A Bandgap-Tuned Tetragonal Perovskite as Zero-Strain Anode for Potassium-Ion Batteries.

PIBs are emerging as a promising energy storage system due to high abundance of potassium resources and theoretical energy density, however, progress of PIBs is severely hindered by structural instability and poor cycling of anode material during continual insertion and extraction of larger-sized K+. Hence, developing anode material with structural stability and stable cycling remains a great challenge. Herein, bandgap-tuned Mo-doped and carbon-coated lead titanate (CMPTO) with zero-strain K+ storage is presented as ultra-stable PIBs anode. Mo doping introduces narrowed bandgap and optimized crystal lattice for enhanced intrinsic electron and ion transfer. Demonstrated by in situ XRD characterizations, the crystal structure stays stable with unchanged peak positions, fully revealing zero-strain characteristic of CMPTO anode during potassium storage for stable cyclic capability. Ultimately, CMPTO anode achieved ultra-stable cycling performance of 7000 cycles at 500 mA g-1 with high capacity retention of 90% and considerable specific capacity of 130.9 mAh g-1 after 600 cycles at 100 mA g-1; with relatively large density, CMPTO realized eminent volumetric capacity of 1111.09 mAh cm-3 and ultra-long cycling life of 10000 cycles at 7041 mA cm-3. This work introduces a promisingly new route into developing anode materials with ultra-stable performance for PIBs.

Hydrophobic modification enhances the microstructure stability of the catalyst layer in alkaline polymer electrolyte fuel cells.

Alkaline polymer electrolyte fuel cells (APEFCs) have achieved notable advancements in peak power density, yet their durability during long-term operation remains a significant challenge. It has been recognized that increasing the hydrophobicity of the catalyst layer can effectively alleviate the performance degradation. However, a microscopic view of how hydrophobicity contributes to the stability of the catalyst layer microstructure is not clear. Here, we construct a membrane electrode assembly (MEA) with enhanced structural stability and durability by incorporating polytetrafluoroethylene (PTFE) particles into the catalyst layer. MEAs modified by this approach exhibit stabilized voltage platforms in current step tests and reduced hysteresis in current-voltage polarization curves during operation, indicating the critical role of PTFE in the removal of the excess water within the catalyst layer. Fuel cells with PTFE modification show more than 45% increase in electrochemical durability. By characterizing with field-emission scanning electron microscopy (FE-SEM) the surface and the internal microstructures of MEAs after durability tests, we find that the catalyst layers modified by PTFE experience much less reduction in porosity and less agglomeration of the solid components. These findings elucidate the microscopic mechanisms by which hydrophobicity promotes a more stable catalyst layer structure, thereby enhancing the durability of APEFCs. This research advances our understanding of hydrophobicity's impact on catalyst layer stability and offers a practical method to enhance the durability of APEFCs.

PD-L1 induces autophagy and primary resistance to EGFR-TKIs in EGFR-mutant lung adenocarcinoma via the MAPK signaling pathway.

Resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is a significant cause of treatment failure and cancer recurrence in non-small cell lung cancer (NSCLC). Approximately 30% of patients with EGFR-activating mutations exhibit primary resistance to EGFR-TKIs. However, the potential mechanisms of primary resistance to EGFR-TKIs remain poorly understood. Recent studies have shown that increased expression of programmed death ligand-1 (PD-L1) is associated with EGFR-TKIs resistance. Therefore, the present study aimed to investigate the mechanism of PD-L1 in primary resistance to EGFR-TKIs in EGFR-mutant lung adenocarcinoma (LUAD) cells. We found that PD-L1 was associated with poor prognosis in patients with EGFR-mutant LUAD, while the combination of EGFR-TKIs with chemotherapy could improve its therapeutic efficacy. In vitro and in vivo experiments revealed that PD-L1 promoted the proliferation and autophagy and inhibited the apoptosis of LUAD cells. Mechanistic studies demonstrated that upregulation of PD-L1 was critical in inducing autophagy through the mitogen-activated protein kinase (MAPK) signaling pathway, which was beneficial for tumor progression and the development of gefitinib resistance. Furthermore, we found that gefitinib combined with pemetrexed could synergistically enhance antitumor efficacy in PD-L1-overexpression LUAD cells. Overall, our study demonstrated that PD-L1 contributed to primary resistance to EGFR-TKIs in EGFR-mutant LUAD cells, which may be mediated by inducing autophagy via the MAPK signaling pathway. These findings not only help improve the prognosis of patients with EGFR-mutant LUAD but also provide a reference for the research of other cancer types.

Advances in the application of non-contact temperature measurement technology for aero-engine blade.

The advancement of the aviation sector has made the temperature measurement technology for aero-engine turbine blades essential for maintaining the engine's safe and steady performance. The non-contact temperature measurement technology is a trending research focus in turbine blade temperature measurement due to its benefits of not requiring direct touch with the object being measured and its suitability for high-temperature and high-speed conditions. This paper provides a concise overview of various key non-contact temperature measurement methods for aero-engines, such as fluorescence temperature measurement, fiber-optic temperature measurement, and radiation temperature measurement. It discusses the temperature measurement principle, technical characteristics, and the current research status both domestically and internationally. Based on this, this Review further discusses the main challenges faced by the non-contact temperature measurement technology and the development trend of the future.

Memristive True Random Number Generator for Security Applications.

This study explores memristor-based true random number generators (TRNGs) through their evolution and optimization, stemming from the concept of memristors first introduced by Leon Chua in 1971 and realized in 2008. We will consider memristor TRNGs coming from various entropy sources for producing high-quality random numbers. However, we must take into account both their strengths and weaknesses. The comparison with CMOS-based TRNGs will serve as an illustration that memristor TRNGs stand out due to their simpler circuits and lower power consumption- thus leading us into a case study involving electroless YMnO3 (YMO) memristors as TRNG entropy sources that demonstrate good security properties by being able to produce unpredictable random numbers effectively. The end of our analysis sees us pinpointing challenges: post-processing algorithm optimization coupled with ensuring reliability over time for memristor-based TRNGs aimed at next-generation security applications.

A preliminary randomized controlled study of the PEERS® program for Taiwanese autistic adolescents: The effectiveness on reducing school bullying and enhancing social function.

Individuals with autism spectrum disorder (ASD) often experience lifelong social communication challenges and are more vulnerable to school bullying. Addressing their social difficulties and school bullying requires evidence-based interventions. PEERS® (Program for the Education and Enrichment of Relational Skills) was adapted and translated for Taiwanese adolescents. This randomized controlled study aimed to examine the effectiveness of the Taiwanese version of PEERS® in reducing school bullying and enhancing social function among autistic adolescents. Twenty-one autistic adolescents (mean age 14.29 ± 1.67 years; female n = 733.33%) were randomized to a treatment group (TG, n = 10) or a delayed treatment control group (DTG, n = 11). The outcome measures (school bullying, social challenges, social skills knowledge, and social skills performance) were assessed at baseline, post-treatment, and follow-up. The group and time interaction analyses revealed greater magnitudes of reduction in general school bullying (p < 0.001), victimization (p < 0.001), perpetration (p = 0.012), social challenges (p = 0.001), and peer conflicts (p < 0.001), and improvement in social knowledge (p < 0.001) in the TG group than the DTG group. The findings suggest that the PEERS® program tailored for Taiwanese adolescents is effective in reducing school bullying, decreasing social challenges, and enhancing social skills among autistic adolescents, with very large effect sizes (Cohen's d ranging from 1.19 to 2.88). Consequently, participation in the PEERS® program is recommended for adolescents with social difficulties to improve their social communication and interactions to offset school bullying and other social challenges related to adverse outcomes.

Energy Intake and Dietary Glycemic Load in Late Morning and Risk of Type 2 Diabetes: The Hispanic Community Health Study/Study of Latinos-A Multicenter Prospective Cohort Study.

OBJECTIVE: To evaluate the association between meal timing and type 2 diabetes risk in U.S. Hispanic/Latino adults. RESEARCH DESIGN AND METHODS: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a multicenter, community-based, prospective cohort study. This study included 8,868 HCHS/SOL adults without diabetes at baseline (2008-2011) and attending the visit 2 examination (2014-2017). Energy intake and glycemic load (GL) in each meal timing were assessed at baseline using two 24-h dietary recalls. Incident diabetes was identified through annual follow-up calls or at visit 2. Hazard ratios (HRs) for incident diabetes were estimated using Cox models, accounting for the complex survey design. RESULTS: The study population (50.9% female) had a baseline mean age of 39.0 (95% CI, 38.4-39.5) years. Over a median (range) follow-up of 5.8 (0.8-9.6) years, 1,262 incident diabetes cases were documented. Greater energy intake and GL in late morning (9:00-11:59 a.m.) were associated with a lower diabetes risk, whereas greater energy intake and GL in other meal timings were not. After accounting for diet quantity and quality, sociodemographic characteristics, lifestyle factors, and chronic conditions, the HRs were 0.94 (95% CI, 0.91-0.97) per 100-kcal energy intake increment and 0.93 (0.89-0.97) per 10-unit GL increment in late morning. Replacing energy intake or GL from early morning (6:00-8:59 a.m.), afternoon (12:00-5:59 p.m.), or evening (6:00-11:59 p.m.) with late-morning equivalents was associated with a comparably lower diabetes risk. CONCLUSIONS: This study identified late morning as a favorable meal timing in Hispanic/Latino adults, providing a novel perspective on type 2 diabetes prevention that warrants confirmation.

Identification of the conductivity type of single-walled carbon nanotubes via dual-modulation dielectric force microscopy.

The conductivity type is one of the most fundamental transport properties of semiconductors, which is usually identified by fabricating the field-effect transistor, the Hall-effect device, etc. However, it is challenging to obtain an Ohmic contact if the sample is down to nanometer-scale because of the small size and intrinsic heterogeneity. Noncontact dielectric force microscopy (DFM) can identify the conductivity type of the sample by applying a DC gate voltage to the tip, which is effective in tuning the accumulation or depletion of charge carriers. Here, we further developed a dual-modulation DFM, which simplified the conductivity type identification from multiple scan times under different DC gate voltages to a single scan under an AC gate voltage. Taking single-walled carbon nanotubes as testing samples, the semiconducting-type sample exhibits a more significant charge carrier accumulation/depletion under each half-period of the AC gate voltage than the metallic-type sample due to the stronger rectification effect. The charge carrier accumulation or depletion of the p-type sample is opposite to that of the n-type sample at the same half-period of the AC gate voltage because of the reversed charge carrier type.

An Active and Regenerable Nanometric High-Entropy Catalyst for Efficient Propane Dehydrogenation.

Propane dehydrogenation (PDH) is crucial for propylene production, but commercially employed Pt-based catalysts face susceptibility to deactivation due to the Pt sintering during reaction and regeneration steps. Here, we report a SiO2 supported nanometric (MnCoCuZnPt) high-entropy PDH catalyst with high activity and stability. The catalyst exhibited a super high propane conversion of 56.6% with 94% selectivity of propylene at 600 °C. The propylene productivity reached 68.5 molC3H6·gPt-1·h-1, nearly three times that of Pt/SiO2 (23.5 molC3H6·gPt-1·h-1) under a weight hourly space velocity of 60 h-1. In a high-entropy nanoparticle, Pt atoms were atomically dispersed through coordination with other metals and exhibited a positive charge, thereby showcasing remarkable catalytic activity. The high-entropy effect contributes to the catalyst a superior stability with a low deactivation constant of 0.0004 h-1 during 200 hours of reaction under the industrial gas composition at 550 °C. Such high-entropy PDH catalyst is easy regenerated through simple air combustion of deposited coke. After the fourth consecutive regeneration cycle, satisfactory catalytic stability was observed, and the element distribution of spent catalysts almost returned to their initial state, with no detectable Pt sintering. This work provides new insights into designing active, stable, and regenerable novel PDH catalysts.

The difference in core-surface temperature indicates the prognosis of heart failure patients.

Aim: To evaluate the difference between core temperature and surface temperature (ΔT) as an index for the prognosis of heart failure (HF). Patients & methods: Core temperature and surface temperature were measured in 253 patients with HF. The association of ΔT with prognostic indicators of HF was analyzed. Results: Patients with ΔT ≥2°C were more likely to have lower left ventricular ejection fraction and lower estimated glomerular filtration rate, higher levels of troponin T, brain natriuretic peptide and procalcitonin, and high blood urea nitrogen/creatinine ratio. The risk of death increased by 32% for a 1°C increase in ΔT and was 4.36-times higher in the ΔT ≥2°C group than in the ΔT <2°C group. Conclusion: ΔT may be used to predict the prognosis of patients with HF.

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The Challenge of a Recall Program from a Community-Based Hepatitis C Screening Campaign: The Effectiveness in HCV Microelimination.

The optimal strategy for the microelimination of HCV within community settings remains ambiguous. We evaluated the percentage of participants who achieved linkage to care (LTC) following the conclusion of a screening campaign and examined the diverse factors influencing LTC among these individuals. The effectiveness of recall intervention for the non-LTC population and its barriers were analyzed. We initiated an HCV patient recall program to identify HCV participants who might not be treated after the HCV screening campaign. The program staff recalled HCV participants who were lost to follow-up via telephone from March 2019 to June 2019. They were informed of HCV treatment's importance, efficacy, availability, and safety. Among 185 participants infected with HCV, 109 (58.9%) obtained LTC. Compared with those who had LTC, those without LTC were older, had lower education levels, were less aware of their HCV infection, less frequently lived in urban areas, and had less health insurance. At the end of the recall program, 125 (67.6%) persons had linkage to care. The proportion of LTC increased by 8.7%. In total, 119 persons had an HCV RNA test, and 82 (68.9%) had viremia. Of the 82 patients with viremia, 78 (95.1%) received antiviral therapy, and 76 (97.4%) achieved a sustained virological response. After a community screening campaign, 59% of participants with anti-HCV-positive tests had LTC. The recall program increased this by 9%. However, 32% of HCV participants still could not be linked to care. Outreach care for non-LTC patients is a method worth trying in order to achieve the microelimination of HCV in rural communities.

Electrifying HCOOH synthesis from CO2 building blocks over Cu-Bi nanorod arrays.

Precise electrochemical synthesis of commodity chemicals and fuels from CO2 building blocks provides a promising route to close the anthropogenic carbon cycle, in which renewable but intermittent electricity could be stored within the greenhouse gas molecules. Here, we report state-of-the-art CO2-to-HCOOH valorization performance over a multiscale optimized Cu-Bi cathodic architecture, delivering a formate Faradaic efficiency exceeding 95% within an aqueous electrolyzer, a C-basis HCOOH purity above 99.8% within a solid-state electrolyzer operated at 100 mA cm-2 for 200 h and an energy efficiency of 39.2%, as well as a tunable aqueous HCOOH concentration ranging from 2.7 to 92.1 wt%. Via a combined two-dimensional reaction phase diagram and finite element analysis, we highlight the role of local geometries of Cu and Bi in branching the adsorption strength for key intermediates like *COOH and *OCHO for CO2 reduction, while the crystal orbital Hamiltonian population analysis rationalizes the vital contribution from moderate binding strength of η2(O,O)-OCHO on Cu-doped Bi surface in promoting HCOOH electrosynthesis. The findings of this study not only shed light on the tuning knobs for precise CO2 valorization, but also provide a different research paradigm for advancing the activity and selectivity optimization in a broad range of electrosynthetic systems.

Web-Based Mindfulness-Based Cognitive Therapy for Adults With a History of Depression: Protocol for a Randomized Controlled Trial.

BACKGROUND: Depression poses a major threat to public health with an increasing prevalence in the United States. Mindfulness-based interventions, such as mindfulness-based cognitive therapy (MBCT), are effective methods for managing depression symptoms and may help fortify existing efforts to address the current disease burden. The in-person group format of MBCT, however, incurs barriers to care such as expenses, childcare needs, and transportation issues. Alternate delivery modalities such as MBCT delivered via the web can be investigated for their capacity to overcome these barriers and still reduce symptoms of depression with adequate feasibility and efficacy. OBJECTIVE: This study protocol aims to examine the feasibility and efficacy of MBCT delivered via the web for the treatment of depression. METHODS: To attain study aims, 2 phases will be implemented using a waitlist control design. A total of 128 eligible participants will be randomized into either an 8-week MBCT intervention group plus treatment as usual (MBCT + TAU; group 1) or an 8-week waitlist control group (group 2). In phase I (8 weeks), group 1 will complete the intervention and group 2 will proceed with TAU. In phase II (8 weeks), group 2 will complete the intervention and group 1 will continue with TAU until reaching an 8-week follow-up. TAU may consist of receiving psychotherapy, pharmacotherapy, or combined treatment. Data collection will be completed at baseline, 8 weeks (postintervention for group 1 and preintervention for group 2), and 16 weeks (follow-up for group 1, postintervention for group 2). The primary outcomes will include (1) current, residual, or chronic depression symptoms and (2) psychiatric distress. Secondary outcomes will include perceived stress and facets of mindfulness. The feasibility will be measured by assessing protocol adherence, retention, attendance, and engagement. Finally, the extent of mindfulness self-practice and executive functioning skills will be assessed as mediators of intervention outcomes. RESULTS: This study began screening and recruitment in December 2022. Data collection from the first cohort occurred in January 2023. By November 2023, a total of 30 participants were enrolled out of 224 who received screening. Data analysis began in February 2024, with an approximate publication of results by August 2024. Institutional review board approval took place on September 11, 2019. CONCLUSIONS: This trial will contribute to examining mindfulness-based interventions, delivered via the web, for improving current, residual, or chronic depression symptoms. It will (1) address the feasibility of MBCT delivered via the web; (2) contribute evidence regarding MBCT's efficacy in reducing depression symptoms and psychiatric distress; and (3) assess the impact of MBCT on several important secondary outcomes. Findings from this study will develop the understanding of the causal pathways between MBCT delivered via the web and depression symptoms further, elucidating the potential for future larger-scale designs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05347719; https://www.clinicaltrials.gov/ct2/show/NCT05347719. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53966.

Quantification of Resection Margin following Sublobar Resection in Lung Cancer Patients through Pre- and Post-Operative CT Image Comparison: Utilizing a CT-Based 3D Reconstruction Algorithm.

Sublobar resection has emerged as a standard treatment option for early-stage peripheral non-small cell lung cancer. Achieving an adequate resection margin is crucial to prevent local tumor recurrence. However, gross measurement of the resection margin may lack accuracy due to the elasticity of lung tissue and interobserver variability. Therefore, this study aimed to develop an objective measurement method, the CT-based 3D reconstruction algorithm, to quantify the resection margin following sublobar resection in lung cancer patients through pre- and post-operative CT image comparison. An automated subvascular matching technique was first developed to ensure accuracy and reproducibility in the matching process. Following the extraction of matched feature points, another key technique involves calculating the displacement field within the image. This is particularly important for mapping discontinuous deformation fields around the surgical resection area. A transformation based on thin-plate spline is used for medical image registration. Upon completing the final step of image registration, the distance at the resection margin was measured. After developing the CT-based 3D reconstruction algorithm, we included 12 cases for resection margin distance measurement, comprising 4 right middle lobectomies, 6 segmentectomies, and 2 wedge resections. The outcomes obtained with our method revealed that the target registration error for all cases was less than 2.5 mm. Our method demonstrated the feasibility of measuring the resection margin following sublobar resection in lung cancer patients through pre- and post-operative CT image comparison. Further validation with a multicenter, large cohort, and analysis of clinical outcome correlation is necessary in future studies.

Adipocyte secreted NRG4 ameliorates age-associated metabolic dysfunction.

With the progressive aging of society, there is an increasing prevalence of age-related diseases that pose a threat to the elderly's quality of life. Adipose tissue, a vital energy reservoir with endocrine functions, is one of the most vulnerable tissues in aging, which in turn influences systematic aging process, including metabolic dysfunction. However, the underlying mechanism is still poorly understood. In this study, we found that NRG4, a novel adipokine, is obviously decreased in adipocyte tissues and serums during aging. Moreover, delivered recombinant NRG4 protein (rNRG4) into aged mice can ameliorate age-associated insulin resistance, glucose disorders and other metabolic disfunction. In addition, rNRG4 treatment alleviates age-associated hepatic steatosis and sarcopenia, accompanied with altered gene signatures. Together, these results indicate that NRG4 plays a key role in the aging process and is a therapeutic target for the treatment of age-associated metabolic dysfunction.

Evaluation of paclitaxel-coated balloon angioplasty for the treatment of symptomatic intracranial in-stent restenosis.

Background: Symptomatic intracranial in-stent restenosis (sISR) poses a major challenge in the management of cerebrovascular diseases, often requiring effective and safe treatment options. Objectives: This study aims to evaluate the efficacy and safety of paclitaxel-coated balloon (PCB) angioplasty for treating sISR. Methods: We conducted a retrospective analysis of five patients aged 49-74 years, who were treated with PCB angioplasty between January 2017 and June 2022. Treatment procedures included pre-operative digital subtraction angiography, antiplatelet therapy, and the use of the SeQuent Please balloon. Patients received aspirin and clopidogrel prior to and after the procedure. Results: The procedure achieved a 100% success rate. The degree of ISR was significantly reduced from an average pre-operative rate of 72±18.9% to a post-operative rate of 34±8.22%. Long-term follow-up showed that the majority of patients did not experience restenosis, confirming the long-term effectiveness of the treatment. Conclusions: PCB angioplasty demonstrates significant potential as an effective and safe treatment option for patients with sISR, especially those considered to be at high risk. This study supports further investigation into PCB angioplasty as a standard treatment for sISR.

Deep Learning Analysis for Predicting Tumor Spread through Air Space in Early-Stage Lung Adenocarcinoma Pathology Images.

The presence of spread through air spaces (STASs) in early-stage lung adenocarcinoma is a significant prognostic factor associated with disease recurrence and poor outcomes. Although current STAS detection methods rely on pathological examinations, the advent of artificial intelligence (AI) offers opportunities for automated histopathological image analysis. This study developed a deep learning (DL) model for STAS prediction and investigated the correlation between the prediction results and patient outcomes. To develop the DL-based STAS prediction model, 1053 digital pathology whole-slide images (WSIs) from the competition dataset were enrolled in the training set, and 227 WSIs from the National Taiwan University Hospital were enrolled for external validation. A YOLOv5-based framework comprising preprocessing, candidate detection, false-positive reduction, and patient-based prediction was proposed for STAS prediction. The model achieved an area under the curve (AUC) of 0.83 in predicting STAS presence, with 72% accuracy, 81% sensitivity, and 63% specificity. Additionally, the DL model demonstrated a prognostic value in disease-free survival compared to that of pathological evaluation. These findings suggest that DL-based STAS prediction could serve as an adjunctive screening tool and facilitate clinical decision-making in patients with early-stage lung adenocarcinoma.

Prospective associations of occupational and leisure-time physical activity with risk of diabetes: a cohort study from the United States.

OBJECTIVES: Leisure-time physical activity (LTPA) can reduce the risk of incident diabetes, whereas the role of occupational physical activity (OPA) in developing diabetes is still unclear due to conflicting evidence. Moreover, the joint associations of OPA and LTPA with incident diabetes among US workers have not yet been systematically examined. The objective of this study was to assess the independent and joint associations of OPA and LTPA with incident diabetes. METHODS: This prospective cohort study included 1406 workers free from diabetes at baseline (2004-2006) from the national, population-based Mid-life in the United States (MIDUS) study. Associations of OPA and LTPA at baseline with incident diabetes during 9 years of follow-up were examined using Poisson regression models. High OPA was defined based on engagement in physical demands at work, and high LTPA was defined as participation in moderate or vigorous LTPA at least once per week. RESULTS: High OPA was associated with an increased risk of diabetes compared to low OPA (adjusted risk ratios and 95% confidence interval = 1.52 [1.04, 2.22]), while high LTPA was associated with a decreased risk of diabetes compared to low LTPA (0.66 [0.44, 0.97]). Diabetes risk was the highest among workers with high OPA and low LTPA (2.30 [1.30, 4.07]). CONCLUSIONS: In a national, population-based prospective cohort study of US workers, high OPA was associated with an elevated risk of diabetes, while high LTPA was associated with a decreased diabetes risk. The combination of high OPA and low LTPA exhibited the greatest risk of diabetes.

DNAJC24 acts directly with PCNA and promotes malignant progression of LUAD by activating phosphorylation of AKT.

Heat shock proteins (HSPs) are a group of highly conserved proteins found in a wide range of organisms. In recent years, members of the HSP family were overexpressed in various tumors and widely involved in oncogenesis, tumor development, and therapeutic resistance. In our previous study, DNAJC24, a member of the DNAJ/HSP40 family of HSPs, was found to be closely associated with the malignant phenotype of hepatocellular carcinoma. However, its relationship with other malignancies needs to be further explored. Herein, we demonstrated that DNAJC24 exhibited upregulated expression in LUAD tissue samples and predicted poor survival in LUAD patients. The upregulation of DNAJC24 expression promoted proliferation and invasion of LUAD cells in A549 and NCI-H1299 cell lines. Further studies revealed that DNAJC24 could regulate the PI3K/AKT signaling pathway by affecting AKT phosphorylation. In addition, a series of experiments such as Co-IP and mass spectrometry confirmed that DNAJC24 could directly interact with PCNA and promoted the malignant phenotypic transformation of LUAD. In conclusion, our results suggested that DNAJC24 played an important role in the progression of LUAD and may serve as a specific prognostic biomarker for LUAD patients. The DNAJC24/PCNA/AKT axis may be a potential target for future individualized and precise treatment of LUAD patients.

Tertiary lymphoid structures as a potential prognostic biomarker for combined hepatocellular-cholangiocarcinoma.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA), as a rare primary hepatic tumor, is challenging to accurately assess in terms of the clinical outcomes and prognostic risk factors in patients. This study aimed to clarify the function of tertiary lymphoid structure (TLS) status in predicting the outcome of cHCC-CCA and to preliminarily explore the possible mechanism of TLS formation. METHODS: The TLSs, with different spatial distributions and densities, of 137 cHCC-CCA were quantified, and their association with prognosis was assessed by Cox regression and Kaplan-Meier analyses. We further validated TLS possible efficacy in predicting immunotherapy responsiveness in two cHCC-CCA case reports. TLS composition and its relationship to CXCL12 expression were analysed by fluorescent multiplex immunohistochemistry. RESULTS: A high intratumoural TLS score was correlated with prolonged survival, whereas a high TLS density in adjacent tissue indicated a worse prognosis in cHCC-CCA. Mature TLSs were related to favorable outcomes and showed more CD8 + T cells infiltrating tumor tissues. We further divided the cHCC-CCA patients into four immune grades by combining the peri-TLS and intra-TLS, and these grades were an independent prognostic factor. In addition, our reported cases suggested a potential value of TLS in predicting immunotherapy response in cHCC-CCA patients. Our findings suggested that CXCL12 expression in cHCC-CCA tissue was significantly correlated with TLS presence. CONCLUSION: The spatial distribution and density of TLSs revealing the characteristics of the cHCC-CCA immune microenvironment, significantly correlated with prognosis and provided a potential immunotherapy response biomarker for cHCC-CCA.