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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.)