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Abstract Vigilance refers to being alertly watchful or paying sustained attention to avoid potential threats. Animals in vigilance states reduce locomotion and have an enhanced sensitivity to aversive stimuli so as to react quickly to dangers. Here we report that an unconventional 5-HT driven mechanism operating at neural circuit level which shapes the internal state underlying vigilance behavior in zebrafish and male mice. The neural signature of internal vigilance state was characterized by persistent low-frequency high-amplitude neuronal synchrony in zebrafish dorsal pallium and mice prefrontal cortex. The neuronal synchronization underlying vigilance was dependent on intense release of 5-HT induced by persistent activation of either DRN 5-HT neuron or local 5-HT axon terminals in related brain regions via activation of 5-HTR7. Thus, we identify a mechanism of vigilance behavior across species that illustrates the interplay between neuromodulators and neural circuits necessary to shape behavior states.

Spinal cord injury (SCI) disrupts communication between the brain-derived descending commands and the intraspinal circuits, the central pattern generator (CPG), that execute movements. Dynamic changes in the interaction of the brain-spinal cord as well as in structure-function relationships play a vital role in the determination of neurological function restoration. These changes also have important clinical implications for the treatment of patients with SCI. After SCI, at both brain and spinal cord levels, detour circuits formation and neuronal plasticity have been linked to functional improvement under the condition of spontaneous recovery as well as electrical stimulation- and rehabilitative training-assisted recovery. The principles governing neural circuit remodeling and the neuronal subtypes specifically involved during the recovery from SCI are largely unknown. In the present review, we focus on how multi-level neural circuits are reconstructed after SCI. We highlight some new studies using rodent and zebrafish SCI models that describe how the intraspinal detour circuits are reconstructed and the important roles of spinal excitatory interneurons.

The mechanisms involved in regeneration of the spinal cord after injury are unclear. Here, the authors show that a subpopulation of intraspinal serotonergic neurons localized at the injury site stimulates axonal regrowth of interneurons via 5-HT1B receptor, resulting in recovery of function following SCI in zebrafish.

Cailong Zhang,1 Na Na,2 Li Liu,3 Yingzhu Qiu4 1Department of Arthrology Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China; 2Department of Obstetrics, Qingdao Eighth People’s Hospital, Qingdao 266000, People’s Republic of China; 3Department of Stereotactic Radiotherapy, Qingdao Central Hospital, Qingdao 266000, People’s Republic of China; 4Department of Spine Surgery, Zibo Central Hospital, Zibo 255000, People’s Republic of ChinaCorrespondence: Yingzhu QiuDepartment of Spine Surgery, Zibo Central Hospital, 56 West Gongqingtuan Road, Zhangdian District, Zibo 255000, People’s Republic of ChinaEmail zhuyinc_1969@163.comObjective: Osteosarcoma (OS) is the most common malignant bone tumor in the pediatric population. The main goal of this study is to investigate the role of hsa_circ_0005909 and the underlying signaling pathway involved in OS.Methods: Cell proliferation was measured using a CCK-8 assay kit and clone formation assay. Change of RNA and protein expression was determined using RNA extract and quantitative real time PCR (RT-qPCR) assay and Western blotting, respectively. CircInteractome was used to predict the target of circRNA and starBase v2.0 was used to predict the target of miRNAs. Luciferase assay was used to confirm the predicted results from CircInteractome, starBase v2.0, and MirTarget2.Results: Expression of circ_0005909 was upregulated in both OS tissues and cell lines. The predicted results from CircInteractome, starBase v2.0, and MirTarget2 demonstrated that circ_0005909 could sponge miR-338-3p and that HGMA1 was the direct target of miR-338-3p. Cell viability and cell clones were inhibited by knockdown of circ_0005909 but increased by dual inhibition of circ_0005909 and miR-338-3p. Phosphorylation of ERK, Akt, and PI3K was inhibited by sh-circ_0005909, while this inhibition was repressed by co-transfection of sh-circ_0005909 and HGMA1.Conclusion: Expression of circ_0005909 was upregulated in both OS tissues and cell lines which upregulated expression of HGMA1 through sponging miR-338-3p, resulting in the activation of MAPK-ERK and PI3K-Akt signaling pathways to promote the development of OS.Keywords: hsa_circ_0005909, osteosarcoma, miR-338-3p, HMGA1

In this work, a mechanical degradation of weathering steel and carbon steel caused by strong acid corrosion has been studied in order to clarify the threat of industrial acid vehicle leakage to steel structure bridge. Twenty-seven specimens of Q345 weathering steel plates and Q345 carbon steel plates were immersed in a 36% hydrochloric acid solution at room temperature, with the corrosion time being 0 h, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h, respectively. Subsequently, the obtained specimens were subjected to a uniaxial tensile test to determine the stress-strain curves. The surface morphology was studied by the noncontact surface topography instrument DSX500. By analyzing the degree of mechanical degradation, the constitutive models of test steels under strong acid corrosion were established. The analysis of results shows that the corrosion rate of carbon steel is higher than that of weathering steel. After 72 hours of corrosion, the mass loss rate of carbon steel and weathering steel was 4.77% and 4.30%, respectively. The maximum corrosion pit depth of carbon steel was 25.52 μm higher than that of weathering steel. The constitutive models were in good agreement with the test results, and the resistance to corrosion degradation and deformation of the weathering steel was higher compared to the carbon steel. The results can serve as a guideline for designing steel constructions of improved durability.

Ning Na,1,* Heng Li,1,* Chengfang Xu,2,* Bin Miao,1 Liangqing Hong,1 Zhengyu Huang,1 Qiu Jiang3 1Department of Kidney Transplantation, 2Department of Obstetrics and Genecology, The Third Affiliated Hospital of Sun Yat-sen University, 3Department of Organ Transplantation, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this work Background: Aldolase A (ALDOA) is a glycolytic enzyme that drives the glycolytic metabolic pathway in mammalian cells. The overexpression of ALDOA was observed in a variety of cancers including clear-cell renal cell carcinoma (ccRCC). However, little was known about the clinicopathological significance and prognostic value of ALDOA in ccRCC patients.Methods: The expression of ALDOA was detected using immunohistochemical staining in 162 formalin-fixed, paraffin-embedded ccRCC sections. Prognostic outcomes correlated with ALDOA were examined using Kaplan–Meier analysis and the Cox proportional hazards model.Results: In patients with ccRCC, increased cytoplasmic ALDOA expression was positively associated with tumor size (P=0.021), TNM stages (P=0.034), lymph node metastasis (P=0.020), and overall survival (OS) (P

Invasive fungal infections by Candida albicans frequently cause mortality in immunocompromised patients. Neutrophils are particularly important for fungal clearance during systemic C. albican infection, yet little has been known regarding which surface receptor controls neutrophils’ antifungal activities. CD137, which is encoded by Tnfrsf9, belongs to the tumor necrosis receptor superfamily and has been shown to regulate neutrophils in Gram-positive bacterial infection. Here, we used genetic and immunological tools to probe the involvement of neutrophil CD137 signaling in innate defense mechanisms against systemic C. albicans infection. We first found that Tnfrsf9−/− mice were susceptible to C. albicans infection, whereas injection of anti-CD137 agonistic antibody protected the host from infection, suggesting that CD137 signaling is indispensable for innate immunity against C. albicans infection. Priming of isolated neutrophils with anti-CD137 antibody promoted their phagocytic and fungicidal activities through phospholipase C. In addition, injection of anti-CD137 antibody significantly augmented restriction of fungal growth in Tnfrsf9−/− mice that received wild-type (WT) neutrophils. In conclusion, our results demonstrate that CD137 signaling contributes to defense mechanisms against systemic C. albicans infection by promoting rapid fungal clearance.

Our aim was to investigate whether guinea pig urothelium-derived bioactivities compatible with the existence of urothelium-derived inhibitory factor could be demonstrated by in vitro serial bioassay and whether purinergic P1 receptor agonists, nitric oxide, nitrite or prostaglandins might explain observed activities. In a cascade superfusion system, urothelium-denuded guinea pig ureters were used as bioassay tissues, recording their spontaneous rhythmic contractions in presence of scopolamine. Urothelium-intact or -denuded guinea pig urinary bladders were used as donor tissues, stimulated by intermittent application of carbachol before or during the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the adenosine/P1 nucleoside receptor antagonist 8-(p-sulfophenyl)theophylline (8-PST) or the cyclo-oxygenase inhibitor diclofenac infused to bath donor and bioassay tissues. The spontaneous contractions of bioassay ureters were unaltered by application of carbachol 1-5 µM in the presence of scopolamine 5-30 µM. When carbachol was applied over the urothelium-denuded bladder, the assay ureter contraction rate was unaltered. Introducing carbachol over the everted urothelium-intact bladder significantly inhibited the contraction frequency of the assay ureter, suggesting the transfer of an inhibitory activity from the bladder to the assay ureter. The transmissible inhibitory activity was not markedly antagonized by L-NAME, 8-PST or diclofenac, while L-NAME nearly abolished nitrite release from the urothelium-intact bladder preparations. We suggest that urothelium-derived inhibitory factor is a transmissible entity over a significant distance as demonstrated in this novel cascade superfusion assay and seems less likely to be nitric oxide, nitrite, an adenosine receptor agonist or subject to inhibition by administration of a cyclo-oxygenase inhibitor.

Background: Kidney disease has become a growing public health problem worldwide, and there is an urgent need to develop reliable models for investigating novel and effective treatment strategies. In recent years, kidney organoids, as novel models different from traditional two-dimensional cells and model animals, have attracted more and more attention. Current advances have allowed the generation of kidney organoids from the directed differentiation of induced pluripotent stem cells (iPSCs), which possess similar characteristics to embryonic stem cells (ESCs), but bypass ethical constraints and have a wide range of sources. Summary: Herein, the methods of generating renal organoids from iPSCs, the applications of iPSC-derived renal organoids in disease modeling, drug effectiveness detection, and regenerative medicine as well as the challenges were reviewed. Key messages: iPSC-derived renal organoids can be used to model kidney diseases, and are great models for studying kidney injury and toxicity. Many efforts are needed to finally apply organoids into clinical application.

Abstract Background Sweet sorghum is used mainly as an energy crop and feed crop in arid and semiarid regions, and ensiling is a satisfactory method for preserving high-quality sweet sorghum. The aim of this study was to reveal the dynamics of the fermentation quality, bacterial communities, and fermentation weight loss (FWL) of sweet sorghum silage during fermentation. Methods Sweet sorghum was harvested at the first inflorescence spikelet stage and ensiled without (CK) or with lactic acid bacterial (LAB) additives (L). After ensiling, samples were collected on days 0, 1, 3, 5, 15, 40, and 100 to assess the fermentation quality, bacterial communities, and FWL. Results For CK and L, on day 1, the pH was 5.77 and 5.57, respectively, and the lactic acid (LA) was 1.30 and 2.81 g/kg dry matter (DM), respectively. Compared with CK, L had a lower pH and higher LA from days 1 to 5 (P

Abstract Background The male sterile lines are an important foundation for heterosis utilization in wheat (Triticum aestivum L.). Thereinto, pollen development is one of the indispensable processes of wheat reproductive development, and its fertility plays an important role in wheat heterosis utilization, and are usually influencing by genes. However, these key genes and their regulatory networks during pollen abortion are poorly understood in wheat. Results DEFECTIVE IN TAPETAL DEVELOPMENT AND FUNCTION 1 (TDF1) is a member of the R2R3-MYB family and has been shown to be essential for early tapetal layer development and pollen grain fertility in rice (Oryza sativa L.) and Arabidopsis thaliana. In order to clarify the function of TDF1 in wheat anthers development, we used OsTDF1 gene as a reference sequence and homologous cloned wheat TaTDF1 gene. TaTDF1 is localized in the nucleus. The average bolting time of Arabidopsis thaliana overexpressed strain (TaTDF1-OE) was 33 d, and its anther could be colored normally by Alexander staining solution, showing red. The dominant Mosaic suppression silence-line (TaTDF1-EAR) was blue-green in color, and the anthers were shrimpy and thin. The TaTDF1 interacting protein (TaMAP65) was confirmed using Yeast Two-Hybrid Assay (Y2H) and Bimolecular-Fluorescence Complementation (BiFC) experiments. The results showed that downregulated expression of TaTDF1 and TaMAP65 could cause anthers to be smaller and shrunken, leading to pollen abortion in TaTDF1 wheat plants induced by virus-induced gene-silencing technology. The expression pattern of TaTDF1 was influenced by TaMAP65. Conclusions Thus, systematically revealing the regulatory mechanism of wheat TaTDF1 during anther and pollen grain development may provide new information on the molecular mechanism of pollen abortion in wheat.

ABSTRACT The use of antibiotics has been prohibited in many countries of the world, in response to concerns over the health and welfare concerns of humans and animals. For this reason, scientists have been working on antibiotic alternatives capable of enhancing the productivity and immunity of poultry birds against diseases, as well as the production of healthy and economical poultry meat and eggs. Various alternatives exist and have been used for several decades, such as probiotics, prebiotics, phytobiotics, essential oils, antimicrobial peptides, organic acids, and synbiotics. A relatively new term, “postbiotic,” is used to refer to cell-free supernatants, metabiotics, biogenics, or simply metabolites. It has been suggested that postbiotics are non-viable bacterial products or metabolic byproducts secreted from probiotic microorganisms that have biologic activity in the host. While probiotics are sensitive to heat and oxygen, postbiotics are stable during industrial processing and storage. Postbiotics enhance poultry growth, improve feed efficiency, reduce intestinal pathogens, and promote overall health, making them valuable contributions for sustainable poultry production. They have many important biological properties, such as promoting immunomodulatory, antioxidant, and anti-inflammatory responses. Postbiotics improve intestinal villi, intestinal barrier functions, increase lactic acid production, and reduce Enterobacteriaceae and fecal pH, all of which lead to better immune reaction and health of the gut, as well as superior growth performance. Similarly, postbiotics reduce the plasma cholesterol and triglyceride levels in birds. This review article presents the most recent research investigating the beneficial effects of postbiotics in poultry.

Abstract Greenhouse gases (GHGs) are generated during fermentation in silages, especially in barley silage. However, little is known regarding the dynamics of GHG production in silages during fermentation. In the present study, GHG accumulation and reduction were assessed in barley silage. Barley was harvested at the milk stage and ensiled without (CK) or with two commercial lactic acid bacterial (LAB) additives (L1 or L2). Gas and GHG (CO2, N2O, and CH4) production, fermentation quality, fermentation weight loss (FWL), and bacterial communities were analyzed at d 0, 1, 3, 6, 15, 35, and 90 after ensiling. Gas and GHG production rapidly increased in CK during the first 3 days and in L1 and L2 during the first day and then decreased (P

Abstract Cardiovascular diseases (CVDs) have emerged as a predominant threat to human health, surpassing the incidence and mortality rates of neoplastic diseases. Extracellular vesicles (EVs) serve as vital mediators in intercellular communication and material exchange. Endothelial progenitor cells (EPCs), recognized as precursors of vascular endothelial cells (ECs), have garnered considerable attention in recent years due to the potential therapeutic value of their derived extracellular vesicles (EPC-EVs) in the context of CVDs. This comprehensive review systematically explores the origins, characteristics, and functions of EPCs, alongside the classification, properties, biogenesis, and extraction techniques of EVs, with particular emphasis on their protective roles in CVDs. Additionally, we delve into the essential bioactive components of EPC-EVs, including microRNAs, long non-coding RNAs, and proteins, analyzing their beneficial effects in promoting angiogenesis, anti-inflammatory and anti-oxidant activities, anti-fibrosis, anti-apoptosis, and myocardial regeneration. Furthermore, this review comprehensively investigates the therapeutic potential of EPC-EVs across various CVDs, encompassing acute myocardial infarction, myocardial ischemia–reperfusion injury, atherosclerosis, non-ischemic cardiomyopathies, and diabetic cardiovascular disease. Lastly, we summarize the potential challenges associated with the clinical application of EPC-EVs and outline future directions, aiming to offer a valuable resource for both theoretical insights and practical applications of EPC-EVs in managing CVDs.

Abstract This review examines various methods of reducing acrylamide levels in processed foods, focusing on thermal and nonthermal methods. Acrylamide, which is mainly formed by the Maillard reaction, poses a health risk and therefore requires the implementation of successful mitigation strategies. The processes by which acrylamide is formed, particularly at temperatures above 120°C, such as frying, roasting, and cooking (however, the practical temperature in the inner of foods does not exceed 120°C), serve as a basis for understanding intervention methods. The effectiveness of thermal technologies, including optimization of time and temperature as well as pretreatment and posttreatment techniques, will be studied in detail. In addition, vacuum‐based technologies such as baking, predrying, frying, deep‐frying, and impregnation are examined to shed light on their underlying mechanisms. Advanced thermal techniques such as microwaves and irradiation will be investigated to evaluate their effectiveness in reducing acrylamide. Furthermore, nonthermal methods, including pulsed electric fields, ultrasound treatments, and novel combinations such as pulsed electric fields and blanching, are being investigated. Various enzymatic interventions with asparaginase and glucose oxidase as well as yeast treatments and fermentations offer a wide range of intervention possibilities. The use of additives/coatings and plant extracts, such as edible coatings, polyphenols, and specific ingredient formulations, has shown promise for acrylamide reduction. This paper highlights the commercial implications, future prospects, and barriers to implementation of these methods. By examining different approaches, this comprehensive analysis emphasizes the importance of using different strategies to successfully reduce acrylamide levels in processed foods and provides guidance to the food industry to improve product safety and quality.

Abstract Single-atom catalysts (SACs) have attracted interest in photodynamic therapy (PDT), while they are normally limited by the side effects on normal tissues and the interference from the Tumor Microenvironment (TME). Here we show a TME-activated in situ synthesis of SACs for efficient tumor-specific water-based PDT. Upon reduction by upregulated GSH in TME, C3N4-Mn SACs are obtained in TME with Mn atomically coordinated into the cavity of C3N4 nanosheets. This in situ synthesis overcomes toxicity from random distribution and catalyst release in healthy tissues. Based on the Ligand-to-Metal charge transfer (LMCT) process, C3N4-Mn SACs exhibit enhanced absorption in the red-light region. Thereby, a water-splitting process is induced by C3N4-Mn SACs under 660 nm irradiation, which initiates the O2-independent generation of highly toxic hydroxyl radical (·OH) for cancer-specific PDT. Subsequently, the ·OH-initiated lipid peroxidation process is demonstrated to devote effective cancer cell death. The in situ synthesized SACs facilitate the precise cancer-specific conversion of inert H2O to reactive ·OH, which facilitates efficient cancer therapy in female mice. This strategy achieves efficient and precise cancer therapy, not only avoiding the side effects on normal tissues but also overcoming tumor hypoxia.

Abstract Proteins containing a ubiquitin regulatory X (UBX) domain are cofactors of Cell Division Cycle 48 (CDC48) and function in protein quality control. However, whether and how UBX-containing proteins participate in host–microbe interactions remain unclear. Here we show that MoNLE1, an effector from the fungal pathogen Magnaporthe oryzae, is a core virulence factor that suppresses rice immunity by specifically interfering with OsPUX8B.2. The UBX domain of OsPUX8B.2 is required for its binding to OsATG8 and OsCDC48-6 and controls its 26 S proteasome–dependent stability. OsPUX8B.2 and OsCDC48-6 positively regulate plant immunity against blast fungus, while the high-temperature tolerance heat-shock protein OsBHT, a putative cytoplasmic substrate of OsPUX8B.2–OsCDC48-6, negatively regulates defense against blast infection. MoNLE1 promotes the nuclear migration and degradation of OsPUX8B.2 and disturbs its association with OsBHT. Given the high conservation of MoNLE1 among fungal isolates, plants with broad and durable blast resistance might be generated by engineering intracellular proteins resistant to MoNLE1.

Over the past few years, there has been a gradual increase in the incidence of cancer, affecting individuals at younger ages. With its refractory nature and substantial fatality rate, cancer presents a notable peril to human existence and wellbeing. Hawthorn, a medicinal food homology plant belonging to the Crataegus genus in the Rosaceae family, holds great value in various applications. Due to its long history of medicinal use, notable effects, and high safety profile, hawthorn has garnered considerable attention and plays a crucial role in cancer treatment. Through the integration of modern network pharmacology technology and traditional Chinese medicine (TCM), a range of anticancer active ingredients in hawthorn have been predicted, identified, and analyzed. Studies have shown that ingredients such as vitexin, isoorientin, ursolic acid, and maslinic acid, along with hawthorn extracts, can effectively modulate cancer-related signaling pathways and manifest anticancer properties via diverse mechanisms. This review employs network pharmacology to excavate the potential anticancer properties of hawthorn. By systematically integrating literature across databases such as PubMed and CNKI, the review explores the bioactive ingredients with anticancer effects, underlying mechanisms and pathways, the synergistic effects of drug combinations, advancements in novel drug delivery systems, and ongoing clinical trials concerning hawthorn’s anticancer properties. Furthermore, the review highlights the preventive health benefits of hawthorn in cancer prevention, offering valuable insights for clinical cancer treatment and the development of TCM with anticancer properties that can be used for both medicinal and edible purposes.