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INTRODUCTION: Taurine is a naturally occurring sulfonic acid involved in various physiological and pathological processes, such as the regulation of calcium signaling, immune function, inflammatory response, and cellular aging. It has the potential to predict tumor malignant transformation and formation. Our previous work discovered the elevated taurine in lung cancer patients. However, the precise impact and mechanism of elevated serum taurine levels on lung cancer progression and the suitability of taurine or taurine-containing drinks for lung cancer patients remain unclear. OBJECTIVES: Our study aimed to systematically investigate the role of taurine in lung cancer, with the ultimate goal of contributing novel strategies for lung cancer treatment. METHODS: Lung cancer C57 and nude mice models, RNA sequencing, and stable transfection were applied to explored the effects and mechanisms of taurine on lung cancer. Tissues of 129 non-small cell lung cancer (NSCLC) patients derived from 2014 to 2017 for immunohistochemistry were collected in Taihe Hospital. RESULTS: Low doses of taurine, as well as taurine-infused beverages at equivalent doses, significantly enhanced lung tumor growth. Equally intriguing is that the promoting effect of taurine on lung cancer progression wanes as the dosage increases. The Nuclear factor erythroid 2-like 1 (Nfe2l1 or Nrf1)-reactive oxygen species (ROS)-PD-1 axis may be a potential mechanism for dual role of taurine in lung cancer progression. However, taurine's impacts on lung cancer progression and the anti-tumor function of Nfe2l1 were mainly determined by the immune competence. Taurine inhitited lung tumor growth probably by inhibiting NF-κB-mediated inflammatory responses in nude mice rather than by affecting Nfe2l1 function. As patients age increased, Nfe2l1 gene and protein gradually returned to the levels observed in healthy individuals, but lost its anti-lung cancer effects. CONCLUSIONS: Taurine emerges as a potential biomarker for lung cancer progression, predicting poor prognosis and unsuitability for specific patients. Lung cancer patients, especially young patients, should be conscious of potential effects of taurine-containing drinks. Conversely, taurine or its drinks may be more suitable for older or immune-deficient patients.

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ETHNOPHARMACOLOGICAL RELEVANCE: Pulmonary fibrosis (PF) is progressive and terminal lung disease, which is also the most common sequelae of Corona Virus Disease 2019 (COVID-19) survivors. Unfortunately, there is currently no cure for PF. ShaShen-MaiDong decoction (SMT), a traditional Chinese medicine, has been employed in treating various lung diseases, which may offer potential therapeutic benefits for PF. AIM OF THE STUDY: To investigate the antifibrotic efficacy of SMT and its major active ingredients as well as the underlying mechanisms for treating PF. MATERIALS AND METHODS: Fist, we build the UPLC-MS based qualitative and quantitative profiling for the quality control of SMT. Then, the antifibrotic efficacy of SMT was investigated in bleomycin (BLM)-induced PF mice model. Network pharmacology was used to predict the mechanism and active components of SMT for the treatment of PF, which was further verified in vitro and in vivo. RESULTS: SMT improved the weight loss and attenuated hydroxyproline, inflammatory cytokines, and collagen deposition in BLM-induced PF mice model in a dose-dependent manner. Mechanistically, as predicted by network pharmacology analysis, SMT and its active compounds (kaempferol, quercetin, and isorhamnetin) regulated the mitogen-activated protein kinase (MAPK) signaling pathways, TGF-ß/Smad signaling pathway, and YAP/TAZ signaling pathway, which was further verified in the PF mice and TGF-ß-induced A549 cell model. Moreover, SMT balanced the proportions of increased CD4+ and decreased CD8+ T cells in the peripheral blood of PF mice model. CONCLUSIONS: Considering the high mortality and complex pathogenesis of fibrotic diseases, our results provide novel evidence that SMT would be beneficial for pulmonary fibrosis therapy by modulating MAPK, TGF-ß/Smad, and YAP/TAZ signaling pathways at same time.

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Objective: This study reviews the development of rhubarb processing and the current status of pharmacological research. We summarized the effects of different processing methods on the active compounds, pharmacological effects, and toxicity of rhubarb, as well as the clinical application of different concoctions, providing reference for further pharmacological research and clinical application of rhubarb. Methods: A comprehensive literature review was conducted using databases such as Pubmed, Embase, National Science and Technology Library, Web of science, CNKI, China Science and Technology Journal Database, SinoMed, and the Pharmacopoeia of the People's Republic of China. Search terms included "rhubarb", "raw rhubarb", "wine rhubarb", "cooked rhubarb", "rhubarb charcoal", "herbal processing", "compounds", "pharmacological effects", "inflammation", "gastrointestinal bleeding", and "tumor". Results: Historical records of rhubarb processing date back to the Han Dynasty, with continual innovations. Currently, the types of rhubarb used in traditional Chinese medicine have stabilized to three species: Rheum palmatum L., Rheum tanguticum Maxim.ex Balf. and Rheum officinale Baill. Common concoctions include raw rhubarb, wine rhubarb, cooked rhubarb and rhubarb charcoal. The active compounds of rhubarb are known to defecation, exhibit antibacterial and anti-inflammatory properties, regulate coagulation, protect the digestive system, and possess anti-tumor activities. Guided by Chinese medicine theory, the use of different rhubarb concoctions can enhance specific effects such as purgation to eliminate accumulation, clearing heat and toxins, cooling blood to stop hemorrhages, activating blood circulation to remove blood stasis, and inducing dampness to descend jaundice, thereby effectively treating various diseases. The therapeutic impact of these concoctions on diseases reflects not only in the changes to the active compounds of rhubarb but also in the formulations of traditional Chinese medicine. Processing has also shown advantages in reducing toxicity. Conclusion: Different processing methods alter the active compounds of rhubarb, thereby enhancing its various pharmacological effects and meeting the therapeutic needs of diverse diseases. Selecting an appropriate processing method based on the patient's specific conditions can maximize its pharmacological properties and improve clinical outcomes.

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Establishing the relationships among hierarchical visual attributes of objects in the visual world is crucial for human cognition. The classic convolution neural network (CNN) can successfully extract hierarchical features but ignore the relationships among features, resulting in shortcomings compared to humans in areas like interpretability and domain generalization. Recently, algorithms have introduced feature relationships by external prior knowledge and special auxiliary modules, which have been proven to bring multiple improvements in many computer vision tasks. However, prior knowledge is often difficult to obtain, and auxiliary modules bring additional consumption of computing and storage resources, which limits the flexibility and practicality of the algorithm. In this paper, we aim to drive the CNN model to learn the relationships among hierarchical deep features without prior knowledge and consumption increasing, while enhancing the fundamental performance of some aspects. Firstly, the task of learning the relationships among hierarchical features in CNN is defined and three key problems related to this task are pointed out, including the quantitative metric of connection intensity, the threshold of useless connections, and the updating strategy of relation graph. Secondly, Relational Embedding Convolution (RE-Conv) layer is proposed for the representation of feature relationships in convolution layer, followed by a scheme called use & disuse strategy which aims to address the three problems of feature relation learning. Finally, the improvements brought by the proposed feature relation learning scheme have been demonstrated through numerous experiments, including interpretability, domain generalization, noise robustness, and inference efficiency. In particular, the proposed scheme outperforms many state-of-the-art methods in the domain generalization community and can be seamlessly integrated with existing methods for further improvement. Meanwhile, it maintains comparable precision to the original CNN model while reducing floating point operations (FLOPs) by approximately 50%.

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BACKGROUND: Adverse reactions are prone to occur in the early stage of chemotherapy and can negatively affect the dietary intake and nutritional status of breast cancer (BC) patients. Consequently, they need to participate in health self-management and lifestyle promotion programs. Early multidisciplinary interventions aim to enhance dietary management behavior and quality of life in chemotherapy-treated BC patients. METHODS: This single-blinded, single-center, randomized controlled trial will include 88 females who have not yet started the early or middle stage of the chemotherapy cycle. A random number table will be used randomly assign females to the intervention group or usual group at a 1:1 ratio. The intervention elements are based on the theoretical guidance of the Integrated Theory of Health Behavior Change (ITHBC). A multidisciplinary team (MDT) comprising oncologists, dietitians, nurses, traditional Chinese medicine (TCM) practitioners, and psychologists will provide the intervention. Intervention sessions will be conducted once a week for 8 weeks, beginning in the early or middle stage of the chemotherapy cycle and continuing through admission and a home-based interval chemotherapy period. The intervention includes face-to-face discussions, online meetings, WeChat messaging, and telephone calls. The themes target adverse reactions, dietary information and habits, self-care self-efficacy, treatment self-regulation, dietary supplement and TCM use, social support, weight management, and outcome expectations. The primary outcome is dietary management behavior measured by the Dietary Management Behavior Questionnaire (DMBQ). Secondary outcomes are self-care self-efficacy assessed by the Strategies Used by People to Promote Health (SUPPH); quality of life measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B); and body mass index (BMI) measured by an electronic meter. All participants will be assessed at baseline and immediately, 1 month, 3 months, 6 months, and 12 months after the intervention. DISCUSSION: Early dietary intervention is needed, as diet is one of the most common health self-management behaviors influenced by chemotherapy. Early multidisciplinary interventions may provide a foundation for dietary self-management and improve nutritional status in the survival period. TRIAL REGISTRATION: This intervention protocol was registered with the Chinese Clinical Trials Registry (ChiCTR2300076503, October 10, 2023).

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The piezoelectric properties of two-dimensional semiconductor nanobubbles present remarkable potential for application in flexible optoelectronic devices, and the piezoelectric field has emerged as an efficacious pathway for both the separation and migration of photogenerated electron-hole pairs, along with inhibition of recombination. However, the comprehension and control of photogenerated carrier dynamics within nanobubbles still remain inadequate. Hence, this study is dedicated to underscore the importance of in situ detection and detailed characterization of photogenerated electron-hole pairs in nanobubbles to enrich understanding and strategic manipulation in two-dimensional semiconductor materials. Utilizing frequency modulation kelvin probe force microscopy (FM-KPFM) and strain gradient distribution techniques, the existence of a piezoelectric field in monolayer WS2 nanobubbles was confirmed. Combining w/o and with illumination FM-KPFM, second-order capacitance gradient technique and in situ nanoscale tip-enhanced photoluminescence characterization techniques, the interrelationships among the piezoelectric effect, interlayer carrier transfer, and the funneling effect for photocarrier dynamics process across various nanobubble sizes were revealed. Notably, for a WS2/graphene bubble height of 15.45 nm, a 0 mV surface potential difference was recorded in the bubble region w/o and with illumination, indicating a mutual offset of piezoelectric effect, interlayer carrier transfer, and the funneling effect. This phenomenon is prevalent in transition metal dichalcogenides materials exhibiting inversion symmetry breaking. The implication of our study is profound for advancing the understanding of the dynamics of photogenerated electron-hole pair in nonuniform strain piezoelectric systems, and offers a reliable framework for the separation and modulation of photogenerated electron-hole pair in flexible optoelectronic devices and photocatalytic applications.

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Plastic pollution has become a global environmental problem, and the large number of microorganisms attached to plastic debris in the environment has become a hot topic due to their rapid response to pollutants and environmental changes. In this study, we used high-throughput sequencing to investigate the microbial community structure of and explore the metagenome in the biofilm of two types of plastic debris, polystyrene (PS) and polyethylene terephthalate (PET), and compared them with a water sample collected at the sampling site. The phylum Proteobacteria dominated both the PET and PS samples, at 93.43% and 65.95%, respectively. The metagenome data indicated that the biofilm is enriched with a number of hydrocarbon (petroleum, microplastics, etc.) degrading genes. Our results show that the type of plastic determined the bacterial community structure of the biofilm, while the environment had relatively little effect.

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High-fidelity online 3D scene reconstruction from monocular videos continues to be challenging, especially for coherent and fine-grained geometry reconstruction. The previous learning-based online 3D reconstruction approaches with neural implicit representations have shown a promising ability for coherent scene reconstruction, but often fail to consistently reconstruct fine-grained geometric details during online reconstruction. This paper presents a new on-the-fly monocular 3D reconstruction approach, named GP-Recon, to perform high-fidelity online neural 3D reconstruction with fine-grained geometric details. We incorporate geometric prior (GP) into a scene's neural geometry learning to better capture its geometric details and, more importantly, propose an online volume rendering optimization to reconstruct and maintain geometric details during the online reconstruction task. The extensive comparisons with state-of-the-art approaches show that our GP-Recon consistently generates more accurate and complete reconstruction results with much better fine-grained details, both quantitatively and qualitatively.

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This study aimed to evaluate the safety of Moringa by comparing the effects of different gavage doses of Moringa. The general behavior, body weight, food intake, blood indexes, serum biochemical indexes, and histopathology of rats were used to determine the safety threshold and to provide a reference for the further development and use of Moringa as animal feed. 40 Sprague Dawley rats were selected and given transoral gavage for 28 consecutive days. The T1, T2 and T3 groups were observed for general behavior, body weight, and food intake. Blood and serum biochemical indices were quantified, and histopathology was performed to evaluate the effect and safety of Moringa. The results of the toxicological test showed that (1) Only T1 groups experienced diarrhea. (2) The body weight and food intake of rats in each group were normal compared with the control group. (3) The hematological and serum biochemical indices of rats in the T1 group were significantly different from those of CK but were in the normal range; (4) The results of microscopic examination of the heart, liver, spleen, lung, and kidney of rats in each group were normal, but inflammation occurred in stomach and jejunum of rats in the T1 group, but not in the ileum. The gastrointestinal tract of rats in the T2 and T3 groups were normal. (5) No abnormal death occurred in any of the treatment groups.The results of this study revealed that gavage of Moringa homogenate at a dose of 6 g/kg BW can cause diarrhea in rats. Although there is no pathological effect on weight, food intake, blood and serum biochemical indicators in rats, there are pathological textures in the gastrointestinal tissue caused by diarrhea. Therefore, the safety threshold of Moringa homogenate should be ≤ 3 g/kg BW.

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Sweet osmanthus (Osmanthus fragrans) is famous in China for its flowers and contains four groups: Albus, Luteus, Aurantiacus, and Asiaticus. Understanding the relationships among these groups and the genetic mechanisms of flower color and aroma biosynthesis are of tremendous interest. In this study, we sequenced representative varieties from two of the four sweet osmanthus groups. Multiomics and phylogenetic analyses of varieties from each of the four groups showed that Asiaticus split first within the species, followed by Aurantiacus and the sister groups Albus and Luteus. We show that the difference in flower color between Aurantiacus and the other three groups was caused by a 4-bp deletion in the promoter region of carotenoid cleavage dioxygenase 4 (OfCCD4) that leads to expression decrease. In addition, we identified 44 gene pairs exhibiting significant structural differences between the multiseasonal flowering variety "Rixianggui" in the Asiaticus group and other autumn-flowering varieties. Through correlation analysis between intermediate products of aromatic components and gene expression, we identified eight genes associated with the linalool and α- and ß-ionone biosynthesis pathways. Overall, our study offers valuable genetic resources for sweet osmanthus, while also providing genetic clues for improving the flower color and multiseasonal flowering of osmanthus and other flowers.

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Texture synthesis is a fundamental problem in computer graphics that would benefit various applications. Existing methods are effective in handling 2D image textures. In contrast, many real-world textures contain meso-structure in the 3D geometry space, such as grass, leaves, and fabrics, which cannot be effectively modeled using only 2D image textures. We propose a novel texture synthesis method with Neural Radiance Fields (NeRF) to capture and synthesize textures from given multi-view images. In the proposed NeRF texture representation, a scene with fine geometric details is disentangled into the meso-structure textures and the underlying base shape. This allows textures with meso-structure to be effectively learned as latent features situated on the base shape, which are fed into a NeRF decoder trained simultaneously to represent the rich view-dependent appearance. Using this implicit representation, we can synthesize NeRF-based textures through patch matching of latent features. However, inconsistencies between the metrics of the reconstructed content space and the latent feature space may compromise the synthesis quality. To enhance matching performance, we further regularize the distribution of latent features by incorporating a clustering constraint. In addition to generating NeRF textures over a planar domain, our method can also synthesize NeRF textures over curved surfaces, which are practically useful. Experimental results and evaluations demonstrate the effectiveness of our approach.

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Numerous neurological disorders share a fatal pathologic process known as glutamate excitotoxicity. Among which, ischemic stroke is the major cause of mortality and disability worldwide. For a long time, the main idea of developing anti-excitotoxic neuroprotective agents was to block glutamate receptors. Despite this, there has been little successful clinical translation to date. After decades of "neuron-centered" views, a growing number of studies have recently revealed the importance of non-neuronal cells. Glial cells, cerebral microvascular endothelial cells, blood cells, and so forth are extensively engaged in glutamate synthesis, release, reuptake, and metabolism. They also express functional glutamate receptors and can listen and respond for fast synaptic transmission. This broadens the thoughts of developing excitotoxicity antagonists. In this review, the critical contribution of non-neuronal cells in glutamate excitotoxicity during ischemic stroke will be emphasized in detail, and the latest research progress as well as corresponding therapeutic strategies will be updated at length, aiming to reconceptualize glutamate excitotoxicity in a non-neuronal perspective.

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OBJECTIVES: This study aims to present long-term follow-up results of the reverse dorsolateral proximal phalangeal island flap designed for reconstruction of large fingertip and pulp defects. METHODS: We examined 18 patients who underwent reverse dorsolateral proximal phalangeal island flap surgery to address ≥2.5 cm fingertip and pulp defects. Mean follow-up was 84.4 months. Sensitivity assessments were conducted using the Semmes-Weinstein monofilament and 2-point discrimination tests. Additionally, we evaluated finger joint active range of motion, complications and cold intolerance. RESULTS: Mild venous congestion was observed in 5 flaps. Significant differences were observed in 2-point discrimination and Semmes-Weinstein monofilament tests between the injured and contralateral sides, specifically in the flaps, the dorsal side of the middle phalanx, and the donor site. The flap's mean static 2-point discrimination was 8.3 mm. Restricted distal interphalangeal joint extension was observed in 2 cases. Total active motion with the flap was good or excellent in the injured fingers, but with a significant difference between injured and contralateral fingers. Additionally, 42% of the injured fingers exhibited hook nail deformity, and 2 patients reported cold intolerance. Despite these issues, most patients has high scores for the appearance and satisfaction aspects of the Michigan Hand Outcomes Questionnaire. CONCLUSION: In moderate or larger fingertip defects, the reverse dorsolateral proximal phalangeal island flap serves as an alternative for reconstructing both fingertip and pulp issues. However, this option involves sacrificing some sensation in the dorsum of the middle phalangeal finger and the donor area. LEVEL OF EVIDENCE: IV, therapeutic study.

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This paper explores the application of Set-based Design (SBD) in the design of a dates harvesting machine. Dates are a popular fruit with significant economic importance, especially in Saudi Arabia. However, the process of harvesting them is highly labour-intensive, and there is a need for an automated solution to improve efficiency and reduce costs. The study begins with a comprehensive review of the literature on other fruit-harvesting machines. The research then proposes an architectural design of a dates harvesting machine based on the understanding of the typical fruit harvesting machines. The dates harvesting machine design proposed in this study consists of several sub-assemblies. Each sub-assembly is designed as a set of alternatives, with different configurations of components, mechanisms and materials. The understanding of the customer requirements of typical date farms helped to identify the list of values that are essential to design the dates harvesting machine. These values were filtered and analysed using an analytical hierarchy process to define three key value attributes of 'design performance', 'safety' and 'cost'. The SBD approach helped to evaluate all the possible combinations of subsystems to identify the optimal solution that meets the customer's requirements and constraints. The SBD methodology resulted in the generation of 576 alternative design configurations which were aggressively narrowed down to 48 design solutions and then into 4 solutions where the final optimized design was selected using the PUGH matrix. The narrowing down is based on the combination of trade-off curves, solution performance and the identified key-value attributes. The proposed dates harvesting machine design shows great promise in improving the efficiency and sustainability of harvesting dates, and it can be adapted for use in agricultural applications.

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Aspirin has shown potential for cancer prevention, but a recent large randomized controlled trial found no evidence for a reduction in cancer risk. Given the anti-inflammatory effects of aspirin, systemic inflammatory diseases (SID), such as osteoporosis, cardiovascular diseases, and metabolic diseases, could potentially modify the aspirin-cancer link. To investigate the impact of aspirin in people with SIDs, we conducted an observational study on a prospective cohort of 478,615 UK Biobank participants. Individuals with at least one of the 41 SIDs displayed a higher cancer risk than those without SIDs. Regular aspirin use showed protective effects exclusively in patients with SID, contrasting an elevated risk among their non-SID counterparts. Nonetheless, aspirin use demonstrated preventative potential only for 9 of 21 SID-associated cancer subtypes. Cholesterol emerged as another key mediator linking SIDs to cancer risk. Notably, regular statin use displayed protective properties in patients with SID but not in their non-SID counterparts. Concurrent use of aspirin and statins exhibited a stronger protective association in patients with SID, covering 14 common cancer subtypes. In summary, patients with SIDs may represent a population particularly responsive to regular aspirin and statin use. Promoting either combined or individual use of these medications within the context of SIDs could offer a promising chemoprevention strategy. SIGNIFICANCE: Individuals with systemic inflammatory diseases derive chemoprotective benefits from aspirin and statins, providing a precision cancer prevention approach to address the personal and public challenges posed by cancer.

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The development of natural products for potential new drugs faces obstacles such as unknown mechanisms, poor solubility, and limited bioavailability, which limit the broadened applicability of natural products. Therefore, there is a need for advanced pharmaceutical formulations of active compounds or natural products. In recent years, novel nano-drug delivery systems (NDDS) for natural products, including nanosuspensions, nanoliposomes, micelle, microemulsions/self-microemulsions, nanocapsules, and solid lipid nanoparticles, have been developed to improve solubility, bioavailability, and tissue distribution as well as for prolonged retention and enhanced permeation. Here, we updated the NDDS delivery systems used for natural products with the potential enhancement in therapeutic efficiency observed with nano-delivery systems.

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PURPOSE: PABPN1 acts as a modulator of poly(A) tail length and alternative polyadenylation. This research was aimed to explore the role of PABPN1 in colorectal cancer (CRC). METHODS: Public databases were performed to analyze expression, location, roles of prognosis and tumor immunity and interaction with RNAs and proteins of PABPN1. To investigate PABPN1 expression in tissues, 78 CRC specimens were collected to conduct IHC, and 30 pairs of frozen CRC and corresponding adjacent normal tissues were used to conduct qRT-PCR and WB. In addition, in vitro experiments were then carried out to identify the role of PABPN1 in CRC. RESULTS: Compared with normal tissues, PABPN1 expression was significant higher in CRC. Its high level predicted poor outcome of CRC. Th1 and Treg had significant negative relationships not only with PABPN1 expression, but also with six molecules interacting with PABPN1, including IFT172, KIAA0895L, RECQL4, WDR6, PABPC1 and NCBP1. In addition, PABPN1 had negative relationships with quite a few immune markers, such as CSF1R, IL-10, CCL2 and so on. In cellular experiments, silencing PABPN1 inhibited proliferation and promoted apoptosis in HCT-116 CRC cells. CONCLUSION: In summary, PABPN1 might become a novel biomarker and correlate with tumor immunity in CRC.

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Introduction: In immunotherapy, antibodies are activated to block immune checkpoints, resist tumour immunosuppression, shrink tumours and prevent a recurrence. As the science behind tumour immunotherapy continuously develops and improves, neoadjuvant immunotherapy bears more prominent advantages: antigen exposure not only enhances the degree of tumour-specific T-cell response but also prolongs the duration of actions. In this study, we evaluated the efficacy and safety of McKeown minimally invasive oesophagectomy (McKeown MIO) following neoadjuvant immunotherapy combined with chemotherapy (NICT) in patients with locally advanced oesophageal cancer (OC). Patients and Methods: In this retrospective study, 94 patients underwent either NICT or neoadjuvant chemotherapy (NCT) followed by MIO at our institution from January 2020 to October 2022. We assessed the therapy-related adverse events and perioperative outcomes and compared them between the two groups. Results: After completing at least two cycles of neoadjuvant therapy, all patients underwent McKeown MIO with negative margins within 4-7 weeks. Demographic data of the two cohorts were similar. Regarding perioperative characteristics, the median intraoperative blood loss was 50 ml in the NICT group, lower than that of the NCT group (100 ml, P < 0.05). In addition, the NICT group had significantly more harvested lymph nodes than the NCT group (P < 0.05). No significant differences were found in post-operative complications. The rate of objective response rate in the NICT group was higher than that in the NCT group (88.3% vs. 58.8%). Regarding tumour regression, the number of patients with TRG Grades 1-3 in the NICT group was more than that in the NCT. Adverse events experienced by the two groups included anaemia and elevated transaminase. We found no difference in the adverse events between the two groups. Conclusions: This study showed the efficacy and feasibility of NICT followed by McKeown MIO in treating locally advanced OC.

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The regulation of flowering time is typically governed by transcription factors or epigenetic modifications. Transcript isoforms can play important roles in flowering regulation. Recently, transcript isoforms were discovered in the key genes, OfAP1 and OfTFL1, of the flowering regulatory network in Osmanthus fragrans. OfAP1-b generates a full-length isoform of OfAP1-b1 as well as an isoform of OfAP1-b2 that lacks the C-terminal domain. Although OfAP1-b2 does not possess an activation domain, it has a complete K domain that allows it to form heterodimers. OfAP1-b2 competes with OfAP1-b1 by binding with OfAGL24 to create non-functional and functional heterodimers. As a result, OfAP1-b1 promotes flowering while OfAP1-b2 delays flowering. OfTFL1 produces two isoforms located in different areas: OfTFL1-1 in the cytoplasm and OfTFL1-2 in the nucleus. When combined with OfFD, OfTFL1-1 does not enter the nucleus to repress AP1 expression, leading to early flowering. Conversely, when combined with OfFD, OfTFL1-2 enters the nucleus to repress AP1 expression, resulting in later flowering. Tissue-specific expression and functional conservation testing of OfAP1 and OfTFL1 support the new model's effectiveness in regulating flowering. Overall, this study provides new insights into regulating flowering time by the competition of isoforms.

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The bone matrix has distinct architecture and biochemistry which present a barrier to synthesizing bone-mimetic regenerative scaffolds. To mimic the natural structures and components of bone, biomimetic structural decellularized extracellular matrix (ECM)/regenerated silk fibroin (RSF) scaffolds incorporated with magnetic nanoparticles (MNP) are prepared using a facile synthetic methodology. The ECM/RSF/MNP scaffold is a hierarchically organized and interconnected porous structure with silk fibroin twined on the collagen nanofibers. The scaffold demonstrates saturation magnetization due to the presence of MNP, along with good cytocompatibility. Moreover, the ß-sheet crystalline domain of RSF and the chelated MNP could mimic the deposition of hydroxyapatite and enhance compressive modulus of the scaffold by ≈20%. The results indicate that an external static magnetic field (SMF) with a magnetic responsive scaffold effectively promotes cell migration, osteogenic differentiation, neogenesis of endotheliocytes in vitro, and new bone formation in a critical-size femur defect rat model. RNA sequencing reveals that the molecular mechanisms underlying this osteogenic effect involve calsequestrin-2-mediated Ca2+ release from the endoplasmic reticulum to activate Ca2+ /calmodulin/calmodulin-dependent kinase II signaling axis. Collectively, bionic magnetic scaffolds with SMF stimulation provide a potent strategy for bone regeneration through internal structural cues, biochemical composition, and external physical stimulation on intracellular Ca2+ homeostasis.

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