A Hybrid Nanotube Stamp System in Intracellular Protein Delivery for Cancer Treatment and NMR Analytical Techniques.

In contrast to intracellular gene transfer, the direct delivery of expressed proteins is a significantly challenging yet essential technique for elucidating cellular functions, including protein complex structure, liquid-liquid phase separation, therapeutic applications, and reprogramming. In this study, we developed a hybrid nanotube (HyNT) stamp system that physically inserts the HyNTs into adhesive cells, enabling the injection of target molecules through HyNT ducts. This system demonstrates the capability to deliver multiple proteins, such as lactate oxidase (LOx) and ubiquitin (UQ), to approximately 1.8 × 107 adhesive cells with a delivery efficiency of 89.9% and a viability of 97.1%. The delivery of LOx enzyme into HeLa cancer cells induced cell death, while enzyme-delivered healthy cells remained viable. Furthermore, our stamp system can deliver an isotope-labeled UQ into adhesive cells for detection by nuclear magnetic resonance (NMR).

Association between polypharmacy and chronic kidney disease among community-dwelling older people: a longitudinal study in southern China.

BACKGROUND: Polypharmacy would increase the risk of adverse drug events and the burden of renal drug excretion among older people. Nevertheless, the association between the number of medication and the risk of chronic kidney disease (CKD) remains controversial. Therefore, this study aims to investigate the association between the number of medication and the incidence of CKD in older people. METHODS: This study investigates the association between the number of medications and CKD in 2672 elderly people (≥ 65 years older) of the community health service center in southern China between 2019 and 2022. Logistic regression analysis was used to evaluate the relationship between polypharmacy and CKD. RESULTS: At baseline, the average age of the study subjects was 71.86 ± 4.60, 61.2% were females, and 53 (2.0%) suffer from polypharmacy. During an average follow-up of 3 years, new-onset CKD developed in 413 (15.5%) participants. Logistic regression analysis revealed that taking a higher number of medications was associated with increase of CKD. Compared with people who didn't take medication, a higher risk of CKD was observed in the older people who taken more than five medications (OR 3.731, 95% CI 1.988, 7.003), followed by those who take four (OR 1.621, 95% CI 1.041, 2.525), three (OR 1.696, 95% CI 1.178, 2.441), two drugs (OR 1.585, 95% CI 1.167, 2.153), or one drug (OR 1.503, 95% CI 1.097, 2.053). Furthermore, age, systolic blood pressure (SBP), white blood cell (WBC), blood urea nitrogen (BUN) and triglyceride (TG) were also independent risk factors CKD (P < 0.05). CONCLUSION: The number of medications was associated with CKD in older people. As the number of medications taken increased, the risk of CKD was increased.

Enhanced pyroptosis induction with pore-forming gene delivery for osteosarcoma microenvironment reshaping.

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.

Stabilization of NCM811 cathode interface through macromolecular compound protective film formed by 2,5-bis(2,2,2-trifluoroethoxy)-benzoic acid additive in lithium metal batteries.

Lithium metal batteries (LMBs) offer substantial promise for next-generation energy storage owing to lithium metal's low reduction potential (-3.045 V vs. the standard hydrogen electrode) and its high specific capacity of 3860 mA h g-1. Among various cathode materials in LMBs, LiNi0.8Co0.1Mn0.1O2 (NCM811) is extensively employed because of its notably high specific capacity (over 200 mA h g-1) and comparatively lower cost. However, structural stress, nickel ions migration, and uneven Li+ deposition in NCM811 particles lead to cracking, irreversible decomposition of active substances, and the growth of mossy Li dendrites, causing severe capacity decline and low Coulomb efficiency in LMBs. In this study, we introduce an effective ethoxyl additive, 2,5-bis(2,2,2-trifluoroethoxy)-benzoic acid (2,5BTBA), directly into the carbonate electrolyte. This additive forms a dense and conductive macromolecular protective film on the NCM811 cathode and lithium metal anode during initial cycles, preventing electrode contact with the electrolyte. Consequently, it safeguards the cathode's structural integrity and enables dense lithium deposition. Adding 3 wt% 2,5BTBA, the Li/NCM811 battery retains a high capacity of 150.60 mA h g-1 and 89.41% retention after 700 cycles at 0.5C, maintaining an average Coulomb efficiency of 99.13%. This study presents an efficient and straightforward strategy to enhance the capacity retention of LMBs.

Electrochemical Restructuring Driven Catalytic Cycle of Bi-Based Heterojunctions for High-Performance Lithium-Sulfur Batteries.

Restructuring is an important phenomenon in catalytic reactions. Conversion-type materials with suitable redox potential may undergo in situ electrochemically driven restructurings and induce highly active catalytic sites in a working lithium-sulfur battery. Herein, driven by the electrochemical conversion reaction of BiVO4, a reversible catalytic cycle of Bi/amorphous Li3VO4 (a-Li3VO4) and Bi2S3/a-Li3VO4 heterojunctions is constructed, which targets the oxidation of Li2S and the conversion of polysulfide, respectively. The heterostructures and electrochemically driven size confinement provide abundant sites for shuttle restraining and sulfur conversion. Especially, the p-block Bi and Bi2S3 could dramatically reduce the conversion energy barriers of Li2S and polysulfide by virtue of the p-p orbital hybridization, promoting bidirectional reactions of the sulfur cathode. As a result, the corresponding sulfur cathode possesses a high reversible capacity of 7.5 mAh cm-2 after 120 cycles under a high sulfur loading of 10.3 mg cm-2 with a current density of 0.38 mA cm-2. This study furnishes a feasible scheme to obtain highly effective catalysts for bidirectional sulfur redox by utilizing the electrochemically induced restructuring.

Giant ab-Plane Birefringence in Quasi-1D Fibrous Red Phosphorus.

Quasi-one-dimensional (quasi-1D) van der Waals crystal fibrous red phosphorus (RP) exhibits pronounced in-plane optical anisotropy, positioning it as a potential candidate for polarization-related micro-nano devices. Unfortunately, a comprehensive investigation into the complex refractive index of fibrous RP and the structure-activity relationship connecting the distinctive quasi-1D structure with optical anisotropy is currently deficient. Herein, we have collectively determined the complex refractive index of the fibrous RP flakes within the ab-plane through Kramers-Kronig (KK) analysis and theoretical calculation. Notably, the maximum birefringence of fibrous RP reaches 0.642@475 nm with an absolute extinction coefficient of only 0.08, superior to the reported traditional optical crystals and the emerging low-dimensional materials as well. The remarkable birefringence can be attributed to the synergistic influence of the large electronic dipole polarizability, anisotropic electron density distribution and the distortion of stereochemically active lone pair (SCALP). This work demonstrates the potential of fibrous RP for polarization-sensitive devices, illuminating possibilities to exploit novel giant birefringent crystals based on the structure-activity relationship.

Monitoring and evaluation of vegetation restoration in the Ebinur Lake Wetland National Nature Reserve under lockdown protection.

For a long time, human activities have been prohibited in ecologically protected areas in the Ebinur Lake Wetland National Nature Reserve (ELWNNR). The implementation of total closure is one of the main methods for ecological protection. For arid zones, there is a lack of in-depth research on whether this measure contributes to ecological restoration in the reserve. The Normalized Difference Vegetation Index (NDVI) is considered to be the best indicator for ecological monitoring and has a key role to play in assessing the ecological impacts of total closure. In this study, we used Sentinel-2, Landsat-8, and Moderate Resolution Imaging Spectroradiometer (MODIS) remote sensing data to select optimal data and utilized Sen slope estimation, Mann-Kendall statistical tests, and the geographical detector model to quantitatively analyze the normalized difference vegetation index (NDVI) dynamics and its driving factors. Results were as follows: (1) The vegetation distribution of the Ebinur Lake Wetland National Nature Reserve (ELWNNR) had obvious spatial heterogeneity, showing low distribution in the middle and high distribution in the surroundings. The correlation coefficients of Landsat-8 and MODIS, Sentinel-2 and MODIS, and Sentinel-2 and Landsat-8 were 0.952, 0.842, and 0.861, respectively. The NDVI calculated from MODIS remote sensing data was higher than the value calculated by Landsat-8 and Sentinel-2 remote sensing images, and Landsat-8 remote sensing data were the most suitable data. (2) NDVI indicated more degraded areas on the whole, but the ecological recovery was obvious in the localized areas where anthropogenic closure was implemented. The ecological environment change was the result of the joint action of man and nature. Man-made intervention will change the local ecological environment, but the overall ecological environment change was still dominated by natural environmental factors. (3) Factors affecting the distribution of NDVI in descending order were as follows: precipitation > evapotranspiration > land use type > elevation > vegetation type > soil type > soil erosion > slope > temperature > slope direction. Precipitation was the main driver of vegetation change in ELWNNR. The synergistic effect of the factors showed two-factor enhancement and nonlinear enhancement, and the combined effect of the driving factors would increase the influence on NDVI.

Establishment of human hematopoietic organoids for evaluation of hematopoietic injury and regeneration effect.

BACKGROUND: Human hematopoietic organoids have a wide application value for modeling human bone marrow diseases, such as acute hematopoietic radiation injury. However, the manufacturing of human hematopoietic organoids is an unaddressed challenge because of the complexity of hematopoietic tissues. METHODS: To manufacture hematopoietic organoids, we obtained CD34+ hematopoietic stem and progenitor cells (HSPCs) from human embryonic stem cells (hESCs) using stepwise induction and immunomagnetic bead-sorting. We then mixed these CD34+ HSPCs with niche-related cells in Gelatin-methacryloyl (GelMA) to form a three-dimensional (3D) hematopoietic organoid. Additionally, we investigated the effects of radiation damage and response to granulocyte colony-stimulating factor (G-CSF) in hematopoietic organoids. RESULTS: The GelMA hydrogel maintained the undifferentiated state of hESCs-derived HSPCs by reducing intracellular reactive oxygen species (ROS) levels. The established hematopoietic organoids in GelMA with niche-related cells were composed of HSPCs and multilineage blood cells and demonstrated the adherence of hematopoietic cells to niche cells. Notably, these hematopoietic organoids exhibited radiation-induced hematopoietic cell injury effect, including increased intracellular ROS levels, γ-H2AX positive cell percentages, and hematopoietic cell apoptosis percentages. Moreover, G-CSF supplementation in the culture medium significantly improved the survival of HSPCs and enhanced myeloid cell regeneration in these hematopoietic organoids after radiation. CONCLUSIONS: These findings substantiate the successful manufacture of a preliminary 3D hematopoietic organoid from hESCs-derived HSPCs, which was utilized for modeling hematopoietic radiation injury and assessing the radiation-mitigating effects of G-CSF in vitro. Our study provides opportunities to further aid in the standard and scalable production of hematopoietic organoids for disease modeling and drug testing.

CircNSD1 promotes cardiac fibrosis through targeting the miR-429-3p/SULF1/Wnt/ß-catenin signaling pathway.

Cardiac fibrosis is a detrimental pathological process, which constitutes the key factor for adverse cardiac structural remodeling leading to heart failure and other critical conditions. Circular RNAs (circRNAs) have emerged as important regulators of various cardiovascular diseases. It is known that several circRNAs regulate gene expression and pathological processes by binding miRNAs. In this study we investigated whether a novel circRNA, named circNSD1, and miR-429-3p formed an axis that controls cardiac fibrosis. We established a mouse model of myocardial infarction (MI) for in vivo studies and a cellular model of cardiac fibrogenesis in primary cultured mouse cardiac fibroblasts treated with TGF-ß1. We showed that miR-429-3p was markedly downregulated in the cardiac fibrosis models. Through gain- and loss-of-function studies we confirmed miR-429-3p as a negative regulator of cardiac fibrosis. In searching for the upstream regulator of miR-429-3p, we identified circNSD1 that we subsequently demonstrated as an endogenous sponge of miR-429-3p. In MI mice, knockdown of circNSD1 alleviated cardiac fibrosis. Moreover, silence of human circNSD1 suppressed the proliferation and collagen production in human cardiac fibroblasts in vitro. We revealed that circNSD1 directly bound miR-429-3p, thereby upregulating SULF1 expression and activating the Wnt/ß-catenin pathway. Collectively, circNSD1 may be a novel target for the treatment of cardiac fibrosis and associated cardiac disease.

Chiral Flipping in Viedma Deracemization.

Understanding deracemization is crucial for progress in chiral chemistry, especially for improving separation techniques. Here, we first report the phenomenon of chiral flipping (or reverse deracemization) in a chiral material (i.e., sodium chlorate crystals) during Viedma deracemization, employing a small-volume reactor system for precise analysis. We observe considerable chiral flipping, influenced by the initial imbalance in the numbers of L- and D-form particles. We developed a simple probabilistic model to further elucidate this behavior. We find that the fluctuation in the populations of chiral crystal particles resulting from their random dissolution and regeneration is the key factor behind chiral flipping. This study not only brings to light this intriguing observation of chiral flipping but also contributes to the enhancement of deracemization techniques.

Low Initial Cell Density Promotes the Differentiation and Maturation of Human Pluripotent Stem Cells into Erythrocytes.

Human pluripotent stem cell (hPSC)-derived red blood cells (RBCs) possess great potential for compensating shortages in transfusion medicine. For better RBC generation from hPSCs, we compared the cell seeding density in the embryoid body formation-based hPSC induction protocol. In the selection of low- and high-density inoculation conditions, we found that low-density culture performed better in the final RBC product with more cell output and increased average cellular hemoglobin content. An elaborate study using flow cytometry demonstrated that low inoculation density promoted endothelial-to-hematopoietic transition, followed by improved hematopoietic progenitor formation and erythrocyte generation. The improved transformation from glycolysis to mitochondrial oxidation and reduced apoptosis might be responsible for this effect. Hints from RNA sequencing suggested that molecules involved in microenvironment interaction and metabolic regulation might respond for the different developmental potential. The possible mediators between outer message and intracellular response could be the nutrition sensors FOXO, PRKAA1 (AMPK), and MTOR genes. It is possible that low inoculation density triggered metabolic regulation signals, promoted mitochondrial oxidation, and resulted in enhanced cell amplification and hematopoietic differentiation. The low cell culture density will improve RBC generation from hPSCs.

Inhibitory Effect of Lactococcus and Enterococcus faecalis on Citrobacter Colitis in Mice.

Probiotics are beneficial for intestinal diseases. Research shows that probiotics can regulate intestinal microbiota and alleviate inflammation. Little research has been done on the effects of probiotics on colitis in mice. The purpose of this study was to investigate the inhibitory effect of the strains isolated and screened from the feces of healthy piglets on the enteritis of rocitrobacter. The compound ratio of isolated Lactobacillus L9 and Enterococcus faecalis L16 was determined, and the optimal compound ratio was selected according to acid production tests and bacteriostatic tests in vitro. The results showed that when the ratio of Lactobacillus L9 to Enterococcus faecalis L16 was 4:1, the pH value was the lowest, and the antibacterial diameter was the largest. Then, in animal experiments, flow cytometry was used to detect the number of T lymphocytes in the spleen and mesenteric lymph nodes of mice immunized with complex lactic acid bacteria. The results showed that the number of T lymphocytes in the spleen and mesenteric lymph nodes of mice immunized with complex lactic acid bacteria significantly increased, which could improve the cellular immunity of mice. The microbiota in mouse feces were sequenced and analyzed, and the results showed that compound lactic acid bacteria could increase the diversity of mouse microbiota. It stabilized the intestinal microbiota structure of mice and resisted the damage of pathogenic bacteria. The combination of lactic acid bacteria was determined to inhibit the intestinal colitis induced by Citrobacter, improve the cellular immune response of the body, and promote the growth of animals.

Droplet-based proteomics reveals CD36 as a marker for progenitors in mammary basal epithelium.

Deep proteomic profiling of rare cell populations has been constrained by sample input requirements. Here, we present DROPPS (droplet-based one-pot preparation for proteomic samples), an accessible low-input platform that generates high-fidelity proteomic profiles of 100-2,500 cells. By applying DROPPS within the mammary epithelium, we elucidated the connection between mitochondrial activity and clonogenicity, identifying CD36 as a marker of progenitor capacity in the basal cell compartment. We anticipate that DROPPS will accelerate biology-driven proteomic research for a multitude of rare cell populations.

Bistable Electrochromic Ionogels via Supramolecular Interactions for Energy-Efficient Displays.

Bistable electrochromic (EC) materials and systems offer significant potential for building decarbonization through their optical modulation and energy efficiency. However, challenges such as limited design strategies and bottlenecks in cost, fabrication, and color have hindered the full commercialization of energy-saving EC windows and displays, with few materials achieving true bistability. Herein, a novel strategy for designing bistable electrochromic materials is proposed by leveraging supramolecular interactions. These interactions facilitate reversible color transitions, stabilize the colored structure, and enable spatial confinement to inhibit diffusion, thereby achieving bistable electrochromism. The mechanisms and materials underlying these unconventional electrochromic systems are substantiated through detailed characterization. This strategy enables the preparation of low-cost and sustainable transparent electrochromic displays with high performance. Notably, the display information remains clearly visible for more than 2 hours without consuming energy. Involving biomass materials and removable device structures also enhances the sustainability and scalability of EC technology applications and development. Our results demonstrate the crucial role of supramolecular chemistry in the development of cutting-edge materials for applications such as energy-saving smart windows. This article is protected by copyright. All rights reserved.

TGF-ß1-triggered BMI1 and SMAD2 cooperatively regulate miR-191 to modulate bone formation.

Transforming growth factor ß 1 (TGF-ß1), as the most abundant signaling molecule in bone matrix, is essential for bone homeostasis. However, the signaling transduction of TGF-ß1 in the bone-forming microenvironment remains unknown. Here, we showed that microRNA-191 (miR-191) was downregulated during osteogenesis and further decreased by osteo-favoring TGF-ß1 in bone marrow mesenchymal stem cells (BMSCs). MiR-191 was lower in bone tissues from children than in those from middle-aged individuals and it was negatively correlated with collagen type I alpha 1 chain (COL1A1). MiR-191 depletion significantly increased osteogenesis and bone formation in vivo. Hydrogels embedded with miR-191-low BMSCs displayed a powerful bone repair effect. Mechanistically, transcription factors BMI1 and SMAD2 coordinately controlled miR-191 level. In detail, BMI1 and pSMAD2 were both upregulated by TGF-ß1 under osteogenic condition. SMAD2 activated miR-191 transcription, while BMI1 competed with SMAD2 for binding to miR-191 promoter region, thus disturbing the activation of SMAD2 on miR-191 and reducing miR-191 level. Altogether, our findings reveal that miR-191 regulated by TGF-ß1-induced BMI1 and SMAD2 negatively modulated bone formation and regeneration, and inhibition of miR-191 might be therapeutically useful to enhance bone repair in clinic.

Investigation of the Influence of Anti-Solvent Precipitation Parameters on the Physical Stability of Amorphous Solids.

Amorphous solids exhibit enhanced solubility and dissolution rates relative to their crystalline counterparts. However, attaining optimal bioavailability presents a challenge, primarily due to the need to maintain the physical stability of amorphous solids. Moreover, the precise manner in which precipitation parameters, including the feeding rate of the anti-solvent, agitation speed, and aging time, influence the physical stability of amorphous solids remains incompletely understood. Consequently, this study aimed to investigate these three parameters during the precipitation process of the anticancer drug, nilotinib free base. The physical stability of the resultant samples was evaluated by employing characterization techniques including powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), focused beam reflectance measurement (FBRM), and data analysis methods such as pair distribution function (PDF), reduced crystallization temperature (Rc), and principal component analysis (PCA). This study's findings indicated that amorphous solids exhibited the greatest physical stability under particular conditions, namely a feeding rate of 5 mL/min, an agitation speed of 500 rpm, and an aging time of 10 min. Furthermore, the physical stability of the amorphous solids was primarily influenced by particle size and distribution, molecular interactions, microstructure, surface area, and interfacial energy. Notably, the parameters involved in the anti-solvent precipitation process, including the feeding rate of the anti-solvent, agitation speed, and aging time, exerted a significant impact on these factors. Consequently, they directly affected the physical stability of amorphous solids. Hence, this study comprehensively elucidated the mechanistic influence of these operational parameters on the physical stability of amorphous solids during the anti-solvent precipitation process.

Evaluating the Efficiency of Boron Nitride Coating in Single-Walled Carbon-Nanotube-Based 1D Heterostructure Films by Optical Spectroscopy.

Single-walled carbon nanotube (SWCNT) films exhibit exceptional optical and electrical properties, making them highly promising for scalable integrated devices. Previously, we employed SWCNT films as templates for the chemical vapor deposition (CVD) synthesis of one-dimensional heterostructure films where boron nitride nanotubes (BNNTs) and molybdenum disulfide nanotubes (MoS2NTs) were coaxially nested over the SWCNT networks. In this work, we have further refined the synthesis method to achieve precise control over the BNNT coating in SWCNT@BNNT heterostructure films. The resulting structure of the SWCNT@BNNT films was thoroughly characterized using a combination of electron microscopy, UV-vis-NIR spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, and Raman spectroscopy. Specifically, we investigated the pressure effect induced by BNNT wrapping on the SWCNTs in the SWCNT@BNNT heterostructure film and demonstrated that the shifts of the SWCNT's G and 2D (G') modes in Raman spectra can be used as a probe of the efficiency of BNNT coating. In addition, we studied the impact of vacuum annealing on the removal of the initial doping in SWCNTs, arising from exposure to ambient atmosphere, and examined the effect of MoO3 doping in SWCNT films by using UV-vis-NIR spectroscopy and Raman spectroscopy. We show that through correlation analysis of the G and 2D (G') modes in Raman spectra, it is possible to discern distinct types of doping effects as well as the influence of applied pressure on the SWCNTs within SWCNT@BNNT heterostructure films. This work contributes to a deeper understanding of the strain and doping effect in both SWCNTs and SWCNT@BNNTs, thereby providing valuable insights for future applications of carbon-nanotube-based one-dimensional heterostructures.

Flexible scaffold-based cheminformatics approach for polypharmacological drug design.

Effective treatments for complex central nervous system (CNS) disorders require drugs with polypharmacology and multifunctionality, yet designing such drugs remains a challenge. Here, we present a flexible scaffold-based cheminformatics approach (FSCA) for the rational design of polypharmacological drugs. FSCA involves fitting a flexible scaffold to different receptors using different binding poses, as exemplified by IHCH-7179, which adopted a "bending-down" binding pose at 5-HT2AR to act as an antagonist and a "stretching-up" binding pose at 5-HT1AR to function as an agonist. IHCH-7179 demonstrated promising results in alleviating cognitive deficits and psychoactive symptoms in mice by blocking 5-HT2AR for psychoactive symptoms and activating 5-HT1AR to alleviate cognitive deficits. By analyzing aminergic receptor structures, we identified two featured motifs, the "agonist filter" and "conformation shaper," which determine ligand binding pose and predict activity at aminergic receptors. With these motifs, FSCA can be applied to the design of polypharmacological ligands at other receptors.

The Progress and Prospects of Immune Cell Therapy for the Treatment of Cancer.

Immune cell therapy as a revolutionary treatment modality, significantly transformed cancer care. It is a specialized form of immunotherapy that utilizes living immune cells as therapeutic reagents for the treatment of cancer. Unlike traditional drugs, cell therapies are considered "living drugs," and these products are currently customized and require advanced manufacturing techniques. Although chimeric antigen receptor (CAR)-T cell therapies have received tremendous attention in the industry regarding the treatment of hematologic malignancies, their effectiveness in treating solid tumors is often restricted, leading to the emergence of alternative immune cell therapies. Tumor-infiltrating lymphocytes (TIL) cell therapy, cytokine-induced killer (CIK) cell therapy, dendritic cell (DC) vaccines, and DC/CIK cell therapy are designed to use the body's natural defense mechanisms to target and eliminate cancer cells, and usually have fewer side effects or risks. On the other hand, cell therapies, such as chimeric antigen receptor-T (CAR-T) cell, T cell receptor (TCR)-T, chimeric antigen receptor-natural killer (CAR-NK), or CAR-macrophages (CAR-M) typically utilize either autologous stem cells, allogeneic or xenogeneic cells, or genetically modified cells, which require higher levels of manipulation and are considered high risk. These high-risk cell therapies typically hold special characteristics in tumor targeting and signal transduction, triggering new anti-tumor immune responses. Recently, significant advances have been achieved in both basic and clinical researches on anti-tumor mechanisms, cell therapy product designs, and technological innovations. With swift technological integration and a high innovation landscape, key future development directions have emerged. To meet the demands of cell therapy technological advancements in treating cancer, we comprehensively and systematically investigate the technological innovation and clinical progress of immune cell therapies in this study. Based on the therapeutic mechanisms and methodological features of immune cell therapies, we analyzed the main technical advantages and clinical transformation risks associated with these therapies. We also analyzed and forecasted the application prospects, providing references for relevant enterprises with the necessary information to make informed decisions regarding their R&D direction selection.

Research on lightweight algorithm for gangue detection based on improved Yolov5.

In order to solve the problems of slow detection speed, large number of parameters and large computational volume of deep learning based gangue target detection method, we propose an improved algorithm for gangue target detection based on Yolov5s. First, the lightweight network EfficientVIT is used as the backbone network to increase the target detection speed. Second, C3_Faster replaces the C3 part in the HEAD module, which reduces the model complexity. once again, the 20 × 20 feature map branch in the Neck region is deleted, which reduces the model complexity; thirdly, the CIOU loss function is replaced by the Mpdiou loss function. The introduction of the SE attention mechanism makes the model pay more attention to critical features to improve detection performance. Experimental results show that the improved model size of the coal gang detection algorithm reduces the compression by 77.8%, the number of parameters by 78.3% the computational cost is reduced by 77.8% and the number of frames is reduced by 30.6%, which can be used as a reference for intelligent coal gangue classification.