ABSTRACT
Isoprothiolane (IPT) resistance has emerged in Magnaporthe oryzae, due to the long-term usage of IPT to control rice blast in China, yet the mechanisms of the resistance remain largely unknown. Through IPT adaptation on PDA medium, we obtained a variety of IPT-resistant mutants. Based on their EC50 values to IPT, the resistant mutants were mainly divided into three distinct categories, i.e., low resistance (LR, 6.5 ≤ EC50 < 13.0 µg/mL), moderate resistance 1 (MR-1, 13.0 ≤ EC50 < 25.0 µg/mL), and moderate resistance 2 (MR-2, 25.0 ≤ EC50 < 35.0 µg/mL). Molecular analysis of MoIRR (Magnaporthe oryzae isoprothiolane resistance related) gene demonstrated that it was associated only with the moderate resistance in MR-2 mutants, indicating that other mechanisms were associated with resistance in LR and MR-1 mutants. In this study, we mainly focused on the characterization of low resistance to IPT in M. oryzae. Mycelial growth and conidial germination were significantly reduced, indicating fitness penalties in LR mutants. Based on the differences of whole genome sequences between parental isolate and LR mutants, we identified a conserved MoVelB gene, encoding the velvet family transcription factor, and genetic transformation of wild type isolate verified that MoVelB gene was associated with the low resistance. Based on molecular analysis, we further demonstrated that the velvet family proteins VelB and VeA were indispensable for IPT toxicity and the deformation of the VelB-VeA-LaeA complex played a vital role for the low IPT-resistance in M. oryzae, most likely through the down-regulation of the secondary metabolism-related genes or CYP450 genes to reduce the toxicity of IPT.
Subject(s)
Ascomycota , Magnaporthe , Oryza , Magnaporthe/genetics , Thiophenes , Oryza/genetics , Plant DiseasesABSTRACT
Organic batteries using redox-active polymers and small organic compounds have become promising candidates for next-generation energy storage devices due to the abundance, environmental benignity, and diverse nature of organic resources. To date, tremendous research efforts have been devoted to developing advanced organic electrode materials and understanding the material structure-performance correlation in organic batteries. In contrast, less attention was paid to the correlation between electrolyte structure and battery performance, despite the critical roles of electrolytes for the dissolution of organic electrode materials, the formation of the electrode-electrolyte interphase, and the solvation/desolvation of charge carriers. In this review, we discuss the prospects and challenges of organic batteries with an emphasis on electrolytes. The differences between organic and inorganic batteries in terms of electrolyte property requirements and charge storage mechanisms are elucidated. To provide a comprehensive and thorough overview of the electrolyte development in organic batteries, the electrolytes are divided into four categories including organic liquid electrolytes, aqueous electrolytes, inorganic solid electrolytes, and polymer-based electrolytes, to introduce different components, concentrations, additives, and applications in various organic batteries with different charge carriers, interphases, and separators. The perspectives and outlook for the future development of advanced electrolytes are also discussed to provide a guidance for the electrolyte design and optimization in organic batteries. We believe that this review will stimulate an in-depth study of electrolytes and accelerate the commercialization of organic batteries.
ABSTRACT
Rechargeable Zn metal batteries (RZMBs) may provide a more sustainable and lower-cost alternative to established battery technologies in meeting energy storage applications of the future. However, the most promising electrolytes for RZMBs are generally aqueous and require high concentrations of salt(s) to bring efficiencies toward commercially viable levels and mitigate water-originated parasitic reactions including hydrogen evolution and corrosion. Electrolytes based on nonaqueous solvents are promising for avoiding these issues, but full cell performance demonstrations with solvents other than water have been very limited. To address these challenges, we investigated MeOH as an alternative electrolyte solvent. These MeOH-based electrolytes exhibited exceptional Zn reversibility over a wide temperature range, with a Coulombic efficiency > 99.5% at 50% Zn utilization without cell short-circuit behavior for > 1,800 h. More important, this remarkable performance translates well to Zn || metal-free organic cathode full cells, supporting < 6% capacity decay after > 800 cycles at -40 °C.
ABSTRACT
Alzheimer's disease is characterized by abnormal ß-amyloid and tau accumulation, mitochondrial dysfunction, oxidative stress, and synaptic dysfunction. Here, we aimed to assess the mechanisms and signalling pathways in the neuroprotective effect of gastrodin, a phenolic glycoside, on murine neuroblastoma N2a cells expressing human Swedish mutant APP (N2a/APP). We found that gastrodin increased the levels of presynaptic-SNAP, synaptophysin, and postsynaptic-PSD95 and reduced phospho-tau Ser396, APP and Aß1-42 levels in N2a/APP cells. Gastrodin treatment reduced reactive oxygen species generation, lipid peroxidation, mitochondrial fragmentation and DNA oxidation; restored mitochondrial membrane potential and intracellular ATP production. Upregulated phospho-GSK-3ß and reduced phospho-ERK and phospho-JNK were involved in the protective effect of gastrodin. In conclusion, we demonstrated the neuroprotective effect of gastrodin in the N2a/APP cell line by ameliorating the impairment on synaptic and mitochondrial function, reducing tau phosphorylation, Aß1-42 levels as well as reactive oxygen species generation. These results provide new mechanistic insights into the potential effect of gastrodin in the treatment of Alzheimer's disease.
Subject(s)
Benzyl Alcohols , Glucosides , Mitochondria , Neuroprotective Agents , Oxidative Stress , Reactive Oxygen Species , Synapses , Glucosides/pharmacology , Benzyl Alcohols/pharmacology , Oxidative Stress/drug effects , Animals , Mice , Mitochondria/drug effects , Mitochondria/metabolism , Neuroprotective Agents/pharmacology , Cell Line, Tumor , Reactive Oxygen Species/metabolism , Synapses/drug effects , Synapses/metabolism , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Amyloid beta-Protein Precursor/genetics , Humans , Alzheimer Disease/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/pathology , tau Proteins/metabolism , Membrane Potential, Mitochondrial/drug effects , Peptide FragmentsABSTRACT
Achieving longitudinal doping of specific ions by surface treatment remains a challenge for perovskite solar cells, which are often limited by dopant and solvent compatibility. Here, with the flowing environment created by CsBr colloidal nanocrystals, ion exchange is induced on the surface of the perovskite film to enable the homogeneous distribution of Cs+ and gradient distribution of Br- simultaneously at whole depth of the film. Meanwhile, assisted by long-chain organic ligands, the excess PbI2 on the surface of perovskite film is converted to a more stable quasi-2D perovskite, which realizes effective passivation of defects on the surface. As a result, the unfavorable n-type doping on the top surface is suppressed, so that the energy level alignment between perovskite and hole transport layer is optimized. On the basis of co-modification of the surface and the bulk, the PCE of champion device reaches 23.22% with enhanced VOC of 1.12 V. Device maintains 97.12% of the initial PCE in dark ambient air at 1% RH after 1056 h without encapsulation, and 91.56% of the initial PCE under light illumination of 1 sun in N2 atmosphere for more than 200 h. The approach demonstrated here provides an effective strategy for the nondestructive introduction of inorganic ions in perovskite film.
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Piezoelectric composite materials can convert mechanical energy into electrical energy, thus promoting battery-free motion-sensing systems. However, their substandard mechanical performance limits the capability of sensors developed using flexible piezoelectric materials. This study introduces a novel design strategy for preparing high-strength flexible piezoelectric composite materials comprising unidirectional carbon fiber-reinforced potassium sodium niobate (K0.5Na0.5NbO3) nanoparticle-filled epoxy resin (UDCF/KNN-EP). The fibers significantly improve the Young's modulus of UDCF/KNN-EP along the fiber direction, which reaches 282.5 MPa. Moreover, the composite exhibits excellent stretchability and piezoelectric response ( V pp â¼ 1.1 V ${V}_{{\mathrm{pp}}}\ \sim \ 1.1\ V$ ) in the cross-fiber direction under cyclic tensile loading. Multiscale finite element analysis is performed via simulation, which allows theoretical examination of the experimental results and the material's mechanical response mechanism. Finally, UDCF/KNN-EP is seamlessly incorporated into athletic gear and used to measure the impact caused by baseball catching and track footfall patterns. This study harnesses the superior strength of carbon fibers to enhance the durability and dependability of self-powered sensors without compromising flexibility in specific directions.
ABSTRACT
Developing low-voltage carboxylate anode materials is critical for achieving low-cost, high-performance, and sustainable Na-ion batteries (NIBs). However, the structure design rationale and structure-performance correlation for organic carboxylates in NIBs remains elusive. Herein, the spatial effect on the performance of carboxylate anode materials is studied by introducing heteroatoms in the conjugation structure and manipulating the positions of carboxylate groups in the aromatic rings. Planar and twisted organic carboxylates are designed and synthesized to gain insight into the impact of geometric structures to the electrochemical performance of carboxylate anodes in NIBs. Among the carboxylates, disodium 2,2'-bipyridine-5,5'-dicarboxylate (2255-Na) with a planar structure outperforms the others in terms of highest specific capacity (210 mAh g-1), longest cycle life (2000 cycles), and best rate capability (up to 5 A g-1). The cyclic stability and redox mechanism of 2255-Na in NIBs are exploited by various characterization techniques. Moreover, high-temperature (up to 100 °C) and all-organic batteries based on a 2255-Na anode, a polyaniline (PANI) cathode, and an ether-based electrolyte are achieved and exhibited exceptional electrochemical performance. Therefore, this work demonstrates that designing organic carboxylates with extended planar conjugation structures is an effective strategy to achieve high-performance and sustainable NIBs.
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Deciduous woody plants like poplar (Populus spp.) have seasonal bud dormancy. It has been challenging to simultaneously delay the onset of bud dormancy in the fall and advance bud break in the spring, as bud dormancy, and bud break were thought to be controlled by different genetic factors. Here, we demonstrate that heterologous expression of the REVEILLE1 gene (named AaRVE1) from Agave (Agave americana) not only delays the onset of bud dormancy but also accelerates bud break in poplar in field trials. AaRVE1 heterologous expression increases poplar biomass yield by 166% in the greenhouse. Furthermore, we reveal that heterologous expression of AaRVE1 increases cytokinin contents, represses multiple dormancy-related genes, and up-regulates bud break-related genes, and that AaRVE1 functions as a transcriptional repressor and regulates the activity of the DORMANCY-ASSOCIATED PROTEIN 1 (DRM1) promoter. Our findings demonstrate that AaRVE1 appears to function as a regulator of bud dormancy and bud break, which has important implications for extending the growing season of deciduous trees in frost-free temperate and subtropical regions to increase crop yield.
Subject(s)
Agave , Populus , Plant Proteins/metabolism , Populus/metabolism , Seasons , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
BACKGROUND: This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data. METHODS: By conducting a retrospective analysis involving 242 eligible patients from 4 centeres, we determined the incidence of OLM in cT1 - 2N0M0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, five models were constucted and we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad_score (GTV and PTV). RESULTS: The initial investigation revealed a 33.9% OLM positivity rate in cT1 - 2N0M0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for cT1 - 2N0M0 SCLC patients. CONCLUSIONS: The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT1 - 2N0M0 SCLC.
Subject(s)
Lung Neoplasms , Lymphatic Metastasis , Small Cell Lung Carcinoma , Tomography, X-Ray Computed , Humans , Lung Neoplasms/epidemiology , Lung Neoplasms/pathology , Lung Neoplasms/diagnostic imaging , Small Cell Lung Carcinoma/diagnostic imaging , Small Cell Lung Carcinoma/epidemiology , Small Cell Lung Carcinoma/pathology , Male , Female , Middle Aged , Retrospective Studies , Aged , Lymphatic Metastasis/diagnostic imaging , Incidence , Tomography, X-Ray Computed/methods , Predictive Value of Tests , Contrast Media , Neoplasm Staging/methods , Adult , Lymph Nodes/pathology , Lymph Nodes/diagnostic imaging , Aged, 80 and over , RadiomicsABSTRACT
BACKGROUND: Lung adenocarcinoma is a high-mortality rate cancer. Within this category, Lung mucinous adenocarcinoma (LMAC) is a rare and distinct subtype of lung adenocarcinoma necessitating further investigation. The study was launched to compare the difference of survival features between LMAC and lung non-mucinous adenocarcinoma (LNMAC) and to investigate the significance and demand for developing a new staging system tailored to LMAC. METHODS: This retrospective study assessed the suitableness of the current staging system for LMAC. It compared the overall survival (OS) between LMAC and LNMAC from 2004 to 2020 (LNMAC: 160,387; LMAC: 6,341) and instituted a novel classification framework for LMAC based on US population. Verification group consisting of patients from two Chinese medical centers from 2010 to 2018 (n = 392) was set to ascertain the applicability of this novel system. The primary endpoint was OS. To minimize the bias, propensity score match (PSM) was employed. Survival analysis and Log-rank test were executed to explore the survival features of LMAC. RESULTS: The results indicated that the existed staging system was not suitable for LMAC. Patients diagnosed with LMAC exhibited a superior OS compared to those with LNMAC in stage IA2 (P < 0.0001), IA3 (P < 0.0001), IB (P = 0.0062), IIA (P = 0.0090), IIB (P = 0.0005). In contrast, a worse OS in stage IVA (P = 0.0103) was found in LMAC patients. The novel classification system proposed for LMAC proved to be highly applicable and demonstrated substantial efficacy, as confirmed by the verification group. CONCLUSION: The newly established classification system was more effective for LMAC, but it necessitates large-scale verification to confirm its applicability and reliability.
Subject(s)
Adenocarcinoma of Lung , Adenocarcinoma, Mucinous , Lung Neoplasms , Neoplasm Staging , Humans , Neoplasm Staging/methods , Male , Female , Retrospective Studies , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/mortality , Middle Aged , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Aged , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/mortality , Adult , Prognosis , Survival AnalysisABSTRACT
The metabolic benefits of intermittent fasting (IF) have been well recognized. However, limited studies have examined the relationship between long-term maternal IF before pregnancy and offspring health. In this study, a C57BL/6J mouse model of long-term IF before pregnancy was established: 4-week-old female mice were subjected to alternate-day fasting for 12 weeks and resumed normal diet after mating. Female mice in the control group were fed ad libitum. Offspring mice were weaned at 6 weeks of age and fed a normal chow diet or a 60% high-fat diet. The effects of long-term pre-pregnancy IF on offspring metabolism and its underlying mechanism were examined. We found that neonatal IF offspring weighted significantly less relevant to control mice. This difference gradually disappeared as a result of catch-up growth. In the IF offspring, adipose tissue mass was significantly increased. This alteration was associated with a considerable deterioration in glucose tolerance. No significant difference in food intake was observed. Further, lipid deposition as well as triglyceride contents in the liver were greatly increased. Maternal IF significantly decreased levels of DNA methyltransferase in the liver of offspring. DNA methylation modifications of molecules associated with the mTORC1 signaling pathway were significantly altered, leading to the significant inhibition of mTORC1 signaling. Overexpression of S6K1 activated hepatic mTORC1 signaling and reversed the metabolic dysfunction in IF offspring. In conclusion, long-term pre-pregnancy IF increases hepatic steatosis and adiposity, as well as impairs glucose metabolism in adult offspring. This occurs through DNA methylation-dependent suppression of hepatic mTORC1 signaling activity.
Subject(s)
Fatty Liver , Intermittent Fasting , Female , Pregnancy , Animals , Mice , Mice, Inbred C57BL , Signal TransductionABSTRACT
Inspired by geckos, fibrillar microstructures hold great promise as controllable and reversible adhesives in the engineering field. However, enhancing the adhesion strength and stability of gecko-inspired adhesives (GIAs) under complex real-world contact conditions, such as rough surfaces and varying force fields, is crucial for its commercialization, yet further research is lacking. Here, we propose a hierarchically designed GIA, which features a silicone foam (SF) backing layer and a film-terminated fibrillar microstructure under a subtle multiscale design. This structure has been proven to have a "multiscale synergistic effect", allowing the material to maintain strong and stable adhesion to surfaces with changing normal pressures and roughness. Specifically, under a high load, the adhesive strength is 2 times more than that of conventional GIA, and it is 1.5 times stronger on rough surfaces compared to conventional GIA. Under high pressure and high surface roughness simultaneously, the adhesive strength is 3.3 times higher compared to conventional GIA. Our research demonstrates that the synergistic effect of multiscale biomimetic adhesion structures is highly effective in enhancing the adhesive strength of GIA under some harsh contact conditions.
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OBJECTIVE: The prognostic stratification for oral tongue squamous cell carcinoma (OTSCC) is heavily based on postoperative pathological depth of invasion (pDOI). This study aims to propose a preoperative MR T-staging system based on tumor size for non-pT4 OTSCC. METHODS: Retrospectively, 280 patients with biopsy-confirmed, non-metastatic, pT1-3 OTSCC, treated between January 2010 and December 2017, were evaluated. Multiple MR sequences, including axial T2-weighted imaging (WI), unenhanced T1WI, and axial, fat-suppressed coronal, and sagittal contrast-enhanced (CE) T1WI, were utilized to measure radiological depth of invasion (rDOI), tumor thickness, and largest diameter. Intra-class correlation (ICC) and univariate and multivariate analyses were used to evaluate measurement reproducibility, and factors' significance, respectively. Cutoff values were established using an exhaustive method. RESULTS: Intra-observer (ICC = 0.81-0.94) and inter-observer (ICC = 0.79-0.90) reliability were excellent for rDOI measurements, and all measurements were significantly associated with overall survival (OS) (all p < .001). Measuring the rDOI on axial CE-T1WI with cutoffs of 8 mm and 12 mm yielded an optimal MR T-staging system for rT1-3 disease (5-year OS of rT1 vs rT2 vs rT3: 94.0% vs 72.8% vs 57.5%). Using multivariate analyses, the proposed T-staging exhibited increasingly worse OS (hazard ratio of rT2 and rT3 versus rT1, 3.56 [1.35-9.6], p = .011; 4.33 [1.59-11.74], p = .004; respectively), which outperformed pathological T-staging based on nonoverlapping Kaplan-Meier curves and improved C-index (0.682 vs. 0.639, p < .001). CONCLUSIONS: rDOI is a critical predictor of OTSCC mortality and facilitates preoperative prognostic stratification, which should be considered in future oral subsite MR T-staging. CLINICAL RELEVANCE STATEMENT: Utilizing axial CE-T1WI, an MR T-staging system for non-pT4 OTSCC was developed by employing rDOI measurement with optimal thresholds of 8 mm and 12 mm, which is comparable with pathological staging and merits consideration in future preoperative oral subsite planning. KEY POINTS: ⢠Tumor morphology, measuring sequences, and observers could impact MR-derived measurements and compromise the consistency with histology. ⢠MR-derived measurements, including radiological depth of invasion (rDOI), tumor thickness, and largest diameter, have a prognostic impact on OS (all p < .001). ⢠rDOI with cutoffs of 8 mm and 12 mm on axial CE-T1WI is an optimal predictor of OS and could facilitate risk stratification in non-pT4 OTSCC disease.
Subject(s)
Carcinoma, Squamous Cell , Magnetic Resonance Imaging , Neoplasm Invasiveness , Neoplasm Staging , Tongue Neoplasms , Humans , Male , Female , Middle Aged , Magnetic Resonance Imaging/methods , Retrospective Studies , Tongue Neoplasms/diagnostic imaging , Tongue Neoplasms/pathology , Tongue Neoplasms/surgery , Aged , Adult , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Reproducibility of Results , Aged, 80 and over , PrognosisABSTRACT
OBJECTIVE: Lower neck cancers (LNCs) include specific tumour types and have some different vascular supply or collaterals from other head and neck cancers. This prospective study evaluated the outcome of endovascular management of post-irradiated carotid blowout syndrome (PCBS) in patients with LNC by comparing reconstructive management (RE) and deconstructive management (DE). METHODS: This was a single centre, prospective cohort study. Patients with LNC complicated by PCBS between 2015 and 2021 were enrolled for RE or DE. RE was performed by stent graft placement covering the pathological lesion and preventive external carotid artery (ECA) embolisation without balloon test occlusion (BTO). DE was performed after successful BTO by permanent coil or adhesive agent embolisation of the internal carotid artery (ICA) and ECA to common carotid artery, or ICA occlusion alone if the pathological lesion was ICA only. Cross occlusion included the proximal and distal ends of the pathological lesion in all patients. Re-bleeding events, haemostatic period, and neurological complications were evaluated. RESULTS: Fifty-nine patients (mean age 58.5 years; 56 male) were enrolled, including 28 patients undergoing RE and 31 patients undergoing DE. Three patients originally grouped to DE were transferred to RE owing to failed BTO. The results of RE vs. DE were as follows: rebleeding events, 13/28 (46%) vs. 10/31 (32%) (p = .27); haemostatic period, 9.4 ± 14.0 months vs. 14.2 ± 27.8 months (p = .59); neurological complication, 4/28 (14%) vs. 5/31 (16%) (p = .84); and survival time, 11.8 ± 14.6 months vs. 15.1 ± 27.5 months (p = .61). CONCLUSION: No difference in rebleeding risk or neurological complications was observed between the DE and RE groups. RE could be used as a potential routine treatment for PCBS in patients with LNC.
Subject(s)
Embolization, Therapeutic , Endovascular Procedures , Head and Neck Neoplasms , Humans , Male , Middle Aged , Female , Head and Neck Neoplasms/radiotherapy , Endovascular Procedures/adverse effects , Endovascular Procedures/instrumentation , Endovascular Procedures/methods , Prospective Studies , Embolization, Therapeutic/adverse effects , Embolization, Therapeutic/methods , Aged , Treatment Outcome , Stents , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Radiation Injuries/etiology , Radiation Injuries/diagnosis , Radiation Injuries/surgery , Carotid Artery Diseases/therapy , Carotid Artery Diseases/etiology , Carotid Artery Diseases/diagnostic imaging , AdultABSTRACT
BACKGROUND. Retropharyngeal lymph node (RLN) metastases have profound prognostic implications in patients with nasopharyngeal carcinoma (NPC). However, the AJCC staging system does not specify a size threshold for determining RLN involvement, resulting in inconsistent thresholds in practice. OBJECTIVE. The purpose of this article was to determine the optimal size threshold for determining the presence of metastatic RLNs on MRI in patients with NPC, in terms of outcome predictions. METHODS. This retrospective study included 1752 patients (median age, 46 years; 1297 men, 455 women) with NPC treated by intensity-modulated radiotherapy (RT) from January 2010 to March 2014 from two hospitals; 438 patients underwent MRI 3-4 months after treatment. Two radiologists measured the minimal axial diameter (MAD) of the largest RLN for each patient using a consensus process. A third radiologist measured MAD in 260 randomly selected patients to assess interobserver agreement. Initial ROC and restricted cubic spline (RCS) analyses were used to derive an optimal MAD threshold for predicting progression-free survival (PFS). The threshold's predictive utility was assessed in multivariable Cox regression analyses, controlling for standard clinical predictors. The threshold's utility for predicting PFS and overall survival (OS) was compared with a 5-mm threshold using Kaplan-Meier curves and log-rank tests. RESULTS. The intraclass correlation coefficient for MAD was 0.943. ROC and RCS analyses yielded an optimal threshold of 6 mm. In multivariable analyses, MAD of 6 mm and greater independently predicted PFS in all patients (HR = 1.35, p = .02), patients with N0 or N1 disease (HR = 1.80, p = .008), and patients who underwent posttreatment MRI (HR = 1.68, p = .04). In patients with N1 disease without cervical lymph node involvement, 5-year PFS was worse for MAD greater than or equal to 6 mm than for MAD that was greater than or equal to 5 mm but less than 6 mm (77.2% vs 89.7%, p = .03). OS was significantly different in patients with stage I and stage II disease defined using a 6-mm threshold (p = .04), but not using a 5-mm threshold (p = .09). The 5-year PFS rate was associated with a post-RT MAD of 6 mm and greater (HR = 1.68, p = .04) but not a post-RT MAD greater than or equal to 5 mm (HR = 1.09, p = .71). CONCLUSION. The findings support a threshold MAD of 6 mm for determining RLN involvement in patients with NPC. CLINICAL IMPACT. Future AJCC staging updates should consider incorporation of the 6-mm threshold for N-category and tumor-stage determinations.
Subject(s)
Nasopharyngeal Neoplasms , Radiotherapy, Intensity-Modulated , Male , Humans , Female , Middle Aged , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/radiotherapy , Retrospective Studies , Neoplasm Staging , Prognosis , Magnetic Resonance Imaging , Lymph Nodes/pathology , Lymphatic Metastasis/pathologyABSTRACT
Mixtures of fungicides with different modes of action are commonly used as disease and resistance management tools, but little is known of mixtures of natural and synthetic products. In this study, mixtures of metabolites from the rhizobacterium Pseudomonas chlororaphis strain ASF009 formulated as Howler EVO with below-label rates (50 µg/ml) of conventional sterol demethylation inhibitor (DMI) fungicides were investigated for control of anthracnose of cherry (Prunus avium) caused by Colletotrichum siamense. Howler mixed with metconazole or propiconazole synergistically reduced disease severity through lesion growth. Real-time PCR showed that difenoconazole, flutriafol, metconazole, and propiconazole induced the expression of DMI target genes CsCYP51A and CsCYP51B in C. siamense. The addition of Howler completely suppressed the DMI fungicide-induced expression of both CYP51 genes. We hypothesize that the downregulation of DMI fungicide-induced expression of the DMI target genes may, at least in part, explain the synergism observed in detached fruit assays.
ABSTRACT
Diabetes is a chronic medical condition that may induce complications such as poor wound healing. Stem cell therapies have shown promise in treating diabetic wounds with pre-clinical and clinical studies. However, little bibliometric analysis has been carried out on stem cells in the treatment of diabetic wounds. In this study, we retrieved relevant papers published from January 1, 2003, to December 31, 2023, from Chinese and English databases. CiteSpace software was used to analyze the authors, institutions, and keywords by standard bibliometric indicators. Our analysis findings indicated that publications on stem cells in the treatment of diabetic wounds kept increasing. The most prolific author was Qian Cai (n = 7) and Mohammad Bayat (n = 16) in Chinese and English databases, respectively. Institutions distribution analysis showed that Chinese institutions conducted most publications, and the most prolific institution was the Chinese People's Liberation Army General Hospital (n = 9) and Shahid Beheshti University of Medical Sciences (n = 17) in Chinese and English databases, respectively. The highest centrality keyword in Chinese and English databases was "wound healing" (0.54) and "in vitro" (0.13), respectively. There were 8 and 11 efficient and convincing keyword clusters produced by a log-likelihood ratio in the Chinese and English databases, respectively. The strongest burst keyword was "exosome" (strength 3.57) and "endothelial progenitor cells" (strength 7.87) in the Chinese and English databases, respectively. These findings indicated a direction for future therapies and research on stem cells in the treatment of diabetic wounds.
Subject(s)
Asian People , Diabetes Mellitus , East Asian People , Humans , Bibliometrics , Diabetes Mellitus/therapy , Stem CellsABSTRACT
OBJECTIVE: To identify major contributors, current research status, and to forecast research trends and future development prospects on acupuncture and moxibustion therapy for herpes zoster (HZ) and postherpetic neuralgia (PHN). METHODS: A systematic search was conducted on the China National Knowledge Infrastructure (CNKI), Weipu, WanFang databases, and the Web of Science Core Collection (WoSCC), PubMed, and Scopus databases. The search strategy included relevant terms for HZ, PHN, acupuncture, and moxibustion. The reference type was limited to articles or reviews, with a publication date from January 1, 2014 to December 31, 2023. Data analysis was performed using CiteSpace software, focusing on author, institution, source, and keyword distributions, and temporal trends. RESULTS: A total of 1612 publications were identified from both Chinese and English databases. The analysis revealed a rising trend in publication numbers in the English database, with a significant increase observed in 2020. In the Chinese database, publication activity exhibited two peaks in 2019 and 2023. Guohua Lin and Jingchun Zeng were the most prolific authors in the Chinese and English databases, respectively. The Chengdu University of TCM and Zhejiang Chinese Medicine University were the most active institutions. The keyword analysis revealed "herpes zoster" as the most frequent keyword in the Chinese database, while "postherpetic neuralgia," "acupuncture," and "management" were prominent in the English database. The study also identified several therapeutic approaches, including fire needle therapy and electroacupuncture, which have shown efficacy in treating HZ and PHN. Animal studies provided insights into the mechanisms of these therapies, suggesting potential modulation of neuroinflammatory markers and intracellular signaling pathways. CONCLUSION: The bibliometric analysis underscores the growing interest in acupuncture and moxibustion therapy for HZ and PHN. It highlights the contributions of key authors and institutions while pinpointing potential areas for future research. The study advocates for the necessity of large-scale, multi-center clinical trials and further basic mechanical research to optimize these therapies. Moreover, it also emphasizes the importance of international collaboration to strengthen the evidence base and expand the global impact of this traditional treatment modality.
Subject(s)
Acupuncture Therapy , Bibliometrics , Herpes Zoster , Moxibustion , Neuralgia, Postherpetic , Humans , Acupuncture Therapy/methods , Acupuncture Therapy/statistics & numerical data , Moxibustion/methods , Neuralgia, Postherpetic/therapy , Herpes Zoster/therapyABSTRACT
BACKGROUND: Lung adenocarcinoma (LUAD) has high morbidity and mortality. Despite substantial advances in treatment, the prognosis of patients with LUAD remains unfavorable. The ceRNA axis has been reported to play an important role in the pathogenesis of LUAD. In addition, cuproptosis is considered an important factor in tumorigenesis. The expression of CBX2 has been associated with the development of multiple tumors, including LUAD. However, the precise molecular mechanisms through which the cuproptosis-related ceRNA network regulates CBX2 remain unclear. METHODS: The DEGs between tumor and normal samples of LUAD were identified in TCGA database. The "ConsensusClusterPlus" R package was used to perform consensus clustering based on the mRNA expression matrix and cuproptosis-related gene expression profile. Then, LASSO-COX regression analysis was performed to identify potential prognostic biomarkers associated with cuproptosis, and the ceRNA network was constructed. Finally, the mechanisms of ceRNA in LUAD was studied by cell experiments. RESULTS: In this study, the AC144450.1/miR-424-5p axis was found to promote the progression of LUAD by acting on CBX2. The expression of AC144450.1 and miR-424-5p can be altered to regulate CBX2 and is correlated with cell proliferation and cell cycle of LUAD. Mechanistically, AC144450.1 affects the expression of CBX2 by acting as the ceRNA of miR-424-5p. In addition, a cuproptosis-related model were constructed in this study to predict the prognosis of LUAD. CONCLUSIONS: This study is the first to demonstrate that the AC144450.1/miR-424-5p/CBX2 axis is involved in LUAD progression and may serve as a novel target for its diagnosis and treatment.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , MicroRNAs , Humans , RNA, Competitive Endogenous , Cell Cycle/genetics , Cell Proliferation/genetics , Adenocarcinoma of Lung/genetics , Lung Neoplasms/genetics , MicroRNAs/genetics , Polycomb Repressive Complex 1/geneticsABSTRACT
Numerous studies have highlighted the correlation between metal intake and deteriorated pulmonary function, emphasizing its pivotal role in the progression of Chronic Obstructive Pulmonary Disease (COPD). However, the efficacy of traditional models is often compromised due to overfitting and high bias in datasets with low-level exposure, rendering them ineffective in delineating the contemporary risk trends associated with pulmonary diseases. To address these limitations, we embarked on developing advanced, interpretable models, crucial for elucidating the intricate mechanisms of metal toxicity and enriching the domain knowledge embedded in toxicity models. In this endeavor, we scrutinized extensive, long-term metal exposure datasets from NHANES to explore the interplay between metal and pulmonary functionality. Employing a variety of machine-learning approaches, we opted for the "Mixer of Experts" model for its proficiency in identifying a myriad of toxicological trends and sensitivities. We conceptualized and illustrated the TSAP (Toxicity Score at Population-level), a metal interpretable scoring system offering performance nearly equivalent to the amalgamation of standard interpretable methods addressing the "black box" conundrum. This streamlined, bifurcated procedural analysis proved instrumental in discerning established risk factors, thereby uncovering Tungsten as a novel contributor to COPD risk. SYNOPSIS: TSAP achieved satisfied performance with transparent interpretability, suggesting tungsten intake need further action for COPD prevention.