High-dose hyperfractionated simultaneous integrated boost radiotherapy versus standard-dose radiotherapy for limited-stage small-cell lung cancer in China: a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: For the past 20 years, twice-daily thoracic radiotherapy with concurrent chemotherapy has been the treatment of choice for limited-stage small-cell lung cancer (LS-SCLC), which has a poor prognosis. We aimed to assess the efficacy and safety of high-dose, accelerated, hyperfractionated, twice-daily thoracic radiotherapy (54 Gy in 30 fractions) versus standard-dose radiotherapy (45 Gy in 30 fractions) as a first-line treatment for LS-SCLC. METHODS: This open-label, randomised, phase 3 trial was performed at 16 public hospitals in China. The key inclusion criteria were patients aged 18-70 years, with histologically or cytologically confirmed LS-SCLC, who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and who were previously untreated or had received one course of cisplatin or carboplatin and etoposide. Eligible patients were randomly assigned (1:1) to receive volumetric-modulated arc radiotherapy (VMAT) of 45 Gy in 30 fractions to the gross tumour volume or VMAT with a simultaneous integrated boost of 54 Gy in 30 fractions to the gross tumour volume starting 0-42 days after the first chemotherapy course. Both groups received 10 fractions of twice-daily thoracic radiotherapy per week. The planning target volume was 45 Gy in 30 fractions in both groups. Patients with responsive disease received prophylactic cranial radiotherapy (25 Gy in 10 fractions). Randomisation was performed using a centralised interactive web response system, stratified by ECOG performance status, disease stage, previous chemotherapy course, and chemotherapy choice. The primary outcome was overall survival in the intention-to-treat population. Safety was analysed in the as-treated population. This study was registered at ClinicalTrials.gov, NCT03214003. FINDINGS: From June 30, 2017, to April 6, 2021, 224 patients (102 [46%] females and 122 [54%] males; median age 64 years [IQR 58-68]) were enrolled and randomly assigned to the 54 Gy group (n=108) or 45 Gy (n=116) group. The median follow-up was 46 months (IQR 33-56). The median overall survival was significantly longer in the 54 Gy group (60·7 months [95% CI 49·2-62·0]) than in the 45 Gy group (39·5 months [27·5-51·4]; hazard ratio 0·55 [95% CI 0·37-0·72]; p=0·003). Treatment was tolerable, and the chemotherapy-related and radiotherapy-related toxicities were similar between the groups. The grade 3-4 radiotherapy toxicities were oesophagitis (14 [13%] of 108 patients in the 54 Gy group vs 14 [12%] of 116 patients in the 45 Gy group; p=0·84) and pneumonitis (five [5%] of 108 patients vs seven [6%] of 116 patients; p=0·663). Only one treatment-related death occurred in the 54 Gy group (myocardial infarction). The study was prematurely terminated by an independent data safety monitoring board on April 30, 2021, based on evidence of sufficient clinical benefit. INTERPRETATION: Compared with standard-dose thoracic radiotherapy (45 Gy), high-dose radiotherapy (54 Gy) improved overall survival without increasing toxicity in a cohort of patients aged 18-70 years with LS-SCLC. Our results support the use of twice-daily accelerated thoracic radiotherapy (54 Gy) with concurrent chemotherapy as an alternative first-line LS-SCLC treatment option. FUNDING: Chinese Society of Clinical Oncology-Linghang Cancer Research, the Wu Jieping Medical Foundation, and Clinical Research Fund For Distinguished Young Scholars of Peking University Cancer Hospital and Beijing Municipal Administration of Hospitals Incubating Program.

Anlotinib hydrochloride consolidation after concurrent chemoradiotherapy in stage III non-small-cell lung cancer: a truncated, randomized, multicenter, clinical study (ALTER-L029).

Anlotinib is an antiangiogenic drug that shows good efficacy and safety in patients with advanced non-small-cell lung cancer (NSCLC). This study aimed to explore the efficacy and safety of anlotinib for consolidation therapy in patients with stage III locally advanced, unresectable NSCLC after concurrent chemoradiotherapy (cCRT). This was a randomized, parallel-controlled, open-label, multicenter, phase II trial of patients with unresectable/nonoperated NSCLC treated with cCRT. The participants were randomized 2:1 to the anlotinib or control group. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the disease control rate (DCR) and overall survival. This study was terminated early due to poor recruitment. Nine and two participants were randomly assigned to the anlotinib and control groups, respectively. One participant in the control group was excluded due to taking prohibited medications before the first efficacy evaluation. In the anlotinib group, the median age was 63 (range, 37-74) years. Two participants achieved partial response, six stable disease, and one progressive disease as best response. The DCR was 88.9%. The median PFS was 11.5 months, and the 12-month PFS rate was 33.9%. All related adverse events were grade 1 or 2. Two participants had a dose adjustment during the study. The evaluable data suggest that anlotinib alone was effective and tolerable in consolidation therapy after cCRT in patients with stage III unresectable NSCLC. The results need to be confirmed by a large-sample trial. This clinical trial was registered on www.clinicaltrials.gov (NCT03743129). Registration date: 6 September 2018.

Bibliometric Mapping of Psychological Flexibility Research: Trends and Future Directions.

In this article, we offer an exhaustive analysis of academic work on psychological flexibility using bibliometric techniques. We identify emerging trends in a dataset of 3535 scholarly articles from the Web of Science database. We highlight key publications, map out the field's intellectual framework, and anticipate future research avenues through co-citation and co-word analytics. The co-citation assessment revealed five distinct clusters, while the co-word analysis showed three. Although research regarding psychological flexibility has gained recent popularity, there remains a need for more scholarly initiatives to achieve a nuanced understanding of this subject.

PolyQ-expanded ataxin-2 aggregation impairs cellular processing-body homeostasis via sequestering the RNA helicase DDX6.

Ataxin-2 (Atx2) is a polyglutamine (polyQ) tract-containing RNA-binding protein, while its polyQ expansion may cause protein aggregation that is implicated in the pathogenesis of neurodegenerative diseases such as spinocerebellar ataxia type 2 (SCA2). However, the molecular mechanism underlying how Atx2 aggregation contributes to the proteinopathies remains elusive. Here, we investigated the influence of Atx2 aggregation on the assembly and functionality of cellular processing bodies (P-bodies) by using biochemical and fluorescence imaging approaches. We have revealed that polyQ-expanded (PQE) Atx2 sequesters the DEAD-box RNA helicase (DDX6), an essential component of P-bodies, into aggregates or puncta via some RNA sequences. The N-terminal like-Sm (LSm) domain of Atx2 (residues 82-184) and the C-terminal helicase domain of DDX6 are responsible for the interaction and specific sequestration. Moreover, sequestration of DDX6 may aggravate pre-mRNA mis-splicing, and interfere with the assembly of cellular P-bodies, releasing the endoribonuclease MARF1 that promotes mRNA decay and translational repression. Rescuing the DDX6 protein level can recover the assembly and functionality of P-bodies, preventing targeted mRNA from degradation. This study provides a line of evidence for sequestration of the P-body components and impairment of the P-body homeostasis in dysregulating RNA metabolism, which is implicated in the disease pathologies and a potential therapeutic target.

Enhancing employee performance through motivation: the mediating roles of green work environments and engagement in Jakarta's logistics sector.

This study aims to analyze the mediating role of employee engagement and the green work environment in the relationship between motivation and the performance of logistics company employees in Jakarta, Indonesia. Employing a causal quantitative research approach, we distributed 222 questionnaires among logistics employees from four surrounding cities in Jakarta, namely Bogor, Depok, Tangerang, and Bekasi. These questionnaires were adapted from past studies. The data were processed using Structural Equation Modeling (SEM) with Partial Least Squares. The results showed that employee performance in logistics companies was positively and significantly influenced by motivation. Furthermore, a green work environment and employee engagement were found to significantly mediate the relationship between motivation and performance. These findings underscore the importance of a green work environment and employee engagement in enhancing motivation and performance in logistics companies. The study implies that employee performance in logistics companies can be elevated through the provision of a green work environment, alongside fostering employee motivation and engagement.

Mapping the evolution of neurofeedback research: a bibliometric analysis of trends and future directions.

Introduction: This study conducts a bibliometric analysis on neurofeedback research to assess its current state and potential future developments. Methods: It examined 3,626 journal articles from the Web of Science (WoS) using co-citation and co-word methods. Results: The co-citation analysis identified three major clusters: "Real-Time fMRI Neurofeedback and Self-Regulation of Brain Activity," "EEG Neurofeedback and Cognitive Performance Enhancement," and "Treatment of ADHD Using Neurofeedback." The co-word analysis highlighted four key clusters: "Neurofeedback in Mental Health Research," "Brain-Computer Interfaces for Stroke Rehabilitation," "Neurofeedback for ADHD in Youth," and "Neural Mechanisms of Emotion and Self-Regulation with Advanced Neuroimaging. Discussion: This in-depth bibliometric study significantly enhances our understanding of the dynamic field of neurofeedback, indicating its potential in treating ADHD and improving performance. It offers non-invasive, ethical alternatives to conventional psychopharmacology and aligns with the trend toward personalized medicine, suggesting specialized solutions for mental health and rehabilitation as a growing focus in medical practice.

Exploration of lymph node recurrence patterns and delineation guidelines of radiation field in middle thoracic oesophageal carcinomas after radical surgery: a real-world study.

BACKGROUND: Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. METHODS: In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. RESULTS: From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. CONCLUSIONS: We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.

Total ginsenosides extend healthspan of aging Drosophila by suppressing imbalances in intestinal stem cells and microbiota.

BACKGROUND: Disruption of stem cell and microbial homeostasis accelerates the aging process. Hence, maintaining these balances effectively delays aging and alleviates the symptoms of age-related diseases. Recent research indicates that targeting endoplasmic reticulum (ER) stress and immune deficiency (IMD) signalling may play a positive role in maintaining homeostasis in aging intestinal stem cells (ISC) and microbial equilibrium. Previous research has suggested that total ginsenosides (TG) derived from Panax ginseng C. A. Meyer may exhibit potential anti-aging properties by mitigating ER stress and mediating the IMD pathway. Nevertheless, it remains unclear whether TG improve ISC and microbial homeostasis by modulating ER stress and the IMD pathway to promote healthy aging. PURPOSE: To elucidate whether TG promotes healthspan in Drosophila and its underlying molecular mechanisms, focusing on its role in regulating ER stress and the IMD pathway to maintain ISC and intestinal microbiota homeostasis. METHODS: High performance liquid chromatography was performed to detect the main saponin monomer in TG. Survival rate, gut length, barrier function, and feeding/excretion behaviour assays were used to evaluate the effects of TG on the lifespan and gut health of Drosophila. At the stem cell level, "esg-luciferase" reporter system, esg-GFP/delta stem cell fluorescent labelling, and phospho-histone H3+ mitotic activity assays were employed to determine whether TG prevented natural aging or oxidative stress-associated ISC over-proliferation in Drosophila. Immunofluorescence staining was used to detect the effects of TG on ER stress during aging. Overexpression or interference of ER stress target genes and their related c-Jun N-terminal kinase (JNK) gene was manipulated using gene editing technology to verify the molecular mechanism by which TG maintains age-related ISC proliferation homeostasis. Molecular docking and isothermal titration calorimetry were used to verify the direct interactions between TG and ER stress target genes. In addition, at the intestinal flora level, 16S rDNA sequencing was used to analyse the effect of TG on the diversity and abundance of Drosophila intestinal flora and the possible functional pathways involved. RT-qPCR was performed to determine whether TG mediated the expression of target genes in the IMD pathway. A dominant bacterial species-specific mono-association analysis were performed to verify whether the effects of TG on IMD target genes and ISC proliferation depended on the direct control of the dominant bacterial species. RESULTS: Our results suggest that administration of TG delays the decline in gut morphology and function in aging Drosophila. TG prevents age-associated ISC hyperproliferation by inhibiting ER stress IRE1-mediated JNK signaling. Furthermore, oral TG prevented aging-associated ISC and gut microbiota dysbiosis by remodelling the gut microbiota and inhibiting Acetobacter-mediated activation of IMD target genes. CONCLUSION: TG promotes healthy aging by inhibiting the excessive proliferation of ISC and alleviating intestinal microbial imbalance, thereby providing new insights for the research and development of anti-aging TG products.

Triggering Chinese lecturers' intrinsic work motivation by value-based leadership and growth mindset: Generation difference by using multigroup analysis.

This cross-sectional study investigated the effects of value-based leadership and growth mindset on the intrinsic work motivation of Chinese lecturers. In addition, this study used age as a categorical moderator to investigate generational differences between the effects of Millennials and their predecessors. A sample of 518 lecturers from various Chinese universities was used to collect data, and SEM-PLS was used to analyse the data. The results showed that value-based leadership and growth mindset had a significant positive impact on both younger and older lecturers' intrinsic work motivation, with the effect of value-based leadership on younger lecturers' intrinsic motivation being significantly stronger than on older lecturers' intrinsic motivation, whereas the effect of growth mindset on intrinsic work motivation did not differ significantly between the younger and older groups. This study contributes to the existing research literature by contrasting the value-based leadership and growth mindset in relation to lecturers' intrinsic work motivation across younger and older groups in Chinese higher education settings, where greater heterogeneity between age groups was identified. The findings also provided university administrators with recommendations for boosting the intrinsic work motivation of lecturers, influencing future education policy.

Surgery of enlarging lesions after stereotactic radiosurgery for brain metastases in patients with non-small cell lung cancer with oncogenic driver mutations frequently reveals radiation necrosis: case series and review.

In brain metastases, radiation necrosis (RN) is a complication that arises after single or multiple fractionated stereotactic radiosurgery (SRS/FSRS), which is challenging to distinguish from local recurrence (LR). Studies have shown increased RN incidence rates in non-small cell lung cancer (NSCLC) patients with oncogenic driver mutations (ODMs) or receiving tyrosine kinase inhibitors (TKIs). This study investigated enlarging brain lesions following SRS/FSRS, for which additional surgeries were performed to distinguish between RN and LR. We investigated seven NSCLC patients with ODMs undergoing SRS/FSRS for BM and undergoing surgery for suspicion of LR on MRI imaging. Descriptive statistics were performed. Among the seven patients, six were EGFR+, while one was ALK+. The median irradiation dose was 30 Gy (range, 20-35 Gy). The median time to develop RN after SRS/FSRS was 11.1 months (range: 6.3-31.2 months). Moreover, gradually enlarging lesions were found in all patients after 6 months post-SRS/FSR. Brain radiation necrosis was pathologically confirmed in all the patients. RN should be suspected in NSCLC patients when lesions keep enlarging after 6 months post-SRS/FSRS, especially for patients with ODMs and receiving TKIs. Further, this case series indicates that further dose reduction might be necessary to avoid RN for such patients.

Transforming higher education institutions through EDI leadership: A bibliometric exploration.

This comprehensive bibliometric study analyzes 1820 journal articles from the Web of Science database to explore Equity, Diversity, and Inclusion (EDI) leadership in higher education institutions (HEIs). Utilizing co-citation and co-word analysis, the study identifies distinct thematic clusters. The co-citation analysis reveals five key themes: Race, Diversity, and Inclusion (RDI), Diversity, Leadership, and Self-Efficacy (DLSE), Gender Dynamics and Leadership Challenges, Women's Representation in Academic Medicine Leadership, and Transformational Leadership in HEIs. Meanwhile, the co-word analysis highlights three critical areas: Transformative Collaborative Resilience in HEIs, Advancing Gender Equality in Academic Medicine and STEM, and Inclusive Educational Leadership in HEIs. These themes collectively provide a deep understanding of the EDI leadership field's intellectual structure, suggesting significant areas for future research and practical application. The study emphasizes the necessity for HEIs to engage comprehensively in EDI leadership research, shedding light on the importance of transformative collaborative resilience, gender equality in STEM, and inclusive leadership. This research offers valuable insights for developing effective EDI leadership policies and practices, highlighting the interconnectedness of these themes in fostering a more equitable, diverse, and inclusive environment in higher education and beyond.

The evolution of smart hotels: A bibliometric review of the past, present and future trends.

This study provides a bibliometric analysis of smart hotel research, drawing from 613 publications in the Web of Science (WoS) database to examine scholarly trends and developments in this dynamic field. Smart hotels, characterized by integrating advanced technologies such as AI, IoT, cloud computing, and big data, aim to redefine customer experiences and operational efficiency. Utilizing co-citation and co-word analysis techniques, the research delves into the depth of literature from past to future trends. In co-citation analysis, clusters including "Sustainable Hotel and Green Hotel", "Theories Integration in Smart Hotel Research", and "Consumers' Decisions about Green Hotels" underscore the pivotal areas of past and current research. Co-word analysis further reveals emergent trend clusters: "The New Era of Sustainable Tourism", "Elevating Standards and Guest Loyalty", and "Hotels' New Sustainable Blueprint in Modern Travel". These clusters reflect the industry's evolving focus on sustainability and technology-enhanced guest experiences. Theoretically, this research bridges gaps in smart hotel literature, proposing new frameworks for understanding customer decisions amid technological advancements and environmental responsibilities. Practically, it offers valuable insights for hotel managers, guiding technology integration strategies for enhanced efficiency and customer loyalty while underscoring the critical role of green strategies and sustainability.

Psychological capital research in HEIs: Bibliometric analysis of current and future trends.

This study presents a comprehensive bibliometric analysis of the literature on psychological capital (PsyCap) within higher education institutions (HEIs). Its main objective is to offer an encompassing perspective on this field's current state and potential developments. To achieve this, the study examines present research trends and predicts future directions using a bibliometric approach. A total of 412 journal articles were gathered from the Web of Science database. The analysis identifies influential publications, outlines the knowledge structure, and forecasts future trends through bibliographic coupling and co-word analyses. The bibliographic coupling revealed five distinct clusters, while the co-word analysis identified four clusters. Despite the growing significance of PsyCap research in HEIs, there remains a need for greater academic efforts to comprehend the research landscape fully. This paper provides valuable insights into the expanding area of PsyCap research within HEIs. In conclusion, the study sheds light on the extensive research conducted on PsyCap in the context of HEIs and offers insights into its potential for further growth.

Research landscape of energy transition and green finance: A bibliometric analysis.

This study utilizes bibliometric analysis to examine historical and present research patterns in the area of energy transition and green finance and to forecast potential future domains. Using the bibliometric method, 328 scholarly articles from the Web of Science database were evaluated. This paper identifies influential publications, maps the research landscape, and forecasts emerging tendencies through co-citation and co-word analyses. Co-citation analysis found three main clusters, while co-word analysis revealed four main clusters. Despite the growing significance of research on energy transition and green finance research, further in-depth investigation is necessary to offer a thorough depiction of the research domain. This research represents a pioneering endeavour in the utilization of bibliometric analysis to investigate the interrelationship between two items. It offers valuable insights into the rapidly expanding field of energy transition and green finance, effectively highlighting its contours and indicating potential future developments.

Ataxin-2 sequesters Raptor into aggregates and impairs cellular mTORC1 signaling.

Ataxin-2 (Atx2) is a polyglutamine (polyQ) protein, in which abnormal expansion of the polyQ tract can trigger protein aggregation and consequently cause spinocerebellar ataxia type 2 (SCA2), but the mechanism underlying how Atx2 aggregation leads to proteinopathy remains elusive. Here, we investigate the molecular mechanism and cellular consequences of Atx2 aggregation by molecular cell biology approaches. We have revealed that either normal or polyQ-expanded Atx2 can sequester Raptor, a component of mammalian target of rapamycin complex 1 (mTORC1), into aggregates based on their specific interaction. Further research indicates that the polyQ tract and the N-terminal region (residues 1-784) of Atx2 are responsible for the specific sequestration. Moreover, this sequestration leads to suppression of the mTORC1 activity as represented by down-regulation of phosphorylated P70S6K, which can be reversed by overexpression of Raptor. As mTORC1 is a key regulator of autophagy, Atx2 aggregation and sequestration also induces autophagy by upregulating LC3-II and reducing phosphorylated ULK1 levels. This study proposes that Atx2 sequesters Raptor into aggregates, thereby impairing cellular mTORC1 signaling and inducing autophagy, and will be beneficial for a better understanding of the pathogenesis of SCA2 and other polyQ diseases.

A metabolomics-driven model for early remission prediction following vedolizumab treatment in patients with moderate-to-severe active ulcerative colitis.

To predict early remission following anti-integrin therapy (vedolizumab [VDZ]) in patients with moderate-to-severe active ulcerative colitis (UC) using non-invasive biomarkers. The clinical data of a cohort of 33 patients with moderate-to-severe active UC admitted to the Department of Gastroenterology at Suzhou Municipal Hospital between January 2021 and December 2022 were collected. Of these, 9 patients declined VDZ treatment, and 21 received VDZ at doses of 300 mg weeks 0, 2, and 6, each administered within a 30-minute infusion period. The treatment regimen aimed to induce remission of clinical symptoms; hence, the same dose was administered every 8 weeks. At weeks 0 and 14, serum C-reactive protein (CRP) and erythrocyte sedimentation rate were measured using a modified Mayo score. In addition to clinical assessment, stool samples at baseline and weeks 14 were collected and evaluated using 16SrRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS). Clinical remission was determined based on the clinical symptoms and partial Mayo scores. In patients who received VDZ, the strains of bifidobacterium longum (P = 0.022) and bacteroides sartorii (P = 0.039) significantly increased after treatment than before treatment. GC-MS analysis showed that taurine (P = 0.047) and putrescine (P = 0.035) significantly decreased after treatment. Furthermore, while acetamide exhibited a notable increase (P = 0.001), arachidic acid (P < 0.001) and behenic acid (P = 0.005) demonstrated statistically significant elevations. The combined prediction model of acetamide, taurine, and putrescine demonstrated a high predictive value of early remission in patients with moderate-to-severe active UC following VDZ treatment (area under the curve = 0.911, P = 0.014).

Who makes a better university adjustment wingman: Parents or friends?

The first year of university is one of the most difficult times in a student's life due to numerous changes that occur. This cross-sectional study explores the concept of parental and peer attachment, which has been researched for its ability to predict students' success in higher education. Yet, less research has investigated the mechanisms underpinning the relationship between attachment and university adjustment among first-year students. Hence, the aim of this study was to examine the impact of parent and peer attachment on first-year university students, and understand how these attachments can facilitate university adjustment through identity exploration. This investigation is underpinned by Bowlby and Ainsworth's attachment theory and Arnett's emerging adulthood theory. Data were collected from 568 first-year students at a public university in Sabah, Malaysia, via adapted questionnaires. Structural equation modelling was employed using SmartPLS Software 3.0 to analyse the data. The study found that identity exploration mediates the relationship between parental trust, peer communication, and university adjustment. The findings of this study provide valuable insights for professionals working with emerging adult clients, especially those in higher education institutions, aiming to enhance the adjustment level among first-year students.

Induction immunochemotherapy followed by radiotherapy for patients with unresectable locally advanced or metastatic esophageal cancer: A propensity score-matched analysis.

BACKGROUND: The study aimed to investigate the efficacy of induction immunochemotherapy before radiotherapy (RT) for patients with locally advanced or metastatic esophageal cancer. METHODS: Patients with unresectable locally advanced or metastatic esophageal cancer who received induction immunochemotherapy followed by RT (ICIs + RT group) and RT alone (RT group) were retrospectively identified in two cancer centers, respectively. Propensity score matching (PSM) was used to balance the potential confounders between the two groups. Overall survival (OS), progression-free survival (PFS), and recurrence patterns were evaluated. RESULTS: A total of 467 patients were reviewed, and 66 were matched in each group. After PSM, the 1- and 2-year OS rates were 84.6% and 57.9% in ICIs + RT group, and 71.1% and 43.0% in RT group (HR 0.60, 95% CI 0.36-1.00, p = 0.050). The absolute increase of restricted mean survival time (RMST) for OS in ICIs + RT group compared with RT group were 0.89 years (p = 0.023) at one year and 2.59 years at two years (p = 0.030). The median PFS time, 1- and 2-year PFS rates were 20.3 months, 69.3%, and 45.7% in ICIs + RT group, and 12.2 months, 51.4%, and 35.8% in RT group (HR 0.64, 95% CI 0.41-0.99, p = 0.045). The cumulative locoregional recurrence (LRR) rate was significantly lower in ICIs + RT group (1-year rate, 17.4% vs. 38.8%, p = 0.011), and distant metastasis (DM) rates were comparable (p = 0.755). Consolidation ICIs was associated with a trend of improved 1-year OS and PFS. CONCLUSION: Induction immunochemotherapy followed by RT might improve locoregional control and survival outcomes for patients with unresectable locally advanced or metastatic esophageal cancer.

Novel ProTide prodrugs of 5-fluoro-2'-deoxyuridine for the treatment of liver cancer.

ProTide prodrug technology has emerged as a promising way for the development of anti-viral and anti-tumor drugs, whereas, there are fewer applications for the treatment of liver cancer. Herein, a series of distinct 3'-ester ProTide prodrugs of 5-fluoro-2'-deoxyuridine (FdUR) were synthesized and evaluated for their anti-liver cancer activity. The most efficient prodrug 11b reached a sub-micromolar activity (IC50 = 0.42 ± 0.13 µM) against HepG2 and over 100-fold and 200-fold improvements compared to 5-FU, respectively. 11b also demonstrated favorable selectivity towards normal liver cells L-02 (IC50 > 100 µM). In vitro metabolic stability studies revealed that 11b is stable in the plasma and could be activated rapidly in the liver, which supported that 11b is liver-targeted. Importantly, to more accurately evaluate the anti-HCC activity of 11b, the liver orthotopic model was built and 11b significantly suppressed tumor growth (TGI = 75.5%) at a dose of 60 mg/kg/2d in vivo without obvious toxicity. Overall, these promising results indicated that 11b could serve as a safe and effective prodrug of 5-FU nucleoside for liver cancer therapy.

Seawater as supplemental moisture: The effect of Co-hydrothermal carbonization products obtained from chicken manure and cornstalk.

The use of seawater as a substitute for pure water as supplemental moisture raises questions about its effect on the physicochemical properties of hydrochar. Therefore, this study aimed to investigate the feasibility of using seawater as supplemental moisture by comparing the physicochemical properties of products obtained through Co-hydrothermal carbonization of chicken manure and cornstalk under seawater and deionized water conditions. By varying the HTC temperature and blending ratios of CM and CS to investigate comprehensively the effect of seawater. Results indicated that the hydrochar yield experienced a variation from 54.54% to 57.40%, while the IC value changed from 7.69% to 8.46% as the ratio of CM:CS shifted from 3:1 to 1:3 under seawater conditions. The higher heating value of the hydrochars obtained under seawater conditions was lower than those obtained under deionized water conditions. This suggests that seawater conditions promote the hydrolysis reaction of organic solid waste. Furthermore, it was observed that when no lignin hydrolysis reaction occurred, seawater conditions had no discernible effect on the fuel quality of the hydrochar. However, at an HTC temperature of 250 °C, the fuel quality of the hydrochar obtained under seawater conditions was notably inferior to that of the hydrochar obtained under deionized water. Thus, an HTC temperature lower than 250 °C is necessary for the hydrothermal carbonization of organic solid waste under seawater conditions. Moreover, the relative content of surface -C-(C, H)/CC of the hydrochar obtained under seawater conditions was lower than that obtained under deionized water conditions, indicating that the hydrochar had a low degree of aromatization. Additionally, there was a significant increase in the immobilized Mg atoms in the hydrochar under seawater conditions, which affected the hydrochar yield and higher heating value of the hydrochar. This research presents a theoretical foundation for preparing solid fuels and materials using hydrothermal carbonization of saltwater as supplemental moisture.