Search

Developing green and efficient delivery systems to promote bioavailability of bioactive ingredients is a sustained demand in food industry. In this work, the astaxanthin (AST)-loaded starch-based fast-dissolving nanofibers with core-shell structure were prepared by emulsion electrospinning technique without using any organic solvent. To load water-insoluble AST in hydrophilic octenyl succinic anhydride starch (OSAS)/polyvinyl alcohol (PVA) nanofiber matrices, AST-loaded nanoscale emulsions (212.19 ± 5.63 nm) with high encapsulation efficiency (91.54 ± 0.14 %) were prepared as a precursor for emulsion electrospinning, using OSAS/PVA aggregates as an emulsifier. The core-shell structure of nanofibers was revealed by the Transmission electron microscopy (TEM), with average diameter of 509.58 ± 12.77 nm, and 88.64 ± 0.49 % for AST were effectively encapsulated in core layer. Nanofiber mats exhibited high encapsulation efficiency (85.11 ± 1.53 %) and excellent storage stability over 7 d. Meanwhile, amorphous transformation of AST enabled it possess higher water solubility, bioaccessibility, and antioxidant properties (97.72 ± 2.17 %) than free AST in aqueous system. The results demonstrated that the green, nontoxic, and biodegradable nanofiber mats prepared by emulsion electrospinning successfully realized the encapsulation and delivery of AST, with broad application prospects in the food and pharmaceutical fields., 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.)

Non-homologous end joining (NHEJ), as one major pathway of DNA double-strand break (DSB) repair, could cause genomic instability, which plays pivotal roles in cancer development. While, chromatin remodeling complexes dictate the selection and orchestration of DSB repair pathways by regulating chromatin dynamics. However, the crosstalk between NHEJ and chromatin remodeling in cancer progress remains unclear. In this study, deficiency of GLTSCR1 causes resistance to DNA damage in colorectal cancer (CRC) cells by promoting NHEJ repair efficiency. Mechanistically, GLTSCR1 interacts with BRD9 to engage in the assembly of the non-canonical BAF complex (GBAF). However, GLTSCR1 deficiency disrupts GBAF and triggers the ubiquitination degradation of BRD9. Furthermore, GLTSCR1 deficiency causes aberrant opening in the promoter region of NHEJ repair-associated genes, which promotes CRC development. While, GLTSCR1 and its binding partner BRD9 are not directly involved in assembling NHEJ repair machinery; instead, they regulate the DNA accessibility of NHEJ repair-associated genes. Collectively, our findings confirm GLTSCR1 deficiency as a critical regulatory event of the NHEJ pathway in CRC development, which might require different therapeutic strategy for GLTSCR1 wild-type and mutant CRC., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Polymer dielectrics play an irreplaceable role in electrostatic capacitors in modern electrical systems, and have been intensively studied with their polarization and breakdown strength (E b ) optimized for high discharged energy density (U d ) at elevated temperatures. Small molecules have been explored as fillers, yet they deteriorate thermal stability of matrix which limits their optimal loading to ~1 wt%. Herein, we develop a polymer blend dielectric consisting of common polyimide and a bifunctional dipolar glass polymer which are synthesized from two small molecule components with wide band-gap and large dipole moment. The bifunctional dipolar glass with large molecular weight not only maintains thermal stability of polymer blends even at a high loading of 10 wt%, but also induces substantial enhancement in polarization and E b than any of individual components does, achieving an ultrahigh U d of 8.34 J cm -3 (150 °C) and 6.21 J cm -3 (200 °C) with a charge-discharge efficiency of 90%., (© 2024. The Author(s).)

Polymers capable of depolymerizing back to their own monomers offer a promising solution to address the challenges in polymer sustainability. Despite significant progress has been achieved in plastics circularity, chemical recycling of thermoplastic elastomers is relatively less concerned, largely because of their intrinsic complex multicomponents. This work creates a homopolymer-based platform towards chemically recyclable but tough thermoplastic elastomers. It is enabled by a semicrystalline polymer with high molecular weight but low crystallinity, which is prepared through ring-opening metathesis polymerization of a fully biobased cyclic olefin. By shifting the ring-chain equilibrium, quantitative conversions were achieved for both forward polymerization and reverse depolymerization. This simple circular, high-performance thermoplastic elastomer platform based on biomass highlights the importance of monomer design in addressing three challenges in sustainable polymers: the feedstock renewability, depolymerization selectivity, and performance trade-offs., (© 2024. The Author(s).)

Background: Vibrotactile stimulation has been studied in its efficacy of reducing freezing of gait (FOG) in patients with Parkinson's disease (PD). However, the results are still controversial. We evaluated the efficacy of a newly developed vibrotactile foot device on freezing severity and gait measures in PD patients with FOG., Objective: To evaluate the efficacy of vibrotactile foot device on PD patients with FOG., Methods: Thirty-three PD patients with FOG were examined during their "off" medication state. The efficacy of the vibrotactile foot device was evaluated using a gait protocol comprising walking trials with vibrotactile stimulation "off" and "on." Walking trials were videotaped for the offline rating by two movement disorder specialists. The Opal inertial sensor unit (128 Hz; Mobility Lab; APDM Inc., Portland, OR, USA) was used for quantitative gait analysis., Results: The results demonstrated 33.1% reduction in number of FOG episodes (P < 0.001) and 32.6% reduction of freezing episodes (P < 0.001). Quantitative gait analysis showed a significant increase in step length (P = 0.033). A moderate negative correlation was observed between the change of percent time frozen and age (r = -0.415, P = 0.016). 73% of participants reported minimal to substantial improvement in walking with this vibrating stimulation delivered by the vibrotactile foot device., Conclusions: The vibrotactile foot device is an efficient device that could significantly reduce freezing severity and provide gait regulation to patients with PD experiencing frequent freezing. It could potentially be used in the home environment for improving the quality of life., (© 2024 International Parkinson and Movement Disorder Society.)

This study aimed to investigate the expression of SF3B1 in non-small cell lung cancer, and its clinical significance, biological function, and molecular mechanisms. SF3B1 mRNA and protein levels were elevated in both lung squamous cell carcinoma and lung adenocarcinoma (LUAD) tissues based on TCGA data and immunohistochemistry. Notably, high SF3B1 expression in LUAD was significantly associated with increased lymph node metastasis. Functional experiments involving SF3B1 knockdown and overexpression demonstrated that SF3B1 facilitated the proliferation, invasion, and migration of LUAD cells. Additionally, the SF3B1 inhibitor pladienolide-B attenuated the aggressive behavior of LUAD cells both in vitro and in vivo. RNA sequencing analysis indicated that differentially expressed genes in the SF3B1 knockdown and SF3B1 inhibitor groups were enriched in ferroptosis-related pathways compared to their respective control groups. The antiferroptotic role of SF3B1 in LUAD cells was validated by detecting glutathione depletion, lipid peroxidation, and observing morphological changes using transmission electron microscopy. This process was confirmed to be independent of apoptosis and autophagy, as evidenced by the effects of the ferroptosis inducer erastin, the apoptosis inhibitor Z-VAD-FMK, and the autophagy inhibitor 3-methyladenine. Rescue experiments indicated that the antiferroptotic role of SF3B1 in LUAD is partially mediated by upregulating the expression of SLC7A11., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

In order to achieve high cell adhesion and growth efficiency on scaffolds for cultured meat, animal materials, especially gelatin, are necessary though the disadvantages of weak mechanical properties and poor stability of their hydrogel scaffolds are present during cell cultivation. Here, we use rice bran as a kind of filling and supporting materials to develop a composite scaffold with gelatin for fish cell cultivation, where rice bran is also inexpensive from high yield fibrous agricultural by-product. The rice bran (with a proportion of 1, 3, 5, 7, 10 to 3 of gelatin) could evenly distributed in the three-dimensional network composed of gelatin hydrogel. It contributed to delaying swelling and degradation rates, fixing water and improving elastic modulus. It is important that rice bran-gelatin hydrogel scaffolds (especially the hydrogel with 70 % rice bran, db) promoted piscine satellite cells (PSCs) proliferation effectively compared to the pure gelatin hydrogel, and the former could also support the differentiation of PSCs. Overall, this work showed a positive promotion to explore new source of scaffold materials like agricultural by-product for reducing the cost of cell cultured meat production., Competing Interests: Declaration of competing interest We declare that this paper has no conflicts of interest and the results reported in this manuscript have not been published elsewhere nor have they been submitted for publication elsewhere., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Analysis of extracellular vesicles (EV) is a promising noninvasive liquid biopsy approach for breast cancer detection, prognosis, and therapeutic monitoring. A comprehensive understanding of the characteristics and proteomic composition of breast cancer-specific EVs from human samples is required to realize the potential of this strategy. In this study, we applied a mass spectrometry-based, data-independent acquisition proteomic approach to characterize human serum EVs derived from patients with breast cancer (n = 126) and healthy donors (n = 70) in a discovery cohort and validated the findings in five independent cohorts. Examination of the EV proteomes enabled the construction of specific EV protein classifiers for diagnosing breast cancer and distinguishing patients with metastatic disease. Of note, TALDO1 was found to be an EV biomarker of distant metastasis of breast cancer. In vitro and in vivo analysis confirmed the role of TALDO1 in stimulating breast cancer invasion and metastasis. Finally, high-throughput molecular docking and virtual screening of a library consisting of 271,380 small molecules identified a potent TALDO1 allosteric inhibitor, AO-022, which could inhibit breast cancer migration in vitro and tumor progression in vivo. Together, this work elucidates the proteomic alterations in the serum EVs of breast cancer patients to guide the development of improved diagnosis, monitoring, and treatment strategies. Significance: Characterization of the proteomic composition of circulating extracellar vesicles in breast cancer patients identifies signatures for diagnosing primary and metastatic tumors and reveals tumor-promoting cargo that can be targeted to improve outcomes., (©2024 The Authors; Published by the American Association for Cancer Research.)

Polysaccharides have garnered significant attention as potential nanoparticle carriers for targeted tumor therapy due to their excellent biodegradability and biocompatibility. Polyguluronic acid (PG) is a homogeneous acidic polysaccharide fragment derived from alginate, which is found in brown algae, possesses excellent bioactivities, unique properties. This study explored the immunomodulatory activity of PG and developed PG-based nanogels through modified disulfide bonds and Ca 2+ dual crosslinking. We characterized their structure, assessed their drug-loading and release properties, and ultimately validated both the safety of the nanocarrier and the in vitro anti-tumor efficacy of the encapsulated drug. Results indicated that PG significantly enhanced the proliferative activity and phagocytosis of RAW264.7 cells while promoting reactive oxygen species (ROS) production and cytokine secretion. The study identified TLR4 as the primary receptor for PG recognition in RAW264.7 cells. Furthermore, PG-based drug-carrying nanogels were prepared, exhibiting uniform sizes of about 184 nm and demonstrating exceptional encapsulation efficiency (82.15 ± 0.82 %) and drug loading capacity (8.12 ± 0.08 %). In vitro release experiments showed that these nanogels could responsively release drugs under conditions of high glutathione (GSH) reduction, facilitating drug accumulation at tumor sites and enhancing therapeutic efficacy. This research not only expands the application of PG in drug delivery systems but also provides valuable insights into leveraging natural immunomodulatory polysaccharides as carriers for targeted drug delivery., 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 development of theragnostic nanosystems integrating FRET (fluorescence resonance energy transfer) imaging and chemodynamic therapy (CDT) for accurate diagnosis and effective treatment of lung tumors is still a big challenge. Herein, a peptide-assembled 3D DNAzyme motor nanodevice is engineered for a self-powered FRET amplifier profiling human neutrophil elastase (HNE) and self-supplied H 2 O 2 enhancing CDT. The nanodevice is prepared by depositing AuNPs on ZIF-8, in which ZIF-8 co-loaded the lysosomal targeting peptide-modified copper peroxides (PCPs) and hairpins (H1, H2, and H3), AuNPs are co-labeled by DNAzyme-peptide (DP) conjugate and H3. In the tumor micro-environment, HNE driven 3D DNAzyme walker followed by an exponential amplification constructed by a synergistic cross-activation between hybridization chain reaction and DNAzyme, generating a self-powered FRET amplifier. The FRET amplifier specifically measures HNE with a sensitivity of 0.026 pM, and successfully images exogenous HNE in living cells and monitors HNE in mouse models. Moreover, the PCPs can target lysosomes, reducing lysosome escape. The self-supplying H 2 O 2 undertaken by PCPs improves the Cu (II)-catalyzed Fenton-like reaction, effectively causing cell apoptosis to inhibit tumor growth. Significantly, the nanodevice successfully screens inhibitors and discriminates the HNE level in normal and lung cancer tissues, suggesting that the nanodevice provides an effective tool for the diagnosis and treatment of lung tumors., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The expansion of the human SRGAP2 family, resulting in a human-specific paralog SRGAP2C, likely contributed to altered evolutionary brain features. The introduction of SRGAP2C in mouse models is associated with changes in cortical neuronal migration, axon guidance, synaptogenesis, and sensory-task performance. Truncated SRGAP2C heterodimerizes with the full-length ancestral gene product SRGAP2A and antagonizes its functions. However, the significance of SRGAP2 duplication beyond neocortex development has not been elucidated due to the embryonic lethality of complete Srgap2 knockout in mice. Using zebrafish, we show that srgap2 knockout results in viable offspring and that these larvae phenocopy "humanized" SRGAP2C larvae, including altered morphometric features (i.e., reduced body length and inter-eye distance) and differential expression of synapse-, axonogenesis-, and vision-related genes. Through single-cell transcriptome analysis, we demonstrate a skewed balance of excitatory and inhibitory neurons that likely contribute to increased susceptibility to seizures displayed by Srgap2 mutant larvae, a phenotype resembling SRGAP2 loss-of-function in a child with early infantile epileptic encephalopathy. Single-cell data also shows strong endogenous expression of srgap2 in microglia with mutants exhibiting altered membrane dynamics and likely delayed maturation of microglial cells. Microglia cells expressing srgap2 were also detected in the developing eye together with altered expression of genes related to axonogenesis in mutant retinal cells. Consistent with the perturbed gene expression in the retina, we found that SRGAP2 mutant larvae exhibited increased sensitivity to broad and fine visual cues. Finally, comparing the transcriptomes of relevant cell types between human (+ SRGAP2C ) and non-human primates (- SRGAP2C ) revealed significant overlaps of gene alterations with mutant cells in our zebrafish models; this suggests that SRGAP2C plays a similar role altering microglia and the visual system in modern humans. Together, our functional characterization of conserved ortholog Srgap2 and human SRGAP2C in zebrafish uncovered novel gene functions and highlights the strength of cross-species analysis in understanding the development of human-specific features.

Microglial activation-mediated neuroinflammation is a major contributor to neuronal damage after cerebral ischemia. The Fractalkine (FKN)/CX3C chemokine receptor 1 (CX3CR1) axis plays a critical role in regulating microglial activation and neuroinflammation. The aim of this study is to ascertain the role and mechanism of FKN/CX3CR1 axis in hypoxic postconditioning (HPC)-induced anti-inflammatory and neuroprotective effects on transient global cerebral ischemia (tGCI). We found that HPC suppressed microglial activation and alleviated neuroinflammation in hippocampal CA1 after tGCI. Meanwhile, HPC upregulated the expression of FKN and CX3CR1 in neurons, but it downregulated the expression of CX3CR1 in glial cells after tGCI. In addition, the overexpression of FKN induced by the administration of FKN-carried lentivirus reduced microglial activation and inhibited neuroinflammation in CA1 after tGCI. Furthermore, silencing CX3CR1 with CX3CRi-carried lentivirus in CA1 after tGCI suppressed microglial activation and neuroinflammation and exerted neuroprotective effects. Finally, the overexpression of FKN caused a marked increase of neuronal CX3CR1 receptors, upregulated the phosphorylation of Akt, and reduced neuronal loss of rats in CA1 after tGCI. These findings demonstrated that HPC protected against neuronal damage in CA1 of tGCI rats through inhibiting microglial activation and activating Akt signaling pathway via FKN/CX3CR1 axis., (© 2024. The Author(s).)

Reservoir projects often have significant impacts on ecosystems. The resulting environmental problems hinder the ecologically sustainable development of project areas. Research focusing on landscape pattern vulnerability could shed light on ecological restoration in disturbed sites. However, few studies have specifically examined reservoir areas in this context. This study investigates the spatial distribution characteristics, change rules, spatial autocorrelation, and driving forces of landscape pattern vulnerability in the Qianping Reservoir area (3859.16 hm 2 ) from 2000 to 2020 using land use data. The findings reveal several key points: (1) Over the study period, cultivated land, grassland, and forest land are the key landscape types, covering more than 90% of the area. Cultivated land decreased by 481.57 hm 2 as other land use types expanded. (2) Vulnerability remained stable in the first decade but sharply increased from 2010 to 2020, showing a trend of spatial aggregation. Reservoir construction and simultaneous ecological restoration efforts led to shifts in vulnerability zones across the landscape. (3) Spatial distribution of landscape pattern vulnerability shows a positive correlation, which strengthened by 2020 compared to earlier years. (4) Man-made factors, particularly land use changes, significantly influence landscape pattern vulnerability, with their impact growing over time. These findings not only provide a scientific basis for ecological restoration and landscape reconstruction in the Qianping Reservoir area but also offer insights applicable to similar environments. Overall, this study enhances theoretical understanding of reservoir landscape pattern vulnerability and contributes valuable perspectives on ecological restoration strategies for reservoir areas., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Following the signing of the Tobacco 21 Amendment (T21) in December 2019 to raise the minimum legal age for the sale of tobacco products from 18 to 21 years in the United States, there is a need to monitor public responses and potential unintended consequences. Social media platforms, such as Twitter (subsequently rebranded as X), can provide rich data on public perceptions., Objective: This study contributes to the literature using Twitter data to assess the knowledge and beliefs of T21., Methods: Twitter data were collected from November 2019 to February 2021 using the Twitter streaming application programming interface with keywords related to vaping or e-cigarettes, such as "vape," "ecig," etc. The temporal trend of the T21 discussion on Twitter was examined using the mean number of daily T21-related tweets. Inductive methods were used to manually code the tweets into different sentiment groups (positive, neutral, and negative) based on the attitude expressed toward the policy by 3 coders with high interrater reliability. Topics discussed were examined within each sentiment group through theme analyses., Results: Among the collected 3197 tweets, 2169 tweets were related to T21, of which 444 tweets (20.5%) showed a positive attitude, 736 (33.9%) showed a negative attitude, and 989 (45.6%) showed a neutral attitude. The temporal trend showed a clear peak in the number of tweets around January 2020, following the enactment of this legislation. For positive tweets, the most frequent topics were "avoidance of further regulation" (120/444, 27%), "Enforce T21" (110/444, 24.8%), and "health benefits" (81/444, 18.2%). For negative tweets, the most frequent topics were "general disagreement or frustration" (207/736, 28.1%) and "will still use tobacco" (188/736, 25.5%). Neutral tweets were primarily "public service announcements (PSA) or news posts" (782/989, 79.1%)., Conclusions: Overall, we find that one-third of tweets displayed a negative attitude toward T21 during the study period. Many were frustrated with T21 and reported that underage consumers could still obtain products. Social media data provide a timely opportunity to monitor public perceptions and responses to regulatory actions. Continued monitoring can inform enforcement efforts and potential unintended consequences of T21., (©Liane M Schneller-Najm, Zidian Xie, Jiarui Chen, Sarah Lee, Emily Xu, Dongmei Li. Originally published in JMIR Infodemiology (https://infodemiology.jmir.org), 25.09.2024.)

High solid anaerobic digestion (HSAD) achieves the benefits of high volumetric loading rates and lower reject water production, which, however, results in much more concentrated reject water with a remarkable increase in organics and nitrogen compared with that from conventional AD with low solid content. The high concentrations of ammonium (2000-3500 mg/L) and COD (3000-4000 mg/L) were reported to exert inhibition on anammox bacteria (AnAOB), posing challenges to the application of the partial nitritation/anammox (PN/A). To date, no cases of PN/A process start-up for sludge HSAD reject water were reported. This study demonstrated the start-up process of a 480 m 3 /d PN/A project without anammox sludge inoculation and treating HSAD reject water from a centralized dewatered sludge treatment plant. The project did not construct new infrastructures but utilized previously constructed tanks to upgrade the process from existing short-cut nitrification-denitrification to a two-stage PN/A process. Although no external anammox sludge inoculation was performed to save seeding sludge cost, the start-up was successfully achieved in about 9 months (273 days) based on a three-step method of "AnAOB enrichment - sludge acclimation - capacity doubling". During start-up, the relative abundance of AnAOB (Candidatus&#95; Kuenenia ) increased from near zero to 12.0%. After start-up, the total inorganic nitrogen (TIN) removal load reached 0.74 kgN/(m 3 •d), with a total nitrogen removal efficiency of over 90%. Compared to the traditional nitrification-denitrification process, the PN/A process remarkably reduces the addition of organic chemicals and aeration energy consumption, saving approximately 4.2 million yuan (RMB) in operational costs annually. In summary, this research provides a full-scale reference for the start-up of the PN/A process treating sludge HSAD reject water., 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. Published by Elsevier Ltd.)

In response to the issue that the fusion process of infrared and visible images is easily affected by lighting factors, in this paper, we propose an adaptive illumination perception fusion mechanism, which was integrated into an infrared and visible image fusion network. Spatial attention mechanisms were applied to both infrared images and visible images for feature extraction. Deep convolutional neural networks were utilized for further feature information extraction. The adaptive illumination perception fusion mechanism is then integrated into the image reconstruction process to reduce the impact of lighting variations in the fused images. A Median Strengthening Channel and Spatial Attention Module (MSCS) was designed to be integrated into the backbone of YOLOv8. In this paper, we used the fusion network to create a dataset named ivifdata for training the target recognition network. The experimental results indicated that the improved YOLOv8 network saw further enhancements of 2.3%, 1.4%, and 8.2% in the Recall, mAP50, and mAP50-95 metrics, respectively. The experiments revealed that the improved YOLOv8 network has advantages in terms of recognition rate and completeness, while also reducing the rates of false negatives and false positives.

Integration of whispering-gallery-mode (WGM) resonators with high-quality factors (Q) into advanced timing, oscillator, and sensing systems demands a platform that enables precise resonance frequency modulation. This study investigates the tuning characteristics of magnetorheological polydimethylsiloxane (MR-PDMS) coated microspheres (µ-spheres) employed as magnetic microresonators, achieving a Q value of 10 7 at the 1550 nm wavelength. Magnetic WGM resonators not only endow the device with magnetic adjustability but also markedly improve thermal resistance. Experimental findings reveal that the magnetic µ-sphere demonstrates a sensitivity of -32.53 MHz/mT, outperforming conventional magnetic WGM resonators. Furthermore, analysis of the temperature dependence shows a reduction in fluctuation to -2.85 MHz/K, thereby greatly enhancing the sensor's practical detection limit.

Upon the pressure of conventional land agriculture and marine environment facing the future of human beings, the emerging of alternative proteins represented by cultured meat is expected with a breakthrough of efficient, safe and sustainable production. However, the cell proliferation efficiency and final myofiber density in current animal-derived scaffolds are still limited. Here, we incorporated five plant-derived edible polymeric glucosyl nanoparticles (GNPs) into gelatin/alginate hydrogels to spontaneously form nanoaggregates where nanotopographies were observed inside. The nanoscale topological morphology significantly enhances the adhesion and proliferation efficiencies of piscine satellite cells (PSCs) in the tailored extracellular matrix of as-prepared scaffold. Physically, the presence of GNP-induced nanoaggregate increases the interaction between ITG-A1 (membrane protein of PSCs) and hydrogel microenvironment, which activates the focal adhesion-integrin-cytoskeleton mechanotransduction signaling to promote cell proliferation. With a controlled diameter of hydrogel filament, these inner topological GNP nanoaggregates can also improve the density, alignment and differentiation efficiency of PSCs. When cultured in vitro for 15 days, the cell density, size and orientation of muscle fibers in the GNP-stimulated cultured fish fillet are very similar to the total cell mass in native fish muscle tissue., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Low-grade glioma (LGG) is a malignancy of the central nervous system that is often treatable with surgical resection and chemoradiation. However, despite an initial positive response to standard therapy, most LGG eventually progress to high-grade gliomas which are nearly uniformly fatal. There is a pressing need for more clinical trials and greater clinical trial accessibility to improve the standard of care of LGG to delay or prevent its progression. In this study, we systematically examined the scope and inclusion of clinical trials for LGG based in the United States. This cross-sectional study analyzes trends in trial design and reported demographic data from completed LGG trials registered on ClinicalTrials.gov between 2010 to 2023. Inclusion criteria, investigational therapies, primary outcomes, and preliminary results were compared and summarized. A total of 14 trials with 1067 participants were included in the study. Most of the trials were not exclusive to LGGs and 14% had mutation-specific inclusion criteria. To date, two of the trials have led to new FDA-approved treatments. All trials reported age and sex, while only 57% reported race and 43% reported ethnicity. Individuals identifying as Black or African American and Asian or Pacific Islander were statistically underrepresented. Lastly, we investigated the geographic distributions of trial sites across the United States, which demonstrated several coverage gaps in the Rocky Mountain and Southeast regions. These findings suggest specific areas for improvement in LGG clinical trial reporting and accessibility.

Rationale: Intrathoracic paragangliomas are typically found within the intricate posterior mediastinal region adjacent to the vertebrae, often presenting with substantial volume. Surgical excision of such tumors presents formidable challenges and is conventionally performed via open surgical procedures., Patient Concerns: In this report, we present the case of a 53-year-old female patient who presented with the discovery of a left intrathoracic mass during a routine physical examination approximately 1 month prior. She complained of chest tightness and chest pain., Diagnoses: She complained of chest tightness and chest pain. Magnetic resonance imaging of the chest and brachial plexus revealed a mass adjacent to the left upper lung hilum, measuring approximately 78 × 63 × 72 mm. The initial suspicion leaned towards a benign lesion. Notably, there was slight compression of the left first thoracic nerve root and mild compression of the middle and lower trunks of the left brachial plexus. Based on the morphological features of the tumor and imaging findings, we suspected its benign nature., Interventions: We opted for robot-assisted thoracic surgery to resect the mediastinal tumor., Outcomes: Subsequent postoperative pathology confirmed the diagnosis as a paraganglioma. The patient did not experience any notable complications post-surgery, and a 6-month follow-up revealed no signs of recurrence., Lessons: The successful application of the robot-assisted thoracic surgery surgical technique underscores its efficacy in minimally invasive resection of sizable intrathoracic tumors situated in the posterior mediastinum., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Ethnopharmacological Relevance: Processed Buthus martensii Karsch (BmK) scorpion, also known as Quan-Xie, is a traditional Chinese medicine that is clinically used for the treatment of NAFLD due to its Tong-Luo-San-Jie effects. Our previous study showed that aqueous extract of processed BmK scorpion venom gland (pVg AE) inhibited macrophage inflammation by targeting Kv1.3 and identified the thermostable peptide BmKK2 as a potent Kv1.3 blocker., Aim of the Study: This study examined the therapeutic effects of processed BmK scorpions on NASH, specifically focusing on the involvement of their anti-inflammatory effects mediated by macrophage-expressed Kv1.3 in NASH., Materials and Methods: In the present study, the anti-NASH effects of pVg AE were evaluated in high-fat diet (HFD)-induced NASH mouse models. Additionally, the in vitro anti-inflammatory mechanisms of pVg AE and BmKK2 were assessed using a palmitic acid (PA)-induced mouse bone marrow-derived macrophages (BMDMs) inflammation model. Protein and cytokine expression related to the Kv1.3-NF-κB pathway was analyzed by real-time PCR, immunoblotting and ELISA. The effect of pVg AE and BmKK2 on potassium channels was detected by whole-cell voltage-clamp recordings on transfected HEK293T cells or mouse BMDMs. Calcium ion imaging was used to evaluate intracellular calcium signaling. Furthermore, the study utilized Kv1.3 siRNA and a BMDMs and hepatocytes co-culture model to investigate the specific role of Kv1.3 in mediating the anti-NASH effects of pVg AE and BmKK2., Results: Lipid accumulation upregulated Kv1.3 expression in macrophages in vivo and in vitro. However, pVg AE significantly reduced Kv1.3 expression and Kv1.3-positive macrophage infiltration. Treatment with pVg AE improved obesity, insulin resistance (IR), hepatic steatosis (HS), inflammation, and fibrosis in HFD-fed mice. Mechanistically, pVg AE and BmKK2 inhibited macrophage inflammation by targeting Kv1.3, which reduced PA-induced intracellular Ca 2+ levels, resulting in the inhibition of the NF-κB pathway and TNFα release., Conclusions: This study demonstrates that Kv1.3-mediated macrophage inflammation is involved in the pathogenesis and treatment of NASH. pVg AE effectively alleviates metabolic stress-induced NASH by inhibiting this inflammation., 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.)

Introduction: Chronic kidney disease (CKD) has an increasing global prevalence and has previously been associated with increased complications and morbidity after spine surgery. Understanding the isolated effect of CKD on short-term patient outcomes is critical for optimizing perioperative risk management and healthcare utilization., Objective: The aim of this study is to utilize coarsened exact matching (CEM) to analyze the isolated effect of CKD on short-term patient outcomes in single-level posterior lumbar fusion surgery., Methods: A retrospective analysis of 4680 consecutive patients undergoing single-level, posterior-only lumbar fusion was performed. Univariate logistic regression comparing the odds of outcomes in patients with CKD (n=40) to patients without medical comorbidities (n=2329) was performed. CEM was then employed to match patients with CKD to those without any comorbidities 1:1 on ten patient characteristics known to affect neurosurgical outcomes. Primary outcomes included intraoperative complications, length of stay, discharge disposition, and 30-day Emergency Department (ED) visits, readmissions, reoperations, and mortality., Results: In a univariate logistic regression, CKD was associated with increased risk of 30-day ED visits (OR=3.53, p=0.003) but not complication, discharge disposition, or 30-day readmissions or reoperations. Between otherwise exactly matched patients (n=72), CKD similarly remained associated with an increased risk of 30-day ED visits (OR=7.00, p=0.034) and not with other outcomes., Conclusion: Between otherwise exactly matched patients undergoing single-level posterior lumbar fusion, CKD was related to increased risk of 30-day ED utilization but not other markers indicative of inferior surgical outcomes. Further study must investigate the reasons for increased ED visitation and implement risk-mitigation strategies for these patients., Competing Interests: Conflicts of Interest The authors have no personal or institutional conflicts of interest related to the data presented in this paper and/or the publication of this manuscript., (Copyright © 2024. Published by Elsevier B.V.)

The proprietary Chinese medicine Jinkui Shenqi Pill (PCM-JKSQP) is a classic compound used for the effective clinical treatment of kidney yang deficiency syndrome (KYDS), a metabolic disease accompanied by kidney injury. However, its active ingredients and therapeutic mechanisms are not clear. This study employed serum pharmacochemistry, network pharmacology, and pharmacokinetics (PK) to identify the bioactive components of PCM-JKSQP and preliminarily clarify its mechanism in treating KYDS. One hundred and forty chemical components of PCM-JKSQP, 47 (20 parent compouds and 27 metabolites) of which were absorbed into the blood, were identified by ultra-high-performance liquid chromatography-quadrupole-orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). The topological parameters of network pharmacology and high concentrations in blood found six parent components as PK markers (cinnamic acid, paeonol, loganin, morroniside, apigenin, and poricoic acid A). PK analysis further identified these six compounds as active ingredients. Protein-protein interaction (PPI) analysis and molecular docking simulation predicted and verified eight core targets (TP53, ESR1, CTNNB1, EP300, EGFR, AKT1, ERBB2, and TNF). Most were concentrated in the MAPK, HIF-1, and PI3K-AKT signaling pathways, indicating that these six active ingredients may mainly exert therapeutic effects through these three pathways via their core targets. The PK results also showed these six components were absorbed quickly, although cinnamic acid and paeonol were rapidly metabolized, with a short half-life and retention time. Loganin and morroniside did not have high peak concentrations, and apigenin and poricoic acid A had long retention times. This study provides a new overall perspective for exploring the bioactive components and mechanisms underlying the effects of PCM-JKSQP in treating KYDS., 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.)

Egg production is an important economic trait in layer ducks and understanding the genetics basis is important for their breeding. In this study, a genome-wide association study (GWAS) for egg production traits in 303 female Longyan Shan-ma ducks was performed based on a genotyping-by-sequencing strategy. Sixty-two single nucleotide polymorphisms (SNPs) associated with egg weight traits were identified (P < 9.48 × 10 -5 ), including 8 SNPs at 5% linkage disequilibrium (LD)-based Bonferroni-corrected genome-wide significance level (P < 4.74 × 10 -6 ). One hundred and nineteen SNPs were associated with egg number traits (P < 9.48 × 10 -5 ), including 13 SNPs with 5% LD-based Bonferroni-corrected genome-wide significance (P < 4.74 × 10 -6 ). These SNPs annotated 146 target genes which contained known candidate genes for egg production traits, such as prolactin and prolactin releasing hormone receptor. This study identified that these associated genes were significantly enriched in egg production-related pathways (P < 0.05), such as the oxytocin signaling, MAPK signaling, and calcium signaling pathways. It was notable that 18 genes were differentially expressed in ovarian tissues between higher and lower egg production in Shan-ma ducks. The identified potential candidate genes and pathways provide insight into the genetic basis underlying the egg production trait of layer ducks., Competing Interests: DISCLOSURES The authors have no conflicts of interest to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study, starch-based nanofiber mats were successfully prepared from aqueous solution by electrospinning and used for probiotic encapsulation for the first time. The physicochemical properties of the octenylsuccinated (OS) starch/poly(vinyl alcohol) (PVA) blend solutions were systematically investigated. Through Fourier transform infrared spectroscopy and X-ray diffraction spectra analysis, it was found that miscibility and hydrogen bonding interactions exist between OS starch and PVA molecules. Thermogravimetric analysis and derivative thermogravimetric analysis revealed that the produced nanofibers possess satisfactory thermal stability. Scanning electron microscopy images and diameter distribution histograms showed that continuous and defect-free nanofibers were obtained and along with the increase in the weight ratio of OS starch, the average diameter gradually decreased. In addition, it was confirmed that the probiotics were successfully encapsulated in nanofiber mats. The survival rates of Lactobacillus plantarum AB-1 and Lactobacillus rhamnosus GG encapsulated in nanofibers were as high as 94.63% and 92.42%, respectively, significantly higher than those of traditional freeze-drying. Moreover, compared to free cells, probiotics encapsulated in nanofiber mats retained better viability after 21 days of storage at 4 and 25°C, and showed remarkably higher survival rates after exposure to simulated gastric and intestinal fluid. This study showed that the developed nanofibers can be a promising encapsulation system for the protection of probiotics., (© 2024 Institute of Food Technologists.)

Background: The prevalence of functional impairment is increasing among middle-aged adults and is associated with adverse health outcomes. Primary care providers (PCPs) and geriatricians may have important insights about optimal approaches to caring for these patients, but little is known about their perspectives., Objective: To examine PCPs' and geriatricians' perspectives on clinical needs and optimal approaches to care for middle-aged patients with functional impairment., Design: Qualitative study using semi-structured interviews., Participants: PCPs and geriatricians from outpatient practices in the San Francisco Bay area., Approach: Interviews focused on characteristics and care needs of middle-aged patients with functional impairment and models of care to address these needs. We analyzed interviews using hybrid deductive-inductive qualitative thematic analysis., Key Results: Clinicians (14 PCPs, 15 geriatricians) described distinct characteristics of functional impairment in middle-aged versus older adults, such as different rates of onset, but similar clinical needs. Despite these similar needs, clinicians identified age-specific barriers to delivering optimal care to middle-aged patients. These included system-level challenges such as limited access to insurance and social services; practice- and clinician-level barriers including inadequate clinician training; and patient-level factors including less access to family caregivers and perceptions of stigma. To overcome these challenges, clinicians suggested clinical approaches including addressing health-related social needs within healthcare systems; implementing practice-based models that are multi-disciplinary, team-based, and coordinated; training clinicians to effectively manage functional impairment; and expanding community-based services and supports to help patients navigate the medical system. Identified needs, challenges, and solutions were generally similar across geriatricians and PCPs., Conclusions: Clinicians face challenges in delivering optimal care to middle-aged patients who have functional impairments similar to their older counterparts but lack access to services and supports available to older people. These findings suggest the importance of increasing access to care models that address functional impairment regardless of age., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Objective: To investigate the value of painless transvaginal four-dimensional hysterosalpingo contrast sonography (TV 4-D HyCoSy) in reducing venous intravasation and its influencing factors through a retrospective comparative study on conventional TV 4-D HyCoSy., Materials and Methods: A total of 451 patients were enrolled in this study from Jan. 2019 to Oct. 2021. There were 249 patients in the painless TV 4-D HyCoSy group and 202 patients in the conventional TV 4-D HyCoSy group. The incidence of venous intravasation and its related influencing factors were analyzed and compared between these two groups. The difficulty of image evaluation for the diagnosis was also compared., Results: There was no significant difference in the baseline characteristics between the painless group and the conventional group (p > 0.05). Compared with the conventional group, the painless group had a lower incidence of venous intravasation (16.9 vs. 24.8%; p = 0.039). Painless TV 4-D HyCoSy was more effective in reducing venous intravasation in patients with primary infertility (p = 0.032) without a history of pelvic surgery (p = 0.008) or ectopic pregnancy (p = 0.018). Logistic regression analysis demonstrated that painless TV 4-D HyCoSy and endometrial thickness > 5 mm were protective factors for venous intravasation. Moreover, the diagnostic procedure was easier in the painless group than in the conventional group (p = 0.002)., Conclusions: Painless TV 4D-HyCoSy may be an effective mode in reducing the incidence of venous intravasation and improving the diagnosis of patency of fallopian tubes., (© 2024. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Significance: Consistent and accurate probe placement is a crucial step towards enhancing the reproducibility of longitudinal and group-based functional neuroimaging studies. While the selection of headgear is central to these efforts, there does not currently exist a standardized design that can accommodate diverse probe configurations and experimental procedures., Aim: We aim to provide the community with an open-source software pipeline for conveniently creating low-cost, 3-D printable neuroimaging head caps with anatomically significant landmarks integrated into the structure of the cap., Approach: We utilize our advanced 3-D head mesh generation toolbox and 10-20 head landmark calculations to quickly convert a subject's anatomical scan or an atlas into a 3-D printable head cap model. The 3-D modeling environment of the open-source Blender platform permits advanced mesh processing features to customize the cap. The design process is streamlined into a Blender add-on named "NeuroCaptain"., Results: Using the intuitive user interface, we create various head cap models using brain atlases, and share those with the community. The resulting mesh-based head cap designs are readily 3-D printable using off-the-shelf printers and filaments while accurately preserving the head topology and landmarks., Conclusions: The methods developed in this work result in a widely accessible tool for community members to design, customize and fabricate caps that incorporate anatomically derived landmarks. This not only permits personalized head cap designs to achieve improved accuracy, but also offers an open platform for the community to propose standardizable head caps to facilitate multi-centered data collection and sharing.

Hepatic stellate cells (HSCs) are a major source of fibrogenic cells and play a central role in liver fibrogenesis. HSC activation depends on metabolic activation, for which it is well established that fatty acid oxidation (FAO) sustains their rapid proliferative rate. Studies have indicated that tanshinones inhibit HSC activation, however, the anti-fibrosis mechanisms of tanshinones are remain unclear. Herein, we reported that cryptotanshinone (CTS), a lipid-soluble ingredient of Salvia miltiorrhiza Bunge, exhibited the strongest inhibitory effects on HSC-LX2 proliferation and activation. CTS could induce lipocyte phenotype in mouse primary HSC and HSC-LX2. Transcriptomic sequencing and qPCR revealed that CTS regulated fatty acid metabolism and inhibited CPT1A and CPT1B expression. Target prediction suggested CTS regulates lipid metabolism by targeting STAT3. Mechanistically, the level of ATP and acetyl-CoA were reduced by the treatment of CTS, indicating that CTS could inhibit the level of FAO. Furthermore, CTS could inhibit the phosphorylation and nuclear translocation of STAT3. Additionally, CPT1A overexpression reversed the efficacy of CTS. Finally, CTS (40 mg/kg/day) attenuated CCl 4 -induced liver fibrosis and inhibited collagen production and HSC activation. Moreover, the results of immunofluorescence showed that α-SMA and p-STAT3 were co-located, and CTS could reduce the levels of p-STAT3 and α-SMA. In summary, CTS alleviated liver fibrosis by inhibiting the p-STAT3/CPT1A-dependent FAO both in vitro and in vivo, making it a potential candidate drug for the treatment of liver fibrosis., 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.)

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor. The aim of this study was to elucidate the role of microenvironment and intrinsic T-type calcium channels (Cav3) in regulating tumor growth and progression., Methods: We grafted syngeneic GBM cells into Cav3.2 knockout mice to assess the role of microenvironment T-Type calcium channels on GBM tumor growth. We performed single-cell RNA-seq (scRNA-seq) of tumors from WT and Cav3.2 KO mice to elucidate the regulation of tumors by the microenvironment. We used neurons from WT and Cav3.2 KO mice in co-culture with GBM stem cells (GSC) to assess the effects of Cav3.2 on neuron/GSC synaptic connections and tumor cell growth., Results: Cav3.2 KO in the microenvironment led to significant reduction of GBM growth and prolongation of animal survival. scRNA-seq showed that microenvironment Cav3.2 regulates neuronal and glial biological processes. Microenvironment Cav3.2 downregulated numerous genes associated with regulating the OPC cell state in GBM tumors such as SOX10 and Olig2. Neuronal Cav3.2 promoted neuron/GSC synaptic connections and GSC growth. Treatment of GSCs with the Cav3 blocker mibefradil downregulated genes associated with neuronal processes. The Cav3 blocker drug mibefradil synergized with temozolomide (TMZ) and radiation to reduce in vivo tumor growth and prolong animal survival., Conclusions: Together these data reveal a role for microenvironment Cav3 in promoting GBM tumor progression through regulating neuronal and glial processes particularly associated with the OPC-cell state. Targeting both intrinsic and microenvironment Cav3 with the inhibitor mibefradil significantly enhanced the anti-GBM effects of TMZ and radiation., Competing Interests: Conflict of Interest The authors have declared that no conflicts of interest exist

Purpose: Esketamine have anesthetic and analgesic properties. This study aimed to observe the enhancing effect of subanesthetic doses of esketamine (0.15-0.3 mg/kg/h) with dexmedetomidine and remifentanil during anesthesia for liposuction surgery., Patients and Methods: A total of 155 subjects were randomized with a 1:1 ratio to Group E (esketamine-dexmedetomidine/remifentanil, n=78) or Group C (saline-dexmedetomidine/remifentanil group, n=77). The primary outcome was satisfaction of patient and surgical team with the procedure. The secondary outcomes were the postoperative Athens Insomnia Scale (AIS) and Hospital Anxiety and Depression Scale (HADS) scores, hemodynamic and respiratory changes, drug consumption, adverse event rates, and predictors associated with patient satisfaction., Results: Patient and surgical team satisfaction with the procedure was significantly higher in Group E than in Group C (4.7 ± 0.6 vs 4.2 ± 0.7, P < 0.001; 4.7 ± 0.5 vs 4.4 ± 0.7, P = 0.005). The postoperative AIS (4 [1, 6] vs 5 [2, 9], P = 0.012) and HADS-A (1 [0, 3] vs 2 [0, 6], P = 0.012) scores were significantly lower in Group E than in Group C. Hemodynamic and respiratory parameters were more stable in Group E than in Group C, with the lower opioids consumption of sufentanil (0 [0, 4] vs 5 [2.5, 7.7], P < 0.001) and remifentanil (700 [480, 900] vs 800 [500, 1200], P = 0.023) in Group E compared to Group C. On ordinal logistics regression, postoperative sleep quality (OR, 0.70; 95% CI, 0.62-0.79), anxiety level (OR, 0.77; 95% CI, 0.62-0.95) and recovery time in post-anesthesia care unit (PACU) (OR, 0.69; 95% CI, 0.56-0.98) were identified as significant predictors associated with patient satisfaction., Conclusion: A subanesthetic dose of esketamine (0.15-0.3 mg/kg/h) as an adjuvant can improves the sedative and analgesic effects of dexmedetomidine and remifentanil during anesthesia for liposuction surgery., Clinical Trial Registration: ChiCTR2400080363., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Chen et al.)

Resistant starch (RS) has the advantage of reshaping gut microbiota for human metabolism and health, like glycemic control, weight loss, etc. Among them, RS3 prepared from pure starch is green and safe, but it is hard to achieve structural control. Here, we regulate the crystal structure of starch with different chain-length distributions (CLDs) via extrusion at low/high shearing levels. The change in CLDs in extruded starch was obtained, and their effects on the fine structure ( Dm , d Bragg , d Lorentz , degree of order and double helix, degree of crystal) of RS and its physicochemical properties were investigated by SAXS, FTIR, XRD and 13 C NMR analyses. The results showed that the RS content under a 250 r/min extrusion condition was the highest at 61.52%. Furthermore, the crystalline system induced by high amylopectin (amylose ≤ 4.78%) and a small amount of amylose (amylose ≥ 27.97%) was favorable for obtaining a high content of RS3-modified products under the extruding environment. The control of the moderate proportion of the A chains ( DP 6-12) in the starch matrix was beneficial to the formation of RS.

Myocardial ischemia-reperfusion (I/R) injury exacerbates cellular damage upon restoring blood flow to ischemic cardiac tissue, causing oxidative stress, inflammation, and apoptosis. This study investigates Nicotinamide Riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD + ), for its cardioprotective effects. Administering NR to mice before I/R injury and evaluating heart function via echocardiography showed that NR significantly improved heart function, increased left ventricular ejection fraction (LVEF) and fractional shortening (FS), and reduced left ventricular end-diastolic (LVDd) and end-systolic diameters (LVSd). NR also restored E/A and E/e' ratios. It reduced cardiomyocyte apoptosis both in vivo and in vitro , inhibiting elevated caspase-3 activity and returning Bax protein levels to normal. In vitro , NR reduced the apoptotic rate in hydrogen peroxide (H2O2)-treated HL-1 cells from 30% to 10%. Mechanistically, NR modulated the SIRT3/mtROS/JNK pathway, reversing H2O2-induced SIRT3 downregulation, reducing mitochondrial reactive oxygen species (mtROS), and inhibiting JNK activation. Using SIRT3-knockout (SIRT3-KO) mice, we confirmed that NR's cardioprotective effects depend on SIRT3. Echocardiography showed that NR's benefits were abrogated in SIRT3-KO mice. In conclusion, NR provides significant cardioprotection against myocardial I/R injury by enhancing NAD+ levels and modulating the SIRT3/mtROS/JNK pathway, suggesting its potential as a novel therapeutic agent for ischemic heart diseases, meriting further clinical research., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The low spatial resolution of diffuse optical tomography (DOT) has motivated the development of high-density DOT systems utilizing spatially-encoded illumination and detection strategies. Data compression methods, through the application of Fourier or Hadamard patterns, have been commonly explored for both illumination and detection but were largely limited to pre-determined patterns regardless of imaging targets. Here, we show that target-optimized detection patterns can yield significantly improved DOT reconstructions in both in silico and experimental tests. Applying reciprocity, we can further iteratively optimize both illumination and detection patterns and show that these simultaneously optimized source/detection patterns outperform predetermined patterns in simulation settings. In addition, we show media-adaptive measurement data compression methods enable wide-field DOT systems to recover highly complex inclusions inside optically-thick media with reduced background artifacts. Furthermore, using truncated optimized patterns shows an improvement of 2-4× in increased speed of data acquisition and reconstruction without significantly losing image quality. The proposed method can be readily extended for additional data dimensions such as spectrum and time., Competing Interests: The authors declare no conflicts of interest., (© 2024 Optica Publishing Group.)

Background: Cognitive impairment is common in patients with Parkinson's disease (PD) and occurs through multiple mechanisms, including Alzheimer's disease (AD) pathology and the involvement of α-synucleinopathies. We aimed to investigate the pathological biomarkers of both PD and AD in plasma and neuronal extracellular vesicles (EVs) and their association with different types of cognitive impairment in PD patients., Methods: A total of 122 patients with PD and 30 healthy controls were included in this cross-sectional cohort study between March 2021 and July 2023. Non-dementia PD patients were divided into amnestic and non-amnestic groups according to the memory domain of a neuropsychological assessment. Plasma and neuronal EV biomarkers, including α-synuclein (α-syn), beta-amyloid (Aβ), total tau (T-tau), phosphorylated tau181 (p-tau181), and glial fibrillary acidic protein (GFAP), were measured using a single-molecule array and a chemiluminescence immunoassay, respectively., Results: Neuronal EV but not plasma α-syn levels, were significantly increased in PD as compared to healthy controls, and they were positively associated with UPDRS part III scores and the severity of cognitive impairment. A lower plasma Aβ42 level and higher neuronal EV T-tau level were found in the amnestic PD group compared to the non-amnestic PD group., Conclusions: The results of the current study demonstrate that neuronal EV α-syn levels can be a sensitive biomarker for assisting in the diagnosis and disease severity prediction of PD. Both AD and PD pathologies are important factors in cognitive impairment associated with PD, and AD pathologies are more involved in amnestic memory deficit in PD.

Study Objective: To explore the risk factors associated with local regeneration of the treated uterine fibroids (UFs) after microwave ablation (MWA) and to develop a nomogram model for predicting the risk of local regeneration., Design: Retrospective study., Setting: The Eighth Affiliated Hospital of Sun Yat-Sen University., Patients: Patients with UFs who underwent MWA at our hospital between October 2020 and April 2023 were included., Intervention: MWA was used for the treatment of UFs., Measurements and Main Results: A total of 47 patients with 68 fibroids were included into this study. Over a median follow-up of 13 months (interquartile range, 8-22 months), local regeneration occurred in 11 UFs. The clinical and imaging characteristics of these patients were recorded and compared. Risk factors for local regeneration were determined through univariate and multivariate Cox regression analysis. Multivariate analysis revealed that the fertility desires, larger size of UFs (≥95.3 cm 3 ), and hyperenhancement of UFs on contrast-enhanced ultrasound were independent risk factors for local regeneration after MWA. A predictive nomogram was constructed to predict the local regeneration after MWA of UFs. The concordance index (C-index) (C-index, 0.924; internal validation C-index, 0.895) and the 1- and 2-year area under the curve values (0.962, 0.927) all indicated that the nomogram had good predictive performance. Calibration and decision curve analysis curves further confirmed the model's accuracy and clinical utility., Conclusion: Fertility desires, larger size of UFs, and hyperenhancement on contrast-enhanced ultrasound were independent predictors of UFs local regeneration after MWA in our study. The nomogram constructed based on the abovementioned independent risk factors may help predict which UFs will develop local regeneration after MWA., (Copyright © 2024 AAGL. Published by Elsevier Inc. All rights reserved.)

The promotion of gut health, a pervasive problem in modern animal husbandry, positively affects organismal health, productivity, and economics. Porcine intestinal epithelial cells (IPEC-J2) continuously proliferate to maintain intestinal homeostasis, including barrier, immune, and absorptive functions. Gut homeostasis is fundamental to organismal health. ADP-ribosylation factor 1 (Arf1), a small GTPase, plays a crucial role in coordinating mTORC1 in response to nutrients, especially amino acid availability in the gut. mTORC1 is the central hub of proliferation. Thus, it seems likely that Arf1 promotes IPEC-J2 cell proliferation. However, the exact role of Arf1 in the porcine gut remains unclear. Therefore, we evaluated the functional role and possible mechanisms of Arf1 in the porcine intestine through Arf1 overexpression and knockdown in IPEC-J2 cells. Arf1 overexpression and knockdown significantly enhanced and inhibited, respectively, IPEC-J2 cell viability, and PCNA expression varied with Arf1 expression. Moreover, the proportion of Ki67-positive cells was significantly greater in the Arf1-overexpressing group than in the control group. These results suggest that Arf1 improves IPEC-J2 cell proliferation. The underlying mechanism was explored by Western blotting. Arf1 overexpression and knockdown significantly enhanced and suppressed, respectively, the levels of p-S6K1 and p-RPS6, which are key downstream targets of the mTORC1 signaling pathway. Collectively, our findings reveal the role of the Arf1-mTORC1 axis in IPEC-J2 cell proliferation and its potential function in regulating intestinal homeostasis and health., (© 2024. The Society for In Vitro Biology.)

Purpose: To investigate the efficacy of ultrasound fusion imaging-assisted microwave ablation (MWA) for patients with colorectal liver metastases (CRLM) based on stratified analysis of tumor size and location., Methods: Patients with CRLM who underwent ultrasound fusion imaging-assisted MWA in our hospital between February 2020 and February 2023 were enrolled into this retrospective study. Ultrasound fusion imaging was used for detection, guidance, monitoring and immediate evaluation throughout the MWA procedures. Technical success, technique efficacy, local tumor progression (LTP), intrahepatic progression and overall survival (OS) were recorded and analyzed. The subgroup analysis of intrahepatic progression of MWA for CRLM was performed according to tumor size and location., Results: A total of 51 patients with 122 nodules were enrolled. Both technical success and technique efficacy were acquired in all nodules. In a median follow-up period of 19 months, 2.5% of the nodules (3/122) were observed LTP. The 1-year and 2-year cumulative intrahepatic progression rates were 38.7% and 52.1% respectively. Patients were divided into subgroups according to tumor size (≥ 30 mm, n = 13; < 30 mm, n = 38) and tumor location (perivascular, n = 20; non-perivascular, n = 31 and subcapsular, n = 36; non-subcapsular, n = 15). The cumulative intrahepatic progression rates were similar between the subgroups regarding tumor size and perivascular location, while significantly higher in the subcapsular group than in the non-subcapsular group (p = 0.021)., Conclusion: Ultrasound fusion imaging-assisted MWA exhibited satisfactory local efficacy for CRLM, especially for non-subcapsular tumors., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ethnopharmacological Relevance: Modified Danzhi Xiaoyao San (MDXS) is an effective clinical prescription for depression in China, which was deprived of Danzhi Xiaoyao San in the Ming Dynasty. MDSX has significant implications for the development of new antidepressants, but its pharmacological mechanism has been rarely studied., Aim of the Study: To reveal the active components and molecular mechanism of MDXS in treating depression through network pharmacology and experimental verification in vivo and in vitro., Materials and Methods: UPLC-Q-TOF-MS/MS was used to identify the chemical components in the MDXS freeze-dried powder, drug-containing serum, and cerebrospinal fluid (CSF). Based on the analysis of prototype components in the CSF, the major constituents, potential therapeutic targets and possible pharmacological mechanisms of MDXS in treating depression were investigated using network pharmacological and molecular docking. Then corticosterone (CORT)-induced mice model of depression was established to investigate the antidepressant effects of MDXS. HT22 cells were cultured to verify the neuroprotective effects and core targets of the active components., Results: There were 81 compounds in MDXS freeze-dried powder, 36 prototype components in serum, and 13 prototype components in CSF were identified, respectively. Network pharmacology analysis showed that these 13 prototype components in the CSF shared 190 common targets with depression, which were mainly enriched in MAPK and PI3K/AKT signaling pathways. PPI analysis suggested that AKT1 and MAPK1 (ERK1/2) were the core targets. Molecular docking revealed that azelaic acid (AA), senkyunolide A (SA), atractylenolide III (ATIII), and tokinolide B (TB) had the highest binding energy with AKT1 and MAPK1. Animal experiments verified that MDXS could reverse CORT-induced depression-like behaviors, improve synaptic plasticity, alleviate neuronal injury in hippocampal CA3 regions, and up-regulate the protein expression of p-ERK1/2 and p-AKT. In HT22 cells, azelaic acid, senkyunolide A, and atractylenolide III significantly protected the cell injury caused by CORT, and up-regulated the protein levels of p-ERK1/2 and p-AKT., Conclusions: These results suggested that MDXS may exert antidepressant effects partially through azelaic acid, senkyunolide A, and atractylenolide III targeting ERK1/2 and AKT., 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.)

This study aimed to investigate the textural changes of cooked germinated brown rice (GBR) during freeze-thaw treatment and propose a strategy for enhancing its texture using magnetic field (MF). Seven freeze-thaw cycles exhibited more pronounced effects compared to 7 days of freezing, resulting in increases in GBR hardness by 85.59 %-164.36 % and decreases in stickiness by 10.34 %-43.55 %. Water loss, structural damage of GBR flour, and starch retrogradation contributed to the deterioration of texture. MF mitigated these effects by inhibiting the transformation of bound water into free water, reducing water loss by 0.39 %-0.57 %, and shortening the phase transition period by 2.0-21.5 min, thereby diminishing structural damage to GBR flour and hindering starch retrogradation. Following MF treatment (5 mT), GBR hardness decreased by 21.00 %, while stickiness increased by 45.71 %. This study elucidates the mechanisms through which MF enhances the texture, offering theoretical insights for the industrial production of high-quality frozen rice products., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Porous starch (PS) was widely prepared for its large effective surface area, pore volume, and superior hydrophilic property, but its application is limited by enzyme and chemical use. In this study, a novel method to prepare PS with controllable hierarchical pores through ultrasound-ethanol precipitation and different amylose-amylopectin ratios is proposed. As shown in porous morphology and parameters, there were macropores, mesopores and micropores in the formed PS. Moreover, we found that the content of amylose (AM) was negatively related with the total pore volume and pore diameter in PS. The different surface tensions created through ethanol evaporation and water migration during oven drying are the main mechanisms of forming pores with controllable sizes. Based on the molecular information and the long-/short-range orders reflected by crystalline pattern, lamellas, and single-/double-helices, we conclude that AM is easier to form V-type inclusion complexes with ethanol. More single helix of V-amylose was transformed from B-type polymorph after ethanol exchange, which had significantly broadened d Lozentz in PS. The TG spectra proved that the novel PS has the stable thermodynamic property. Overall, the finding of an objective regular between AM and pore sizes of PS in this study may support the other work related to PS., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

CD8 + T cells play a crucial role in anti-tumor immunity, but their function can be impaired by exhaustion induced by prolonged antigen stimulation. Mitochondrial dysfunction, a hallmark of the tumor microenvironment (TME), has been linked to various pathologies, but its specific role in CD8 + T cell exhaustion remains underexplored. Here, we established an in vitro model of CD8 + T cell exhaustion by co-culturing OVA-specific OT1 CD8 + T cells with OVA-expressing MC38 tumor cells. Next, we investigated the impact of mitochondrial dysfunction on exhaustion using pharmacological inhibitors targeting the electron transport chain. The role of the mitochondrial complex I component NDUFA10 was further examined through genetic knockout in CD8 + T cells using CRISPR-Cas9. Inhibition of the mitochondrial electron transport chain significantly accelerated CD8 + T cell exhaustion in vitro. Knockout of NDUFA10 in CD8 + T cells led to enhanced tumor growth and increased exhaustion of tumor-infiltrating CD8 + T cells in a Rag1 -/- tumor-bearing transfer model. This study highlights the critical role of mitochondrial function in regulating CD8 + T cell exhaustion and anti-tumor activity, providing new insights into the metabolic underpinnings of immune dysfunction in cancer., 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 Inc. All rights reserved.)

Objectives: To investigate the efficacy and safety of ultrasound (US)-guided microwave ablation (MWA) without artificial ascites (AA) inpatients with sub-cardiac (SC) liver cancers., Methods: This retrospective study included patients with the left lobe and caudate lobe of the liver cancer who underwent US-guided MWA in our institute from January 2020 to December 2022. According to whether the target lesion was located ≤5 mm from the pericardium, patients were divided into the SC group and the non-sub-cardiac (NSC) group. In the SC group, AA was not employed during the ablation procedure. The results of technical success, technical efficiency, local tumour progression (LTP), and major complications were recorded., Results: A total of 79 patients with 87 lesions were enrolled. There were 38 patients with 38 lesions in the SC group and 41 patients with 49 lesions in the NSC group. The median follow-up of all patients was 15 (range, 3-44) months. There was no significant difference in technical success rates (100% vs 100%), technique efficiency rates (100% vs 95.7%), LTP rates (2.63% vs 0%,), and major complication rates (2.63% vs 7.32%) between the SC group and the NSC group (P > .05). No cardiac-related complications occurred., Conclusions: US-guided MWA without AA for SC liver cancers was safe and effective., Advances in Knowledge: The clinical prognosis of thermal ablation without AA in the treatment of SC liver cancers is still unclear. The finding of this study provided evidence supporting the efficacy and safety of US-guided MWA without AA for treating this tricky location., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Dual-mode signal output platforms have demonstrated considerable promise due to their improved anti-interference capability and inherent signal self-correction. Nevertheless, traditional discrete-distributed signal probes often encounter significant drawbacks, including limited mass transfer efficiency, diminished signal strength, and instability in intricate biochemical environments. In response to these challenges, a scalable and hyper-compacted 3D DNA nanoplatform resembling "periodic focusing heliostat" has been developed for synergistically enhanced fluorescence (FL) and surface-enhanced Raman spectroscopy (SERS) biosensing of miRNA in cancer cells. Our approach utilized a distinctive assembly strategy integrating gold nanostars (GNS) as fundamental "heliostat units" linked by palindromic DNA sequences to facilitate each other hand-in-hand cascade alignment and condensed into large scale nanostructures. This configuration was further augmented by the incorporation of gold nanoparticles (GNP) via strong Au-S bonds, resulting in a sturdy framework for improved signal transduction. The initiation of this assembly process was mediated by the hybridization of dsDNA to miRNA-21, which served as a primer for polymerization and nicking reactions, thus generating a multifunctional T2 probe. This probe is intricately designed with three distinct parts: a 3'-palindromic end for structural integrity, a central region for capturing SERS-active probes (Cy3-P2), and a 5'-segment for attaching fluorescence reporters. Upon integration T2 into the GNS-based heliostat unit, it promotes palindromic arm-induced aggregation and plasma exciton coupling between plasma nanoparticles and signal transduction tags. This clustered arrangement creates a high-density "hot spot" array that maximizes the local electromagnetic fields necessary for enhanced SERS and FL response. This superstructure supports enhanced aggregation-induced signal amplification for both SERS and FL, offering exceptional sensitivity with LOD as low as 0.0306 pM and 0.409 pM. The efficacy of this method was demonstrated in the evaluation of miRNA-21 in various cancer cell lines., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

3D printing technology, especially coaxial 3D mode of multiple-component shaping, has great potential in the manufacture of personalized nutritional foods. However, integrating and stabilizing functional objectives of different natures remains a challenge for 3D customized foods. Here, we used starch nanoparticle (SNP) to assisted soy protein (SPI) emulsion to load hydrophilic and hydrophobic bioactives (anthocyanin, AC, and curcumin, Cur). The addition of SNP significantly improved the storage stability of the emulsion. Xanthan gum (XG) was also added to the SNP/SPI system to enhance its rheology and form an emulsion gel as inner core of coaxial 3D printing. Low field nuclear magnetic resonance and emulsification analyses showed that AC/Cur@SNP/SPI/XG functional inner core had a strong water binding state and good stability. After printing with outer layer, the SNP/SPI coaxial sample had the lowest deviation rate of 0.8 %. Also, SNP/SPI coaxial sample showed higher AC (90.2 %) and Cur (90.8 %) retention compared to pure starch (S), pure SNP, pure SPI, and S/SPI samples as well as SNP/SPI sample printed without outer layer. In summary, this study provides a new perspective for the manufacture of customized products as multifunctional foods, feeds and even potential delivery of drugs., 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.)

High-grade glioma is the most frequent and lethal primary tumor of the central nervous system. Despite advances in surgical, pharmacological, and cell-directed therapies, there have been no updates to the standard of care in over a decade. This cross-sectional study analyzes patient and trial data from 201 interventional trials completed between 2010 and 2023, encompassing 18,563 participants. Although we found that all trials reported participant age and sex, only 52% of trials reported participant demographics, resulting in 51% of total participant demographics being unreported. The majority of studies did not report ethnicity, with approximately 60% of participants unreported. Additionally, males were significantly underrepresented in trials, comprising 60% of participants despite representing 75% of glioblastoma patients. Improved demographic reporting has been observed since 2011; however, it is inconsistent. Furthermore, we cataloged the geographic diversity of trials across the United States and found significant coverage deserts in relatively rural, but highly affected, areas such as Montana and Maine. We found a wider distribution of trials in both urban and wealthier regions, which indicates extensive coverage gaps and decreased access to participation for patients of a lower socioeconomic status.

Background: In randomized clinical trials, treatment effects may vary, and this possibility is referred to as heterogeneity of treatment effect (HTE). One way to quantify HTE is to partition participants into subgroups based on individual's risk of experiencing an outcome, then measuring treatment effect by subgroup. Given the limited availability of externally validated outcome risk prediction models, internal models (created using the same dataset in which heterogeneity of treatment analyses also will be performed) are commonly developed for subgroup identification. We aim to compare different methods for generating internally developed outcome risk prediction models for subject partitioning in HTE analysis., Methods: Three approaches were selected for generating subgroups for the 2,441 participants from the United States enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial. An extant proportional hazards-based outcomes predictive risk model developed on the overall ASPREE cohort of 19,114 participants was identified and was used to partition United States' participants by risk of experiencing a composite outcome of death, dementia, or persistent physical disability. Next, two supervised non-parametric machine learning outcome classifiers, decision trees and random forests, were used to develop multivariable risk prediction models and partition participants into subgroups with varied risks of experiencing the composite outcome. Then, we assessed how the partitioning from the proportional hazard model compared to those generated by the machine learning models in an HTE analysis of the 5-year absolute risk reduction (ARR) and hazard ratio for aspirin vs. placebo in each subgroup. Cochran's Q test was used to detect if ARR varied significantly by subgroup., Results: The proportional hazard model was used to generate 5 subgroups using the quintiles of the estimated risk scores; the decision tree model was used to generate 6 subgroups (6 automatically determined tree leaves); and the random forest model was used to generate 5 subgroups using the quintiles of the prediction probability as risk scores. Using the semi-parametric proportional hazards model, the ARR at 5 years was 15.1% (95% CI 4.0-26.3%) for participants with the highest 20% of predicted risk. Using the random forest model, the ARR at 5 years was 13.7% (95% CI 3.1-24.4%) for participants with the highest 20% of predicted risk. The highest outcome risk group in the decision tree model also exhibited a risk reduction, but the confidence interval was wider (5-year ARR = 17.0%, 95% CI= -5.4-39.4%). Cochran's Q test indicated ARR varied significantly only by subgroups created using the proportional hazards model. The hazard ratio for aspirin vs. placebo therapy did not significantly vary by subgroup in any of the models. The highest risk groups for the proportional hazards model and random forest model contained 230 participants each, while the highest risk group in the decision tree model contained 41 participants., Conclusions: The choice of technique for internally developed models for outcome risk subgroups influences HTE analyses. The rationale for the use of a particular subgroup determination model in HTE analyses needs to be explicitly defined based on desired levels of explainability (with features importance), uncertainty of prediction, chances of overfitting, and assumptions regarding the underlying data structure. Replication of these analyses using data from other mid-size clinical trials may help to establish guidance for selecting an outcomes risk prediction modelling technique for HTE analyses., (© 2024. The Author(s).)