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Fang-bo Li,1,* Ping Lu,2,* Hai-tao Wu,1 Ming-han Wang,1 Jing-dong Wang1 1Graduate School, Guangzhou Sport University, Guangzhou, Guangdong, 510500, People’s Republic of China; 2School of PE and Health, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fang-bo Li, Graduate School, Guangzhou Sport University, Linhe West Road, Tianhe District, Guangzhou, Guangdong, 510500, People’s Republic of China, Tel +86 18860292906, Email 975394244@qq.comObjective: To assess the therapeutic impacts of exercise, massage, and music interventions on college students experiencing depression by employing a mesh meta-analysis approach. This research intends to offer valuable insights to aid in the development of non-pharmaceutical treatment strategies for depression.Methods: We conducted a thorough search across various databases including Cochrane, PubMed, Embase, Web of Science, CNKI, and Wanfang to explore the effects of music, massage, aerobic exercise, fitness Qigong, yoga, tai chi, ball games, strength training, dance, whole body vibration training, and high-intensity interval training on the treatment of depression in college students. The search period was from January 1, 2023, which marks the establishment of each database. Subsequently, a mesh meta-analysis was performed using the “Stata 15.1” software, incorporating outcome indicators from 24 included literature comprising a total of 1458 patients.Results: Based on the ranking of the optimal intervention effects of various non-pharmaceutical methods, the order, from highest to lowest probability, was as follows: high-intensity interval training (96%), yoga (94.90%), dance (78.30%), music (73.30%), ball games (62.50%), strength training (51.70%), aerobic training (45.30%), tai chi (35.40%), vibration training (27.30%), massage (20.10%), qigong (14.30%), and no intervention (1.00%). This ranking aligns closely with the findings obtained from pairwise comparisons between different interventions.Conclusion: High-intensity interval training is likely to yield the most effective therapeutic results for college students with depression. In the pairwise comparison of different interventions, High-intensity interval training is also better than most interventions. However, to establish its intervention effect more conclusively, further validation through additional high-quality randomized controlled trials is necessary.Keywords: depression, music, exercise, college student, network meta-analysis

Yang Chai, Hai-Tao Wu, Chuan-Dong Liang, Chun-Yue You, Ming-Xiang Xie, Shun-Wu Xiao Department of Neurosurgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, People’s Republic of ChinaCorrespondence: Shun-Wu XiaoDepartment of Neurosurgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, People’s Republic of ChinaEmail xiaoshunwu34576346@163.comObjective: Glioma is one of the most common central nervous system malignant tumors, accounting for 45%– 60% of adult intracranial tumors. However, the clinical treatment of glioma is limited. It is of great significance to seek new therapeutic methods for glioma via gene therapy.Materials and Methods: Microarray is used to identify the lncRNAs that are differentially expressed in glioma. The expression of long non-coding RNA (lncRNA) ROR1-AS1 and miR-4686 was detected by qRT-PCR. Exosomes were isolated from the supernatant of normal and cancerous cells, and TEM was used for exosomes identification. MTT assay, wound healing assay, transwell assay, and colony formation assay were used to detect the exo-ROR1-AS1 function on proliferation, migration, and invasion in glioma cells. Luciferase assay and RIP assay were used to identify the relationship between lncRNA ROR1-AS1 and miR-4686. The effect of exo-ROR1-AS1 on tumorigenesis of glioma was confirmed by the xenograft nude mice model.Results: ROR1-AS1 was up-regulated in glioma tissues, and the high expression of ROR1-AS1 indicated a poor prognosis in glioma patients. Interestingly, ROR1-AS1 was packaged into exosomes and derived from tumor cells. Functional analysis showed exo-ROR1-AS1 promoted the progression of glioma cell lines SHG44 and U251. Furthermore, ROR1-AS1 acted as a sponge of miR-4686 and inhibited its expression. Functionally, forced expression of miR-4686 removed the promoted effects of lncRNA ROR1-AS1 on glioma development. In vivo tumorigenesis experiments showed that exo-ROR1-AS1 promoted glioma development via miR-4686 axis.Conclusion: Our study suggested tumor cells derived exo-ROR1-AS1 promoted glioma progression by inhibiting miR-4686, which might be a potential therapeutic target for glioma clinical treatment.Keywords: glioma, lncRNA ROR1-AS1, exosome, miR-4686, tumorigenesis

Ching-Han Lin,1,* Shang-Yu Lee,2,* Chun-Cheng Zhang,3 Ye-Fong Du,1 Hao-Chang Hung,1 Hung-Tsung Wu,4 Horng-Yih Ou1 1Department of Internal Medicine, Division of Endocrinology and Metabolism, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 2Department of Internal Medicine, Division of Endocrinology and Metabolism, Chi-Mei Medical Center, 3Department of Internal Medicine, Division of Holistic Care, Chi-Mei Medical Center, 4Research Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, Taiwan *These authors contributed equally to this work Abstract: Fenretinide is a novel anticancer agent reported to exhibit anti-invasive and antimetastatic activities. It has also been shown to improve obesity and diabetes, although the effects of fenretinide on hypertension are still unknown, and the detailed mechanisms remain unclear. In this study, we have shown that treatment with lipopolysaccharide (LPS) decreased the expression of peroxisome proliferator-activated receptor γ (PPARγ) in RAW264.7 macrophages, and pretreatment with fenretinide reversed the effect of LPS on PPARγ expression. In addition, LPS-induced pro-inflammatory cytokine production, including tumor necrosis factor-α, interleukin 6, and monocyte chemoattractant protein 1 were dose-dependently reversed by fenretinide, and the effects of fenretinide on LPS-induced pro-inflammatory cytokine production were blocked by treatment with PPARγ antagonist. Moreover, fenretinide decreased LPS-induced inducible nitric oxide synthase expression and nitrogen oxide production. These effects were blocked by the pretreatment with PPARγ antagonist in a dose-dependent manner, indicating fenretinide activated PPARγ to exert anti-inflammation activity. In view of the role of inflammation in hypertension and the anti-inflammatory action of fenretinide, we found that administration of fenretinide in spontaneously hypertensive rats significantly decreased blood pressure. Taken together, these results indicate that fenretinide might be a potent antihypertensive agent that works by suppressing inflammation via activating PPARγ. Keywords: fenretinide, hypertension, inflammation, macrophage, peroxisome proliferator-activated receptor γ

Nonalcoholic fatty liver disease is frequently associated with type 2 diabetes; however, this idea is challenged by recent studies because hepatic steatosis is not always associated with insulin resistance (IR). Oleic acid (OA) is known to induce hepatic steatosis with normal insulin sensitivity; however, the mechanism is still unknown. Previous studies depict that activation of peroxisome proliferator-activated receptor δ (PPARδ) improves hepatic steatosis and IR, whereas the role of PPARδ in the improvement of insulin sensitivity by OA is unknown. Here we induced steatosis in HepG2 cells by incubation with OA and OA significantly increased the expression of PPARδ through a calcium-dependent pathway. OA also induced the expression of G protein-coupled receptor 40 (GPR40), and deletion of GPR40 by small interfering ribonucleic acid transfection partially reversed the effect of OA on PPARδ. Inhibition of phospholipase C (PLC) by U73122 also reversed OA-induced PPARδ expression. Otherwise, deletion of PPARδ augmented the OA-induced steatosis in HepG2 cells. Furthermore, IR was developed in OA-treated HepG2 cells with PPARδ deletion, while insulin-related signals and insulin-stimulated glycogen synthesis were reduced through increase of phosphatase and tensin homolog (PTEN) expression. In conclusion, OA activates GPR40-PLC-calcium pathway to increase the expression of PPARδ and PPARδ further decreased the expression of PTEN to regulate insulin sensitivity in hepatic steatosis. [ABSTRACT FROM AUTHOR]

Many studies have proven that the polymethylmethacrylate (PMMA) augmentation of the pedicle screw can significantly increase stiffness and strength of spinal fixation. Some major complications have also been reported. However, there are no reports discussing cement distribution and its morphology in the osteoporotic vertebral body, which is critical in the analysis of the biomechanical strength of the pedicle screw and the risk of cement leakage after pedicle screw augmentation. In this study, we used computed tomography (CT) to evaluate the cement distribution in the osteoporotic vertebral body after PMMA augmentation of a pedicle screw and to analyze the factors leading to cement leakage. Two groups of patients were studied. Group A consisted 25 osteoporotic patients (mean age of 73 years) with spinal instrumentation who had a total of 145 pedicle screws and cement augmentation with biopsy needles. Group B consisted of 23 osteoporotic patients (mean age of 74.6 years) with spinal instrumentation who had a total of 125 cannulated pedicle screws with cement augmentation. All patients had CT evaluation of the cement distribution in the vertebral body after the surgery. The cement distribution in the vertebrae was divided into four zones in the axial CT view: anterior one-third, middle third, and posterior third of vertebral body, and the pedicle. The morphology of the cement distribution around the pedicle screw was defined as scattered type or concentrate type. The leakage pattern was divided to anterior-lateral, posterior-lateral, and canal leakage. The correlations among bone mineral density (BMD), the cement leakage rate, and cement distribution morphology were also analyzed. The results showed that most augmented pedicle screws had cement extension into three of the four zones of the vertebral body (66.3%), followed by two zones (20%), all four zones (11.5%), and only one zone (2.2%). Overall, 123 screws (84.8%) in Group A and 108 screws (86.4%) in Group B had cement concentrate type distribution. The cement leakage rate in Group A is 18.3% and 13.6% in Group B. Patients with a BMD <0.6 g/cm(2) had significantly higher rates of cement leakage and tended toward a scattered cement distribution. There was only one patient who had a symptomatic leakage (sciatica) in Group B. We concluded that the cement distribution after pedicle screw augmentation with biopsy needle or cannulated screw technique was mostly localized in three zones of the vertebral body, and patients with lower BMD had a higher risk of cement leakage and scattered cement distribution. [ABSTRACT FROM AUTHOR]

Contents [ABSTRACT FROM AUTHOR]

In response to the urgent need for advanced climate change mitigation tools, this study introduces an innovative CO 2 gas sensor based on p-p-type heterostructures designed for effective operation at room temperature. This sensor represents a significant step forward, utilizing the synergistic effects of p-p heterojunctions to enhance the effective interfacial area, thereby improving sensitivity. The incorporation of CuO nanoparticles and rGO sheets also optimizes gas transport channels, enhancing the sensor's performance. Our CuO/rGO heterostructures, with 5 wt % rGO, have shown a notable maximum response of 39.6-500 ppm of CO 2 at 25 °C, and a low detection limit of 2 ppm, indicating their potential as high-performance, room-temperature CO 2 sensors. The prepared sensor demonstrates long-term stability, maintaining 98% of its initial performance over a 30-day period when tested at 1-day intervals. Additionally, the sensor remains stable under conditions of over 40% relative humidity. Furthermore, a first-principles study provides insights into the interaction mechanisms with CO 2 molecules, enhancing our understanding of the sensor's operation. This research contributes to the development of CO 2 monitoring solutions, offering a practical and cost-effective approach to environmental monitoring in the context of global climate change efforts.

Aims: One effective clinical strategy to combat obesity is intragastric botulinum toxin (BTX) injection, which increases gastric emptying time and regulates appetite. However, it remains unknown if and how BTX affects ghrelin levels., Materials and Methods: An obese animal model was established by feeding male mice with high-fat diet (HFD). BTX was administered by subserosal injection in the antrum via an upper midline laparotomy. The mice were monitored in terms of body weight and blood biochemical parameters. Glucose utility and insulin sensitivity were measured by intraperitoneal glucose and insulin tolerance tests. Additionally, stomach and liver were histologically examined after BTX treatment. AGS gastric adenocarcinoma cells were used to investigate the molecular mechanism by which BTX affects ghrelin expression., Key Findings: In HFD-fed mice, BTX injection significantly decreased both food intake and body weight over a 3-week monitoring period. Moreover, HFD-induced hyperglycemia, hyperinsulinemia, dyslipidemia and obesity readouts were improved after BTX injection. Importantly, mice also exhibited decreased plasma and gastric ghrelin levels after BTX injection. In cultured AGS cells, BTX significantly increased reactive oxygen species (ROS) levels and activated nuclear factor-κB (NF-κB), which led to decreased ghrelin expression. Pre-treatment with inhibitors of either ROS or NF-κB reversed the effects of BTX on ghrelin expression in the cultured cells., Significance: BTX decreases ghrelin expression in HFD-fed animals and in AGS cells through an ROS/NF-κB-dependent pathway. This mechanism may contribute to decreased food intake in obese subjects receiving intragastric BTX injection for weight control., Competing Interests: Declaration of competing interest We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Previous studies have investigated complexation and coacervation of scallop Patinopecten yessoensis male gonad hydrolysates (SMGHs) and polysaccharides influenced by pH and blending ratio. It has been found that SMGHs/polysaccharide composite shows better gel properties under strongly acidic conditions. Thus, the complexation and coacervation of SMGHs and gellan gum (GG) were investigated via turbidimetric titration at different pH values (1-12) and biopolymer blending ratios (9.5:0.5-6:4)., Results: Both pH c and pH φ1 exhibited ratio-independent behavior with constant values at approximately pH 5.8 and pH 3.8, respectively, dividing SMGHs/GG blends into three phases named mixed polymers, soluble complexes and insoluble coacervates, respectively. Overall, SMGHs and GG exhibited synergistic gelation under neutral and acidic conditions, with the initial storage modulus (G') increasing by approximately 42.5-, 573.7- and 3421-fold and 97.7-, 550.3- and 0.5-fold, respectively, at pH 7, 5 and 3, compared with SMGHs and GG. As pH decreased from 7 to 3, the initial G' and viscosity η values of SMGHs/GG gels increased by 20.1- and 2.3-fold, respectively, exhibiting the greatest increase in gel strength. Moreover, the free water in the SMGHs/GG system significantly shifted toward lower relaxation times attributed to the immobilization of the outer hydration layers. SMGHs/GG gels in the insoluble phase exhibited denser networks and rougher surfaces, supporting the enhanced rheological properties and water retention capacity of the gel., Conclusion: This work provides a basic foundation for the development of pH-driven SMGHs/GG gelation by examining complexation and coacervation processes. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Soft gels based on protein-polysaccharide composite systems play a crucial role in the dietary management of people with dysphagia. The effect of chia seed gum (CSG) on the gelling and swallowing properties of heat-induced whey protein isolate (WPI) gels (3.125-75 mg/mL) was investigated. The results showed that adding CSG reduced the gelation concentration of WPI and weak gels could form at 12.5 mg/mL WPI concentration. In addition, the viscoelasticity and water-binding capacity of the WPI/CSG composite gels were gradually enhanced with increasing WPI concentrations. The WPI/CSG composite systems can be classified as level 2-5 dysphagia-oriented foods according to the International Dysphagia Diet Standardization Initiative (IDDSI) framework. The incorporation of CSG promoted the cross-linking of protein aggregates and the formation of compact and continuous network structures, resulting in improved gelling properties of composite systems. This study contributes to the development of novel soft gel-type dysphagia foods with better textural characteristics., 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 Ltd. All rights reserved.)

Purpose: The human AlkB homolog (ALKBH) dioxygenase superfamily plays a crucial role in gene regulation and is implicated in cancer progression. Under hypoxic conditions, hypoxia-inducible factors (HIFs) dynamically regulate methylation by controlling various dioxygenases, thereby modulating gene expression. However, the role of hypoxia-responsive AlkB dioxygenase remains unclear., Methods: The molecular events were examined using real-time PCR and Western blot analysis. Tumor cell aggressiveness was evaluated through migration, invasion, MTT, trypan blue exclusion, and colony formation assays. In vivo metastatic models and xenograft experiments were conducted to evaluate tumor progression., Results: Here, we examined the expression of the ALKBH superfamily under hypoxic conditions and found that ALKBH4 expression was negatively regulated by hypoxia. Knockdown of ALKBH4 enhanced the epithelial-mesenchymal transition (EMT), cell migration, invasion, and growth in vitro. The silencing of ALKBH4 enhanced metastatic ability and tumor growth in vivo. Conversely, overexpression of ALLKBH4 reversed these observations. Furthermore, overexpression of ALKBH4 significantly reversed hypoxia/HIF-1α-induced EMT, cell migration, invasion, tumor metastasis, and tumorigenicity. Notably, high expression of ALKBH4 was associated with better outcomes in head and neck cancer and breast cancer patients. Enrichment analysis also revealed that ALKBH4 was negatively enriched in hypoxia-related pathways. Clinically, a negative correlation between ALKBH4 and HIF-1α protein expression has been observed in tissues from both head and neck cancers and breast cancers., Conclusion: These findings collectively suggest that ALKBH4 acts as a tumor suppressor and holds therapeutic potential for hypoxic tumors., (© 2024. The Author(s).)

Background: This study investigated the contribution of 11 polysaccharides (2%, w/w), including pectin (PC), κ-carrageenan (KC), ι-carrageenan (IC), gellan gum (GG), guar gum (GM), sodium alginate (SA), konjac gum (KG), gum arabic (GA), fucoidan (FC), locust bean gum (LBG), and curdlan (CD), to the gel and microstructural properties of Meretrix meretrix clam gel (MMG)., Results: The hardness, springiness and chewiness of MMG with KC, IC, GG, SA and FC addition increased by ~10%-250%, while PC, GM, KG and LBG groups decreased by ~0.6% to 69%. KC, IC, SA, GG and FC decreased the cooking loss rate (CLR) by 69.4% to 88.7% and correspondingly enhanced the water holding capacity (WHC) by 10.2% to 21.4%, which was accompanied by an increased bound water and immobilized water area and high hydrogen proton density. The addition of KC transformed the MMG microstructure from a loose network with large pores to a compact, dense network, reducing lacunarity by 57.9%. The primary intermolecular forces in MMG with the incorporation of KC, IC, GG, SA and FC were hydrophobic interactions and disulfide bonds, which increased by 32.8%-105.3% and 45.6%-114.5% than MMG alone, respectively., Conclusion: Collectively, KC, IC, GG, SA and FC could improve the gel properties of MMG and the strongest synergistic combination was found in the MMG/KC system. This study suggests that the incorporation of polysaccharides is a strategy with potential for modifying the gel properties of shellfish surimi products. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Despite complete resection, 20%-50% of patients with localized renal cell carcinoma (RCC) experience recurrence within 5 years. Accurate assessment of prognosis in high-risk patients would aid in improving outcomes. Here we evaluate the use of circulating tumor DNA (ctDNA) in RCC using banked samples and clinical data from a single institution., Methods: The cohort consisted of 45 RCC patients (≥pT1b) who underwent complete resection. The presence of ctDNA in plasma was determined using a personalized, tumor-informed ctDNA assay (Signatera RUO, Natera, Inc.). Relationships with outcomes and other relevant clinical variables were assessed. The median follow-up was 62 months., Results: Plasma ctDNA was detected in 18 out of 36 patients (50%) pre-operatively and was associated with increased tumor size (mean 9.3 cm vs. 7.0 cm, P < .05) and high Fuhrman grade (60% grades III-IV vs 27% grade II, P = .07). The presence of ctDNA, either pre-operatively or at any time post-operatively, was associated with inferior relapse-free survival (HR = 2.70, P = .046; HR = 3.23, P = .003, respectively). Among patients who were ctDNA positive at any time point, the sensitivity of relapse prediction was 84% with a PPV of 90%. Of note, ctDNA positivity at a post-surgical time point revealed a PPV of 100% and NPV of 64%. The lack of ctDNA detection at both time points yielded an NPV of 80%., Conclusions: Detection of plasma ctDNA using a personalized assay is prognostic of recurrence in patients with resected RCC. Herein, we describe a successful approach for its application and identify potential limitations to be addressed in future studies., (© The Author(s) 2024. Published by Oxford University Press.)

The prevalence of obesity in the United States has continued to increase over the past several decades. Understanding how diet-induced obesity modulates mucosal immunity is of clinical relevance. We previously showed that consumption of a high fat, high sugar "Western" diet (WD) reduces the density and function of small intestinal Paneth cells, a small intestinal epithelial cell type with innate immune function. We hypothesized that obesity could also result in repressed gut adaptive immunity. Using small intestinal intraepithelial lymphocytes (IEL) as a readout, we found that in non-inflammatory bowel disease (IBD) subjects, high body mass index correlated with reduced IEL density. We recapitulated this in wild type (WT) mice fed with WD. A 4-week WD consumption was able to reduce IEL but not splenic, blood, or bone marrow lymphocytes, and the effect was reversible after another 2 weeks of standard diet (SD) washout. Importantly, WD-associated IEL reduction was not dependent on the presence of gut microbiota, as WD-fed germ-free mice also showed IEL reduction. We further found that WD-mediated Farnesoid X Receptor (FXR) activation in the gut triggered IEL reduction, and this was partially mediated by intestinal phagocytes. Activated FXR signaling stimulated phagocytes to secrete type I IFN, and inhibition of either FXR or type I IFN signaling within the phagocytes prevented WD-mediated IEL loss. Therefore, WD consumption represses both innate and adaptive immunity in the gut. These findings have significant clinical implications in the understanding of how diet modulates mucosal immunity., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T. Stappenbeck advises Janssen, Boehringer Ingelheim, Kallyope, Takada, and Roche. T.C. Liu has research contracts with Denali Therapeutics and Interline Therapeutics. All other authors declare no relevant competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The purpose of the experimental interventional study was to examine the influence of intraocularly applied amphiregulin, a member of the epidermal growth factor (EGF) family, on axial length in young non-human primates. It included three non-human primates (Macaca mulatta), aged 4-6 years. The left eyes received three intravitreal injections of amphiregulin (400ng/50 μl) in intervals of 4 weeks, while the right eyes received three intravitreal injections of phosphate buffered solution (50 μl) at the same time points. Ocular biometry was performed in weekly intervals. At baseline, the left eyes (study eyes) were shorter than the right (control) eyes (20.69 ± 0.21 mm versus 20.79 ± 0.24 mm; P < 0.001), with an inter-eye axial length (AL) difference (left minus right eye) of -0.10 ± 0.23 mm. Inter-eye AL difference increased (P < 0.001) to 0.15 ± 0.18 mm at study end, at 12 weeks after baseline. Axial elongation during the study was higher (P < 0.001) in the left eyes (20.69 ± 0.21 mm to 21.05 ± 0.29 mm or 0.36 ± 0.30 mm) than in the right eyes (20.79 ± 0.24 mm to 20.90 ± 0.31 mm or 0.11 ± 0.17 mm). In a parallel manner, inter-eye difference in vitreous cavity depth combined with lens thickness (left eye minus right eye) increased from -0.04 ± 0.17 mm at baseline to -0.02 ± 0.21 mm (P = 0.02), 0.04 ± 0.10 mm (P = 0.002), and to 0.42 ± 0.67 mm (P < 0.001) at 5, 6, and 12 weeks after baseline, respectively. The results suggest that intravitreally applied amphiregulin as EGF family member led to an increase in axial length in adolescent non-human primates. It supports the hypothesis of amphiregulin as EGF family member being involved in the process of axial elongation., Competing Interests: Declaration of competing interest J.B. Jonas, S. Panda-Jonas: European patent EP 3 271 392, JP 2021–119 187, and US 11 008 385: "Agents for use in the therapeutic or prophylactic treatment of myopia or hyperopia; Patent application: European patent application: WO 2021/198 369 A1; PCT/EP2021/058 500: Agents for use in the therapeutic or prophylactic treatment of retinal pigment epithelium-associated diseases. All other authors explicitly state that they have no conflicts of interest in connection with this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The presence of prolonged symptoms after COVID infection worsens the workability and quality of life. 200 adults with long COVID syndrome were enrolled after medical, physical, and mental screening, and were divided into two groups based on their performance. The intervention group (n = 100) received supervised rehabilitation at Department of Pulmonology, Semmelweis University with the registration number 160/2021 between 01/APR/2021-31/DEC/2022, while an age-matched control group (n = 100) received a single check-up. To evaluate the long-term effects of the rehabilitation, the intervention group was involved in a 2- and 3-month follow-up, carrying out cardiopulmonary exercise test. Our study contributes understanding long COVID rehabilitation, emphasizing the potential benefits of structured cardiopulmonary rehabilitation in enhancing patient outcomes and well-being. Significant difference was found between intervention group and control group at baseline visit in pulmonary parameters, as forced vital capacity, forced expiratory volume, forced expiratory volume, transfer factor for carbon monoxide, transfer coefficient for carbon monoxide, and oxygen saturation (all p < 0.05). Our follow-up study proved that a 2-week long, patient-centered pulmonary rehabilitation program has a positive long-term effect on people with symptomatic long COVID syndrome. Our data showed significant improvement between two and three months in maximal oxygen consumption (p < 0.05). Multidisciplinary, individualized approach may be a key element of a successful cardiopulmonary rehabilitation in long COVID conditions, which improves workload, quality of life, respiratory function, and status of patients with long COVID syndrome., (© 2024. The Author(s).)

Background: 3-Monochloro-propanediol esters (3-MCPDEs), commonly found in refined edible oils and related products, have generated concerns due to their nephrotoxicity and carcinogenicity, yet clinical evidence remains limited., Objectives: In this study, we aimed to assess, for the first time, the accumulation of 3-MCPDEs in human kidney tissues, focusing on 68 participants, some with and others without renal cell carcinoma (RCC)., Methods: An analytical method for 3-MCPDE determination in kidney tissues underwent partial validation to ensure its suitability for sample analysis. The analyst was blind to the sample groups., Results: Results revealed significantly higher 3-MCPDE levels in RCC patients compared to non-RCC counterparts (0.22 vs. 0.01 µg/g) ( p < 0.01). Moreover, no significant correlation was found between 3-MCPDE levels and tumor stage or size in the RCC group., Conclusions: Accumulation of 3-MCPDEs in humans, with significantly higher levels was observed in kidney tumor specimens compared to non-patients. These findings suggest minimizing the intake of 3-MCPD and its esters in diets in order to reduce potential negative health impacts.

Background: To examine if pregnancy affects the prognosis of uveal melanoma (UM) patients undergoing plaque brachytherapy (PBT) and to assess if PBT has any subsequent impact on pregnancy outcomes., Methods: A retrospective, single-center study was carried out at Beijing Tongren Hospital, focusing on women of childbearing age diagnosed with UM and treated with iodine-125 plaque brachytherapy. Both the outcomes of pregnancies and the health status of the fetuses were monitored. Survival analyses were conducted using the Kaplan-Meier method, with endpoints being metastasis and death., Results: A total of 13 patients who had full-term pregnancies and 96 non-pregnant women matched by age and tumor size were included. The mean follow-up time was 67.0 ± 27.7 months (median:66.0 months, range:21.0 to 116.0 months). In the pregnant group, two patients developed metastases, one of whom died shortly after delivery; local recurrence of UM occurred in 2 patients after or during delivery, and 2 other patients developed secondary glaucoma due to radiation retinopathy. None of the other pregnant patients reported any signs of disease progression. In the control group, 18 metastasis cases including 12 deaths were documented. Pregnant patients and matched control subjects showed no statistical difference in both Metastasis-free survival (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.15-2.86; P = 0.576) and overall survival (HR: 0.48, 95% CI: 0.06-3.66; P = 0.464). All pregnant patients carried the pregnancy to term and delivered healthy children with no report of placental or infant metastases to date., Conclusion: Pregnancy does not appear to negatively impact the prognosis of UM patients undergoing PBT. PBT showed no observable detriment to maternal fertility and exhibited no teratogenic effects on the fetus. However, the long-term implications of PBT on pregnancy remain uncertain, necessitating additional, prolonged follow-up studies., (© 2024. The Author(s).)

Background: In early breast cancer (EBC) patients, we aimed to determine whether circulating tumor DNA (ctDNA) analysis following primary surgery, before systemic therapy, identified molecular residual disease and was associated with risk of relapse and relapse-free survival (RFS)., Methods: Plasma was collected, retrospectively, before surgery, 1-14 weeks post-operatively, and before adjuvant therapy, and in a subset of patients after adjuvant therapy. A personalized, tumor-informed, multiplex PCR next generation sequencing assay (Signatera™) was used for ctDNA detection and quantification. The primary objective was to compare RFS and distant recurrence-free survival (DRFS) in patients with detected versus non-detected ctDNA., Results: A total of 48 patients with EBC (median age 50.5 years) [34 hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), 5 HER2+, 9 triple-negative breast cancer) were included. ctDNA was detected in 64.5% (20/31) of patients before surgery, and 35.4% (17/48) after surgery. ctDNA detection before surgery was associated with tumor grade (P = 0.019), ctDNA detection after surgery was associated with receptor subtype (P = 0.01). Patients with ctDNA detected after surgery had worse DRFS [hazard ratio = 5.5, 95% confidence interval (CI) 1.1-28.5, P = 0.04]. RFS in patients with ctDNA detected after surgery was worse than in those with lack of ctDNA detection, although not statistically significant (hazard ratio = 3.7, 95% CI 0.9-15.7, P = 0.073). Patients with ctDNA detected preoperatively or post-operatively had a trend towards worse RFS (hazard ratio = 7.8, 95% CI 0.9-63.7, P = 0.05) and DRFS (hazard ratio = 6.8, 95% CI 0.8-57, P = 0.07) compared with those with ctDNA undetected at both timepoints. ctDNA detection anticipated clinical relapse with a median lead time of 16 months., Conclusions: In patients with treatment-naive EBC, ctDNA is detectable after surgery. The absence of ctDNA at a single post-surgical timepoint is associated with improved DRFS, supporting the development of future trials studying de-escalation of systemic therapy., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Molybdenum cofactor deficiency type A has successfully been treated in a small number of children with daily intravenous administration of cyclic pyranopterin monophosphate. Pharmacodynamic data for this novel treatment have not been published and alternative dosing intervals have not been explored. We monitored pharmacodynamic biomarkers of sulfite oxidase and xanthine oxidoreductase activity in three patients with MoCD-A for a period of 2 to 9 months after discontinuation of cPMP substitution. We found that the clinical and metabolic effects were sustained for longer than expected, over 7 days at least. Our data implicate a biological half-life of the molybdenum cofactor dependent enzyme activities of approximately 3 days and suggest the possibility that less frequent than once daily dosing intervals could be a safe alternative to current practice., Competing Interests: Declaration of competing interest BCS was principal investigator for clinical trials sponsored by Alexion Pharma International, and Origin Biosciences Inc. He reports a personal fee for attendance at an Advisory Board meeting and an unconditional educational grant from Origin Biosciences Inc. KB, HTW, AH, EE and VK have no conflict of interests to report. cPMP for the treatment of patients was provided free of charge on compassionate grounds from Colbourne Pharmaceuticals GmbH and Origin BioSciences Inc., respectively., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Antimicrobial therapy plays a crucial role in the management of CDI patients. However, the standard agent for treating CDIs is limited to oral fidaxomicin or vancomycin. For patients made nil by mouth, there is a clinically urgent and essential need to develop an intravenous antibiotic., Methods: For C. difficile with the lowest MIC of nemonoxacin and vancomycin, the inhibitory effects were tested using the kinetic time-kill assay and ex vivo co-culture model. The effectiveness of nemonoxacin and vancomycin in inhibiting spore germination, the sporicidal activity, and the treatment of mice with CDIs were compared., Results: For clinical isolates and laboratory strains, lower MICs of nemonoxacin against C. difficile than levofloxacin and ciprofloxacin were observed, even in those harboring point mutations in the quinolone-resistance determining region. Although nemonoxacin failed to suppress spore outgrowth and germination in C. difficile , it exhibited an effective inhibitory effect against C. difficile in the kinetic time-kill assay and the ex vivo co-culture model. Mice receiving intraperitoneal nemonoxacin had less weight loss, higher cecum weight, a longer colon length, and lower expression of the tcdB gene, compared with untreated mice. Notably, there were no significant differences observed in weight loss, cecum weight, colon length, or tcdB gene expression between mice treated with vancomycin and those treated with any dose of nemonoxacin. Similarly, no significant differences were found between mice receiving combination therapy of intraperitoneal nemonoxacin plus oral vancomycin and those treated with intraperitoneal nemonoxacin or oral vancomycin alone., Discussion: The potential role of nemonoxacin, which can be administered parenterally, for treating CDIs was evidenced through the in vitro , ex vivo , and mouse models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee, Yan, Wu, Ko, Tsai and Hung.)

Objective. Sleep spindles contain crucial brain dynamics information. We introduce the novel non-linear time-frequency (TF) analysis tool 'Concentration of Frequency and Time' (ConceFT) to create an interpretable automated algorithm for sleep spindle annotation in EEG data and to measure spindle instantaneous frequencies (IFs). Approach. ConceFT effectively reduces stochastic EEG influence, enhancing spindle visibility in the TF representation. Our automated spindle detection algorithm, ConceFT-Spindle (ConceFT-S), is compared to A7 (non-deep learning) and SUMO (deep learning) using Dream and Montreal Archive of Sleep Studies (MASS) benchmark databases. We also quantify spindle IF dynamics. Main results. ConceFT-S achieves F1 scores of 0.765 in Dream and 0.791 in MASS, which surpass A7 and SUMO. We reveal that spindle IF is generally nonlinear. Significance. ConceFT offers an accurate, interpretable EEG-based sleep spindle detection algorithm and enables spindle IF quantification., (© 2024 Institute of Physics and Engineering in Medicine.)

Perovskite solar cells have been proven to enhance cell characteristics by introducing passivation materials that suppress defect formation. Defect states between the electron transport layer and the absorption layer reduce electron extraction and carrier transport capabilities, leading to a significant decline in device performance and stability, as well as an increased probability of non-radiative recombination. This study proposes the use of an amino acid (L-Histidine) self-assembled monolayer material between the transport layer and the perovskite absorption layer. Surface analysis revealed that the introduction of L-Histidine improved both the uniformity and roughness of the perovskite film surface. X-ray photoelectron spectroscopic analysis showed a reduction in oxygen vacancies in the lattice and an increase in Ti 4+ , indicating that L-Histidine successfully passivated trap states at the perovskite and TiO 2 electron transport layer interface. In terms of device performance, the introduction of L-Histidine significantly improved the fill factor (FF) because the reduction in interface defects could suppress charge accumulation and reduce device hysteresis. The FF of large-area solar modules (25 cm 2 ) with L-Histidine increased from 55% to 73%, and the power conversion efficiency (PCE) reached 16.5%. After 500 h of aging tests, the PCE still maintained 91% of its original efficiency. This study demonstrates the significant impact of L-Histidine on transport properties and showcases its potential for application in the development of large-area perovskite module processes.

Dysphagia has emerged as a serious health issue facing contemporary society. Consuming thickened liquids is an effective approach for improving the swallowing safety for dysphagia patients. The thickening effect of chia seed gum (CSG), a novel thickener, in different dispersing media (water, orange juice, and skim milk) was investigated. Moreover, the potential application of CSG for dysphagia management was evaluated by comparison with xanthan gum (XG) and guar gum (GG). The thickened liquids prepared with 0.4 %-1.2 % (w/v) CSG, XG, and GG could be classified into levels 1-4, 2-4, and 1-3, respectively, according to the International Dysphagia Diet Standardization Initiative (IDDSI) framework. All the thickened liquids displayed shear-thinning characteristics that facilitated safe swallowing. The viscosities (η 50 ) of CSG dissolved in water (0.202-1.027 Pa·s) were significantly greater than those of CSG dissolved in orange juice (0.070-0.690 Pa·s) and skim milk (0.081-0.739 Pa·s), indicating that CSG had a greater thickening effect in water than in orange juice and skim milk. Compared with those prepared with GG, the thickened liquids prepared with CSG and XG exhibited greater viscoelasticity, better water-holding capacity, and more compact networks. The findings suggested that CSG can be used as a potential thickener for thickening liquid foods to manage dysphagia., 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 B.V.)

Breast cancer ranks as the most prevalent cancer globally, surpassing lung cancer, with recurrence/metastasis to be its main account for the cancer-related mortality. MicroRNAs (miRNAs) participate critically in various physiological and pathological processes through posttranscriptional regulation of downstream genes. Our preliminary findings identified miR-338-5p, potentially linked to metastasis in breast cancer, a previously unexplored area. Analysis of the GSE38867 dataset revealed the decreased miR-338-5p expression in metastatic breast cancer compared to normal tissues. Cellular function experiments and a xenograft tumor model demonstrated the inhibitory function of miR-338-5p on the progression of breast cancer in vitro and in vivo . Furthermore, it downregulated the expression of mesenchymal biomarkers and NOTCH1 significantly. With the predicting targets of miR-338-5p and transcription factors of the NOTCH1 gene, coupled with dual luciferase reporter assays, it is identified ETS1 as the interactor between miR-338-5p and NOTCH1. In breast cancer tissues, as well as in our xenograft tumor model, expression of ETS1 and NOTCH1 was positively correlated using immunohistochemical staining. This study reports, for the first time, on the miR-338-5p/ETS1/NOTCH1 axis and its pivotal role in breast cancer proliferation and metastasis. These findings propose a novel therapeutic strategy for breast cancer patients and lays a foundation for its clinical detection and treatment evaluation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The individual ingredients of 1,3-Propanediol, Soline, and Fucocert ® (PSF) are often used as cosmetic formulations in skin care. In addition, the mixture of Lecigel, Cetiol ® CC, Activonol-6, and Activonol-M (LCAA) is often used as a cosmetic base. However, whether the combination of LCAA with PSF (LCAA-PSF) exerts a therapeutic effect on psoriasis remains unclear. In this study, mice induced with imiquimod (IMQ) were divided into three groups and administered 100 mg/day of LCAA, 100 mg/day of LCAA-PSF, or Vaseline on the dorsal skin of each mouse. Weight-matched mice treated with Vaseline alone were used as controls. Hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay(ELISA) were used to assess tissue morphology and inflammatory cytokines. RNA sequencing analysis was used to predict the mechanism underlying the action of LCAA-PSF against psoriasis, while immunohistochemical analysis validation was used to identify pertinent molecular pathways. The results demonstrated that LCAA-PSF alleviated IMQ-induced keratinocyte differentiation/ proliferation bydecreasingthe serum levels of inflammatory cytokines such as IL-6, TNF-α, IL-23, and IL-17A and the epidermisof TGFβ, Ki67, CK5/6, and VEGF expression, which is associated with angiogenesis and keratinocyte differentiation/ proliferation. These findings highlight the antipsoriatic activity of LCAA-PSF in a psoriasis-like mouse model and suggest this may occurvia the inhibition of inflammatory factor secretionand the TGFβ-related signal pathway.

Calcium β-hydroxy-β-methylbutyrate (CaHMB), a functional calcium salt, is used to maintain and improve muscle health. Here, a new hydrogel material prepared from alginate (ALG) with three M/G ratios (1:1, 2:1, and 1:2) and CaHMB (0-2 mg/mL) was investigated. CaHMB regulates the formation and properties of ALG hydrogels through chelation and hydrogen bonding. When the M/G ratio was 2:1, the anionic groups of CaHMB containing carboxyl and hydroxyl groups formed hydrogen bonds with the polysaccharide chains, hindering the capture of Ca 2+ by the G-residue fragments of ALG, which in turn retarded the gelation process. The noncalcium cross-linked polysaccharide chain structure of ALG and the anionic group of CaHMB also affected the water distribution in the hydrogel, especially when M residue content ≥G residue content. Lower M/G ratios and higher CaHMB concentrations could increase the number of "egg box" crosslinking junctions of calcium alginate, and the microstructure was denser in the gel pores, resulting in a stronger gel strength and more free water bound in the gel matrix. This study provides a theoretical and methodological basis for the design of novel hydrogels by studying the crosslinking features of ALG/CaHMB., 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.)

The proliferation of neural stem cells (NSCs) is precisely regulated by extracellular environmental factors. In situ hypoxia, one of the key factors involved in the regulation of NSC characteristics, has attracted increasing amounts of attention. Numerous studies have demonstrated that hypoxia can significantly promote the formation of neurospheres and the proliferation of NSCs in vitro and that intermittent hypoxia can promote the proliferation of endogenous NSCs in vivo. In this article, the effects of different concentrations of oxygen on NSC proliferation and differentiation both in vivo and in vitro are reviewed, and the potential applications of hypoxia-preconditioned NSCs, as well as research progress and challenges in the treatment of central nervous system diseases, are further summarized. Here, the critical role of oxygen in the neurogenesis of NSCs is emphasized, and insights into the use of hypoxia to regulate NSC characteristics are provided.

Low physical activity (PA) measured by accelerometers and low heart rate variability (HRV) measured from short-term ECG recordings are associated with worse cognitive function. Wearable long-term ECG monitors are now widely used, and some devices also include an accelerometer. The objective of this study was to evaluate whether PA or HRV measured from long-term ECG monitors was associated with cognitive function among older adults. A total of 1590 ARIC participants had free-living PA and HRV measured over 14 days using the Zio ® XT Patch [aged 72-94 years, 58% female, 32% Black]. Cognitive function was measured by cognitive factor scores and adjudicated dementia or mild cognitive impairment (MCI) status. Adjusted linear or multinomial regression models examined whether higher PA or higher HRV was cross-sectionally associated with higher factor scores or lower odds of MCI/dementia. Each 1-unit increase in the total amount of PA was associated with higher global cognition (β = 0.30, 95% CI: 0.16-0.44) and executive function scores (β = 0.38, 95% CI: 0.22-0.53) and lower odds of MCI (OR = 0.38, 95% CI: 0.22-0.67) or dementia (OR = 0.25, 95% CI: 0.08-0.74). HRV (i.e., SDNN and rMSSD) was not associated with cognitive function. More research is needed to define the role of wearable ECG monitors as a tool for digital phenotyping of dementia.

The prevalence of non-alcoholic fatty liver disease (NAFLD) has dramatically increased in recent years, and it is highly associated with metabolic diseases, as well as the development of hepatocellular carcinoma. However, effective therapeutic strategies for the treatment of NAFLD are still scarce. Although hydrogen-rich water shows beneficial effects for hepatic steatosis, the inconvenience limits the application of this antioxidant. In light of this, hydrogen-rich coral calcium (HRCC) was developed due to its convenience and quantifiable characteristics. However, the effects of HRCC on NAFLD are still unknown. In the present study, we found that HRCC treatment improved methionine-and-choline-deficient diet (MCD)-induced hepatic steatosis, increased aspartate aminotransferase and alanine aminotransferase levels, and elevated hepatic inflammatory factor expressions in mice. In addition to the increased expressions of antioxidative enzymes, we found that HRCC increased the expressions of bile acid biosynthesis-related genes, including Cyp8b1 and Cyp27a1 . Increased hepatic bile acid contents, such as muricholic acids, 23 nor-deoxycholic acid, glycoursodeoxycholic acid, and cholic acids, were also confirmed in MCD mice treated with HRCC. Since the biogenesis of bile acids is associated with the constitution of gut microbiome, the alterations in gut microbiome by HRCC were evaluated. We found that HRCC significantly changed the constitution of gut microbiome in MCD mice and increased the contents of Anaerobacterium, Acutalibacter, Anaerosacchariphilus, and Corynebacterium. Taken together, HRCC improved MCD-induced NAFLD through anti-inflammatory mechanisms and by increasing antioxidative activities. Additionally, HRCC might alter gut microbiome to change hepatic bile acid contents, exerting beneficial effects for the treatment of NAFLD.

Background: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder with varied clinical courses and prognoses, not only did the patients suffer from physical impairment, but also various physical and psychiatric comorbidities. Growing evidence have suggested that mental disorders in SLE patients, can lead to various adverse consequences., Aim: To explored the features and influencing factors of mental health in patients with SLE and clarifying the correlations between mental health and personality characteristics and perceived social support. The results would provide a basis for psychological intervention in patients with SLE., Methods: The clinical data of 168 patients with SLE admitted at the First Affiliated Hospital of Hainan Medical University between June 2020 and June 2022 were collected. Psychological assessment and correlation analysis were conducted using the Symptom Checklist-90 (SCL-90) and Perceived Social Support Scale, and the collected data were compared with the national norms in China. The relevant factors influencing mental health were identified by statistical analysis. A general information questionnaire, the Revised Life Orientation Test, and Short-Form 36-Item Health Survey were employed to assess optimism level and quality of life (QoL), respectively., Results: Patients with SLE obtained higher scores for the somatization, depression, anxiety, and phobic anxiety subscales than national norms ( P < 0.05). A correlation was identified between total social support and total SCL-90 score or each subscale ( P < 0.05). The factors significantly affecting patients' mental health were hormone dosage and disease activity index (DAI) ( P < 0.05). The average optimism score of patients with SLE was 14.36 ± 4.42, and 30 cases were in the middle and lower levels. A positive correlation was found between optimism level and QoL scores., Conclusion: Patients with SLE develop psychological disorders at varying degrees, which are significantly influenced by hormone dosage and DAI. Patients' mental health should be closely monitored during clinical diagnosis and treatment and provided adequate support in establishing positive, healthy thinking and behavior patterns and improving their optimism level and QoL., Competing Interests: Conflict-of-interest statement: There is no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective. Assessing signal quality is crucial for biomedical signal processing, yet a precise mathematical model for defining signal quality is often lacking, posing challenges for experts in labeling signal qualities. The situation is even worse in the free living environment. Approach. We propose to model a PPG signal by the adaptive non-harmonic model (ANHM) and apply a decomposition algorithm to explore its structure, based on which we advocate a reconsideration of the concept of signal quality. Main results. We demonstrate the necessity of this reconsideration and highlight the relationship between signal quality and signal decomposition with examples recorded from the free living environment. We also demonstrate that relying on mean and instantaneous heart rates derived from PPG signals labeled as high quality by experts without proper reconsideration might be problematic. Significance. A new method, distinct from visually inspecting the raw PPG signal to assess its quality, is needed. Our proposed ANHM model, combined with advanced signal processing tools, shows potential for establishing a systematic signal decomposition based signal quality assessment model., (© 2024 Institute of Physics and Engineering in Medicine.)

The development of novel drugs from basic science to clinical practice requires several years, much effort, and cost. Drug repurposing can promote the utilization of clinical drugs in cancer therapy. Recent studies have shown the potential effects of lomitapide on treating malignancies, which is currently used for the treatment of familial hypercholesterolemia. We systematically review possible functions and mechanisms of lomitapide as an anti-tumor compound, regarding the aspects of apoptosis, autophagy, and metabolism of tumor cells, to support repurposing lomitapide for the clinical treatment of tumors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

It remains challenging to comprehensively understand the packing models of conjugated polymers, in which side chains play extremely critical roles. The side chains are typically flexible and non-conductive and are widely used to improve the polymer solubility in organic solutions. Herein, a buffer chain model is proposed to describe link between conjugated backbone and side chains for understanding the relationship of crystallization competition of conductive conjugated backbones and non-conductive side chains. A longer buffer chain is beneficial for alleviating such crystallization competition and further promoting the spontaneous packing of conjugated backbones, resulting in enhanced charge transport properties. Our results provide a novel concept for designing conjugated polymers towards ordered organization and enhanced electronic properties and highlight the importance of balancing the competitive interactions between different parts of conjugated polymers., (© 2024 Wiley-VCH GmbH.)

Purpose: Linear accelerator-based stereotactic radiosurgery (SRS) has become a mainstay for simultaneous management of multiple intracranial targets. Recent improvements in treatment planning systems (TPS) have enabled treatment of multiple brain metastases using dynamic conformal arcs (DCA) and a single treatment isocenter. However, as the volume of healthy tissue receiving at least 12 Gy (V12) is linked to the probability of developing radionecrosis, balancing target coverage while minimizing V12 is a critical factor affecting SRS plan quality. Current TPS allow users to adjust various parameters influencing plan optimization. The purpose of this work is to quantify the effect of negative margins on V12 for cranial SRS plans managing multiple brain metastases., Methods: Using the Brainlab Elements v3.0 TPS (Brainlab, Munich, Germany), we calculated V10, V12, V15, monitor units, and conformity index for seventeen SRS plans treating 2-10 metastases on our Elekta Versa HD (Elekta, Stockholm, Sweden) linear accelerator. We compared plans optimized using 70%-90% prescription isodose lines (IDL) in 5% increments., Results: Irrespective of the number of treated metastases, optimization at a lower prescription IDL reduced V10, V12, and V15 and increased MU compared to the 90% IDL (p < 0.01). However, comparing the 70% and 75% IDL optimizations, there was little difference in tissue sparing. The conformity index showed no consistent trends at different IDLs due to a significant spread in case data., Conclusion: For our plans treating up to 10 metastases, diminishing returns for tissue sparing at IDLs below 80% paired with increasing treatment MU and dosimetric hot spot made optimization at lower IDLs less favorable. In our clinic, after consulting with a physician, it was determined that optimization at the 80% IDL achieved the best balance of V12, treatment MU, and maximum dose. Clinics implementing LINAC-based SRS programs may consider using similar evaluations to develop their own clinical protocols., (© 2024 The Authors. Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

This study focused on binary hydrogels constructed from lotus rhizome starch (LRS) and three types of carrageenan ( κ -C, ι -C, and λ -C). The enthalpy of LRS gelatinization was reduced by 32.1%-88.4% with the incorporation of carrageenan. Compared with ι -C and λ -C, the conformations of κ -C more facilitated the development of the binary hydrogel network structure. The ability of the LRS/carrageenan binary hydrogel to immobilize water was mainly related to the effect of different types of carrageenan on starch molecular ordering. LRS-based hydrogels were recognized as level 4 in the International Dysphagia Diet Standardization Initiative (IDDSI) framework. Nevertheless, the incorporation of carrageenan significantly reduced the ability of the LRS hydrogel to resist stress under large deformations, which might be favorable to oral processing and swallowing. This research provides preliminary evidence for relevant industries to use carrageenan to adjust LRS hydrogel properties and improve the quality of starch-based foods for dysphagia management., 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).)

Esophageal cancer is a common malignancy worldwide with a poor prognosis without radical resection. Neoadjuvant concurrent chemoradiotherapy (NACRT) followed by esophagectomy is widely used for treating locally advanced esophageal cancer in the thorax. The study aimed to assess mutation profiles and their correlation with therapeutic outcomes in patients diagnosed with locally advanced thoracic esophageal squamous cell carcinoma (ESCC). A retrospective analysis was conducted on 62 patients with ESCC who underwent NACRT. All patients received concurrent chemoradiotherapy (CCRT) utilizing intensity-modulated radiation therapy alongside concurrent chemotherapy with a cisplatin-based regimen. A 35-gene next-generation sequencing (NGS) panel detecting 402 genetic variants was used, which has been proven predictive in ESCC patients who received definitive chemoradiation. The 35-gene mutation profiles were analyzed in pre-treatment biopsies. The results reveled there were variants correlated with pathological complete remission or partial response, overall survival, and progression-free survival. A combination of p.Pro1319Ser and p.Arg2159Gly mutations in the MUC17 gene demonstrated an adverse impact on pathological response (OR [95% CI] = 7.00 (3.07-15.94), P < 0.001). Additionally, the variants located in the MUC17, MUC4 , and MYH4 genes exhibited notably effects on tumor recurrence or mortality. Patients harboring either the MUC17 p.Thr2702Val or MUC4 p.Thr3355Ser mutation displayed a more than four-fold increased risk for disease recurrence or mortality. We concluded that specific mutations correlated to the pathological complete response in ESCC receiving neoadjuvant chemoradiation can be identified through the utilization of 35-gene expression profiles. Further investigation into the pathophysiological roles of MUC17 and MUC4 mutations in ESCC is warranted., Competing Interests: None., (AJCR Copyright © 2024.)

The sleep-wake cycle regulates interstitial fluid and cerebrospinal fluid (CSF) tau levels in both mouse and human by mechanisms that remain unestablished. Here, we reveal a novel pathway by which wakefulness increases extracellular tau levels in mouse and humans. In mice, higher body temperature (BT) associated with wakefulness and sleep deprivation increased CSF tau. In vitro , wakefulness temperatures upregulated tau secretion via a temperature-dependent increase in activity and expression of unconventional protein secretion pathway-1 components, namely caspase-3-mediated C-terminal cleavage of tau (TauC3), and membrane expression of PIP 2 and syndecan-3. In humans, the increase in both CSF and plasma tau levels observed post-wakefulness correlated with BT increase during wakefulness. Our findings suggest sleep-wake variation in BT may contribute to regulating extracellular tau levels, highlighting the importance of thermoregulation in pathways linking sleep disturbance to neurodegeneration, and the potential for thermal intervention to prevent or delay tau-mediated neurodegeneration., Competing Interests: Competing interests: All authors declare no competing interests.

The conduction efficiency of ions in excitable tissues and of charged species in organic conjugated materials both benefit from having ordered domains and anisotropic pathways. In this study, a photocurrent-generating cardiac biointerface is presented, particularly for investigating the sensitivity of cardiomyocytes to geometrically comply to biomacromolecular cues differentially assembled on a conductive nanogrooved substrate. Through a polymeric surface-templated approach, photoconductive substrates with symmetric peptide-quaterthiophene (4T)-peptide units assembled as 1D nanostructures on nanoimprinted polyalkylthiophene (P3HT) surface are developed. The 4T-based peptides studied here can form 1D nanostructures on prepatterned polyalkylthiophene substrates, as directed by hydrogen bonding, aromatic interactions between 4T and P3HT, and physical confinement on the nanogrooves. It is observed that smaller 4T-peptide units that can achieve a higher degree of assembly order within the polymeric templates serve as a more efficient driver of cardiac cytoskeletal anisotropy than merely presenting aligned -RGD bioadhesive epitopes on a nanotopographic surface. These results unravel some insights on how cardiomyocytes perceive submicrometer dimensionality, local molecular order, and characteristics of surface cues in their immediate environment. Overall, the work offers a cardiac patterning platform that presents the possibility of a gene modification-free cardiac photostimulation approach while controlling the conduction directionality of the biotic and abiotic components., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.