Comparison of long-term quality of life and their predictors in survivors between paediatric and adult nasopharyngeal carcinoma in the intensity-modulated radiotherapy era.

BACKGROUND: To compare the differences in long-term quality of life (QoL) between survivors of paediatric and adult patients with nasopharyngeal carcinoma (NPC) and assess the clinical factors that predict long-term QoL. METHODS: We enrolled 420 long-term NPC survivors who were alive for at least 8 years after treatment, including 195 paediatric and 225 adult patients diagnosed and treated with intensity-modulated radiotherapy (IMRT) at Sun Yat-sen University Cancer Centre (SYSUCC) between 2011 and 2015. Data on clinical factors and EORTC QLQ-C30 were collected from all participants. The QoL of paediatric and adult NPC survivors was compared. RESULTS: The paediatric group had significantly better outcomes in global health status (paediatric: 80.2 ± 12.7; adult: 77.2 ± 11.5; P = 0.027), physical function (paediatric: 98.5 ± 4.6; adult: 95.1 ± 7.0; P < 0.001), role function (paediatric: 97.0 ± 9.2; adult: 90.5 ± 15.2; P < 0.001), social function (paediatric: 96.0 ± 8.9; adult: 93.5 ± 11.8; P = 0.038), insomnia (paediatric: 1.9 ± 7.8; adult: 13.1 ± 22.3; P < 0.001), constipation (paediatric: 1.3 ± 7.5; adult: 8.0 ± 17.4; P < 0.001), diarrhea (paediatric: 0.7 ± 4.6; adult: 2.8 ± 9.3; P = 0.010), and financial difficulties (paediatric: 1.9 ± 7.8; adult: 11.0 ± 19.8; P < 0.001), but poorer cognitive function (paediatric: 88.3 ± 9.9; adult: 93.8 ± 12.6; P < 0.001) than the adult group. Pretreatment clinical factors, including T stage, N stage, and pre-treatment EBV (Epstein-Barr Virus) DNA, showed a strong association with QoL. However, the factors that affected the QoL outcomes differed between the two groups. In survivors of paediatric cancer, global health status/QoL was strongly correlated with T stage (P < 0.001) and clinical stage (P = 0.018), whereas it was strongly correlated with pre-treatment EBV DNA (P = 0.008) in adults. CONCLUSION: Paediatric survivors of NPC have a significantly better QoL than adult NPC survivors. Moreover, pre-treatment T stage, N stage, and EBV DNA significantly influenced the overall health status of the survivors. These results highlight the need to tailor care to both age groups to promote better long-term health outcomes.

Comparison of pathologic response and survival outcomes between neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant immunochemotherapy (nICT) in patients with locally advanced esophageal squamous cell carcinoma: a propensity score-matched analysis.

BACKGROUND: In locally advanced, operable esophageal squamous cell carcinoma (ESCC), neoadjuvant immunochemotherapy (nICT) has shown results that are somewhat comparable to those of standard neoadjuvant chemoradiotherapy (nCRT). The impact of these neoadjuvant treatments on survival outcomes, however, has yet to be elucidated. METHODS: This study included 489 patients with locally advanced ESCC who underwent surgery at Sichuan Cancer Hospital after receiving neoadjuvant treatment between June 2017 and September 2023. Patients were categorized into nCRT and nICT groups based on whether they received neoadjuvant treatment. To mitigate potential biases and balance covariates between the two cohorts, 1:2 propensity score matching (PSM) was conducted using a caliper width of 0.05. RESULTS: After PSM, the baseline characteristics of the 360 patients remained balanced between the two groups. The findings indicated a superior pathological response in the nCRT group, as evidenced by significantly greater rates of complete response (32.87% vs 14.58%, P < 0.001) and favorable tumor regression grade (TRG), as well as reduced ypT stages and less perineural and angioinvasion, despite comparable ypN stages. Despite the improvement in complete pathological response (pCR) in the nCRT group, the 3-year disease-free survival (DFS) and overall survival (OS) rates did not significantly differ between the groups (DFS: 58.32% vs 56.16%, P = 0.67; OS: 69.96% vs 71.99%, P = 0.99). Crucially, The nICT group showed a lower incidence of grade 3 and 4 adverse events in Leukopenia (2.8% vs 29%; P < 0.001) and Neutropenia (2.8% vs 24%; P < 0.001) during neoadjuvant treatment, comparing with nCRT group. CONCLUSIONS: Our preliminary findings suggest that nICT followed by surgery offers comparable survival rates to nCRT, despite being less effective in pathologic outcomes. Nonetheless, nICT is a safe and feasible strategy for locally advanced ESCC, warranting further exploration to understand its impact on long-term survival.

Analysis of dislocation defects in compositionally step-graded α-(Al x Ga1-x )2O3 layers.

The ultra-wide bandgap semiconductor α-Ga2O3 can be heteroepitaxially grown on a sapphire substrate. However, due to a lattice mismatch of about 4.6% with a sapphire substrate, many dislocation defects occur in α-Ga2O3 films. To reduce the dislocation density, compositionally step-graded α-(Al x Ga1-x )2O3 layers were fabricated on a c-plane sapphire substrate using mist CVD. TEM measurements revealed few dislocations in the initial layer of α-(Al0.96Ga0.04)2O3, but numerous dislocations were observed in the subsequent layer of α-(Al0.84Ga0.16)2O3. However, the step-graded α-(Al x Ga1-x )2O3 layers exhibited bending of the dislocations under both compressive and tensile strains due to compositional differences of α-(Al x Ga1-x )2O3, resulting in about 50% reduction of the dislocation density in the high-Ga-composition layer of α-(Al x Ga1-x )2O3. The introduction of multiple 50 nm α-Ga2O3 layers into the compositionally step-graded α-(Al x Ga1-x )2O3 layers resulted in a notable reduction in dislocation defects at the interface between the sandwiched α-Ga2O3 layers. It is assumed that the dislocations were bent by the strain caused by the composition change, resulting in a decrease in the number of dislocations. It is anticipated that further reduction of dislocation density will be achieved by optimizing the composition change and thicknesses of layers that provide effective strain for dislocation bending, and by stacking these layers.

Analysis of Influencing Factors and Construction of Predictive Model for Persistent Cough After Lung Cancer Resection Under Thoracoscopy.

Objective: This study aims to explore the influencing factors of cough after pulmonary resection (CAP) after thoracoscopic lung resection in lung cancer patients and to develop a predictive model. Methods: A total of 374 lung cancer patients who underwent lung resection in our hospital from March 2020 to October 2023 were randomly divided into a modeling group (n=262) and a validation group (n=112). Based on the occurrence of CAP in the modeling group, the patients were divided into a CAP group (n=85) and a non-CAP group (n=177). Multivariate Logistic regression analysis was used to identify the influencing factors of CAP in lung cancer patients. A nomogram model for predicting the risk of CAP was constructed using R4.3.1. The consistency of the model's predictions was evaluated, and a clinical decision curve (DCA) was drawn to assess the clinical utility of the nomogram. The predictive performance of the model was evaluated using ROC curves and the Hosmer-Lemeshow test. Results: Multivariate Logistic regression analysis showed that smoking history (OR=6.285, 95% CI: 3.031-13.036), preoperative respiratory function training (OR=20.293, 95% CI: 7.518-54.779), surgical scope (OR=20.667, 95% CI: 7.734-55.228), and peribronchial lymph node dissection (OR=5.883, 95% CI: 2.829-12.235) were significant influencing factors of CAP in lung cancer patients (P<0.05). ROC curves indicated good discriminatory power of the model, and the Hosmer-Lemeshow test showed a high degree of agreement between predicted and actual probabilities. The DCA curve revealed that the nomogram model had high clinical value when the high-risk threshold was between 0.08 and 0.98. Conclusion: The nomogram model based on smoking history, preoperative respiratory function training, surgical scope, and peribronchial lymph node dissection has high predictive performance for CAP in lung cancer patients. It is useful for clinical prediction, guiding preoperative preparation, and postoperative care.

Radiomics Combined with ACR TI-RADS for Thyroid Nodules: Diagnostic Performance, Unnecessary Biopsy Rate, and Nomogram Construction.

RATIONALE AND OBJECTIVES: To develop a radiomics model with enhanced diagnostic performance, reduced unnecessary fine needle aspiration biopsy (FNA) rate, and improved clinical net benefit for thyroid nodules. METHODS: We conducted a retrospective study of 217 thyroid nodules. Lesions were divided into training (n = 152) and verification (n = 65) cohorts. Three radiomics scores were derived from B-mode ultrasound (B-US) and strain elastography (SE) images, alone and in combination. A radiomics nomogram was constructed by combining high-frequency ultrasonic features and the best-performing radiomics score. The area under the receiver operating characteristic curve (AUC), unnecessary FNA rate, and decision curve analysis (DCA) results for the nomogram were compared to those obtained with the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) score and the combined TI-RADS+SE+ contrast-enhanced ultrasound (CEUS) advanced clinical score. RESULTS: The three radiomics scores (B-US, SE, B-US+SE) achieved training AUCs of 0.753 (0.668-0.825), 0.761 (0.674-0.838), and 0.795 (0.715-0.871), and validation AUCs of 0.732 (0.579-0.867), 0.753 (0.609-0.892), and 0.752 (0.592-0.899) respectively. The AUC of the nomogram for the entire patient cohort was 0.909 (0.864-0.954), which was higher than that of the ACR TI-RADS score (P < 0.001) and equivalent to the TI-RADS+SE+CEUS score (P = 0.753). Similarly, the unnecessary FNA rate of the radiomics nomogram was significantly lower than that of the ACR TI-RADS score (P = 0.007) and equivalent to the TI-RADS+SE+CEUS score (P = 0.457). DCA also showed that the radiomics nomogram brought more net clinical benefit than the ACR TI-RADS score but was similar to that of the TI-RADS+SE+CEUS score. CONCLUSION: The radiomics nomogram developed in this study can be used as an objective, accurate, cost-effective, and noninvasive method for the characterization of thyroid nodules.

Burden of biliary tract carcinoma in China (1990-2021): Findings from the 2021 Global Burden of Disease Study.

Biliary tract carcinoma (BTC) is a group of malignant tumors that originate in the digestive system and occurs with a high incidence in China. Few consistent and comparable assessments of BTC disease burden have been conducted at national or subnational levels, and little is known about the demographic, temporal, and geographic patterns of epidemiological characteristics and disease burden of BTC in China. The incidence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs) due to premature death and years lived with disability (YLDs) of BTC were comprehensively examined by age, sex, and calendar year in the Chinese population, using the methodological framework and analytical strategies used for the 2021 Global Burden of Disease study. All-age incidence increased from 17,077 to 51,720 between 1990 and 2021, and the age-standardized incidence rate rose by 13.62%; all-age deaths increased from 17,251 to 37,833, but the age-standardized mortality rate fell by nearly one-fifth. The DALYs rose by 89.57% while the age-standardized DALY rate fell by 23.24%. Variations of the tendencies in BTC burden were found between sexes and age groups. Data for each provincial region indicate that coastal eastern provincial regions have higher incidence and YLD levels, whereas northern provincial regions have higher mortality, DALY, and YLL levels. The proportions of DALYs attributable to high body mass index (BMI) illustrate the growing attribution obesity has made, and high BMI usually puts more burden on northern provincial regions. These results provide evidence to support precise, targeted, and customed public health strategies aimed at enhancing biliary tract health among the Chinese population.

Bioinformatics and biomedical informatics with ChatGPT: Year one review.

The year 2023 marked a significant surge in the exploration of applying large language model chatbots, notably Chat Generative Pre-trained Transformer (ChatGPT), across various disciplines. We surveyed the application of ChatGPT in bioinformatics and biomedical informatics throughout the year, covering omics, genetics, biomedical text mining, drug discovery, biomedical image understanding, bioinformatics programming, and bioinformatics education. Our survey delineates the current strengths and limitations of this chatbot in bioinformatics and offers insights into potential avenues for future developments.

Cation/Anion Doping Strategy for Na4MnV(PO4)3 with High Energy Density and Long Cycling Life through Construction by Aspergillus niger.

Na4MnV(PO4)3 (NMVP) has gained attention for its high redox potential, good cycling stability, and competitive price but suffers from poor intrinsic electronic conductivity and Jahn-Teller effect from Mn3+. In this work, cation/anion doping strategy was used for Aspergillus niger-bioderived carbon-coated NMVP (NMVP/AN) to improve the structural stability and electrochemical performance, where Al3+ doping inhibited the dissolution of Mn and enhanced the Mn3+/Mn2+ redox pair activity; besides, F- doping not only weakens the Na2-O bond but also endows the hierarchical and porous structure of NMVP/AN, which led to a more rapid and fluid transfer of Na+. The elaborately designed Na3.9Mn0.9Al0.1V(PO4)3/AN (NMAVP/AN) exhibits 105.9 mA h g-1 at 0.5 C, and the as-prepared Na3.1MnV(PO3.7F0.3)3/AN (NMVPF/AN) delivers 104.1 mA h g-1 at 5 C. Further demonstration of the hard carbon//NMAVP/AN full cell manifests the good potential of Al3+-doped NMVP/AN for practical applications (100.6 mA h g-1 at 1 C). These findings open up the possibility of unlocking the high-performance Na superionic conductor (NASICON).

A Novel Rhodamine B Derivative as a "Turn-on" Fluorescent Sensor for Cu2+ with High Selectivity and Sensitivity.

The number of "turn-on" fluorescent probes for Cu2+ is relatively limited, and interference from other metal cations presents a significant challenge for these sensors. In this study, we synthesized and characterized a rhodamine B-based sensor, designated as RBHP, using 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone (PMBP) and rhodamine B hydrazide. Selectivity, sensitivity, solvent effects, water content, and pH of RBHP in relation to Cu²âº were conducted. RBHP exhibited an exceptionally low fluorescence background signal in acetonitrile and demonstrated a "turn-on" fluorescent response to Cu²âº. The PMBP-based acylhydrazone moiety and acetonitrile as the detection solvent are crucial for the selective detection. RBHP shows potential as a highly selective and sensitive fluorescent sensor for Cu2+.

Perchlorate-tolerant bacterial strains isolated from the Mars-analog Qaidam Basin soils exposed to Earth's near space.

Earth's lower near space of 20-40 km above sea level with polyextreme conditions serves as a unique Mars analog for astrobiological research to investigate the limits of life on Earth and planetary protection considerations for Mars exploration. In this study, we exposed Mars-like desert regolith to near space at a float altitude of ~35 km and isolated four bacterial strains after exposure. In addition to stress tolerance to extreme environmental stressors, these strains represent a remarkable tolerance to perchlorate that is widespread in present-day Martian soils. These extremophilic bacterial strains screened through near-space exposure could serve as promising candidates for future astrobiological research in space stations or in laboratory-based planetary simulation environments.

Uridine triphosphate hybrid catalyst for carbon­carbon bond formation reactions with enhanced enantioselectivity by mercury(II) ions.

DNA hybrid catalysts are constructed by embedding active metal species into the chiral scaffolds of DNA, which have been successfully applied to some important aqueous-phase enantioselective transformations. Owing to simple components and inherent chirality, nucleotide hybrid catalysts are emerging in response to soving the unclear locations of catalytic centers and the plausible catalytic mechanisms in DNA-based asymmetric catalysis. However, the tertiary structure of nucleotides lacks tunability, severely impeding further design of nucleotide hybrid catalysts for potential applications. To this end, a design strategy for tunable nucleotide hybrid catalysts is put forward by introducing metal-mediated base pairs. Herein, we found that the formation of uracil­mercury(II)-uracil (U-Hg2+-U) base pairs could enhance the enantioselectivity in uracil-containing nucleotide-based asymmetric reactions. Compared with uracil triphosphate (UTP) complexing with Cu2+ ions (UTP∙Cu2+), the presence of Hg2+ ions gave rise to an increased enantiomeric excess (ee) of 38 % in Diels-Alder reactions and 22 % ee in Michael reactions. The Hg2+-tuning behaviors of UTP hybrid catalyst have been demonstrated to largely depend on nucleotides, Hg2+ concentrations, metal cofactors, additives and reaction types. Based on ultraviolet-visible, circular dichroism and nuclear magnetic resonance spectroscopic techniques, the chiral enhancement of Hg2+-containing UTP hybrid catalyst is proved to largely depend on the formation of U-Hg2+-U base pairs and the plausible cross-linked structure of UTP-Hg2+-UTP/Cu2+ assembly. This work provides a tunable strategy based on the concept of metal-mediated base pairs, allowing further design of potent oligonucleotide-based catalysts for other enantioselective reactions.

Why does distilled liquor (Baijiu) have a yellowish color: A comprehensive analysis.

Elucidating the mechanisms underlying Baijiu production is a shared aspiration among academic groups specializing in the field of Baijiu research. This study comprehensively examined the mechanisms underlying the yellowish coloration of Baijiu through a synergistic application of chromatographic, spectroscopic, and physical methodologies. Aging of Baijiu in earthenware pots involves the infiltration of mineral ions such as iron, aluminum, and calcium; however, these ions are detected at extremely low concentrations and are therefore not linked to the development of Baijiu's yellowish color. Instead, the yellowish coloration is attributed to the diverse colorants generated during the high-temperature fermentation of small-molecule sugars derived from the saccharification of grain materials. Although these colorants exist in minimal quantities and exhibit spectral absorption peaks ranging from 300 to 450 nm, their overlapping spectra collectively contribute to the light-absorbing properties of Baijiu across a broad wavelength range, ultimately accounting for its characteristic yellowish color.

Case report: A novel FBXW7 gene variant causes global developmental delay.

Objective: To investigate a case of neurodevelopmental disorder caused by mutation of FBXW7. Methods: Clinical data were collected from the patient, trio-WES (whole-exome sequencing) was performed on the patient and his parents (trio), and the results were verified by Sanger sequencing. RESULTS: The patient was a 2-year and 1-month old male who presented with facial dysmorphism (prominent forehead, ocular hypertelorism, and low nasal bridge), global developmental delay, language impairment, hypertonia, labial hemangioma, hydrocele, and overgrowth. The trio-WES confirmed that the child had a pathogenic de novo FBXW7 gene variant, c.1612C>T (p.G1n538*), a heretofore unreported locus. Conclusion: This case of developmental delay, hypotonia, and impaired language (OMIM: #620012) related to a mutation in FBXW7, is a rare genetic disorder, newly identified in recent years, and seldom reported. The presence of hypertonia, labial hemangioma, and hydrocele in this child suggests significant phenotypic heterogeneity of the disease, and the discovery of new mutant loci enriches the spectrum of pathogenic variants of the disease.

Circulating extracellular vesicles as novel biomarkers for pulmonary arterial hypertension in patients with systemic lupus erythematosus.

Introduction: Pulmonary arterial hypertension (PAH) is a serious complication of systemic lupus erythematosus (SLE) with increased mortality. A prothrombotic state may contribute to pathogenesis of SLE-PAH. Extracellular vesicles (EVs) are known to be associated with thrombosis. Here, we investigated circulating EVs and their associations with SLE-PAH. Methods: Eighteen SLE-PAH patients, 36 SLE-non-PAH patients, and 36 healthy controls (HCs) were enrolled. Flow cytometry was used to analyze circulating EVs from leukocytes (LEVs), red blood cells (REVs), platelets (PEVs), endothelial cells (EEVs), and Annexin V+ EVs with membrane phosphatidylserine (PS) exposure. Results: Plasma levels of all EV subgroups were elevated in SLE patients with or without PAH compared to HCs. Furthermore, plasma Annexin V+ EVs, LEVs, PEVs, REVs, EEVs, and Annexin V+ REVs were significantly elevated in SLE-PAH patients compared to SLE-non-PAH patients. Additionally, PAH patients with moderate/high SLE showed a significant increase in LEVs, PEVs, REVs, Annexin V+ EVs, and Annexin V+ REVs compared to SLE-non-PAH patients. However, PAH patients with inactive/mild SLE only exhibited elevations in Annexin V+ EVs, REVs, and Annexin V+ REVs. In the SLE-PAH patients, EEVs were positively correlated with pulmonary arterial systolic pressure, while PEVs and EEVs were positively correlated with right ventricular diameter. Moreover, the receiver operating characteristic curve indicated that Annexin V+ EVs, LEVs, PEVs, REVs, EEVs and Annexin V+ REVs could predict the presence of PAH in SLE patients. Importantly, multivariate logistic regression analysis showed that circulating levels of LEVs or REVs, anti-nRNP antibody, and serositis were independent risk factors for PAH in SLE patients. Discussion: Findings reveal that specific subgroups of circulating EVs contribute to the hypercoagulation state and the severity of SLE-PAH. Higher plasma levels of LEVs or REVs may serve as biomarkers for SLE-PAH.

Machine Learning Model to Predict Early Recurrence in Patients with Perihilar Cholangiocarcinoma Planned Treatment with Curative Resection: A Multicenter Study.

BACKGROUND & AIMS: Early recurrence is the leading cause of death for patients with perihilar cholangiocarcinoma (pCCA) after surgery. Identifying high-risk patients preoperatively is important. This study aimed to construct a preoperative prediction model for the early recurrence of pCCA patients planned treatment with curative resection. METHODS: This study ultimately enrolled 400 pCCA patients after curative resection in five hospitals between 2013 and 2019. They were randomly divided into training (n=300) and testing groups (n=100) at a ratio of 3:1. Associated variables were identified via LASSO regression. Four machine learning models were constructed: support vector machine (SVM), random forest (RF), logistic regression, and K-nearest neighbors (KNN). The predictive ability of the models was evaluated via receiver operating characteristic (ROC) curves, precision-recall curve (PRC) curves, and decision curve analysis (DCA). KaplanMeier survival curves were drawn for the high/low-risk population. RESULTS: Five factors, CA19-9, tumor size, total bilirubin, hepatic artery invasion, and portal vein invasion, were selected by LASSO regression. In both the training and testing groups, the ROC curve (AUC: 0.983 vs 0.952) and the PRC (0.981 vs 0.939) showed that RF was the best. The cutoff value for distinguishing high- and low-risk patients was 0.51. KM survival curves revealed that in both groups, there was a significant difference in RFS between high- and low-risk patients (P<0.001). CONCLUSION: This study used preoperative variables from a large, multicenter database to construct a machine learning model that could effectively predict the early recurrence of pCCA patients planned treatment with curative resection and help clinicians make better treatment decisions.

Breast Cancer Patient Flap Management After Mastectomy: A Best Practice Implementation Project.

BACKGROUND: Breast cancer is a prevalent malignancy in women, with mastectomy as the main surgery. Common postmastectomy complications are seroma (15%-81%), infections (2.9%-3.8%), and flap necrosis (10%-18%), severely impacting quality of life and costs. However, there's a lack of standardized flap care protocols and limited staff knowledge. OBJECTIVES: This study aims to apply best evidence for flap management post-mastectomy to standardize practices, reduce complications, and enhance patient's quality of life. METHODS: This project followed JBI PACES and GRiP principles, implementing evidence-based practices in a Chinese tertiary hospital between January and May 2023. It entailed evidence identification, integration into clinical context, protocol development, baseline audits, barrier/enabler analysis. The study compared pre- and post-evidence implementation rates of flap complications, healthcare staff's knowledge/skill scores on mastectomy flap management, and audit indicator adherence by both staff and patients. RESULTS: After evidence application, flap ischemia/necrosis rates dropped from 8.57% to 5.56% (P < .001), wound infection rates after surgery reduced from 5.71% to 2.78% (P < .001), and seroma rates decreased from 17.14% to 2.78% (P < .001). Healthcare staff's knowledge and skill scores for flap management following mastectomy increased from 50.67 ±18.32 preimplementation to 98.33 ± 4.01 (t = -13.90, P < .001). Audit criterion compliance rates increased from 8.57% to 94.29% to between 91.67% and 100%, with statistically significant differences in all 15 criteria (P < .001). CONCLUSIONS: Evidence-based management of flaps after mastectomy improves healthcare staff's knowledge and skills, enhances nursing quality, effectively reduces flap complications in patients, and boosts their quality of life.

A Prime-Boost Vaccination Approach Induces Lung Resident Memory CD8+ T Cells Derived from Central Memory T Cells That Prevent Tumor Lung Metastasis.

Memory T cells play a key role in immune protection against cancer. Vaccine-induced tissue-resident memory T (TRM) cells in the lung have been shown to protect against lung metastasis. Identifying the source of lung TRM cells can help to improve strategies, preventing tumor metastasis. Here, we found that a prime-boost vaccination approach using intramuscular DNA vaccine priming, followed by intranasal live-attenuated influenza-vectored vaccine (LAIV) boosting induced higher frequencies of lung CD8+ TRM cells compared with other vaccination regimens. Vaccine-induced lung CD8+ TRM cells, but not circulating memory T cells, conferred significant protection against metastatic melanoma and mesothelioma. Central memory T (TCM) cells induced by the DNA vaccination were major precursors of lung TRM cells established after the intranasal LAIV boost. Single-cell RNA sequencing analysis indicated that transcriptional reprogramming of TCM cells for differentiation into TRM cells in the lungs started as early as day 2 post the LAIV boost. Intranasal LAIV altered the mucosal microenvironment to recruit TCM cells via CXCR3-dependent chemotaxis and induced CD8+ TRM-associated transcriptional programs. These results identified TCM cells as the source of vaccine-induced CD8+ TRM cells that protect against lung metastasis. Significance: Prime-boost vaccination shapes the mucosal microenvironment and reprograms central memory T cells to generate lung resident memory T cells that protect against lung metastasis, providing insights for the optimization of vaccine strategies.

Targeting both ferroptosis and pyroptosis may represent potential therapies for acute liver failure.

In this editorial, we comment on the article published in the recent issue of the World Journal of Gastroenterology. Acute liver failure (ALF) is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function. Ferroptosis and pyroptosis, cell death forms that can be initiated or blocked concurrently, can play significant roles in developing inflammation and various malignancies. However, their roles in ALF remain unclear. The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF, and revealed that the silent information regulator sirtuin 1 (SIRT1) inhibits both pathways through p53, dramatically reducing inflammation and protecting hepatocytes. This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF. Thus, we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms. Additionally, we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways, as well as examples of SIRT1 activators being used as disease treatment strategies, providing new insights into the therapy of ALF.