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Postoperative cognitive dysfunction (POCD) is a common complication following surgeries involving general anesthesia. Although the CCL5-CCR5 axis is implicated in various neurological conditions, its role in POCD remains unclear. In our POCD model, we observed an increase in CCL5 and CCR5 levels concurrent with microglial activation and significant upregulation of inflammatory cytokines IL-6 and IL-1β. Administration of MVC, a CCR5 antagonist, alleviated neuroinflammation, prevented dendritic spine loss, and improved cognitive deficits by inhibiting the CCR5/CREB/NLRP1 pathway. However, the cognitive benefits of MVC were reversed by the CREB inhibitor 666-15. Our findings highlight the potential of targeting the CCL5-CCR5 axis as a therapeutic strategy for preventing and treating POCD., (Copyright © 2024. Published by Elsevier Inc.)

Poly (ADP-ribose) Polymerase inhibitors (PARPi) have demonstrated remarkable clinical efficacy in treating ovarian cancer (OV) with BRCA1/2 mutations. However, drug resistance inevitably limits their clinical applications and there is an urgent need for improved therapeutic strategies to enhance the clinical utility of PARPi, such as Olaparib. Here, compelling evidence indicates that sensitivity of PARPi is associated with cell cycle dysfunction. Through high-throughput drug screening with a cell cycle kinase inhibitor library, XL413, a potent cell division cycle 7 (CDC7) inhibitor, is identified which can synergistically enhance the anti-tumor efficacy of Olaparib. Mechanistically, the combined administration of XL413 and Olaparib demonstrates considerable DNA damage and DNA replication stress, leading to increased sensitivity to Olaparib. Additionally, a robust type-I interferon response is triggered through the induction of the cGAS/STING signaling pathway. Using murine syngeneic tumor models, the combination treatment further demonstrates enhanced antitumor immunity, resulting in tumor regression. Collectively, this study presents an effective treatment strategy for patients with advanced OV by combining CDC7 inhibitors (CDC7i) and PARPi, offering a promising therapeutic approach for patients with limited response to PARPi., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: This study aimed to identify large duplications (>5 Mb) that are harmless through long-term clinical follow-ups of fetuses and phenotype analyses of carrier family members., Methods: We retrospectively analyzed fetuses undergoing prenatal diagnosis and who had >5 Mb chromosomal duplications. Routine karyotyping and single-nucleotide polymorphism array analysis were performed to identify the source and location information of the duplicated segments. Genotype-phenotype analyses were conducted based on genetic information and phenotypes during postnatal follow-up., Results: Eight eligible cases were included. All fetuses carried maternal or paternal duplications ranging in length from 5.3 to 12.2 Mb. The locations were as follows: 2q32.3q33.1 (Chr2:192322509-199548704), 4q22.1 (Chr4: 88347368-93602855), 4q34.2q35.2 (Chr4:176956406-189189971), 4q34.3q35.2 (Chr4:180613345-189353740), 5p14.3p14.1 (Chr5:19093749-28557664), 10q22.2q23.2 (Chr10:77448435-88786593), 12q21.31q21.32 (Chr12:81983257-87322734), and 13q14.11q14.2 (Chr13: 40825382-47633710). Karyotyping revealed that these duplications occurred within their respective chromosomal regions, except in pedigrees 6 and 7. In the eight pedigrees, the coordinates and lengths of duplicated segments in family members were matched with those in fetuses. Neither the fetuses nor other carriers were clinically symptomatic., Conclusion: Our findings revealed that the eight pedigrees carrying duplications >5 Mb were asymptomatic, providing new data to inform genetic counseling for the observed segments., Impact: We focused on unrelated fetuses among eight pedigrees who carried duplications of different chromosomal segments. These duplications had been stably transmitted through 2 or 3 generations of normal individuals. Importantly, phenotypic abnormalities were lacking, which was unexpected given that the maximum segment size was approximately 12.2 Mb. We found that duplications in these regions were benign in the context of prenatal genetic counseling. These results provide a foundation for addressing genotype-phenotype correlations. To our knowledge, this is the first description of normal phenotypes in individuals with duplications in these regions., Competing Interests: Competing interests The authors declare no potential conflicts of interest concerning the research, authorship, and/or publication of this article. Consent to participate Written informed consent was obtained from the patients. Ethical approval This study was approved by the Ethics Committee of Southwest Hospital, Third Military Medical University (Army Medical University). The approval number is (B)KY2021023., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Neuropathic pain (NP) is a highly challenging condition with complex pathological mechanisms, and the spinal gamma aminobutyric acid A receptor receptor plays a crucial role in its progression. Recent studies have revealed a potential interaction between neuroplastin 65 (NP65) and gamma aminobutyric acid A receptor α2 subunit (GABAAR-α2) on the cell surface. We hypothesize that NP65 is involved in the pathogenesis of NP by regulating the level of GABAAR-α2., Methods: A chronic constrictive injury (CCI) pain model was established in male Sprague-Dawley rats to verify the change in spinal NP65 expression. Alterations in pain behavior and GABAAR-α2 protein expression were observed after intrathecal injection of NP65 overexpressing adeno-associated virus (AAV) in CCI rats. In vitro investigations on Neuroblastoma 2a cells, the effect of NP65 on GABAAR-α2 expression via the calcineurin-nuclear factor of activated T-cell 4 (CaN-NFATc4) signaling pathway was evaluated by manipulating NP65 expression., Results: The expression level of NP65 protein and mRNA in the CCI group were significantly decreased ( P < .05; analysis of variance [ANOVA]). After intrathecal injection of NP65, overexpression of AAV and pain behavior in CCI rats were significantly alleviated, and levels of GABAAR-α2 were upregulated. In vitro experiments verified alterations in the expression of GABAAR-α2, CaN, and phosphorylated NFATc4 on the application of NP65 with plasmid or small interfering RNA, respectively. After the application of the specific CaN inhibitor cyclosporine A (CsA), the changes in NP65 expression did not produce subsequent alterations in the expression of GABAAR-α2, CaN, or phosphorylated NFATc4 proteins., Conclusions: NP65 modulates the level of GABAAR-α2 through the CaN-NFATc4 signaling pathway, which may serve as the underlying mechanism of NP., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

Introduction: In recent years, the visible light intensity of lawns has significantly decreased due to obstructions caused by urban shading objects. Carex has a competitive advantage over other turfgrass in low-light conditions and extensive management. Therefore, exploring their survival strategy in low-light environments is of great significance., Methods: This study focuses on two species of Carex , Carex parva and Carex scabrirostris , and investigates their response to low-light conditions (150 μmol/m 2 /s) by simulating urban lawn conditions. Biomass allocation characteristics, leaf anatomical features, biochemical parameters, root morphology and photosynthetic parameters were measured., Results: (a) Peroxidase activity, specific leaf area, and relative water content are key factors influencing the photosynthetic capacity of the two Carex species. (b) Under low-light conditions, photosynthetic parameters, leaf physiological indicators, and biomass allocation of the two Carex species were significantly affected ( p <0.05). Both Carex species increased their investment in leaf biomass, maintained lateral root growth, and cleared reactive oxygen species to maintain their physiological balance. (c) In the simulated urban low-light environment, neither C. parva nor C. scabrirostris produced dauciform roots., Discussion: In terms of response strategies, C. scabrirostris is a high-photosynthesis investing species with high productivity under low-light conditions, whereas C. parva exhibits minimal response, indicating a slow investment. C. scabrirostris has greater potential for application in low-light environments compared to C. parva . These results provide a theoretical basis for the cultivation and application of these two Carex species, as well as the expansion of turfgrass germplasm resources., 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 Liu, Fan, Yang, Chen, Huang and Ji.)

Coral reef ecosystems have been severely ravaged by global warming and eutrophication. Eutrophication often originates from nitrogen (N) overloading that creates stoichiometric phosphorus (P) limitation, which can be aggravated by sea surface temperature rises that enhances stratification. However, how P-limitation interacts with thermal stress to impact coral-Symbiodiniaceae mutualism is poorly understood and underexplored. Here, we investigated the effect of P-limitation (P-depleted vs. P-replete) superimposed on heat stress (31 °C vs. 25 °C) on a Symbiodinium strain newly isolated from the coral host by a 14-day incubation experiment. The heat and P-limitation co-stress induced an increase in alkaline phosphatase activity and reppressed cell division, photosynthetic efficiency, and expression of N uptake and assimilation genes. Moreover, P limitation intensified downregulation of carbon fixation (light and dark reaction) and metabolism (glycolysis) pathways in heat stressed Symbiodinium. Notably, co-stress elicited a marked transcriptional downregulation of genes encoding photosynthates transporters and microbe-associated molecular patterns, potentially undermining the mutualism potential. This work sheds light on the interactive effects of P-limitation and heat stress on coral symbionts, indicating that nutrient imbalance in the coral reef ecosystem can intensify heat-stress effects on the mutualistic capacity of Symbiodiniaceae., 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.)

Severe pneumonia (SP) is a prevalent respiratory ailment characterized by high mortality and poor prognosis. Current scoring systems for pneumonia are not only time-consuming but also exhibit limitations in early SP prediction. To address this gap, this study aimed to develop a machine-learning model using inflammatory markers from peripheral blood for early prediction of SP. A total of 204 pneumonia patients from seven medical centers were studied, with 143 (68 SP cases) in the training cohort and 61 (32 SP cases) in the test cohort. Clinical characteristics and laboratory test results were collected at diagnosis. Various models including Logistic Regression, Random Forest, Naïve Bayes, XGBoost, Support Vector Machine, and Decision Tree were built and evaluated. Seven predictors-age, sex, WBC count, T-lymphocyte count, NLR, CRP, TNF-α, IL-4/IFN-γ ratio, IL-6/IL-10 ratio-were selected through LASSO regression and clinical insight. The XGBoost model, exhibiting best performance, achieved an AUC of 0.901 (95 % CI : 0.827 to 0.985) in the test cohort, with an accuracy of 0.803, sensitivity of 0.844, specificity of 0.759, and F1&#95;score of 0.818. Indeed, SHAP analysis emphasized the significance of elevated WBC counts, older age, and elevated CRP as the top predictors. The use of inflammatory biomarkers in this concise predictive model shows significant potential for the rapid assessment of SP risk, thereby facilitating timely preventive interventions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

PP mesh is a widely used prosthetic material in hernia repair. However, visceral adhesion is one of the worst complications of this operation. Hence, an anti-adhesive PP mesh is developed by coating porous polyvinyl alcohol (PVA) hydrogel on PP surface via freezing-thawing process method. The compressive modulus of porous PVA hydrogel coating is first regulated by the addition of porogen sodium bicarbonate (NaHCO 3 ) at various quality ratios with PVA. As expected, the porous hydrogel coating displayed modulus more closely resembling that of native abdominal wall tissue. In vitro tests demonstrate the modified PP mesh show superior coating stability, excellent hemocompatibility, and good cytocompatibility. In vivo experiments illustrate that PP mesh coated by the PVA4 hydrogel that mimicked the modulus of native abdominal wall could prevent adhesion effectively. Based on this, the rapamycin (RPM) is loaded into the porous PVA4 hydrogel coating to further improve anti-adhesive property of PP mesh. The Hematoxylin and eosin (H&E) and Masson trichrome (MT) staining results verified that the resulting mesh could alleviate the inflammation response and reduce the deposition of collagen around the implantation zone. The biomimetic mechanical property and anti-adhesive property of modified PP mesh make it a valuable candidate for application in hernioplasty., (© 2024 Wiley‐VCH GmbH.)

Background: The microglial activation has been implicated in cancer-induced bone pain. Recent studies have revealed that microglia mediate synaptic pruning in the central nervous system, where the cluster of differentiation 47-signal regulatory protein α (CD47-SIRPα) axis creates a "don't eat me" signal and elicits an antiphagocytic effect to protect synapses against elimination. To date, the synaptic phagocytosis in microglia has never been investigated in the murine cancer-induced bone pain model. The present experiments sought to explore whether microglia phagocytize synapses in mice with bone cancer pain as well as the possible mechanisms., Methods: Male C3H/HeN mice were used to induce bone cancer pain. Minocycline and S-ketamine were injected into D14. The number of spontaneous flinches (NSF) and paw withdrawal mechanical thresholds (PWMT) were measured on D0, D4, D7, D10, D14, D21, and D28. Hematoxylin and eosin staining presented bone lesions. Western blotting examined the Gephyrin, CD47, and SIRPα expression. Flow cytometry evaluated the proportion of SIRPα + cells in the spine. Immunofluorescence and 3-dimensional reconstruction showed the Gephyrin puncta inside microglial lysosomes., Results: Mice embedded with tumor cells induced persistent spontaneous pain and mechanical hyperalgesia. Hematoxylin and eosin staining revealed bone destruction and tumor infiltration in marrow cavities. Microglia underwent a responsive and proliferative burst (t = -16.831, P < .001). Western blotting manifested lowered Gephyrin expression in the tumor group (D4, D7, D10, D14, D21, and D28: P < .001). Immunofluorescence and 3-dimensional reconstruction showed larger volumes of Gephyrin puncta inside microglial lysosomes (t = -23.273, P < .001; t = -27.997, P < .001). Treatment with minocycline or S-ketamine exhibited pain relief and antiphagocytic effects (t = -6.191, P < .001, t = -7.083, P < .001; t = -20.767, P < .001, t = -17.080, P < .001; t = 11.789, P < .001, t = 16.777, P < .001; t = 8.868, P < .001, t = 21.319, P < .001). Last but not least, the levels of CD47 and SIRPα proteins were downregulated (D10: P = .004, D14, D21, and D28: P < .001; D10, D14, D21, and D28: P < .001). Flow cytometry and immunofluorescence substantiated reduced microglial SIRPα (t = 11.311, P < .001; t = 12.189, P < .001)., Conclusions: Microglia-mediated GABAergic synapse pruning in the spinal cord dorsal horn in bone cancer pain mice, which might be associated with the declined CD47-SIRPα signal. Our research uncovered an innovative mechanism that highlighted microglia-mediated synaptic phagocytosis in a murine cancer-induced bone pain model., Competing Interests: The authors declared no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Background: Bone age assessment (BAA) is crucial for the diagnosis of growth disorders and the optimization of treatments. However, the random error caused by different observers' experiences and the low consistency of repeated assessments harms the quality of such assessments. Thus, automated assessment methods are needed., Methods: Previous research has sought to design localization modules in a strongly or weakly supervised fashion to aggregate part regions to better recognize subtle differences. Conversely, we sought to efficiently deliver information between multi-granularity regions for fine-grained feature learning and to directly model long-distance relationships for global understanding. The proposed method has been named the "Multi-Granularity and Multi-Attention Net (2M-Net)". Specifically, we first applied the jigsaw method to generate related tasks emphasizing regions with different granularities, and we then trained the model on these tasks using a hierarchical sharing mechanism. In effect, the training signals from the extra tasks created as an inductive bias, enabling 2M-Net to discover task relatedness without the need for annotations. Next, the self-attention mechanism acted as a plug-and-play module to effectively enhance the feature representation capabilities. Finally, multi-scale features were applied for prediction., Results: A public data set of 14,236 hand radiographs, provided by the Radiological Society of North America (RSNA), was used to develop and validate 2M-Net. In the public benchmark testing, the mean absolute error (MAE) between the bone age estimates of the model and of the reviewer was 3.98 months (3.89 months for males and 4.07 months for females)., Conclusions: By using the jigsaw method to construct a multi-task learning strategy and inserting the self-attention module for efficient global modeling, we established 2M-Net, which is comparable to the previous best method in terms of performance., 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-23-806/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objective: To determine the association between the preoperative Bioenergetic Health Index (BHI) of platelets and the occurrence of postoperative delirium (POD) in elderly patients., Methods: Elderly patients scheduled for major abdominal surgery under general anesthesia were included. The presence of POD was assessed within the 3 days after surgery. Seahorse XF analysis and transmission electron microscopy were utilized to evaluate the mitochondrial metabolism and morphology of platelets., Results: A total of 20 out of 162 participants developed POD. Participants with POD showed lower preoperative Mini-Mental State Examination scores and total protein levels, fewer educational years, longer surgery duration, higher mean platelet volume, and lower platelet BHI compared with those without POD. Damaged mitochondria with swollen appearance and distorted cristae was detected in platelets from participants with POD. Preoperative platelet BHI was independently associated with the occurrence of POD after adjusting for age, education, preoperative Mini-Mental State Examination score, preoperative mean platelet volume and total protein levels, surgical type and duration, and lymphocyte counts on the first postoperative day (OR 0.11, 95% CI 0.03-0.37, p < 0.001). The areas under the receiver operating curves for predicting POD were 0.83 (95% CI 0.76-0.88) for platelet BHI. It showed a sensitivity of 85.00% and specificity of 73.24%, with an optimal cutoff value of 1.61. Using a serial combination (mean platelet volume followed by BHI) yielded a sensitivity of 80.00% and specificity of 82.39%., Interpretation: Preoperative platelet BHI was independently associated with the occurrence of POD in elderly patients and has the potential as a screening biomarker for POD risk. ANN NEUROL 2024;96:74-86., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Micro-nanomotors (MNMs) are micro/nanoscale intelligent devices with vast potential in the fields of drug delivery, precision medicine, biosensing, and environmental remediation. Their primary advantage lies in their ability to convert various forms of external energy (such as magnetic, ultrasonic, and light energy) into their own propulsive force. Additionally, MNMs offer high controllability and modifiability, enabling them to navigate in the microscopic world. Importantly, recent research has harnessed the unique advantages of MNMs to synergize their capabilities in neuromodulation. This mini-review presents the significant progress and pioneering achievements in the use of MNMs for neuromodulation, with the aim of inspiring readers to explore the broader biomedical applications of these MNMs. Through continuous innovation and diligent exploration, MNMs show promise to have a profound impact on the field of biomedicine.

Loss of ferroptosis contributes to the development of human cancer, and restoration of ferroptosis has been demonstrated as a potential therapeutic strategy in cancer treatment. However, the mechanisms of how ferroptosis escape contributes to ovarian cancer (OV) development are not well elucidated. Here, we show that ferroptosis negative regulation signatures correlated with the tumorigenesis of OV and were associated with poor prognosis, suggesting that restoration of ferroptosis represents a potential therapeutic strategy in OV. High-throughput drug screening with a kinase inhibitor library identified MEK inhibitors as ferroptosis inducers in OV cells. We further demonstrated that MEK inhibitor-resistant OV cells were less vulnerable to trametinib-induced ferroptosis. Mechanistically, mTOR/eIF4E binding protein 1 (4EBP1) signaling promoted solute carrier family 7 member 11 (SLC7A11) protein synthesis, leading to ferroptosis inhibition in MEK inhibitor-resistant cells. Dual inhibition of MEK and mTOR/4EBP1 signaling restrained the protein synthesis of SLC7A11 via suppression of the mTOR/4EBP1 axis to reactivate ferroptosis in resistant cells. Together, these findings provide a promising therapeutic option for OV treatment through ferroptosis restoration by the combined inhibition of MEK and mTOR/4EBP1 pathways.

Polypropylene (PP) mesh is the most widely used prosthetic material in hernia repair. However, the efficacy of implanted PP mesh is often compromised by adhesion between viscera and PP mesh. Thus, there is a recognized need for developing an anti-adhesive PP mesh. Here, a composite hydrogel coated PP mesh with the prevention of adhesion after hernia repair was designed. The composite hydrogel coating was prepared from polyvinyl alcohol (PVA) and hyaluronic acid (HA) by using the freezing-thawing (FT) method. To overcome the shortcoming of the long time of the traditional freezing-thawing method, a small molecule 3,4-dihydroxyphenylacetic acid (DHPA) was introduced to promote the formation of composite hydrogel. The as-prepared composite hydrogel coating displayed modulus more closely resembling that of native abdominal wall tissue. In vitro studies illustrated that the resulting meshes showed excellent coating stability, hemocompatibility, and non-cytotoxicity. In vivo experiments using a rat abdominal wall defect model demonstrated that the composite hydrogel coated PP mesh could prevent the formation of adhesion, alleviate the inflammatory response, and reduce the deposition of collagen around the damaged tissue. These disclosed results manifested that the PP mesh coated with HA/PVA composite hydrogel might be a promising application in preventing adhesion for hernia repair., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Phosphorus in the soil is mostly too insoluble for plants to utilize, resulting in inhibited aboveground biomass, while Carex can maintain their aboveground biomass through the presence of dauciform roots. However, dauciform roots lead to both morphological and physiological changes in the root system, making their primary mechanism unclear., Methods: A greenhouse experiment was conducted on three Carex species, in which Al-P, Ca-P, Fe-P, and K-P were employed as sole phosphorus sources. The plants were harvested and assessed after 30, 60 and 90 days., Results: (1) The density of dauciform roots was positively correlated with root length and specific root length, positively influencing aboveground biomass at all three stages. (2) The aboveground phosphorus concentration showed a negative correlation with both dauciform root density and aboveground biomass in the first two stages, which became positive in the third stage. (3) Aboveground biomass correlated negatively with the aboveground Al concentration, and positively with Ca and Fe concentration (except Al-P). (4) Root morphological traits emerged as critical factors in dauciform roots' promotion of aboveground biomass accumulation., Conclusion: Despite the difference among insoluble phosphorus, dauciform roots have a contributing effect on aboveground growth status over time, mainly by regulating root morphological traits. This study contributes to our understanding of short-term variation in dauciform roots and their regulatory mechanisms that enhance Carex aboveground biomass under low available phosphorus conditions., 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 Huang, Fan, Wang, Jiang, Liu, Ji and Li.)

Background: Sleep loss is a common public health problem that causes hyperalgesia, especially that after surgery, which reduces the quality of life seriously., Methods: The 48-h sleep restriction (SR) mouse model was created using restriction chambers. In vivo imaging, transmission electron microscopy (TEM), immunofluorescence staining and Western blot were performed to detect the status of the blood-spinal cord barrier (BSCB). Paw withdrawal mechanical threshold (PWMT) was measured to track mouse pain behavior. The role of infiltrating regulatory T cells (Tregs) and endothelial cells (ECs) in mouse glycolysis and BSCB damage were analyzed using flow cytometry, Western blot, CCK-8 assay, colorimetric method and lactate administration., Results: The 48-h SR made mice in sleep disruption status and caused an acute damage to the BSCB, resulting in hyperalgesia and neuroinflammation in the spinal cord. In SR mice, the levels of glycolysis and glycolysis enzymes of ECs in the BSCB were found significantly decreased [CON group vs. SR group: CD31 + Glut1 + cells: p < 0.001], which could cause dysfunction of ECs and this was confirmed in vitro. Increased numbers of infiltrating T cells [p < 0.0001] and Treg population [p < 0.05] were detected in the mouse spinal cord after 48-h SR. In the co-cultured system of ECs and Tregs in vitro, the competition of Tregs for glucose resulted in the glycolysis disorder of ECs [Glut1: p < 0.01, ENO1: p < 0.05, LDHα: p < 0.05; complete tubular structures formed: p < 0.0001; CCK8 assay: p < 0.001 on 24h, p < 0.0001 on 48h; glycolysis level: p < 0.0001]. An administration of sodium lactate partially rescued the function of ECs and relieved SR-induced hyperalgesia. Furthermore, the mTOR signaling pathway was excessively activated in ECs after SR in vivo and those under the inhibition of glycolysis or co-cultured with Tregs in vitro., Conclusions: Affected by glycolysis disorders of ECs due to glucose competition with infiltrating Tregs through regulating the mTOR signaling pathway, hyperalgesia induced by 48-h SR is attributed to neuroinflammation and damages to the barriers, which can be relieved by lactate supplementation., (© 2024. The Author(s).)

Ulcerative colitis (UC) is an idiopathic chronic intestinal inflammation. An increasing body of evidence shows that macrophages play an important role in the pathogenesis of UC. Interferon regulatory factor 4 (IRF4) is crucial for the development of autoimmune diseases via regulating immune cells. This research was designed to explore the function of IRF4 in UC and its association with macrophage polarization. The in vitro model of UC was established by stimulating colonic epithelial cells with tumor necrosis factor α (TNF-α). A mouse model of UC was constructed by injecting C57BL/6 mice with dextran sulfate sodium salt. Flow cytometry was used to assess percentage of CD11b + CD86 + and CD11b + CD206 + cells in bone marrow macrophages. Occult blood tests were used to detect hematochezia. Hematoxylin and eosin staining assay was used to assess colon pathological changes. Enzyme-linked immunosorbent assay (ELISA) was used to detect concentrations of inflammatory cytokines. The interaction of IRF4 and B-cell lymphoma 6 (Bcl6) was confirmed using GST pull-down and coimmunoprecipitation assays. Our findings revealed that IRF4 promoted cell apoptosis and stimulated M1 macrophage polarization in vitro. Furthermore, IRF4 aggravated symptoms of the mouse model of UC and aggravated M1 macrophage polarization in vivo. IRF4 negatively regulated Bcl6 expression. Downregulation of Bcl6 promoted apoptosis and M1 macrophage polarization in the presence of IRF4 in vitro and in vivo. Moreover, Bcl6 positively mediated the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In conclusion, IRF4 aggravated UC progression through promoting M1 macrophage polarization via Bcl6/JAK2/STAT3 pathway. These findings suggested that IRF4 might be a good target to competitively inhibit or to treat with UC., (© 2024 Wiley Periodicals LLC.)

ConspectusPolycyclic (hetero)aromatic hydrocarbons (PAHs) have emerged as a focal point in current interdisciplinary research, spanning the realms of chemistry, physics, and materials science. Possessing distinctive optical, electronic, and magnetic properties, these π-functional materials exhibit significant potential across diverse applications, including molecular electronic devices, organic spintronics, and biomedical functions, among others. Despite the extensive documentation of various PAHs over the decades, the efficient and precise synthesis of π-extended PAHs remains a formidable challenge, hindering their broader application. This challenge is primarily attributed to the intricate and often elusive nature of their synthesis, compounded by issues related to low solubility and unfavored stability.The development of π-building blocks that can be facilely and modularly transformed into diverse π-frameworks constitutes a potent strategy for the creation of novel PAH materials. For instance, based on the classic perylene diimide (PDI) unit, researchers such as Würthner, Wang, and Nuckolls have successfully synthesized a plethora of structurally diverse PAHs, as well as numerous other π-functional materials. However, until now the availability of such versatile building blocks is still severely limited, especially for those simultaneously having a facile preparation process, adequate solubilizing groups, favored material stability, and critically, rich possibilities for structural extension spaces.In this Account, we present an overview of our invention of a highly versatile bay -/ ortho -octa-substituted perylene building block, designated as Per-4Br , for the construction of a series of novel PAH scaffolds with tailor-made structures and rich optoelectronic and magnetic properties. First, starting with a brief discussion of current challenges associated with the bottom-up synthesis of π-extended PAHs, we rationalize the key features of Per-4Br that enable facile access to new PAH molecules including its ease of large-scale preparation, favored material stability and solubility, and multiple flexible reaction sites, with a comparison to the PDI motif. Then, we showcase our rational design and sophisticated synthesis of a body of neutral or charged, closed- or open-shell, curved, or planar PAHs via controlled annulative π-extensions in different directions such as peripheral, diagonal, or multiple dimensions of the Per-4Br skeleton. In this part, the fundamental structure-property relationships between molecular conformations, electronic structures, and self-assembly behaviors of these PAHs and their unique physiochemical properties such as unusual open-shell ground states, global aromaticity, state-associated/stimuli-responsive magnetic activity, and charge transport characteristics will be emphatically elaborated. Finally, we offer our perspective on the continued advancement of π-functional materials based on Per-4Br , which, we posit, may stimulate heightened research interest in the versatile structural motifs typified by Per-4Br , consequently catalyzing further progress in the realm of organic π-functional materials.

Mucoadhesive films based on tamarind seed polysaccharide and guar gum (TSP-GG) were formulated for buccal delivery of resveratrol. Resveratrol-bovine serum albumin nanoparticles (Res-BSA) were prepared and dispersed in TSP-GG to improve its buccal mucoadhesiveness. The impregnation of Res-BSA induced the dense internal structures of TSP-GG and improved its strength and rigidity. Structural characterization showed that resveratrol existed in an amorphous state in the films containing Res-BSA, and hydrogen bonding was formed between Res-BSA and the film matrices. The films containing Res-BSA exhibited good uniformity in thickness, weight, and resveratrol content, and their surface pH was near neutral, ranging between 6.78 and 7.09. Increasing Res-BSA content reduced the water contact angle of TSP-GG (from 75.9° to 59.6°). The swelling and erosion studies indicated the favorable hydration capacity and erosion resistance of the films containing Res-BSA. Additionally, the addition of Res-BSA imparted enhanced ex vivo mucoadhesive force, in the range of 1.53 N to 1.98 N, and extended ex vivo residence time, between 17.9 h and 18.9 h, to TSP-GG. The current study implied that the composite systems of TSP-GG and Res-BSA may be a novel platform for buccal mucosal delivery of resveratrol., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study aimed to analyze myocardial work in patients with atrial fibrillation (AF) using a noninvasive pressure strain loop (PSL) technique to provide a basis for the quantitative assessment of left ventricular (LV) systolic function., Methods: LV myocardial work of 107 AF patients (56 with paroxysmal atrial fibrillation and 51 with persistent atrial fibrillation) and 55 healthy individuals were assessed by the noninvasive PSL and then compared., Results: Global longitudinal strain (GLS) in absolute values, global work index (GWI), global constructive work (GCW), and global work efficiency (GWE) were significantly lower in the AF group than control group, whereas peak strain dispersion (PSD) and global wasted work (GWW) were significantly higher (P < .05). Further subdivision according to the AF type revealed that, compared with the controls, GLS in absolute values and GWE decreased significantly; PSD and GWW increased significantly in the paroxysmal AF group (P < .05). Nevertheless, GWI and GCW were not significantly different between paroxysmal AF and control groups (P > .05). Compared to paroxysmal AF, persistent AF induced a further decrease in absolute GLS and GWE and a further increase in GWW (P < .05), but PSD did not increase further (P > .05). Multiple linear regression analysis showed that GWI and GCW were independently associated with systolic blood pressure. GWW was associated with types of AF and left atrial volume index (LAVI). GWE was correlated with age, types of AF, disease duration, and LAVI. Receiver operating characteristic curve analysis showed that the area under the curve predicting myocardial injury was higher for GWE and GWW than for GLS (area under the curve:  .880,  .846, and  .821, respectively)., Conclusions: Non-invasive PSL can quantitatively assess LV systolic function in patients with different kinds of AF and detect early subclinical myocardial injury in patients with paroxysmal AF. GWE and GWW outperform GLS and LV ejection fraction when assessing myocardial injury. Systolic blood pressure, type of AF, LVAI, disease duration, and age may be associated with myocardial injury in patients with AF., (© 2024 Wiley Periodicals LLC.)

Resistance to neoadjuvant chemotherapy leads to poor prognosis of locally advanced rectal cancer (LARC), representing an unmet clinical need that demands further exploration of therapeutic strategies to improve clinical outcomes. Here, we identified a noncanonical role of RB1 for modulating chromatin activity that contributes to oxaliplatin resistance in colorectal cancer (CRC). We demonstrate that oxaliplatin induces RB1 phosphorylation, which is associated with the resistance to neoadjuvant oxaliplatin-based chemotherapy in LARC. Inhibition of RB1 phosphorylation by CDK4/6 inhibitor results in vulnerability to oxaliplatin in both intrinsic and acquired chemoresistant CRC. Mechanistically, we show that RB1 modulates chromatin activity through the TEAD4/HDAC1 complex to epigenetically suppress the expression of DNA repair genes. Antagonizing RB1 phosphorylation through CDK4/6 inhibition enforces RB1/TEAD4/HDAC1 repressor activity, leading to DNA repair defects, thus sensitizing oxaliplatin treatment in LARC. Our study identifies a RB1 function in regulating chromatin activity through TEAD4/HDAC1. It also provides the combination of CDK4/6 inhibitor with oxaliplatin as a potential synthetic lethality strategy to mitigate oxaliplatin resistance in LARC, whereby phosphorylated RB1/TEAD4 can serve as potential biomarkers to guide the patient stratification., Competing Interests: Competing interests statement:The authors declare no competing interest.

The intervention process for children with autism spectrum disorder (ASD) is inextricably associated with their parents' mental health problems, such as hopelessness, which may adversely affect resilience and indirectly impact the effectiveness of interventions for their children. Hence, the motivation to help parents of children with ASD reduce hopelessness prompted us to conduct the present study and explore the interrelationship between hopelessness symptoms and resilience. This study evaluated hopelessness and resilience using the Beck Hopelessness Scale (BHS) and the Connor-Davidson Resilience Scale (CD-RISC). Participants met the criteria for their children's ASD diagnosis by a psychiatrist (N = 448; 54.69% mothers; Mean age  = 34.59 years, SD age  = 4.94 years). Moreover, we used symptom network analysis to examine the variability in network structure between fathers and mothers. The flow function was applied to examine which hopelessness symptoms were directly or indirectly associated with resilience. The results showed that #BHS11 (i.e., unpleasantness-ahead) was the central symptom found in the network structure for all parents and fathers, while #BHS17 (i.e., no-future-satisfaction) was the central symptom in the network structure for mothers. Additionally, #BHS6 ([NOT] expect-to-succeed) was directly and positively associated with resilience in all three network structures (i.e., all parents, fathers, and mothers). The results of the present study provide evidence that influential symptoms should be addressed and offer guidance for further interventions to reduce hopelessness and enhance resilience among parents of children with ASD., (© 2023 The Authors. PsyCh Journal published by Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Typical (peridinin-containing) dinoflagellates possess plastid genomes composed of small plasmids named "minicircles". Despite the ecological importance of dinoflagellate photosynthesis in corals and marine ecosystems, the structural characteristics, replication dynamics, and evolutionary forcing of dinoflagellate plastid genomes remain poorly understood. Here, we sequenced the plastid genome of the symbiodiniacean species Fugacium kawagutii and conducted comparative analyses. We identified psbT-coding minicircles, features previously not found in Symbiodiniaceae. The copy number of F. kawagutii minicircles showed a strong diel dynamics, changing between 3.89 and 34.3 copies/cell and peaking in mid-light period. We found that F. kawagutii minicircles are the shortest among all dinoflagellates examined to date. Besides, the core regions of the minicircles are highly conserved within genus in Symbiodiniaceae. Furthermore, the codon usage bias of the plastid genomes in Heterocapsaceae, Amphidiniaceae, and Prorocentraceae species are greatly influenced by selection pressure, and in Pyrocystaceae, Symbiodiniaceae, Peridiniaceae, and Ceratiaceae species are influenced by both natural selection pressure and mutation pressure, indicating a family-level distinction in codon usage evolution in dinoflagellates. Phylogenetic analysis using 12 plastid-encoded proteins and five nucleus-encoded plastid proteins revealed accelerated evolution trend of both plastid- and nucleus-encoded plastid proteins in peridinin- and fucoxanthin-dinoflagellate plastids compared to plastid proteins of nondinoflagellate algae. These findings shed new light on the structure and evolution of plastid genomes in dinoflagellates, which will facilitate further studies on the evolutionary forcing and function of the diverse dinoflagellate plastids. The accelerated evolution documented here suggests plastid-encoded sequences are potentially useful for resolving closely related dinoflagellates., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Background: Human disease onset and progression are strongly associated with aberrant long noncoding RNA (lncRNA) expression, highlighting the functional regulatory role of lncRNA. Actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1), a member of lncRNAs, is located on the antisense strand of Actin filament-associated protein 1 (AFAP1)., Methods: We conducted a comprehensive review of AFAP1-AS1's functions in gynecology and urogenital systems using the "PubMed" database., Results: Our analysis reveals that AFAP1-AS1 is overexpressed and engages in the initiation and process of gynecological and urogenital diseases. The regulatory mechanisms employed by AFAP1-AS1 involve four major strategies: gene-level effects, competition for microRNA (miRNA) repression, protein binding, participation in signaling networks that influence cellular processes such as proliferative phenotype, migration, invasiveness, epithelial-mesenchymal transition (EMT), cycle regulation, drug resistance, and more. Furthermore, AFAP1-AS1 is implicated in guiding clinicopathological characteristics., Conclusion: AFAP1-AS1 holds promise as a potent diagnostics and treatment option for gynecological and genitourinary systems in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Tissue adhesives have attracted intense and increasing interest due to their multiple biomedical applications. Despite the rapid development of adhesive hydrogels, huge challenges remain for materials that can ensure strong adhesion and seal hemostasis in aqueous and blood environments. To address this issue, we have developed an innovative design of PAA-based coacervate hydrogel with strong wet adhesion capability through a simple mixture of PAA copolymers with oxidized-carboxymethylcellulose (OCMC), and tannic acid (TA) as the main components, and structurally enhanced with natural clays (Laponite XLG). The absorbed TA provides solid adhesion to dry and wet substrates via multiple interactions, which endows the XLG-enhanced coacervate with the desired underwater adhesive strength. More importantly, the dielectric constant is introduced to evaluate the polarity of the tested samples, which may be used as guidance for the design of mussel-inspired adhesives with even better underwater adhesive properties. In vivo hemorrhage experiments further confirmed that the hydrogel adhesive dramatically shortened the hemostatic time to tens of seconds. Overall, the persistent adhesion and acceptable cytocompatibility of the hydrogel nanocomposite make it a promising alternative suture-free approach for rapid hemostasis at different length scales and is expected to be extended to clinical application for other organ injuries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Ambient temperatures trigger hospitalisation, mortality, and emergency department visits for myocardial infarction (MI). However, nonoptimum temperature-related risks of fatal and nonfatal MI have not yet been compared., Methods: From 2007 to 2019, 416,894 MI events (233,071 fatal and 183,823 nonfatal) were identified in Beijing, China. A time-series analysis with a distributed-lag nonlinear model was used to compare the relative and population-attributable risks of fatal and nonfatal MI associated with nonoptimum temperatures., Results: The reference was the optimum temperature of 24.3°C. For single-lag effects, cold (-5.2°C) and heat (29.6°C) effects had associations that persisted for more days for fatal MI than for nonfatal MI. For cumulative-lag effects over 0 to 21 days, cold effects were higher for fatal MI (relative risk [RR] 1.99, 95% confidence interval [CI] 1.68-2.35) than for nonfatal MI (RR 1.60, 95% CI 1.32-1.94) with a P value for difference in effect sizes of 0.048. In addition, heat effects were higher for fatal MI (RR 1.33, 95% CI 1.24-1.44) than for nonfatal MI (RR 0.99, 95% CI 0.91-1.08) with a P value for difference in effect sizes of 0.002. The attributable fraction of nonoptimum temperatures was higher for fatal MI (25.6%, 95% CI 19.7%-30.6%) than for nonfatal MI (19.1%, 95% CI 12.1%-25.0%)., Conclusions: Fatal MI was more closely associated with nonoptimum temperatures than nonfatal MI, as evidenced by single-lag effects that have associations which persisted for more days, higher cumulative-lag effects, and higher attributable risks for fatal MI. Strategies are needed to mitigate the adverse effects of nonoptimum temperatures., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In the natural habitats of China, dauciform roots were only described in degraded alpine meadows. It was found that the presence of dauciform roots of Carex filispica was related to the advantage of multiple functional traits after trampling, reflecting short-term resistance. However, the long-term response of dauciform roots to trampling and the recovery of C. filispica with and without dauciform roots to trampling require further studies. In this study, different intensities of trampling (0, 50, 200 and 500 passages) were performed in an alpine meadow. One year later, individuals with and without dauciform roots were separated and their functional traits related to the economic spectrum of leaves and roots were measured as a reflection of recovery from trampling. The results showed that: (1) 1 year after trampling, the number of dauciform roots showed an increase with trampling intensity; (2) 1 year later, there was no significant difference in the response of economic spectrum traits among trampling intensities, or between plants with and without dauciform roots; (3) the number of dauciform roots was positively correlated with the leaf area of both individuals with and without dauciform roots, as well as with the biomass of those without dauciform roots; and (4) plants with more resource-conservative roots showed an advantage after trampling recovery: specifically, plants with dauciform roots showed such an advantage in the control group, which was lost with a leaning towards resource-acquisitive roots and an increased density of dauciform roots once trampled. In contrast, plants without dauciform roots showed a significant advantage of conservative roots only after trampling. In conclusion, the presence of dauciform roots is related to the plants' position on the root economic spectrum, thereby influencing the recovery of C. filispica from trampling. Carex filispica showed strong recovery from trampling after 1 year, which makes it an adequate choice for ecological restoration in alpine meadows. Dauciform roots showed a positive correlation with the aboveground growth of both plants with and without them, however, it requires a lab-controlled study to confirm whether there is indeed a positive effect on the growth of neighbouring plants., Competing Interests: This manuscript is approved by all authors for publication with no conflict of interest. The work described was original research that has not been published previously, or is it under consideration for publication elsewhere., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Heat stress can cause testicular damage and affect male fertility. Tanshinone IIA (TSA) is a monomer substance derived from plants, with antioxidant and anti-apoptotic effects. Whether it can repair testicular damage caused by heat stress is unclear. This study aims to construct a mouse testicular heat stress injury model and intervene with TSA. Various methods such as histopathology, high-throughput sequencing, bioinformatics analysis, and molecular biology were used to investigate whether TSA can alleviate heat stress-induced testicular injury and its mechanism. Results showed that heat stress significantly reduced the diameter of the mouse seminiferous tubules, increased cell apoptosis in the testicular tissue, and significantly decreased testosterone levels. After TSA intervention, testicular morphology and cell apoptosis improved significantly, and testosterone secretion function was restored. High-throughput transcriptome sequencing found that key differentially expressed genes between the HS group and the control and TSA groups clustered in the apoptosis and TGFβ signaling pathways. Using western blot technology, we found that the HS group upregulated TGFβ1/Smad2/Smad3 pathway protein expression, causing cell apoptosis, testicular tissue organic lesions, and affecting testicular secretion function. Through TSA intervention, we found that it can inhibit TGFβ1/Smad2/Smad3 pathway protein expression, thereby restoring testicular damage caused by heat stress. This study confirms that TSA can effectively restore testicular damage caused by heat stress in mice, possibly by inhibiting the TGFβ1/Smad2/Smad3 pathway to suppress apoptosis., (© 2023. The Author(s), under exclusive licence to Cell Stress Society International.)

Background and Aims: Special root structures that can dissolve insoluble phosphorus locked in soil are supposed to contribute not only to the growing status of themselves but also to the neighbouring plants. However, whether dauciform roots have any effect on the neighbouring plants and how does it respond to meadow degradation had not been studied., Methods: Alpine meadows with different degradation statuses were selected and the functional traits of Carex filispica and the co-occurring species Polygonum viviparum were measured to explore their response to degradation, as well as the response of Polygonum viviparum to the dauciform roots of Carex filispica ., Results: The results showed that 1) the number of dauciform roots decreased with the intensifying degradation, positively related to available phosphorus in the soil and negatively related to the aboveground phosphorus of Carex filispica . 2) Carex filispica and Polygonum viviparum are similar in specific leaf area and specific root area, yet different in the phosphorus content. The available phosphorus in the soil was negatively related to the aboveground phosphorus of Carex filispica and positively related to that of Polygonum viviparum . 3) When lightly degraded, the proportion of dauciform roots had positive effects on the aboveground resource-acquiring traits of Polygonum viviparum , which were no longer significant at heavy degradation. 4) Polygonum viviparum and Carex filispica without dauciform roots have similar performance: a decrease of belowground carbon with the increasing degradation, and a trend toward resource conservation with the increasing proportion of dauciform roots, which did not exist in Carex filispica with dauciform roots., Conclusion: Our study found that dauciform roots had a beneficial effect on the resource acquisition of their neighbouring plants. However, due to the uncontrollable nature of natural habitats, whether this effect is stable and strong enough to be performed in ecological restoration requires further lab-controlled studies., 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 © 2023 Fan, Huang, Liu, Jiang and Ji.)

Tartary buckwheat is popular because of its rich nutrients. However, the difficulty in shelling restricts food production. The gene ALCATRAZ (AtALC) plays a key role in silique dehiscence in Arabidopsis thaliana. In this study, an atalc mutant was obtained by CRISPR/Cas9, and a FtALC gene homologous to AtALC was complemented into the atalc mutant to verify its function. Phenotypic observations showed that three atalc mutant lines did not dehiscence, while ComFtALC lines recovered the dehiscence phenotype. The contents of lignin, cellulose, hemicellulose, and pectin in the siliques of all the atalc mutant lines were significantly higher than those in the wild-type and ComFtALC lines. Moreover, FtALC was found to regulate the expression of cell wall pathway genes. Finally, the interaction of FtALC with FtSHP and FtIND was verified by yeast two-hybrid, bimolecular fluorescent complimentary (BIFC) and firefly luciferase completion imaging assays (LCIs). Our findings enrich the silique regulatory network and lay the foundation for the cultivation of easily shelled tartary buckwheat varieties., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The availability of physical activity (PA) facilities in neighborhoods is hypothesized to influence cardiovascular disease (CVD), but evidence from individual-level long-term cohort studies is limited. We aimed to assess the association between neighborhood exposure to PA facilities and CVD incidence., Methods: A total of 4658 participants from the Chinese Multi-provincial Cohort Study without CVD at baseline (2007-2008) were followed for the incidence of CVD, coronary heart disease (CHD), and stroke. Availability of PA facilities was defined as both the presence and the density of PA facilities within a 500-m buffer zone around the participants' residential addresses. Time-dependent Cox regression models were performed to estimate the associations between the availability of PA facilities and risks of incident CVD, CHD, and stroke., Results: During a median follow-up of 12.1 years, there were 518 CVD events, 188 CHD events, and 355 stroke events. Analyses with the presence indicator revealed significantly lower risks of CVD (hazard ratio [HR] 0.80, 95% confidence interval ([CI] 0.65-0.99) and stroke (HR 0.76, 95% CI 0.60-0.97) in participants with PA facilities in the 500-m buffer zone compared with participants with no nearby facilities in fully adjusted models. In analyses with the density indicator, exposure to 2 and ≥ 3 PA facilities was associated with 35% (HR 0.65, 95% CI 0.47-0.91) and 28% (HR 0.72, 95% CI 0.56-0.92) lower risks of CVD and 40% (HR 0.60, 95% CI 0.40-0.90) and 38% (HR 0.62, 95% CI 0.46-0.84) lower risks of stroke compared with those without any PA facilities in 500-m buffer, respectively. Effect modifications between presence of PA facilities and a history of hypertension for incident stroke (P = 0.049), and a history of diabetes for incident CVD (P = 0.013) and stroke (P = 0.009) were noted., Conclusions: Residing in neighborhoods with better availability of PA facilities was associated with a lower risk of incident CVD. Urban planning intervention policies that increase the availability of PA facilities could contribute to CVD prevention., (© 2023. The Author(s).)

Pulse diagnosis equipment used in Traditional Chinese Medicine (TCM) has long been developed for collecting pulse information and in TCM research. However, it is still difficult to implement pulse taking automatically or efficiently in clinical practice. Here, we present a digital protocol for TCM pulse information collection based on bionic pulse diagnosis equipment, which ensures high efficiency, reliability and data integrity of pulse diagnosis information. A four-degree-of-freedom pulse taking platform together with a wrist bracket can satisfy the spatial positioning and angle requirements for individually adaptive pulse acquisition. Three-dimensional reconstruction of a wrist surface and an image localization model are combined to provide coordinates of the acquisition position and detection direction automatically. Three series elastic joints can not only simulate the TCM pulse taking method that "Three fingers in a straight line, the middle finger determining the 'Guan' location and finger pulp pressing on the radial artery," but also simultaneously carry out the force-controlled multi-gradient pressing process. In terms of pulse information integrity, this proposed protocol can generate rich pulse information, including basic individual information, pulse localization distribution, multi-gradient dynamic pulse force time series, and objective pulse parameters, which can help establish the fundamental data sets that are required as the pulse phenotype for subsequent comprehensive analysis of pulse diagnosis. The implementation of this scheme is beneficial to promote the standardization of the digitalized collection of pulse information, the effectiveness of detecting abnormal health status, and the promotion of the fundamental and clinical research of TCM, such as TCM pulse phenomics., Competing Interests: Conflict of InterestsAll authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the participant matter or materials discussed in this manuscript., (© International Human Phenome Institutes (Shanghai) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: The drought and phosphorus deficiency have inevitably become environmental issues globally in the future. The analysis of plants functional trait variation and response strategies under the stress of phosphorus deficiency and drought is important to explore their ability to respond to potential ecological stress., Methods: In this study, Carex breviculmis was selected as the research object, and a 14-week pot experiment was conducted in a greenhouse, with two phosphorus treatment (add 0.5mmol/L or 0.05μmol/L phosphorus) and four drought treatment (add 0-5%PEG6000), totaling eight treatments. Biomass allocation characteristics, leaf anatomical characteristics, biochemical parameters, root morphology, chemical element content, and photosynthetic parameters were measured., Results: The results showed that the anatomical characteristics, chemical elements, and photosynthetic parameters of Carex breviculmis responded more significantly to main effect of phosphorus deficiency. Stomatal width, leaf phosphorus content and maximum net photosynthetic rate decreased by 11.38%, 59.39%, 38.18% significantly ( p <0.05), while the change in biomass was not significant ( p >0.05). Biomass allocation characteristics and root morphology responded more significantly to main effect of drought. Severe drought significantly decreased leaf fresh weight by 61% and increased root shoot ratio by 223.3% compared to the control group ( p <0.05). The combined effect of severe drought and phosphorus deficiency produced the highest leaf N/P ratio (291.1% of the control) and MDA concentration (243.6% of the control). Correlation analysis and redundancy analysis showed that the contributions of phosphorus and drought to functional trait variation were similar. Lower epidermal cell thickness was positively correlated with maximum net photosynthetic rate, leaf phosphorus, chlorophyll ab, and leaf fresh weight ( p <0.05)., Discussion: In terms of response strategy, Carex breviculmis was affected at the microscopic level under phosphorus deficiency stress, but could maintain the aboveground and underground biomass well through a series of mechanisms. When affected by drought, it adopted the strategy of reducing leaf yield and improving root efficiency to maintain life activities. Carex breviculmis could maintain its traits well under low phosphorus and moderate drought, or better conditions. So it may have good ecological service potential in corresponding areas if promoted. This study also provided a reference for plant response to combined drought and phosphorus deficiency stresses., 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 © 2023 Jiang, Tang, Fan, Bai, Wang, Huang, Li and Ji.)

Objective: To evaluate whether the fetal fraction of cell-free DNA at the first and second trimesters is associated with spontaneous preterm birth., Methods: This was a retrospective cohort study with singleton pregnancies who underwent noninvasive prenatal testing. According to pregnancy outcome, eligible patients were divided into a delivery group ≥37 weeks of pregnancy (term group) and <37 weeks of pregnancy (spontaneous preterm group). Stepwise linear regression was used to identify maternal characteristics associated with the fetal fraction of cell-free DNA. Logistic regression analysis was performed to evaluate the association between the fetal fraction of cell-free DNA and spontaneous preterm birth, adjusted for confounding factors., Results: 14,020 cases were included in the study, 13292 cases (94.81%) in the term group and 728 cases (5.19%) in the spontaneous preterm group. The cell-free fraction of fetal DNA was inversely correlated with maternal age and body mass index. Positively correlated with gestational age, fertility, and assisted reproductive technology. After adjusting for the covariates, logistic regression analysis revealed no statistically significant association between the fetal fraction of cell-free DNA and spontaneous preterm birth., Conclusion: In our original study, we found no association between the fetal fraction on NIPT and subsequent spontaneous preterm birth.

Background: Ubiquitin-mediated degradation of the Mas-related G protein-coupled receptor C (MrgC) reduces the number of receptors. However, the specific deubiquitinating enzyme antagonize this process has not been reported. In this study, we investigated the effect of ubiquitin-specific protease-48 (USP48) on bone cancer pain (BCP) and its effect on MrgC., Methods: A mouse model of BCP was established. BCP behaviours of mice were assessed after intrathecal injection of adeno-associated virus (AAV)-USP48. USP48 and MrgC interactions were studied by immunoprecipitation. Overexpression and knockdown of USP48 were conducted in N2a cells to investigate the effect of USP48 on MrgC receptor number and ubiquitination., Results: Spinal cord level USP48 expression was reduced in mice with BCP. Intrathecal injection of AAV-USP48 increased paw withdrawal mechanical threshold and reduced spontaneous flinching in mice. In N2a cells, there were increased number of MrgC receptors after overexpression of USP48 and decreased number of MrgC receptors after knockdown of USP48. USP48 interacted with MrgC and overexpression of USP48 altered the level of ubiquitination of MrgC., Conclusion: USP48 antagonizes ubiquitin-mediated autophagic degradation of MrgC and alleviates BCP in a murine animal model. Our findings may provide a new perspective for the treatment of BCP., Significance: Our finding may provide an important theoretical basis as well as an intervention target for clinical development of drugs for BCP., (© 2023 European Pain Federation - EFIC ®.)

The assessment of bone age is important for evaluating child development, optimizing the treatment for endocrine diseases, etc. And the well-known Tanner-Whitehouse (TW) clinical method improves the quantitative description of skeletal development based on setting up a series of distinguishable stages for each bone individually. However, the assessment is affected by rater variability, which makes the assessment result not reliable enough in clinical practice. The main goal of this work is to achieve a reliable and accurate skeletal maturity determination by proposing an automated bone age assessment method called PEARLS, which is based on the TW3-RUS system (analysis of the radius, ulna, phalanges, and metacarpal bones). The proposed method comprises the point estimation of anchor (PEA) module for accurately localizing specific bones, the ranking learning (RL) module for producing a continuous stage representation of each bone by encoding the ordinal relationship between stage labels into the learning process, and the scoring (S) module for outputting the bone age directly based on two standard transform curves. The development of each module in PEARLS is based on different datasets. Finally, corresponding results are presented to evaluate the system performance in localizing specific bones, determining the skeletal maturity stage, and assessing the bone age. The mean average precision of point estimation is 86.29%, the average stage determination precision is 97.33% overall bones, and the average bone age assessment accuracy is 96.8% within 1 year for the female and male cohorts., (© 2023. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Background: Enhancer of zeste homolog 2 (EZH2), the key catalytic subunit of polycomb repressive complex 2 (PRC2), is overexpressed and plays an oncogenic role in various cancers through catalysis-dependent or catalysis-independent pathways. However, the related mechanisms contributing to ovarian cancer (OC) are not well understood., Methods: The levels of EZH2 and H3K27me3 were evaluated in 105 OC patients by immunohistochemistry (IHC) staining, and these patients were stratified based on these levels. Canonical and noncanonical binding sites of EZH2 were defined by chromatin immunoprecipitation sequencing (ChIP-Seq). The EZH2 solo targets were obtained by integrative analysis of ChIP-Seq and RNA sequencing data. In vitro and in vivo experiments were performed to determine the role of EZH2 in OC growth., Results: We showed that a subgroup of OC patients with high EZH2 expression but low H3K27me3 exhibited the worst prognosis, with limited therapeutic options. We demonstrated that induction of EZH2 degradation but not catalytic inhibition profoundly blocked OC cell proliferation and tumorigenicity in vitro and in vivo. Integrative analysis of genome-wide chromatin and transcriptome profiles revealed extensive EZH2 occupancy not only at genomic loci marked by H3K27me3 but also at promoters independent of PRC2, indicating a noncanonical role of EZH2 in OC. Mechanistically, EZH2 transcriptionally upregulated IDH2 to potentiate metabolic rewiring by enhancing tricarboxylic acid cycle (TCA cycle) activity, which contributed to the growth of OC., Conclusions: These data reveal a novel oncogenic role of EZH2 in OC and identify potential therapeutic strategies for OC by targeting the noncatalytic activity of EZH2., (© 2023. The Author(s).)

Cryo-electron microscopy (cryo-EM) is a widely used structural determination technique. Because of the extremely low signal-to-noise ratio (SNR) of images captured by cryo-EM, clustering single-particle cryo-EM images with high accuracy is challenging. To address this, we proposed an iterative denoising and clustering method based on a deep convolutional variational autoencoder and K-means++. The proposed method contains two modules: a denoising ResNet variational autoencoder (DRVAE), and Balance size K-means++ (BSK-means++). First, the DRVAE is trained in a fully unsupervised manner to initialize the neural network and obtain preliminary denoised images. Second, BSK-means++ is built for clustering denoised images, and images closer to class centers are divided into reliable samples. Third, the training of DRVAE is continued, while the class-average images are used as pseudo supervision of reliable samples to reserve more detailed information of denoised images. Finally, the second and third steps mentioned above can be performed jointly and iteratively until convergence occurs. The experimental results showed that the proposed method can generate reliable class average images and achieve better clustering accuracy and normalized mutual information than current methods. This study confirmed that DRVAE with BSK-means++ could achieve a good denoise performance on single-particle cryo-EM images, which can help researchers obtain information such as symmetry and heterogeneity of the target particles. In addition, the proposed method avoids the extreme imbalance of class size, which improves the reliability of the clustering result.

Background: The brain area stimulated during repetitive transcranial magnetic stimulation (rTMS) treatment is important in altered states of consciousness. However, the functional contribution of the M1 region during the treatment of high-frequency rTMS remains unclear., Objective: The aim of this study was to examine the clinical [the Glasgow coma scale (GCS) and the coma recovery scale-revised (CRS-R)] and neurophysiological (EEG reactivity and SSEP) responses in vegetative state (VS) patients following traumatic brain injury (TBI) before and after a protocol of high-frequency rTMS over the M1 region., Methods: Ninety-nine patients in a VS following TBI were recruited so that their clinical and neurophysiological responses could be evaluated in this study. These patients were randomly allocated into three experimental groups: rTMS over the M1 region (test group; n = 33), rTMS over the left dorsolateral prefrontal cortex (DLPFC) (control group; n = 33) and placebo rTMS over the M1 region (placebo group; n = 33). Each rTMS treatment lasted 20 min and was carried out once a day. The duration of this protocol was a month with 20 treatments (5 times per week) occurring with that time., Results: We found that the clinical and neurophysiological responses improved after treatment in the test, control, and placebo groups; the improvement was highest in the test group compared to that in the control and placebo groups., Conclusions: Our results demonstrate an effective method of high-frequency rTMS over the M1 region for consciousness recovery after severe brain injury., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Xp22.31 deletion and duplication have been described in various studies, but different laboratories interpret pathogenicity differently., Objectives: Our study aimed to refine the genotype-phenotype associations between Xp22.31 copy number variants in fetuses, with the aim of providing data support to genetic counseling., Methods: We retrospectively analyzed karyotyping and single nucleotide polymorphism array results from 87 fetuses and their family members. Phenotypic data were obtained through follow-up visits., Results: The percentage of fetuses carrying the Xp22.31 deletions (9 females, 12 males) was 24.1% (n = 21), while duplications (38 females, 28 males) accounted for 75.9% (n = 66). Here, we noted that the typical region (from 6.4 to 8.1 Mb, hg19) was detected in the highest ratio, either in the fetuses with deletions (76.2%, 16 of 21) or duplications (69.7%, 46 of 66). In female deletion carriers, termination of pregnancy was chosen for two fetuses, and the remaining seven were born without distinct phenotypic abnormalities. In male deletion carriers, termination of pregnancy was chosen for four fetuses, and the remaining eight of them displayed ichthyosis without neurodevelopmental anomalies. In two of these cases, the chromosomal imbalance was inherited from the maternal grandfathers, who also only had ichthyosis phenotypes. Among the 66 duplication carriers, two cases were lost at follow-up, and pregnancy was terminated for eight cases. There were no other clinical findings in the rest of the 56 fetuses, including two with Xp22.31 tetrasomy, for either male or female carriers., Conclusion: Our observations provide support for genetic counseling in male and female carriers of Xp22.31 copy number variants. Most of them are asymptomatic in male deletion carriers, except for skin findings. Our study is consistent with the view that the Xp22.31 duplication may be a benign variant in both sexes., (© 2023. The Author(s).)

Background: Hip or knee osteoarthritis (OA) is one of the main causes of disability worldwide and occurs mostly in the older adults. Total hip or knee arthroplasty is the most effective method to treat OA. However, severe postsurgical pain leading to a poor prognosis. So, investigating the population genetics and genes related to severe chronic pain in older adult patients after lower extremity arthroplasty is helpful to improve the quality of treatment., Methods: We collected blood samples from elderly patients who underwent lower extremity arthroplasty from September 2020 to February 2021 at the Drum Tower Hospital Affiliated to Nanjing University Medical School. The enrolled patients provided measures of pain intensity using the numerical rating scale on the 90th day after surgery. Patients were divided into the case group (Group A) and the control group (Group B) including 10 patients respectively by the numerical rating scale. DNA was isolated from the blood samples of the two groups for whole-exome sequencing., Results: In total, 661 variants were identified in the 507 gene regions that were significantly different between both groups (P < 0.05), including CASP5, RASGEF1A, CYP4B1, etc. These genes are mainly involved in biological processes, including cell-cell adhesion, ECM-receptor interaction, metabolism, secretion of bioactive substances, ion binding and transport, regulation of DNA methylation, and chromatin assembly., Conclusions: The current study shows some variants within genes are significantly associated with severe postsurgical chronic pain in older adult patients after lower extremity arthroplasty, indicating a genetic predisposition for chronic postsurgical pain. The study was registered according to ICMJE guidelines. The trial registration number is ChiCTR2000031655 and registration date is April 6th, 2020., (© 2023. The Author(s).)

In China, dauciform roots were hardly studied and only reported in alpine meadows, where sedges showed a different tendency from other functional groups such as grasses and forbs with degradation. In addition, Carex species were proved to have shifting scaling relationships among LES (leaf economics spectrum) traits under disturbance. So, are these unique performances of sedges related to the presence of dauciform roots, and if so, how? An alpine meadow dominated by Carex filispica in Baima Snow Mountain was selected, and quantitative trampling was performed (0, 50, 200, and 500 passes). The cover and dauciform root properties of Carex filispica were measured, as well as the morphological, chemical traits and biomass of leaves and roots, their correlations and the differences between individuals with and without dauciform roots were analyzed. After the trampling, individuals with dauciform roots showed multiple resource-acquisitive traits: Larger, thicker leaves, more aboveground biomass, higher efficiency of nutrient utilization, and slenderer roots. Additionally, they had a tighter correlation among belowground biomass, morphological and chemical traits, as well as dauciform root properties and morphology of leaves, suggesting that their traits were more related than those without dauciform roots. The presence of dauciform roots in Carex filispica was related to advantages in multiple traits after trampling, which is consistent with and might be responsible for the unique performances of sedges., Competing Interests: This manuscript is approved by all authors for publication with no conflict of interest. The work described was original research that has not been published previously, nor under consideration for publication elsewhere., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Polypropylene (PP) mesh has been widely used in hernia repair as prosthesis material owing to its excellent balanced biocompatibility and mechanical properties. However, abdominal adhesion between the visceral and PP mesh is still a major problem. Therefore, anti-adhesive PP mesh was designed with poly(vinyl alcohol) (PVA) hydrogel and liposomes drug delivery system. First, PVA hydrogel coating was formed on the surface of PP mesh with freezing-thawing processing cycles (FTP). Subsequently, the lyophilized PVA 10 -c-PP was immersed in rapamycin (RPM)-loaded liposome solution until swelling equilibrated to obtain the anti-adhesion mesh RPM@LPS/PVA 10 -c-PP. It was demonstrated that the hydrogel coating can stably fix on the surface of PP mesh even after immersed in PBS solution at 37 °C or 40 °C for up to 30 days. In vitro cell tests revealed the excellent cytocompatibility and the potential to inhibit cell adhesion of the modified PP mesh. Moreover, the anti-adhesive effects of the RPM@LPS/PVA 10 -c-PP mesh was evaluated through in vivo experiments. The RPM@LPS/PVA 10 -c-PP mesh exhibited less adhesion than original PP mesh throughout the duration of implantation. At 30 days, the adhesion score of RPM@LPS/PVA 10 -c-PP mesh was 1.37 ± 0.75, however the original PP was 3 ± 0.71. Furthermore, the results of H&E and Masson trichrome staining proved that the RPM@LPS/PVA 10 -c-PP mesh showed slighter inflammation response and significant looser fibrous tissue surrounded the PP filaments as compared to the native PP. The current findings manifested that this type of RPM@LPS/PVA 10 -c-PP might be a potential candidate for anti-adhesion treatment. DATA AVAILABILITY: Data will be made available on request., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: The present study aimed to develop and validate nomograms to predict the survival of patients with breast invasive micropapillary carcinoma (IMPC) to aid objective decision-making., Design: Prognostic factors were identified using Cox proportional hazards regression analyses and used to construct nomograms to predict overall survival (OS) and breast cancer-specific survival (BCSS) at 3 and 5 years. Kaplan-Meier analysis, calibration curves, the area under the curve (AUC) and the concordance index (C-index) evaluated the nomograms' performance. Decision curve analysis (DCA), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to compare the nomograms with the American Joint Committee on Cancer (AJCC) staging system., Setting: Patient data were collected from the Surveillance, Epidemiology, and End Results (SEER) database. This database holds data related to the incidence of cancer acquired from 18 population-based cancer registries in the US., Participants: We ruled out 1893 patients and allowed the incorporation of 1340 patients into the present study., Results: The C-index of the AJCC8 stage was lower than that of the OS nomogram (0.670 vs 0.766) and the OS nomograms had higher AUCs than the AJCC8 stage (3 years: 0.839 vs 0.735, 5 years: 0.787 vs 0.658). On calibration plots, the predicted and actual outcomes agreed well, and DCA revealed that the nomograms had better clinical utility compared with the conventional prognosis tool. In the training cohort, the NRI for OS was 0.227, and for BCSS was 0.182, while the IDI for OS was 0.070, and for BCSS was 0.078 (both p<0.001), confirming its accuracy. The Kaplan-Meier curves for nomogram-based risk stratification showed significant differences (p<0.001)., Conclusions: The nomograms showed excellent discrimination and clinical utility to predict OS and BCSS at 3 and 5 years, and could identify high-risk patients, thus providing IMPC patients with personalised treatment strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Plant nitrogen (N) uptake preference is a key factor affecting plant nutrient acquisition, vegetation composition and ecosystem function. However, few studies have investigated the contribution of different N sources to plant N strategies, especially during the process of primary succession of a glacial retreat area. By measuring the natural abundance of N isotopes (δ 15 N) of dominant plants and soil, we estimated the relative contribution of different N forms (ammonium-NH 4 + , nitrate-NO 3 - and soluble organic N-DON) and absorption preferences of nine dominant plants of three stages (12, 40 and 120 years old) of the Hailuogou glacier retreat area. Along with the chronosequence of primary succession, dominant plants preferred to absorb NO 3 - in the early (73.5%) and middle (46.5%) stages. At the late stage, soil NH 4 + contributed more than 60.0%, In addition, the contribution of DON to the total N uptake of plants was nearly 19.4%. Thus, the dominant plants' preference for NO 3 - in the first two stages changes to NH 4 + in the late stages during primary succession. The contribution of DON to the N source of dominant plants should not be ignored. It suggests that the shift of N uptake preference of dominant plants may reflect the adjustment of their N acquisition strategy, in response to the changes in their physiological traits and soil nutrient conditions. Better knowledge of plant preferences for different N forms could significantly improve our understanding on the potential feedbacks of plant N acquisition strategies to environmental changes, and provide valuable suggestions for the sustainable management of plantations during different successional stages.

Regional imbalance is a typical feature of economic and social development in China, and place-based policies aimed at promoting balanced regional development may bring challenges to low-carbon goals. This study uses the panel data of China's prefecture-level cities from 2003 to 2019 to investigate the impact of place-based policies on carbon emission efficiency using a quasi-experimental method. Results indicate that place-based policies significantly reduce the regional total-factor carbon emission efficiency. The difference-in-differences method based on propensity score matching and entropy balancing matching consistently supports the finding that carbon emission efficiency decreases after policy intervention. Place-based policies lead to a significant decline in capital allocation efficiency but have an insignificant impact on labor allocation efficiency. Moreover, place-based policies result in the expansion of carbon-intensive industries but hinder the progress of the financial technology of financial institutions. Nevertheless, place-based policies do not lead to the deterioration of environmental quality. Among the advantages of these policies are the significant promotion of regional digitization and increased fiscal expenditure on science and technology. Political promotion, carbon regulation, trade policies, and other conditional factors may be optimally designed to promote low-carbon development in the old revolutionary areas.

Spiny-surfaced species of Prorocentrum form harmful algal blooms, and its taxonomic identity is obscure due to the size and shape variability. Molecular phylogenies reveal two major clades: one for P. cordatum with sequences mainly retrieved as P. minimum, and the other for P. shikokuense with sequences also retrieved as P. dentatum and P. donghaiense. Several closely related clades still need to be characterized. Here, we provide nuclear SSU and LSU rRNA genes, and nuclear ITS region (ITS1-5.8S gene-ITS2) sequences of the strain CCMP3122 isolated from Florida (initially named P. donghaiense) and strains Prorocentrum sp. RCC6871-2 from the Ross Sea, Antarctica. We describe Prorocentrum thermophilum sp. nov. based on the strain CCMP3122, a species also distributed in the open waters of the Gulf of Mexico, New Zealand, and the Arabian Gulf; and Prorocentrum criophilum sp. nov. based on the strain RCC6872, which is distributed in the Antarctic Ocean and Arctic Sea. Prorocentrum thermophilum is roundish (~14 μm long, ~12 μm wide), with an inconspicuous anterior spine-like prolongation under light microscopy, valves with tiny, short knobs (5-7 per μm 2 ), and several (<7) large trichocyst pores (~0.3 μm) in the right valve, as well as smaller pores (~0.15 μm). Prorocentrum criophilum is round in valve view (~11 μm long, 10 μm wide) and asymmetrically roundish in lateral view, the periflagellar area was not discernible under light microscopy, valves with very tiny, short knobs (6-10 per μm 2 ), and at least 12 large pores in the right valve. Other potentially undescribed species of spiny-surfaced Prorocentrum are discussed., (© 2022 Phycological Society of America.)

Sleep deprivation, a common perioperative period health problem, causes ocular discomfort and affects postsurgical pain. However, the mechanism of sleep deprivation-induced increased pain sensitivity is elusive. This study aims to explore the role of ROS in sleep deprivation (SD)-induced hyperalgesia and the underlying mechanism. A 48-h continuous SD was performed prior to the hind paw incision pain modeling in mice. We measured ROS levels, microglial activation, DNA damage and protein levels of iNOS, NLRP3, p-P65 and P65 in mouse spinal dorsal cord. The involvement of ROS in SD-induced prolongation of postsurgical pain was further confirmed by intrathecal injection of ROS inhibitor, phenyl-N-tert-butylnitrone (PBN). Pretreatment of 48-h SD in mice significantly prolonged postsurgical pain recovery, manifesting as lowered paw withdrawal mechanical threshold and paw withdrawal thermal latency. It caused ROS increase and upregulation of iNOS on both Day 1 and 7 in mouse spinal dorsal cord. In addition, upregulation of NLRP3 and p-P65, microglial activation and DNA damage were observed in mice pretreated with 48-h SD prior to the incision. Notably, intrathecal injection of PBN significantly reversed the harmful effects of SD on postsurgical pain recovery, hyperalgesia, microglial activation and DNA damage via the NF-κB signaling pathway. Collectively, ROS increase is responsible for SD-induced hyperalgesia through activating microglial, triggering DNA damage and enhancing NLRP3 inflammasome activity in the spinal dorsal cord., (© 2022. The Author(s).)

Prevalent copy number alteration is the most prominent genetic characteristic associated with ovarian cancer (OV) development, but its role in immune evasion has not been fully elucidated. In this study, we identified RAD21, a key component of the cohesin complex, as a frequently amplified oncogene that could modulate immune response in OV. Through interrogating the RAD21-regulated transcriptional program, we found that RAD21 directly interacts with YAP/TEAD4 transcriptional corepressors and recruits the NuRD complex to suppress interferon (IFN) signaling. In multiple clinical cohorts, RAD21 overexpression is inversely correlated with IFN signature gene expression in OV. We further demonstrated in murine syngeneic tumor models that RAD21 ablation potentiated anti-PD-1 efficacy with increased intratumoral CD8+ T cell effector activity. Our study identifies a RAD21-YAP/TEAD4-NuRD corepressor complex in immune modulation, and thus provides a potential target and biomarker for precision immunotherapy in OV.

Background: Livestock and poultry skeletal muscle development was regulated by a variety of genetic factors playing an essential role in this process. In our de novo sequencing, a missense mutation in ISPD exon 2 showed a selected signature for well-developed muscles. However, the relationship between this mutation and muscle phenotypes remains unclear., Results: Based on the genotype bias of this missense mutation in gamecock chickens, we compared the cross-section of muscle fibers among the individuals with different genotypes with the results showing a genotype preference of this missense mutation in the chickens with hypertrophic muscle fibers. Comparing TT- and CC-genotype ISPD showed that TT- genotype was associated with heavier skeletal muscle and a better effect on myogenesis and myofiber stability. At cellular level, ISPD was identified to inhibit myoblast proliferation, differentiation and antagonize of muscular atrophy., Conclusion: It can be concluded that the missense mutation of Arg84Lys in ISPD was associated with well-developed muscles and demonstrated to improve chicken muscles' development., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)