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The important role of gasotransmitters in physiology and pathophysiology suggest employing gasotransmitters for biomedical treatment. Unfortunately, the difficulty in storage and controlled delivery of these gaseous molecules hindered the development of effective gasotransmitters-based therapies. The design of a safe, facile, and wide-scale method to delivery multiple gasotransmitters is a great challenge. Herein, we use an ultrasonic assisted preparation γ-cyclodextrin metal organic framework (γ-CD-MOF) as a broad-spectrum delivery vehicle for various gasotransmitters, such as SO2, NO, and H2S. The release rate of gasotransmitters could be tuned by modifying the γ-CD-MOF with different Pluronics. The biological relevance of the exogenous gasotransmitters produced by this method is evidenced by the DNA cleavage ability and the anti-inflammatory effects. Furthermore, the γ-CD-MOF composed of food-grade γ-CD and nontoxic metal salts shows good biocompatibility and particle size (180 nm). Therefore, γ-CD-MOF is expected to be an excellent tool for the study of co-delivery and cooperative therapy of gasotransmitters.

Using pediatric anthropomorphic phantoms (APs), we aimed to determine the scanning tube voltage/current combinations that could achieve optimal image quality and avoid excessive radiation exposure in pediatric patients. A 64-slice scanner was used to scan a standard test phantom to determine the volume CT dose indices (CTDIvol), and three pediatric anthropomorphic phantoms (APs) with highly accurate anatomy and tissue-equivalent materials were studied. These specialized APs represented the average 1-year-old, 5-year-old, and 10-year-old children, respectively. The physical phantoms were constructed with brain tissue-equivalent materials having a density of ρ = 1.07 g/cm3, comprising 22 numbered 2.54-cm-thick sections for the 1-year-old, 26 sections for the 5-year-old, and 32 sections for the 10-year-old. They were scanned to acquire brain CT images and determine the standard deviations (SDs), effective doses (EDs), and contrast-to noise ratios (CNRs). The APs were scanned by 21 combinations of tube voltages/currents (80, 100, or 120 kVp/10, 40, 80, 120, 150, 200, or 250 mA) and rotation time/pitch settings of 1 s/0.984:1. The optimal tube voltage/current combinations yielding optimal image quality were 80 kVp/80 mA for the 1-year-old AP; 80 kVp/120 mA for the 5-year-old AP; and 80 kVp/150 mA for the 10-year-old AP. Because these scanning tube voltages/currents yielded SDs, respectively, of 12.81, 13.09, and 12.26 HU, along with small EDs of 0.31, 0.34, and 0.31 mSv, these parameters and the induced values were expediently defined as optimal. The optimal tube voltages/currents that yielded optimal brain image quality, SDs, CNRs, and EDs herein are novel and essentially important. Clinical translation of these optimal values may allow CT diagnosis with low radiation doses to children's heads.

High-salt diet (HSD) is a major risk factor for renal injury, and gut microbiota may play a role in this process. In this study, we investigated the potential role of gut microbiota in HSD-related renal injury and the microbial mechanisms involved. Through function observation, mechanism screening, and further verification using transcriptomic and metabolomic profiling and bioinformatics, we found that HSD caused renal dysfunction, inflammation, hypoimmunity, and serious renal damage in conventional mice, but this effect was absent in germ-free (GF) mice. Differential gene set enrichment analyses of the gut and kidney identified the steroid hormone biosynthesis pathway as a main culprit. For further verification, differential metabolite set enrichment analyses of feces indicated the involvement of the steroid hormone biosynthesis pathway. Through comprehensive profiling of intestinal and renal tissues along with fecal samples, we detected three genes and two metabolites showing prominent enrichment in the steroid hormone biosynthesis pathway. RT-qPCR suggested that the core gene Cyp1a1 , which depends on the interplay between HSD and gut microbiota, was inhibited in both the gut and kidney in HSD-related renal injury. Finally, dehydroepiandrosterone decreased the mRNA expression of Cyp1a1 in the gut and kidney. The data suggest that HSD promotes renal injury by manipulating the gut-kidney axis via gut microbiota and strengthening the steroid hormone biosynthesis pathway. The study expands the current knowledge on the gut microbial control of the gut-kidney axis in HSD-related renal injury, which finally provides novel insights into the therapeutic strategies for preventing or attenuating HSD-related kidney diseases.

The large-scale automated manufacture of extracellular vesicles (EVs) is crucial for meeting the growing demand for EV-based therapies, enabling the standardized, efficient, and scalable production of EVs for clinical translation.We developed a fully automated collection technology and optimized machinery (FACTORY), achieving large-scale automated manufacture of EVs.The EVs manufactured via FACTORY maintain normal biological activity while meeting stringent quality standards: sterility, mycoplasma-free status, low endotoxin levels, and high consistency.The FACTORY platform allows researchers across disciplines to obtain EVs through a one-click operation, ensuring batch-to-batch consistency in isolation technology and comparability of research outcomes, thereby accelerating the clinical translation of EV-based applications. Extracellular vesicles (EVs) hold significant potential as therapeutic agents and drug carriers. However, current isolation techniques severely limit their clinical application, due to heavy reliance on manual operation, making large-scale isolation of EVs impractical and failing to meet the requirements for clinical translation. Here, we set up the fully automated collection technology and optimum machinery (FACTORY) platform, allowing the efficient collection of high-quality EVs. The platform integrates continuous flow centrifugation and tangential flow filtration (TFF) technologies, achieving a seamless process for the removal of impurities and collection of EVs, thereby ensuring that large scale-manufactured EVs are sterile, mycoplasma free, and low in endotoxins, and exhibit good consistency. We successfully obtained a substantial quantity of EVs utilizing FACTORY, and systematically characterized their EV-specific markers, biological functions, and therapeutic effects. Results indicated that FACTORY significantly promotes the clinical translation of EVs, thereby laying a solid foundation for their application in drug delivery and beyond. [Display omitted] The FACTORY platform addresses the urgent need for scalable, automated, and efficient methods for collecting EVs, which hold great promise in clinical therapeutics. Currently, FACTORY is assessed at Technology Readiness Level (TRL) 6, indicating its readiness for real-world implementation. By integrating continuous flow centrifugation and tangential flow filtration (TFF), FACTORY enables large-scale EV isolation with high yield, sterility, and batch-to-batch consistency. Experimental results show that FACTORY produces a higher yield of EVs compared with traditional ultracentrifugation, with comparable purity and morphology. In addition, FACTORY-isolated EVs meet critical safety criteria, including sterility, mycoplasma-free status, and minimal endotoxin levels. The FACTORY platform holds significant promise for advancing EV-based therapeutics, with potential applications in regenerative medicine, drug delivery, and immunomodulation. Its scalability, automation, and ability to produce high-quality EVs position it as a transformative tool for clinical and industrial use, paving the way for broader adoption in emerging medical fields, including medical aesthetics and targeted therapy development. This study developed the fully automated collection technology and optimum machinery (FACTORY) platform for extracellular vesicles (EVs), integrating continuous flow centrifugation and tangential flow filtration. The platform allows one-click, large-scale isolation of high-quality EVs with exceptional consistency, accelerating the clinical translation of EV-based applications.

Aims The effects of subthalamic nucleus (STN)‐deep brain stimulation (DBS) on brain topological metrics, functional connectivity (FC), and white matter integrity were studied in levodopa‐treated Parkinson’s disease (PD) patients before and after DBS. Methods Clinical assessment, resting‐state functional MRI (rs‐fMRI), and diffusion tensor imaging (DTI) were performed pre‐ and post‐DBS in 15 PD patients, using a within‐subject design. The rs‐fMRI identified brain network topological metric and FC changes using graph‐theory‐ and seed‐based methods. White matter integrity was determined by DTI and tract‐based spatial statistics. Results Unified Parkinson's Disease Rating Scale III (UPDRS‐ III) scores were significantly improved by 35.3% (p < 0.01) after DBS in PD patients, compared with pre‐DBS patients without medication. Post‐DBS PD patients showed a significant decrease in the graph‐theory‐based degree and cost in the middle temporal gyrus and temporo‐occipital part‐Right. Changes in FC were seen in four brain regions, and a decrease in white matter integrity was seen in the left anterior corona radiata. The topological metrics changes were correlated with Beck Depression Inventory II (BDI‐II) and the FC changes with UPDRS‐III scores. Conclusion STN‐DBS modulated graph‐theoretical metrics, FC, and white matter integrity. Brain connectivity changes observed with multi‐modal imaging were also associated with postoperative clinical improvement. These findings suggest that the effects of STN‐DBS are caused by brain network alterations. This study uses multi‐modal images to explore the effectiveness of post‐deep brain stimulation (DBS) in Parkinson's disease (PD) patients. The result finds functional connectivity (FC) change in some brain areas. Moreover, Post‐DBS PD patients revealed a significant decrease in the graph‐theory‐based degree and cost in the middle temporal gyrus, temporo‐occipital part‐Right (toMTG‐R). Changes in topological metrics correlated with improved Beck Depression Inventory‐II and the FC changes with Unified Parkinson’s Disease Rating Scale‐III.

The ESCRT (endosomal sorting complex required for transport) machinery is essential for various cellular processes, yet its role in head and neck squamous cell carcinoma (HNSCC) is poorly understood. We utilized The Cancer Genome Atlas (TCGA) datasets to analyze the expression of ESCRT genes. Bulk RNA-sequencing data and HNSCC tissue microarrays (TMAs) were used to evaluate VPS25 expression and its clinical significance. Single-cell RNA sequencing of tumor tissues and VPS25 knockdown experiments in CAL27 cells were used to investigate its biological functions. Immunohistochemistry, spatial transcriptomics, and immunotherapy datasets highlighted the involvement of VPS25 in immune suppression and its potential as a predictive biomarker. The results demonstrated significant VPS25 overexpression in HNSCC tissues, which correlated with poor clinical outcomes. It promoted tumor cell proliferation and migration while reducing immune cell infiltration in the tumor microenvironment (TME). Additionally, by upregulating PVR expression in tumor cells, VPS25 activated the immunosuppressive PVR-TIGIT signaling axis, thereby facilitating immune evasion. Furthermore, VPS25 emerged as a potential biomarker for predicting immunotherapy response. These findings highlight VPS25 as a pivotal regulator of tumor progression and immune evasion in HNSCC and a promising target for therapeutic strategies.

Exposure to ionizing radiation can cause cancer, especially in children. In computed tomography (CT), a trade-off exists between the radiation dose and image quality. Few studies have investigated the effect of dose reduction on image quality in pediatric neck CT. We aimed to assess the effect of peak kilovoltage on the radiation dose and image quality in pediatric neck multidetector-row CT. Measurements were made using three phantoms representative of children aged 1, 5, and 10 years, with tube voltages of 80, 100, and 120 kilovoltage peak (kVp); tube current of 10, 40, 80, 120, 150, 200, and 250 mA; and exposure time = 0.5 s (pitch, 0.984:1). Radiation dose estimates were derived from the dose-length product with a 64-multidetector-row CT scanner. Images obtained from the control protocol (120 kVp) were compared with the 80- and 100-kVp protocols. The effective dose (ED) was determined for each protocol and compared with the 120-kVp protocol. Quantitative analysis entailed noise measurements by recording the standard deviation of attenuation for a circular 1-cm 2 region of interest placed on homogeneous soft tissue structures in the phantom. The mean noise of the various kVp protocols was compared using the unpaired Student t-test. Reduction of ED was 37.58% and 68.58% for neck CT with 100 kVp and 80 kVp, respectively. The image noise level increased with the decrease in peak kilovoltage. Noise values were higher at 80 kVp at all neck levels, but did not increase at 100 kVp, compared to 120 kVp in the three phantoms. The measured noise difference was the greatest at 80 kVp (absolute increases<2.5 HU). The subjective image quality did not differ among the protocols. Thus, reducing voltage from 120 to 80 kVp for neck CT may achieve ED reduction of 68.58%, without compromising image quality.

High strength porous titanium implants are widely used for the reconstruction of craniofacial defects because of their similar mechanical properties to those of bone. The recent introduction of electron beam melting (EBM) technique allows a direct digitally enabled fabrication of patient specific porous titanium implants, whereas both their in vitro and in vivo biological performance need further investigation. In the present study, we fabricated porous Ti6Al4V implants with controlled porous structure by EBM process, analyzed their mechanical properties, and conducted the surface modification with biomimetic approach. The bioactivities of EBM porous titanium in vitro and in vivo were evaluated between implants with and without biomimetic apatite coating. The physical property of the porous implants, containing the compressive strength being 163 - 286 MPa and the Young's modulus being 14.5-38.5 GPa, is similar to cortical bone. The in vitro culture of osteoblasts on the porous Ti6Al4V implants has shown a favorable circumstance for cell attachment and proliferation as well as cell morphology and spreading, which were comparable with the implants coating with bone-like apatite. In vivo, histological analysis has obtained a rapid ingrowth of bone tissue from calvarial margins toward the center of bone defect in 12 weeks. We observed similar increasing rate of bone ingrowth and percentage of bone formation within coated and uncoated implants, all of which achieved a successful bridging of the defect in 12 weeks after the implantation. This study demonstrated that the EBM porous Ti6Al4V implant not only reduced the stress-shielding but also exerted appropriate osteoconductive properties, as well as the apatite coated group. The results opened up the possibility of using purely porous titanium alloy scaffolds to reconstruct specific bone defects in the maxillofacial and orthopedic fields.

Resveratrol is one of the most well-known drugs used in the treatment of aging. However, the potential mechanisms of resveratrol on intestinal aging have not yet been fully investigated. Herein, we aimed to further explore the pharmacological mechanisms of resveratrol as a therapy for intestinal aging. We performed network construction and enrichment analysis via network pharmacology. Then a further animal experimental validation containing 20 female C57BL/6J (wild type, WT) and 16 female ATF4+/- (knock down, KD) naturally aging mice and oral supplementary resveratrol (44 mg/kg/day) for 30 days were conducted. The expression of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), linear alkylethoxylate (AE), and malondialdehyde (MDA) were measured by ELISA, the observation of pathological changes and apoptosis in intestinal tissue were performed by HE, PAS, and TUNEL staining, the ATF4/Chop/Bcl-2/Bax signaling pathway-related proteins and mRNAs expression were measured by western blotting and real-time PCR. The network pharmacology showed 132 targets of resveratrol on aging. The enrichment analysis showed resveratrol antiaging involved mainly included protein heterodimerization activity, apoptosis, etc. Then ATF4/Chop/Bcl-2/Bax signaling pathway in biological process of apoptosis was selected to verify the potential mechanisms. Animal studies showed resveratrol upregulated the relative expression of SOD, GSH-Px, CAT, AE, whereas it downregulated the relative expression of MDA in intestine compared with the control group. There was also higher relative expression of SOD, GSH-Px, CAT, AE, and lower relative expression of MDA in KD mice than that in WT mice. Moreover, there was higher relative expression of SOD, GSH-Px, CAT, AE, and lower relative expression of MDA in KD mice than that in WT mice after resveratrol treatment. Decreased ATF4, Chop, Bax but increased Bcl-2 proteins and mRNAs expression were determined after resveratrol treatment compared with the control group; lower ATF4, Chop, Bax but higher Bcl-2 proteins and mRNAs expression were found in KD mice than that in WT mice. Additionally, lower relative proteins and mRNAs expression of ATF4, Chop, Bax and higher relative expression of Bcl-2 in KD mice than that in WT mice after resveratrol treatment. These findings demonstrated that resveratrol substantially inhibited intestinal aging via downregulating ATF4/Chop/Bcl-2/Bax signaling pathway.

Background: Currently, there are many different drugs to improve Alzheimer’s disease (AD) from different pathways. As a supplement and alternative medicine, traditional Chinese medicine (TCM) targets multiple pathways which may be different from classical Western medicine, which may be orchestrated with Western medicine to materialize multiplying efficacy in AD patients. Objective: To investigate the therapeutic effect and assess the available preclinical evidence and possible mechanisms of β-asarone which was extracted from Acorus gramineus Soland (Araceae, AGS) for AD based on rat and mouse animal models. Methods: PubMed, Embase, Scopus, Cochrane Library, BIOSIS Previews, Web of Science, EBSCO, and Google Scholar were searched from inception to 5 May 2022. Rat and mouse experiments assessing the therapeutic effects of β-asarone for AD were included. Primary outcomes were neuroethology, including escape latency and times of crossing platform. Second outcomes were cell apoptosis, including Bax and Bcl-2. The weighted mean difference (WMD) was generated for continuous variables. The relative outcomes were analyzed with the aid of Get Data Graph Digitizer 2.26 and software STATA version 16.0 MP. Results: For the primary endpoint, compared with the modeling group, β-asarone significantly decreased the escape latency (WMD = -12.61, 95% CI: -18.66 to -6.57) and increased the times of crossing platform (WMD = 1.50, 95% CI: 0.31–2.70). For the secondary endpoint, β-asarone remarkably reduced the relative expression of the amyloid precursor protein (APP) (WMD = −2.25, 95% CI: −2.49 to −2.01), decreased the expression of the apoptosis-related protein, associated X protein (Bax) (WMD = −2.40, 95% CI: −3.51 to −1.29), lowered the expression of apoptosis-related protein, B-cell lymphoma-2 (Bcl-2) (WMD = 0.42, 95% CI: 0.38–0.46), and decreased the signal pathway-related proteins, phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) (WMD = −0.70, 95% CI: −0.93 to −0.47) over the control group. Conclusion: β-asarone spectacularly improved the learning ability and memory in rats and mice, which might be correlated with its potential neuroprotective effect through multiple signaling pathways.