Molecular Mechanisms of Plant Responses to Copper: From Deficiency to Excess.

Copper (Cu) is an essential nutrient for plant growth and development. This metal serves as a constituent element or enzyme cofactor that participates in many biochemical pathways and plays a key role in photosynthesis, respiration, ethylene sensing, and antioxidant systems. The physiological significance of Cu uptake and compartmentalization in plants has been underestimated, despite the importance of Cu in cellular metabolic processes. As a micronutrient, Cu has low cellular requirements in plants. However, its bioavailability may be significantly reduced in alkaline or organic matter-rich soils. Cu deficiency is a severe and widespread nutritional disorder that affects plants. In contrast, excessive levels of available Cu in soil can inhibit plant photosynthesis and induce cellular oxidative stress. This can affect plant productivity and potentially pose serious health risks to humans via bioaccumulation in the food chain. Plants have evolved mechanisms to strictly regulate Cu uptake, transport, and cellular homeostasis during long-term environmental adaptation. This review provides a comprehensive overview of the diverse functions of Cu chelators, chaperones, and transporters involved in Cu homeostasis and their regulatory mechanisms in plant responses to varying Cu availability conditions. Finally, we identified that future research needs to enhance our understanding of the mechanisms regulating Cu deficiency or stress in plants. This will pave the way for improving the Cu utilization efficiency and/or Cu tolerance of crops grown in alkaline or Cu-contaminated soils.

Evolution of Digital Health and Exploration of Patented Technologies (2017-2021): Bibliometric Analysis.

BACKGROUND: The significant impact of digital health emerged prominently during the COVID-19 pandemic. Despite this, there is a paucity of bibliometric analyses focusing on technologies within the field of digital health patents. Patents offer a wealth of insights into technologies, commercial prospects, and competitive landscapes, often undisclosed in other publications. Given the rapid evolution of the digital health industry, safeguarding algorithms, software, and advanced surgical devices through patent systems is imperative. The patent system simultaneously acts as a valuable repository of technological knowledge, accessible to researchers. This accessibility facilitates the enhancement of existing technologies and the advancement of medical equipment, ultimately contributing to public health improvement and meeting public demands. OBJECTIVE: The primary objective of this study is to gain a more profound understanding of technology hotspots and development trends within the field of digital health. METHODS: Using a bibliometric analysis methodology, we assessed the global technological output reflected in patents on digital health published between 2017 and 2021. Using Citespace5.1R8 and Excel 2016, we conducted bibliometric visualization and comparative analyses of key metrics, including national contributions, institutional affiliations, inventor profiles, and technology topics. RESULTS: A total of 15,763 digital health patents were identified as published between 2017 and 2021. The China National Intellectual Property Administration secured the top position with 7253 published patents, whereas Koninklijke Philips emerged as the leading institution with 329 patents. Notably, Assaf Govari emerged as the most prolific inventor. Technology hot spots encompassed categories such as "Medical Equipment and Information Systems," "Image Analysis," and "Electrical Diagnosis," classified by Derwent Manual Code. A patent related to the technique of receiving and transmitting data through microchips garnered the highest citation, attributed to the patentee Covidien LP. CONCLUSIONS: The trajectory of digital health patents has been growing since 2017, primarily propelled by China, the United States, and Japan. Applications in health interventions and enhancements in surgical devices represent the predominant scenarios for digital health technology. Algorithms emerged as the pivotal technologies protected by patents, whereas techniques related to data transfer, storage, and exchange in the digital health domain are anticipated to be focal points in forthcoming basic research.

A three-dimensional liquid diode for soft, integrated permeable electronics.

Wearable electronics with great breathability enable a comfortable wearing experience and facilitate continuous biosignal monitoring over extended periods1-3. However, current research on permeable electronics is predominantly at the stage of electrode and substrate development, which is far behind practical applications with comprehensive integration with diverse electronic components (for example, circuitry, electronics, encapsulation)4-8. Achieving permeability and multifunctionality in a singular, integrated wearable electronic system remains a formidable challenge. Here we present a general strategy for integrated moisture-permeable wearable electronics based on three-dimensional liquid diode (3D LD) configurations. By constructing spatially heterogeneous wettability, the 3D LD unidirectionally self-pumps the sweat from the skin to the outlet at a maximum flow rate of 11.6 ml cm-2 min-1, 4,000 times greater than the physiological sweat rate during exercise, presenting exceptional skin-friendliness, user comfort and stable signal-reading behaviour even under sweating conditions. A detachable design incorporating a replaceable vapour/sweat-discharging substrate enables the reuse of soft circuitry/electronics, increasing its sustainability and cost-effectiveness. We demonstrated this fundamental technology in both advanced skin-integrated electronics and textile-integrated electronics, highlighting its potential for scalable, user-friendly wearable devices.

A prognostic nomogram integrating carcinoembryonic antigen levels for predicting overall survival in elderly patients with stage II-III colorectal cancer.

Background: With the aging of the population, colorectal surgeons will have to face more elderly colorectal cancer (CRC) patients in the future. We aim to analyze independent risk factors affecting overall survival in elderly (age ≥65 years) patients with stage II-III CRC and construct a nomogram to predict patient survival. Methods: A total of 3,016 elderly CRC patients with stage II-III were obtained from the SEER database. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analyses were used to screen independent prognostic factors, and a survival prediction nomogram was constructed based on the results. The consistency index (C-index), decision curve analysis (DCA), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were used to compare the predictive ability between the nomogram and tumor-node-metastasis (TNM) stage system. All patients were classified into high-risk and low-risk groups based on risk scores calculated by nomogram. The Kaplan-Meier method was used to compare the survival differences between two groups. Results: The 3- and 5-year area under the curve (AUC) values of the prediction nomogram model were 76.6% and 74.8%, respectively. The AIC, BIC, and C-index values of the nomogram model were 6,032.502, 15,728.72, and 0.707, respectively, which were better than the TNM staging system. Kaplan-Meier survival analysis showed a significant survival difference between high-risk and low-risk groups (P<0.0001). Conclusions: We constructed a prediction nomogram for stage II-III elderly CRC patients by combining pre-treatment carcinoembryonic antigen (CEA) levels, which can accurately predict patient survival. This facilitates clinicians to accurately assess patient prognosis and identify high-risk patients to adopt more aggressive and effective treatment strategies.

MircoRNA-25-3p in skin precursor cell-induced Schwann cell-derived extracellular vesicles promotes axon regeneration by targeting Tgif1.

Nerve injury often leads to severe dysfunction because of the lack of axon regeneration in adult mammal. Intriguingly a series of extracellular vesicles (EVs) have the obvious ability to accelerate the nerve repair. However, the detailed molecular mechanisms to describe that EVs switch neuron from a transmitter to a regenerative state have not been elucidated. This study elucidated the microRNA (miRNA) expression profiles of two types of EVs that promote nerve regeneration. The functions of these miRNAs were screened in vitro. Among the 12 overlapping miRNAs, miR-25-3p was selected for further analysis as it markedly promoted axon regeneration both in vivo and in vitro. Furthermore, knockdown experiments confirmed that PTEN and Klf4, which are the major inhibitors of axon regeneration, were the direct targets of miR-25-3p in dorsal root ganglion (DRG) neurons. The utilization of luciferase reporter assays and functional tests provided evidence that miR-25-3p enhances axon regeneration by targeting Tgif1. Additionally, miR-25-3p upregulated the phosphorylation of Erk. Furthermore, Rapamycin modulated the expression of miR-25-3p in DRG neurons. Finally, the pro-axon regeneration effects of EVs were confirmed by overexpressing miR-25-3p and Tgif1 knockdown in the optic nerve crush model. Thus, the enrichment of miR-25-3p in EVs suggests that it regulates axon regeneration, proving a potential cell-free treatment strategy for nerve injury.

Gastrointestinal Dysmotility Predisposes to Colitis through Regulation of Gut Microbial Composition and Linoleic Acid Metabolism.

Disrupted gastrointestinal (GI) motility is highly prevalent in patients with inflammatory bowel disease (IBD), but its potential causative role remains unknown. Herein, the role and the mechanism of impaired GI motility in colitis pathogenesis are investigated. Increased colonic mucosal inflammation is found in patients with chronic constipation (CC). Mice with GI dysmotility induced by genetic mutation or chemical insult exhibit increased susceptibility to colitis, dependent on the gut microbiota. GI dysmotility markedly decreases the abundance of Lactobacillus animlalis and increases the abundance of Akkermansia muciniphila. The reduction in L. animlalis, leads to the accumulation of linoleic acid due to compromised conversion to conjugated linoleic acid. The accumulation of linoleic acid inhibits Treg cell differentiation and increases colitis susceptibility via inducing macrophage infiltration and proinflammatory cytokine expression in macrophage. Lactobacillus and A. muciniphila abnormalities are also observed in CC and IBD patients, and mice receiving fecal microbiota from CC patients displayed an increased susceptibility to colitis. These findings suggest that GI dysmotility predisposes host to colitis development by modulating the composition of microbiota and facilitating linoleic acid accumulation. Targeted modulation of microbiota and linoleic acid metabolism may be promising to protect patients with motility disorder from intestinal inflammation.

Identification of Candidate Expansin Genes Associated with Seed Weight in Pomegranate (Punica granatum L.).

Seed weight is an important target trait in pomegranate breeding and culture. Expansins act by loosening plant cell walls and cellulosic materials, permitting turgor-driven cell enlargement. However, the role of expansin genes (EXPs) in pomegranate seed weight remains elusive. A total of 29 PgrEXPs were identified in the 'Dabenzi' genome. These genes were classified into four subfamilies and 14 subgroups, including 22 PgrEXPAs, 5 PgrEXPBs, 1 PgrEXPLA, and 1 PgrEXPLB. Transcriptome analysis of PgrEXPs in different tissues (root, leaf, flower, peel, and seed testa) in 'Dabenzi', and the seed testa of the hard-seeded pomegranate cultivar 'Dabenzi' and soft-seeded cultivar 'Tunisia' at three development stages showed that three PgrEXPs (PgrEXPA11, PgrEXPA22, PgrEXPA6) were highly expressed throughout seed development, especially in the sarcotesta. SNP/Indel markers of these PgrEXPs were developed and used to genotype 101 pomegranate accessions. The association of polymorphic PgrEXPs with seed weight-related traits (100-seed weight, 100-kernel weight, 100-sarcotesta weight, and the percentage of 100-sarcotesta to 100-seed weight) were analyzed. PgrEXP22 was significantly associated with 100-seed weight and 100-sarcotesta weight and is a likely candidate for regulating seed weight and sarcotesta development in particular. This study provides an effective tool for the genetic improvement of seed weight in pomegranate breeding programs.

Magnetic soft microfiberbots for robotic embolization.

Cerebral aneurysms and brain tumors are leading life-threatening diseases worldwide. By deliberately occluding the target lesion to reduce the blood supply, embolization has been widely used clinically to treat cerebral aneurysms and brain tumors. Conventional embolization is usually performed by threading a catheter through blood vessels to the target lesion, which is often limited by the poor steerability of the catheter in complex neurovascular networks, especially in submillimeter regions. Here, we propose magnetic soft microfiberbots with high steerability, reliable maneuverability, and multimodal shape reconfigurability to perform robotic embolization in submillimeter regions via a remote, untethered, and magnetically controllable manner. Magnetic soft microfiberbots were fabricated by thermal drawing magnetic soft composite into microfibers, followed by magnetizing and molding procedures to endow a helical magnetic polarity. By controlling magnetic fields, magnetic soft microfiberbots exhibit reversible elongated/aggregated shape morphing and helical propulsion in flow conditions, allowing for controllable navigation through complex vasculature and robotic embolization in submillimeter regions. We performed in vitro embolization of aneurysm and tumor in neurovascular phantoms and in vivo embolization of a rabbit femoral artery model under real-time fluoroscopy. These studies demonstrate the potential clinical value of our work, paving the way for a robotic embolization scheme in robotic settings.

Patterned Manipulated Surface Based on Femtosecond Laser with Adjustable Wetting Speed and Directional Fluid Delivery.

Recently, due to the crucial roles of multifunctional liquid manipulation surfaces in biomedical transportation, microfluidics, and chemical engineering, the demand for controllable and functional aspects of directed liquid transportation has increased significantly. However, designing an intelligent manipulation surface that is easy to manufacture and fully functional remains an immense challenge. To address this challenge, a smart surface that can regulate the rate of liquid transport within a patterned channel by temperature is reported. A synergistically controlled approach of poly(N-isopropylacrylamide) and micropillar shape-memory polymers (SMPs) was used to modulate the wetting rate of liquids on surfaces. By femtosecond laser direct writing, temperature-responsive composite surfaces are embedded in the microstructure of shape-memory polymers (SMPs) in a patterned manner, resulting in the preparation of novel programmable liquid manipulation surfaces incorporating boundaries possessing asymmetric wettability. Since the smart surface is based on SMP, the superhydrophobic part in the superhydrophobic/controllable wettability patterning platform is also programmed for droplet directional transport, which takes advantage of the difference in wettability between the rewritable indentation track and the periphery to allow droplets to flow into the temperature-controlled velocity track, enriching the functionality of the surface. In addition, based on its excellent controllability and patterning, the surface has been shown to be used in microfluidic circuit chips with self-cleaning properties, which provides new ideas for circuit timing control. This study provides promising prospects for the effective development of multifunctional liquid steering surfaces, lab-on-a-chip, and microfluidic devices.

Heterogeneity of diabetic dyslipidemia, data from the NHANES (2011-2016).

Epidemiologic studies have demonstrated that diabetes amplifies the effects of dyslipidemia as a risk factor for cardiovascular disease (CVD). A better understanding of lipid profiles is important for lipid-lowering treatment and reducing cardiovascular risk in populations with diabetes. To describe the dyslipidemia patterns in patient with and without diabetes in the adult US population. Data from National Health and Nutrition Examination Survey (NHANES) 2011 to 2016 was analyzed. Surprisingly, 49.9% of the people with diabetes have both normal triglycerides (TGs) and normal high-density lipoprotein cholesterol (HDL-C). 33.4% of the people with diabetes have elevated TGs and 36.1% of them have low HDL-C. Only 19.3% of them have both elevated TGs and low HDL-C. Among people without diabetes, 67.5% have normal TGs and normal HDL-C, 28.0% have elevated TGs, 23.9% have low HDL-C and 8.8% have both elevated TGs and low HDL-C. The differences in the proportions of individuals with both elevated TGs and low HDL-C between the diabetic group and the nondiabetic group were more obvious in females: 7.7% in women without diabetes and 22.7% in women with diabetes. The proportion of individuals in the TG↑HDL-C↓group in the population with diabetes exhibited a decreasing trend in age groups > 30 years old, and the 30 to 40 years group of individuals with diabetes had the highest proportion of atherogenic dyslipidemia. The low-density lipoprotein cholesterol (LDL-C) to apoB ratio is generally lower in people with diabetes, with the lowest level in the TG↑HDL-C↓group. Dyslipidemia patterns in diabetes patients are highly heterogeneous. Deep phenotyping sub-groups of dyslipidemia is warranted to identify higher-risk patients for evaluation of non-LDL-C therapies. This explained at least partially of the difficult search for novel therapies in the post-LDL-C era.

Mechanochemical synthesis of organoselenium compounds.

We disclose herein a strategy for the rapid synthesis of versatile organoselenium compounds under mild conditions. In this work, magnesium-based selenium nucleophiles are formed in situ from easily available organic halides, magnesium metal, and elemental selenium via mechanical stimulation. This process occurs under liquid-assisted grinding (LAG) conditions, requires no complicated pre-activation procedures, and operates broadly across a diverse range of aryl, heteroaryl, and alkyl substrates. In this work, symmetrical diselenides are efficiently obtained after work-up in the air, while one-pot nucleophilic addition reactions with various electrophiles allow the comprehensive synthesis of unsymmetrical monoselenides with high functional group tolerance. Notably, the method is applied to regioselective selenylation reactions of diiodoarenes and polyaromatic aryl halides that are difficult to operate via solution approaches. Besides selenium, elemental sulfur and tellurium are also competent in this process, which showcases the potential of the methodology for the facile synthesis of organochalcogen compounds.

Energy consumption analysis of power grid distribution transformers based on an improved genetic algorithm.

With the promotion of energy transformation, the utilization ratio of electrical power is progressively rising. Since electrical power is challenging to store, real-time production and consumption become imperative, imposing significant demands on the dependability and operational efficiency of electrical power apparatus. Suppose the load distribution among multiple transformers within a transformer network exhibits inequality. In such instances, it will amplify the total energy consumption during the voltage conversion process, and local, long-term high-load transformer networks become more susceptible to failures. In this article, we scrutinize the matter of transformer energy utilization in the context of electricity transmission within grid systems. We propose a methodology grounded on genetic algorithms to optimize transformer energy usage by dynamically redistributing loads among diverse transformers based on their operational status monitoring. In our experimentation, we employed three distinct approaches to enhance energy efficiency. The experimental findings evince that this approach facilitates swifter attainment of the optimal power level and diminishes the overall energy consumption during transformer operation. Moreover, it exhibits a heightened responsiveness to fluctuations in power demand from the electrical grid. Experimental results manifest that this technique can truncate monitoring time by 27% and curtail the overall energy consumption of the distribution transformer network by 11.81%. Lastly, we deliberate upon the potential applications of genetic algorithms in the realm of power equipment management and energy optimization issues.

Design of a trichogramma balls UAV delivery system and quality analysis of delivery operation.

The field boundaries in our country are complex. In attempts to control pests via trichogramma-dominated biological control, the long-term practice of manual trichogramma release has resulted in low control efficiency, thereby impeding sustainable agricultural development. Currently, the novel approach involves utilizing Unmanned Aerial Vehicles (UAVs) for trichogramma balls delivery; however, the system is still in its nascent stages, presenting opportunities for enhancement in terms of stability and accuracy. Furthermore, there is a notable absence of comprehensive operational quality assessment standards. In this study, we establish a stable and accurate trichogramma balls delivery system using a four-axis plant protection UAV and introduce a comprehensive evaluation method for trichogramma balls delivery system. When dealing with fields with complex boundaries, it is beneficial to divide them into rectangular, trapezoidal, and stepped small fields at the boundary and perform operations within these small fields. According to our proposed evaluation method, when only considering the effect of field operations, the most effective boundary division shape is trapezoidal, followed by rectangular. and the worst is stepped. If both field operation effectiveness and the utilization effect of placed trichogramma balls are considered, the optimal shape is trapezoidal, then stepped, with rectangular being the least effective. Consequently, for UAV sub-area operations in complex boundary fields, it is advisable to divide the boundaries into trapezoids wherever possible. Field experiment results indicate that the system's delivery area can reach up to 4158 m²/min and the coverage rate of released trichogramma balls can exceed 97%. The system design methodology and comprehensive operational quality evaluation method proposed in this article provide technical support and scientific basis for the application and promotion of UAV delivery trichogramma balls system. This is conducive to the high-quality development of agriculture.

Smart Surfaces with pH-Responsiveness Enhanced by Multiscale Hierarchical Structures Fabricated by Laser Direct Writing.

In contemporary applications, smart surfaces capable of altering their properties in response to external stimuli have garnered significant attention. Nonetheless, the efficient creation of smart surfaces exhibiting robust and rapid responsiveness and meticulous controllability on a large scale remains a challenge. This paper introduces an innovative approach to fabricate smart surfaces with strong pH-responsiveness, combining femtosecond laser direct writing (LDW) processing technology with stimulus-responsive polymer grafting. The proposed model involves the grafting of poly(2-diethylaminoethyl methacrylate) (PDEAEMA) onto rough and patterned Au/polystyrene (PS) bilayer surfaces through Au-SH bonding. The incorporation of LDW processing technology extends the choice of microstructures and roughness achievable on material surfaces, while PDEAEMA imparts pH responsiveness. Our findings revealed that the difference in contact angle between acidic and basic droplets on the rough PDEAEMA-g-Au surface (∼118°) greatly surpasses that on the flat PDEAEMA-g-Au surface (∼72°). Next, by leveraging the precision control over surface microstructures enabled by the LDW processing technique, this difference was further augmented to ∼127° on the optimized patterned PDEAEMA-g-Au surface. Further, we created two distinct combined smart surfaces with varying wettability profiles on which the hydrophilic-hydrophobic boundaries exhibit reliable asymmetric wettability for acidic and basic droplets. Additionally, we prepared a separator, realizing a better visual distinction between acid and base and collecting them separately. Given the effective abilities found in this study, we postulate that our smart surfaces hold substantial potential across diverse applications, encompassing microfluidic devices, intelligent sensors, and biomedicine.

Wearable and battery-free wound dressing system for wireless and early sepsis diagnosis.

Sepsis is a severe organ dysfunction typically caused by wound infection which leads to septic shock, organ failure or even death if no early diagnosis and property medical treatment were taken. Herein, we report a soft, wearable and battery-free wound dressing system (WDS) for wireless and real-time monitoring of wound condition and sepsis-related biomarker (procalcitonin [PCT]) in wound exudate for early sepsis detection. The battery-free WDS powered by near-field communication enables wireless data transmission, signal processing and power supply, which allows portable intelligent wound caring. The exudate collection associates with soft silicone based microfluidic technologies (exudate collection time within 15 s), that can filtrate contamination at the cell level and enable a superior filtration rate up to 95% with adopting microsphere structures. The battery-free WDS also includes state-of-the-art biosensors, which can accurate detect the pH value, wound temperature, and PCT level and thus for sepsis diagnosis. In vivo studies of SD rats prove the capability of the WDS for continuously monitoring wound condition and PCT concentration in the exudate. As a result, the reported fully integrated WDS provides a potential solution for further developing wearable, multifunctional and on-site disease diagnosis.

Palladium-catalyzed [4 + 2] cycloaddition of 2-methylidenetrimethylene carbonate or methylene cyclic carbamate with sulfamate-derived cyclic imines.

A palladium-catalyzed [4 + 2] cycloaddition of 2-methylidenetrimethylene carbonate or methylene cyclic carbamate with sulfamate-derived cyclic imines has been successfully developed under mild reaction conditions, affording pharmacologically interesting oxazine or hydropyrimidine derivatives in high yields (up to 99% yield). Furthermore, the cycloaddition reactions could be efficiently scaled up and several synthetic transformations were accomplished for the construction of other useful 1,3-oxazine and hydropyrimidinone derivatives.

Design, synthesis and bioactivity evaluation of selenium-containing PI3Kδ inhibitors.

PI3Kδ inhibitors play an important role in the treatment of leukemia, lymphoma and autoimmune diseases. Herein, using our reported compounds as the lead compound, we designed and synthesized a series of selenium-containing PI3Kδ inhibitors based on quinazoline and pyrido[3,2-d]pyrimidine skeletons. Among them, compound Se15 showed sub-nanomolar inhibition against PI3Kδ and strong δ-selectivity. Moreover, Se15 showed potent anti-proliferative effect on SU-DHL-6 cells with an IC50 value of 0.16 µM. Molecular docking study showed that Se15 was able to form multiple hydrogen bonds with PI3Kδ and was close proximity and stacking with PI3Kδ selective region. In conclusion, the Se-containing compound Se15 bearing pyrido[3,2-d]pyrimidine scaffold is a novel potent and selective PI3Kδ inhibitor. The introduction of selenium can enrich the structure of PI3Kδ inhibitors and provide a new idea for design of novel PI3Kδ inhibitors.

The effect of cognitive behavioral therapy on chemotherapy-induced side effects and immune function in colorectal cancer patients undergoing chemotherapy: study protocol for a randomized controlled trial.

Background: Colorectal cancer (CRC) was one of the most widely diagnosed cancers in the United States in 2021. CRC patients may experience significant psychological stress and are susceptible to depression and anxiety. Previous studies have shown that cognitive behavioral therapy (CBT) can reduce fatigue and improve quality of life among breast cancer patients. However, as a non-pharmaceutical treatment, it remains unclear whether CBT improves chemotherapy-induced side effects and immune function in CRC patients. In this study, we will conduct a randomized controlled trial (RCT) among CRC patients undergoing chemotherapy to determine whether CBT can reduce the side effects of chemotherapy and improve the immune function of CRC patients. Methods: The study will be a single-center RCT. CRC patients undergoing chemotherapy will receive either eight sessions of group-based CBT (every 2-3 weeks) or usual care (usual oncology care). Each participant will undergo assessments at baseline (T0), immediately post-intervention (T1), 3 months post-intervention (T2), and 6 months post-intervention (T3). The primary outcome will include chemotherapy-induced side effects in CRC patients. The secondary outcome will be immune function (measured by levels of inflammatory cytokines). Other outcomes will include the levels of tumor markers, assessments of psychological status (perception of stress, depression and anxiety, self-efficacy, sleep quality, quality of life, social support condition, and cognitive function), and necessary laboratory examinations (biochemical index and blood cell counts) among CRC patients undergoing chemotherapy. Discussion: Our study will provide clinical evidence regarding whether CBT should be generalized in clinical treatment and the extent to which CBT reduces chemotherapy-induced side effects for CRC patients. Trial Registration: ClinicalTrials.gov registration number NCT04741308.

Biomimetic nanoparticles to enhance the reverse cholesterol transport for selectively inhibiting development into foam cell in atherosclerosis.

A disorder of cholesterol homeostasis is one of the main initiating factors in the progression of atherosclerosis (AS). Metabolism and removal of excess cholesterol facilitates the prevention of foam cell formation. However, the failure of treatment with drugs (e.g. methotrexate, MTX) to effectively regulate progression of disease may be related to the limited drug bioavailability and rapid clearance by immune system. Thus, based on the inflammatory lesion "recruitment" properties of macrophages, MTX nanoparticles (MTX NPs) camouflaged with macrophage membranes (MM@MTX NPs) were constructed for the target to AS plaques. MM@MTX NPs exhibited a uniform hydrodynamic size around ~ 360 nm and controlled drug release properties (~ 72% at 12 h). After the macrophage membranes (MM) functionalized "homing" target delivery to AS plaques, MM@MTX NPs improved the solubility of cholesterol by the functionalized ß-cyclodextrin (ß-CD) component and significantly elevate cholesterol efflux by the loaded MTX mediated the increased expression levels of ABCA1, SR-B1, CYP27A1, resulting in efficiently inhibiting the formation of foam cells. Furthermore, MM@MTX NPs could significantly reduce the area of plaque, aortic plaque and cholesterol crystals deposition in ApoE-/- mice and exhibited biocompatibility. It is suggested that MM@MTX NPs were a safe and efficient therapeutic platform for AS.