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1.
J Ethnopharmacol ; : 118275, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38729534

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Jian-Zhong decoction (DJZD) is a herbal formula clinically used for abdominal pain and diarrhea induced by spleen-Yang deficiency syndrome. Recently, treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with DJZD has received increasing attention, but the underlying mechanism of action remains elusive. AIM OF THE STUDY: We aimed to evaluate the therapeutic effect of DJZD on IBS-D rats and to elucidate the underlying mechanisms. MATERIALS AND METHODS: An IBS-D rats model was constructed using a two-factor superposition method of neonatal maternal separation and Senna folium aqueous extract lavage. Moreover, the effect of DJZD was evaluated based on the body weight, rectal temperature, abdominal withdrawal reflex (AWR), and Bristol stool scale score (BSS). The factors that regulate the DJZD effects on IBS-D were estimated using whole microbial genome, transcriptome sequencing (RNA-Seq), flow cytometry, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analyses. RESULTS: We found that DJZD alleviated the symptoms of IBS-D rats, with the low-dose (2.4 g/kg) as the better ones, as shown by the higher body mass and lower AWR score and BSS. At the phylum level, the relative abundance of Bacteroidetes was obviously increased, and at the genus level, Bacteroides was increased, while that of Firmicutes_bacterium_424 and Ruminococcus gnavus was decreased in DJZD group. The significantly enriched GO terms after treatment with DJZD mainly included the immune response, positive regulation of activated T cell proliferation, and positive regulation of interleukin-17 (IL-17) production. Importantly, flow cytometry analysis further revealed that the T helper cell type 17/regulatory T cell (Th17/Treg) balance contributed to the DJZD-induced alleviation of IBS-D symptoms, as DJZD downregulated Th17/Treg ratio and Th17 cell-related cytokines IL-17 and IL-6 levels in the colon. CONCLUSIONS: These results demonstrate that DJZD has a good therapeutic effect on IBS-D rats, probably by maintaining the homeostasis of gut microbiota and regulating Th17/Treg balance and its related inflammatory factors.

2.
Mem Cognit ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744775

ABSTRACT

Working- and long-term memory are often studied in isolation. To better understand the specific limitations of working memory, effort is made to reduce the potential influence of long-term memory on performance in working memory tasks (e.g., asking participants to remember artificial, abstract items rather than familiar real-world objects). However, in everyday life we use working- and long-term memory in tandem. Here, our goal was to characterize how long-term memory can be recruited to circumvent capacity limits in a typical visual working memory task (i.e., remembering colored squares). Prior work has shown that incidental repetitions of working memory arrays often do not improve visual working memory performance - even after dozens of incidental repetitions, working memory performance often shows no improvement for repeated arrays. Here, we used a whole-report working memory task with explicit rather than incidental repetitions of arrays. In contrast to prior work with incidental repetitions, in two behavioral experiments we found that explicit repetitions of arrays yielded robust improvement to working memory performance, even after a single repetition. Participants performed above chance at recognizing repeated arrays in a later long-term memory test, consistent with the idea that long-term memory was used to rapidly improve performance across array repetitions. Finally, we analyzed inter-item response times and we found a response time signature of chunk formation that only emerged after the array was repeated (inter-response time slowing after two to three items); thus, inter-item response times may be useful for examining the coordinated interaction of visual working and long-term memory in future work.

3.
Cell ; 187(10): 2521-2535.e21, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38697107

ABSTRACT

Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.


Subject(s)
Immunotherapy , Tumor Microenvironment , Animals , Immunotherapy/methods , Mice , Dogs , Humans , Dendritic Cells/immunology , Dendritic Cells/metabolism , Cytokines/metabolism , Glioblastoma/therapy , Glioblastoma/immunology , Mice, Inbred C57BL , Female , Glioma/therapy , Glioma/immunology , Antigens, Neoplasm/immunology , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , RNA, Messenger/metabolism , RNA, Messenger/genetics , RNA/metabolism , RNA/therapeutic use , Cell Line, Tumor , Neoplasms/therapy , Neoplasms/immunology , Brain Neoplasms/therapy , Brain Neoplasms/immunology
4.
J Transl Med ; 22(1): 369, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637862

ABSTRACT

BACKGROUND: Patients with inflammatory bowel disease (IBD), dysbiosis, and immunosuppression who receive fecal microbiota transplantation (FMT) from healthy donors are at an increased risk of developing bacteremia. This study investigates the efficacy of a mixture of seven short-chain fatty acid (SCFA)-producing bacterial strains (7-mix), the resulting culture supernatant mixture (mix-sup), and FMT for treating experimental ulcerative colitis (UC) and evaluates underlying mechanisms. METHODS: Utilizing culturomics, we isolated and cultured SCFA-producing bacteria from the stool of healthy donors. We used a mouse model of acute UC induced by dextran sulfate sodium (DSS) to assess the effects of 7-mix, mix-sup, and FMT on intestinal inflammation and barrier function, microbial abundance and diversity, and gut macrophage polarization by flow cytometry, immunohistochemistry, 16S rRNA gene sequencing, and transwell assays. RESULTS: The abundance of several SCFA-producing bacterial taxa decreased in patients with UC. Seven-mix and mix-sup suppressed the inflammatory response and enhanced intestinal mucosal barrier function in the mouse model of UC to an extent similar to or superior to that of FMT. Moreover, 7-mix and mix-sup increased the abundance of SCFA-producing bacteria and SCFA concentrations in colitic mice. The effects of these interventions on the inflammatory response and gut barrier function were mediated by JAK/STAT3/FOXO3 axis inactivation in macrophages by inducing M2 macrophage polarization in vivo and in vitro. CONCLUSIONS: Our approach provides new opportunities to rationally harness live gut probiotic strains and metabolites to reduce intestinal inflammation, restore gut microbial composition, and expedite the development of safe and effective treatments for IBD.


Subject(s)
Colitis, Ulcerative , Colitis , Gastrointestinal Microbiome , Inflammatory Bowel Diseases , STAT3 Transcription Factor , Humans , Mice , Animals , Colitis, Ulcerative/therapy , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/metabolism , Fatty Acids, Volatile/adverse effects , Fatty Acids, Volatile/metabolism , Bacteria/metabolism , Disease Models, Animal , Inflammation , Dextran Sulfate/adverse effects , Mice, Inbred C57BL , Colon , Forkhead Box Protein O3/metabolism
5.
Environ Int ; 187: 108670, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38669720

ABSTRACT

Antibiotics are extensively utilized in the livestock and poultry industry and can accumulate in animals and the environment, leading to potential health risks for humans via food and water consumption. Research on antibiotic toxicity, particularly their impact as endocrine disruptors on the male reproductive system, is still in its nascent stages. This review highlights the toxic effect of antibiotics on the male reproductive system, detailing the common routes of exposure and the detrimental impact and mechanisms of various antibiotic classes. Additionally, it discusses the protective role of food-derived active substances against the reproductive toxicity induced by antibiotics. This review aims to raise awareness about the reproductive toxicity of antibiotics in males and to outline the challenges that must be addressed in future research.

6.
Biochem Biophys Res Commun ; 710: 149895, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38593620

ABSTRACT

Neurotoxicity is a common side effect of certain types of therapeutic drugs, posing a major hurdle for their clinical application. Accumulating evidence suggests that ferroptosis is involved in the neurotoxicity induced by these drugs. Therefore, targeting ferroptosis is considered to be a reasonable approach to prevent such side effect. Arctigenin (ATG) is a major bioactive ingredient of Arctium lappa L., a popular medicinal plant in Asia, and has been reported to have multiple bioactivities including neuroprotection. However, the mechanisms underlying the neuroprotection of ATG has not been well elucidated. The purpose of this study was to investigate whether the neuroprotection of ATG was associated with its ability to protect neuronal cells from ferroptosis. Using neuronal cell ferroptosis model induced by either classic ferroptosis induces or therapeutic drugs, we demonstrated for the first time that ATG in the nanomolar concentration range effectively prevented neuronal cell ferroptosis induced by classic ferroptosis inducer sulfasalazine (SAS) and erastin (Era), or therapeutic drug oxaliplatin (OXA) and 5-fluorouracil (5-FU). Mechanistically, we uncovered that the anti-ferroptotic effect of ATG was attributed to its ability to activate SLC7A11-cystine-cysteine axis. The findings of the present study implicate that ATG holds great potential to be developed as a novel agent for preventing SLC7A11 inhibition-mediated neurotoxicity.


Subject(s)
Antineoplastic Agents , Ferroptosis , Furans , Lignans , Neurotoxicity Syndromes , Humans , Cysteine , Cystine , Fluorouracil , Antineoplastic Agents/pharmacology , Amino Acid Transport System y+
7.
Clin Transl Radiat Oncol ; 46: 100767, 2024 May.
Article in English | MEDLINE | ID: mdl-38576855

ABSTRACT

Centrally located hepatocellular carcinoma (HCC) is difficult to be radically resected due to its special location close to major hepatic vessels. Thus, we aimed to assess whether stereotactic body radiation therapy (SBRT) can be an effective and safe approach for centrally located HCC. This retrospective study included 172 patients with centrally located HCC who were treated with SBRT. Overall survival (OS) was analyzed as the primary endpoint. Rates of progression-free survival (PFS), local control, intrahepatic relapse, extrahepatic metastasis and toxicities were analyzed as secondary endpoints. The OS rates of 1-, 3-, and 5-year were 97.7%, 86.7%, and 76.3%, respectively. The PFS/local control rates of 1-, 3-, and 5-year were 94.1%/98.2%, 76.8%/94.9%, and 59.3%/92.3%, respectively. The cumulative incidence of intrahepatic relapse/extrahepatic metastases of 1-, 3-, and 5-year were 3.7%/2.9%, 25.0%/7.4%, and 33.3%/9.8%, respectively. Both univariate and multivariate analyses revealed that patients received BED10 at 100 Gy or more had better OS. Radiation-related adverse events were mild to moderate according to Common Terminology Criteria for Adverse Events, and no toxicities over grade 3 were observed. Patients with centrally located HCC in our cohort who received SBRT had similar OS and PFS rates compared to those reported in literatures who received surgery with neoadjuvant or adjuvant intensity-modulated radiation therapy. These results indicate that SBRT is an effective and well-tolerated method for patients with centrally located HCC, suggesting that it may serve as a reasonable alternative treatment for these kind of patients.

8.
Opt Express ; 32(7): 12243-12256, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38571053

ABSTRACT

Integral imaging is a kind of true three-dimensional (3D) display technology that uses a lens array to reconstruct vivid 3D images with full parallax and true color. In order to present a high-quality 3D image, it's vital to correct the axial position error caused by the misalignment and deformation of the lens array which makes the reconstructed lights deviate from the correct directions, resulting in severe voxel drifting and image blurring. We proposed a sub-pixel marking method to measure the axial position error of the lenses with great accuracy by addressing the sub-pixels under each lens and forming a homologous sub-pixel pair. The proposed measurement method relies on the geometric center alignment of image points, which is specifically expressed as the overlap between the test 3D voxel and the reference 3D voxel. Hence, measurement accuracy could be higher. Additionally, a depth-based sub-pixel correction method was proposed to eliminate the voxel drifting. The proposed correction method takes the voxel depth into consideration in the correction coefficient, and achieves accurate error correction for 3D images with different depths. The experimental results well confirmed that the proposed measuring and correction methods can greatly suppress the voxel drifting caused by the axial position error of the lenses, and greatly improve the 3D image quality.

9.
Heliyon ; 10(7): e28553, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38596011

ABSTRACT

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder, characterized by progressive limb weakness, dysphagia, dysphonia, and respiratory failure due to degeneration of upper and lower motor neurons. The pathogenesis of ALS is still unclear. Neuroinflammation has been found to be involved in its development and progression. Cytokines play a significant role in the inflammatory process. This study aims to identify novel biomarkers that may assist in the diagnosis of ALS. Methods: In Fujian Medical University Union Hospital and Huashan Hospital Fudan University, two independent centers, we prospectively recruited 50 ALS patients, and 41 healthy controls (25 ALS and 26 controls in the first stage and 25 ALS and 15 controls in the validation stage). An 18-plex Luminex kit was used to screen the serum cytokines levels in the first stage. Commercial ELISA kits were used to measure the levels of target cytokines in the validation stage. A single-molecule array HD-X platform was applied to assess the levels of serum neurofilament light chain (NFL). Results: The levels of serum IL-18 were markedly increased in patients with ALS in the first stage (p = 0.016). The ROC curve showed an area under the curve at 0.695 (95% CI 0.50-0.84) in distinguishing ALS patients from healthy controls. The IL-21 was decreased in elderly patients when grouped by 55 years old (the medium age). Furthermore, the IL-5, IL-13, IL-18, and NFL had a positive relationship with the disease progression of ALS. We also found that serum IL-18 was markedly increased in ALS patients in the validation stage (167.67 [148.25-175.59] vs 116.44 [102.43-122.19]pg/ml, p < 0.0015). Conclusion: In this study, we identified systemic cytokine profile changes in the serum of ALS patients, especially the elevated IL-18, as well as the decreased IL-21 in elder patients. These changes in serum cytokine profiles may shed new light on an in-depth understanding of the immunopathogenic characteristics of ALS.

10.
Anticancer Drugs ; 35(6): 501-511, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38478015

ABSTRACT

Taxol is widely used in the treatment of nasopharyngeal carcinoma (NPC); nevertheless, the acquired resistance of NPC to Taxol remains one of the major obstacles in clinical treatment. In this study, we aimed to investigate the role and mechanism of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in Taxol resistance of NPC. Taxol-resistant NPC cell lines were established by exposing to gradually increased concentration of Taxol. Relative mRNA and protein levels were tested using qRT-PCR and western blot, respectively. NPC cell viability and apoptosis were assessed by cell counting kit-8 and flow cytometry analysis, respectively. Cell migration and invasion capacities were measured using transwell assay. Interaction between IGF2BP1 and AKT2 was examined by RNA immunoprecipitation assay. The N6-methyladenosine level of AKT2 was tested using methylated RNA immunoprecipitation-qPCR. IGF2BP1 expression was enhanced in Taxol-resistant NPC cell lines. Knockdown of IGF2BP1 strikingly enhanced the sensitivity of NPC cells to Taxol and repressed the migration and invasion of NPC cells. Mechanistically, IGF2BP1 elevated the expression of AKT2 by increasing its mRNA stability. Furthermore, overexpression of AKT2 reversed the inhibitory roles of IGF2BP1 silence on Taxol resistance and metastasis. Our results indicated that IGF2BP1 knockdown enhanced the sensitivity of NPC cells to Taxol by decreasing the expression of AKT2, implying that IGF2BP1 might be promising candidate target for NPC treatment.


Subject(s)
Apoptosis , Cell Movement , Drug Resistance, Neoplasm , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Paclitaxel , Proto-Oncogene Proteins c-akt , RNA-Binding Proteins , Humans , Paclitaxel/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/genetics , Drug Resistance, Neoplasm/drug effects , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/genetics , Cell Movement/drug effects , Apoptosis/drug effects , Cell Line, Tumor , Antineoplastic Agents, Phytogenic/pharmacology , Up-Regulation , Cell Proliferation/drug effects , Adenosine/analogs & derivatives , Adenosine/pharmacology , Gene Expression Regulation, Neoplastic/drug effects
11.
Article in English | MEDLINE | ID: mdl-38489169

ABSTRACT

BACKGROUND: At present, most articles mainly focused on the diagnosis of thyroid nodules by using artificial intelligence (AI), and there was little research on the detection performance of AI in thyroid nodules. OBJECTIVE: To explore the value of a real-time AI based on computer-aided diagnosis system in the detection of thyroid nodules and to analyze the factors influencing the detection accuracy. METHODS: From June 1, 2022 to December 31, 2023, 224 consecutive patients with 587 thyroid nodules were prospective collected. Based on the detection results determined by two experienced radiologists (both with more than 15 years experience in thyroid diagnosis), the detection ability of thyroid nodules of radiologists with different experience levels (junior radiologist with 1 year experience and senior radiologist with 5 years experience in thyroid diagnosis) and real-time AI were compared. According to the logistic regression analysis, the factors influencing the real-time AI detection of thyroid nodules were analyzed. RESULTS: The detection rate of thyroid nodules by real-time AI was significantly higher than that of junior radiologist (P = 0.013), but lower than that of senior radiologist (P = 0.001). Multivariate logistic regression analysis showed that nodules size, superior pole, outside (near carotid artery), close to vessel, echogenicity (isoechoic, hyperechoic, mixed-echoic), morphology (not very regular, irregular), margin (unclear), ACR TI-RADS category 4 and 5 were significant independent influencing factors (all P < 0.05). With the combination of real-time AI and radiologists, junior and senior radiologist increased the detection rate to 97.4% (P < 0.001) and 99.1% (P = 0.015) respectively. CONCLUSONS: The real-time AI has good performance in thyroid nodule detection and can be a good auxiliary tool in the clinical work of radiologists.

12.
BMC Microbiol ; 24(1): 91, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38500062

ABSTRACT

BACKGROUND: Probiotics are a potentially effective therapy for inflammatory bowel disease (IBD); IBD is linked to impaired gut microbiota and intestinal immunity. However, the utilization of an antibiotic cocktail (Abx) prior to the probiotic intervention remains controversial. This study aims to identify the effect of Abx pretreatment from dextran sulfate sodium (DSS)-induced colitis and to evaluate whether Abx pretreatment has an enhanced effect on the protection of Clostridium butyricum Miyairi588 (CBM) from colitis. RESULTS: The inflammation, dysbiosis, and dysfunction of gut microbiota as well as T cell response were both enhanced by Abx pretreatment. Additionally, CBM significantly alleviated the DSS-induced colitis and impaired gut epithelial barrier, and Abx pretreatment could enhance these protective effects. Furthermore, CBM increased the benefit bacteria abundance and short-chain fatty acids (SCFAs) level with Abx pretreatment. CBM intervention after Abx pretreatment regulated the imbalance of cytokines and transcription factors, which corresponded to lower infiltration of Th1 and Th17 cells, and increased Th2 cells. CONCLUSIONS: Abx pretreatment reinforced the function of CBM in ameliorating inflammation and barrier damage by increasing beneficial taxa, eliminating pathogens, and inducing a protective Th2 cell response. This study reveals a link between Abx pretreatment, microbiota, and immune response changes in colitis, which provides a reference for the further application of Abx pretreatment before microbiota-based intervention.


Subject(s)
Colitis , Inflammatory Bowel Diseases , Probiotics , Humans , Animals , Mice , Anti-Bacterial Agents/adverse effects , Th2 Cells , Th17 Cells , Colitis/chemically induced , Colitis/prevention & control , Probiotics/pharmacology , Inflammation , Immunity , Mice, Inbred C57BL , Disease Models, Animal
13.
Int J Mol Sci ; 25(5)2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38473706

ABSTRACT

Acute kidney injury (AKI) is a common clinical problem with high morbidity and mortality. The discovery of ferroptosis has provided novel insights into the mechanisms underlying AKI and paves the way for developing ferroptosis-based approaches to treat AKI. Glycyrol (GC) is a representative coumarin compound isolated from licorice that demonstrates various pharmacological activities. However, its potential for a protective effect against kidney injury remains unknown. We hypothesized that GC might be able to protect against AKI via suppression of ferroptosis. This hypothesis was tested in a cell-culture model of RSL3-induced nephrocyte ferroptosis and a mouse model of folic acid-induced AKI. The results showed that GC exerted a significant protective effect against nephrocyte ferroptosis in vitro and was effective against folic acid-induced AKI in vivo, where it was mechanistically associated with suppressing HO-1-mediated heme degradation. Collectively, the findings of the present study support the hypothesis that GC holds considerable potential to be developed as a novel agent for treating ferroptosis-related AKI.


Subject(s)
Acute Kidney Injury , Animals , Mice , Flavonoids , Cell Culture Techniques , Folic Acid
14.
Mater Horiz ; 11(8): 1908-1922, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38334032

ABSTRACT

Transgranular brittle fracture is the dominant failure mode of brittle materials, including ceramics and ceramic matrix composites. However, strengthening these materials without sacrificing their toughness has been a big challenge. In this study, an innovative approach is proposed to achieve coordinated strengthening and toughening of ceramics-based composites by introducing specific ductile coherent nanoparticles into ceramic grains. As an example, the WC-Co cemented tungsten carbides were used to demonstrate how this brittle material can achieve ultrahigh strength without losing toughness by seeding metallic nanoparticles inside WC grains. The mechanisms for inducing the formation and modulating the amount, size, and distribution of such nanophase within the ceramic grains were disclosed. The fraction of transgranular ruptures of the brittle ceramic phase was reduced significantly due to the presence of the ductile coherent in-grain nanoparticles. Both the strength and strain limit of the cemented carbides were remarkably increased compared to their counterparts reported in the literature. The coordinated strengthening and toughening strategy proposed in this work is applicable to a broad range of ceramics and ceramic matrix composites to obtain superior comprehensive mechanical properties.

15.
Radiother Oncol ; 194: 110154, 2024 May.
Article in English | MEDLINE | ID: mdl-38367938

ABSTRACT

BACKGROUND AND PURPOSE: The delineation of clinical target volume (CTV) for primary nasopharyngeal carcinoma (NPC) is currently controversial and the international guideline still recommend a uniform border for CTV regardless of the tumor extent. We conducted this prospective, real-world study to evaluate the clinical outcomes of our individualized CTV delineation method based on distance plus substructures. MATERIALS AND METHODS: We preliminarily investigated the local extension patterns of NPC on 354 newly diagnosed patients and defined the structures surrounding the nasopharynx as Level-1 to Level-4 substructures stratified by the risk of invasion. We then enrolled patients with newly diagnosed NPC without distant metastasis to investigate our individualized CTV delineation protocol. All patients received intensity modulated radiotherapy. CTV1 and CTV2 were prescribed doses of 60 Gy and 54 Gy in 30 âˆ¼ 33 fractions. The primary endpoint was local recurrence-free survival (LRFS); secondary endpoints included regional control and survival, estimated using the Kaplan-Meier method. The local failure patterns were also analyzed. RESULTS: From January 2008 to December 2012 and from January 2013 to September 2019, 356 and 648 patients were enrolled, named as training set and validation set, respectively. With a median follow-up of 104.6 (interquartile, 73.1-126.9) and 51.4 (39.5-78.5) months, 31 (8.7 %) and 38 (5.9 %) patients in training and validation sets experienced local recurrence, and the 5-year LRFS was 93.0 % and 93.2 %, respectively; 63 (17.7 %) and 39 (6 %) patients died in training and validation sets, and the 5-year overall survival (OS) was 88.5 % and 93.4 %, respectively. For the whole study cohort (N = 1004) with a median follow-up of 66.6 (41.5-98.0) months, the 5-year LRFS and OS was 93.2 % and 91.5 %. The grade 3 late toxicities included xerostomia, subcutaneous fibrosis, hearing impairment, trismus, visuality impairment and skin atrophy, with a total incidence of 1.5 %. Sixty-seven of 69 (97.1 %) local recurrence was in high-dose area. CONCLUSION: Our individualized CTV delineation method can achieve favorable local tumor control and long-term survival outcomes with acceptable late toxicities.


Subject(s)
Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Neoplasm Invasiveness , Radiotherapy, Intensity-Modulated , Humans , Male , Female , Prospective Studies , Middle Aged , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/mortality , Radiotherapy, Intensity-Modulated/methods , Radiotherapy, Intensity-Modulated/adverse effects , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/mortality , Adult , Aged , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Young Adult
16.
Int J Biol Macromol ; 261(Pt 2): 129843, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38302027

ABSTRACT

Homologous recombination plays a key role in double-strand break repair, stalled replication fork repair, and meiosis. The RecA/Rad51 family recombinases catalyze the DNA strand invasion reaction that occurs during homologous recombination. However, the high sequence differences between homologous groups have hindered the thoroughly studies of this ancient protein family. The dynamic mechanisms of the family, particularly at the residual level, remain poorly understood. In this work, five representative RecA/Rad51 recombinase family members from all major kingdoms of living organisms: prokaryotes, eukaryotes, archaea, and viruses, were selected to explore the molecular mechanisms behind their conserved biological significance. A variety of techniques, including all-atom molecular dynamics simulation, perturbation response scanning, and protein structure network analysis, were used to examine the flexibility and correlation of protein domains, distribution of sensors and effectors and conserved hub residues. Furthermore, the potential communication routes between the ATP-binding region and the DNA-binding region of each recombinase were identified. Our results demonstrate the conserved molecular dynamics of these recombinases in the early stage of homologous recombination, including cooperative motions between regions, conserved sensing and effecting functional residue distribution, and conserved hub residues. Meanwhile, the unique ATP-DNA communication routes of each recombinase was also revealed. These results provide new insights into the mechanism of RecA/Rad51 family proteins, and provide new theoretical guidance for the development of allosteric inhibitors and the application of RecA/Rad51 family proteins.


Subject(s)
Rad51 Recombinase , Rec A Recombinases , Rad51 Recombinase/genetics , Rad51 Recombinase/chemistry , Rad51 Recombinase/metabolism , Rec A Recombinases/genetics , Rec A Recombinases/chemistry , Rec A Recombinases/metabolism , DNA-Binding Proteins/metabolism , DNA, Single-Stranded , DNA/chemistry , Recombinases/genetics , Recombinases/metabolism , Adenosine Triphosphate
17.
Acta Radiol ; : 2841851231217227, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38321752

ABSTRACT

BACKGROUND: Accurate differentiation of extremity soft-tissue tumors (ESTTs) is important for treatment planning. PURPOSE: To develop and validate an ultrasound (US) image-based radiomics signature to predict ESTTs malignancy. MATERIAL AND METHODS: A dataset of US images from 108 ESTTs were retrospectively enrolled and divided into the training cohort (78 ESTTs) and validation cohort (30 ESTTs). A total of 1037 radiomics features were extracted from each US image. The most useful predictive radiomics features were selected by the maximum relevance and minimum redundancy method, least absolute shrinkage, and selection operator algorithm in the training cohort. A US-based radiomics signature was built based on these selected radiomics features. In addition, a conventional radiologic model based on the US features from the interpretation of two experienced radiologists was developed by a multivariate logistic regression algorithm. The diagnostic performances of the selected radiomics features, the US-based radiomics signature, and the conventional radiologic model for differentiating ESTTs were evaluated and compared in the validation cohort. RESULTS: In the validation cohort, the area under the curve (AUC), sensitivity, and specificity of the US-based radiomics signature for predicting ESTTs malignancy were 0.866, 84.2%, and 81.8%, respectively. The US-based radiomics signature had better diagnostic predictability for predicting ESTT malignancy than the best single radiomics feature and the conventional radiologic model (AUC = 0.866 vs. 0.719 vs. 0.681 for the validation cohort, all P <0.05). CONCLUSION: The US-based radiomics signature could provide a potential imaging biomarker to accurately predict ESTT malignancy.

18.
Curr Med Chem ; 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38347784

ABSTRACT

Antioxidant research has recently become a popular topic. Medicinal plants are important sources of novel active compounds. Diarylheptanoids, a typical family of secondary plant metabolites, are of great interest owing to their extensive spectrum of biological activities. They possess a unique 1,7-diphenylmethane structural skeleton. Thus, this review summarizes the natural linear or macrocyclic diarylheptanoids with antioxidant activity in the last two decades. In addition, the relationships between the structural characteristics of natural diarylheptanoids and their antioxidant capacity were also discussed. All the available data highlight the potential of natural diarylheptanoids as novel antioxidants.

19.
J Org Chem ; 89(6): 4037-4041, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38389323

ABSTRACT

This study delves into the ion recognition capabilities of a novel host molecule, emphasizing the role of conformational locking in dictating ion selectivity. By employing the Buchwald-Hartwig cross-coupling reaction, we have notably shifted the ion receptor's selectivity from K+ to Na+. The findings are supported by computational simulations that reveal differences in binding energies and molecular strain impacting ion recognition. This innovative structural modification broadens the scope for alterations at the calix[4]arene's lower rim, paving the way for new methods and strategies in modulating ion recognition selectivity.

20.
J Exp Psychol Gen ; 153(4): 1131-1138, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38300543

ABSTRACT

Some stimuli are more memorable than others. Humans have demonstrated partial access to the properties that make a given stimulus more or less memorable. Recently, a deep neural network named ResMem was shown to successfully decode the memorability of visual stimuli as well. However, it remains unknown whether ResMem's predictions of memorability reflect the influence of stimulus-intrinsic properties or other stimulus-extrinsic factors that are known to induce interindividual consistency in memory performance (e.g., interstimulus similarity). Additionally, it is not clear whether ResMem and humans share access to overlapping properties of memorability. Here, in three experiments, we show that ResMem predicts stimulus-intrinsic memorability independent of stimulus-extrinsic factors, and that it captures aspects of memorability that are inaccessible to human observers. Taken together, our results confirm the multifaceted nature of memorability and establish a method for isolating its aspects that are largely inaccessible to humans. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Cognition , Memory , Humans , Neural Networks, Computer
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