 2.9, P = 0.040), rates of PKEP (90.9% vs. 72.2%, P = 0.037), CSEA (69.7% vs. 42.6%, P = 0.014) and III/IV ASA score (33.3% vs. 14.8%, P = 0.043), but lower GS (26.2 ± 8.2 vs. 33.3 ± 6.5 kg, P < 0.001). Multivariate analyses identified BMI and GS as independent risk factors for post-operative SUI., Conclusions: The GS was found to be negatively correlated with post-operative SUI within 12 weeks after EEP and was an independent predictor of SUI at 4 weeks postoperatively., Competing Interests: Declarations. Ethical approval: This study was approved by the Ethics Committee of Beijing Friendship Hospital (No. BFH20241115003) and was carried out in accordance with the ethical principles outlined in the Declaration of Helsinki. All patients provided written informed consent before participation in the study. The confidentiality of patient information was maintained throughout the study, and all personal identifiers were removed from the data to protect patient privacy. The study was conducted with the highest level of integrity and adherence to ethical standards. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The pluripotency-related T-box family transcription factor TBX3 maintains mESC self-renewal and plays a key role in the development of several tissues, including the heart, mammary glands, limbs, and lungs. However, the role of TBX3 during porcine preimplantation embryo development remains unclear. In our research, TBX3 was knocked down by injecting dsRNA to explore the function of TBX3. TBX3 expression gradually increases during early embryonic development. TBX3 knockdown resulted in decreased in the rate of four-cell and blastocyst. Depletion of TBX3 decreased the level of H3K9Ac/H3K27Ac and decreased ZGA gene expression at the four-cell stage. Furthermore, TBX3 knockdown led to a decrease in ZSACN4 protein level, DNMT1 and intracellular 5mc levels were increased, and then induced telomeres shorten and DNA damaged. Additionally, TBX3 knockdown significantly decreased histone acetylation and pluripotency genes NANOG/OCT4 expression in blastocysts. TBX3 knockdown induced apoptosis in blastocysts. Taken together, TBX3 regulate histone acetylation and play important roles in zygotic genome activation and early embryonic development in pigs., Competing Interests: Conflict of Interest: The authors have no competing interest to declare., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Microscopy Society of America. 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.)

Chronic heart failure (CHF) poses a significant threat to human health. The stress hyperglycemia ratio (SHR) is a novel metric for accurately assessing stress hyperglycemia, which has been correlated with adverse outcomes in various major diseases. However, it remains unclear whether SHR is associated with 28-day mortality in patients with pre-existing CHF who were admitted to intensive care units (ICUs). This study retrospectively recruited patients who were admitted to ICUs with both acute critical illness and pre-existing CHF from the Medical Information Mart for Intensive Care (MIMIC) database. Characteristics were compared between the survival and non-survival groups. The relationship between SHR and 28-day all-cause mortality was analyzed using restricted cubic splines, receiver operating characteristic (ROC) curves, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. The importance of the potential risk factors was assessed using the Boruta algorithm. Prediction models were constructed using machine learning algorithms. A total of 913 patients were enrolled. The risk of 28-day mortality increased with higher SHR levels (P < 0.001). SHR was independently associated with 28-day all-cause mortality, with an unadjusted hazard ratio (HR) of 1.45 (P < 0.001) and an adjusted HR of 1.43 (P < 0.001). Subgroup analysis found that none of the potential risk factors, such as demographics, comorbidities, and drugs, affected the relationship (P for interaction > 0.05). The area under the ROC (AUC) curve for SHR was larger than those for admission blood glucose and HbA1c; the cut-off for SHR was 0.57. Patients with SHR higher than the cut-off had a significantly lower 28-day survival probability (P < 0.001). SHR was identified as one of the key factors for 28-day mortality by the Boruta algorithm. The predictive performance was verified through four machine learning algorithms, with the neural network algorithm being the best (AUC 0.801). For patients with both acute critical illness and pre-existing CHF, SHR was an independent predictor of 28-day all-cause mortality. Its prognostic performance surpasses those of HbA1c and blood glucose, and prognostic models based on SHR provide clinicians with an effective tool to make therapeutic decisions., Competing Interests: Declarations. Ethics approval: The study was conducted in accordance with the guidelines of the Helsinki Declaration. As the MIMIC-IV database is publicly available, and all data are de-identified to remove patients’ information. The approval was obtained from the Institutional Review Board in advance, and ethical review was not required., (© 2025. The Author(s).)

Objective: To analyze the clinical features of nasal pleomorphic adenoma and to share clinical insights into its diagnosis and treatment. Methods: This was a case series study. Clinical data of 12 patients with nasal pleomorphic adenoma, confirmed by histopathology, admitted to the Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Qingdao University from 2014 to 2023, were retrospectively analyzed. This cohort included 3 males and 9 females, aged 12-84 years old. The pathogenesis, clinical manifestations, imaging features, pathological features, treatment methods and prognosis were analyzed. Results: Among the 12 patients with nasal pleomorphic adenoma, the most common symptom was nasal obstruction (8 cases), and the most common site was nasal septum (7 cases). Of the 12 patients, 9 had benign tumors, and 3 had malignant tumors. Postoperative follow-up ranged from 10 months to 9 years. One benign case recurred at 5 years after surgery and was left untreated after recurrence. The remaining 11 cases had shown no recurrence to date. Conclusions: Nasal pleomorphic adenoma is rare in clinical practice, typically occurring in the nasal septum. The primary symptom is nasal obstruction. Diagnosis is primarily based on histopathology, and surgical resection is the primary treatment.

Protein secretion is an essential process that drives cell growth and communication. Enrichment of soluble secretory proteins into ER-derived transport carriers occurs via transmembrane cargo receptors that connect lumenal cargo to the cytosolic COPII coat. Here, we find that the cargo receptor, SURF4, recruits different SEC24 cargo adaptor paralogs of the COPII coat to export different cargoes. The secreted protease, PCSK9, requires both SURF4 and a co-receptor, TMED10, for export via SEC24A. In contrast, secretion of Cab45 and NUCB1 requires SEC24C/D. We further show that ER export signals of Cab45 and NUCB1 bind co-translationally to SURF4 via a lumenal pocket, contrasting prevailing models of receptor engagement only upon protein folding/maturation. Bioinformatics analyses suggest that strong SURF4-binding motifs are features of proteases, receptor-binding ligands, and Ca2+-binding proteins. We propose that certain classes of proteins are fast-tracked for rapid export to protect the health of the ER lumen., (© 2024 MRC Laboratory of Molecular Biology.)

Background: With the continuous advancement of medical technology, the survival rate of preterm infants is gradually improving, However, due to the underdeveloped function of various organs and systems, preterm infants are often exposed to light, noise, medical as well as nursing operations and other stimuli during their hospitalization in neonatal intensive care unit (NICU); it is highly susceptible to a number of problems, such as pain, unstable vital signs, growth retardation, and sleep disruption., Objective: This article reviews the research progress of music intervention in nursing of premature infants in NICU with both traditional and conventional care., Methods: This article reviews the research background, methodology/design, and measurement/application effects of music interventions, including Chinese and Western traditional music, in the care of preterm infants in NICU. All scholarly literature retrieved from MEDLINE\PubMed, Science Citation Index Expanded, Google scholar, CNKI scholar, Scopus and PubsHub., Results: As a simple and effective non-pharmacological intervention, music intervention can effectively alleviate neonatal surgical pain, increase heart rate and oxygen saturation, promote sleep, growth and development, and improve neurological development., Conclusions: This review provide theoretical references for clinical practice.

Large metacarpal and phalangeal bone defects are a hot topic for orthopedic surgeons due to its high clinical incidence, disability rate, and postsurgical amputation rate, along with its difficult treatment, long treatment course, high cost, and poor effect, all of which have a negative impact on the appearance and function of the patient's hands. There are currently a variety of treatment options for large metacarpal and phalangeal bone defects, each with its own benefits and drawbacks. However, there is no treatment method capable of perfectly resolving all the problems of patients with these defects. In this paper, the authors introduce several common plans for and progress of large metacarpal and phalangeal bone defect treatment., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

The development of high-performance strains and the continuous breakthrough of strain screening technology also pose challenges to downstream fermentation optimization and scale-up. Therefore, neural network models are utilized to optimize the fermentation process to meet the goals of boosting yield or lowering cost, with the use of artificial intelligence technology in conjunction with the peculiarities of the fermentation process. High-performance strains' yield rise and fermentation process amplification will be sped up with the aid of neural network models. This paper offers a helpful review for anyone interested in state-of-the-art microbial fermentation processes, as it thoroughly reviews the application of neural network models in predicting fermentation yield, optimizing the fermentation process, and monitoring the fermentation process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Using the e^{+}e^{-} collision data collected with the BESIII detector operating at the BEPCII collider, at center-of-mass energies from the threshold to 4.95 GeV, we present precise measurements of the cross section for the process e^{+}e^{-}→D&#95;{s}^{+}D&#95;{s}^{-} using a single-tag method. The resulting cross section line shape exhibits several new structures, thereby offering an input for a future coupled-channel analysis and model tests, which are critical to understand vector charmonium-like states with masses between 4 and 5 GeV.

Chalcogenides are the most important infrared nonlinear optical (NLO) material candidates, and the exploration of high-performance ones is attractive and challengeable. Hitherto, there is no NLO scandium (Sc) chalcogenides experimentally studied. Here, new quaternary Sc thiophosphate CsScP 2 S 7 (CSPS) was synthesized by the facile metal oxide-boron-sulfur/reactive flux hybrid solid-state method. It crystallizes in the monoclinic chiral space group C2, and the layered structure is composed by the new ScP 2 S 11 functional motifs built by ScS 6 octahedra and P 2 S 7 dimers, and the structure-performance analysis reveals that the hyperpolarizability of ScP 2 S 11 is much greater than the assembled units (ScS 6 and PS 4 ), which makes the first NLO Sc chalcogenide CSPS exhibits strong NLO response (0.8 × AGS) and high laser-induced damage threshold (LIDT) (4.3 × AGS), and a wide bandgap of 3.10 eV. With the coordination number's reduction of rare-earth (RE) ion and the rearrangement of P 2 S 7 dimers, the centrosymmetric structure of CsREP 2 S 7 family can be broken via substitution with the smallest RE element Sc to form the noncentrosymmetric structure. This work not only discovers a new high-performance infrared NLO material, but also will inspire researchers to explore more potential NLO Sc chalcogenides., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Electrochemical nitrate reduction reaction offers a sustainable and efficient pathway for ammonia synthesis. Maintaining satisfactory Faradaic efficiency for long-term nitrate reduction under ampere-level current density remains challenging due to the inevitable hydrogen evolution, particularly in pure nitrate solutions. Herein, we present the application of electron deficiency of Ru metals to boost the repelling effect of counter K + ions via the electric-field-dependent synergy of interfacial water and cations, and thus largely promote nitrate reduction reaction with a high yield and well-maintained Faradaic efficiency under ampere-level current density. The pronounced electron deficiency of Ru metals boosts the repelling effect on hydrated K + ions, as indicated by the distance of K + ions to catalyst surface, which can loosen the water layer to depress hydrogen evolution and accelerate nitrate conversion. Consequently, the optimized electrode loaded with electron-deficient Ru atomic layers can directly produce 0.26 M ammonia solution in pure nitrate solution in 6 h, providing a high yield (74.8 mg mg cat -1 h -1 ) and well-maintained the Faradaic efficiency for over 120 h under ampere-level reduction., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Functional traits of desert plants exhibit remarkable responsiveness, adaptability and plasticity to environmental heterogeneity., Methods: In this study, we measured six crucial plant functional traits (leaf carbon, leaf nitrogen, leaf phosphorus, leaf thickness, chlorophyll concentration, and plant height) and employed exemplar analysis to elucidate the effects of soil environmental heterogeneity on intraspecific traits variation in the high-moisture-salinity and low-moisture-salinity habitats of the Ebinur LakeWetland National Nature Reserve., Results: The results showed that (1) The soil moisture and electrical conductivity heterogeneity showed significant differences between the two moisture-salinity habitats. Moreover, soil nutrient in high moisture-salinity habitat exhibited higher heterogeneity than in low moisture-salinity habitat. The order of intraspecific trait variation among different life forms was herbs > shrubs > trees in both the soil moisture-salinity habitats. (2) At the community level, intraspecific variation of leaf carbon, nitrogen, plant height and chlorophyll content in high moisture-salinity habitat was higher than that in low moisture-salinity habitat, while the opposite was true for leaf thickness and leaf phosphorus content. (3) Our findings revealed a positive impact of soil heterogeneity on intraspecific traits variation. In high moisture-salinity habitat, the heterogeneity of soil organic carbon had the highest explanatory power for intraspecific traits variation, reaching up to 20.22%, followed by soil total nitrogen (9.55%) and soil total phosphorus (3.49%). By comparison, in low-moisture-salinity habitat, the heterogeneity of soil moisture alone contributes the highest explanatory power for intraspecific traits variation in community-level, reaching up to 13.89%, followed by the heterogeneity of soil total nitrogen (3.76%)., Discussion: This study emphasizes the differences in soil heterogeneity and intraspecific trait variation among plant life forms under various soil moisture-salinity habitats and confirms the significant promoting effect of soil heterogeneity on intraspecific trait variation of desert plant. Our findings provide valuable theoretical basis and reference for predicting plant adaptation strategies under environmental change scenarios., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Zhang, Yang, Tian, Song, Li and Zhou.)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by the accumulation of fat in the liver, excluding excessive alcohol consumption and other known causes of liver injury. Animal models are often used to explore different pathogenic mechanisms and therapeutic targets of MASLD. The aim of this study is to apply an artificial intelligence (AI) system based on second-harmonic generation (SHG)/two-photon-excited fluorescence (TPEF) technology to automatically assess the dynamic patterns of hepatic steatosis in MASLD mouse models., Methods: We evaluated the characteristics of hepatic steatosis in mouse models of MASLD using AI analysis based on SHG/TPEF images. Six different models of MASLD were induced in C57BL/6 mice by feeding with a western or high-fat diet, with or without fructose in their drinking water, and/or by weekly injections of carbon tetrachloride., Results: Body weight, serum lipids, and liver enzyme markers increased at 8 and 16 weeks in each model compared to baseline. Steatosis grade showed a steady upward trend. However, the non-alcoholic steatohepatitis (NASH) Clinical Research Network (CRN) histological scoring method detected no significant difference between 8 and 16 weeks. In contrast, AI analysis was able to quantify dynamic changes in the area, number, and size of hepatic steatosis automatically and objectively, making it more suitable for preclinical MASLD animal experiments., Conclusions: AI recognition technology may be a new tool for the accurate diagnosis of steatosis in MASLD, providing a more precise and objective method for evaluating steatosis in preclinical murine MASLD models under various experimental and treatment conditions.

GWASs have identified many loci associated with osteoporosis, but the underlying genetic regulatory mechanisms and the potential drug target need to be explored. Here, a new regulatory mechanism is found that a GWAS intergenic SNP (rs4683184) functions as an enhancer to influence the binding affinity of transcription factor RUNX2, whose phase separation can mediate the long-range chromatin interaction between enhancer and target gene XCR1 (a member of the GPCR family), leading to changes of XCR1 expression and osteoblast differentiation. Bone-targeting AAV of Xcr1 can improve bone formation in osteoporosis mice, suggesting that XCR1 can be a new susceptibility gene for osteoporosis. This study is the first to link non-coding SNP with phase separation, providing a new insight into long-range chromatin regulation mechanisms with susceptibility to complex diseases, and finding a potential target for the development of osteoporosis drugs and corresponding translational research., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Schizophrenia is a kind of neurodevelopmental mental disorder in which patients begin to experience changes early in their development, typically manifesting around or after puberty and has a fluctuating course. Environmental disturbances during adolescence may be a risk factor for schizophrenia-like deficits. As a better treatment option, preventive intervention prior to schizophrenia may be more beneficial than direct treatment. More effective stress-relieving interventions during the critical puberty period may prevent schizophrenia-like neuronal changes and the transition to schizophrenia in adulthood. Pyridoxine deficiency alters the function of NMDA (n-methyl-D-aspartic acid) receptors and plays a key role in learning and memory. In this study, we prepared a progeny model of schizophrenia by exposing pregnant rats to methoxymethanol acetate (MAM) on gestational day 17. The offspring rats were injected intraperitoneally with pyridoxine daily from birth to prepuberty PND12-PND21), and behavioral changes in the offspring rats were observed in adulthood. Cannabinoid receptor interacting protein 1 (CNRIP1) and cannabinoid receptor-1 (CB1R), which regulate memory, cognitive and motor activity, were detected in the prefrontal cortex (PFC) and hippocampus of the offspring rats, and the cell proliferation in the hippocampal dentate gyrus (DG) was also observed. The results showed that the MAM rats spent less time the open arm in the elevated plus maze test, decreased discrimination coefficient in novel object recognition test, and decreased prepulse inhibition, while the MAM rats supplemented with pyridoxine in prepuberty did not show any of the above abnormal behavioral changes in adulthood. By examining related proteins in the PFC and hippocampus, we found that only CB1R protein expression was downregulated in the PFC, whereas CNRIP1 expression was not only elevated in the hippocampus, but also significantly increased in pyridoxine- supplemented MAM rats. Meanwhile, pyridoxine supplementation alleviated the reduction of doublecortin (DCX)-positive cells and Ki67-positive cells in MAM rats. These results indicate that prepuberty pyridoxine supplementation has a positive effect on the prevention of cognitive deficits and sensorimotor gating impairment in MAM-induced schizophrenia-like rats, accompanied by changes in the CB1R and CNRIP1 expression in PFC and hippocampus, as well as the regeneration of neurons in the DG region., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chemotherapeutic agents, such as paclitaxel (PTX), induce neuroplastic changes and alter gene expression in the prefrontal cortex (PFC), which may be associated with chemotherapy-induced pain and negative emotions. Notably, DNA methylation undergoes adaptive changes in neurological disorders, emerging as a promising target for neuromodulation. In this study, systemic administration of PTX leads to a decrease in the expression of the DNA methyltransferase DNMT3a, while concurrently upregulating the expression of Gabrb1 mRNA and its encoded GABA A Rβ1 protein in the medial PFC (mPFC) of male mice. Overexpression of DNMT3a in the mPFC alleviates PTX-induced pain hypersensitivity, and anxiety-like behavior in these mice. Additionally, it reverses the PTX-induced increase in inhibitory synaptic transmission in the pyramidal neurons of the mPFC. Mechanistically, the upregulation of GABA A Rβ1 in the mPFC is linked to the reduced expression of DNMT3a and DNA hypomethylation at the promoter region of the Gabrb1 gene. Furthermore, a long-term diet rich in methyl donors alleviates PTX-induced pain hypersensitivity and anxiety-like behavior in mice. These findings suggest that the DNMT3a-mediated upregulation of GABA A Rβ1 in the mPFC contributes to PTX-induced neuropathic pain and anxiety, highlighting DNA methylation-dependent epigenetic regulation as a potential therapeutic target for addressing chemotherapy-induced cortical dysfunction., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

We report the precise measurements of the cross section of e^{+}e^{-}→hadrons at center-of-mass energies from 3.645 to 3.871 GeV. We thereby perform the most precise study of the cross sections and find a complex system composed of three resonances of R(3760), R(3780), and R(3810). For the first time, we measure the R(3810) electronic width to be (19.4±7.4±12.1)  eV. For the R(3760) resonance, we measure the mass to be (3751.9±3.8±2.8)  MeV/c^{2}, the total width to be (32.8±5.8±8.7)  MeV, and the electronic width to be (184±75±86)  eV. For the R(3780) resonance, we measure its mass to be (3778.7±0.5±0.3)  MeV/c^{2}, total width to be (20.3±0.8±1.7)  MeV, and electronic width to be (265±67±83)  eV. Forty-seven years ago, the ψ(3770) resonance was discovered, and was subsequently interpreted as the 1^{3}D&#95;{1}-wave dominant state of charmonium. However, our analysis of the total-hadron cross sections indicates that the ψ(3770) is not a single state, but a complex system composed of the R(3760), R(3780), and R(3810) resonances. Among these, we interpret the R(3780) is a resonance dominated by the 1^{3}D&#95;{1} charmonium state.

Soft matters, particularly giant molecular self-assembly, have successfully replicated complex structures previously exclusive to metal alloys. These superlattices are constructed from mesoatoms─supramolecular spherical motifs of aggregated molecules, and the formation of superlattices critically depends on the volume distributions of these mesoatoms. Herein, we introduce two general methods to control volume asymmetry (i.e., the volumes' ratio of the largest to smallest mesoatoms, V L /V S ) within giant molecular self-assembly. Leveraging the spontaneous increase in the mesoatomic volume ratio in unary systems and self-sorted binary blends, we systematically adjust the volume asymmetry from 1.0 to 9.0 across 24 unary systems and 56 binary blends of giant molecules, uncovering the formation of various superlattices, including BCC, Frank-Kasper A15, σ, Laves C14, C15, NaZn 13 , AlB 2 , and notably, the first NaCl like superlattice in homogeneous soft matter self-assembly. A geometric-based analysis, combined with experimental results, further establishes a quantitative relationship between volume asymmetry and the corresponding superlattice formations, thus laying a solid foundation for superlattice engineering within giant molecular systems to mimic and even beyond metal alloys. The lattice parameters of various unit cells range from approximately 5 to 20 nm. Our investigation in giant molecules could guide the advancement of mesoscopic, periodic soft matter materials.

Integrated biochemical and biophysical signals regulate embryonic development. Correct neural tube formation is critical for the development of central nervous system. However, the role of microgravity in neurodevelopment and its underlying molecular mechanisms remain unclear. In this study, the effects of stimulated microgravity (SMG) on the development of human brain organoids are investigated. SMG impairs N-cadherin-based adherens junction formation, leading to neural tube defects associated with dysregulated self-renewal capacity and neuroepithelial disorganization in human brain organoids. Bulk gene expression analyses reveal that SMG alters Hippo and BMP signaling in brain organoids. The neuropathological deficits in SMG-treated organoids can be rescued by regulating YAP/BMP/ID1 axis. Furthermore, sing-cell RNA sequencing data show that SMG results in perturbations in the number and function of neural stem and progenitor cell subpopulations. One of these subpopulations senses SMG cues and transmits BMP signals to the subpopulation responsible for tube morphogenesis, ultimately affecting the proliferating cell population. Finally, SMG intervention leads to persistent neurologic damage even after returning to normal gravity conditions. Collectively, this study reveals molecular and cellular abnormalities associated with SMG during human brain development, providing opportunities for countermeasures to maintain normal neurodevelopment in space., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Nanoplastics are widely distributed in the environment and can accumulate in organisms. Increasing attention has been paid to the toxic effects of nanoplastics in wastewater biological treatment processes. In this study, polystyrene nanoplastics with different charges were synthesized and used in sequencing batch activated sludge reactors for short-term nanoplastic exposure experiments. Both positively and negatively charged nanoplastics inhibited the nitrogen removal efficiency and gene expressions of nitrification and denitrification-related genes of activated sludge. The inhibiting effect on nitrification of both nanoplastics was enhanced with increasing concentration. The study further evaluated the molecular mechanisms by which differently charged nanoplastics affect denitrification efficiency using the model denitrifying bacterium Pseudomonas stutzeri （ P. stutzeri ） . The results showed that both positively and negatively charged nanoplastics affected the efficiency of biological denitrification by P. stutzeri , mainly including the promotion of NO 3 - to NO 2 - conversion and the significant acceleration of N 2 O production. Meanwhile, negatively charged nanoplastics inhibited the growth of P. stutzeri and disrupted the cell membrane of the bacterium； however, no change was observed in the expression of denitrification-related functional genes and the nanoplastics might have affected the enzymatic activities of Nir and Nos, which in turn affected the bioprocessing efficiency. This study can provide a certain reference for the evaluation of the biosafety of nanoplastics and provide a certain support for the stable operation of wastewater treatment plants.

Scientifically recognizing and mastering the spatial-temporal response of habitat quality to land use change and its internal mechanism is the basis of seeking sustainable development in arid areas. Based on the data of land use in 1990, 2000, 2010, and 2020, the land use transfer matrix model, dynamic attitude and state degree model, InVEST model, and geographically weighted regression model were adopted. The research results were as follows： ① From 1990 to 2020, the area of unused land in Hexi Corridor changed the most, with a decrease of 3 021 km 2 and the cultivated land, construction land, and water area increased by 2 343.60 km 2 , 739.28 km 2 , and 416.56 km 2 , respectively. During the study period, the dynamic attitude and state index of construction land changed the most, which was closely related to the rapid urbanization over the past 30 years. ② From 1990 to 2020, the overall habitat quality in Hexi Corridor was at a low level； however, it showed an upward trend, showing a spatial differentiation pattern of "high in the south and low in the north." From 1990 to 2020, the habitat quality in the study area had a spatial agglomeration effect and the H-H and H-L aggregation areas increased significantly. ③ Under the joint action of natural and man-made mechanisms, the social, economic, natural, and scientific factors had a profound impact on the relationship and change mechanism between land use change and habitat quality. The research results can provide scientific support for optimizing the spatial layout of land and ecological integration protection and system management of inland river basins.

Background: Patients with acute pancreatitis (AP) have different sites of pancreatic involvement. The aim of this study was to investigate the differences in magnetic resonance imaging (MRI) findings and clinical features of different sites of involvement (subtypes) in AP, with a view to complement and complete the classification of AP based on anatomical imaging features., Methods: We consecutively collected data from inpatients with AP from January 2018 to October 2022 at a tertiary care hospital. The patients with AP were classified into three subtypes by MRI: type I mainly involved the head of the pancreas; type II mainly involved the body and tail of the pancreas; and type III involved the entire pancreas (head, body, and tail simultaneously). We examined the MRI findings and clinical features of the three subtypes, including their prevalence, gender, etiology, age, assessment of severity, prevalence of hypertension, diabetes mellitus, coronary artery disease, laboratory markers, prognosis, necrosis, and the incidence of complications. The three subgroups were analyzed using one-way analysis of variance (ANOVA), Kruskal-Wallis H-test, Chi-squared test or Fisher's exact probability method depending on the data distribution, and logistic regression and linear regression were used to determine the risk factors for poor short-term prognosis of AP and the number of days in hospital. Results were considered statistically significant at P<0.05., Results: Among the 240 patients recruited, the mean age was 51±15 years (range, 12-89 years); 146 (60.83%) were male and 94 (39.17%) were female. Biliary pancreatitis accounted for 45.00% (108/240), hyperlipidemic pancreatitis for 33.75% (81/240), alcoholic pancreatitis for 8.75% (21/240), and unknown etiology for 12.5% (30/240). Some 81.25% (195/240) of the cases were edematous pancreatitis, whereas 18.75% (45/240) were necrotizing pancreatitis. Overall, 75 patients (31.25%) had type I AP, 108 patients (45.00%) had type II AP, and 57 patients (23.75%) had type III AP. These three subtypes were significantly different in terms of etiology, incidence of diabetes, C-reactive protein (CRP), severity, incidence of necrosis, local complications, clinical and imaging severity scores, and prognosis (P<0.05). Total pancreatic involvement (Type III) was the most severe subtype, with hyperlipidemia as the main cause. Regression analysis revealed that subtype classification is an important risk factor for prognosis., Conclusions: We classified AP into three subtypes based on different sites of involvement and revealed the MRI features and clinical characteristics of each subtype of AP. The subtype classification helps to characterize AP from the imaging dimension and predict the prognosis. The results of this study could be a target for future studies to adopt new classification methods., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-693/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background: cfDNA fragmentomics-based liquid biopsy is a potential option for noninvasive bladder cancer (BLCA) detection that remains an unmet clinical need., Methods: We assessed the diagnostic performance of cfDNA hotspot-driven machine-learning models in a cohort of 55 BLCA patients, 51 subjects with benign conditions, and 11 healthy volunteers. We further performed functional bioinformatics analysis for biological understanding and interpretation of the tool's diagnostic capability., Results: Urinary cfDNA hotspots-based machine-learning model enabled effective BLCA detection, achieving high performance (area under curve 0.96) and an 87% sensitivity at 100% specificity. It outperformed models using other cfDNA-derived features. In stage-stratified analysis, the sensitivity at 100% specificity of the urine hotspots-based model was 71% and 92% for early (low-grade Ta and T1) and advanced (high-grade T1 and muscle-invasive) disease, respectively. Biologically, cfDNA hotspots effectively retrieved regulatory elements and were correlated with the cell of origin. Urine cfDNA hotspots specifically captured BLCA-related molecular features, including key functional pathways, chromosome loci associated with BLCA risk as identified in genome-wide association studies, or presenting frequent somatic alterations in BLCA tumors, and the transcription factor regulatory landscape., Conclusions: Our findings support the applicability of urine cfDNA fragmentation hotspots for noninvasive BLCA diagnosis, as well as for future translational study regarding its molecular pathology and heterogeneity., (© Association for Diagnostics & Laboratory Medicine 2024. 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.)

Hyperuricemia (HUA) is a common complication of chronic kidney disease (CKD). Conversely, HUA can promote the disease progression of CKD. However, the molecular mechanism of HUA in CKD development remains unclear. In the present study, we applied ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to analyze the serum metabolite profiling of 47 HUA patients, 41 non-hyperuricemic CKD (NUA-CKD) patients, and 51 CKD and HUA (HUA-CKD) patients, and then subjected to multivariate statistical analysis, metabolic pathway analysis and diagnostic performance evaluation. Metabolic profiling of serums showed that 40 differential metabolites (fold-change threshold (FC) > 1.5 or<2/3, variable importance in projection (VIP) > 1, and p  < 0.05) were screened in HUA-CKD and HUA patients, and 24 differential metabolites (FC > 1.2 or<0.83, VIP>1, and p  < 0.05) were screened in HUA-CKD and NUA-CKD patients. According to the analysis of metabolic pathways, significant changes existed in three metabolic pathways (compared with the HUA group) and two metabolic pathways (compared with the HUA-CKD group) in HUA-CKD patients. Glycerophospholipid metabolism was a significant pathway in HUA-CKD. Our findings show that the metabolic disorder in HUA-CKD patients was more serious than that in NUA-CKD or HUA patients. A theoretical basis is provided for HUA to accelerate CKD progress.

Methionine adenosyltransferase 2A (MAT2A) is an essential enzyme in the methionine cycle that generates S-adenosylmethionine (SAM) by reacting with methionine and ATP. SAM acts as a methyl donors for histone and DNA methylation, which plays key roles in zygotic genome activation (ZGA). However, the effects of MAT2A on porcine ZGA remain unclear. To investigate the function of MAT2A and its underlying mechanism in porcine ZGA, MAT2A was knocked down by double-stranded RNA injection at the 1-cell stage. MAT2A is highly expressed at every stage of porcine embryo development. The percentages of four-cell-stage embryos and blastocysts were lower in the MAT2A-knockdown (KD) group than in the control group. Notably, depletion of MAT2A decreased the levels of H3K4me2, H3K9me2/3, and H3K27me3 at the four-cell stage, whereas MAT2A KD reduced the transcriptional activity of ZGA genes. MAT2A KD decreased embryonic ectoderm development (EED) and enhancer of zeste homolog 2 (EZH2) expression. Exogenous SAM supplementation rescued histone methylation levels and developmental arrest induced by MAT2A KD. Additionally, MAT2A KD significantly increased DNA damage and apoptosis. In conclusion, MAT2A is involved in regulating transcriptional activity and is essential for regulating histone methylation during porcine ZGA., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To develop and assess an automated Sub-arc Collimator Angle Optimization (SACAO) algorithm and Cumulative Blocking Index Ratio (CBIR) metrics for single-isocenter coplanar volumetric modulated arc therapy (VMAT) to treat multiple brain metastases. This study included 31 patients with multiple brain metastases, each having 2 to 8 targets. Initially, for each control point, the MLC blocking index was calculated at different collimator angles, resulting in a two-dimensional heatmap. Optimal sub-arc segmentation and collimator angle optimization were achieved using an interval dynamic programming algorithm. Subsequently, VMAT plans were designed using two approaches: SACAO and the conventional Full-Arc Fixed Collimator Angle. CBIR was calculated as the ratio of the cumulative blocking index between the two plan approaches. Finally, dosimetric and planning parameters of both plans were compared. Normal brain tissue, brainstem, and eyes received better protection in the SACAO group (P < 0.05).Query Notable reductions in the SACAO group included 11.47% in gradient index (GI), 15.03% in monitor units (MU), 15.73% in mean control point Jaw area (A Jaw,mean ), and 19.14% in mean control point Jaw-X width (W Jaw-X,mean ), all statistically significant (P < 0.001). Furthermore, CBIR showed a strong negative correlation with the degree of plan improvement. The SACAO method enhanced protection of normal organs while improving transmission efficiency and optimization performance of VMAT. In particular, the CBIR metrics show promise in quantifying the differences specifically in the 'island blocking problem' between SACAO and conventional VMAT, and in guiding the enhanced application of the SACAO algorithm., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests. Ethics approval: This retrospective study was approved by the Hunan Cancer Hospital Medical Ethics Review Committee, with the ethical approval number being the 52nd of the 2024 Scientific Research Ethics Review., (© 2024. Australasian College of Physical Scientists and Engineers in Medicine.)

Purpose: Investigating the effects of unequal sub-arc personalized collimator angle selection on the quality of Volumetric Modulated Arc Therapy (VMAT) plans for treating multiple brain metastases., Methods: This study included 21 patients, each with 2-4 target volumes of multiple brain metastases. Two stereotactic radiotherapy (SRT) approaches were utilized: sub-arc collimator VMAT (SAC-VMAT) and fixed collimator VMAT (FC-VMAT). In the SAC-VMAT group, multi-leaf collimators (MLC) shaped the target area, dividing the full arc into four unequal sub-arcs under the beam's eye view (BEV). Each sub-arc had an appropriate collimator angle selected to mitigate 'island blocking problems'. Conversely, the FC-VMAT group used a fixed collimator angle of 15° or 345°. A comparative analysis of the dosimetric parameters of the target volumes and normal tissues, along with the monitor units (MU), was conducted between the two groups., Results: The mean dose and dose-volume to normal brain tissue (2-26 Gy, with a step of 2 Gy) were significantly lower in the SAC-VMAT group (P < 0.01). There was no statistical difference between the two groups in dose to the target volumes, conformity index (CI), homogeneity index (HI), and other normal tissues (P > 0.05). Compared with the FA-VMAT group, the SAC-VMAT group significantly reduced the gradient index (GI) (4.5 ± 0.59 vs 5.2 ± 0.75, P < 0.001) and MU (1774.33 ± 181.77 vs 2001.0 ± 344.86, P < 0.001). Notably, with an increase in the number of PTV, the SAC-VMAT group demonstrated more significant improvements in the dose-volume of normal brain tissue, GI, and MU., Conclusions: In this study, personalized selection of the unequal sub-arc collimator angle ensured the prescribed dose to the PTV, CI, and HI, while significantly reducing the GI, MU, and the dose to normal brain tissue in the VMAT plan for multi-target brain metastases in the cohort of cases with 2-4 target volumes. Particularly as the number of targets increase, the advantages of this method become more pronounced., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To construct and internally validate a nomogram that predicts the likelihood of postoperative delirium in a cohort of elderly individuals undergoing hip arthroplasty., Methods: Data for a total of 681 elderly patients underwent hip arthroplasty were retrospectively collected and divided into a model ( n  = 477) and a validation cohort ( n  = 204) according to the principle of 7:3 distribution temporally. The assessment of postoperative cognitive function was conducted through the utilization of The Confusion Assessment Method (CAM). The nomogram model for postoperative cognitive impairments was established by a combination of Lasso regression and logistic regression. The receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) were used to evaluate the performance., Results: The nomogram utilized various predictors, including age, body mass index (BMI), education, preoperative Barthel Index, preoperative hemoglobin level, history of diabetes, and history of cerebrovascular disease, to forecast the likelihood of postoperative delirium in patients. The area under the ROC curves (AUC) for the nomogram, incorporating the aforementioned predictors, was 0.836 (95% CI: 0.797-0.875) for the training set and 0.817 (95% CI: 0.755-0.880) for the validation set. The calibration curves for both sets indicated a good agreement between the nomogram's predictions and the actual probabilities., Conclusion: The use of this novel nomogram can help clinicians predict the likelihood of delirium after hip arthroplasty in elderly patients and help prevent and manage it in advance.

Atherosclerosis (AS) is a chronic multifactorial disease with damage to vascular endothelial cells (VECs). This study sought to delve into the mechanism of methyltransferase-like 14 (METTL14) in iron overload-induced lipid peroxidative damage in AS. AS mouse model and cell model were established. Levels of METTL14/circRNA coded by the Arhgap12 (circARHGAP12)/Aspartate β-hydroxylase (ASPH) were determined. AS plaque area/lipid deposition/lipid metabolism in AS mice and iron overload in VECs were evaluated. N6-methyladenosine (m6A) level and METTL14 enrichment and human antigen R (HuR) in circARHGAP12 or ASPH were measured. The mRNA stability of circARHGAP12 or ASPH was analyzed. We observed that METTL14 was upregulated in AS mice. METTL14 downregulation reduced plaque area/lipid deposition/iron overload/peroxidative damage in AS mice. In cell models, METTL14 downregulation could VEC injury/iron overload/lipid peroxidative damage. Mechanically, METTL14 increased the stability and expression of circARHGAP12 through m6A modification, further stabilized ASPH mRNA, and promoted ASPH transcription by binding to HuR. Overexpression of circARHGAP12 or inhibition of ASPH averted the protective role of METTL14 downregulation against iron overload-induced peroxidative damage in AS. In conclusion, METTL14-mediated m6A modification upregulated circARHGAP12 and ASPH to aggravate overload-induced lipid peroxidative damage and facilitate AS progression., (© 2024 Wiley Periodicals LLC.)

Statins therapy is efficacious in diminishing the risk of major cardiovascular events in diabetic patients. However, our research has uncovered a correlation between the prolonged administration of statins and an elevated risk of myocardial dysfunction in patients with type II diabetes mellitus (TIIDM). Here, we report the induction of sterol regulatory element-binding protein 1 (SREBP1) activation, associated lipid peroxidation, and the consequent diabetic myocardial dysfunction after statin treatment and explored the underlying mechanisms. In db/db mice, we observed that 40 weeks atorvastatin (5 and 10 mg/kg) and rosuvastatin (20 mg/kg) administration exacerbated diabetic myocardial dysfunction by echocardiography and cardiomyocyte contractility assay, increased myocardial inflammation and fibrosis as shown by CD68, IL-1β, Masson's staining and Collagen1A1 immunohistochemistry (IHC) staining, increased respiratory exchange ratio (RER) by metabolic cage system assessment, exacerbated mitochondrial structural pathological changes by transmission electron microscopy (TEM) examination, increased deposition of lipid and glycogen by TEM, Oil-red and periodic acid-schiff stain (PAS) staining, which were corresponded with augmented levels of myocardial SREBP1 protein and lipid peroxidation marked by 4-hydroxynonenal (4-HNE) staining. Comparable myocardial fibrosis was also observed in KK-ay and low-dose streptozotocin (STZ)-induced TIIDM mice. Elevated SREBP1 levels were observed in the heart tissues from diabetic patients, which was positively correlated with their myocardial dysfunction. To elucidate the role of statin induced SREBP1 in lipid peroxidation and lipid deposition and related mechanism, we cultured neonatal mouse primary cardiomyocytes (NMPCs) and treated them with atorvastatin (10 μM, 24 h), tracing with [U- 13 C]-glucose and evaluating for SREBP1 expression and localization. We found that statin treatment elevated de novo lipogenesis (DNL) and the levels of SREBP1 cleavage-activating protein (SCAP), reduced the interaction of SCAP with insulin-induced gene 1 (Insig1), and enhance SCAP/SREBP1 translocation to the Golgi, which facilitate SREBP1 cleavage leading to its nuclear trans-localization and activation in NMPCs. Ultimately, SREBP1 knockdown or l-carnitine mitigated long-term statins therapy induced lipid peroxidation and myocardial fibrosis in low-dose STZ treated SREBP1 +/- mice and l-carnitine treated db/db mice. In conclusion, we demonstrated that statin therapy may augment DNL by activating SREBP1, resulting in myocardial lipid peroxidation and lipid deposition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: To investigate the N-glycans related to the metformin efficacy in patients with type 2 diabetes mellitus (T2DM)., Materials and Methods: We enrolled 141 healthy controls and 195 newly diagnosed T2DM patients treated with metformin for 3 months. Serum N-glycan profile was determined by DNA sequencer - assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). The N-glycan model was established by logistic regression analysis. Receiver operating characteristic curve (ROC) analysis was used to analyze the predictive power of the N-glycan model for metformin efficacy., Results: The abundances of several N-glycans in serum of T2DM patients at baseline were significantly different from those of healthy controls and tended to recover the N-glycan of controls after 3 months treatment. Serum N-glycans changes were more significant in the good response group (FPG <7 mmol/L) after metformin treatment. In addition, the abundance of peak9 at baseline had an opposite tendency between HbA1c increased and decreased groups post-treatment, which could be a biomarker for predicting metformin efficacy. Peak9 combined with other 11 N-glycans at baseline was used to establish the predictive model to distinguish non-response from response patients (AUROC = 0.780, sensitivity = 70.6% and specificity = 77.5%)., Conclusions: Serum N-glycans may have potential value as biomarkers for indicating the efficacy of metformin.

E-waste recycling employees represent a specific population with a high potential for exposure to dechlorane plus (DP). However, the impact of skin-adherent DP on human exposure within this group has not been well characterized. This study aimed to address this gap by collecting handwipe and matched serum samples (n = 86 pairs) of Chinese e-waste recycling employees. In vivo human dermal bioavailability of DP was also examined to achieve effective exposure estimation. As a result, DP was detected in all handwipe and serum samples, indicating the occurrence of widespread exposure in the study population. For all the participants, the median level of ∑DP (the sum of syn-DP and anti-DP) in the serum was 45.1 ng g -1 lipid weight (lw), while handwipe samples showed the loading of 10.8 ng per wipe. Notably, significant associations were found between DP handwipe loadings and matched serum levels (p<0.05). Next, the in vivo human dermal bioavailability was estimated to be 9.54% for ∑DP. Based on this value, the estimated average daily dose was 0.231 ng kg -1 d -1 (median values), contributing 10.9% to serum levels of ∑DP. The significant associations and 10.9% percentage contribution together underscore the non-negligible influence of dermal absorption on DP internal doses in the e-waste recycling employees. Moreover, the extremely high levels of DP (up to 3.64E+04 ng g -1 lw) detected in serum highlight the extent of DP accumulation in humans. Continuous monitoring and assessment are warranted among e-waste workers due to the persistent organic pollutant properties of DP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Gut-brain axis dysfunction has emerged as a key contributor to the pathogenesis of Crohn's disease (CD). The elucidation of neural alterations may provide novel insights into its management. We aimed to develop a multiparameter brain MRI-based radiomics model (RM) for characterizing neural alterations in CD patients and to interpret these alterations using multiomics traits., Methods: This prospective study enrolled 230 CD patients and 46 healthy controls (HCs). Participants voluntarily underwent brain MRI and psychological assessment (n = 155), blood metabolomics analysis (n = 260), and/or fecal 16S rRNA sequencing (n = 182). The RM was developed using 13 features selected from 13,870 first-order features extracted from multiparameter brain MRI in training cohort (CD, n = 75; HCs, n = 32) and validated in test cohort (CD, n = 34; HCs, n = 14). Multiomics data (including gut microbiomics, blood metabolomics, and brain radiomics) were compared between CD patients and HCs., Results: In the training cohort, area under the receiver operating characteristic curve (AUC) of RM for distinguishing CD patients from HCs was 0.991 (95% confidence interval (CI), 0.975-1.000). In test cohort, RM showed an AUC of 0.956 (95% CI, 0.881-1.000). CD-enriched blood metabolites such as triacylglycerol (TAG) exhibited significant correlations with both brain features detected by RM and CD-enriched microbiota (e.g., Veillonella). One notable correlation was found between Veillonella and Ctx-Lh-Middle-Temporal-CBF-p90 (r = 0.41). Mediation analysis further revealed that dysbiosis, such as of Veillonella, may regulate the blood flow in the middle temporal cortex through TAG., Conclusion: We developed a multiparameter MRI-based RM that characterized the neural alterations of CD patients, and multiomics data offer potential evidence to support the validity of our model. Our study may offer clues to help provide potential therapeutic targets., Critical Relevance Statement: Our brain-gut axis study developed a novel model using multiparameter MRI and radiomics to characterize brain changes in patients with Crohn's disease. We validated this model's effectiveness using multiomics data, making it a potential biomarker for better patient management., Key Points: Utilizing multiparametric MRI and radiomics techniques could unveil Crohn's disease's neurophenotype. The neurophenotype radiomics model is interpreted using multiomics data. This model may serve as a novel biomarker for Crohn's disease management., Competing Interests: Declarations. Ethics approval and consent to participate: This prospective study was approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University (No. [2021]215-2), and there was informed consent for all patients. Consent for publication: All authors approved the final manuscript and the submission to this journal. Competing interests: C.Z. is an employee of Siemens Healthineers, but he had no control over the inclusion of any data or information that might have presented a conflict of interest. All authors declare no relevant relationships., (© 2024. The Author(s).)

Due to their wide applications, occurrence and "PFAS-like" environmental behaviors, ionic liquids (ILs) represent a new challenge for the environmental monitoring community, who require robust analytical methods that can determine accurately and efficiently their environmentally relevant concentrations. A new passive sampling method based on the diffusive gradients in thin films (DGT) technique was developed for the measurement of imidazole-based ILs in waters using a mixed-mode cation exchange (MCX) resin as the adsorbent. The selected binding gel had a high binding capacity (>170 μg per disc) for ILs. Diffusion coefficients measured using a diffusion cell correlated well with alkyl chain lengths ( r 2 = 0.95) and retention times ( r 2 = 0.88), providing a simple and rapid prediction approach for other ILs. The assembled MCX-DGT sampler exhibited a linear accumulation for at least 120 h. MCX-DGT also showed good performance under typical freshwater conditions (pH 5-8, ionic strength 0.001-0.01 M, and humic acid 0-5 mg L -1 ), while still being problematic for aquatic conditions with higher ionic strength (>0.1 M) or DOM (>10 mg L -1 ). Laboratory deployment (for up to 3 days) in spiked natural freshwater (SNW) resulted in linear mass uptakes for the short-chain ILs (C2-C8), and their DGT-measured concentrations agreed well with solution concentrations. However, MCX-DGT significantly overestimated the concentrations of the long-chain ILs (C10-C12) when deployed in SNW for one day or more, which is attributed to the strong competitive adsorption of the long-chain ILs by natural organic matter. In situ field evaluation along with grab sampling found no target ILs in a wastewater treatment plant and its receiving river, implying that these new chemicals might not be widely used in South China now. This is the first report on the DGT technique for ILs and might provide an effective tool for monitoring short chain length ILs in the aquatic environment in the near future.

Background: Prader-Willi Syndrome (PWS) is a rare disorder that was initially documented by Prader and Willi in 1956. Despite significant advancements in the understanding of PWS over recent decades, no bibliometric studies have been reported on this field. We aimed to analyze and explore the research trends and hotspots of PWS using a bibliometric analysis to understand the future development of basic and clinical research., Methods: The literature regarding PWS was retrieved from the Web of Science Core Collection Science Citation Index Expanded (SCI-Expanded) database. Data were extracted from the articles or review articles, and analyzed using CiteSpace and VOSviewer software., Results: A total of 1,895 related studies have been published in 64 countries or regions. The United States has published the most articles, followed by the United Kingdom, Italy, Netherlands, and France. University of Florida (The United States), University of Kansas (The United States), University of Alberta (Canada), University of Cambridge (the United Kingdom), and Dutch Growth Research Foundation (Netherlands) were the top five most productive institutions. Butler, Merlin G. and his colleagues have made the most outstanding contributions in the field of PWS research. Keyword co-occurrence analysis showed that genomic imprinting, uniparental disomy, obesity, hyperphagia, hypothalamus, growth hormone treatment, and ghrelin appeared with the higher frequency. Furthermore, oxytocin, magel2, and management were the latest bursts keywords., Conclusion: Our findings indicated that genetic mechanism, diagnose, and emerging therapies will be the hotspots and frontiers in PWS research., Competing Interests: Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

Objective: To investigate the genetic, clinical, and post-treatment characteristics of patients with glycogen storage disease type Ⅲ (GSD Ⅲ). Methods: A retrospective cohort analysis was performed on the genetic and clinical data of 26 cases with GSD Ⅲ who visited the Children's Hospital affiliated with Fudan University from June 2017 to December 2023. The patients were divided into non-missense variation and missense variation groups according to the types of mutation in the AGL gene.The correlation between genotype and phenotype was analyzed. All patients were treated with uncooked cornstarch after diagnosis. The changes before and after treatment were compared in patients who underwent more than twelve months of follow-up. A P value of <0.05 was used to denote statistical significance. Results: Among the 26 cases enrolled, 13 were female and 13 were male, and the median age of diagnosis was 28 (6 to 134) months. A total of thirty-five different types of AGL gene variation were detected, with c.1735+1G＞T (9/52, 17.3%) as the hotspot variation. The common clinical manifestations were elevated aminotransferases (26/26, 100%), hepatomegaly (25/26, 96.2%), fasting hypoglycemia (25/26, 96.2%), hyperketonemia (16/18, 88.9%), hypertriglyceridemia (TG) (20/26, 76.9%), elevated CK (16/25, 64.0%), and an abnormal electrocardiogram (12/16, 75.0%). Four cases (15.4%) had symptoms of myopathy at diagnosis. Liver biopsy was performed in eighteen cases, among whom 83.3% (15/18) had liver fibrosis≥S2. The number of cases with elevated levels of CK ( P ＝0.031) and ALT ( P ＝0.038)was pronounced in the non-missense variation group compared to that in the missense variation group. There were no statistically significant differences in age, height, liver size, degree of fibrosis, fasting blood glucose (Glu) and TG ( P >0.05). The median follow-up time of 14 cases was 40.5 (20-73) months, with improvement in body stature, reduced liver size, decreased ALT and TG, and improved Glu. However, four (28.6%) cases had new myopathy symptoms with raised CK ( P <0.05) and with advancing age, increased ALT diminished while CK level elevated ( P <0.05). Conclusions: The common clinical manifestations at the early stage of the GSD Ⅲdiagnosis are elevated aminotransferases, hepatomegaly, fasting hypoglycemia, hyperketonemia, high triglycerides, elevated CK, and fibrotic liver in China. Myopathy symptoms may arise following uncooked cornstarch treatment; however, there is significant improvement in height, liver-related, and metabolic parameters.

Objective: This study aimed to investigate the effects of esketamine (Esk) combined with dexmedetomidine (Dex) on postoperative delirium (POD) and quality of recovery (QoR) in elderly patients undergoing thoracoscopic radical lung cancer surgery., Methods: In this prospective, randomized, and controlled study, 172 elderly patients undergoing thoracoscopic radical lung cancer surgery were divided into two groups: the Esk + Dex group (n = 86) and the Dex group a (n = 86). The primary outcome was the incidence of POD within 7 days after surgery and the overall Quality of Recovery-15 (QoR - 15) scores within 3 days after surgery. Secondary outcomes included postoperative adverse reactions, extubation time, PACU stay, and hospitalization time. Serum levels of IL-6, IL-10, S100β protein, NSE, CD3 + , CD4 + , and CD8 + were detected from T0 to T5., Results: Compared with the Dex group, the incidence of POD in the Esk + Dex group was significantly lower at 7 days after surgery (14.6% vs 30.9%; P = 0.013). The QoR - 15 score was significantly increased 3 days after surgery (P < 0.01). Levels of IL-6 and CD8 + were significantly decreased, and IL - 10 levels were significantly increased at T1-T2 (P < 0.05). At T1-T4, NSE levels were significantly decreased, while CD3 + and CD4 + /CD8 + values were significantly increased (P < 0.01). At T1-T5, serum S100β protein concentration decreased significantly, and CD4 + value increased significantly (P < 0.01). The incidence of nausea/vomiting and hyperalgesia decreased significantly 48 hours after surgery (P < 0.01). The duration of extubation, PACU stay, and postoperative hospitalization were significantly shortened., Conclusions: Esketamine combined with dexmedetomidine can significantly reduce the POD incidence and improve the QoR in patients undergoing thoracoscopic radical lung cancer surgery, which may be related to the improvement of cellular immune function.

Isocitrate dehydrogenase 2 (IDH2) and glutamate dehydrogenase 1 (GLUD1) are key enzymes involved in the production of α-ketoglutarate (α-KG), a metabolite central to the tricarboxylic acid cycle and glutamine metabolism. In this study, we investigated the impact of IDH2 and GLUD1 on early porcine embryonic development following IDH2 and GLUD1 knockdown (KD) via double-stranded RNA (dsRNA) microinjection. Results showed that KD reduced α-KG levels, leading to delayed embryonic development, decreased blastocyst formation, increased apoptosis, reduced blastomere proliferation, and pluripotency. Additionally, IDH2 and GLUD1 KD induced abnormally high levels of trimethylation of lysine 20 of histone H4 (H4K20me3) at the 4-cell stage, likely resulting in transcriptional repression of embryonic genome activation (EGA)-related genes. Notably, KD of lysine methyltransferase 5C ( KMT5C ) and supplementation with exogenous α-KG reduced H4K20me3 expression and partially rescued these defects, suggesting a critical role of IDH2 and GLUD1 in the epigenetic regulation and proper development of porcine embryos. Overall, this study highlights the significance of IDH2 and GLUD1 in maintaining normal embryonic development through their influence on α-KG production and subsequent epigenetic modifications.

Unravelling the volcanic history of the enigmatic lunar farside is essential for understanding the hemispheric dichotomy of the Moon 1-3 . Cratering chronology established for the lunar nearside has been used to suggest long-lived volcanism on the farside of the Moon 3,4 but without sample verification. We describe two episodes of basaltic volcanism identified by Pb-Pb dating of basalt fragments returned by the Chang'e-6 mission. One high-Al basalt fragment, dated at 4,203 ± 4 million years ago (Ma), has a source 238 U/ 204 Pb ratio (µ value) of approximately 1,620, implying a KREEP-rich (K, rare earth elements and P) source for this oldest-known example of basaltic volcanism among returned samples. The main volcanic episode of the Chang'e-6 basalt documents a surprisingly young eruption age of 2,807 ± 3 Ma, which has not been observed on the nearside of the Moon. The initial Pb isotope compositions of these younger basalts indicate a derivation from a source with a µ value of approximately 360, indicating a KREEP-poor mantle source. Mare volcanism on the lunar farside thus persisted for over 1.4 billion years, even if the source was depleted in heat-producing elements. The consistency between the 2.8-billion-year basalt age and the crater-counting age indicates that the cratering chronology model established for the lunar nearside is also applicable to the farside of the Moon., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Pteroceltis tatarinowii Maxim is a famous paper-making tree endemic to China with a wide distribution. Leaves of this tree growing in different habitats show a certain plasticity, which is important for their ecological adaption. Here, the photosynthesis ability, hydraulic properties, and anatomy of P. tatarinowii leaves from a limestone forest (Langya Mountain) and a cultivated forest (Xiaoling Village) in Anhui province were compared. The results showed that leaves from Xiaoling Village had higher net photosynthesis rate and hydraulic conductivity, which were closely related to their higher vein density, stomatal density and palisade tissue thickness than leaves from Langya Mountain. However, lower leaf water potentials at turgor loss point and at 50% loss of conductivity, as well as a higher leaf hardness, for Langya Mountain leaves indicated their higher hydraulic safety and drought resistance than those of leaves from Xiaoling Village. This study reveals a hydraulic trade-off between efficiency and safety for P. tatarinowii leaves growing in distinct habitats. Further studies should include more habitats and different vegetation communities to clarify the ecological adaption so as to provide a scientific basis for the protection of this species.

The reconstruction of damaged neural circuits is critical for neurological repair after brain injury. Classical brain-computer interfaces (BCIs) allow direct communication between the brain and external controllers to compensate for lost functions. Importantly, there is increasing potential for generalized BCIs to input information into the brains to restore damage, but their effectiveness is limited when a large injured cavity is caused. Notably, it might be overcome by transplantation of brain organoids into the damaged region. Here, we construct innovative BCIs mediated by implantable organoids, coined as organoid-brain-computer interfaces (OBCIs). We assess the prolonged safety and feasibility of the OBCIs, and explore neuroregulatory strategies. OBCI stimulation promotes progressive differentiation of grafts and enhances structural-functional connections within organoids and the host brain, promising to repair the damaged brain via regenerating and regulating, potentially directing neurons to preselected targets and recovering functional neural networks in the future., (© 2024. The Author(s).)

Human brain organoids represent a remarkable platform for modelling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses revealed that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injured somatosensory cortices of adult mice, longitudinal electrophysiological recordings and histological assays revealed that ultrasound-treated organoid grafts undergo advanced maturation. They also exhibit enhanced pain-related gamma-band activity and more disseminated projections into the host brain than the untreated groups. Finally, low-intensity ultrasound ameliorates neuropathological deficits in a microcephaly brain organoid model. Hence, low-intensity ultrasound stimulation advances the development and integration of brain organoids, providing a strategy for treating neurodevelopmental disorders and repairing cortical damage., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. 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.)