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Background: Esophageal cancer is one of the most common malignant tumors in the world. It is urgent to prevent the development and progression of esophageal cancer. Cancer stem cells (CSCs) were reported to have the ability to initiate tumorigenesis, and reducing the stem cell-like characteristics of tumors is an important strategy to inhibit the occurrence and development of tumors. miRNAs are key regulators of the stemness of cancer. Here, we aimed to investigate the role and regulatory mechanism of miR-191-3p in the stemness properties of esophageal cancer cells., Methods: Esophageal cancer cells with stable expression of miR-191-3p were established by lentivirus system. CCK-8 assay, transwell assay, wound healing assay were used to evaluate the effect of miR-191-3p on proliferation and metastasis of esophageal cancer cells. The expression of stemness-related markers (NANOG, OCT4, SOX2), ALDH activity, sphere-forming assay and subcutaneous tumor model in nude mice were performed to evaluate the stemness properties of esophageal cancer cells in vitro and in vivo. Dual-luciferase reporter assay was used to verify the molecular mechanism., Result: Here we found that overexpression of miR-191-3p promoted the stemness properties of esophageal cancer cells in vitro and in vivo, including increasing esophageal cancer cell proliferation and metastasis ability, the expression of stemness-related markers NANOG, OCT4, and SOX2, ALDH activity, the number of spheres formed and tumor growth. Bioinformatic analysis and dual-luciferase assay demonstrated that regulator of G protein signaling 1 (RGS1) was the directed target gene of miR-191-3p and attenuated the promotion effect of miR-191-3p on the stemness of esophageal cancer cells. Furthermore, we found that RGS1 knockdown activated the PI3K/AKT pathway by negatively regulating CXCR4 to promote the stemness of esophageal cancer cells., Conclusions: Our findings revealed that RGS1 targeted by miR-191-3p inhibited the stemness of esophageal cancer cells by suppressing the CXCR4/PI3K/AKT pathway, which provide potential prognostic markers and therapeutic targets in the future., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Stachyose is a new functional oligosaccharide that exists naturally in plants, including Stachys sieboldii and Rehmannia glutinosa. Because of its low sweetness, low-calorie content, and robust stability, it has been used to improve food quality and develop functional foods. In addition, owing to its targeted regulatory effect on beneficial microorganisms in the gut and its influence on body health, evidence suggests that stachyose's physiological function may be attributed to its interaction with the host. Notably, stachyose's physiological characteristics and functions are largely affected by its extraction process, purity, physical composition, and chemical structure. Therefore, the present review mainly describes the source, extraction, and purification processes, physiological functions, and applications of stachyose in the food processing industry, which would aid in elucidating the biochemical reactions of stachyose in the body, and its future application prospects in the field of food., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Due to the escalating occurrence and high casualty rates of accidents involving Electric Two-Wheelers (E2Ws), it has become a major safety concern on the roads. Additionally, with the widespread adoption of current autonomous driving technology, a greater challenge has arisen for the safety of vulnerable road participants. Most existing trajectory planning methods primarily focus on the safety, comfort, and dynamics of autonomous vehicles themselves, often overlooking the protection of vulnerable road users (VRUs), typically E2W riders. This paper aims to investigate the kinematic response of E2Ws in vehicle collisions, including the 15 ms Head Injury Criterion (HIC 15 ). It analyzes the impact of key collision parameters on head injuries, establishes injury prediction models for anticipated scenarios, and proposes a trajectory planning framework for autonomous vehicles based on predicting head injuries of VRUs. Firstly, a multi-rigid-body model of two-wheeler-vehicle collision was established based on a real accident database, incorporating four critical collision parameters (initial collision velocity, initial collision position, and collision angle). The accuracy of the multi-rigid-body model was validated through verifications with real fatal accidents to parameterize the collision scenario. Secondly, a large-scale effective crash dataset has been established by the multi-parameterized crash simulation automation framework combined with Monte Carlo sampling algorithm. The training and testing of the injury prediction model were implemented based on the MLP + XGBoost regression algorithm on this dataset to explore the potential relationship between the head injuries of the E2W riders and the crash variables. Finally, based on the proposed injury prediction model, this paper generated a trajectory planning framework for autonomous vehicles based on head collision injury prediction for VRUs, aiming to achieve a fair distribution of collision risks among road users. The accident reconstruction results show that the maximum error in the final relative positions of the E2W, the car, and the E2W rider compared to the real accident scene is 11 %, demonstrating the reliability of the reconstructed model. The injury prediction results indicate that the MLP + XGBoost regression prediction model used in this article achieved an R 2 of 0.92 on the test set. Additionally, the effectiveness and feasibility of the proposed trajectory planning algorithm were validated in a manually designed autonomous driving traffic flow scenario., 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. Published by Elsevier Ltd.)

The role of programmed death ligand 1 (PD-L1) has been extensively investigated in adaptive immune system. However, increasing data show that innate immune responses are also affected by the immune checkpoint molecule. It has been demonstrated that regulation of PD-L1 signaling in macrophages may be a potential therapeutic method for acute respiratory distress syndrome (ARDS). However, the PD-L1 expression pattern in local macrophages and whole lung tissues remains mysterious, hindering optimization of the potential treatment program. Therefore, we aim to determine the PD-L1 expression pattern during ARDS. Our findings show that PD-L1 levels are markedly increased in lipopolysaccharide (LPS)-stimulated lung tissues, which might be attributable to an increase in the gene expression by immune cells, including macrophages and neutrophils. In vitro experiments are performed to explore the mechanism involved in LPS-induced PD-L1 production. We find that PD-L1 generation is controlled by transcription factors early growth response 1 (Egr-1) and CCAAT/enhancer binding protein delta (C/EBPδ). Strikingly, PD-L1 production is enhanced by phosphoinositide-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway via up-regulation of Egr-1 and C/EBPδ expressions. Additionally, we observe that expressions of Egr-1 and C/EBPδ mutually reinforce each other. Moreover, we observe that PD-L1 is protective for ARDS due to its regulatory role in macrophage-associated inflammatory response. In summary, during LPS-induced ARDS, PD-L1 expression, which is beneficial for the disease, is increased via the PI3K-AKT1-Egr-1/C/EBPδ signaling pathway, providing theoretical basis for application of methods controlling PD-L1 signaling in macrophages for ARDS treatment in clinic., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Multifunctional group compounds, 2-acyl-3-sulfonamidobut-2-enoates, are efficiently constructed using solid calcium carbide as an alkyne source through the simultaneous formation of two bonds in one step. The salient features of this protocol are the use of an inexpensive, abundant, and easy-to-use alkyne source as a substitute for flammable and explosive gaseous acetylene, low-cost catalyst, mild conditions, wide substrate scope, high stereoselectivity, satisfactory yield, and simple manipulation. This method can also be extended to the gram scale.

An efficient method for the construction of 5-arylpyrazolo[1,5- a ]pyrimidines using calcium carbide as a solid alkyne source instead of flammable and explosive gaseous acetylene, pyrazole-3-amine and (hetero)aromatic aldehydes as starting materials in the presence of a copper mediator is described. Meanwhile, 2-arylpyrimido[1,2- b ]indazoles are also synthesized under similar conditions using indazole-3-amine as a substitute for pyrazole-3-amine as a starting material. The method has salient features such as the use of an inexpensive and easy-to-handle alkyne source, commercially available substrates, wide functional group tolerance, a low-cost mediator, and simple workup procedures. This protocol can also be extended to gram-scale synthesis.

Accumulating studies have highlighted the great potential of postbiotics in alleviating diseases and protecting host health. Compared with traditional functional foods (such as probiotics and prebiotics), postbiotics have the advantages of a single composition, high physiological activity, long shelf life, easy absorption, and high targeting, etc. The development of postbiotics has led to a wide range of potential applications in functional food and drug development. However, the lack of clinical trial data, mechanism analyses, safety evaluations, and effective regulatory frameworks has limited the application of postbiotic products. This review describes the definition, classification, sources, and preparation methods of postbiotics, the progress and mechanism of preclinical and clinical research in improving host diseases, and their application in food. Strengthen understanding of the recognition and development of related products to lay a theoretical foundation., 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 Author(s).)

Dietary fiber targets the regulation of the intestinal flora and thus affects host health, however, the complex relationship between these factors lacks direct evidence. In this study, the regulatory effects of Konjac glucomannan (KGM) on key metabolites of host intestinal flora were examined by using in vitro fermentation. The results showed that KGM could be utilized by the intestinal flora, which inhibited the relative abundance of Paeniclostridium , Lachnoclostridium , Phascolarctobacterium , and Bacteroides and enriched the relative abundance of Desulfovibrio , Sutterella, etc. Fermentation is accompanied by the production of short-chain acids, including acetic and propionic acids. Metabolomics revealed that KGM significantly promoted amino acid metabolism, lipid metabolism, and the biosynthesis of other secondary metabolites. Correlation analysis results showed that the increase of panose and N-(1-carboxy-3-carboxanilidopropyl) alanylproline content was positively correlated with the relative abundance of Megamonas . These results provide evidence that KGM affects host health by regulating gut microbiota and its metabolites., Competing Interests: None., (© 2024 The Author(s).)

Citrus fiber, a by-product of citrus processing that has significant nutritional and bioactive properties, has gained attention as a promising raw material with extensive developmental potential in the food, pharmaceutical, and feed industries. However, the lack of in-depth understanding regarding citrus fiber, including its structure, modification, mechanism of action, and potential applications is holding back its development and utilization in functional foods and drugs. This review explores the status of extraction methods and modifications applied to citrus fiber to augment its health benefits. With the aim of introducing readers to the potential health benefits of citrus fibers, we have placed special emphasis on their regulatory mechanisms in the context of various conditions, including type 2 diabetes mellitus, cardiovascular disease, obesity, and cancer. Furthermore, this review highlights the applications and prospects of citrus fiber, aiming to provide a theoretical basis for the utilization and exploration of this valuable resource., 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.)

Cacumen platycladi (CP) is a frequently used traditional Chinese medicine to treat hair loss. In this study, CP fermented by Lactiplantibacillus plantarum CCFM1348 increased the proliferation of human dermal papilla cells. In an in vivo assay, compared to nonfermented CP, postbiotics (fermented CP) and synbiotics (live bacteria with nonfermented CP) promoted hair growth in mice. The Wnt/β-catenin signaling pathway plays crucial roles in the development of hair follicles, including growth cycle restart and maintenance. Both postbiotics and synbiotics upregulated β-catenin, a major factor of the Wnt/β-catenin signaling pathway. Postbiotics and synbiotics also increased the vascular endothelial growth factor expression and decreased the BAX/Bcl2 ratio in the dorsal skin of mice. These results suggest that fermented CP by L. plantarum CCFM1348 may promote hair growth through regulating the Wnt/β-catenin signaling pathway, promoting the expression of growth factors and reducing apoptosis.

With the threshold for crop growth data collection having been markedly decreased by sensor miniaturization and cost reduction, unmanned aerial vehicle (UAV)-based low-altitude remote sensing has shown remarkable advantages in field phenotyping experiments. However, the requirement of interdisciplinary knowledge and the complexity of the workflow have seriously hindered researchers from extracting plot-level phenotypic data from multisource and multitemporal UAV images. To address these challenges, we developed the Integrated High-Throughput Universal Phenotyping (IHUP) software as a data producer and study accelerator that included 4 functional modules: preprocessing, data extraction, data management, and data analysis. Data extraction and analysis requiring complex and multidisciplinary knowledge were simplified through integrated and automated processing. Within a graphical user interface, users can compute image feature information, structural traits, and vegetation indices (VIs), which are indicators of morphological and biochemical traits, in an integrated and high-throughput manner. To fulfill data requirements for different crops, extraction methods such as VI calculation formulae can be customized. To demonstrate and test the composition and performance of the software, we conducted case-related rice drought phenotype monitoring experiments. In combination with a rice leaf rolling score predictive model, leaf rolling score, plant height, VIs, fresh weight, and drought weight were efficiently extracted from multiphase continuous monitoring data. Despite the significant impact of image processing during plot clipping on processing efficiency, the software can extract traits from approximately 500 plots/min in most application cases. The software offers a user-friendly graphical user interface and interfaces for customizing or integrating various feature extraction algorithms, thereby significantly reducing barriers for nonexperts. It holds the promise of significantly accelerating data production in UAV phenotyping experiments., Competing Interests: Competing interests: The authors declare that they have no competing interests. Mention of a commercial product is solely for the purpose of providing specific information and should not be construed as a product endorsement by the authors or the institutions with which the authors are affiliated., (Copyright © 2024 Botao Wang et al.)

Optical box traps offer new possibilities for quantum-gas experiments. Building on their exquisite spatial and temporal control, we propose to engineer system-reservoir configurations using box traps, in view of preparing and manipulating topological atomic states in optical lattices. First, we consider the injection of particles from the reservoir to the system: this scenario is shown to be particularly well suited to activating energy-selective chiral edge currents, but also to prepare fractional Chern insulating ground states. Then, we devise a practical evaporative-cooling scheme to effectively cool down atomic gases into topological ground states. Our open-system approach to optical-lattice settings provides a new path for the investigation of ultracold quantum matter, including strongly correlated and topological phases.

Spherical nucleic acids (SNAs) have been used to construct various nanobiosensors with gold nanoparticles (AuNPs) as nuclei. The SNAs play a critical role in biosensing due to their various physical and chemical properties, programmability, and specificity recognition ability. In this study, CRISPR-responsive self-assembled spherical nucleic acid (CRISPR-rsSNA) detection probes were constructed by conjugating fluorescein-labeled probes to the surface of AuNPs to improve the sensing performance. Also, the mechanism of ssDNA and the role of different fluorescent groups in the self-assembly process of CRISPR-rsSNA were explored. Then, CRISPR-rsSNA and reverse transcription-recombinase polymerase amplification (RT-RPA) were combined to develop an ultrasensitive fluorescence-detection strategy for norovirus. In the presence of the virus, the target RNA sequence of the virus was transformed and amplified by RT-RPA. The resulting dsDNA activated the trans-cleavage activity of CRISPR cas12a, resulting in disintegrating the outer nucleic acid structure of the CRISPR-rsSNA at a diffusible rate, which released reporter molecules. Norovirus was quantitated by fluorescence detection. This strategy facilitated the detection of the norovirus at the attomolar level. An RT-RPA kit for norovirus detected would be developed based on this method. The proposed method would be used for the detection of different viruses just by changing the target RNA and crRNA of the CRISPR cas12a system which provided a foundation for high-throughput detection of various substances.

Gentamicin (GM) is one of the commonly used antibiotics in the aminoglycoside class but is ototoxic, which constantly impacts the quality of human life. Pyrroloquinoline quinone (PQQ) as a redox cofactor produced by bacteria was found in soil and foods that exert an antioxidant and redox modulator. It is well documented that the PQQ can alleviate inflammatory responses and cytotoxicity. However, our understanding of PQQ in ototoxicity remains unclear. We reported that PQQ could protect against GM-induced ototoxicity in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells in vitro. To evaluate reactive oxygen species (ROS) production and mitochondrial function, ROS and JC-1 staining, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) measurements in living cells, mitochondrial dynamics analysis was performed. GM-mediated damage was performed by reducing the production of ROS and inhibiting mitochondria biogenesis and dynamics. PQQ ameliorated the cellular oxidative stress and recovered mitochondrial membrane potential, facilitating the recovery of mitochondrial biogenesis and dynamics. Our in vitro findings improve our understanding of the GM-induced ototoxicity with therapeutic implications for PQQ., (© 2023 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.)

Background: Middle turbinectomy (MT) has always been controversial. MT significantly alters the anatomy and redistributes the inhaled air. The current study is designed to quantify the effect of MT with varying resection volumes on airflow and associated pollen inhalation exposure characteristics in the nasal airways., Methods: Six realistic models following bilateral comprehensive Functional Endoscopic Sinus Surgery (FESS) deriving from CT images were constructed and their corresponding post-MT models with four types of MT procedures were virtually conducted. Inhalation exposure to pollen particles was simulated by the Computational Fluid-Particle Dynamics (CFPD) approach and validated through in vitro experiments., Results: Following the excision of the middle turbinate, a significant escalation in airflow was observed within the upper-middle region of the nasal cavities. Pollen deposition was observed to be more prominent in the nasal septum, laryngopharynx, and maxillary sinus, varying with the types of MT procedures. Notably, particles with diameters smaller than 50 μm exhibited two distinct "high peaks" and three "small peaks" within the nasal airways., Conclusion: MT resulted in increased airflow volume within the upper-middle region of the nasal cavities. Following MT, notable shifts in pollen particle deposition hot spots were observed, transitioning from the nasal vestibule, nasal septum, and middle meatus to the nasal septum and laryngopharynx. These findings are anticipated to contribute valuable perspectives on pollen inhalation exposure risk assessments following diverse MT surgical interventions., 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.)

Pectin is a complex and functionally rich natural plant polysaccharide that is widely used in food, medical, and cosmetic industries. It can be modified to improve its properties and expand its applications. Modification methods for natural pectin can be divided into physical, chemical, enzymatic, and compound methods. Different modification methods can result in modified pectins (MPs) exhibiting different physicochemical properties and biological activities. The objectives of this paper were to review the various pectin modification methods explored over the last decade, compare their differences, summarize the impact of different modification methods on the biological activity and physicochemical properties of pectin, and describe the applications of MPs in food and pharmaceutical fields. Finally, suggestions and perspectives for the development of MPs are discussed. This review offers a theoretical reference for the rational and efficient processing of pectin and the expansion of its applications., 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.)

As a member of the PGAMs family, PGAM2 has been proved to catalyze the reversible reaction of 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) in the glycolytic pathway. However, it is unclear whether PGAM2 has a role in regulating differentiation in goat intramuscular preadipocytes. Here, this study was carried to clone the open reading frame (ORF) of goat PGAM2 , elucidate its molecular and expressional characteristics, and evaluate the involvement in adipogenesis of intramuscular preadipocytes. According to our findings, the cloned goat PGAM2 gene was 784 bp in full length, including 762 bp of ORF and encoding a protein of 253 amino acids. The expressional level of PGAM2 peaked at 48 hours after induced adipogenic differentiation and was highest in the skeletal muscle of triceps. Moreover, overexpression of PGAM2 transfected by its overexpression plasmid promotes lipid accumulation of goat intramuscular adipocyte as shown by Oil Red O and bodipy staining, accompanied by up-regulating the mRNA levels of peroxisome proliferator-activated receptor γ ( PPARγ ) ( p  < 0.001), sterol regulatory element-binding protein 1 ( SREBP1 ) ( p  < 0.001), CCAAT/Enhancer-binding protein α ( C/EBPα ) ( p  < 0.01) and lipoprotein lipase ( LPL ) ( p  < 0.01). Taken together, these findings indicate that PGAM2 is a positive regulator for goat intramuscular adipocytes and provide new insights into improvement intramuscular fat deposition in goat meat.

To understand inhaled nanoparticle transport and deposition characteristics in pediatric nasal airways with adenoid hypertrophy (AH), with a specific emphasis on the olfactory region, virtual nanoparticle inhalation studies were conducted on anatomically accurate child nasal airway models. The computational fluid-particle dynamics (CFPD) method was employed, and numerical simulations were performed to compare the airflow and nanoparticle deposition patterns between nasal airways with nasopharyngeal obstruction before adenoidectomy and healthy nasal airways after virtual adenoidectomy. The influence of different inhalation rates and exhalation phase on olfactory regional nanoparticle deposition features was systematically analyzed. We found that nasopharyngeal obstruction resulted in significant uneven airflow distribution in the nasal cavity. The deposited nanoparticles were concentrated in the middle meatus, septum, inferior meatus and nasal vestibule. The deposition efficiency (DE) in the olfactory region decreases with increasing nanoparticle size (1-10 nm) during inhalation. After adenoidectomy, the pediatric olfactory region DE increased significantly while nasopharynx DE dramatically decreased. When the inhalation rate decreased, the deposition pattern in the olfactory region significantly altered, exhibiting an initial rise followed by a subsequent decline, reaching peak deposition at 2 nm. During exhalation, the pediatric olfactory region DE was substantially lower than during inhalation, and the olfactory region DE in the pre-operative models were found to be significantly higher than that of the post-operative models. In conclusions, ventilation and particle deposition in the olfactory region were significantly improved in post-operative models. Inhalation rate and exhalation process can significantly affect nanoparticle deposition in the olfactory region., Competing Interests: Declaration of competing interest All authors report no potential competing interests. The content of the manuscript has not been published or submitted for publication elsewhere, and all authors have approved the manuscript for the submission to Computers in Biology and Medicine., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Lactulose is a common component in foods. However, the effect of lactulose on intestinal flora and overall metabolic levels remains unclear. Therefore, this study aims to explore the regulative role of lactulose on intestinal flora and serum metabolites via in vitro simulated colonic fermentation model and in vivo colitis mouse model. The results showed that lactulose significantly enriched beneficial bacteria including Dubosiella and Bifidobacterium , and reduced pathogenic bacteria such as Fusobacterium . Moreover, lactulose significantly inhibited dextran sodium sulfate-induced body weight loss, colon shortening, colonic inflammatory infiltration, and pro-inflammatory cytokines IL-6, TNF-α, IL-17, and IL-1β. Lactulose significantly affected serum metabolome in colitis mice and total 24 metabolites representing a high inter-group difference were obtained. Correlation analysis revealed that the changes in serum metabolites were closely associated with the role of intestinal flora, and thus affected phenotypic indicators. Our study provides a reference for nutritional characteristics and application scenarios of dietary lactulose., 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., (© 2023 The Author(s).)

To improve the diagnostic accuracy of adenoid hypertrophy (AH) in children and prevent further complications in time, it is important to study and quantify the effects of different degrees of AH on pediatric upper airway (UA) aerodynamics. In this study, based on computed tomography (CT) scans of a child with AH, UA models with different degrees of obstruction (adenoidal-nasopharyngeal (AN) ratio of 0.9, 0.8, 0.7, and 0.6) and no obstruction (AN ratio of 0.5) were constructed through virtual surgery to quantitatively analyze the aerodynamic characteristics of UA with different degrees of obstruction in terms of the peak velocity, pressure drop (△P), and maximum wall shear stress (WSS). We found that two obvious whirlpools are formed in the anterior upper part of the pediatric nasal cavity and in the oropharynx, which is caused by the sudden increase in the nasal cross-section area, resulting in local flow separation and counterflow. In addition, when the AN ratio was ≥ 0.7, the airflow velocity peaked at the protruding area in the nasopharynx, with an increase 1.1-2.7 times greater than that in the nasal valve area; the △P in the nasopharynx was significantly increased, with an increase 1.1-6.8 times greater than that in the nasal cavity; and the maximum WSS of the posterior wall of the nasopharynx was 1.1-4.4 times larger than that of the nasal cavity. The results showed that the size of the adenoid plays an important role in the patency of the pediatric UA., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The nasal swell body（NSB） consists of the nasal septal cartilage, nasal bone, and swollen soft tissue, all of which are visible during endoscopic and imaging examinations. Although the function of the NSB remains uncertain, there is evidence to suggest that it plays a vital role in regulating nasal airflow and filtering inhaled air. Based on anatomical and histological evidence, it is hypothesized that the NSB is indispensable in these processes. This study aims to investigate the impact of NSB on nasal aerodynamics and the deposition of allergen particles under physiological conditions. Methods: The three-dimensional （3D） nasal models were reconstructed from computed tomography （CT） scans of the paranasal sinus and nasal cavity in 30 healthy adult volunteers from Northwest China, providing basis for the construction of models without NSB following virtual NSB-removal surgery. To analyze the distribution of airflow in the nasal cavity, nasal resistance, heating and humidification efficiency, and pollen particle deposition rate at various anatomical sites, we employed the computed fluid dynamics（CFD） method for numerical simulation and quantitative analysis. In addition, we created fully transparent segmented nasal cavity models through 3D printing, which were used to conduct bionic experiments to measure nasal resistance and allergen particle deposition. Results: ①The average width and length of the NSB in healthy adults in Northwest China were （12.85±1.74） mm and （28.30±1.92） mm, respectively. ②After NSB removal, there was no significant change in total nasal resistance, and cross-sectional airflow velocity remained essentially unaltered except for a decrease in topical airflow velocity in the NSB plane. ③There was no discernible difference in the nasal heating and humidification function following the removal of the NSB; ④After NSB removal, the deposition fraction（DF） of Artemisia pollen in the nasal septum decreased, and the DFs post-and pre-NSB removal were（22.79±6.61）% vs （30.70±12.27）%, respectively; the DF in the lower airway increased, and the DFs post-and pre-NSB removal were（24.12±6.59）% vs （17.00±5.57）%, respectively. Conclusion: This study is the first to explore the effects of NSB on nasal airflow, heating and humidification, and allergen particle deposition in a healthy population. After NSB removal from the healthy nasal cavities: ①nasal airflow distribution was mildly altered while nasal resistance showed no significantly changed; ②nasal heating and humidification were not significantly changed; ③the nasal septum's ability to filter out Artemisia pollen was diminished, which could lead to increased deposition of Artemisia pollen in the lower airway., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

It has been reported that colitis is one of risk factors in colorectal cancer (CRC). Intervention of intestinal inflammation and in the early stage of tumorigenesis is of great significance to control the incidence and mortality of CRC. In recent years, natural active products of traditional Chinese medicine have been confirmed that they had made great progress in disease prevention. Here, we showed that Dioscin, a natural active product of Dioscorea nipponica Makino, inhibited initiation and tumorigenesis of AOM/DSS-induced colitis-associated colon cancer (CAC), including alleviating colonic inflammation, improving intestinal barrier function and decreasing tumor burden. In addition, we also explored the immunoregulatory effect of Dioscin on mice. The results showed that Dioscin modulated M1/M2 macrophages phenotype in spleen and decreased monocytic myeloid-derived suppressor cells (M-MDSCs) population in blood and spleen of mice. The in vitro assay demonstrated that Dioscin promoted M1 as well as inhibited M2 macrophages phenotype in LPS- or IL-4-induced bone marrow-derived macrophages (BMDMs) model. Based on the plasticity of MDSCs and its ability to differentiate into M1/M2 macrophages, we here found that Dioscin increased M1- and decreased M2-like phenotype during the process of MDSCs differentiation in vitro, suggesting Dioscin promoted MDSCs differentiate into M1 as well as inhibited its differentiation into M2 macrophages. Taken together, our study indicated that Dioscin had the inhibitory effect on the initial of tumorigenesis at early stage of CAC via the ant-inflammatory effect, which provided a natural active candidate for effective prevention of CAC., 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. Published by Elsevier B.V.)

Whether proline deficiency is a metabolic vulnerability in colorectal tumors is unknown. The aim of this study was to investigate the effects of proline metabolism-related genes and exogenous proline on the progression of colorectal cancer (CRC). We aimed to further clarify the role of pyrroline-5-carboxylate reductase (PYCR) 2, a key enzyme of proline synthesis, in the regulation of colorectal intraperitoneal metastatic tumors. This study was carried out based on The Cancer Genome Atlas (TCGA) data, database analysis, single-cell functional analysis, tissue microarray, cell experiments, and animal models. We found that, PYCR2 mRNA and protein levels were upregulated in CRC. The mRNA level of PYCR2 was closely related to the prognosis and tumor metastasis of CRC patients. The upregulated PYCR2 expression was at least partly due to low promoter methylation levels. The nomogram constructed based on PYCR2 expression and clinical characteristics of CRC showed good accuracy in predicting lymph node metastasis. Pycr2 knockdown inhibited epithelial-mesenchymal transition (EMT) of mouse CRC cells. Proline supplementation did not rescue the inhibition of mouse CRC cell proliferation and migration by Pycr2 knockdown. Proline supplementation also did not rescue the suppression of subcutaneous tumors and intraperitoneal metastatic tumors in mice by Pycr2 knockdown. PYCR2 co-expressed genes in TCGA-CRC were enriched in epigenetic modification-related biological processes and molecular functions. Four small molecules with the lowest binding energy to the PYCR2 protein were identified. Collectively, Pycr2 knockdown inhibited mouse CRC progression in a proline-independent approach. PYCR2 may be a promising tumor metastasis predictor and therapeutic target in CRC., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Hyaluronic acid (HA) is key to the stability of the internal environment of tissues. HA content in tissues gradually decreases with age, causing age-related health problems. Exogenous HA supplements are used to prevent or treat these problems including skin dryness and wrinkles, intestinal imbalance, xerophthalmia, and arthritis after absorption. Moreover, some probiotics are able to promote endogenous HA synthesis and alleviate symptoms caused by HA loss, thus introducing potential preventative or therapeutic applications of HA and probiotics. Here, we review the oral absorption, metabolism, and biological function of HA as well as the potential role of probiotics and HA in increasing the efficacy of HA supplements., 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 © 2022 Elsevier Ltd. All rights reserved.)

Periodontitis has a known association with pathological calcification in the cardiovascular system. Considering the close anatomic and circulatory association between dental pulp and the periodontium, this study aimed to evaluate the prevalence of pulp calcification (PC) under different periodontal conditions, as well as the associations of PC with the degree of periodontal damage, via cone beam computed tomography (CBCT) examination. In this study, 55 patients were categorized into three groups according to periodontal condition: group 1 (healthy controls), group 2 (periodontitis stage I-II), and group 3 (periodontitis stage III-IV). PC and radiographic bone loss (RBL) was assessed by CBCT in sagittal, axial, and coronal views, and statistical analyses were conducted. PC was identified in 378 of 1170 teeth (32.3%). The prevalence significantly differed among the three groups (P < 0.001). Group 2 had a 2.43-fold (P < 0.001, 95% confidence interval [CI] 1.64-3.61) higher risk of PC than group 1; and the risk of PC was 3.04-fold (P < 0.001, 95% CI 2.06-4.48) higher in group 3 than group 1. Teeth with more severe RBL exhibited a higher prevalence of PC (P < 0.001). Molar teeth had a higher risk of PC than incisors and premolars. In conclusion, the occurrence of PC is related to the periodontal state, and the prevalence of PC is higher in teeth with periodontitis; tooth type and periodontitis status are important risk factors for PC., (© 2022. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Excessive residues of semicarbazide (SEM) can accumulate in animals after the original drug has been abused, posing a risk to human health. Herein, based on multifunctional silica-initiated dual mode signal response, a novel competitive-type immunosensor was constructed for ultrasensitive detection of SEM. As a preliminary signal amplification platform for immunosensors, polyethyleneimine reduced graphene oxide composite gold nanorods (PEI-rGO/AuNRs) modified gold electrodes (AuE) provide a high specific surface area and high electrical conductivity. The thionine-aminated silica nanospheres-AuPt (thi-SiO 2 @AuPt) were synthesized by a racile coprecipitation method for enzyme immobilization and redox species loading. The multifunctional silica nanosphere conjugated with labeling antibodies (Ab 2 ) was employed as an immunoprobe. The per unit concentration target of SEM can be determined by differential pulse voltammetry (DPV) to detect the thi loaded on the immunoprobe, which can also be determined by square wave voltammetry (SWV) to detect the current generated by the reaction system of H 2 O 2 and hydroquinone (HQ) catalyzed by the immunoprobe with peroxidase. Under optimal conditions, the proposed immunosensor displayed a wide linear range from 1 μg-0.01 ng/mL and low detection limits (S/N = 3) of 0.488 pg/mL and 0.0157 ng/mL, respectively. Ultimately, the developed method exhibits excellent performance in practical applications, providing promising probabilities for SEM detection., 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 © 2022 Elsevier B.V. All rights reserved.)

Previously, we isolated a novel Phocaeicola strain, Phocaeicola faecalis FXJYN30E22, from the feces of a healthy human from China. Metagenomic analysis revealed that the distribution of FXJYN30E22 differed in the intestinal tract of different hosts. We aimed to determine whether FXJYN30E22 protects against ulcerative colitis by employing a mouse model. In this study, dextran sulfate sodium was used to construct the UC model. The disease activity index, colon length, body weight changes, and histological scores were used as the pathological indicators to assess the anti-inflammatory effect of P. faecalis FXJYN30E22. Further, cytokine levels, tight junction mRNA expression levels, and short-chain fatty acid (SCFA) concentrations were also analyzed. Phocaeicola faecalis FXJYN30E22 could reduce the DSS-induced increase in DAI score, and enhance the colon length and body weight. Phocaeicola faecalis FXJYN30E22 could enhance TJ protein concentration and modulate the level of cytokines to reach levels close to those of the control group. FXJYN30E22 could also upregulate the concentrations of SCFA, which include acetate and butyrate. Based on the correlation analysis, four factors, including interleukin (IL)-6, IL-10, IL-1β levels, and propionate concentration, were related to the protective roles of FXJYN30E22 in UC mice to different degrees. According to an analysis of the genomic information, the potential protective effects of strain FXJYN30E22 may be associated with the secretion of SCFA by specific genes. These findings suggest that oral P. faecalis FXJYN30E22 could help maintain the epithelial barrier by regulating cytokine levels and secreting SCFA., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The heading date and effective tiller percentage are important traits in rice, and they directly affect plant architecture and yield. Both traits are related to the ratio of the panicle number to the maximum tiller number, referred to as the panicle ratio (PR). In this study, an automatic PR estimation model (PRNet) based on a deep convolutional neural network was developed. Ultra-high-definition unmanned aerial vehicle (UAV) images were collected from cultivated rice varieties planted in 2384 experimental plots in 2019 and 2020 and in a large field in 2021. The determination coefficient between estimated PR and ground-measured PR reached 0.935, and the root mean square error values for the estimations of the heading date and effective tiller percentage were 0.687 d and 4.84%, respectively. Based on the analysis of the results, various factors affecting PR estimation and strategies for improving PR estimation accuracy were investigated. The satisfactory results obtained in this study demonstrate the feasibility of using UAVs and deep learning techniques to replace ground-based manual methods to accurately extract phenotypic information of crop micro targets (such as grains per panicle, panicle flowering, etc.) for rice and potentially for other cereal crops in future research., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Herein, a highly efficient Z-scheme SnS 2 /MIL-88B (Fe) (SnSFe) heterojunction was successfully synthesized to use both as photocatalysts and persulfate (PS) activator for ibuprofen (IBP) degradation. Flower-liked SnS 2 was uniformly loaded on MIL-88B (Fe), and SnSFe retained the original polyhedral morphology of MIL-88B (Fe). The highest removal of IBP was achieved in the presence of SnSFe with 0.5% SnS 2 (SnSFe0.5). Characteristic results and density functional theory calculations demonstrated that the enhanced degradation of IBP was due to the difference in Fermi energy levels of SnS 2 and MIL-88B (Fe) leading to electrons transferred from SnS 2 to MIL-88B (Fe), and SnO bond was formed in SnSFe. , OH and O 2 - were the main active species in SnSFe0.5/PS/visible light system. Z-scheme heterojunction of SnSFe was constructed to propose the degradation mechanism. This research revealed that the synergism of photocatalysis and PS activation using SnS 2 /Fe-based MOFs composites possessed great potentials in wastewater remediation., 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 © 2022 Elsevier Inc. All rights reserved.)

Imaging mass cytometry (IMC) is a new technology integrating mass spectrometry, high-resolution laser ablation and immunohistochemistry/cytochemistry. A unique high-dimensional perspective comprehensively and accurately depicts the complex interaction of phenotype, signalling pathway and tumour microenvironment and is widely used in solid tumours. However, the application scenarios of IMC in basic medicine and clinical research in solid tumours lack systematic introduction and classification. This paper reviews the application of IMC in depicting the panorama of the tumour microenvironment, revealing tumour spatial heterogeneity, clarifying tumour pharmacological mechanisms, assisting in new drug development, and dynamically evaluating the efficacy of immunotherapy in solid tumours., Competing Interests: Declaration of competing interest 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 © 2022 Elsevier Ltd. All rights reserved.)

In order to solve the problem of cervical spondylosis in the early stage of various cervical spondylosis, effective treatment can prevent the deterioration of the disease. This paper presents the results of a clinical trial examining magnetic resonance imaging in the treatment of cervical spondylosis with flotation therapy and selected 68 patients with cervical spondylosis. According to research commodity, using a rigorous randomized controlled trial, 34 cases were divided into a control group (acupuncture group). The needles were kept for 30 minutes once a day. The treatment group (acupuncture combined with floating acupuncture group) was treated with acupuncture on the 1st, 3rd, and 5th days and floating acupuncture on the 2nd, 4th, and 6th days, respectively. Both groups were treated for 6 consecutive days and rested for 1 day. After 2 weeks of treatment, the simplified McGill Pain Scale (MPQ), visual analogue scale (VAS), and neck pain scale (NPQ) were observed and recorded to compare the curative effects. Finally, Excel software is used to manage the data, and SPSS21.0 is used for statistical analysis. Measurements of gender, age, disease, VAS, simple MPQ, and NPQ of the two groups were compared in the two groups, P > 0.05, which was not significant and comparable. After treatment, VAS, simple MPQ, and NPQ of the two groups were compared in and between groups, the total P < 0.05, with the mean data. Topics . Acupuncture combined with float needle and acupuncture therapy can improve the pain and breathing of cervical spondylosis and improve the quality of life of patients, but acupuncture combined with needle float is more pronounced than acupuncture groups., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Xianqiang Liu et al.)

A variety of opinions exist on the potential of probiotics to provide relief from chronic constipation with much focus being placed on their mechanism of action and causes of heterogeneity in the results of different studies. We aimed to determine the efficacy and safety of ingesting Bifidobacterium bifidum ( B . bifidum ) CCFM16 for 28 days to relieve constipation and to understand the mechanism of action. Using Rome IV criterion, 53 and 50 participants diagnosed with chronic constipation were included in the probiotic group and placebo group, respectively. Spontaneous bowel movements (SBMs) per week, stool consistency (Bristol Stool Form Scale [BSFS]), the proportion of SBM responders, patient assessment of constipation symptoms (PAC-SYM), and quality of life (PAC-QoL) were evaluated. The gut microbiota, short-chain fatty acids (SCFAs) and other indicators were also assessed. B . bifidum CCFM16 treatment improved the stool consistency and increased the proportion of SBM responders, but the differences in PAC-SYM and PAC-QoL were statistically insignificant between the groups. Analysis of the SCFAs and microbiome revealed that CCFM16 significantly increased the acetic acid and butyric acid concentrations and enhanced the Firmicutes/Bacteroidetes ratio. Levels of Clostridia were particularly increased and were associated with the increase in butyric acid. In addition, we found the other side of Clostridia; several taxa in the order Clostridiales were observed to prevent CCFM16 from proper functioning in the pre-treatment microbiome. In conclusion, CCFM16 can potentially and efficaciously relieve chronic constipation in Chinese adults by regulating the gut microbiota and SCFA metabolism. The two sides of Clostridia illustrate its importance in microbial therapy for constipation.

In China, approximately 70% of beverage alcohol is consumed in the form of spirits. An estimated 25% of all alcohol consumed is unrecorded, mostly spirits (bai jiu), produced outside regulatory systems in small neighborhood distilleries, mostly in rural areas. Unrecorded bai jiu drinkers are generally older, male, prefer higher-strength bai jiu, and drink daily and mostly at home. To explore possible regional differences, researchers used interview data from 2919 bai jiu drinkers in rural areas in Hebei, Anhui, and Hubei provinces in China. Results confirmed that patterns varied by province. The sample in Hubei preferred unrecorded bai jiu with a more stable preference to alcohol type, tended to drink less frequently, and reported experiencing less drinking pressure, suggesting lower-risk drinking patterns in this region. The Hebei and Anhui sample reported higher frequency and greater amount of alcohol consumption, were more likely to experience drinking pressure, indicating higher-risk patterns in alcohol use in these two regions. The results provide needed details about regional differences in unrecorded bai jiu drinking patterns that are not evident in aggregated data and suggest variations in drinking patterns that may reflect local geography, local values, traditions, and ethnic differences.

A novel competitive-type electrochemical immunosensor based on square wave voltammetry (SWV) response was developed for the quantitative detection of 1-Aminohydantoin (AHD). To improve the conductivity of this immunosensor nanocomposites with good electrical conductivity were prepared as a signal amplification platform for the immunosensor by growing Au nanoparticles on the surface of Ce-based metal-organic framework (Ce-MOF). In addition, methylene blue (MB)-loaded Au@Pt and coating antigen (OVA-AHD) connected as a signal label. When the target was introduced, it competed with the coating antigen for the Ab, which led to a reduction in the number of signal probes bound to the Ab. The concentration of AHD can be determined by SWV detection of the MB signal loaded on the signal labels. Under optimal conditions, the wide linear range of 0.001-1000 μg /L and a low detection limit of 1.35 × 10 -7 μg/L were achieved. Ultimately, the developed method displayed excellent specificity in practical applications, providing a promising probability to detect nitrofuran metabolites residues to guarantee food safety., 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 © 2021 Elsevier B.V. All rights reserved.)

Objective: To investigate the causal relationship between the minimum cross-sectional area of nasal cavity and nasal resistance. Methods: Thirty transparent detachable 3D printing nasal cavity models were made. The airway was completely blocked with sealing material at different anatomical sections. Then ventilatable nasal drainage tubes with different cross-sectional areas were used to pass through the nasal cavity. Nasal resistance was measured. SPSS was used for statistical analysis. Results: ①The postoperative nasal resistances of patients and 3D printing nasal cavity models were （0.38±0.15）Pa· s/mL and （0.39±0.02）Pa· s/mL respectively. There was no statistical difference between the two groups.The preoperative nasal resistance of patients was （0.56±0.09）Pa· s/mL, and the postoperative nasal resistance of the models was significantly descreased by 31% compared with preoperative nasal resistance of the patients, with statistically significant difference（ P <0.05）. ②When the ventilatable nasal drainage tubes with a cross-sectional area of 3.14 square millimeters was located in the the upper part of common meatus and the nasal valve area, the nasal cavity is moderately blocked, and the nasal resistances were （1.80±0.30） times and （2.02±0.36） times of that before the obstruction respectively. When the ventilatable nasal drainage tube was located in the lower part of common meatus,the nasal resistance was （1.68±0.28） times of that before the obstruction. ③When the ventilatable nasal drainage tubes with a cross-sectional area of 6.28 square millimeters and were located in the lower part of common meatus, the upper part of common meatus and nasal valve area, the nasal resistances were （1.44±0.23） times, （1.50±0.25） times and （1.60±0.27） times of those before obstruction, respectively. ④When the ventilatable nasal drainage tubes with a cross-sectional area of 9.42 square millimeters were located in the above areas, nasal ventilation was nearly normal without obvious nasal obstruction. The nasal resistances were （1.17±0.18） times, （1.26±0.21） times and （1.33±0.24） times of those before obstruction, respectively. ⑤The nasal resistance was statistically significant correlated with the cross-sectional area of the ventilation tubes and the obstruction sites. The correlation coefficients were -0.895 and 0.339, respectively （ P <0.05）. Conclusion: ①3D printing can quickly and accurately replicate anatomical structure of the nasal cavity, and can be used as a research method for quantifitative measurement of nasal resistance. ②The minimum cross-sectional area of nasal cavitiy is the main determinant of nasal resistance. ③The obstruction site is the secondary determinant of nasal resistance. When the degree of nasal obstruction is the same , the nasal resistance in the nasal valve area is sightly higher than that in the common meatus., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

The poor immunotherapy of pancreatic cancer is mainly due to its complex immunosuppressive microenvironment. The Mediterranean diet contributes to low cancer incidence. Hydroxytyrosol (HT) derived from olive oil has multiple health-promoting effects, but its therapeutic effect on pancreatic cancer remains controversial. Here, we evaluated the inhibitory effect of HT on mouse pancreatic cancer, and the effect of HT on the immune microenvironment. We found that HT can inhibit the proliferation of Panc 02 cells through signal transducer and activator of transcription (STAT) 3/Cyclin D1 signaling pathway. In the tumor-bearing mice treated with HT, the orthotopic pancreatic tumors were suppressed, accompanied by a decrease in the proportion of myeloid-derived suppressor cells (MDSCs) and an increase in the proportion of M1 macrophages. In addition, we found that HT inhibited the expression of immunosuppressive molecules in bone marrow (BM)-derived MDSCs, as well as down-regulated CCAAT/enhancer-binding protein beta (C/EBPβ) and phosphorylation of STAT3. Moreover, HT enhanced the anti-tumor effect of anti-CD47 antibody in vivo . HT combined with plumbagin (PLB) induced more Panc 02 cells death than HT or PLB alone. This combination therapy not only inhibited the accumulation of MDSCs, but also promoted the infiltration of CD4 + and CD8 + T cells in the tumors. In summary, HT is a potential immunomodulatory drug for the treatment of pancreatic cancer., 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 © 2021 Wang, Yang, Liu, Xun, Zhuo, Zhang, Zhang and Wang.)

Background: Colorectal cancer is one of the most common malignancy in the world. It has been reported that cancer stem cells (CSCs) serve as the primary drivers of tumorigenesis and tumor progression. There is an urgent need to explore novel molecules that regulate CSCs or their signatures. Increasing evidence has shown that miRNAs are involved in tumorigenesis and progression. Here, we aim to explore the regulatory effect and mechanism of miR-3065-3p on the stemness of colorectal cancer., Methods: The expression of miR-3065-3p in colorectal cancer and the association of miR-3065-3p expression with prognosis of patients with colorectal cancer were analyzed using TCGA dataset or clinical cases. Gain or loss of function in different models, including colorectal cancer cell lines and orthotopic xenograft or liver metastatic mouse model, were used to investigate the effects of miR-3065-3p on colorectal cancer stemness and metastasis in vitro and in vivo. Cancer stemness was analyzed by detecting the ability of migration and invasion, NANOG, OCT4, and SOX2 expression, ALDH activity and sphere formation. In addition, the interaction of miR-3065-3p and cytokine receptor-like factor 1 (CRLF1) was analyzed theoretically and identified by the luciferase reporter assay. Moreover, the correlation between CRLF1 expression and miR-3065-3p was analyzed in colorectal cancer tissues. Finally, the effect of CRLF1 on the stemness and metastasis of colorectal cancer in vitro and in vivo was assessed., Results: In this report, we found that miR-3065-3p was overexpressed in colorectal cancer and that its high expression was associated with poor prognosis of patients with colorectal cancer. miR-3065-3p promotes the stemness and metastasis of colorectal cancer. Furthermore, CRLF1 was the downstream target of miR-3065-3p and inhibited the stemness of colorectal cancer. In addition, CRLF1 expression was negatively correlated with miR-3065-3p in colorectal cancer tissues. And, CRLF1 mediated the effects of miR-3065-3p on promoting stemness of colorectal cancer cells., Conclusion: Our data suggest that miR-3065-3p promoted the stemness and metastasis of colorectal cancer by targeting CRLF1. miR-3065-3p might serve as a promising prognostic marker as well as a therapeutic target for colorectal cancer., (© 2021. The Author(s).)

Albiziae Cortex (AC) is a well-known traditional Chinese medicine with sedative-hypnotic effects and neuroprotective ability. However, the bioactive components of AC responsible for the neuro-protective actitivity remain unknown. Here, we investigated the anti-neuroinflammatory effects of (-)-syringaresinol (SYR) extracted from AC in microglia cells and wild-type mice. As a result, (-)-SYR significantly reduced lipopolysaccharide (LPS)-induced production of interleukin - 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin -1 beta (IL-1β), cycloxygenase-2 (COX-2), and nitric oxide (NO) in BV2 microglia cells. (-)-SYR also significantly reduced M1 marker CD40 expression and increased M2 marker CD206 expression. Moreover, we found that (-)-SYR inhibited LPS-induced NF-κB activation by suppressing the translocation of NF-κB p65 into the nucleus in a concentration-dependent manner. Meanwhile, estrogen receptor β (ERβ) was found to be implied in the anti-inflammatory activity of (-)-SYR in BV2 microglia. In vivo experiments revealed that administration of (-)-SYR in mice significantly reduced microglia/astrocytes activation and mRNA levels of proinflammatory mediators. Taken together, our data indicated that (-)-SYR exerted the anti-neuroinflammatory effects by inhibiting NF-κB activation and modulation of microglia polarization, and via interaction with ERβ. The anti-neuroinflammatory activity of (-)-SYR may provide a new therapeutic avenue for the treatment of brain diseases associated with inflammation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Tumor metastasis remains a major challenge for patients with breast cancer. Aberrant epigenetic factor lysine-specific demethylase 6B (KDM6B) has been associated with tumor progression. Here, we show that KDM6B is significantly down-regulated in human breast cancer tissues, and its low expression is associated with poor prognosis of patients with breast cancer. Furthermore, overexpression of KDM6B remarkably inhibited cell proliferation, invasion, migration and epithelial-mesenchymal transition markers of breast cancer cells in vitro and tumor growth and lung metastasis in vivo. Notably, the expression of KDM6B in breast cancer tissues was negatively correlated with that of β-catenin, and overexpression of KDM6B decreased the expression of β-catenin and its accumulation in the nucleus of breast cancer cells. Overall, our findings provide novel insights into suppression of metastasis of breast cancer cells by KDM6B via β-catenin and suggest involvement of the KDM6B-Wnt/β-catenin axis in breast cancer progression., (© 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Purpose: To assess the influence of pain care and hospice care on the quality of life of patients with advanced gastric cancer., Methods: 136 patients with advanced gastric cancer were randomly divided into a experimental group (n=68) and a control group (n=68). The experimental group received pain care combined with hospice care, and control group received routine nursing. We measured quality of life and pain relief to assess the effect of pain care and hospice care., Results: After nursing, the visual analogue scale (VAS) of the two groups decreased, the VAS score of the experimental group was lower than that of the control group (P < 0.05). Compared with the control group, the scores of SF-36 questionnaire (physiological function, psychological function, physical pain, emotional function, social function, and mental health) of the control group were lower than those of the experimental group (P < 0.05)., Conclusions: Pain care and hospice care can effectively reduce the pain degree of patients with advanced gastric cancer and improve the quality of nursing., Competing Interests: None., (AJTR Copyright © 2021.)

The rate of obesity is rapidly increasing and has become a health and economic burden worldwide. As recent studies have revealed that the gut microbiota is closely linked to obesity, researchers have used various approaches to modulate the gut microbiota to treat the condition. Dietary composition and energy intake strongly affect the composition and function of the gut microbiota. Intestinal microbial changes alter the composition of bile acids and fatty acids and regulate bacterial lipopolysaccharide production, all of which influence energy metabolism and immunity. Evidence also suggests that remodeling the gut microbiota through intake of probiotics, prebiotics, fermented foods, and dietary plants, as well as by fecal microbiota transplantation, are feasible methods to remediate obesity., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Oridonin is a diterpenoid isolated from Rabdosia rubescens that has potent anticancer activity. This study set out to investigate the antitumor effects of oridonin in pancreatic carcinoma (PC) and their underlying mechanisms., Methods: To investigate the antitumor effects of oridonin, we developed an orthotopic C57BL/6 mouse model of PC. After successful establishment of the model, the mice were given a daily intraperitoneal injection of phosphate-buffered saline containing 0.1% dimethyl sulfoxide or oridonin for 2 weeks. In vitro experiments including MTT assay and flow cytometry were performed to examine cell viability and apoptosis. Panc-1 and Panc02 cells were transfected with a green fluorescent protein (GFP)-LC3 plasmid. After the cells had been treated with or without 20 μM oridonin and 10 μM 3-MA, the formation of GFP-LC3 puncta was detected by fluorescence microscopy. The levels of the autophagy-related proteins Beclin-1, LC3, and p62 were measured by western blotting., Results: Oridonin inhibited the proliferation of PC cells and induced their apoptosis in vitro and in vivo . Treatment with oridonin also led to an increase in the quantity of LC3B II protein and upregulation of the p62 and Beclin-1 levels in PC cells. The effects of oridonin on PC cell proliferation, apoptosis, and autophagy were mediated via the simultaneous inhibition of the phosphoinositide 3-kinase pathway and activation of the c-Jun N-terminal kinase pathway., Conclusions: Our study is the first to confirm the antitumor and autophagy-activating effects of oridonin on PC cells. In light of these results, oridonin may be a promising therapeutic agent for PC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-2630). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Recent single-cell RNA sequencing (scRNA-seq) analyses have offered much insight into the gene expression profiles in early-stage kidney development. However, comprehensive gene expression profiles from mid- and late-stage kidney development are lacking. In the present study, by using the scRNA-seq technique, we analyzed 54,704 rat kidney cells from just after birth to adulthood (six time points: postnatal days 0, 2, 5, 10, 20, and 56) including the mid and late stages of kidney development. Twenty-five original clusters and 13 different cell types were identified during these stages. Gene expression in these 13 cell types was mapped, and single cell atlas of the rat kidney from birth to maturity ( http://youngbearlab.com ) was built to enable users to search for a gene of interest and to evaluate its expression in different cells. The variation trend of six major types of kidney cells-intercalated cells of the collecting duct (CD-ICs), principal cells of the collecting duct (CD-PCs), cells of the distal convoluted tubules (DCTs), cells of the loop of Henle (LOH), podocytes (PDs), and cells of the proximal tubules (PTs)-during six postnatal time points was demonstrated. The trajectory of rat kidney development and the order of induction of the six major types of kidney cells from just after birth to maturity were determined. In addition, features of the dynamically changing genes as well as transcription factors during postnatal rat kidney development were identified. The present study provides a resource for achieving a deep understanding of the molecular basis of and regulatory events in the mid and late stages of kidney development.

The decrease in ovarian hormone secretion that occurs during menopause results in an increase in body weight and adipose tissue mass. Probiotics and soy isoflavones (SIFs) could affect the gut microbiota and exert anti-obesity effects. The objective of this study was to investigate the effects of probiotics and a diet containing SIF (SIF diet) on ovariectomized mice with menopausal obesity, including the gut microbiome. The results demonstrate that Bifidobacterium longum 15M1 can reverse menopausal obesity, whilst the combination of Lactobacillus plantarum 30M5 and a SIF diet was more effective in alleviating menopausal lipid metabolism disorder than either components alone. Probiotics and SIFs play different anti-obesity roles in menopausal mice. Furthermore, 30M5 alters the metabolites of the gut microbiota that increase the circulating estrogen level, upregulates the expression of estrogen receptor α in abdominal adipose tissue and improves the production of short-chain fatty acids (SCFAs). A SIF diet can significantly alter the structure of the fecal bacterial community and enrich the pathways related to SCFAs production. Moreover, 30M5 and a SIF diet acted synergistically to effectively resolve abnormal serum lipid levels in ovariectomized mice, and these effects appear to be associated with regulation of the diversity and structure of the intestinal microbiota to enhance SCFAs production and promote estrogen circulation.

Probiotic therapy targeting gut-brain axis has been proven to be effective in treating autistic patients. The present study aimed to assess the ability of three Lactobacillus strains (L. helveticus CCFM1076, L. acidophilus La28, and L. acidophilus JCM 1132) to alleviate autistic-like behavioral symptoms in VPA-treated rats from weaning to sexual maturation. For the first time, we assessed the synthesis of 5-hydroxytryptamine (5HT) and the metabolic capacity of the 5HT system in the peripheral and central nervous systems (PNS and CNS, respectively) based on tryptophan metabolism based on VPA-induced autism model. We also assessed gut microbiota, and short-chain fatty acids (SCFAs) at the end of week 8. While improving autistic-like behavioral symptoms, we found L. helveticus CCFM1076 was more beneficial in regulating 5HT anabolism and catabolism, balancing excitatory and inhibitory neurotransmitter release in the PNS and CNS, and increasing oxytocin (OT) synthesis in the hypothalamus. A significant correlation was noted between 5HT levels and the release of GABA, glutamate (Glu), and OT, suggesting that 5HT plays a vital role in the neuroendocrine network. Analyses of the gut microbiota and SCFA levels revealed greater Turicibacter abundance and lower butyric acid levels in VPA-treated rats, which have been reported to be associated with 5HT levels. L. helveticus CCFM1076 helped reduce Turicibacter abundance and up-regulate butyric acid levels, while L. acidophilus La28 and L. acidophilus JCM 1132 did not. L. helveticus CCFM1076 restored neurotransmitter homeostasis by improving the balance of the 5HT system in the PNS and CNS, thereby ameliorating autistic-like behaviors. This finding will help in the development of bioproducts for treating autism and in the establishment of a treatment model mimicking the intestinal environment of autistic patients.

The incidence of obesity, which is closely associated with the gut microbiota and chronic inflammation, has rapidly increased in the past 40 years. Therefore, the probiotic-based modification of the intestinal microbiota composition has been developed as a strategy for the treatment of obesity. In this study, we selected four Bifidobacterium adolescentis strains isolated from the feces of newborn and elderly humans to investigate whether supplementation with B. adolescentis of various origins could alleviate obesity in mice. Male C57BL/6J mice fed a high-fat diet (HFD, 60% energy as fat) received one of the following 14-week interventions: (i) B. adolescentis N4&#95;N3, (ii) B. adolescentis Z25, (iii) B. adolescentis 17&#95;3, (iv) B. adolescentis 2016&#95;7&#95;2, and (v) phosphate-buffered saline. The metabolic parameters, thermogenesis, and immunity of all treated mice were measured. Cecal and colonic microbial profiles were determined by 16S rRNA gene sequencing. Intestinal concentrations of short-chain fatty acids (SCFAs) were measured by gas chromatography-mass spectrometry (GC-MS). The B. adolescentis strains isolated from the feces of elderly humans ( B. adolescentis Z25, 17&#95;3, and 2016&#95;7&#95;2) decreased the body weight or weight gain of mice, whilst the strain isolated from the newborn ( B. adolescentis N4&#95;N3) increased the body weight of mice. The B. adolescentis strains isolated from the elderly also increased serum leptin concentrations and induced the expression of thermogenesis- and lipid metabolism-related genes in brown adipose tissue. All the B. adolescentis strains alleviated inflammations in the spleen and brain and modified the cecal and colonic microbiota. Particularly, all strains reversed the HFD-induced depletion of Bifidobacterium and reduced the development of beta-lactam resistance. In addition, the B. adolescentis strains isolated from the elderly increased the relative abundances of potentially beneficial genera, such as Bacteroides , Parabacteroides, and Faecalibaculum . We speculate that such increased abundance of commensal bacteria may have mediated the alleviation of obesity, as B. adolescentis supplementation decreased the intestinal production of SCFAs, thereby reducing energy delivery to the host mice. Our results revealed that certain strains of B. adolescentis can alleviate obesity and modify the gut microbiota of mice. The tested strains of B. adolescentis showed different effects on lipid metabolism and immunity regulation, with these effects related to whether they had been isolated from the feces of newborn or elderly humans. This indicates that B. adolescentis from different sources may have disparate effects on host health possibly due to the transmission of origin-specific functions to the host.

Background: Callosal Angle (CA) and Evans Index (EI) are considered as imaging biomarkers to diagnose normal-pressure hydrocephalus using traditional MR measurement methods., Objective: The current study aimed to evaluate the differential diagnostic value of CA and EI in Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD)., Methods: Five-hundred and two subjects were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, which included 168 Normal Controls (NC), 233 MCI and 101 AD patients. The structural MR images were interactively applied with multiplanar reconstruction to measure the CA and EI., Results: CA presented no significant difference among NC, MCI and AD groups (H value = 3.848, P value = 0.146), and EI demonstrated higher value in MCI and AD groups than that in NC groups (P = 0.000 and 0.001, respectively). MCI group had significant larger EI (0.29±0.04) than (0.27±0.03) NC group in 70-75 years old sub-groups. ROC showed that the area under the curve was 0.704±0.045 for NC-MCI in 70-75 years old groups. The correlation analysis indicated that EI was significantly negatively related to MMSE scores of MCI patients (r = -0.131, P = 0.046)., Conclusion: EI might serve as a screening imaging biomarker for MCI in 70-75 years old patients, and show limited differential value for the diagnosis of AD. CA could present no diagnostic value for MCI and AD in the current study., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)