Emerging strategies for treating autoimmune disease with genetically modified dendritic cells.

Gene editing of living cells has become a crucial tool in medical research, enabling scientists to address fundamental biological questions and develop novel strategies for disease treatment. This technology has particularly revolutionized adoptive transfer cell therapy products, leading to significant advancements in tumor treatment and offering promising outcomes in managing transplant rejection, autoimmune disorders, and inflammatory diseases. While recent clinical trials have demonstrated the safety of tolerogenic dendritic cell (TolDC) immunotherapy, concerns remain regarding its effectiveness. This review aims to discuss the application of gene editing techniques to enhance the tolerance function of dendritic cells (DCs), with a particular focus on preclinical strategies that are currently being investigated to optimize the tolerogenic phenotype and function of DCs. We explore potential approaches for in vitro generation of TolDCs and provide an overview of emerging strategies for modifying DCs. Additionally, we highlight the primary challenges hindering the clinical adoption of TolDC therapeutics and propose future research directions in this field.

Surface Coordination Modulated Morphological Anisotropic Engineering of Iron-Benzoquinone Frameworks for Lithium-Ion Batteries.

Morphological anisotropic engineering is powerful to synthesize metal-organic frameworks (MOF) with versatile physicochemical properties for diverse applications ranging from gas storage/separation to electrocatalysis and batteries, etc. Herein, we developed a carbon substrate guided strategy for facet-anisotropic growth of Fe-THBQ (tetrahydroxy-1,4-benzoquinone) frameworks, which is built with cubic Fe octamer bridged by two parallel THBQ ligands along three orthogonal axes, extending to a three-dimensional (3D) framework with pcu-e network topology. The electronegative O-containing functional groups on carbon surfaces compete with THBQ linkers to interact with the unsaturated coordinated Fe cations on the {111} facets and selectively inhibit crystal growth along the <111> direction. The morphology of Fe-THBQ evolves from thermodynamically favored truncated cube to cuboctahedron depending on the O-containing functional groups on carbon substrate. The Fe-THBQ with varied morphologies exhibits facet-dependent performances for lithium storage. This work will shed lights on morphology modulation of MOFs for promising applications.

Modular Cascade of Flow Reactors: Continuous Flow Synthesis of Water-Insoluble Diazo Dyes in Aqueous System.

Continuous flow synthesis is pivotal in dye production to address batch-to-batch variations. However, synthesizing water-insoluble dyes in an aqueous system poses a challenge that can lead to clogging. This study successfully achieved the safe and efficient synthesis of azo dyes by selecting and optimizing flow reactor modules for different reaction types in the two-step reaction and implementing cascade cooperation. Integrating continuous flow microreactor with continuous stirred tank reactor (CSTR) enabled the continuous flow synthesis of Sudan Yellow 3G without introducing water-soluble functional groups or using organic solvents to enhance solubility. Optimizing conditions (acidity/alkalinity, temperature, residence time) within the initial modular continuous flow reactor resulted in a remarkable 99.5% isolated yield, 98.6% purity, and a production rate of 2.90 g · h-1. Scaling-up based on different reactor module characteristics further increased the production rate to 74.4 g·h-1 while maintaining high yield and purity. The construction of this small 3D-printing modular cascaded reactor and process scaling-up provide technical support for continuous flow synthesis of water-insoluble dyes, particularly high-market-share azo dyes. Moreover, this versatile methodology proves applicable to continuous flow processes involving various homogeneous and heterogeneous reaction cascades.

Emerging roles and mechanisms of lncRNAs in fruit and vegetables.

With the development of genome sequencing technologies, many long non-coding RNAs (lncRNAs) have been identified in fruit and vegetables. lncRNAs are primarily transcribed and spliced by RNA polymerase II (Pol II) or plant-specific Pol IV/V, and exhibit limited evolutionary conservation. lncRNAs intricately regulate various aspects of fruit and vegetables, including pigment accumulation, reproductive tissue development, fruit ripening, and responses to biotic and abiotic stresses, through diverse mechanisms such as gene expression modulation, interaction with hormones and transcription factors, microRNA regulation, and involvement in alternative splicing. This review presents a comprehensive overview of lncRNA classification, basic characteristics, and, most importantly, recent advances in understanding their functions and regulatory mechanisms.

Interfacial Engineering for Oriented Crystal Growth toward Dendrite-Free Zn Anode for Aqueous Zinc Metal Battery.

Zn deposition with a surface-preferred (002) crystal plane has attracted extensive attention due to its inhibited dendrite growth and side reactions. However, the nucleation and growth of the Zn(002) crystal plane are closely related to the interfacial properties. Herein, oriented growth of Zn(002) crystal plane is realized on Ag-modified surface that is directly visualized by in situ atomic force microscopy. A solid solution HCP-Zn (~1.10 at. % solubility of Ag, 30 °C) is formed on the Ag coated Zn foil (Zn@Ag) and possesses the same crystal structure as Zn to reduce its nucleation barrier caused by their lattice mismatch. It merits oriented Zn deposition and corrosion-resistant surface, and presents long cycling stability in symmetric cells and full cells coupled with V2O5 cathode. This work provides insights into interfacial regulation of Zn anodes for high-performance aqueous zinc metal batteries.

Echinatin mitigates sevoflurane-induced neurotoxicity through regulation of ferroptosis and iron homeostasis.

Surgery and anesthesia are vital medical interventions, but concerns over their potential cognitive side effects, particularly with the use of inhalational anesthetics like sevoflurane, have surfaced. This study delves into the neuroprotective potential of Echinatin against sevoflurane-induced neurotoxicity and the underlying mechanisms. Echinatin, a natural compound, has exhibited anti-inflammatory, antioxidant, and anticancer properties. Sevoflurane, while a popular anesthetic, is associated with perioperative neurocognitive disorders (PND) and neurotoxicity. Our investigation began with cellular models, where Echinatin demonstrated a significant reduction in sevoflurane-induced apoptosis. Mechanistically, we identified ferroptosis, a novel form of programmed cell death characterized by iron accumulation and lipid peroxidation, as a key player in sevoflurane-induced neuronal injury. Echinatin notably suppressed ferroptosis in sevoflurane-exposed cells, suggesting a pivotal role in neuroprotection. Expanding our research to a murine model, we observed perturbations in iron homeostasis, inflammatory cytokines, and antioxidants due to sevoflurane exposure. Echinatin treatment effectively restored iron balance, mitigated inflammation, and preserved antioxidant levels in vivo. Behavioral assessments using the Morris water maze further confirmed Echinatin's neuroprotective potential, as it ameliorated sevoflurane-induced spatial learning and memory impairments. In conclusion, our study unveils Echinatin as a promising candidate for mitigating sevoflurane-induced neurotoxicity. Through the regulation of ferroptosis, iron homeostasis, and inflammation, Echinatin demonstrates significant neuroprotection both in vitro and in vivo. These findings illuminate the potential for Echinatin to enhance the safety of surgical procedures involving sevoflurane anesthesia, minimizing the risk of cognitive deficits and neurotoxicity.

Regulating Ion-Dipole Interactions in Weakly Solvating Electrolyte towards Ultra-Low Temperature Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) are recognized as promising energy storage devices. However, they suffer from rapid capacity decay at ultra-low temperatures due to high Na+ desolvation energy barrier and unstable solid electrolyte interphase (SEI). Herein, a weakly solvating electrolyte (WSE) with decreased ion-dipole interactions is designed for stable sodium storage in hard carbon (HC) anode at ultra-low temperatures. 2-methyltetrahydrofuran with low solvating power is incorporated into tetrahydrofuran to regulate the interactions between Na+ and solvents. The reduced Na+-dipole interactions facilitate more anionic coordination in the first solvation sheath, which consistently maintains anion-enhanced solvation structures from room to low temperatures to promote inorganic-rich SEI formation. These enable WSE with a low freezing point of -83.3 °C and faster Na+ desolvation kinetics. The HC anode thus affords reversible capacities of 243.2 and 205.4 mAh g-1 at 50 mA g-1 at -40 and -60 °C, respectively, and the full cell of HC||Na3V2(PO4)3 yields an extended lifespan over 250 cycles with high capacity retention of ~100 % at -40 °C. This work sheds new lights on the ion-dipole regulation for ultra-low temperature SIBs.

Copper and conjugated carbonyls of metal-organic polymers as dual redox centers for Na storage.

Metal-organic polymers (MOPs) are fascinating electrode materials for high-performance sodium-ion batteries due to their multiple redox centers and low cost. Herein, a flower-like π-d conjugated MOP (Cu-TABQ) was synthesized using tetramino-benzoquinone (TABQ) as an organic ligand and Cu2+ as a transition metal node under the slow release of Cu2+ from [Cu(NH3)4]2+ and subsequent dehydrogenation. It possesses dual redox centers of Cu2+/Cu+ and C[double bond, length as m-dash]O/C-O to render a three-electron transfer reaction for each coordination unit with a high reversible capacity of 322.9 mA h g-1 at 50 mA g-1 in the voltage range of 1.0 to 3.0 V. The flower-like structure enhances fast Na+ diffusion and highly reversible organic/inorganic redox centers. This results in excellent cycling performance with almost no degradation within 700 cycles and great rate performance with 198.8 mA h g-1 at 4000 mA g-1. The investigation of the Na-storage mechanism and attractive performance will shed light on the insightful design of MOP cathode materials for further batteries.

Sustainable Aqueous Batteries Based on Bipolar Dissociation of Aluminum Hydroxyacetate Electrolyte.

Rechargeable aqueous batteries are potential systems for large-scale energy storage due to their high safety and low cost. However, developing aqueous batteries with high sustainability, affordability, and reversibility is urgent and challenging. Here we report an amphoteric aluminum hydroxyacetate (AlAc(OH)2) electrolyte with the ability of bipolar ionization of H+ and OH-, which facilitates the redox reactions at both the anthraquinone (AQ) anode and nickel hydroxide (Ni(OH)2) cathode. The bipolar ionization ability of the AlAc(OH)2(H2O)3 solvation structure results from the strong polarization ability of Al3+ and OH-. The H+/OH- dissociation ability with a dissociation constant of 5.0/3.0 is stronger than that of water (14.0), which boosts the simultaneous stable redox reactions of electrodes. Specifically, H+ uptake prevents the AQ anode from the formation of an ionic bond, suppressing the electrode dissolution, whereas OH- provides the local alkaline environment for the stable conversion reaction of the Ni(OH)2 cathode. The AQ anode in the designed AQ||Ni(OH)2 battery delivers a discharge capacity of 243.9 mAh g-1 and a capacity retention of 78.2% after 300 cycles with high reversibility. Moreover, a pouch cell with a discharge capacity of 0.90 Ah was assembled, exhibiting an energy density of 44.7 Wh kg-1 based on the total mass of the battery. This work significantly widens the types of aqueous batteries and represents a design philosophy of bipolar electrolytes and distinct electrochemical reactions with H+ and OH-.

Regulation of Coordination Chemistry for Ultrastable Layered Oxide Cathode Materials of Sodium-Ion Batteries.

Layered transition-metal (TM) oxide cathodes have attracted growing attention in sodium-ion batteries (SIBs). However, their practical implementation is plagued by Jahn-Teller distortion and irreversible cation migration, leading to severe voltage decay and structure instability. Herein, O3-Na0.898K0.058Ni0.396Fe0.098Mn0.396Ti0.092O2 (KT-NFM) is reported as an ultrastable cathode material via multisite substitution with rigid KO6 pillars and flexible TiO6 octahedra. The K pillars induce contracted TMO2 slabs and their strong Coulombic repulsion to inhibit Ni/Fe migration; and Ti incorporation reinforces the hybridization of Ni(3deg*)-O(2p) to mitigate the undesired O3-O'3 phase transition. These enable the reversible redox of Ni2+↔Ni3 . 20+ and Fe3+↔Fe3.69+ for 138.6 mAh g-1 and ultrastable cycles with >90% capacity retention after 2000 cycles in a pouch cell of KT-NFM||hard carbon. This will provide insights into the design of ultrastable layered cathode materials of sodium-ion batteries and beyond.

Regulation of anion-Na+ coordination chemistry in electrolyte solvates for low-temperature sodium-ion batteries.

High-performance sodium storage at low temperature is urgent with the increasingly stringent demand for energy storage systems. However, the aggravated capacity loss is induced by the sluggish interfacial kinetics, which originates from the interfacial Na+ desolvation. Herein, all-fluorinated anions with ultrahigh electron donicity, trifluoroacetate (TFA-), are introduced into the diglyme (G2)-based electrolyte for the anion-reinforced solvates in a wide temperature range. The unique solvation structure with TFA- anions and decreased G2 molecules occupying the inner sheath accelerates desolvation of Na+ to exhibit decreased desolvation energy from 4.16 to 3.49 kJ mol-1 and 24.74 to 16.55 kJ mol-1 beyond and below -20 °C, respectively, compared with that in 1.0 M NaPF6-G2. These enable the cell of Na||Na3V2(PO4)3 to deliver 60.2% of its room-temperature capacity and high capacity retention of 99.2% after 100 cycles at -40 °C. This work highlights regulation of solvation chemistry for highly stable sodium-ion batteries at low temperature.

Negative Lattice Expansion in an O3-Type Transition-Metal Oxide Cathode for Highly Stable Sodium-Ion Batteries.

The sodium extraction/insertion in layered transition-metal oxide (TMO) cathode materials are typically accompanied by slab sliding and lattice changes, leading to microstructure destruction and capacity decay. Herein, negative lattice expansion is observed in an O3 type Ni-based layered cathode of Na0.9 Ni0.32 Zn0.08 Fe0.1 Mn0.3 Ti0.2 O2 upon Na+ extraction. It is attributed to the weak Zn2+ -O2- orbital hybridization and increased electron density of the surrounding oxygen for reinforced interlayer O-O repulsive force. This enables gliding of TMO slabs for the intergrowth phase transition of P3→OP2 to alleviate lattice strain with moderate lattice shrinkage, which exhibits general interslab spacings and volume changes as low as 2.4 % and 1.9 %, respectively. The strong Ti-O bonds accommodate the internal distortion of TMO6 octahedra due to the flexibility of TiO6 octahedra during cycling. These endow a high specific capacity of 144.9 mAh g-1 and excellent cycling performance of pouch-type sodium-ion batteries with 93 % capacity retention after 3600 cycles.

New Reaction Pathway of Superoxide Disproportionation Induced by a Soluble Catalyst in Li-O2 Batteries.

Aprotic Li-O2 battery has attracted considerable interest for high theoretical energy density, however the disproportionation of the intermediate of superoxide (O2 - ) during discharge and charge leads to slow reaction kinetics and large voltage hysteresis. Herein, the chemically stable ruthenium tris(bipyridine) (RB) cations are employed as a soluble catalyst to alternate the pathway of O2 - disproportionation and its kinetics in both the discharge and charge processes. RB captures O2 - dimer and promotes their intramolecular charge transfer, and it decreases the energy barrier of the disproportionation reaction from 7.70 to 0.70 kcal mol-1 . This facilitates the discharge and charge processes and simultaneously mitigates O2 - and singlet oxygen related side reactions. These endow the Li-O2 battery with reduced discharge/charge voltage gap of 0.72 V and prolonged lifespan for over 230 cycles when coupled with RuO2 catalyst. This work highlights the vital role of superoxide disproportionation for Li-O2 battery.

Facilitating endoscopic full-thickness resection for gastric submucosal tumors with a novel snare traction method (with video).

BACKGROUND AND AIM: Endoscopic full-thickness resection (EFTR) is a promising technique in treating gastric submucosal tumors originating from the muscularis propria (SMT-MPs). However, it is challenging without counter-traction. METHODS: A snare was inserted through the forceps channel to grasp the part of the tumor or the mucosa connected to the tumor. The outer sheath and inner wire of snare in vitro were fixed by a pair of hemostatic forceps. The handle of snare was cut off, and the endoscope was pulled out without affecting the traction state of snare. Snare-assisted EFTR (EFTR-S) was then performed with counter-traction. One hundred and four patients with gastric SMT-MPs who received the procedure of EFTR with or without snare traction method were retrospectively analyzed using univariate and multiple regressions, and covariates were adjusted in the multiple analysis. RESULTS: Compared with EFTR group (n = 36), EFTR-S group (n = 68) showed a higher operative success rate (95.6% vs 72.2%, P = 0.001), a lower incidence of intraoperative hemorrhage (4.4% vs 16.7%, P = 0.038) and shorter operative time among operative successes (53.6 ± 16.6 min vs 67.7 ± 33.4 min, P < 0.001). Univariate logistic analysis showed that snare traction represented a significant factor, which could improve operative successful rate (odds ratio, 8.3; 95% confidence interval, 2.1 to 32.7; P = 0.002). Postoperative outcomes and adverse events among operative successes were similar between the two groups. CONCLUSIONS: This novel snare traction method may provide an effective counter-traction and reduce the difficulty of EFTR for gastric SMT-MPs.

Exosomal microRNA Therapy for Non-Small-Cell Lung Cancer.

With the progress of molecular diagnosis research on non-small cell lung cancer (NSCLC) cells, four identified categories of microRNAs have been found to be related to disease diagnosis, diagnosis of treatment resistance, prediction of prognosis, and drugs for treatment. To date, nine target mRNA/signal pathways have been confirmed for microRNA drug therapy both in vitro and in vivo. When microRNA drugs enter blood vessels, they target the tumor site and play a similar role to that of targeted drugs. However, whether they will produce serious off-target effects remains unknown, and further clinical research is needed. This review provides the first summary of microRNA therapy for NSCLC.

Subcutaneous device-free islet transplantation.

Diabetes mellitus is a chronic metabolic disease, characterized by high blood sugar levels; it affects more than 500 million individuals worldwide. Type 1 diabetes mellitus (T1DM) is results from insufficient insulin secretion by islets; its treatment requires lifelong use of insulin injections, which leads to a large economic burden on patients. Islet transplantation may be a promising effective treatment for T1DM. Clinically, this process currently involves directly infusing islet cells into the hepatic portal vein; however, transplantation at this site often elicits immediate blood-mediated inflammatory and acute immune responses. Subcutaneous islet transplantation is an attractive alternative to islet transplantation because it is simpler, demonstrates lower surgical complication risks, and enables graft monitoring and removal. In this article, we review the current methods of subcutaneous device-free islet transplantation. Recent subcutaneous islet transplantation techniques with high success rate have involved the use of bioengineering technology and biomaterial cotransplantation-including cell and cell growth factor co-transplantation and hydrogel- or simulated extracellular matrix-wrapped subcutaneous co-transplantation. In general, current subcutaneous device-free islet transplantation modalities can simplify the surgical process and improve the posttransplantation graft survival rate, thus aiding effective T1DM management.

circ_0000337 Promotes the Progression of Cervical Cancer by miR-155-5p/RAB3B Axis.

Current study aims to investigate the biological function of circular RNA (circRNA, circ_0000337) in cervical cancer (CC). Bioinformatic analyses were used to predict targets for circ_0000337 and miR-155-5p, and analyze the gene expression differences between cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tissues and normal tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were applied to assess mRNA and protein expressions of circ_0000337, microRNA-155-5p (miR-155-5p) and member RAS oncogene family (RAB3B), respectively. Following the establishment of gain/loss-of-function models, CCK-8 was performed to evaluate cell proliferation. Bioinformatics analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were used to identify the interaction in circ_0000337, miR-155-5p, and RAB3B. Circ_0000337 and RAB3B were upregulated, while miR-155-5p was downregulated in CC tissues and cell lines. circ_0000337 overexpression promoted cell proliferation, circ_0000337 knock down inhibited cell proliferation by sponging miR-155-5p. RAB3B was a target of miR-155-5p which was positively regulated by circ_0000337. In the collected CC tissues, there was a negative correlation between miR-155-5p and circ_0000337 or RAB3B, and a positive correlation between circ_0000337 and RAB3B. miR-155-5p was positively, while RAB3B was negatively correlated with OS in patients with CC, and they were negatively correlated. In conclusion, circ_0000337 upregulates RAB3B by sponging miR-155-5p to promote CC cell proliferation.

Boosting the Ultrastable High-Na-Content P2-type Layered Cathode Materials with Zero-Strain Cation Storage via a Lithium Dual-Site Substitution Approach.

P2-type layered transition-metal (TM) oxides, NaxTMO2, are highly promising as cathode materials for sodium-ion batteries (SIBs) due to their excellent rate capability and affordability. However, P2-type NaxTMO2 is afflicted by issues such as Na+/vacancy ordering and multiple phase transitions during Na-extraction/insertion, leading to staircase-like voltage profiles. In this study, we employ a combination of high Na content and Li dual-site substitution strategies to enhance the structural stability of a P2-type layered oxide (Na0.80Li0.024[Li0.065Ni0.22Mn0.66]O2). The experimental results reveal that these approaches facilitate the oxidation of Mn ions to a higher valence state, thereby affecting the local environment of both TM and Na ions. The resulting modification in the local structure significantly improves the Na-ion storage capabilities as required for cathode materials in SIBs. Furthermore, it induces a solid-solution reaction and enables nearly zero-strain operation (ΔV = 0.7%) in the Na0.80Li0.024[Li0.065Ni0.22Mn0.66]O2 cathode during cycling. The assembled full cells demonstrate an exceptional rate performance, with a retention rate of 87% at 10 C compared to that of 0.1 C, as well as an ultrastable cycling capability, maintaining a capacity retention of 73% at 2 C after 1000 cycles. These findings offer valuable insights into the electronic and structural chemistry of ultrastable cathode materials with "zero-strain" Na-ion storage.

Application of methyl jasmonate to control chilling tolerance of postharvest fruit and vegetables: a meta-analysis and eliciting metabolism review.

Chilling injury is one of the most significant limitations for low temperature storage of postharvest fruits and vegetables, causing quality deterioration and economic loss. Increasing studies indicated that methyl jasmonate (MeJA) is critical in regulating the postharvest fruit and vegetables chilling tolerance. Based on a meta-analysis, the review analyzed the action of exogenous MeJA application on the chilling index in postharvest fruit and vegetables and summarized MeJA's mechanisms for controlling postharvest chilling injury. The meta-analysis found that MeJA treatment remarkably inhibited postharvest fruit and vegetable chilling injury. Moreover, we concluded the following function mechanism of MeJA on postharvest fruit and vegetable chilling tolerance: (1) Enhancing membrane integrity and energy supply, (2) Increasing antioxidant activity, (3) Enhancing arginine pathway, (4) Enhancing sugar metabolism, (5) Regulating phenolic metabolism, (6) Activating CBF pathway, (7) Regulating HSP accumulation and expression, and (8) Crosstalk with phytohormone. Finally, we summarized the regulatory mechanisms of MeJA on postharvest fruit and vegetable biological processes at the transcriptional and post-translational levels.

Identification of a TRP channel-related risk model for predicting prognosis and therapeutic effects of patients with hepatocellular carcinoma.

PURPOSE: TRP channels have been implicated in cancer progression. Our study seeks to establish a prognostic model for hepatocellular carcinoma (HCC) by utilizing genes related to TRP channels. METHODS: We used the TCGA and ICGC databases as training and validation cohorts, respectively. We calculated the risk scores using Lasso-Cox regression analysis based on the expression levels of prognostic genes and performed survival analysis to compare overall survival between high- and low-risk groups. Then we compared the clinicopathologic characteristics and conducted biological functional analysis. We also explored immune cell infiltration and compared the drug sensitivity. RESULTS: Using bioinformatics algorithms, we identified 11 TRP-related genes and calculated the risk scores. Patients in the high-risk group demonstrated worse overall survival, as well as more advanced T stage and pathologic stage. The risk score showed a significant association with the cell cycle. The high-risk group had more ICI and RTK targets with elevated expression and showed better therapeutic effect to chemotherapy including 5-fluorouracil, camptothecin, docetaxel, doxorubicin, gemcitabine, and paclitaxel. Overall, an individualized nomogram was constructed by integrating the risk score and requisite clinicopathologic parameters to predict the overall survival of HCC patients. CONCLUSIONS: We successfully established a highly accurate prognostic model for predicting overall survival and therapeutic effects using TRP channel-related genes.