Potential Strategy Research Articles

Galloyl-boosted gold nanorods: Unleashing personalized cancer immunotherapy potential

Cancer immunotherapy has emerged as a potent treatment strategy by harnessing the host immune system to target cancer cells. However, challenges including low tumor vaccine immunogenicity and tumor heterogeneity hinder its clinical efficacy. To address these issues, we propose a novel nanoplatform integrating photothermal material gold nanorods (GNRs) with polyphenols for enhanced immunotherapy efficacy via photothermal therapy. Polyphenols, natural compounds with phenolic hydroxyl groups, are known for their ability to bind tightly to various molecules, making them ideal for antigen capture. We synthesized GNRs modified with polyphenols (GNR-PA and GNR-GA) and demonstrated their ability to induce immunogenic cell death upon laser irradiation, releasing tumor-associated antigens (TAAs). The surface polyphenols on GNRs effectively captured released TAAs to shield them from clearance. In vivo studies confirmed increased accumulation of GNR-GA in lymph nodes and enhanced dendritic cell maturation, leading to promoted effector T cell infiltration into tumors. Furthermore, treatment combined with PD-1/PD-L1 pathway blockade demonstrated potent tumor regression and systemic immunotherapy efficacy. Our findings highlight the potential of this photothermal nanoplatform as a promising strategy to overcome the limitations of current cancer immunotherapy approaches and improve therapeutic outcomes.

Comparative efficacy of different exercise modalities on metabolic profiles and liver functions in non-alcoholic fatty liver disease: a network meta-analysis.

Research evidence suggests that exercise is a potent therapeutic strategy for non-alcoholic fatty liver disease (NAFLD). Many investigations have delved into the curative potential of diverse exercise regimens on NAFLD. This investigation synthesizes findings from randomized controlled trials via a network meta-analysis to evaluate the efficacy of exercise-based interventions on NAFLD. We conducted a search across five electronic databases (Web of Science, EMBASE, PubMed, SCOPUS, and CNKI)to identify randomized controlled trials (RCTs) comparing the effects of different exercise modalities on metabolic profiles and liver functions in patients with NAFLD. The literature search was comprehensive up to 15, December 2023. The selected studies were subjected to a rigorous quality appraisal and risk of bias analysis in accordance with the Cochrane Handbook's guidelines, version 5.1.0. We employed Stata/MP 17 for the network meta-analysis, presenting effect sizes as standardized mean differences (SMD). This study aggregated results from 28 studies, involving a total of 1,606 participants. The network meta-analysis revealed that aerobic exercise was the most effective intervention for improving BMI in patients with NAFLD, demonstrating a significant decrease in BMI (-0.72, 95%CI: -0.98 to -0.46; p < 0.05; Surface Under the Cumulative Ranking (SUCRA) = 79.8%). HIIT was the top intervention for enhancing HDL-C (0.12, 95% CI: 0.04 to 0.20; p < 0.05; SUCRA = 76.1%). Resistance exercise was the most effective for reducing LDL-C (-0.20, 95% CI: -0.33 to -0.06; p < 0.05; SUCRA = 69.7%). Mind-body exercise showed superior effectiveness in improving TC (-0.67, 95% CI: -1.10 to -0.24; p < 0.05; SUCRA = 89.7%), TG = -0.67, 95% CI: -1.10 to -0.24; p < 0.05; SUCRA = 99.6%), AST (-8.07, 95% CI: -12.88 to -3.25; p < 0.05; SUCRA = 76.1%), ALT (-12.56, 95% CI: -17.54 to -7.58; p < 0.05; SUCRA = 99.5%), and GGT (-13.77, 95% CI: -22.00 to -5.54; p < 0.05; SUCRA = 81.8%). This network meta-analysis demonstrates that exercise interventions positively affect various metabolic profiles and liver functions in NAFLD patients. Mind-body exercises are particularly effective, surpassing other exercise forms in improving metabolic profiles and liver functions. https://www.crd.york.ac.uk/PROSPERO/, identifier registration number CRD42024526332.

First-principles study of the electronic, optical adsorption, and photocatalytic water-splitting properties of a strain-tuned SiC/WS2 heterojunction

Heterojunction is widely acknowledged as a potent strategy as an effective means for achieving quality electronic, optical adsorption, and photocatalytic water-splitting properties. Strain also can regulate these properties effectively. In this study, we have fabricated and studied a heterojunction comprised SiC and WS2. Utilizing a first-principles method, we systematically investigated the SiC/WS2 heterojunction's structure, stability, electronic, and optical properties, as well as its photocatalytic water splitting characteristics under strain engineering. Our calculations reveal that the SiC/WS2 heterojunction is a type-II heterostructure with two stable structures, which exhibits a direct bandgap and well performance in the visible light region, facilitating efficient separation of photogenerated electron-hole pairs. We have explored and discussed the impacts of biaxial strain on the various properties. The bandgaps of System-A and B are 1.778 eV and 1.820 eV, respectively, without strain. Under strain from −6% to 10%, they initially rise, peak at 1.858 eV and 1.899 eV respectively at −2% strain, then decline. Without strain, effective mass mh/me for both structures are 1.642 and 1.673. Under positive strain, they increase, decrease, then increase again, peaking at 6% with 2.116 and 2.260. At −2% strain, values drop to 0.901 and 0.910 for A and B, respectively. Our calculations also demonstrate that the SiC/WS2 heterostructure qualifies as a promising photocatalytic material, fulfilling the criteria for water splitting under strain conditions of −4%, −2%, and 0%. And the heterojunction with System-B under −4% strain has the optimal performance in photocatalytic water splitting. At a strain of −4%, System-B achieves the maximum η′STH of 16.91%. In conclusion, our study not only offers fundamental insights into the utilization of SiC/WS2 heterojunctions for photocatalytic water splitting, but also provides the foundational design principles of heterojunctions.

Friends because of foes: synchronous movement within predator-prey domains.

For prey, movement synchrony represents a potent antipredator strategy. Prey, however, must balance the costs and benefits of using conspecifics to mediate risk. Thus, the emergent patterns of risk-driven sociality depend on variation in space and in the predators and prey themselves. We applied the concept of predator-prey habitat domain, the space in which animals acquire food resources, to test the conditions under which individuals synchronize their movements relative to predator and prey habitat domains. We tested the response of movement synchrony of prey to predator-prey domains in two populations of ungulates that vary in their gregariousness and predator community: (i) elk, which are preyed on by wolves; and (ii) caribou, which are preyed on by coyotes and black bears. Prey in both communities responded to cursorial predators by increasing synchrony during seasons of greater predation pressure. Elk moved more synchronously in the wolf habitat domain during winter and caribou moved more synchronously in the coyote habitat domains during spring. In the winter, caribou increased movement synchrony when coyote and caribou domains overlapped. By integrating habitat domains with movement ecology, we provide a compelling argument for social behaviours and collective movement as an antipredator response. This article is part of the theme issue 'The spatial-social interface: A theoretical and empirical integration'.

Enhancing melanoma therapy by modulating the immunosuppressive microenvironment with an MMP-2 sensitive and nHA/GNE co-encapsulated hydrogel

The immunosuppressive tumor microenvironment, such as lactic acid and matrix metalloproteinases (MMPs) overexpression, has been well confirmed to be adverse for tumor therapy. In current study, a tumor microenvironment modulatory hydrogel was successfully developed to treat melanoma by taking advantage of the synergistic effects of nano-hydroxyapatite (nHA) with well-documented selective anti-tumor action, lactate dehydrogenase A inhibitor (R)-GNE-140 (GNE), and matrix metalloproteinase-2 (MMP-2) sensitive peptide. The hydrogel was acquired by the reaction of 4-arm-polyethylene glycol-maleic anhydride (4-arm-PEG-MAL) and MMP-2 sensitive peptide (CC-14), in which nHA and GNE were co-encapsulated physically. The in vitro degradation tests confirmed the accelerated release of nHA and GNE from the hydrogel under less-acidic (pH 6.8) and MMP-2 containing conditions compared to those neutral or without MMP-2 conditions, demonstrating the pH and MMP-2 responsive properties of as-prepared hydrogel. Findings from in vitro cell experiments revealed that the hydrogel could stop the proliferation of melanoma cells by stacking cell cycle via lactic acid metabolic dysregulation and boosting cell apoptosis via nHA direct killing effect. Moreover, after hydrogel treatment, the rate of migration and aggressiveness of melanoma cells both reduced significantly. An in vivo anti-melanoma study showed that the hydrogel could inhibit tumor growth significantly and result in more CD8+ T cells and antigen-presenting cells but less Treg cells infiltration, ultimately leading to an enhanced therapeutic efficacy. As thus, the fabricated hydrogel demonstrated great promise for treating melanoma and could be a new potent strategy for efficient melanoma therapy. Statement of significanceNano-hydroxyapatite (nHA) has the capability of selectively killing cancer cells. The study reported a tumor microenvironment (TME) modulatory hydrogel with the goal of enhancing melanoma therapy efficacy by combining nHA administration with immunosuppressive microenvironment modulation. The hydrogel demonstrated pH and MMP-2 sensitivity. Hence, controlled release of nHA and lactate dehydrogenase A inhibitor (GNE) could be observed, and in situ MMP-2 consumption at the tumor site occurred. The hydrogel effectively inhibited the growth of melanoma cells. Furthermore, hydrogel increased the production of CD8+ T cells and antigen-presenting cells while decreasing the infiltration of Treg cells at the tumor site. This could transform the initial “cold” tumor into a “hot” tumor, ultimately resulting in an enhanced therapeutic effect.

Engineering a Surfactant Trap via Postassembly Modification of an Imine Cage.

Imine self-assembly stands as a potent strategy for the preparation of molecular organic cages. However, challenges persist, such as water insolubility and limited recognition properties due to constraints in the application of specific components during the self-assembly process. In this study, we addressed these limitations by initially employing a locking strategy, followed by a postassembly modification. This sequential approach enables precise control over both the solubility and host-guest properties of an imine-based cage. The resulting structure demonstrates water solubility and exhibits an exceptional capacity to selectively interact with anionic surfactants, inducing their precipitation. Remarkably, each cage precipitates 24 equiv of anionic surfactants even at concentrations much lower than the surfactant's critical micelle concentration (CMC), ensuring their complete removal. Molecular simulations elucidate how anionic surfactants specifically interact with the cage to facilitate aggregation below the surfactant CMC and induce precipitation as a micellar cross-linker. This innovative class of cages paves the way for the advancement of materials tailored for environmental remediation.

Citrus aurantifolia-derived carbon quantum dots with red fluorescence emission for codelivery with curcumin as theranostic liposomes for lung cancer

BackgroundCarbon dots (CDs) derived from Citrus aurantifolia represent a promising platform for advanced cancer therapy and diagnostics (theranostics). These CDs are synthesized through a sustainable and cost-effective hydrothermal method, utilizing fruit juice as a green carbon source. Despite the potential, research on the synthesis of citrus-based CDs, especially regarding their red fluorescence emission, which is crucial for enhanced tissue penetration and biomedical efficacy, remains limited.ResultsIn this study, CDs were successfully synthesized from C. aurantifolia fruit, yielding nanoparticles below 5 nm in size (PDI 0.231 ± 0.04). Characterization revealed favorable optical properties, including excitation-dependent fluorescent behavior with prominent red emission under higher excitation wavelengths, a quantum yield of 8.17%, and stable photoluminescence. Chemical composition analysis using XPS, FTIR, and XRD confirmed the purity and structure of the CDs.To explore their biomedical application, CDs were co-loaded with curcumin into liposomes. The formulations had a mean size of 177.2 ± 3.6 nm (PDI 0.270 ± 0.012), demonstrated efficient drug entrapment (60.32 ± 2.24%), and exhibited rapid release kinetics, with 90.21 ± 2.16% of the drug release within 8 h. In vitro studies using A549 lung cancer cells demonstrated superior cellular uptake and cytotoxicity of Cur-CD-loaded liposomes compared to curcumin alone (Cur-Suspension), achieving IC50 values of 0.093 ± 0.011 µg/ml and 0.016 ± 0.006 µg/ml, respectively.ConclusionThis research underscores C. aurantifolia as a viable natural source for green CD synthesis. The obtained CDs with red fluorescence emission, optimized through reaction conditions and excitation wavelengths, hold promise for enhanced biological applications, particularly in the realm of lung cancer therapy. The findings advocate for further exploration and refinement of citrus-based CDs as versatile theranostic agents, capitalizing on their sustainable origins and potent biomedical properties. The combination of citrus-derived CDs with curcumin loaded into liposomal formulations represents a potent theranostic strategy for lung cancer treatment, leveraging the unique properties of CDs and their potential for targeted and effective therapy.Graphical abstract

Deciphering the code: the pivotal role of lncRNAs in advancing TNBC therapy.

Triple-negative breast cancer (TNBC) represents the most formidable subtype of breast cancer, characterized by a notable dearth in targeted therapeutic options. Deciphering the underlying molecular mechanisms of TNBC is pivotal for improving patient outcomes. Recent scientific advancements have spotlighted long non-coding RNAs (lncRNAs) as key players in the genesis, progression, and metastasis of cancers. This review delineates the significant influence of lncRNAs on the advancement, detection, and neoadjuvant chemotherapy efficacy in TNBC, detailing the diverse expression patterns of aberrant lncRNAs. The paper explores the specific mechanisms by which lncRNAs regulate gene expression in both the nucleus and cytoplasm, with a special focus on their involvement in TNBC's post-transcriptional landscape. Thorough investigations into TNBC-associated lncRNAs not only forge new avenues for early diagnosis and potent treatment strategies but also highlight these molecules as promising therapeutic targets, heralding an era of personalized and precision medicine in TNBC management.

The Cutting-edge of CRISPR for Cancer Treatment and its Future Prospects.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a versatile technology that allows precise modification of genes. One of its most promising applications is in cancer treatment. By targeting and editing specific genes involved in cancer development and progression, CRISPR has the potential to become a powerful tool in the fight against cancer. This review aims to assess the recent progress in CRISPR technology for cancer research and to examine the obstacles and potential strategies to address them. The two most commonly used CRISPR systems for gene editing are CRISPR/Cas9 and CRISPR/Cas12a. CRISPR/Cas9 employs different repairing systems, including homologous recombination (HR) and nonhomologous end joining (NHEJ), to introduce precise modifications to the target genes. However, off-target effects and low editing efficiency are some of the main challenges associated with this technology. To overcome these issues, researchers are exploring new delivery methods and developing CRISPR/Cas systems with improved specificity. Moreover, there are ethical concerns surrounding using CRISPR in gene editing, including the potential for unintended consequences and the creation of genetically modified organisms. It is important to address these issues through rigorous testing and strict regulations. Despite these challenges, the potential benefits of CRISPR in cancer therapy cannot be overlooked. By introducing precise modifications to cancer cells, CRISPR could offer a targeted and effective treatment option for patients with different types of cancer. Further investigation and development of CRISPR technology are necessary to overcome the existing challenges and harness its full potential in cancer therapy.

Therapeutic CRISPR epigenome editing of inflammatory receptors in the intervertebral disc

Low back pain (LBP) ranks among the leading causes of disability worldwide and generates a tremendous socioeconomic cost. Disc degeneration, a leading contributor to LBP, can be characterized by the breakdown of the extracellular matrix of the intervertebral disc (IVD), disc height loss, and inflammation. The inflammatory cytokine TNF-α has multiple signaling pathways, including proinflammatory signaling through Tumor Necrosis Factor Receptor 1 (TNFR1), and has been implicated as a primary mediator of disc degeneration. We tested our ability to regulate the TNFR1 signaling pathway in vivo, utilizing Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) epigenome editing to slow the progression of disc degeneration in rats. Sprague-Dawley rats were treated with TNF-α and CRISPR interference (CRISPRi)-based epigenome-editing therapeutics targeting TNFR1, showing decreased behavioral pain in a disc degeneration model. Surprisingly, while treatment with the vectors alone was therapeutic, the TNF-α injection became therapeutic after TNFR1 modulation. These results suggest direct inflammatory receptor modulation as a potent strategy for treating disc degeneration.

Inside the Black Box of Deliberate Practice: How do Coaches Coach to Improve Trauma Triage

IntroductionDeliberate practice, goal-oriented training with feedback from a coach, is a common tool for improving physicians’ performance. However, little is known about how coaches foster performance improvement. MethodsA content analysis of video-recorded training sessions was performed to analyze the coaches’ behaviors during a pilot randomized trial of deliberate practice in trauma triage. The intervention consisted of three video-conference sessions during which trial physicians, under the supervision of a coach, played a customized video game designed to review trauma triage principles. A multidisciplinary team specified tasks (e.g., create collaborative learning environment) that coaches should complete, and suggested 19 coaching strategies (e.g., encourage culture of error) to allow execution of these tasks. Two independent raters translated those strategies into a coding framework and applied it deductively to the recorded sessions. The frequencies of the coaching strategies were summarized, and tested for variation across coaches and time. ResultsThirty physicians received the intervention across two 1-mo blocks. Most (28 [93%]) completed three sessions, each covering two (interquartile range 1-2) triage principles. Coaches used coaching strategies 18 (interquartile range 14.5-22) times per triage principle, using some often (2-3 times/principle) and others infrequently (<1 time/principle). The three coaches used similar numbers (20 versus 16 versus 18.5, P = 0.07) and types of strategies. However, use increased over time (16.8 [Block 1] versus 20 [Block 2] P = 0.018). ConclusionsCoaches used 19 coaching strategies to deliver this deliberate practice intervention, with behavior that evolved over time. Future trials should isolate the most potent strategies and should assess the best method of standardizing coaching.

Improving the surface characteristics of metallic glass thin ribbons by laser gas nitriding

The single-roll cooling method excels in producing metallic glass ribbons (MGRs), offering rapid cooling rates and exceptional thickness consistency. Nevertheless, a large number of defects including micro-pits and micro-gaps usually appear on the surface of MGRs after the roll forming process, significantly impacting their service life and performance. Laser gas nitriding is a cutting-edge surface modification technology that has been extensively used to improve the comprehensive performance of various metal components. Herein, an attempt was made to simultaneously improve the surface quality and mechanical properties of Zr41.2Ti13.8Cu12.5Ni10Be22.5 MGRs by nanosecond pulsed laser irradiation in a flowing nitrogen atmosphere. The effects of laser irradiation parameters on the surface characteristics of the laser gas nitrided regions were systematically investigated. The experimental results showed that the surface quality of MGRs after laser gas nitriding was enhanced, accompanied by a simultaneous improvement in hardness and scratch resistance. This study underscores laser gas nitriding as a potent strategy to augment the comprehensive surface characteristics of MGRs. This enhancement is poised to significantly extend their service life and reinforce their reliability when utilized as structural and functional materials in sectors such as machinery, national defense, and aerospace.

Natural compound phloretin restores periodontal immune homeostasis via HIF-1α-regulated PI3K/Akt and glycolysis in macrophages

Periodontitis is a chronic inflammatory disease that affects about 45 %-50 % of adults worldwide, but the efficacy of current clinical therapies is unsatisfactory due to the complicated periodontal immune microenvironment. Thus, developing drugs that can regulate innate immune cells (e.g., macrophages) is a potent strategy to treat periodontitis. Here, we report that phloretin, a food plant-derived natural compound, is sufficient to alleviate periodontitis through immune regulation. In vivo, phloretin treatment could significantly reduce alveolar bone resorption and periodontal inflammation in mouse periodontitis models. In vitro, phloretin could suppress proinflammatory (M1-like) polarization and cytokine release in macrophages induced by LPS. Mechanistically, the immune regulatory role of phloretin in macrophages may be due to its metabolic regulation effect. Phloretin might restore the balance of M1/M2 macrophage transition in periodontitis by inhibiting HIF-1α-mediated glycolysis and PI3k/Akt pathways, thereby reducing the proinflammatory effect and immune disorder caused by over-activated M1 macrophages. Together, this study highlights that natural compound, such as phloretin, can restore periodontal immune homeostasis by metabolic regulation of macrophages, which may provide novel insight into the treatment of periodontitis.

Revamping Hepatocellular Carcinoma Immunotherapy: The Advent of Microbial Neoantigen Vaccines.

Immunotherapy has revolutionized the treatment paradigm for hepatocellular carcinoma (HCC). However, its efficacy varies significantly with each patient's genetic composition and the complex interactions with their microbiome, both of which are pivotal in shaping anti-tumor immunity. The emergence of microbial neoantigens, a novel class of tumor vaccines, heralds a transformative shift in HCC therapy. This review explores the untapped potential of microbial neoantigens as innovative tumor vaccines, poised to redefine current HCC treatment modalities. For instance, neoantigens derived from the microbiome have demonstrated the capacity to enhance anti-tumor immunity in colorectal cancer, suggesting similar applications in HCC. By harnessing these unique neoantigens, we propose a framework for a personalized immunotherapeutic response, aiming to deliver a more precise and potent treatment strategy for HCC. Leveraging these neoantigens could significantly advance personalized medicine, potentially revolutionizing patient outcomes in HCC therapy.

The Therapeutic Mechanisms of Honey in Mitigating Toxicity from Anticancer Chemotherapy Toxicity: A Review.

Within the domain of conventional oncochemotherapeutics, anticancer chemotherapy (AC) has emerged as a potent strategy for the treatment of cancers. AC is the mainstay strategy for solid and non-solid cancer treatment. Its mechanistic action targets the blockage of DNA transcription and the dysregulation of cell cycle machinery in cancer cells, leading to the activation of death pathways. However, the attendant side effect of toxicity inflicted by AC on healthy tissues presents a formidable challenge. The crucial culprit in the AC side effect of toxicity is unknown, although oxidative stress, mitochondrial impairment, inflammatory cascades, autophagy dysregulation, apoptosis, and certain aberrant signaling have been implicated. Honey is a natural bee product with significant health benefits and pharmacological properties. Interestingly, the literature reports that honey may proffer a protection mechanism for delicate tissue/organs against the side effect of toxicity from AC. Thus, this review delves into the prospective role of honey as an alleviator of the AC side effect of toxicity; it provides an elucidation of the mechanisms of AC toxicity and honey's molecular mechanisms of mitigation. The review endeavors to unravel the specific molecular cascades by which honey orchestrates its mitigating effects, with the overarching objective of refining its application as an adjuvant natural product. Honey supplementation prevents AC toxicity via the inhibition of oxidative stress, NF-κB-mediated inflammation, and caspase-dependent apoptosis cascades. Although there is a need for increased mechanistic studies, honey is a natural product that could mitigate the various toxicities induced by AC.

Effects of low-volume court-based sprint interval training on anaerobic capacity and sport-specific performance in competitive tennis players

Sprint interval training (SIT) is a potent exercise strategy to enhance athletes’ anaerobic capacity in a time-efficient manner. This study aimed to investigate the impact of low-volume, court-based SIT on the anaerobic capacity and sport-specific performance in competitive tennis players. Twenty-four competitive collegiate tennis players were randomly assigned to either the SIT group (n = 12; three sessions per week of court-based repeated-sprint training) or the traditional endurance training (ET) group (n = 12; three sessions per week of 45-min continuous treadmill running, n = 12) for a 6-weeks intervention. Baseline and post-intervention assessments included the Wingate Anaerobic Test, elimination rate of blood lactate (BLAer), tennis-specific repeated sprint ability (RSA), and the Yo-Yo Intermittent Recovery Test Level 2 (YoYo-IR2). The results showed that SIT group demonstrated significant improvements in peak and average power during the Wingate test (p = 0.07; p < 0.001), along with a notable increase in YoYo-IR2 performance (7.8% increase, p = 0.04). Significant decreases were observed in both mean (5.1% decrease, p = 0.02) and sum RSA time (5.2% decrease, p = 0.02) in the tennis-specific RSA assessments. Additionally, the SIT group showed significantly higher effective training time and TRIMP in the 90–100% HRmax zone compared to the ET group (p < 0.01). This study underscores the potential benefits of low-volume, court-based SIT in enhancing anaerobic capacity and sport-specific performance in competitive tennis players, in comparison to traditional ET.

Enhancing the Resolution of Satellite Ocean Data Using Discretized Satellite Gridding Neural Networks

Ocean satellite data are often impeded by intrinsic limitations in resolution and accuracy. However, conventional data reconstruction approaches encounter substantial challenges when facing the nonlinear oceanic system and high-resolution fusion of variables. This research presents a Discrete Satellite Gridding Neural Network (DSGNN), a new machine learning method that processes satellite data within a discrete grid framework. By transforming the positional information of grid elements into a standardized vector format, the DSGNN significantly elevates the accuracy and resolution of data fusion through a neural network model. This method’s innovative aspect lies in its discretization and fusion technique, which not only enhances the spatial resolution of oceanic data but also, through the integration of multi-element datasets, better reflects the true physical state of the ocean. A comprehensive analysis of the reconstructed datasets indicates the DSGNN’s consistency and reliability across different seasons and oceanic regions, especially in its adept handling of complex nonlinear interactions and small-scale oceanic features. The DSGNN method has demonstrated exceptional competence in reconstructing global ocean datasets, maintaining small error variance, and achieving high congruence with in situ observations, which is almost equivalent to 1/12° hybrid coordinate ocean model (HYCOM) data. This study offers a novel and potent strategy for the high-resolution reconstruction and fusion of ocean satellite datasets.

UV-activated green-synthesized ZnO NPs from Camellia sinensis extract: a potent antimicrobial strategy

UV-activated green-synthesized ZnO NPs from Camellia sinensis extract: a potent antimicrobial strategy

Unique tau- and synuclein-dependent metabolic reprogramming in neurons distinct from normal aging.

Neuronal cells are highly specialized cells and have a specific metabolic profile to support their function. It has been demonstrated that the metabolic profiles of different cells/tissues undergo significant reprogramming with advancing age, which has often been considered a contributing factor towards aging-related diseases including Alzheimer's (AD) and Parkinson's (PD) diseases. However, it is unclear if the metabolic changes associated with normal aging predispose neurons to disease conditions or a distinct set of metabolic alterations happen in neurons in AD or PD which might contribute to disease pathologies. To decipher the changes in neuronal metabolism with age, in AD, or in PD, we performed high-throughput steady-state metabolite profiling on heads in wildtype Drosophila and in Drosophila models relevant to AD and PD. Intriguingly, we found that the spectrum of affected metabolic pathways is dramatically different between normal aging, Tau, or Synuclein overexpressing neurons. Genetic targeting of the purine and glutamate metabolism pathways, which were dysregulated in both old age and disease conditions partially rescued the neurodegenerative phenotype associated with the overexpression of wildtype and mutant tau. Our findings support a "two-hit model" to explain the pathological manifestations associated with AD where both aging- and Tau/Synuclein- driven metabolic reprogramming events cooperate with each other, and targeting both could be a potent therapeutic strategy.

Enhanced Efficacy of Gastric Cancer Treatment through Targeted Exosome Delivery of 17-DMAG Anticancer Agent.

In this study, we explored the potential of genetically engineered exosomes as vehicles for precise drug delivery in gastric cancer therapy. A novel antitumor strategy using biocompatible exosomes (Ex) was devised by genetically engineering adipose-derived stem cells to express an MKN45-binding peptide (DE532) on their surfaces. 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) was encapsulated in engineered exosomes, resulting in 17-DMAG-loaded DE532 exosomes. In both in vitro and in vivo experiments using mouse gastric cancer xenograft models, we demonstrated that 17-DMAG-loaded DE532 Ex exhibited superior targetability over DE532 Ex, 17-DMAG-loaded Ex, and Ex. Administration of the 17-DMAG-loaded DE532 Ex yielded remarkable antitumor effects, as evidenced by the smallest tumor size, lowest tumor growth rate, and lowest excised tumor weight. Further mechanistic examinations revealed that the 17-DMAG-loaded DE532 Ex induced the highest upregulation of the pro-apoptotic marker B-cell lymphoma-2-like protein 11 and the lowest downregulation of the anti-apoptotic marker B-cell lymphoma-extra large. Concurrently, the 17-DMAG-loaded DE532 Ex demonstrated the lowest suppression of antioxidant enzymes, such as superoxide dismutase 2 and catalase, within tumor tissues. These findings underscore the potential of 17-DMAG-loaded DE532 exosomes as a potent therapeutic strategy for gastric cancer, characterized by precise targetability and the potential to minimize adverse effects.