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The prevention and treatment of metabolic disorders, such as non-alcoholic fatty liver disease (NAFLD), have emerged as critical global health challenges. Current lipid-lowering pharmacotherapies are associated with side effects, including hepatotoxicity, rhabdomyolysis, and decreased erythrocyte counts, underscoring the urgent need for safer therapeutic alternatives. Hepatocyte nuclear factor 4α (HNF4α) has been identified as a pivotal regulator of lipid metabolism, making it an attractive target for drug development. In this study, we investigated the structural characteristics and binding interactions of four HNF4α agonists: Alverine, Benfluorex, N-trans caffeoyltyramine (NCT), and N-trans feruloyltyramine (NFT). Our results indicate that the conjugated structure formed by the amide bond and the aromatic ring in NCT and NFT enhances electron density, potentially contributing to their increased specificity for HNF4α relative to Alverine and Benfluorex. Additionally, electrostatic interactions between the aromatic moieties of the compounds and HNF4α residues were found to play a crucial role in ligand binding. Leveraging these insights, we performed a high-throughput virtual screening of 2131 natural compounds, using the binding modes of NCT and NFT as reference templates. Rosmarinic acid emerged as a promising HNF4α agonist, exhibiting a high consensus score and favorable binding affinity. Subsequent biological assays demonstrated that rosmarinic acid significantly inhibited HepG2 cell proliferation which related to the enhancement of autophagy. After the knockdown of P2 isoform of HNF4α, HepG2 was more sensitive to the administration of NCT and rosmarinic acid. Furthermore, the proliferation of DLD-1 cell, which only expresses the P2 isoform of HNF4α, was not significantly inhibited by the administration of NCT and rosmarinic acid. Collectively, these findings suggest that rosmarinic acid is a promising HNF4α agonist which is more effective to activate the P1 isoform of HNF4α and holds potential as an effective treatment for NAFLD, providing a foundation for the development of novel lipid-lowering drugs with enhanced efficacy and reduced side effect. Data Availability: Data will be made available on request.

Abstract Background This meta-analysis was performed to comprehensively evaluate the efficacy and safety of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) versus uniportal endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) for the treatment of lumbar degenerative diseases. Methods We electronically searched PubMed, Embase, Scopus, Web of Science, the Cochrane Library, the Wanfang Database, and China National Knowledge Infrastructure to identify controlled clinical studies on the efficacy and safety of UBE-TLIF and Endo-TLIF for lumbar degenerative diseases from database establishment to December 2023. Two researchers screened the literature, extracted data, and evaluated the risk of bias of the included studies. They also recorded the authors, sample size, operative time, intraoperative blood loss, hospital length of stay, complication rate, fusion rate, visual analogue scale scores, and Oswestry disability index in each study. The meta-analysis was performed using RevMan 5.4 software provided by the Cochrane Library. Results Five studies involving 314 patients met the inclusion criteria for this meta-analysis. The UBE-TLIF group comprised 154 patients, and the Endo-TLIF group comprised 160 patients. UBE-TLIF was superior to Endo-TLIF in terms of the operative time and fusion rate. There were no significant differences in the intraoperative blood loss, hospital length of stay, complication rate, visual analogue scale scores, or Oswestry disability index between the two groups. Conclusion Both UBE-TLIF and Endo-TLIF can achieve satisfactory clinical results with respect to improving low back and leg pain in patients with lumbar degenerative diseases. However, UBE-TLIF has the advantages of a shorter operative time and higher fusion rate. Trial registration This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42023495076).

Abstract Background Postoperative and ongoing treatment of breast cancer is traumatic to women with breast cancer and may lead to positive and negative psychological diseases, which can affect the prognosis of patients with breast cancer. Positive affect (PA) and negative affect (NA) significantly impact the prognosis of postoperative breast cancer patients. However, the effects of specific emotions on patient prognosis and the relationships between them are still unclear. Methods A case–control study was conducted to investigate the characteristics of PA and NA and their effects on Quality of Life (QoL) in breast cancer patients. 442 postoperative breast cancer patients and 444 healthy women were recruited from November to December 2021. For the observation group, participants were eligible if they (1) were aged between 16 and 80 years and (2) had a confirmed pathological diagnosis of breast cancer and (3) possessed the ability to read text, voluntarily agreed to participate, provided informed consent, and cooperated with the study procedures. The control group consisted of individuals without breast cancer who met all other criteria, as stated above. Patients were excluded from the study if they (1) had severe comorbid conditions causing functional impairment or life-threatening risks or (2) suffered from mental disorders or were unconscious at the time of the study. For the control group, individuals with a pathological diagnosis of breast cancer were also excluded. All other exclusion criteria were consistent with those for the observation group. The demographic information and clinicopathological information of the participants were collected. The Positive Affect and Negative Affect Scale (PANAS) is a scale containing 20 emotional scores related to emotion and is used to assess the level of positive and negative affect. The Quality of Life Questionnaire Core 30 (QLQ-C30) was used to assess the quality of life of cancer patients in 15 domains. SPSS 24.0 was used to analyze and process the data. Independent-sample t-tests, one-way ANOVA and Pearson correlation analysis, were used to analyze PA and NA in different treatment phases. Polynomial regression and response surface analysis were conducted to assess the relationships among PA, NA, and QoL. The results were considered statistically significant at P 0.05). During the initial treatment phase, the highest proportion of patients had an NA greater than the PA (PA

Abstract Objective This study retrospectively analyzed the relationship between serum-free triiodothyronine (FT3) levels and the prognosis of coronary atherosclerotic cardiopathy (CHD) in patients from alpine regions treated with drug-coated balloons (DCB). Methods Data from 201 CHD patients with DCB at Hulunbuir People’s Hospital between September 2019 and August 2023 were included. Patients were divided into two groups based on the occurrence of major adverse cardiovascular events (MACE) after surgery. Univariate and multivariate logistic regression analyses were conducted to identify risk factors. The predictive efficiency of these risk factors for MACE was evaluated using the ROC curve. Results The poor prognosis group had significantly higher ages, a greater proportion of patients with a history of previous coronary interventions, and elevated levels of N-terminal pro-B-type natriuretic peptide compared to the good prognosis group. In contrast, FT3 levels were significantly lower (P 0.05). Multivariate binary logistic regression analysis identified FT3 level as an independent predictor factor of MACE in CHD patients treated with DCB. The optimal cut-off value for FT3 in predicting adverse prognosis following DCB surgery was 3.30 pmol/L, with a sensitivity of 72.5%, specificity of 62.8%, and an area under the curve (AUC) of 0.741 (P

Abstract Background This study investigates the effectiveness and safety of aripiprazole oral solution in Chinese patients with schizophrenia. Methods This was a multicenter, single-arm phase IV study involving 134 patients in China in the acute stage of schizophrenia from May 2021 to July 2022. The patients received aripiprazole oral solution 10 − 30 mg/d for 12 weeks. The effectiveness endpoints included the Positive and Negative Symptom Scale (PANSS) and the Clinical Global Impression (CGI) scale score. The safety endpoints included adverse events, laboratory inspection indicators (including the serum prolactin level [PRL]), and waist circumferences (WC). Results Ultimately, 86 patients (64.18%) completed the trial, and 21 patients (15.67%) dropped out due to poor effectiveness. From baseline to week eight, 43.28% of patients had a PANSS reduction of ≥ 50%, 82.84% of patients improved in the CGI-Improvement (CGI-I scale score of 1 − 3), and the percentage of patients with abnormal PRL and waist circumferences decreased significantly. In total, 45 patients (33.58%) experienced mild adverse drug reactions predominately manifested as extrapyramidal symptoms (EPSs; 9.70%), constipation (8.96%), and palpitations (7.46%). Upon further subgroup analysis, aripiprazole oral solution demonstrated significantly improved effectiveness in first-episode schizophrenia patients and those with symptoms of agitation. Conclusions Aripiprazole oral solution displayed positive clinical effectiveness and favorable tolerability in Chinese patients in the acute stage of schizophrenia. Clinical trial registration Clinical trial registration number: ChiCTR2100044653. Name of trial registration: A real-world study of Aripiprazole Oral Solution in the treatment of schizophrenia (Registration date: 25/03/2021). The full trial protocol can be accessed at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ).

Abstract Sustainable employability refers to an individual’s ability to work and maintain employment over a long-term period. Despite significant progress in current research on sustainable employability, improvements are needed in areas such as consistency in definition, research on specific populations, industry-specific challenges, and methodological limitations. The current bibliometric analysis aims to address these areas by systematically studying published articles on sustainable employability from 2014 to 2024. A total of 170 articles on sustainable employability were retrieved from January 2014 to January 2024 using the Web of Science database. Various bibliometric information was collected, including the number of publications, keywords, countries of origin, journal names, research hotspots, national cooperation, and journal citation data. The Netherlands published the highest number of papers on sustainable employability. Additionally, sustainable employability has remained a research hotspot over the past decade. The complexity and multidimensionality of this field highlights the increasing focus on employees’ psychological characteristics, work environment, and health management, emphasizing the importance of interdisciplinary collaboration in research.

Abstract In an extension of MSSM with two triplets and a singlet, called the TNMSSM, there are seven neutralinos which can enrich the study of cold dark matter if one expects that the weakly interacting massive particle (WIMP) is responsible for the observation of Planck satellite. Such a model, compared to the MSSM, can naturally offer a solution to the $$\mu $$ μ problem, and its lightest neutralino, which is bino-like, can also provide a correct relic density by using the coannihilation mechanism due to the newly added triplinos. Taking into account the related experimental measurements, such as the bound on the SM-like Higgs mass, the B meson rare decays, the anomalous magnetic moment of the muon $$a_\mu $$ a μ , the Large Hadron Collider (LHC) measurements and the latest dark matter direct detection experiment LUX-ZEPLIN (LZ), the TNMSSM parameter space can be strictly limited. In respect to all the constraints mentioned above, we find that a bino-like neutralino with a mass in the region $$[100, 450]~\textrm{GeV}$$ [ 100 , 450 ] GeV can successfully account for the correct dark matter relic density. Additionally, most of the viable parameter space can be tested in the near future experiments such as the Xenon-nT experiment or LHC.

Abstract The formation of human collagen requires the presence of Prolyl 3-hydroxylase 1 (P3H1), but the regulatory mechanism of P3H1 remained insufficiently understood. Our study aimed to identify the role of P3H1 in clear cell renal cell carcinoma (ccRCC). P3H1 expression in ccRCC was validated using multiple databases and in vitro experiments. We performed a correlation analysis of P3H1 with drug sensitivity, immune checkpoints, and immune cell infiltration using transcriptome and single-cell sequencing. Drawing upon the Encyclopedia of RNA Interactomes database, we selected P3H1 as the focal point of our investigation, meticulously uncovering the intricate network of microRNAs and lncRNAs that potentially orchestrate ceRNA mechanisms. This study employs a multidimensional approach integrating vitro assays and multi-omics bioinformatics analyses to investigate P3H1’s impact on ccRCC prognosis, immune modulation, immune checkpoints, ceRNA regulatory network, drug sensitivity, and therapeutic responses, aiming to uncover new insights into its therapeutic potential and inform future clinical strategies.

Abstract Fluorinated or fluoroalkylated alcohols are common structural motifs in biologically active molecules, natural products, and pharmaceuticals. However, pentafluorosulfanyl (SF5) alcohols, a unique class of SF5 compounds that serve as synthetically valuable building blocks, are difficult to prepare with current methodologies. In this article, we present a single-step, metal-free, and photo-induced hydroxypentafluorosulfanylation of styrenes or α,β-unsaturated esters/amide, producing a series of structurally diverse pentafluorosulfanyl alcohols with up to 89% yields. This reaction is mild and operationally simple, using molecular oxygen as the hydroxy source. The protocol is suitable for a wide range of alkenes, including natural products and drug molecule derivatives. The formed SF5 alcohol units can be readily converted into diverse functionalized SF5 compounds, such as α-SF5 ketones, SF5 diols, and SF5 cyclic carbonates. The potential applications of these SF5 compounds in pharmaceutical and material sciences are vast, making this research a step forward in the field.

Abstract Objective The present study aims to investigate the ultrasound and magnetic resonance imaging (MRI) characteristics of kaposiform hemangioen dothelioma (KHE). Methods A retrospective analysis was conducted on the clinical data of children diagnosed with KHE through postoperative pathology. Patients were divided into two groups: the KHE group and the KHE with Kasabach-Merritt Phenomenon (KMP) group (KMP group). Laboratory indicators, ultrasound, and MRI data were collected and analyzed statistically to summarize the imaging characteristics of the disease. Results The levels of platelets and fibrinogen in the KHE group were significantly higher than those in the KMP group, while D-dimer levels, prothrombin time, and activated partial thromboplastin time were lower (P

Abstract Background The use of prehospital tranexamic acid (TXA) in patients with trauma has attracted considerable attention. This systematic review and meta-analysis aimed to provide the best evidence for clinicians. Methods All related literature in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (Central) databases were searched systematically from their establishment to July 1, 2023. The outcome measures included 24-hour and 28–30-day mortality and adverse events (multiple organ dysfunction syndrome, acute respiratory distress syndrome, thrombotic events, and infection events). The Revised Cochrane Risk of Bias Tool for Randomized Trials was used to evaluate the quality of the randomized controlled trials (RCTs). The Methodological Index for Nonrandomized Studies (MINORS) was used to evaluate the risk of bias in non-RCTs. The required information size was estimated using trial sequential analysis. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to evaluate the evidence quality. Results Eleven studies (comprising 11,259 patients) were included; two of these were RCTs. The overall risks of bias were low in the RCTs. ROBINS-I risk of bias was Moderate in 3 studies, serious in 5 studies, and critical in 1 study. A significant reduction in 24-hour mortality was observed (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.71–0.94). A subgroup analysis that included only RCTs revealed that prehospital TXA was associated with reduced 28–30-day mortality (OR, 0.80; 95% CI, 0.66–0.97) and increased risks of thromboembolism (OR, 1.22; 95% CI, 1.03–1.44) and infection (OR, 1.13; 95% CI, 1.00–1.28) events. The blood products for transfusion decreased by 2.3 units on average (weighted mean difference [WMD], − 2.30; 95%CI, − 3.59 to − 1.01). Conclusions This updated systematic review showed that prehospital TXA reduced the 24-hour and 28–38-day mortality and blood transfusion but increased the risks of infection and thromboembolism in patients with trauma. Future RCTs with larger and more homogeneous samples will help verify our results.

Abstract During pregnancy the immune system needs to maintain immune tolerance of the foetus while also responding to infection, which can cause premature activation of the inflammatory pathways leading to the onset of labour and preterm birth. The vaginal microbiome is an important modifier of preterm birth risk, with Lactobacillus dominance during pregnancy associated with term delivery while high microbial diversity is associated with an increased risk of preterm birth. Glycans on glycoproteins along the lower female reproductive tract are fundamental to microbiota-host interactions and the mediation of inflammatory responses. However, the specific glycan epitopes involved in these processes are not well understood. To address this, we conducted glycomic analyses of cervicovaginal fluid (CVF) from 36 pregnant women at high risk of preterm birth and 4 non-pregnant women. Our analysis of N- and O-glycans revealed a rich CVF glycome. While O-glycans were shown to be the main carriers of ABO blood group epitopes, the main features of N-glycans were the presence of abundant paucimannose and high mannose glycans, and a remarkable diversity of complex bi-, tri-, and tetra-antennary glycans decorated with fucose and sialic acid. We identified immuno-regulatory epitopes, such as Lewis antigens, and found that fucosylation was negatively correlated to pro-inflammatory factors, such as IL-1β, MMP-8, C3a and C5a, while glycans with only sialylated antennae were mainly positively correlated to those. Similarly, paucimannose glycans showed a positive correlation to pro-inflammatory factors. We revealed a high abundance of glycans which have previously been identified as hallmarks of cancer and viral glycosylation, such as Man8 and Man9 high mannose glycans. Although each pregnant woman had a unique glycomic profile, longitudinal studies showed that the main glycosylation features were consistent throughout pregnancy in women who delivered at term, whereas women who experienced extreme preterm birth exhibited sharp changes in the CVF glycome shortly before delivery. These findings shed light on the processes underlying the role of glycosylation in maintaining a healthy vaginal microbiome and associated host immune responses. In addition, these discoveries facilitate our understanding of the lower female reproductive tract which has broad implications for women’s health.

Abstract Objective To investigate the impact of response to induction chemotherapy (IC) on survival outcomes in patients with locally advanced nasopharyngeal carcinoma (LANPC) and evaluate the efficacy of adding nimotuzumab to concurrent chemoradiotherapy (CCRT) based on different responses to IC. Methods We retrospectively included patients with stage III-IVA NPC who underwent IC with and without nimotuzumab during CCRT. Statistical analysis included the chi-square test, propensity score matching, Kaplan-Meier survival analysis, and Cox proportional hazards model. Results Among 383 identified patients, 216 (56.4%) received nimotuzumab during CCRT, while 167 (43.6%) did not. Following IC, 269 (70.2%) patients showed a complete response (CR) or partial response (PR), and 114 (29.8%) had stable disease (SD) or progressive disease (PD). The response to IC independently influenced disease-free survival (DFS) and overall survival (OS). Patients achieving CR/PR demonstrated significantly higher 3-year DFS (80.3% vs. 70.6%, P = 0.031) and OS (90.9% vs. 83.2%, P = 0.038) than those with SD/PD. The addition of nimotuzumab during CCRT significantly improved DFS (P = 0.006) and OS (P = 0.037) for CR/PR patients but not for those with SD/PD. Conclusions This study emphasizes the importance of IC response in LANPC and highlights the potential benefits of nimotuzumab during CCRT for improving survival outcomes in CR/PR patients. Tailored treatment approaches for SD/PD patients warrant further investigation.

Abstract Genes encoding subunits of SWI/SNF (BAF) chromatin remodeling complexes are mutated in nearly 25% of cancers. To gain insight into the mechanisms by which SWI/SNF mutations drive cancer, we contributed ten rhabdoid tumor (RT) cell lines mutant for SWI/SNF subunit SMARCB1 to a genome-scale CRISPR–Cas9 depletion screen performed across 896 cell lines. We identify PHF6 as specifically essential for RT cell survival and demonstrate that dependency on Phf6 extends to Smarcb1-deficient cancers in vivo. As mutations in either SWI/SNF or PHF6 can cause the neurodevelopmental disorder Coffin-Siris syndrome, our findings of a dependency suggest a previously unrecognized functional link. We demonstrate that PHF6 co-localizes with SWI/SNF complexes at promoters, where it is essential for maintenance of an active chromatin state. We show that in the absence of SMARCB1, PHF6 loss disrupts the recruitment and stability of residual SWI/SNF complex members, collectively resulting in the loss of active chromatin at promoters and stalling of RNA Polymerase II progression. Our work establishes a mechanistic basis for the shared syndromic features of SWI/SNF and PHF6 mutations in CSS and the basis for selective dependency on PHF6 in SMARCB1-mutant cancers.

Spermatogenesis in Lepidoptera holds significant importance due to its unique process of dichotomous spermatogenesis, yielding eupyrene and apyrene spermatozoa through a complex molecular mechanism. While E3 ubiquitin ligases are known to play vital roles in spermatogenesis across various processes, their functions in dichotomous spermatogenesis remain less known. We utilized the RNAi, biochemical and microscopic procedures to unravel the function of ScE3 Siah in dichotomous spermatogenesis of adult Sitotroga cerealella. In S. cerealella E3 ligase Siah predominantly expressed in adult tissues. Knockdown of ScE3 Siah leads to disruptions in testes and sperm morphology, affecting the structure of eupyrene and apyrene sperm bundles and causing defective ultrastructure in eupyrene sperm. This disruption results in a reduction in the number of dichotomous sperms and significantly reduces their motility. Moreover, ScE3 Siah knockdown inhibits the transfer and motility of dichotomous sperm, impacting spermatophore formation in females and ultimately reducing egg production. Understanding the role of ScE3 Siah is not only crucial for comprehending the complex processes involved in dichotomous spermatogenesis and fertilization but also provides an avenue for sustainable pest control management.

BackgroundDeutetrabenazine is a widely used drug for the treatment of tardive dyskinesia (TD), and post-marketing testing is important. There is a lack of real-world, large-sample safety studies of deutetrabenazine. In this study, a pharmacovigilance analysis of deutetrabenazine was performed based on the FDA Adverse Event Reporting System (FAERS) database to evaluate its relevant safety signals for clinical reference.MethodsAdverse events (AEs) of FAERS with deutetrabenazine as the primary suspect drug were collected from the first quarter (Q1) of 2017 to Q1 of 2024. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) were used to mine AEs risk signals of deutetrabenazine. AEs were standardized and classified using the System Organ Class (SOC) and Preferred Terms (PTs) from Medical Dictionary for Regulatory Activities (MedDRA) version 23.0.ResultsA total of 3,583 AEs with deutetrabenazine as the primary suspect drug were collected in this study. We found that these AEs involved 23 SOCs, and the positive signals were mainly concentrated in systemic disease and various reactions at the site of administration (n = 1816, ROR = 1.23, PRR = 1.18, IC = 0.24, EBGM = 1.18), neurological disorders (n = 1736, ROR = 3.02, PRR = 2.60, IC = 1.38, EBGM = 2.60) and psychiatric disorders (n = 1,659, ROR = 4.15, PRR = 3.52, IC = 1.82, EBGM = 3.52). We eventually identified 100 valid PTs that met the criteria of the four algorithms. Drug ineffective, dyskinesia, depression, somnolence, suicidal ideation were considered to be the common PTs of deutetrabenazine. Tongue thrust (n = 4, ROR 253.47, PRR 253.35, IC 7.88, EBGM 235.95), grunting (n = 5, ROR 78.49, PRR 78.45, IC 6.26, EBGM 76.71) and drooling (n = 17, ROR 13.21, PRR 13.19, IC 3.72, EBGM 13.14) were not mentioned in the specification, but the high signal intensity suggested that they may be the potential adverse reactions.ConclusionThe efficacy of deutetrabenazine may be accompanied by some potential adverse effects in several systems. Adverse events in psychiatric, neurologic, gastrointestinal and respiratory need to be monitored in clinical practice.

ABSTRACT Objective This study aimed to synthesize and encapsulate findings from recent research (May 1, 2018 to August 1, 2023) on neurofeedback interventions for children diagnosed with attention deficit hyperactivity disorder (ADHD). Methods A comprehensive search was conducted across major databases and platforms, including randomized controlled trials s focusing on children aged 5–11 years with ADHD. The inclusion was broad, not restricted by ADHD subtype, gender, IQ, socioeconomic status, or coexisting conditions. Results From the study screening process, 13 studies were included in the network meta‐analysis, involving 1370 children. Most neurofeedback therapies surpassed placebo in ADHD symptoms. In the acceptability outcome, five neurofeedback therapies (HEG, SCP training, TBR training, SMR training, and active control) outperformed the inactive control, physical activity, and EMG therapies. Conclusions The potential efficacy of nonpharmacological interventions in ADHD management among children is illuminated. The findings advocate for a holistic, child‐centered approach, emphasizing the need for further in‐depth research to understand and refine these interventions.

Abstract Immunotherapies employing PD‐1/PD‐L1 immune checkpoint inhibitors (ICIs) are vital for primary liver cancer (PLC), but response rates remain unsatisfying. Accurate differentiation of responders from non‐responders to immunotherapy is imperative. Here, single‐cell‐scaled mass cytometry analysis on sequential peripheral blood mononuclear cells (PBMCs) from ICI‐treated PLC patients is conducted, and tissue residence of immune subpopulations is assessed via multiplex immunohistochemistry. In the discovery cohort (n = 24), responders have lower baseline B cell and HLA‐DR+CD8+T cell, and higher CD14+CD16− classical monocyte (CM) proportions. CMs decrease more in responders PBMCs, while HLA‐DR+CD8+T cells conformably amplify after ICI‐exposure. Responsive individuals display upregulated exhaustion and activation markers in peripheral immune lineages. In the expanded cohort of 77 patients, the augment of the B cells in non‐responders is re‐confirmed. Responders demonstrate much higher enrichment of B cells or tertiary lymphoid structures in tumor compared to non‐responders. A prospective model that excelled in early discrimination of responders is developed using generalized linear model and achieves a satisfactory AUC over 0.9 in all three independent cohorts. Integratedly, the study unveils dynamic immune landscapes in PLC patients undergoing ICI‐based therapy, aiding in PLC patient stratification for ICI‐based treatment and fostering new response monitoring strategies.

The rice-wheat rotation system has been shown to improve agricultural productivity with associated economic benefits. The degree of phosphorus saturation (DPS) refers to saturation of soil sorption sites with phosphorus (P), and reflects the tendency of soil P fixation or release. A current knowledge gap is to investigate how a rice-wheat rotation system affects soil DPS, which is closely related to P loss to the environment. In the present field study, a rice-wheat rotation was established and different fertilization treatments were implemented, and the Anthrosol soils collected from the rice season and the wheat season, were evaluated. Sequential extraction, Langmuir model, and structural equation modeling were used to reveal the proportion of P fractions, P sorption capacity, and the relationships between the degree of P saturation and soil properties, in order to reveal the geochemical mechanisms of P transformation. A higher degree of P saturation is always found in the rice season soils rather than in the wheat season soils, which should be attributed to the lower P retention capacity and the higher presence of P in forms with greater mobility potential in the rice season soils. The reduction of the proportion of residual P fraction coupled with the enhancement of NaHCO3-P/NaOH-P/HCl-P fractions indicated a prevalence of P mobilization due to flooding during the rice planting period. Simultaneously, lower P sorption capacity was also found in the rice season soils. Structural equation modelling was able to confirm that the change of P sorption capacity together with the enhancement proportion labile P in total P, and mobilization of soil residual P combined to affect the degree of P saturation. Management interventions, such as flooding, induced changes from crystalline iron oxides to amorphous iron oxides and this may have enhanced the release of P retained by crystalline iron oxides, which contributed to the mobilization of P in the soils after the rice season. This knowledge can be utilized to avoid P losses to the environment, while still achieving efficient P utilization.

Alzheimer’s disease (AD) is a neurodegenerative disorder that severely impacts cognitive function, posing significant physical and psychological burdens on patients and substantial economic challenges to families and society, particularly in aging populations where its prevalence is rising. Current diagnostic and therapeutic strategies, including pharmacological treatments and non-pharmacological interventions, exhibit considerable limitations in early diagnosis, etiological treatment, and disease management. This study aims to investigate the application of artificial intelligence (AI) in the early diagnosis and progression monitoring of AD through a bibliometric analysis of relevant literature. A systematic search in the Web of Science Core Collection identified 530 publications related to AI and AD, consisting of 361 original research articles and 169 review articles, with a notable increase in annual publication rates, particularly between 2019 and 2024. The United States and China emerged as leading contributors, emphasizing the importance of international collaboration. Institutional analysis revealed that Harvard University and Indiana University System are at the forefront, highlighting the role of academic institutions in fostering interdisciplinary research. Furthermore, the Journal of Alzheimer’s Disease was identified as the most influential publication outlet. Key highly cited papers provided essential theoretical foundations for ongoing research. This study underscores the growing relevance of AI in AD research and suggests promising avenues for future investigations, particularly in enhancing diagnostic accuracy and therapeutic strategies through advanced data analytics and machine learning techniques.

This study aimed to investigate back-crack locations of water softening-caused retrogressive bedrock–overburden landslides. First, six laboratory model tests of the Wuhuamiao landslide were performed to investigate the back-crack locations. Then, an analytical model was developed and used to calculate the laboratory back-crack locations. The practical effectiveness of the analytical model was finally evaluated using real Wuhuamiao and Jiangdingya landslides. The test results showed that all six model tests successfully reproduced the retrogressive bedrock–overburden landslides having two sliding masses, a front sliding mass and a rear sliding mass. Each sliding mass had a back crack. The back-crack inclinations varied widely from 59.7° to 77.2° for the six front sliding masses, while the back-crack inclinations varied widely from 59.2° to 69.6° for the six rear sliding masses. The wide variation is mainly due to the difference in the spatial location of sliding mass and the basic shear surface (BSS) location. For the fourteen back-crack surfaces of laboratory and real landslides, the calculated locations were broadly consistent with the measured or published locations.

Agricultural modernization urgently requires precise control of pear tree leaf diseases, with accurate identification and segmentation of disease spots becoming crucial aspects for ensuring crop health. Addressing potential issues such as missed segmentation, missegmentation, and low segmentation accuracy in the traditional DeepLabv3+ model for this task, this study proposes an innovative approach based on an improved DeepLabv3+ network model. To enhance computational efficiency, MobileNetV2 is introduced as the backbone network. This reduces the model’s computational load and significantly improves segmentation speed, making it more suitable for real-time applications. Secondly, after the ASPP (Atrous Spatial Pyramid Pooling) convolution, the Squeeze-and-Excitation (SE) attention mechanism is introduced, integrating the features of pear tree leaf diseases to make the network focus more on the critical components of disease spots, thereby enhancing segmentation accuracy. Finally, the loss function is optimized by employing a linear combination of the cross-entropy loss function and Dice loss, encompassing comprehensive overall image loss and accurate loss calculation for the target area. Experimental validation demonstrates a significant improvement in the enhanced DeepLabv3+ across metrics such as MIoU, mPA, mPr, and mRecall, reaching 86.32%, 88.97%, 91.10%, and 88.97%, respectively. The improved model excels in pear tree leaf disease segmentation compared to traditional methods like DeepLabv3+, SegNet, FCN, and PSPNet. This confirms the enhanced model’s outstanding performance and generalization ability in segmenting pear tree leaf lesions, highlighting its potential value in practical applications.

Background The therapeutic benefit of concurrent chemoradiotherapy (CCRT) in elderly nasopharyngeal carcinoma (NPC) patients remains controversial. This study aimed to investigate the efficacy and toxicity of lobaplatin-based CCRT in elderly patients with NPC.Methods We included stage II–IVA NPC patients aged ≥65 years who received lobaplatin concomitant with intensity-modulated radiation therapy (IMRT) between March 2019 and January 2023. Objective response rates and treatment-related toxicity were assessed. Kaplan–Meier’s analysis was performed to calculate survival rates.Results A total of 29 patients were included with a median age of 67 years. There were 19 patients (65.5%) who had comorbidities. All patients had serum EBV-DNA detective before treatment; the median EBV-DNA load was 236 IU/mL. There were 25 (86.2%) patients treated with induction chemotherapy, and the overall response rate was 92.0%. All patients received IMRT and concurrent chemotherapy with lobaplatin. During the CCRT, the most common adverse effect was haematological toxicity. Three patients (10.3%) had grade 3 leucopenia, three patients (10.3%) had grade 3 neutropenia, and eight patients (27.6%) had grade 3–4 thrombocytopenia. The rate of grade 3 mucositis was 34.5%. No patients had liver and kidney dysfunction. The median weight loss was 4 kg during CCRT. After three months of CCRT, the total response rate was 100%. EBV-DNA was not detected in any patients. The median follow-up was 32.1 months. The 3-year locoregional recurrence-free survival, distant metastasis-free survival, progression-free survival and overall survival were 95.8%, 85.7%, 82.5% and 100%, respectively.Conclusions Lobaplatin-based CCRT is safe and feasible for elderly NPC patients, with satisfactory short-term survival outcomes and acceptable toxicities. A phase 2 trial is ongoing to investigate the role of lobaplatin-based CCRT on long-term survival and treatment toxicities for this population.

Background To investigate the prognostic implications of histology among nasopharyngeal carcinoma (NPC) using the data from a Chinese cohort and the Surveillance, Epidemiology, and End Results (SEER) database.Methods We included patients diagnosed with WHO II and III subtypes NPC from two independent cohorts (Xiamen [XM]-NPC cohort and SEER-NPC cohort).Results We identified 726 patients in the XM-NPC cohort and 1334 patients in the SEER cohort. In the XM-NPC cohort, 94 (12.9%) and 632 (87.1%) patients had WHO II and III subtypes, respectively. In the SEER-NPC cohort, 839 (62.9%) and 495 (37.1%) patients had WHO II and III subtypes, respectively. WHO II subtype patients had a higher smoking rate than the WHO III subtype (57.4% vs. 43.4%) in the XM-NPC cohort. There were no significant differences in age, gender, tumor stage, or nodal stage between the two subtypes in both cohorts. In the XM-NPC cohort, patients with the WHO II subtype had worse locoregional relapse-free survival (82.2% vs. 89.5%, p = 0.063), distant metastasis-free survival (72.4% vs. 85.9%, p = 0.028), disease-free survival (61.6% vs. 78.8%, p = 0.003), and overall survival (OS) (71.7% vs. 84.0%, p = 0.035) than those with WHO III subtype. In the SEER-NPC cohort, patients with the WHO II subtype had worse NPC-specific survival (81.1% vs. 89.4%, p

BackgroundAlzheimer’s disease (AD) is a neurodegenerative disorder marked by cognitive decline and memory loss. Recent research underscores the crucial role of astrocytes in AD. This study reviews research trends and contributions on astrocytes in AD from 2000 to 2024, shedding light on the evolving research landscape.MethodsWe conducted a bibliometric analysis using data from the Web of Science Core Collection, covering publications from January 1, 2000, to July 6, 2024, on “Alzheimer’s disease” and “astrocytes.” We identified 5,252 relevant English articles and reviews. For data visualization and analysis, we used VOSviewer, CiteSpace, and the R package “bibliometrix,” examining collaboration networks, co-citation networks, keyword co-occurrence, and thematic evolution.ResultsBetween 2000 and 2024, 5,252 publications were identified, including 4,125 original research articles and 1,127 review articles. Publications increased significantly after 2016. The United States had the most contributions (1,468), followed by China (836). Major institutions were the University of California system (517) and Harvard University (402). The Journal of Alzheimer’s Disease published the most articles (215). Verkhratsky A was the top author with 51 papers and 1,585 co-citations.ConclusionOur extensive bibliometric analysis indicates a significant increase in research on astrocytes in AD over the past 20 years. This study emphasizes the growing acknowledgment of astrocytes’ crucial role in AD pathogenesis and points to future research on their mechanisms and therapeutic potential.

Inflammatory bowel disease remains a high recurrence rate and broad populations all over the world. Liquiritigenin isolated from licorice possess anti-inflammatory and antioxidative activities, suggesting its potential of treating ulcerative colitis (UC). In this study, we explored the effect of oral liquiritigenin on the DSS-induced mice colitis and underlying mechanisms in the aspect of gut microbiome and intestinal barrier dysfunction. The results showed liquiritigenin had protective effects against DSS-induced mice colitis, including attenuating weight loss, disease activity index score elevation, colon length shortening and histological lesions. In addition, the treatment with liquiritigenin significantly reduced the plasma cytokine levels, TNF-α, IL-1β and IL-6 levels as well as the expression of iNOS and COX-2 compared to control group. Liquiritigenin supplementation also led to a restoration of oxidative homeostasis, as indicated by a decrease of myeloperoxidase (MPO) and malondialdehyde (MDA) levels and an increase in reduced glutathione (GSH) and total Superoxide Dismutase (T-SOD) activities in the colitis mice. In regulation of mice gut microbiota, liquiritigenin augmented probiotics abundance (e.g., Akkermansia), decreased harmful bacteria (e.g., Turicibacter), and restored Firmicutes/Bacteroidetes balance. Furthermore, the mRNA levels of tight junction (TJ), including ZO-1, occludin, and claudin-1 were downregulated in colitis mice, whereas these changes were reversed by liquiritigenin. As indicated by TEM images and Endoplasmic reticulum stress (ERs) marker genes expression like GRP78, IRE1α, ATF6 and PERK that mice with colitis treated by oral liquiritigenin trended to attenuate ER stress. Collectively, the ameliorating role of liquiritigenin in gut inflammation can be attributed to intestinal barrier modulation, gut microbiome regulation, and ER stress alleviation. These findings provide a new perspective for developing liquiritigenin as a promising functional compound of food origin for preventing and mitigating UC.

Abstract This study presents the construction of an urban underground sensing system using distributed acoustic sensing (DAS) technology, which utilizes the existing optical fiber infrastructure around urban roads for communication. To address the challenges posed by the complexity and variability of DAS data in infrastructure monitoring environments such as urban roads, as well as the difficulty and poor effectiveness of raw data visualization, a novel method for visualizing DAS data is proposed. This method involves preprocessing the data through wavelet threshold denoising, combining it with the root-mean-square (RMS) energy index to generate a visualization, and applying the dynamic threshold method to remove and suppress abnormal data indicators. Finally, this paper tested the visualization performance to assess the effectiveness of the proposed method in improving urban road safety management. The study focused on three typical urban road safety risk events: vehicle driving, construction, and road subsurface cavity incidents. The results demonstrate the efficacy of the data visualization method, showing improved visualization of vehicle trajectory directions and numbers, construction segment behaviors, and approximate road subsurface cavity locations in the time domain compared to the original data.

Abstract Head and neck epithelial tissue tumors may be identified as head and neck squamous cell carcinoma (HNSC). Numerous malignancies are encouraged by dysregulation of the FGF19-β-Klotho (KLB) axis in the tumor microenvironment. Using protein databases and RT-qPCR, we examined KLB expression in HNSC. In HNSC, higher KLB expression was linked to longer survival times and better prognoses. Furthermore, variations in drug susceptibility and immunological infiltration were noted according to KLB expression levels. These results underscore the importance of KLB in the course and management of HNSC by indicating that it may function as a possible prognostic marker and influence immunological and therapeutic responses in these individuals. Further study on HNSC is necessary to investigate KLB's potential as a therapeutic target and prognostic indicator.

Abstract Background and aims Inflammation is initiates the propagation phase of aortic valve calcification. The activation of NLRP3 signaling in macrophages plays a crucial role in the progression of calcific aortic valve stenosis (CAVS). IFN-γ regulates NLRP3 activity in macrophages. This study aimed to explore the mechanism of IFN-γ regulation and its impact on CAVS progression and valve interstitial cell transdifferentiation. Methods and results The number of Th1 cells and the expression of IFN-γ and STAT1 in the aortic valve, spleen and peripheral blood increased significantly as CAVS progressed. To explore the mechanisms underlying the roles of Th1 cells and IFN-γ, we treated CAVS mice with IFN-γ-AAV9 or an anti-IFN-γ neutralizing antibody. While IFN-γ promoted aortic valve calcification and dysfunction, it significantly decreased NLRP3 signaling in splenic macrophages and Ly6C+ monocytes. In vitro coculture showed that Th1 cells inhibited NLPR3 activation in ox-LDL-treated macrophages through the IFN-γR1/IFN-γR2-STAT1 pathway. Compared with untreated medium, conditioned medium from Th1-treated bone marrow–derived macrophages reduced the osteogenic calcification of valvular interstitial cells. Conclusion Inhibition of the NLRP3 inflammasome by Th1 cells protects against valvular interstitial cell calcification as a negative feedback mechanism of adaptive immunity toward innate immunity. This study provides a precision medicine strategy for CAVS based on the targeting of anti-inflammatory mechanisms. Graphical Abstract

Abstract Background Tumor-associated macrophages (TAMs) constitute a substantial part of human hepatocellular carcinoma (HCC). The present study was devised to explore TAM diversity and their roles in HCC progression. Methods Through the integration of multiple 10 × single-cell transcriptomic data derived from HCC samples and the use of consensus nonnegative matrix factorization (an unsupervised clustering algorithm), TAM molecular subtypes and expression programs were evaluated in detail. The roles played by these TAM subtypes in HCC were further probed through pseudotime, enrichment, and intercellular communication analyses. Lastly, vitro experiments were performed to validate the relationship between CD63, which is an inflammatory TAM expression program marker, and tumor cell lines. Results We found that the inflammatory expression program in TAMs had a more obvious interaction with HCC cells, and CD63, as a marker gene of the inflammatory expression program, was associated with poor prognosis of HCC patients. Both bulk RNA-seq and vitro experiments confirmed that higher TAM CD63 expression was associated with the growth of HCC cells as well as their epithelial-mesenchymal transition, metastasis, invasion, and the reprogramming of lipid metabolism. Conclusions These analyses revealed that the TAM inflammatory expression program in HCC is closely associated with malignant tumor cells, with the hub gene CD63 thus representing an ideal target for therapeutic intervention in this cancer type.

Abstract Membrane budding, which underlies fundamental processes like endocytosis, intracellular trafficking, and viral infection, is thought to involve membrane coat-forming proteins, including the most observed clathrin, to form Ω-shape profiles and helix-forming proteins like dynamin to constrict Ω-profiles’ pores and thus mediate fission. Challenging this fundamental concept, we report that polymerized clathrin is required for Ω-profiles’ pore closure and that clathrin around Ω-profiles’ base/pore region mediates pore constriction/closure in neuroendocrine chromaffin cells. Mathematical modeling suggests that clathrin polymerization at Ω-profiles’ base/pore region generates forces from its intrinsically curved shape to constrict/close the pore. This new fission function may exert broader impacts than clathrin’s well-known coat-forming function during clathrin (coat)-dependent endocytosis, because it underlies not only clathrin (coat)-dependent endocytosis, but also diverse endocytic modes, including ultrafast, fast, slow, bulk, and overshoot endocytosis previously considered clathrin (coat)-independent in chromaffin cells. It mediates kiss-and-run fusion (fusion pore closure) previously considered bona fide clathrin-independent, and limits the vesicular content release rate. Furthermore, analogous to results in chromaffin cells, we found that clathrin is essential for fast and slow endocytosis at hippocampal synapses where clathrin was previously considered dispensable, suggesting clathrin in mediating synaptic vesicle endocytosis and fission. These results suggest that clathrin and likely other intrinsically curved coat proteins are a new class of fission proteins underlying vesicle budding and fusion. The half-a-century concept and studies that attribute vesicle-coat contents’ function to Ω-profile formation and classify budding as coat-protein (e.g., clathrin)-dependent or -independent may need to be re-defined and re-examined by considering clathrin’s pivotal role in pore constriction/closure.

Abstract Background Traumatic fractures occur frequently worldwide. However, research remains limited on the association between short-term exposure to temperature and traumatic fractures. This study aims to explore the impact of apparent temperature (AT) on emergency visits (EVs) due to traumatic fractures. Methods Based on EVs data for traumatic fractures and the contemporary meteorological data, a generalized Poisson regression model along with a distributed lag nonlinear model (DLNM) were undertaken to determine the impact of AT on traumatic fracture EVs. Subgroup analysis by gender and age and sensitivity analysis were also performed. Results A total of 25,094 EVs for traumatic fractures were included in the study. We observed a wide “J”-shaped relationship between AT and risk of traumatic fractures, with AT above 9.5 °C positively associated with EVs due to traumatic fractures. The heat effects became significant at cumulative lag 0–11 days, and the relative risk (RR) for moderate heat (95th percentile, 35.7 °C) and extreme heat (99.5th percentile, 38.8 °C) effect was 1.311 (95% CI: 1.132–1.518) and 1.418 (95% CI: 1.191–1.688) at cumulative lag 0–14 days, respectively. The cold effects were consistently non-significant on single or cumulative lag days across 0–14 days. The heat effects were higher among male and those aged 18–65 years old. The sensitivity analysis results remained robust. Conclusion Higher AT is associated with cumulative and delayed higher traumatic fracture EVs. The male and those aged 18–65 years are more susceptible to higher AT.

Abstract Colorectal cancer (CRC) arises via the progressive accumulation of dysregulation in key genes including oncogenes and tumor-suppressor genes. Prostaglandin-endoperoxide synthase 2 (PTGS2, also called COX2) acts as an oncogenic driver in CRC. Here, we explored the upstream transcription factors (TFs) responsible for elevating PTGS2 expression in CRC cells. The results showed that PTGS2 silencing repressed cell growth, migration and invasion in HCT116 and SW480 CRC cells. The two fragments (499–981 bp) and (1053–1434 bp) were confirmed as the core TF binding profiles of the PTGS2 promoter. PTGS2 expression positively correlated with RUNX1 level in colon adenocarcinoma (COAD) samples using the TCGA-COAD dataset. Furthermore, RUNX1 acted as a positive regulator of PTGS2 expression by promoting transcriptional activation of the PTGS2 promoter via the 1086–1096 bp binding motif. In conclusion, our study demonstrates that PTGS2 upregulation induced by the TF RUNX1 promotes CRC cell growth, migration and invasion, providing an increased rationale for the use of PTGS2 inhibitors in CRC prevention and treatment.

Abstract Background Radioresistance is a key clinical constraint on the efficacy of radiotherapy in lung cancer patients. REV1 DNA directed polymerase (REV1) plays an important role in repairing DNA damage and maintaining genomic stability. However, its role in the resistance to radiotherapy in lung cancer is not clear. This study aims to clarify the role of REV1 in lung cancer radioresistance, identify the intrinsic mechanisms involved, and provide a theoretical basis for the clinical translation of this new target for lung cancer treatment. Methods The effect of targeting REV1 on the radiosensitivity was verified by in vivo and in vitro experiments. RNA sequencing (RNA-seq) combined with nontargeted metabolomics analysis was used to explore the downstream targets of REV1. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify the content of specific amino acids. The coimmunoprecipitation (co-IP) and GST pull-down assays were used to validate the interaction between proteins. A ubiquitination library screening system was constructed to investigate the regulatory proteins upstream of REV1. Results Targeting REV1 could enhance the radiosensitivity in vivo, while this effect was not obvious in vitro. RNA sequencing combined with nontargeted metabolomics revealed that the difference result was related to metabolism, and that the expression of glycine, serine, and threonine (Gly/Ser/Thr) metabolism signaling pathways was downregulated following REV1 knockdown. LC-MS/MS demonstrated that REV1 knockdown results in reduced levels of these three amino acids and that cystathionine γ-lyase (CTH) was the key to its function. REV1 enhances the interaction of CTH with the E3 ubiquitin ligase Rad18 and promotes ubiquitination degradation of CTH by Rad18. Screening of the ubiquitination compound library revealed that the ubiquitin-specific peptidase 9 X-linked (USP9X) is the upstream regulatory protein of REV1 by the ubiquitin-proteasome system, which remodels the intracellular Gly/Ser/Thr metabolism. Conclusion USP9X mediates the deubiquitination of REV1, and aberrantly expressed REV1 acts as a scaffolding protein to assist Rad18 in interacting with CTH, promoting the ubiquitination and degradation of CTH and inducing remodeling of the Gly/Ser/Thr metabolism, which leads to radioresistance. A novel inhibitor of REV1, JH-RE-06, was shown to enhance lung cancer cell radiosensitivity, with good prospects for clinical translation.

Abstract Background C-X-C motif chemokine ligand (CXCL8), also known as interleukin-8, is a prototypical CXC family chemokine bearing a glutamic acid-leucine-arginine (ELR) motif that plays key roles in the onset and progression of a range of cancers in humans. Many prior studies have focused on exploring the relationship between CXCL8 gene polymorphisms and the risk of cancer. However, the statistical power of many of these reports was limited, yielding ambiguous or conflicting results in many cases. Methods Accordingly, the PubMed, Wanfang, Scopus and Web of Science databases were searched for articles published until July 20, 2023 using the keywords ‘IL-8’ or ‘interleukin-8’ or ‘CXCL8’, ‘polymorphism’ and ‘cancer’ or ‘tumor’. Odds ratios (ORs) and 95% confidence intervals (CIs) were utilized to examine the association. The CXCL8 +781 polymorphism genotypes were assessed with a TaqMan assay. Results About 29 related publications was conducted in an effort to better understand the association between these polymorphisms and disease risk. The CXCL8 -353A/T polymorphism was associated with an increased overall cancer risk [A vs. T, odds ratio (OR) = 1.255, 95% confidence interval (CI) (1.079–1.459), P heterogeneity = 0.449, P = 0.003]. The CXCL8 +781 T/C allele was similarly associated with a higher risk of cancer among Caucasians [TT vs. TC + CC, OR = 1.320, 95%CI (1.046–1.666), P heterogeneity = 0.375, P = 0.019]. Furthermore, oral cancer patients carrying the CXCL8 +781 TT + TC genotypes exhibited pronounced increases in serum levels of CXCL8 as compared to the CC genotype (P

Abstract In this paper, we present an improved calculation for the decay rate of the rare Z-boson decay into $$J/\psi + J/\psi .$$ J / ψ + J / ψ . This decay is dominated by the photon fragmentation mechanism, i.e., the transition $$Z\rightarrow J/\psi + \gamma ^{*}$$ Z → J / ψ + γ ∗ followed by the fragmentation $$\gamma ^{*}\rightarrow J/\psi .$$ γ ∗ → J / ψ . In our calculation, the amplitude of $$\gamma ^{*}\rightarrow J/\psi $$ γ ∗ → J / ψ is extracted from the measured value of $$\Gamma (J/\psi \rightarrow e^+ e^-),$$ Γ ( J / ψ → e + e - ) , and the amplitude of $$Z\rightarrow J/\psi + \gamma ^{*}$$ Z → J / ψ + γ ∗ is calculate through the light-cone approach. The higher-order QCD and relativistic corrections in the amplitude of $$\gamma ^{*}\rightarrow J/\psi $$ γ ∗ → J / ψ and the large logarithms of $$m_{_Z}^2/m_c^2$$ m Z 2 / m c 2 that appear in the amplitude of $$Z\rightarrow J/\psi + \gamma ^{*}$$ Z → J / ψ + γ ∗ are resummed in our calculation. Besides, the non-fragmentation amplitude is calculated based on the NRQCD factorization, and the next-to-leading order QCD and relativistic corrections are included. The obtained branching fraction for this Z decay channel is $$8.66 ^{+1.48} _{-0.69}\times 10^{-11}.$$ 8 . 66 - 0.69 + 1.48 × 10 - 11 .

Purpose: To investigate the clinical value of Clinical Treatment Score Post-5 Years (CTS5) to predict the survival benefits of postmastectomy radiotherapy (PMRT) of patients with T1-2N1 luminal breast cancer (BC). Methods: Patients who were diagnosed with T1-2N1 luminal BC between 2010 and 2015 were included in the Surveillance, Epidemiology, and End Results database. The chi-square test, binomial logistic regression, Kaplan-Meier analysis, and multivariable Cox proportional hazard model were used for statistical analyses. Results: A total of 11190 patients were included with a median follow-up time of 76 months. Regarding the CTS5 classification, 1641 (14.7 %), 3915 (35.0 %), and 5633 (50.3 %) patients had low-risk, intermediate-risk, and high-risk diseases, respectively. Patients with younger age, T2 stage, higher tumor grade, a higher number of positive lymph nodes, infiltrating lobular carcinoma subtype, and receipt of chemotherapy were associated with the receipt of PMRT (all P

Objectives: Alpha fetoprotein(AFP) overexpression connecting with macrophage dysfunction remain poorly defined. In this study, explore AFP regulates macrophage immunomodulation in hepatocellular carcinoma(HCC) through comprehensive in vitro and in vivo studies. Methods: Immunohistochemical and immunofluorescence staining was used to analyze the relativity of AFP and cellular membrane CD47 expression in clinical 30 HCC tissues, and the expression of AFP and CD47 in HCC cells. The intelligent living-cell high-throughput imaging analyzer was applied to dynamically track and image of macrophages to phagocytize HCC cells. The effect of AFP on regulating the level of CD47 in cellular membrane and growth of tumor in vivo was performed by animal experiment. The association of AFP and CD47 in HCC cells was detected by single cell analysis. Results: The present results indicated that AFP upregulated the localization of CD47 on the HCC cell surface. CD47 overexpression stimulates HCC to escape immune surveillance by transmitting “don't eat me” signals to macrophages, lead to inhibit macrophage to phagocytize HCC cells. Mechanistically, the results demonstrated that AFP enhanced CD47 membrane translocation by interacting with Hu-Antigen R(HuR), an RNA-binding protein that regulates mRNA stability and translation. AFP alters the subcellular distribution of HuR, increasing its cytoplasmic accumulation and binding to CD47 transcript. Conclusions: AFP enhanced CD47 membrane translocation by interacting with HuR. These findings proved that AFP could inhibit macrophage to phagocytize HCC cells by upregulating the localization of CD47 on the HCC cell surface. Combination of AFP with CD47 blockade may be a potential therapeutic strategy for HCC treatment.