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Context: Ultrasound (US) is the most economical and widely used method for detecting lesions in parathyroid regions. Identifying typically parathyroid adenomas as hypoechoic nodules with clear margins. However, 10 % of lesions exhibit atypical features, such as the dual concentric sign, and the cognition of them still needs to be improved. Objective: To promote understanding of clinical and histopathological features for parathyroid lesions with the dual concentric echo sign and to investigate its pathogenesis and methods for distinguishing from cervical lymph nodes to improve US diagnostic accuracy. Methods: Retrospectively, patients were categorized into three groups: Group 1, with 36 patients showing parathyroid lesions with dual concentric echo signs; Group 2, with 40 patients displaying classic hypoechoic parathyroid lesions; and Group 3, comprising 36 patients with identified lymph nodes, which were all examined from January 2018 to December 2019. The clinical data on demographics, clinical symptoms, serum levels, histopathologic findings, and US image characteristics were thoroughly reviewed. Results: According to the clinical data, no significant differences in demographics or lesion sizes were observed in Group 1 and Group 2 (p > 0.05). No significant variances were noted in biochemical markers, including PTH, T-25OHD, and ALP. However, a notable difference was identified in adjusted serum calcium levels, which were significantly lower in Group 1 compared to Group 2 (p

The ubiquity of refractory organic matter in aquatic environments necessitates innovative removal strategies. Sulfate radical-based advanced oxidation has emerged as an attractive solution, offering high selectivity, enduring efficacy, and anti-interference ability. Among many technologies, sulfite activation, leveraging its cost-effectiveness and lower toxicity compared to conventional persulfates, stands out. Yet, the activation process often relies on transition metals, suffering from low atom utilization. Here we introduce a series of single-atom catalysts (SACs) employing transition metals on g-C3N4 substrates, effectively activating sulfite for acetaminophen degradation. We highlight the superior performance of Fe/CN, which demonstrates a degradation rate constant significantly surpassing those of Ni/CN and Cu/CN. Our investigation into the electronic and spin polarization characteristics of these catalysts reveals their critical role in catalytic efficiency, with oxysulfur radical-mediated reactions predominating. Notably, under visible light, the catalytic activity is enhanced, attributed to an increased generation of oxysulfur radicals and a strengthened electron donation-back donation dynamic. The proximity of Fe/CN's d-band center to the Fermi level, alongside its high spin polarization, is shown to improve sulfite adsorption and reduce the HOMO-LUMO gap, thereby accelerating photo-assisted sulfite activation. This work advances the understanding of SACs in environmental applications and lays the groundwork for future water treatment technologies.

Abstract Fluorescent‐patterned materials are widely used in information storage and encryption. However, preparing a patterned fluorescent display on a matrix currently requires a time‐consuming (hours or even days) and complex multi‐step process. Herein, a rapid and mild technique developed for the in‐situ controllable synthesis of fluorescent nitrogen‐doped carbon dots (NCDs) on eco‐friendly transparent wood films (TEMPO‐oxidized carboxyl wood film [TOWF]) within a few minutes was developed. A wood skeleton was employed as the carbon precursor for NCD synthesis as well as the matrix for the uniform and controlled distribution of NCDs. Moreover, the in‐situ synthesis mechanism for preparing NCDs in TOWF was proposed. The resulting fluorescent wood films have excellent tensile strength (310.00 ± 15.57 MPa), high transmittance (76.2%), high haze (95.0%), UV‐blocking properties in the full ultraviolet (UV) range, and fluorescent performance that can be modified by changing the heating parameters. Fluorescent patterning was simply achieved by regulating the in‐situ NCD synthesis regions, and the fluorescent patterns were formed within 10 s. These fluorescent‐patterned wood films can effectively store and encrypt information, and they can interact with external information through a transparent matrix. This work provides a green and efficient strategy for fabricating fluorescent information storage and encryption materials.

Abstract Objectives To develop a nomogram using pretreatment ultrasound (US) and contrast-enhanced ultrasound (CEUS) to predict the clinical response of neoadjuvant chemotherapy (NAC) in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC). Methods A total of 111 patients with pancreatic ductal adenocarcinoma (PDAC) treated with NAC between October 2017 and February 2022 were retrospectively enrolled. The patients were randomly divided (7:3) into training and validation cohorts. The pretreatment US and CEUS features were reviewed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of clinical response in the training cohort. Then a prediction nomogram model based on the independent predictors was constructed. The area under the curve (AUC), calibration plot, C-index and decision curve analysis (DCA) were used to assess the nomogram’s performance, calibration, discrimination and clinical benefit. Results The multivariate logistic regression analysis showed that the taller-than-wide shape in the longitudinal plane (odds ratio [OR]:0.20, p = 0.01), time from injection of contrast agent to peak enhancement (OR:3.64; p = 0.05) and Peaktumor/ Peaknormal (OR:1.51; p = 0.03) were independent predictors of clinical response to NAC. The predictive nomogram developed based on the above imaging features showed AUCs were 0.852 and 0.854 in the primary and validation cohorts, respectively. Good calibration was achieved in the training datasets, with C-index of 0.852. DCA verified the clinical usefulness of the nomogram. Conclusions The nomogram based on pretreatment US and CEUS can effectively predict the clinical response of NAC in patients with BRPC and LAPC; it may help guide personalized treatment.

Plywood is lightweight, strong, and durable, making it a widely used material in building decoration and furniture areas. In this study, formaldehyde-free, high-strength plywood was prepared through the incorporation of carbon fiber fabrics (CFFs) as reinforcement layers and their bonding with maleic anhydride polyethylene (MAPE) films. Various tests were performed to assess the impact of the carbon fiber fabric positioning on the physical and mechanical properties of plywood, including tensile shear strength, flexural strength, water absorption, thickness swelling, and electro-thermal properties. The results revealed that the plywood with CFFs exhibited significantly higher mechanical properties than plywood without CFFs. Particularly, the addition of CFFs increased the tensile strength of the plywood by nearly 54.43%, regardless of the CFFs’ position. The symmetric placement of CFFs near the bottom and upper layers of the plywood resulted in a maximum modulus of rupture of 85.6 MPa. These findings were validated by numerical simulations. Scanning electron microscopy analysis of the plywood microstructures revealed that MAPE penetrated both the vessels and xylem of the wood veneers and the pores of the CFFs, thereby improving the mechanical properties of the plywood. Plywood reinforced with CFFs exhibited increased water absorption and thickness swelling after immersion. Additionally, the placement of CFFs influenced the electro-thermal properties of the plywood. Plywood with CFFs positioned near the bottom and upper surfaces exhibited superior thermal conductivity. Overall, this study presents a feasible method for developing high-performance, formaldehyde-free plywood and sustainable wood-based structural materials with potential applications in geothermal flooring.

To investigate the role of sugar metabolism in desiccation-sensitive seeds, we performed a natural desiccation treatment on Phoebe chekiangensis seeds in a room and systematically analyzed the changes in seed germination, sugar compounds, malondialdehyde, and relative electrical conductivity during the seed desiccation. The results revealed that the initial moisture content of P. chekiangensis seed was very high (37.06%) and the seed was sensitive to desiccation, the germination percentage of the seed decreased to 5.33% when the seed was desiccated to 22.04% of moisture content, therefore, the seeds were considered recalcitrant. Based on the logistic model, we know that the moisture content of the seeds is 29.05% when the germination percentage drops to 50% and that it is desirable to keep the seed moisture content above 31.74% during ambient transportation. During seed desiccation, sucrose and trehalose contents exhibited increasing trends, and raffinose also increased during the late stage of desiccation, however, low levels of the non-reducing sugar accumulations may not prevent the loss of seed viability caused by desiccation. Glucose and fructose predominated among sugar compounds, and they showed a slight increase followed by a significant decrease. Their depletion may have contributed to the accumulation of sucrose and raffinose family oligosaccharides. Correlation analysis revealed a significant relationship between the accumulation of sucrose, trehalose, and soluble sugars, and the reduction in seed viability. Sucrose showed a significant negative correlation with glucose and fructose. Trehalose also exhibited the same pattern of correlation. These results provided additional data and theoretical support for understanding the mechanism of sugar metabolism in seed desiccation sensitivity.

The World Health Organization has recently published a list of 12 drug-resistant bacteria that posed a significant threat to human health, and Pseudomonas aeruginosa (P. aeruginosa) was among them. In China, P. aeruginosa is a common pathogen in hospital acquired pneumonia, accounting for 16.9–22.0%. It is a ubiquitous opportunistic pathogen that can infect individuals with weakened immune systems, leading to hospital-acquired acute and systemic infections. The excessive use of antibiotics has led to the development of various mechanisms in P. aeruginosa to resist conventional drugs. Thus, there is an emergence of multidrug-resistant strains, posing a major challenge to conventional antibiotics and therapeutic approaches. Antimicrobial peptides are an integral component of host defense and have been found in many living organisms. Most antimicrobial peptides are characterized by negligible host toxicity and low resistance rates, making them become promising for use as antimicrobial products. This review particularly focuses on summarizing the inhibitory activity of natural antimicrobial peptides against P. aeruginosa planktonic cells and biofilms, as well as the drug interactions when these peptides used in combination with conventional antibiotics. Moreover, the underlying mechanism of these antimicrobial peptides against P. aeruginosa strains was mainly related to destroy the membrane structure through interacting with LPS or increasing ROS levels, or targeting cellular components, leaded to cell lysis. Hopefully, this analysis will provide valuable experimental data on developing novel compounds to combat P. aeruginosa.

Diabetic nephropathy (DN) is a common microvascular complication of both type 1 and type 2 diabetes mellitus and often advances to end-stage renal disease. Oxidative stress plays an important role in the pathogenesis and progress of DN. Hydrogen sulfide (H2S) is considered as a promising candidate for the management of DN. But the antioxidant effects of H2S in DN have not been fully studied. In mouse model induced by high-fat diet and streptozotocin, GYY4137, a H2S donor, ameliorated albuminuria at weeks 6 & 8 and decreased serum creatinine at week 8, but not hyperglycemia. Renal nitrotyrosine and urinary 8-isoprostane were reduced along with the suppressed levels of renal laminin and kidney-injury-molecule 1. Renal NADPH oxidase (NOX) 2 was lower but heme oxygenase (HO) 2, paraoxonase (PON) 1, PON2 were higher in DN+GYY than DN group. NOX1, NOX4, HO1, superoxide dismutases 1–3 were similar between groups. Except for a rise at HO2, all the affected enzymes were unchanged in mRNA levels. The affected reactive-oxygen-species (ROS) enzymes were mainly located in the renal sodium-hydrogen-exchanger positive proximal tubules with similar distribution but changed immunofluorence in GYY4137 treated DN mice. Kidney morphological alterations in DN mice under light and electrical-microscopes were also improved by GYY4137. Thus, exogenous H2S administration may improve the renal oxidative damage in DN by reducing ROS production and enhancing ROS cleavage in kidney via the affected enzymes. This study may shed a light on therapeutic applications in diabetic nephropathy with H2S donors in the future.

Abstract Bone metastasis has a significant influence on the prognosis of prostate cancer(PCa) patients. In this review, we discussed the current application of PCa bone metastasis diagnosis with single-photon emission computed tomography (SPECT) and positron emission tomography/computed tomography (PET/CT) computer-aided diagnosis(CAD) systems. A literature search identified articles concentrated on PCa bone metastasis and PET/CT or SPECT CAD systems using the PubMed database. We summarized the previous studies focused on CAD systems and manual quantitative markers calculation, and the coincidence rate was acceptable. We also analyzed the quantification methods, advantages, and disadvantages of CAD systems. CAD systems can detect abnormal lesions of PCa patients’ 99mTc-MDP-SPECT, 18F-FDG-PET/CT, 18F-NaF-PET/CT, and 68 Ga-PSMA PET/CT images automated or semi-automated. CAD systems can also calculate the quantitative markers, which can quantify PCa patients’ whole-body bone metastasis tumor burden accurately and quickly and give a standardized and objective result. SPECT and PET/CT CAD systems are potential tools to monitor and quantify bone metastasis lesions of PCa patients simply and accurately, the future clinical application of CAD systems in diagnosing PCa bone metastasis lesions is necessary and feasible.

Contemporary aero-engines aim for enhanced efficiency and weight reduction. They are designed to increase rotor operational speed while reducing rotor bending stiffness. This may result in bending deformation in rotor systems within the operational speed range. Such deformation can change the relative positions of rotor components, potentially causing increased mass asymmetry or unbalance. Traditional rotor dynamic models typically assume a constant rotor state. They approximate unbalance using constant mass eccentricities at certain rotor cross-sections. However, this approach has its limitations. This paper focuses on a high-speed jointed rotor system. A distributed rotational inertia load excitation model is proposed. This model explicitly considers the rotor’s variable unbalance state at different operational speeds. The study involves both simulations and experimental investigations. The results show that at high speeds, bending deformation causes the unbalance and rotational inertia load to shift from a concentrated to a distributed state. Notably, the localized rotational inertia moment from thin-disk components like turbine disks becomes significant at high speeds. This results in a rapid increase in bearing load with rotational speed. It also profoundly affects the rotor’s joints, causing interfacial slip and sudden changes in rotor vibration characteristics.

As the efficiency of advanced aero engines improves, the operational speed of their rotors increases. This heightened operational speed makes the rotor dynamics highly sensitive to changes in the rotor’s mass asymmetry state, or unbalance state. During the use of a dual-spool turbofan engine, when its supercritical high-pressure rotor (HPR) exceeds a certain operational speed, the rotor’s vibration spikes and continues to increase with the operational speed until it drops sharply near the maximum operational speed. Analysis of the bolt joints in the faulty rotor reveals various phenomena such as joint interface damage, changes in bolt loosening torque distribution, and alterations in rotor initial unbalance. This paper proposes that at high operational speeds, the bolt joint of the HPR undergoes sudden angular deformation, resulting in the slanting of the principal axis of inertia of the turbine disk. This slant leads to changes in the unbalanced state of the HPR. The additional unbalance causes a sudden rotational inertia load excitation, triggering the rotor vibration failure. Subsequently, a rotor dynamic model that incorporates the angular deformation of the joints is established to simulate how this joint deformation influences the dynamic response of the rotor. The simulation results align well with the observed failure phenomenon and validate the proposed failure mechanism. Finally, troubleshooting measures are proposed and implemented in the faulty engine, effectively mitigating the vibration fault.

Abstract. Background:. Contrast-enhanced ultrasound (CEUS) can detect lesions hidden in inflammatory regions and find necrosis or areas of severe fibrosis within the lesion. This retrospective study aimed to compare the diagnostic accuracy of solid pancreatic lesions using percutaneous ultrasound (US)-guided fine-needle aspiration (FNA) with or without CEUS assessment. Methods:. Clinical, imaging, and pathologic data of 181 patients from January 2014 to December 2018 in Pecking Union Medical College Hospital, with solid pancreatic masses who underwent percutaneous US-FNA and ThinPrep cytologic test were retrospectively evaluated. Patients were divided into CEUS and US groups according to whether CEUS was performed before the biopsy. According to FNA cytology diagnoses, we combined non-diagnostic, neoplastic, and negative cases into a negative category. The positive category included malignant, suspicious, and atypical cases. The final diagnosis was confirmed by pathology or clinical and radiological follow-up for at least 12 months. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of US-FNA were evaluated between the two groups. Results:. This study enrolled 107 male and 74 female patients (average age: 60 years). There were 58 cases in the US group and 123 cases in the CEUS group. No statistically significant differences in age, gender, or lesion size were found between the two groups. The diagnostic accuracy of the CEUS group was 95.1% (117/123), which was higher than the 86.2% (50/58) observed in the US group (P = 0.036). The sensitivity, specificity, PPV, and NPV of the CEUS group were increased by 7.5%, 16.7%, 3.4%, and 18.8%, respectively, compared with the US group. However, the differences of the two groups were not statistically significant. Conclusions:. Compared with the conventional US, the use of CEUS could improve the biopsy accuracy and avoid the need for a repeat biopsy, especially for some complicated FNA cases.

Paper microzones method (PMZs) has attracted the attention of scientists as they can detect changes in substance content with just one drop of solution and are not limited by the experimental site. Herein, MIL-53(Fe) was synthesized and analyzed for the first time by paper microzones (PMZs) method to explore the possibility of green chemistry approach to analyze catalyst performance. Firstly, the prediction and kinetic analysis of the methyl orange (MO) adsorption performance of MIL-53(Fe) was carried out by PMZs method, then its integrated adsorption-photocatalytic performance on tetracycline was briefly verified and elaborated the related mechanism. By measuring the color values of MO droplets under different color channels, it can be further seen that the color values in gray as well as in Red(B), Green(G), and Blue(B) channels are significantly different in the range of 0 mg/L∼30 mg/L, and the order of contrast is B>gray>G>R. The LOD value of PMZs method was 1.217 mg/L, LOQ value was 3.689 mg/L, and the R2 value of linear correlation coefficient was 0.978. The photocatalytic results showed that MIL-53(Fe) had a good adsorption-photocatalytic synergistic effect. Hence, it can be found that the photocatalytic experiments were carried out smoothly after the prediction and comparative analysis of the catalyst performance by PMZs method, thus saving the time and cost for screening the adsorption performance of the adsorbent. Our results show that the PMZs method combined with material characterization can better verify the adsorption properties when studying the adsorption performance of MIL-53 (Fe) on MO, which brings new research ideas and green chemistry concepts to the related research field.

Cancer immunotherapy, especially immune-checkpoint inhibitors (ICIs), has paved a new way for the treatment of many types of malignancies, particularly advanced-stage cancers. Accumulating evidence suggests that as a molecular imaging modality, positron emission tomography/computed tomography (PET/CT) can play a vital role in the management of ICIs therapy by using different molecular probes and metabolic parameters. In this review, we will provide a comprehensive overview of the clinical data to support the importance of 18F-fluorodeoxyglucose PET/CT (18F-FDG PET/CT) imaging in the treatment of ICIs, including the evaluation of the tumor microenvironment, discovery of immune-related adverse events, evaluation of therapeutic efficacy, and prediction of therapeutic prognosis. We also discuss perspectives on the development direction of 18F-FDG PET/CT imaging, with a particular emphasis on possible challenges in the future. In addition, we summarize the researches on novel PET molecular probes that are expected to potentially promote the precise application of ICIs.

In order to elucidate the importance of grafting in the compatibilization process of silane coupling agents, poplar veneer was treated with silane coupling agents and grafted under different heating conditions. The treated veneers were used composited with PE film to prepare different plywood samples. XPS and WCA were used to analyze the effect of grafting conditions on the surface properties of the silane-treated veneer. The results showed that free silanols can physically be adsorbed onto all silane-treated veneer surfaces, forming hydrogen–Si–O–Si– bonds and therefore increasing the water contact angle. Only under heating conditions could the –Si–O–Si– be converted into covalent –Si–O–C– bonds, which helped to improve the bonding strength. When silane-treated veneer was grafted at 120 °C for 90 min, the tensile shear strength of plywood reached 1.03 MPa, meeting the requirements of GB/T 9846.3-2004 for outdoor materials. Enhanced interlock between silane-modified veneer and PE film was observed under the optimal grafting condition by SEM. The better interface structure allowed improvement of thermal stability. DMA results showed that the retention rate in storage modulus at 130 °C was 60% for the grafted sample, while the retention rate for the ungrafted sample was only 31%.

Contrast-enhanced ultrasound (CEUS) is a promising imaging modality in predicting the efficacy of neoadjuvant chemotherapy for pancreatic cancer, a tumor with high mortality. In this study, we proposed a deep-learning-based strategy for analyzing CEUS videos to predict the prognosis of pancreatic cancer neoadjuvant chemotherapy. Pre-trained convolutional neural network (CNN) models were used for binary classification of the chemotherapy as effective or ineffective, with CEUS videos collected before chemotherapy as the model input, and with the efficacy after chemotherapy as the reference standard. We proposed two deep learning models. The first CNN model used videos of ultrasound (US) and CEUS (US+CEUS), while the second CNN model only used videos of selected regions of interest (ROIs) within CEUS (CEUS-ROI). A total of 38 patients with strict restriction of clinical factors were enrolled, with 76 original CEUS videos collected. After data augmentation, 760 and 720 videos were included for the two CNN models, respectively. Seventy-six-fold and 72-fold cross-validations were performed to validate the classification performance of the two CNN models. The areas under the curve were 0.892 and 0.908 for the two models. The accuracy, recall, precision and F1 score were 0.829, 0.759, 0.786, and 0.772 for the first model. Those were 0.864, 0.930, 0.866, and 0.897 for the second model. A total of 38.2% and 40.3% of the original videos could be clearly distinguished by the deep learning models when the naked eye made an inaccurate classification. This study is the first to demonstrate the feasibility and potential of deep learning models based on pre-chemotherapy CEUS videos in predicting the efficacy of neoadjuvant chemotherapy for pancreas cancer.

Metalenses have attracted much attention from researchers because they are thin, multifunctional and easy to integrate. However, due to the limitation of fabrication techniques and the influence of working wavelength, it is difficult to realize a large aperture. In this paper, we design and simulate polarization-insensitive, orthogonal linearly polarized and orthogonal circularly polarized synthetic aperture metalenses. We use a synthetic aperture to improve the cutoff frequency of the metalens and achieve an equivalent large-aperture metalens. We compare the modulation transfer function and focusing efficiency of synthetic aperture metalenses with different array structures. This work provides an effective solution to the needs of large-aperture metalenses, and metalenses with different polarizations can play an important role in polarization imaging.

Camouflaged target segmentation has been widely used in both civil and military applications, such as wildlife behaviour monitoring, crop pest control, and battle reconnaissance. However, it is difficult to distinguish camouflaged objects and natural backgrounds using traditional grey-level feature extraction. In this paper, a compressive bidirectional reflection distribution function-based feature extraction method is proposed for effective camouflaged object segmentation. First, multidimensional grey-level features are extracted from multiple images with different illumination angles in the same scene. Then, the multidimensional grey-level features are expanded based on Chebyshev polynomials. Next, the first several coefficients are integrated as a new optical feature, which is named the compressive bidirectional reflection distribution function feature. Finally, the camouflaged object can be effectively segmented from the background by compressive feature clustering. Both qualitative and quantitative experimental results prove that our method has remarkable advantages over conventional single-angle or multi-angle grey-level feature-based methods in terms of segmentation precision and running speed.

Infrared ocean image simulation has been widely used in water-pollution prevention, meteorological observation and melting-ice monitoring. However, in actual remote sensing observation scenes, the simulation images provided by conventional algorithms are lacking sufficient wave details because the viewing angle and the scale of simulation images are simplex. In this paper, an infrared ocean image simulation algorithm based on the Pierson–Moskowitz spectrum and a bidirectional reflectance distribution function is proposed. First, a 3D model of ocean surface is set up based on Pierson–Moskowitz spectrum. Then, the imaging position is calculated by the pinhole camera imaging method, which describes how each point of the 3D model is mapping to the 2D image. Next, by using a bidirectional reflectance distribution function, the radiation intensity from every point of the ocean model to the camera is computed. Finally, we figure up the sum of the radiation intensity received by every point of the detector and obtain the infrared simulation ocean image by quantizing the radiation intensity sum to grayscale. The entropy of the simulation images is 2.725, which is, respectively, improved by 71.86% and 16.83% compared with two other algorithms. The Kullback–Leibler divergence of the simulation images is 11.446, which is improved by 0.54% and 0.59% compared with other algorithms. The quantitative experimental results prove that the authenticity and clarity of the presented simulation images have remarkable advantages over conventional algorithms.

Invasive fungal infections are an emerging problem worldwide, which bring huge health challenges. Candida albicans, the most common opportunistic fungal pathogen, can cause bloodstream infections with high mortality in susceptible hosts. At present, available antifungal agents used in clinical practice are limited, and most of them also have some serious adverse effects. The emergence of drug resistance because of the wide use of antifungal agents is a new limitation to successful patient therapy. Drug combination therapy is increasingly becoming a way to enhance antifungal efficacy, and reduce drug resistance and potential toxicity. Panobinostat, as a pan-histone deacetylase inhibitor, has been approved by the United States Food and Drug Administration as novel antitumor agents. In this study, the antifungal effects and mechanisms of panobinostat combined with fluconazole (FLC) against C. albicans were explored for the first time. The results indicated that panobinostat could work synergistically with FLC against resistant C. albicans, the minimal inhibitory concentration (MIC) of panobinostat could decrease from 128 to 0.5–2 μg/ml and the MIC of FLC could decrease from >512 to 0.25–0.5 μg/ml, and the fractional inhibitory concentration index (FICI) value ranged from 0.0024 to 0.0166. It was not only synergized against planktonic cells but also against C. albicans biofilms performed ≤8 h when panobinostat is combined with fluconazole; the sessile MIC (sMIC) of panobinostat could decrease from >128 to 0.5–8 μg/ml and the sMIC of FLC from >1024 to 0.5–2 μg/ml, and the FICI value was 0.05). These findings might provide novel insights into the antifungal drug discovery and the treatment of candidiasis caused by C. albicans.

In recent years, fungal infections have become a serious health problem. Candida albicans are considered as the fourth most common isolates associated with approximately 40% mortality in bloodstream infections among hospitalized patients. Due to various limitations of classical antifungals used currently, such as limited kinds of drugs, inevitable toxicities, and high price, there is an urgent need to explore new antifungal agents based on novel targets. Generally, nutrient metabolism is involved with fungal virulence, and glucose is one of the important nutrients in C. albicans. C. albicans can obtain and metabolize glucose through a variety of pathways; in theory, many enzymes in these pathways can be potential targets for developing new antifungal agents, and several studies have confirmed that compounds which interfere with alpha-glucosidase, acid trehalase, trehalose-6-phosphate synthase, class II fructose bisphosphate aldolases, and glucosamine-6-phosphate synthase in these pathways do have antifungal activities. In this review, the glucose metabolism pathways in C. albicans, the potential antifungal targets based on these pathways, and some compounds which have antifungal activities by inhibiting several enzymes in these pathways are summarized. We believe that our review will be helpful to the exploration of new antifungal drugs with novel antifungal targets.

Over the last few decades, candidiasis has exhibited an increasing incidence worldwide, causing high mortality in immunocompromised patients. Candida albicans is one of the leading opportunistic fungal pathogens. However, due to the increased use of antifungal agents, resistance of C. albicans to conventional agents, especially fluconazole, has frequently emerged. Therefore, research on the use of combinations of current drugs to sensitize antifungal agents and overcome fungal resistance has attracted considerable attention. This study demonstrated for the first time that D-penicillamine (PCA) combined with fluconazole showed a synergistic effect against C. albicans. PCA combined with fluconazole not only showed synergistic effects against planktonic cells of C. albicans, but also showed synergistic effects against C. albicans biofilms formed within 12 h in vitro. In addition, a Galleria mellonella infection model was used to evaluate the in vivo effects of this drug combination. The results showed that the combination of the two drugs could improve the survival rate, decrease the fungal burden, and reduce the tissue invasion of G. mellonella larvae. Finally, we explored the potential synergistic mechanisms of the drug combination, mainly including inhibition of the morphological transformation, reduction of the intracellular calcium concentration, and the activation of metacaspase, which is closely related to cell apoptosis. These findings might provide novel insights into antifungal drug discovery and the treatment of candidiasis caused by C. albicans.

While the ApoE ε4 allele is a known risk factor for mild cognitive impairment (MCI) and Alzheimer's disease, brain region specific effects remain elusive. In this study, we investigate whether the ApoE ε4 allele exhibits brain region specific effects in longitudinal glucose uptake among patients with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed FDG PET images, MRIs, and demographic information were downloaded from the ADNI database. An iterative reblurred Van Cittertiteration method was used for partial volume correction (PVC) on all PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. Longitudinal changes in ROI FDG standardized uptake value ratio (SUVR) relative to cerebellum in 24 ApoE ε4 carriers and 24 age-matched ApoE ε4 non-carriers were measured for up to 84-months (median 72 months, SD = 11.2 months) and compared using a generalized linear mixed effects model controlling for gender, education, baseline age, and follow-up period. Additionally, voxelwise analysis was performed by implementing a paired t-test comparing matched baseline and 72 month FDG SUVR images in ApoE carriers and non-carriers separately. Results with PVC were compared with ones from non-PVC based analysis. After applying PVC, the superior fontal, parietal, lateral temporal, medial temporal, caudate, thalamus, and post-cingulate, and amygdala regions had greater longitudinal decreases in FDG uptake in ApoE ε4 carriers with MCI compared to non-carriers with MCI. Similar forebrain and limbic clusters were found through voxelwise analysis. Compared to the PVC based analysis, fewer significant ApoE-associated regions and clusters were found in the non-PVC based PET analysis. Our findings suggest that the ApoE ε4 genotype is associated with a longitudinal decline in glucose uptake in 8 forebrain and limbic brain regions in the context of MCI. In conclusion, this 84-months longitudinal FDG PET study demonstrates a novel ApoE ε4-associated brain-region specific glucose metabolism pattern in patients with MCI. Partial volume correction improved FDG PET quantification. Keywords: Alzheimer's disease, Mild cognitive impairment, ApoE ε4, FDG PET, Longitudinal, Partial volume correction

With the growing depletion of wood-based materials and concerns over emissions of formaldehyde from traditional wood fibre composites, there is a desire for environment-friendly binders. Herein, we report a green wood fibre composite with specific bonding strength and water resistance that is superior to a commercial system by using wood fibres and chitosan-based adhesives. When the mass ratio of solid content in the adhesive and absolute dry wood fibres was 3%, the bonding strength and water resistance of the wood fibre composite reached the optimal level, which was significantly improved over that of wood fibre composites without adhesive and completely met the requirements of the Chinese national standard GB/T 11718-2009. Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) characterizations revealed that the excellent performance of the binder might partly be due to the amide linkages and hydrogen bonding between wood fibres and the chitosan-based adhesive. We believe that this strategy could open new insights into the design of environment-friendly wood fibre composites with high bonding strength and water resistance for multifunctional applications.

Cerebrospinal fluid (CSF) biomarkers, such as α-synuclein (α-syn), amyloid beta peptide 1-42 (Aβ1-42), phosphorylated tau (181P) (p-tau), and total tau (t-tau), have long been associated with the development of Parkinson disease (PD) and other neurodegenerative diseases. In this investigation, we reported the assessment of CSF biomarkers and their correlations with vesicular monoamine transporter 2 (VMAT2) bindings measured with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-AV133) that is being developed as a biomarker for PD. We test the hypothesis that monoaminergic degeneration was correlated with CSF biomarker levels in untreated PD patients.The available online data from the Parkinson's Progression Markers Initiative study (PPMI) project were collected and analyzed, which include demographic information, clinical evaluations, CSF biomarkers (α-syn, Aβ1-42, p-tau, and t-tau), 18F-AV133 brain PET, and T1 weighted MRIs. Region of interest (ROI) and voxel-wise Pearson correlation between standardized uptake value ratio (SUVR) and CSF biomarkers were calculated.Our major findings are: 1) Compared with controls, CSF α-syn and tau levels decreased significantly in PD; 2) α-syn was closely correlated with Aβ1-42 and tau in PD, especially in early-onset patients; and 3) hypothesis-driven ROI analysis found a significant negative correlation between CSF Aβ1-42 levels and VMAT2 densities in post cingulate, left caudate, left anterior putamen, and left ventral striatum in PDs. CSF t-tau and p-tau levels were significantly negatively related to VMAT2 SUVRs in substantia nigra and left ventral striatum, respectively. Voxel-wise analysis showed that left caudate, parahippocampal gyrus, insula and temporal lobe were negatively correlated with Aβ1-42. In addition, superior frontal gyrus and transverse temporal gyrus were negatively correlated with CSF p-tau levels.These results suggest that monoaminergic degeneration in PD is correlated with CSF biomarkers associated with cognitive impairment in neurodegenerative diseases including Alzheimer's disease. The association between loss of dopamine synaptic function and pathologic protein accumulations in PD indicates an important role of CSF biomarkers in PD development.

OBJECTIVE:To evaluate the potential clinical value of quantitative functional FDG PET and pathological amyloid-β PET with cerebrospinal fluid (CSF) biomarkers and clinical assessments in the prediction of Alzheimer's disease (AD) progression. METHODS:We studied 82 subjects for up to 96 months (median = 84 months) in a longitudinal Alzheimer's Disease Neuroimaging Initiative (ADNI) project. All preprocessed PET images were spatially normalized to standard Montreal Neurologic Institute space. Regions of interest (ROI) were defined on MRI template, and standard uptake values ratios (SUVRs) to the cerebellum for FDG and amyloid-β PET were calculated. Predictive values of single and multiparametric PET biomarkers with and without clinical assessments and CSF biomarkers for AD progression were evaluated using receiver operating characteristic (ROC) analysis and logistic regression model. RESULTS:The posterior precuneus and cingulate SUVRs were identified for both FDG and amyloid-β PET in predicating progression in normal controls (NCs) and subjects with mild cognitive impairment (MCI). FDG parietal and lateral temporal SUVRs were suggested for monitoring NCs and MCI group progression, respectively. 18F-AV45 global cortex attained (78.6%, 74.5%, 75.4%) (sensitivity, specificity, accuracy) in predicting NC progression, which is comparable to the 11C-PiB global cortex SUVR's in predicting MCI to AD. A logistic regression model to combine FDG parietal and posterior precuneus SUVR and Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) Total Mod was identified in predicating NC progression with (80.0%, 94.9%, 93.9%) (sensitivity, specificity, accuracy). The selected model including FDG posterior cingulate SUVR, ADAS-Cog Total Mod, and Mini-Mental State Exam (MMSE) scores for predicating MCI to AD attained (96.4%, 81.2%, 83.6%) (sensitivity, specificity, accuracy). 11C-PiB medial temporal SUVR with MMSE significantly increased 11C-PiB PET AUC to 0.915 (p

(1) Background: The great potential of RNA interference (RNAi)-based gene therapy is premised on the effective delivery of small interfering RNAs (siRNAs) to target tissues and cells. Hence, we aimed at developing and examining a novel integrin αvβ3-specific delivery carrier for targeted transfection of siRNA to malignant tumor cells; (2) Methods: Arginine-glycine-aspartate motif (RGD) was adopted as a tissue target for specific recognition of integrin αvβ3. To enable siRNA binding, a chimeric peptide was synthesized by adding nonamer arginine residues (9R) at the carboxy terminus of cyclic-RGD dimer, designated as c(RGD)2-9R. The efficiency of 9R peptide transferring siRNA was biologically evaluated in vitro by flow cytometry, confocal microscopy, and Western blot; (3) Results: An optimal 10:1 molar ratio of c(RGD)2-9R to siRNA was confirmed by the electrophoresis on agarose gels. Both the flow cytometry and confocal microscopy results testified that transfection of c(RGD)2-9R as an siRNA delivery carrier was obviously higher than the naked-siRNA group. The results of Western blot demonstrated that these 9R peptides were able to transduce siRNA to HepG2 cells in vitro, resulting in efficient gene silencing; and (4) Conclusion: The chimeric peptide of c(RGD)2-9R can be developed as an effective siRNA delivery carrier and shows potential as a new strategy for RNAi-based gene therapy.