The Evolution of Microfluidic-Based Drug-Loading Techniques for Cells and Their Derivatives.

Conventional drug delivery techniques face challenges related to targeting and adverse reactions. Recent years have witnessed significant advancements in nanoparticle-based drug carriers. Nevertheless, concerns persist regarding their safety and insufficient metabolism. Employing cells and their derivatives, such as cell membranes and extracellular vesicles (EVs), as drug carriers effectively addresses the challenges associated with nanoparticle carriers. However, an essential hurdle remains in efficiently loading drugs into these carriers. With the advancement of microfluidic technology and its advantages in precise manipulation at the micro- and nanoscales, as well as minimal sample loss, it has found extensive application in the loading of drugs using cells and their derivatives, thereby fostering the development of drug-loading techniques. This paper outlines the characteristics and benefits of utilizing cells and their derivatives as drug carriers and provides an overview of current drug-loading techniques, particularly those rooted in microfluidic technology. The significant potential for microfluidic technology in targeted disease therapy through drug delivery systems employing cells and their derivatives, is foreseen.

Unlocking a Fast Track for Magnesium Migration in Cu1.8S1-xSex via Anion-Tuning Chemistry.

Rechargeable magnesium batteries (rMBs) are promising candidates for next-generation batteries in which sulfides are widely used as cathode materials. The slow kinetics, low redox reversibility, and poor magnesium storage stability induced by the large Coulombic resistance and ionic polarization of Mg2+ ions have obstructed the development of high-performance rMBs. Herein, a Cu1.8S1-xSex cathode material with a two-dimensional sheet structure has been prepared by an anion-tuning strategy, achieving improved magnesium storage capacity and cycling stability. Element-specific synchrotron radiation analysis is evidence that selenium incorporation has indeed changed the chemical state of Cu species. Density functional theory calculations combined with kinetics analysis reveal that the anionic substitution endows the Cu1.8S1-xSex electrode with favorable charge-transfer kinetics and low ion diffusion barrier. The principal magnesium storage mechanisms and structural evolution process have been revealed in details based on a series of ex situ investigations. Our findings provide an effective heteroatom-tuning tactic of optimizing electrode structure toward advanced energy storage devices.

Interfacial Coupling toward Bismuth Sulfide/MXene Heterostructures Empowering Reversible Magnesium Storage.

Bismuth-based compounds based on conversion-alloying reactions of multielectron transfer have attracted extensive attention as alternative anode candidates for rechargeable magnesium batteries (rMBs). However, the inadequate magnesium storage capability induced by the sluggish kinetics, poor reversibility, and terrible structural stability impedes their practical utilization. Herein, monodispersed Bi2S3 anchored on MXene has been prepared via a simple self-assembly strategy to induce the interfacial bonding of Ti-S and Ti-O-Bi. Unique superiority, including good electrical conductivity, high mechanical strength, and rapid charge transfer, is cleverly integrated together in the Bi2S3/MXene heterostructures, which endowed heterostructures with enhanced magnesium storage performance. Density functional theory calculations combined with kinetic behavior analyses confirm the favorable charge transfer and low ion diffusion barrier in hybrids. Furthermore, a stepwise insertion-conversion-alloying reaction mechanism is revealed in depth by ex situ investigations, which may also account for promoting performance. This work provides significant inspirations for constructing ingenious multicompositional hybrids by strong interfacial coupling engineering toward high-performance energy storage devices.

A stepwise multi-stage continuous dielectrophoresis separation microfluidic chip with microfilter structures.

The separation of target microparticles using microfluidic systems owns extensive applications in biomedical, chemical, and materials science fields. Integration of microfluidic sorting systems employing dielectrophoresis (DEP) technology has been widely investigated. However, enhancing separation efficiency, purity, stability, and integration remains a pressing issue. This study proposes a stepwise multi-stage continuous DEP separation microfluidic chip with a microfilter structure. By leveraging a stepwise electrode configuration, a gradient electric field is generated to drive target microparticles along the electric field gradient, thereby enhancing separation efficiency. Innovative integration of a microfilter structure facilitates simultaneous filtration and improves flow field distribution, thus enhancing system stability. Through the synergistic effect of stepwise electrodes and the microfilter structure, superior coupling of electric and flow fields is achieved, consequently improving the sorting purity, separation efficiency, and system stability of the DEP-based microfluidic sorting system. Validation through simulation and separation of polystyrene microspheres demonstrates the excellent particle separation performance of the proposed system. It evidently shows potential for seamless extension to various biological microparticle sorting applications, harboring significant prospects in the biomedical domain field.

Application of artificial intelligence in cancer diagnosis and tumor nanomedicine.

Cancer is a major health concern due to its high incidence and mortality rates. Advances in cancer research, particularly in artificial intelligence (AI) and deep learning, have shown significant progress. The swift evolution of AI in healthcare, especially in tools like computer-aided diagnosis, has the potential to revolutionize early cancer detection. This technology offers improved speed, accuracy, and sensitivity, bringing a transformative impact on cancer diagnosis, treatment, and management. This paper provides a concise overview of the application of artificial intelligence in the realms of medicine and nanomedicine, with a specific emphasis on the significance and challenges associated with cancer diagnosis. It explores the pivotal role of AI in cancer diagnosis, leveraging structured, unstructured, and multimodal fusion data. Additionally, the article delves into the applications of AI in nanomedicine sensors and nano-oncology drugs. The fundamentals of deep learning and convolutional neural networks are clarified, underscoring their relevance to AI-driven cancer diagnosis. A comparative analysis is presented, highlighting the accuracy and efficiency of traditional methods juxtaposed with AI-based approaches. The discussion not only assesses the current state of AI in cancer diagnosis but also delves into the challenges faced by AI in this context. Furthermore, the article envisions the future development direction and potential application of artificial intelligence in cancer diagnosis, offering a hopeful prospect for enhanced cancer detection and improved patient prognosis.

Resection of the tumor in the trigone of the lateral ventricle via the contralateral posterior interhemispheric transfalcine transprecuneus approach with multi-modern neurosurgery technology: a case report.

Choroid plexus papilloma (CPP) is a rare benign intracranial tumor origin that predominantly manifests in the lateral ventricle in children, accounting for 0.3%-0.6% of all primary intracranial tumors. It is extremely rare to have the CPP in the trigone of the lateral ventricle through the contralateral posterior interhemispheric transfalcine transprecuneus approach (PITTA). Herein, we report this rare case. A 7-year-old girl presented with headache. Magnetic resonance imaging of the brain showed periatrial lesions, and histopathological examination confirmed CPP (WHO grade I). The contralateral PITTA is a safe, effective, reasonable, and appropriate for some lesions in the trigone of the lateral ventricle. It provides a wider surgical angle (especially for the lateral extension) and reduces the risk of disturbance of the optic radiation compared with the conventional approaches. The use of multiple modern neurosurgical techniques, including interventional embolization, intraoperative navigation, microscope, and electrophysiological monitoring, make the procedure much easier and more accurate, and the neuroendoscope adds to the visualization of the microscope and can reduce surgical complications.

Engineering Sb/Zn4(OH)6SO4·5H2O interfacial layer by in situ chemically reacting for stable Zn anode.

Rechargeable aqueous zinc ion batteries with abundant resources and high safety have gained extensive attention in energy storage technology. However, the cycle stability is largely limited by notorious Zn dendrite growth and water-induced interfacial side reactions. Here, a uniform and robust protection layer consisting of metal antimony (Sb) nanoparticles and micrometer-size sheets Zn4(OH)6SO4·5H2O (ZHS) is purposely designed to stabilize Zn anode via an in situ chemical reaction strategy. The two-phase protection layers (Sb/ZHS) induce a reinforcement effect on the Zn anode (Zn@Sb/ZHS). Specifically, Sb nanoparticles play the part of nucleation sites to facilitate uniform Zn plating and homogenize the electric field around the Zn surface. ZHS micrometer-size sheets possess sufficient electrolyte wettability, fast ion transfer kinetics, and anti-corrosion, thus guaranteeing uniform ion flux and inhibiting H2O decomposition. As expected, the symmetric Zn@Sb/ZHS//Zn@Sb/ZHS cells achieve a minimal voltage hysteresis and a reversible cycle of over 2000 h at 1 mA cm-2. By pairing with the MnO2 cathode, the full cell exhibits a significantly improved stability (∼94.17 % initial capacity after 1500 cycles). This study provides a new strategy to design artificial protection layers.

Revisiting the Transferability of Few-Shot Image Classification: A Frequency Spectrum Perspective.

Few-shot learning, especially few-shot image classification (FSIC), endeavors to recognize new categories using only a handful of labeled images by transferring knowledge from a model trained on base categories. Despite numerous efforts to address the challenge of deficient transferability caused by the distribution shift between the base and new classes, the fundamental principles remain a subject of debate. In this paper, we elucidate why a decline in performance occurs and what information is transferred during the testing phase, examining it from a frequency spectrum perspective. Specifically, we adopt causality on the frequency space for FSIC. With our causal assumption, non-causal frequencies (e.g., background knowledge) act as confounders between causal frequencies (e.g., object information) and predictions. Our experimental results reveal that different frequency components represent distinct semantics, and non-causal frequencies adversely affect transferability, resulting in suboptimal performance. Subsequently, we suggest a straightforward but potent approach, namely the Frequency Spectrum Mask (FRSM), to weight the frequency and mitigate the impact of non-causal frequencies. Extensive experiments demonstrate that the proposed FRSM method significantly enhanced the transferability of the FSIC model across nine testing datasets.

Characterization and efficacy against carbapenem-resistant Acinetobacter baumannii of a novel Friunavirus phage from sewage.

Carbapenem-resistant Acinetobacter baumannii (CRAB) has become a new threat in recent years, owing to its rapidly increasing resistance to antibiotics and new effective therapies are needed to combat this pathogen. Phage therapy is considered to be the most promising alternative for treating CRAB infections. In this study, a novel phage, Ab_WF01, which can lyse clinical CRAB, was isolated and characterized from hospital sewage. The multiplicity of infection, morphology, one-step growth curve, stability, sensitivity, and lytic activity of the phage were also investigated. The genome of phage Ab_WF01 was 41, 317 bp in size with a GC content of 39.12% and encoded 51 open reading frames (ORFs). tRNA, virulence, and antibiotic resistance genes were not detected in the phage genome. Comparative genomic and phylogenetic analyses suggest that phage Ab_WF01 is a novel species of the genus Friunavirus, subfamily Beijerinckvirinae, and family Autographiviridae. The in vivo results showed that phage Ab_WF01 significantly increased the survival rate of CRAB-infected Galleria mellonella (from 0% to 70% at 48 h) and mice (from 0% to 60% for 7 days). Moreover, after day 3 post-infection, phage Ab_WF01 reduced inflammatory response, with strongly ameliorated histological damage and bacterial clearance in infected tissue organs (lungs, liver, and spleen) in mouse CRAB infection model. Taken together, these results show that phage Ab_WF01 holds great promise as a potential alternative agent with excellent stability for against CRAB infections.

Efficacy and safety of tranexamic acid in cervical spine surgery: a systematic review and meta-analysis.

Background: Tranexamic acid (TXA) is an antifibrinolytic drug associated with reduced blood loss in a range of surgical specialties. This meta-analysis aimed to compare the efficacy and safety of TXA in cervical surgery, focusing on its effects on intraoperative blood loss and related outcomes. Methods: We searched the PubMed, EMBASE, Medline, and Cochrane Library databases to identify all literature related to TXA used in cervical spinal surgery. Intraoperative blood loss, postoperative drainage volume, total blood loss, postoperative hematological variables, and complications were analyzed. Results: Eight trials met the inclusion criteria. The pooled results showed that intraoperative blood loss, total blood loss, and postoperative drainage volume were significantly lower in the TXA group than in the control group. The hemoglobin and hematocrit on postoperative day 1 was significantly higher in the TXA group than in the control group. There was no significant difference in complications between the two groups. Conclusion: The available evidence indicates that TXA effectively reduces blood loss in cervical spinal surgery while maintaining a favorable safety profile, without increasing associated risks. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023459652.

Temporal and spatial biosonar activity of the recently established uppermost Yangtze finless porpoise population downstream of the Gezhouba Dam: Correlation with hydropower cascade development, shipping, hydrological regime, and light intensity.

Numerous dams disrupt freshwater animals. The uppermost population of the critically endangered Yangtze finless porpoise has been newly formed below the Gezhouba Dam, however, information regarding the local porpoise is scarce. Passive acoustic monitoring was used to detect the behaviors of porpoises below the Gezhouba Dam. The influence of shipping, pandemic lockdown, hydrological regime, and light intensity on the biosonar activity of dolphins was also examined using Generalized linear models. Over the course of 4 years (2019-2022), approximately 848, 596, and 676 effective monitoring days were investigated at the three sites, from upstream to downstream. Observations revealed significant spatio-temporal biosonar activity. Proportion of days that are porpoise positive were 73%, 54%, and 61%, while porpoise buzz signals accounted for 78.49%, 62.35%, and 81.30% of all porpoise biosonar at the three stations. The biosonar activity of porpoises was much higher at the confluence area, particularly at the MZ site, during the absence of boat traffic, and during the Pandemic shutdown. Temporal trends of monthly, seasonal, and yearly variation were also visible, with the highest number of porpoises biosonar detected in the summer season and in 2020. Significant correlations also exist between the hydrological regime and light intensity and porpoise activity, with much higher detections during nighttime and full moon periods. Hydropower cascade development, establishment of a natural reserve, fish release initiatives, and implementation of fishing restrictions may facilitate the proliferation of the porpoise population downstream of the Gezhouba Dam within the Yichang section of the Yangtze River. Prioritizing restoration designs that match natural flow regimes, optimize boat traffic, and reduce noise pollution is crucial for promoting the conservation of the local porpoises.

Increased Yangtze finless porpoise presence in urban Wuhan waters of the Yangtze River during fishing closures.

Wuhan, a highly urbanized and rapidly growing region within China's Yangtze Economic Zone, has historically been identified as a gap area for the critically endangered Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis) based on daytime visual surveys. However, there has been a noticeable increase in porpoise sightings since 2020. This study employed passive acoustic monitoring to investigate porpoise distribution in Wuhan between 2020 and 2022. Generalized linear models were used to explore the relationship between shipping, hydrological patterns, light intensity, and porpoise biosonar activity. Over 603 days of effective monitoring, the daily positive rate for porpoise biosonar detection reached 43%, with feeding-related buzz signals accounting for 55% of all porpoise biosonar signals. However, the proportion of minutes during which porpoise presence was detected was 0.18%, suggesting that while porpoises may frequent the area, their visits were brief and mainly focused on feeding. A significant temporal trend emerged, showing higher porpoise biosonar detection during winter (especially in February) and 2022. Additionally, periods without boat traffic correlated with increased porpoise activity. Hydrological conditions and light levels exhibited significant negative correlations with porpoise activity. Specifically, porpoise sonar detections were notably higher during the night, twilight, and new moon phases. It is highly conceivable that both fishing bans and COVID-19 pandemic-related lockdowns contributed to the heightened presence of porpoises in Wuhan. The rapid development of municipal transportation and shipping in Wuhan and resulting underwater noise pollution have emerged as a significant threat to the local porpoise population. Accordingly, it is imperative for regulatory bodies to effectively address this environmental stressor and formulate targeted protection measures to ensure the conservation of the finless porpoise.

Heterostructures Assembled from Bi2O2CO3 and MXene for Boosted Potassium-Ion Storage by Arousing the Built-in Electric Field.

Bismuth-based materials have been recognized as the appealing anodes for potassium-ion batteries (PIBs) due to their high theoretical capacity. However, the kinetics sluggishness and capacity decline induced by the structure distortion predominately retard their further development. Here, a heterostructure of polyaniline intercalated Bi2O2CO3/MXene (BOC-PA/MXene) hybrids is reported via simple self-assembly strategy. The ingenious design of heterointerface-rich architecture motivates significantly the interior self-built-in electric field (IEF) and high-density electron flow, thus accelerating the charge transfer and boosting ion diffusion. As a result, the hybrids realize a high reversible specific capacity, satisfying rate capability as well as long-term cycling stability. The in/ex situ characterizations further elucidate the stepwise intercalation-conversion-alloying reaction mechanism of BOC-PA/MXene. More encouragingly, the full cell investigation further highlights its competitive merits for practical application in further PIBs. The present work not only opens the way to the design of other electrodes with an appropriate working mechanism but also offers inspiration for built-in electric-field engineering toward high-performance energy storage devices.

Microglial ApoD-induced NLRC4 inflammasome activation promotes Alzheimer's disease progression.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease with no effective therapies. It is well known that chronic neuroinflammation plays a critical role in the onset and progression of AD. Well-balanced neuronal-microglial interactions are essential for brain functions. However, determining the role of microglia-the primary immune cells in the brain-in neuroinflammation in AD and the associated molecular basis has been challenging. METHODS: Inflammatory factors in the sera of AD patients were detected and their association with microglia activation was analyzed. The mechanism for microglial inflammation was investigated. IL6 and TNF-α were found to be significantly increased in the AD stage. RESULTS: Our analysis revealed that microglia were extensively activated in AD cerebra, releasing sufficient amounts of cytokines to impair the neural stem cells (NSCs) function. Moreover, the ApoD-induced NLRC4 inflammasome was activated in microglia, which gave rise to the proinflammatory phenotype. Targeting the microglial ApoD promoted NSC self-renewal and inhibited neuron apoptosis. These findings demonstrate the critical role of ApoD in microglial inflammasome activation, and for the first time reveal that microglia-induced inflammation suppresses neuronal proliferation. CONCLUSION: Our studies establish the cellular basis for microglia activation in AD progression and shed light on cellular interactions important for AD treatment.

CD14-CD10-CD45+HLA-DR-SSC+ neutrophils may be granulocytic myeloid-derived suppressor cell-like cells and relate to disease progression in non-Hodgkin's lymphoma patients.

We explored the frequency of CD14-CD10-CD45+HLA-DR-SSC++ neutrophils (CD10- neutrophils) in patients with non-Hodgkin's lymphoma (NHL), and their immunologic characteristics and clinical significance. Patients with NHL who were newly diagnosed (NDP; n = 33), in remission (RMP; n = 28) and relapsed (RLP; n = 29) were included, and 47 volunteers were recruited as healthy controls (HCs). The frequency of CD10- neutrophils in the peripheral blood from HC and patients with NHL was detected. CD10- and CD10+ neutrophils were sorted, and their cytology was analyzed. CD3+ T cells were also isolated and cultured with the autologous CD10- or CD10+ neutrophils, after which the proliferation and death rates of T cells were determined. The levels of arginase-1 (Arg-1) and reactive oxygen species (ROS) in CD10+ or CD10- neutrophils were examined. Few CD10- neutrophils were detected in HCs but were significantly elevated in patients with NHL, especially in NDP and RLP. In addition, CD10- neutrophils in NDP with advanced stage and high risk were markedly higher than those in NDP with limited stage and low risk. In RMP and RLP, the relapse-free survival and overall survival in patients with high CD10- neutrophils were shorter than those with low CD10- neutrophils. CD10- neutrophils from patients with NHL, which mainly consist of immature neutrophils, inhibit T-cell proliferation and facilitate T-cell death. Furthermore, a significant increase was observed in Arg-1 expression, along with an increase to a certain extent in ROS. CD10- neutrophils in patients with NHL have characteristics of myeloid-derived suppressor cells and may be related to disease progression and poor prognosis.

TIMP1/CHI3L1 facilitates glioma progression and immunosuppression via NF-κB activation.

Gliomas are highly heterogeneous brain tumours that are resistant to therapies. The molecular signatures of gliomas play a high-ranking role in tumour prognosis and treatment. In addition, patients with gliomas with a mesenchymal phenotype manifest overpowering immunosuppression and sophisticated resistance to treatment. Thus, studies on gene/protein coexpression networks and hub genes in gliomas holds promise in determining effective treatment strategies. Therefore, in this study, we aimed to. Using average linkage hierarchical clustering, 13 modules and 224 hub genes were described. Top ten hub genes (CLIC1, EMP3, TIMP1, CCDC109B, CASP4, MSN, ANXA2P2, CHI3L1, TAGLN2, S100A11), selected from the most meaningful module, were associated with poor prognosis. String analysis, co-immunoprecipitation and immunofluorescence revealed a significant correlation between TIMP1 and CHI3L1. Furthermore, we found, both in vivo and in vitro, that TIMP1 promoted gliomagenesis via CHI3L1 overexpression as well as NF-κB activation. TIMP1 expression correlated with tumour immune infiltration and immune checkpoint-related gene expression. In addition, TIMP1 resulted in immunosuppressive macrophage polarization. In summary, TIMP1/CHI3L1 might be perceived as a diagnostic marker and an immunotherapy target for gliomas.

SRRM2 may be a potential biomarker and immunotherapy target for multiple myeloma: a real-world study based on flow cytometry detection.

Serine/arginine repetitive matrix 2 (SRRM2) has been implicated in tumorigenesis, cancer development, and drug resistance through aberrant splicing; however, its correlation with multiple myeloma (MM) has not been reported. We investigated the potential of SRRM2 as a biomarker and immunotherapeutic target in MM by examining its expression in MM cells using flow cytometry. Our study included 95 patients with plasma cell disease, including 80 MM cases, and we detected SRRM2 expression on plasma cells and normal blood cells to analyze its relationship with clinical profiles. We found widespread positive expression of SRRM2 on plasma cells with little expression on normal blood cells, and its expression on abnormal plasma cells was higher than that on normal plasma cells. Comparative analysis with clinical data suggests that SRRM2 expression on plasma cells correlates with MM treatment response. MM patients with high SRRM2 expression had higher levels of serum ß2-mg and LDH, ISS staging, and plasma cell infiltration, as well as high-risk mSMART 3.0 stratification and cytogenetic abnormalities, particularly 1q21 amplification. In patients with previous MM, high SRRM2 expression on plasma cells was associated with higher plasma cell infiltration, high-risk mSMART 3.0 risk stratification, cytogenetic abnormalities, more relapses, and fewer autologous stem cell transplant treatments. In summary, SRRM2 may serve as a novel biomarker and immunotherapeutic target for MM. Its expression level on plasma cells can help in risk stratification of MM and monitoring of treatment response.

FUS-Mediated CircFGFR1 Accelerates the Development of Papillary Thyroid Carcinoma by Stabilizing FGFR1 Protein.

Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer and its incidence is rising globally. The molecular mechanisms of PTC progression remain unclear, hindering the development of effective treatments. This study focuses on hsa_circ_0008016 (circFGFR1), a circular RNA significantly up-regulated in PTC cells. Silencing circFGFR1 inhibited PTC cell proliferation and increased cell apoptosis, suggesting its role in PTC progression. The RNA-binding protein FUS was identified as a promoter of circFGFR1 formation. While circFGFR1 does not influence FGFR1 mRNA translation, it inhibits ubiquitination and degradation of FGFR1 protein, prolonging its half-life. CircFGFR1 also interacts with protein CBL, inhibiting CBL-mediated ubiquitination of FGFR1 proteins. Rescue assays confirmed circFGFR1 promotes PTC cell growth through mediating FGFR1. This study highlights the potential of circFGFR1 as a therapeutic target, offering insights into PTC's molecular mechanisms, and paving the way for novel treatment strategies.

A Fully Elastic Wearable Electrochemical Sweat Detection System of Tree-Bionic Microfluidic Structure for Real-Time Monitoring.

Fresh sweat contains a diverse range of physiological indicators that can effectively reflect changes in the body. However, existing wearable sweat detection systems face challenges in efficiently collecting and detecting fresh sweat in real-time. Additionally, they often lack the necessary deformation capabilities, resulting in discomfort for the wearer. Here, a fully elastic wearable electrochemical sweat detection system is developed that integrates a sweat-collecting microfluidic chip, a multi-parameter electrochemical sensor, a micro-heater, and a sweat detection elastic circuit board system. The unique tree-bionic structure of the microfluidic chip significantly enhances the efficiency of fresh sweat collection and discharge, enabling real-time detection by the electrochemical sensors. The sweat multi-parameter electrochemical sensor offers high-precision and high-sensitivity measurements of sodium ions, potassium ions, lactate, and glucose. The electronic system is built on an elastic circuit board that matches perfectly to wrinkled skin, ensuring improved wearing comfort and enabling multi-channel data sampling, processing, and wireless transmission. This state-of-the-art system represents a significant advancement in the field of elastic wearable sweat detection and holds promising potential for extending its capabilities to the detection of other sweat markers or various wearable applications.