Self-assembled methodologies for the construction of DNA nanostructures and biological applications.

Over the past decades, deoxyribonucleic acid (DNA), as a versatile building block, has been widely employed to construct functionalized nanostructures. Among the diverse types of materials, DNA related nanostructures have gained growing attention due to their intrinsic programmability, favorable biocompatibility, and strong molecular recognition capability. The conventional construction strategy for building DNA structures is based on Watson-Crick base-pairing rules, which are mainly driven by the hydrogen bonding of bases. However, hydrogen bonding-based DNA nanostructures cannot meet the requirements of specific morphology and multifunctionality. Currently, various functional elements have been introduced to expand the synthetic methodologies for constructing the DNA hybrid nanostructures, including small molecules, peptide polymers, organic ligands and transition metal ions. Besides, the potential applications for these DNA hybrid nanostructures have also been explored. It has been demonstrated that DNA hybrid structures with various properties can be extensively applied in the fields of magnetic resonance, luminescence imaging, biomedical detection, and drug delivery systems. In this review, we highlight the pioneering contributions to the methodologies of DNA-based nanostructure assembly. Furthermore, the recent advances in drug delivery systems and biomedical diagnosis based on DNA hybrid nanostructures are briefly summarized.

Activation of NOTCH signaling impedes cell proliferation and survival in acute megakaryoblastic leukemia.

The genetic lesions that drive acute megakaryoblastic leukemia (AMKL) have not been fully elucidated. To search for genetic alterations in AMKL, we performed targeted deep sequencing in 34 AMKL patient samples and 8 AMKL cell lines, and detected frequent genetic mutations in NOTCH pathway, besides previously reported alternations in GATA-1 and JAK-STAT pathway. Pharmacological and genetic NOTCH activation, but not inhibition, significantly suppressed AMKL cell proliferation in both in vitro and in vivo assays employing a patient derived xenograft model. These results suggest that NOTCH inactivation underlies AMKL leukemogenesis and NOTCH activation holds a potential of therapeutic application for AMKL.

Innovative Delivery System Combining CRISPR-Cas12f for Combatting Antimicrobial Resistance in Gram-Negative Bacteria.

Antimicrobial resistance poses a significant global challenge, demanding innovative approaches, such as the CRISPR-Cas-mediated resistance plasmid or gene-curing system, to effectively combat this urgent crisis. To enable successful curing of antimicrobial genes or plasmids through CRISPR-Cas technology, the development of an efficient broad-host-range delivery system is paramount. In this study, we have successfully designed and constructed a novel functional gene delivery plasmid, pQ-mini, utilizing the backbone of a broad-host-range Inc.Q plasmid. Moreover, we have integrated the CRISPR-Cas12f system into the pQ-mini plasmid to enable gene-curing in broad-host of bacteria. Our findings demonstrate that pQ-mini facilitates the highly efficient transfer of genetic elements to diverse bacteria, particularly in various species in the order of Enterobacterales, exhibiting a broader host range and superior conjugation efficiency compared to the commonly used pMB1-like plasmid. Notably, pQ-mini effectively delivers the CRISPR-Cas12f system to antimicrobial-resistant strains, resulting in remarkable curing efficiencies for plasmid-borne mcr-1 or blaKPC genes that are comparable to those achieved by the previously reported pCasCure system. In conclusion, our study successfully establishes and optimizes pQ-mini as a broad-host-range functional gene delivery vector. Furthermore, in combination with the CRISPR-Cas system, pQ-mini demonstrates its potential for broad-host delivery, highlighting its promising role as a novel antimicrobial tool against the growing threat of antimicrobial resistance.

Characterization of Salmonella Phage P1-CTX and the Potential Mechanism Underlying the Acquisition of the blaCTX-M-27 Gene.

The P1 phage has garnered attention as a carrier of antibiotic resistance genes (ARGs) in Enterobacteriaceae. However, the transferability of ARGs by P1-like phages carrying ARGs, in addition to the mechanism underlying ARG acquisition, remain largely unknown. In this study, we elucidated the biological characteristics, the induction and transmission abilities, and the acquisition mechanism of the blaCTX-M-27 gene in the P1 phage. The P1-CTX phage exhibited distinct lytic plaques and possessed a complete head and tail structure. Additionally, the P1-CTX phage was induced successfully under various conditions, including UV exposure, heat treatment at 42 °C, and subinhibitory concentrations (sub-MICs) of antibiotics. Moreover, the P1-CTX phage could mobilize the blaCTX-M-27 gene into three strains of Escherichia coli (E. coli) and the following seven different serotypes of Salmonella: Rissen, Derby, Kentucky, Typhimurium, Cerro, Senftenberg, and Muenster. The mechanism underlying ARG acquisition by the P1-CTX phage involved Tn1721 transposition-mediated movement of blaCTX-M-27 into the ref and mat genes within its genome. To our knowledge, this is the first report documenting the dynamic processes of ARG acquisition by a phage. Furthermore, this study enriches the research on the mechanism underlying the phage acquisition of drug resistance genes and provides a basis for determining the risk of drug resistance during phage transmission.

A novel radiomics-based technique for identifying vulnerable coronary plaques: a follow-up study.

BACKGROUND: Previous reports have suggested that coronary computed tomography angiography (CCTA)-based radiomics analysis is a potentially helpful tool for assessing vulnerable plaques. We aimed to investigate whether coronary radiomic analysis of CCTA images could identify vulnerable plaques in patients with stable angina pectoris. METHODS: This retrospective study included patients initially diagnosed with stable angina pectoris. Patients were randomly divided into either the training or test dataset at an 8 : 2 ratio. Radiomics features were extracted from CCTA images. Radiomics models for predicting vulnerable plaques were developed using the support vector machine (SVM) algorithm. The model performance was assessed using the area under the curve (AUC); the accuracy, sensitivity, and specificity were calculated to compare the diagnostic performance using the two cohorts. RESULTS: A total of 158 patients were included in the analysis. The SVM radiomics model performed well in predicting vulnerable plaques, with AUC values of 0.977 and 0.875 for the training and test cohorts, respectively. With optimal cutoff values, the radiomics model showed accuracies of 0.91 and 0.882 in the training and test cohorts, respectively. CONCLUSION: Although further larger population studies are necessary, this novel CCTA radiomics model may identify vulnerable plaques in patients with stable angina pectoris.

An Organodiphosphate-Containing Polyoxoniobate Ring and Its Assembly into a Three-Dimensional Framework through Hydrogen Bonding.

In this work, a novel organodiphosphate-containing inorganic-organic hybrid polyoxoniobate (PONb) ring {(PO3CH2CH2PO3H)4Nb8O16}4- (Nb8P8) has been achieved by a one-pot hydrothermal method. The ring is constructed from a tetragonal {Nb8O36} motif and four {PO3CH2CH2PO3H} ligands. Interestingly, Nb8P8 can be joined together via K-H2O clusters {K2(H2O)4(OH)2} to form one-dimensional chains {[K2(H2O)4(OH)2]Nb8P8}n and further linked by {Cu(en)2}2+ (en = ethylenediamine) complexes, resulting in a three-dimensional supramolecular framework {[Cu(en)2]2[K2(H2O)4(OH)2]Nb8P8}·3en·H2O (1). 1 exhibits good chemical and thermal stability and has a high water vapor adsorption capacity of ≤224 cm3 g-1 (22.71 mol·mol-1) at 298 K, outperforming most of the known polyoxometalate-based materials. Impedance measurements prove that 1 can transfer protons with moderate conductivity. This study not only contributes to the structural diversity of organodiphosphate-containing PONbs and PONb rings but also provides a reference for the development of PONb-based materials with unique performance.

GM1 Ameliorates Neuronal Injury in Rats after Cerebral Ischemia and Reperfusion: Potential Contribution of Effects on SPTBN1-mediated Signaling.

Monosialoganglioside GM1 (GM1) has long been used as a therapeutic agent for neurological diseases in the clinical treatment of ischemic stroke. However, the mechanism underlying the neuroprotective function of GM1 is still obscure until now. In this study, we investigated the effects of GM1 in ischemia and reperfusion (I/R) brain injury models. Middle cerebral artery occlusion and reperfusion (MCAO/R) rats were treated with GM1 (60 mg·kg-1·d-1, tail vein injection) for 2 weeks. The results showed that GM1 substantially attenuated the MCAO/R-induced neurological dysfunction and inhibited the inflammatory responses and cell apoptosis in ischemic parietal cortex. We further revealed that GM1 inhibited the activation of NFκB/MAPK signaling pathway induced by MCAO/R injury. To explore its underlying mechanism of the neuroprotective effect, transcriptome sequencing was introduced to screen the differentially expressed genes (DEGs). By function enrichment and PPI network analyses, Sptbn1 was identified as a node gene in the network regulated by GM1 treatment. In the MCAO/R model of rats and oxygen-glucose deprivation and reperfusion (OGD/R) model of primary culture of rat cortical neurons, we first found that SPTBN1 was involved in the attenuation of I/R induced neuronal injury after GM1 administration. In SPTBN1-knockdown SH-SY5Y cells, the treatment with GM1 (20 µM) significantly increased SPTBN1 level. Moreover, OGD/R decreased SPTBN1 level in SPTBN1-overexpressed SH-SY5Y cells. These results indicated that GM1 might achieve its potent neuroprotective effects by regulating inflammatory response, cell apoptosis, and cytomembrane and cytoskeleton signals through SPTBN1. Therefore, SPTBN1 may be a potential target for the treatment of ischemic stroke.

VGluT2 neuron subtypes in the paraventricular thalamic nucleus regulate depression in paraquat-induced Parkinson's disease.

Parkinson's disease (PD) is a prevalent neurodegenerative disease and approximately one third of patients with PD are estimated to experience depression. Paraquat (PQ) is the most widely used herbicide worldwide and PQ exposure is reported to induce PD with depression. However, the specific brain region and neural networks underlying the etiology of depression in PD, especially in the PQ-induced model, have not yet been elucidated. Here, we report that the VGluT2-positive glutamatergic neurons in the paraventricular thalamic nucleus (PVT) promote depression in the PQ-induced PD mouse model. Our results show that PVTVGluT2 neurons are activated by PQ and their activation increases the susceptibility to depression in PD mice. Conversely, inhibition of PVTVGluT2 neurons reversed the depressive-behavioral changes induced by PQ. Similar to the effects of intervention the soma of PVTVGluT2 neurons, stimulation of their projections into the central amygdaloid nucleus (CeA) also strongly influenced depression in PD mice. PQ induced malfunctioning of the glutamate system and changes in the dendritic and synaptic morphology in the CeA through its role on PVTVGluT2 neuronal activation. In summary, our results demonstrate that PVTVGluT2 neurons are key neuronal subtypes for depression in PQ-induced PD and promote depression processes through the PVTVGluT2-CeA pathway.

Development of Stable Water-Soluble Supratomic Silver Clusters Utilizing A Polyoxoniobate-Protected Strategy: Giant Core-Shell-Type Ag8@Nb162 Fluorescent Nanocluster.

Atomically precise low-nuclearity (n<10) silver nanoclusters (AgNCs) have garnered significant interest due to their size-dependent optical properties and diverse applications. However, their synthesis has remained challenging, primarily due to their inherent instability. The present study introduces a new feasible approach for clustering silver ions utilizing highly negative and redox-inert polyoxoniobates (PONbs) as all-inorganic ligands. This strategy not only enables the creation of novel Ag-PONb composite nanoclusters but also facilitates the synthesis of stable low-nuclearity AgNCs. Using this method, we have successfully synthesized a small octanuclear rhombic [Ag8]6+ AgNC stabilized by six highly negative [LiNb27O75]14- polyoxoanions. This marks the first PONb-protected superatomic AgNC, designated as {Ag8@(LiNb27O75)6} (Ag8@Nb162), with an aesthetically spherical core-shell structure. The crystalline Ag8@Nb162 is stable under ambient conditions, What's more, it is water-soluble and able to maintain its molecular cluster structure intact in water. Further, the stable small [Ag8]6+ AgNC has interesting temperature- and pH-dependent reversible fluorescence response, based on which a multiple optical encryption mode for anti-counterfeit technology was demonstrated. This work offers a promising avenue for the synthesis of fascinating and stable PONb-protected AgNCs and sheds light on the development of new-type optical functional materials.

High-Performance Zinc-Ion Hybrid Supercapacitor from Guilin Sanhua Liquor Lees-Derived Carbon Materials.

Aqueous zinc-ion hybrid supercapacitors (ZHSCs) have attracted considerable attention because they are inexpensive and safe. However, the inadequate energy densities, power densities, and cycling performance of current ZHSC energy-storage devices are impediments that need to be overcome to enable the further development and commercialization of this technology. To address these issues, in this study, we prepared carbon-based ZHSCs using a series of porous carbon materials derived from Sanhua liquor lees (SLPCs). Among them, the best performance was observed for SLPC-A13, which exhibited excellent properties and a high-surface-area structure (2667 m2 g-1) with abundant micropores. The Zn//SLPC-A13 device was assembled by using 2 mol L-1 ZnSO4, SLPC-A13, and Zn foil as the electrolyte, cathode, and anode, respectively. The Zn//SLPC-A13 device delivered an ultrahigh energy density of 137 Wh kg-1 at a power density of 462 W kg-1. Remarkably, Zn//SLPC-A13 retained 100% of its specific capacitance after 120,000 cycles of long-term charge/discharge testing, with 62% retained after 250,000 cycles. This outstanding performance is primarily attributed to the SLPC-A13 carbon material, which promotes the rapid adsorption and desorption of ions, and the charge-discharge process, which roughens the Zn anode in a manner that improves reversible Zn-ion plating/stripping efficiency. This study provides ideas for the preparation of ZHSC cathode materials.

Pathological variations and immune response in Channa argus infected with pathogenic Nocardia seriolae strain.

Nocardia seriolae pathogen causes chronic granulomatous disease, reportedly affecting over 40 species of marine and freshwater cultured fish. Hence, research is required to address and eliminate this significant threat to the aquaculture industry. In this respect, a reliable and reproducible infection model needs to be established to better understand the biology of this pathogen and its interactions with the host during infection, as well as to develop new vaccines or other effective treatment methods. In this study, we examined the pathogenicity of the pathogen and the immune response of snakehead (Channa argus) juvenile to N. seriolae using a range of methods and analyses, including pathogen isolation and identification, histopathology, Kaplan-Meier survival curve analysis, and determination of the median lethal dose (LD50) and cytokine expression. We have preliminarily established a N. seriolae - C. argus model. According to our morphological and phylogenetic analysis data, the isolated strain was identified as N. seriolae and named NSE01. Eighteen days post-infection of healthy juvenile C. argus with N. seriolae NSE01, the mortality rate in all four experimental groups (intraperitoneally injected with 1 × 105 CFU/mL - 1 × 108 CFU/mL of bacterial suspension) (n = 120) was 100 %. The LD50 of N. seriolae NSE01 for juvenile C. argus was determined to be 1.13 × 106 CFU/fish. Infected juvenile C. argus had significant pathological changes, including visceral tissue swelling, hemorrhage, and the presence of numerous nodules of varying sizes in multiple tissues. Further histopathological examination revealed typical systemic granuloma formation. Additionally, following infection with N. seriolae NSE01, the gene expression of important cytokines, such as Toll-like receptor genes TLR2, TLR13, interleukin-1 receptor genes IL1R1, IL1R2, and interferon regulatory factor IRF2 were significantly upregulated in different tissues, indicating their potential involvement in the host immune response and regulation against N. seriolae. In conclusion, juvenile C. argus can serve as a suitable model for N. seriolae infection. The establishment of this animal model will facilitate the study of the pathogenesis of nocardiosis and the development of vaccines.

Microglial exosomes in paraquat-induced Parkinson's disease: Neuroprotection and biomarker clues.

The exact mechanisms underlying the initiation and exacerbation of Parkinson's disease (PD) by paraquat remain unclear. We have revealed that exosomes mediate neurotoxicity induced by low dose paraquat exposure by transmitting intercellular signaling. Exposure to 40 µM paraquat promoted exosome release from mouse microglia cells (BV2) in vitro. Paraquat exposure at 100 µM caused degeneration of mouse dopaminergic MN9D cells and inhibited microglia exosome uptake by fluorescently labeling exosomes. We established an incubation model for exosomes and dopaminergic neuron cells under PQ treatment. The results indicated that microglial exosomes alleviated degeneration, increasing proliferation and PD-related protein expression of dopaminergic neurons; however, paraquat reversed this effect. Then, through exosome high-throughput sequencing and qRT-PCR experiments, miR-92a-3p and miR-24-3p were observed to transfer from exosomes to dopaminergic neurons, inhibited by paraquat. The specificity of miR-92a-3p and miR-24-3p was verified in PD patients exosomes, indicating the potential diagnostic value of the exosomal miRNAs in paraquat-induced PD. These results suggest glia-neuron communication in paraquat-induced neurodegeneration and may identify stable paraquat-mediated PD biomarkers, offering clues for early recognition and prevention of pesticide-induced degenerative diseases.

Quality improvement to holographic microscopy reconstruction based on Kramers-Kronig relations and phase background fitting.

Spectrum aliasing in off-axis digital holography may result in poor image reconstruction quality. This study proposes a method to eliminate the zero-order spectrum and enhance image quality based on Kramers-Kronig relations and phase background fitting. The Kramers-Kronig relations are employed to derive the quotient of the complex wavefront of object and the reference beam, and phase background fitting is performed in a compensatory way to yield the object complex wavefront. The effectiveness of the proposed approach is validated via simulations and experiments. The results show significantly improved off-axis digital holographic microscopy reconstruction quality, making the proposed method a promising option for holographic microscopy imaging.

Single-cell RNA-sequencing of cellular heterogeneity and pathogenic mechanisms in paraquat-induced Parkinson's disease with depression.

Parkinson's disease (PD) is among the most prevalent neurodegenerative diseases, and approximately one third of patients with PD are estimated to have depression. Paraquat (PQ) exposure is an important environmental risk factor for PD. In this study, we established a mouse model of PQ-induced PD with depression to comprehensively investigate cellular heterogeneity and the mechanisms underlying the progression of depression in the context of PD. We utilized single-cell RNA-seq (scRNA-seq) to acquire the transcriptomic atlas of individual cells from model mice and characterize the gene expression profiles in each differentially expressed cell type. We identified a specific glutamatergic neuron cluster responsible for the development of heterogeneous depression-associated changes and established a comprehensive gene expression atlas. Furthermore, functional enrichment and cell trajectory analyses revealed that the mechanisms underlying the progression of PD with depression were associated with specific glutamatergic neurons. Together, our findings provide a valuable resource for deciphering the cellular heterogeneity of PD with depression. The suggested connection between intrinsic transcriptional states of neurons and the progression of depression can provide insight into potential biomarkers and specific targets for anti-depression treatment in patients with PD. SYNOPSIS: Our results obtained using model mice confirm the core effects of PQ exposure on glutamatergic neurons and their potential role in the development of PD with depression.

Hydro-meteorological factors and inflowing nutrients drive water quality in an impounded lake of China's South-to-North Water Diversion Project.

Freshwater lakes play a vital role in global hydrological and biogeochemical cycles, serving various functions and maintaining ecological balance. However, freshwater resources are more vulnerable to deterioration due to multiple stressors. Gaoyou Lake is one of the impounded lakes of the Eastern route of South-to-North Water Diversion Project in China, and as an important source of drinking water, the lake has been routinely monitored. Long-term monitoring of water quality in Gaoyou Lake showed that concentrations of nutrients and chlorophyll a as well as trophic state in the water column increased while water transparency decreased, indicating that the water quality has declined during the last 12 years. Specifically, there was a notable and statistically significant increase in chlorophyll a concentrations, averaging an annual rate of 9.9%. Despite a slight decline in trophic level index until 2014, subsequent years saw an upward trend, ranging from 50.7 to 56.4 and indicating a light eutrophic state. Spatially, the western area displayed higher nutrient and chlorophyll a concentrations. Changes in hydro-meteorological variables and nutrients from inflowing rivers were the main factors correlated with water quality in Gaoyou Lake. Thus, pollution source apportionment and management within Huaihe River basin should be considered to reduce the external loadings of nutrients in order to improve and sustain long-term water quality.

LncRNA NR_030777 promotes mitophagy by targeting CDK1-related mitochondrial fission and ATG12 to attenuate paraquat-induced Parkinson's disease.

With the evidence emerging that abnormal expression of long noncoding RNAs (lncRNAs) are involved in onset of Parkinson's disease (PD), the role of NR_030777 contributing to this disease is of great interest. We recently found that a novel lncRNA "NR_030777" demonstrates protective effects on PQ-induced neurodegeneration. However, the underlying molecular mechanisms of NR_030777 in the regulation of mitochondrial fission and mitophagy involved in PQ-induced neuronal damage remain to be explored. NR_030777 brain conditional overexpressing mice as well as in vitro primary neuronal cells from cerebral cortex and Neuro2a cells were adopted. Immunofluorescence, Immunohistochemistry, qRT-PCR and Western blotting were used to evaluate the expression levels of RNA and proteins. RNA immunoprecipitation and RNA pulldown experiment were used to evaluate the interaction of NR_030777 with its target proteins. NR_030777 and mitophagy were increased, and tyrosine hydroxylase (TH) levels recovered after NR_030777 overexpression upon PQ treatment. The overexpression and knockdown of NR_030777 unveiled that NR_030777 positively regulated mitophagy such as the upregulation of LC3B-II:I, ATG12-ATG5, p62 and NBR1. Moreover, the application of mdivi-1, a DRP-1 inhibitor, in combination with NR_030777 genetic modified cells unveiled that NR_030777 promoted DRP1-mediated mitochondrial fission and mitophagy. Furthermore, NR_030777 were directly bound to CDK1 to increase p-DRP1 levels at the Ser616 site, leading to mitochondrial fission and mitophagy. On the other hand, NR_030777 acted directly on ATG12 within the ATG12-ATG5 complex in the 800-1400 nt region to modulate the membrane formation. Accordingly, NR_030777 deficiency in neuron cells compromised cell mitophagy. Finally, the above findings were confirmed using NR_030777-overexpressing mice. NR_030777 exerted a protective effect on PQ-exposed mice by enhancing mitophagy. Our data provide the first scientific evidence for the precise invention of PQ-induced PD. Our findings further propose a breakthrough for understanding the regulatory relationship between NR_030777, CDK1, ATG12 and mitophagy in PQ-induced PD.

Exploring the impact of PEGylation on pharmacokinetics: a size-dependent effect of polyethylene glycol on prostate-specific membrane antigen inhibitors.

BACKGROUND: Prostate cancer is the second most frequent cancer and the fifth leading cause of cancer-related deaths in men. Prostate-specific membrane antigen (PSMA) as a target has gained increasing attention. This research aims to investigate and understand how altering size of PEG impacts the in vitro and in vivo behavior and performance of PSMA inhibitors, with a specific focus on their pharmacokinetic characteristics and targeting properties. RESULTS: Two 68Ga-labeled PSMA-targeted radiotracers were developed, namely [68Ga]Ga-PP4-WD and [68Ga]Ga-PP8-WD, with varying sizes of polyethylene glycol (PEG). [68Ga]Ga-PP4-WD and [68Ga]Ga-PP8-WD had excellent affinity for PSMA with IC50 being 8.06 ± 0.91, 6.13 ± 0.79 nM, respectively. Both tracers enabled clear visualization of LNCaP tumors in PET images with excellent tumor-to-background contrast. They also revealed highly efficient uptake and internalization into LNCaP cells, increasing over time. The biodistribution studies demonstrated that both radioligands exhibited significant and specific uptake into LNCaP tumors. Furthermore, they were rapidly cleared through the renal pathway, as evidenced by [68Ga]Ga-PP4-WD and [68Ga]Ga-PP8-WD showing a tenfold and a fivefold less in renal uptake, respectively, compared to [68Ga]Ga-Flu-1 in 30 min. Both in vitro and in vivo experiments demonstrated that PEG size significantly impacted tumor-targeting and pharmacokinetic properties. CONCLUSIONS: These radiotracers have demonstrated their effectiveness in significantly reducing kidney uptake while maintaining the absorbed dose in tumors. Both radiotracers exhibited strong binding and internalization characteristics in vitro, displayed high specificity and affinity for PSMA in vivo.

Differential requirement for IL-2 and IL-23 in the differentiation and effector functions of Th17/ILC3-like cells in a human T cell line.

A well-documented Achilles heel of current cancer immunotherapy approaches is T cell exhaustion within solid tumor tissues. The proinflammatory cytokine interleukin (IL)-23 has been utilized to augment chimeric antigen receptor (CAR) T cell survival and tumor immunity. However, in-depth interrogation of molecular events downstream of IL-23/IL-23 receptor signaling is hampered by a paucity of suitable cell models. The current study investigates the differential contribution of IL-2 and IL-23 to the maintenance and differentiation of the IL-23 responsive Kit225 T-cell line. We observed that IL-23 enhanced cellular fitness and survival but was insufficient to drive proliferation. IL-23 rapidly induced phosphorylation of STAT1, STAT3, and STAT4, and messenger RNA expression of IL17A, the archetypal effector cytokine of T helper 17 (Th17) cells, but not their lineage markers RORC and NCR1. These observations suggest that IL-23 endowed Th17/ILC3-like effector function but did not promote their differentiation. In contrast, spontaneous differentiation of Kit225 cells toward a Th17/ILC3-like phenotype was induced by prolonged IL-2 withdrawal. This was marked by strongly elevated basal IL17A and IL17F expression and the secretion of IL-17. Together, our data present Kit225 cells as a valuable model for studying the interplay between cytokines and their contribution to T cell survival, proliferation, and differentiation.

Application on perioperative ERAS concept in elderly lung cancer patients undergoing surgery.

Investigating the applying effects of the enhanced recovery after surgery (ERAS) in the perioperative period of elderly lung cancer patients undergoing the surgery. We randomly selected 98 elderly patients with lung cancer who were admitted to our hospital and underwent surgery from January 2022 to September 2023 as study subjects. The control group received conventional care during the perioperative period, and the intervention group received ERAS-guided care measures. The differences in perioperative-related indices, pulmonary function, pain level, inflammatory factors, and postoperative complication rates between these 2 groups were compared. The postoperative extubation time, the activity time since getting out of bad and hospital stay were lower in the observation group than those in the control group (P < .05). At 3 days postoperatively, the FEV1, forced vital capacity and maximum ventilation volume of these 2 groups were lower than those of their same groups before surgery, and those of the observation group were higher than those of the control group (P < .05). At 3 days postoperatively, the numerical rating scale in both groups were lower than those of their same groups at 6 hours postoperatively, and the numerical rating scale of the observation group was lower than that of the control group (P < .05). At 3 days postoperatively, tumor necrosis factor-α, IL-6, and CRP in both groups were higher than those in their same groups before surgery, and those of the observation group was lower than those of the control group (P < .05). The incidence of postoperative complications in the observation group was lower than that in the control group (P < .05). ERAS applied in the perioperative period of elderly lung cancer patients undergoing surgery can shorten the hospital stay, promote the postoperative recovery on pulmonary function, alleviate inflammation, and reduce the risk of postoperative complications.