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Global concern continues to mount regarding the accumulation of microplastics (MPs) in soil. However, little is known about how various types of MPs influence the properties of soil ecosystems. Here, we evaluated the effects of six different types of MPs, including low-density polyethylene (LDPE), polyamide (PA), polystyrene (PS), polyhydroxy-alkanoates (PHA), polybutadiene styrene (PBS), and polylactide (PLA), on soil physicochemical properties, enzyme activities, and microbial communities. At the end of a 230-day soil incubation, we observed significant changes in soil moisture content, soil organic carbon, pH, NH4+-N, NO3--N, and available phosphorus. The addition of MPs had a significant influence on the activities of soil β-glucosidase, acid phosphatase, urease, and fluorescein diacetate hydrolase, with effects varying with MP type. Results of 16S rRNA gene high throughput sequencing showed that MP exposure had little effect on soil microbial alpha diversity, but that PHA contamination significantly reduced ACE, Chao1, and Shannon index values. MP contamination also altered soil microbial community composition. In particular, the relative abundance of Firmicutes increased significantly while the relative abundance of Actinobacteriota, Proteobacteria (especially the nitrogen-fixing rhizobia), and Acidobacteriota decreased following exposure to PHA. Redundancy analysis showed that acid phosphatase and pH were the two main environmental factors affecting bacterial community structure at the phylum and order levels. Furthermore, Tax4Fun2 analysis found that MP treatment disrupted fundamental bacterial metabolic pathways. Our findings indicate that different types of MPs can affect soil fertility, bacterial community structure, and function in various ways, and highlight that biodegradable MPs may alter soil bacterial communities more than conventional MPs.

[Objective] In the early operation stage of Jinan Metro Line 3, multiple sporadic high-speed circuit breaker closing failures are reported. To improve the reliability of train operation, it is necessary to optimize the high-speed circuit breaker control circuit in the traction system. [Method] According to the relevant closing command and the component status when a closure failure of the high-speed circuit breaker on Line 3 train occurs, and in accordance with the control logic principle of the high-speed breaker, the causes of the occasional closure failure are analyzed and the optimization measures are put forward. [Result & Conclusion] The causes of the occasional closure failure are that in the process of closure control of high-speed circuit breaker, the induced electromotive force generated at both ends of the high-speed circuit breaker coil makes the closing power insufficient, resulting in the failure closure of the breaker. The improvement measure is to connect freewheel diodes at both ends of the high-speed circuit coil to suppress the induced electromotive force generated by the above coil. With the above improvement measure, the closure failure of the high-speed circuit breaker caused by induced electromotive force never occurs again, and the reliability of train operation is effectively improved.

Folates, a crucial B-group vitamin, serve as a significant functional food supplement. Nevertheless, considerable obstacles persist in improving folates stability in liquid products. In this study, folic acid (FA) and 5-methyltetrahydrofolate (MTFA), two approved sources of folates, were encapsulated with sodium caseinate (NaCas) to enhance their stability. The protective effect of NaCas on folate molecules was investigated using experimental and computational methods. Meanwhile, the influence of divalent calcium ion (Ca2+) on the properties of the NaCas-MTFA complex was examined to evaluate the potential application of calcium 5-methyltetrahydrofolate (CaMTFA). Fluorescence tests showed both folates had static quenching behavior and bound to NaCas with a binding constant of 104–105 M−1. Hydrophobic interactions were crucial in NaCas-FA complex formation, while hydrogen bonding drove NaCas-MTFA binding. The encapsulation of caseinate notably slowed down the degradation of folates under both light and dark conditions. Moreover, the addition of a low concentration of Ca2+ did not adversely impact the binding mechanism of the NaCas-MTFA complex or the degradation curve of MTFA. The results of this study could serve as a valuable resource for the utilization of caseinates in incorporating folates, specifically MTFA, in the creation of natural liquid dietary supplements.

Due to the absence of definitive diagnostic criteria, there remains a lack of consensus regarding the risk assessment of central lymph node metastasis (CLNM) and the necessity for prophylactic lymph node surgery in ultrasound-diagnosed thyroid cancer. The localization of thyroid nodules is a recognized predictor of CLNM; however, quantifying this relationship is challenging due to variable measurements. In this study, we developed a differential isomorphism-based alignment method combined with a graph transformer to accurately extract localization and morphological information of thyroid nodules, thereby predicting CLNM. We collected 88,796 ultrasound images from 48,969 patients who underwent central lymph node (CLN) surgery and utilized these images to train our predictive model, ACE-Net. Furthermore, we employed an interpretable methodology to explore the factors influencing CLNM and generated a risk heatmap to visually represent the distribution of CLNM risk across different thyroid regions. ACE-Net demonstrated superior performance in 6 external multicenter tests (AUC = 0.826), surpassing the predictive accuracy of human experts (accuracy = 0.561). The risk heatmap enabled the identification of high-risk areas for CLNM, likely correlating with lymphatic metastatic pathways. Additionally, it was observed that the likelihood of metastasis exceeded 80% when the nodal margin’s minimum distance from the thyroid capsule was less than 1.25 mm. ACE-Net’s capacity to effectively predict CLNM and provide interpretable disease-related insights can importantly reduce unnecessary lymph node dissections by 37.9%, without missing positive cases, thus offering a valuable tool for clinical decision-making.

Lutein (Lut) and zeaxanthin (Zx) are promising healthy food ingredients; however, the low solubilities, stabilities, and bioavailabilities limit their applications in the food and beverage industries. A protein-based complex represents an efficient protective carrier for hydrophobic ligands, and its ligand-binding properties are influenced by the formulation conditions, particularly the pH level. This study explored the effects of various pH values (2.5–9.5) on the characteristics of whey protein isolate (WPI)–Lut/Zx complexes using multiple spectroscopic techniques, including ultraviolet–visible (UV–Vis), fluorescence, and Fourier transform infrared (FTIR) spectroscopies and dynamic light scattering (DLS). UV–Vis and DLS spectra revealed that Lut/Zx were present as H-aggregates in aqueous solutions, whereas WPI occurred as nanoparticles. The produced WPI–Lut/Zx complexes exhibited binding constants of 104–105 M−1, which gradually increased with increasing pH from 2.5 to 9.5. FTIR spectra demonstrated that pH variations and Lut/Zx addition caused detectable changes in the secondary WPI structure. Moreover, the WPI–Lut/Zx complexes effectively improved the physicochemical stabilities and antioxidant activities of Lut/Zx aggregates during long-term storage and achieved bioaccessibilities above 70% in a simulated gastrointestinal digestion process. The comprehensive data obtained in this study offer a basis for formulating strategies that can be potentially used in developing commercially available WPI complex-based xanthophyll-rich foods.

Carotenoids, which are inherent pigments occurring in plants and microorganisms, manifest a diverse array of vivid hues. Owing to their multifarious health advantages, carotenoids have engendered substantial interest among scholars and consumers alike. Presently, carotenoids are extensively employed in the realms of food, nutrition and health commodities, pharmaceuticals, and cosmetics, rendering them an indispensable constituent of our quotidian existence. Therefore, the objective of this review is to present a succinct and methodical examination of the sources, constituents, and factors influencing formation of carotenoids. Particular attention will be given to encapsulation strategies that maintain intrinsic characteristics, as the growing desire for carotenoids is propelled by individuals’ escalating standards of living. Moreover, the applications of natural carotenoids in multiple fields, including pharmaceutical, food and feed, as well as cosmetics, are discussed in detail. Finally, this article explores the main challenges hindering the future advancement of carotenoids, aiming at facilitating their effective integration into the circular economy.

Paxlovid®, a co-packaged medication comprised of separate tablets containing two active ingredients, nirmatrelvir (NRV) and ritonavir (RTV), exhibits good effectiveness against coronavirus disease 2019 (COVID-19). However, the size of the NRV/RTV tablets makes them difficult for some patients to swallow, especially the elderly and those with dysphagia. Therefore, an oral liquid formulation that can overcome this shortcoming and improve patient compliance is required. In this study, we developed a liquid formulation containing NRV and RTV by adopting strategies that used co-solvents and surfactants to enhance the solubility and inhibit possible recrystallization. The in vitro release results showed that NRV and RTV could be maintained at high concentrations in solution for a certain period in the investigated media. In vivo studies in rats showed that the oral bioavailability of NRV/RTV solution was significantly enhanced. Compared to Paxlovid® tablets, the AUC(0–t) of NRV and RTV increased by 6.1 and 3.8 times, respectively, while the Cmax increased by 5.5 times for both. Furthermore, the promoting effect of the absorption of RTV on the bioavailability of NRV was confirmed. Experiments with a beagle showed a similar trend. Stability studies were also conducted at 4 °C, 25 °C, and 40 °C for 90 days, indicating that the oral liquid formulation was physically and chemically stable. This study can be used as a valuable resource for developing and applying oral liquid NRV/RTV formulations in a clinical context.

On May 22, 2021, an earthquake of M7.4 occurred in Maduo County, Qinghai Province, causing the collapse of the Yematan bridge and the Yematan No.2 bridge in Maduo County. According to the earthquake intensity announced by China Earthquake Administration, the earthquake intensity of the Yematan bridge is IX. However, the lack of strong seismic stations and the unrecorded time history of ground motion near the bridge is also hindering the research work on earthquake-induced failure mechanisms of the Yematan bridge. Therefore, this paper attempts to use the empirical Green's function method and refer to the concept of self-heterotopic skin transplantation in medicine to preliminarily evaluate the main characteristics of the ground motion intensity at the Yematan bridge, and try to give the possible range of peak ground acceleration (PGA) and the ground motion time history. The latest China seismic intensity table (GB/T17742—2020) and the design response spectra of the fifth generation seismic zoning map (GB18306—2015) are compared. The results show that: (1) the range of PGA (320~620 cm/s2) obtained in this paper matches well with the range of PGA (402~830 cm/s2) in China seismic intensity table (GB/T17742—2020); (2) The ground motion response spectrum synthesized matches well with the acceleration design response spectrum of extremely rare ground motions at the Yematan bridge in the fifth generation seismic zoning map (GB18306—2015), which indicates that the acceleration time history synthesized in this paper can cause the beam falling failure of the bridge. Our results show that the characteristics of ground motion intensity near the Yematan bridge are very possible and have a certain reference value. It can be used as the time history input of ground motion for the Yematan bridge and provide data support for the study of the collapse mechanism of bridge.

BackgroundThyroid Cancer (TC) is the most common malignant disease of endocrine system, and its incidence rate is increasing year by year. Early diagnosis, management of malignant nodules and scientific treatment are crucial for TC prognosis. The first aim is the construction of a classification model for TC based on risk factors. The second aim is the construction of a prediction model for metastasis based on risk factors.MethodsWe retrospectively collected approximately 70 preoperative demographic and laboratory test indices from 1735 TC patients. Machine learning pipelines including linear regression model ridge, Logistic Regression (LR) and eXtreme Gradient Boosting (XGBoost) were used to select the best model for predicting deterioration and metastasis of TC. A comprehensive comparative analysis with the prediction model using only thyroid imaging reporting and data system (TI-RADS).ResultsThe XGBoost model achieved the best performance in the final thyroid nodule diagnosis (AUC: 0.84) and metastasis (AUC: 0.72-0.77) predictions. Its AUCs for predicting Grade 4 TC deterioration and metastasis reached 0.84 and 0.97, respectively, while none of the AUCs for Only TI-RADS reached 0.70. Based on multivariate analysis and feature selection, age, obesity, prothrombin time, fibrinogen, and HBeAb were common significant risk factors for tumor progression and metastasis. Monocyte, D-dimer, T3, FT3, and albumin were common protective factors. Tumor size (11.14 ± 7.14 mm) is the most important indicator of metastasis formation. In addition, GGT, glucose, platelet volume distribution width, and neutrophil percentage also contributed to the development of metastases. The abnormal levels of blood lipid and uric acid were closely related to the deterioration of tumor. The dual role of mean erythrocytic hemoglobin concentration in TC needs to be verified in a larger patient cohort. We have established a free online tool (http://www.cancer-thyroid.com/) that is available to all clinicians for the prognosis of patients at high risk of TC.ConclusionIt is feasible to use XGBoost algorithm, combined with preoperative laboratory test indexes and demographic characteristics to predict tumor progression and metastasis in patients with TC, and its performance is better than that of Only using TI-RADS. The web tools we developed can help physicians with less clinical experience to choose the appropriate clinical decision or secondary confirmation of diagnosis results.

Abstract Head and neck cancer (HNC) tumorigenesis involves a combination of multiple genetic alteration processes. Tumour necrosis factor-alpha-induced proteins (TNFAIPs) are involved in tumour development and progression, but few studies have been conducted on these factors in HNC. We aimed to analyse TNFAIPs and assess their potential as prognostic biomarkers and therapeutic targets using the Oncomine, UALCAN, Human Protein Atlas, LinkedOmics, cBioPortal, GeneMANIA, Enrichr, and Tumor IMmune Estimation Resource databases. We found that the transcript levels of TNFAIP1, TNFAIP3, EFNA1, TNFAIP6 and TNFAIP8 were increased, while those of TNFAIP8L3 and STEAP4 were reduced in HNC tissues versus normal tissues. The EFNA1, TNFAIP8 and TNFAIP8L3 expression levels were significantly correlated with the pathological stage. In HNC patients, high PTX3 and TNFAIP6 transcript levels were significantly associated with shorter overall survival (OS). Moreover, genetic alterations in TNFAIP1, TNFAIP6, and STEAP4 resulted in poorer disease-free survival, progression-free survival, and OS, respectively. TNFAIPs may mediate HNC tumorigenesis by regulating PI3K-Akt, Ras and other signalling pathways. TNFAIPs are also closely correlated with the infiltration of immune cells, including B cells, CD8+ T cells, CD4+ T cells, etc. The data above indicate that TNFAIPs may be potential biomarkers and therapeutic targets for HNC.

Several polyphenol compounds commonly found in plant foods provide health benefits that promote their applications in food and pharmaceutical fields. The co-loading of proteins can improve the biological activity and synergy of combined polyphenols. Herein, multi-spectroscopic techniques and molecular docking were employed to investigate the interactions of native/heat treated β-lactoglobulin (β-LG/H-β-LG) with (−)-epicatechin gallate (ECG) and/or piceatannol (PIC). Furthermore, the synergistic antioxidant activity and cytotoxicity of ECG and PIC were demonstrated. The loading of β-LG/H-β-LG protected the antioxidant activity of ECG and PIC in the delivery systems and enhanced their cytotoxicity, stability, and bioaccessibility. Compared to the corresponding complexes, the nanoparticles of β-LG/H-β-LG had a greater impact on the functional properties and synergistic effects of ECG and PIC. The experimental results may provide a theoretical basis for the practical application of ECG and PIC co-loaded by H-β-LG, particularly H-β-LG nanoparticles in the food and pharmaceutical industries.

Combinatorial chemo-photodynamic therapy is regared as effective cancer therapy strategy, which could be realized via multiple nano-drug delivery system. Herein, novel high payload nanoparticles stabilized by amphiphilic block polymer cholesterol-b-poly(ethylene glycol) (PEG)2000 (Chol-PEG2000) were fabricated for loading chemotherapeutic drug 10-hydroxycamptothecin (HCPT) and photosensitizer chlorin e6 (Ce6). The obtained HCPT/Ce6 NPs showed uniform rod-like morphology with a hydration diameter of 178.9 ± 4.0 nm and excellent stability in aqueous solution. HCPT and Ce6 in the NPs displayed differential release profile, which was benefit for preferentially exerting the photodynamic effect and subsequently enhancing the sensitivity of the cells to HCPT. Under laser irradiation, the NPs demonstrated fantastic in vitro and in vivo anticancer efficiency due to combinational chemo-photodynamic therapy, enhanced cellular uptake effectiveness, and superb intracellular ROS productivity. Besides, the NPs were proved as absent of systemic toxicity. In summary, this nanoparticle delivery system could be hopefully utilized as effective cancer therapy strategy for synergistically exerting combined chemo-photodynamic therapy in clinic.

A ternary amorphous solid dispersion (ASD) system consisting of drug/polymer/surfactant is receiving increased attention to improve the oral bioavailability of poorly water-soluble drugs. The effect of polymers has been extensively studied, while the impact of surfactants has not yet to be studied to the same extent. Challenging questions to be answered are whether the surfactants should be added with the drug or separately and the resulting differences between the two operating processes. By adjusting the liquid feeding zone for Span 20 in the hot-melt twin screw extruder equipment, we investigated the effect of Span 20 on the properties of the polyvinylpyrrolidone/vinyl acetate (PVPVA)-based ASD formulations of ritonavir. We found that with the delayed feeding positions of Span 20 in the twin screw extruder, the ability of the ternary ASDs to maintain the supersaturation of the milled extrudates was observed to be significantly enhanced. Furthermore, adding surfactant after a thorough mixing of polymer and drug could decrease the molecular mobility of ternary ASD formulations. In addition, the effects of Span 20 on the complex viscosity and structure of PVPVA were also investigated. The delayed addition of Span 20 could improve the complex viscosity of PVPVA, thus leading to the drug precipitation inhibition. In conclusion, the delayed addition of Span 20 in the twin screw extruder and prolonging the mixing time of the drug and polymer may be critical to the maintenance of supersaturation.

High-fat diet (HFD) intake is commonly related to a substantial risk of cognitive impairment for senior citizens over 65 years of age, which constitutes a profound global health burden with several economic and social consequences. It is critical to investigate the effects of long-term HFD consumption on cognitive function and to inspect the potential underlying mechanisms. In the present study, 9-month-old male C57BL/6 mice were randomly assigned to either a normal diet (ND, 10 kcal% fat) or an HFD diet (60 kcal% fat) for 10 months. Then a series of behavioral tests, and histological and biochemistry examinations of the hippocampus and cortex proceeded. We found that long-term HFD-fed aged mice exhibited cognitive function decline in the object place recognition test (OPR). Compared with the ND group, the HFD-fed mice showed Tau hyperphosphorylation at ps214 in the hippocampus and at ps422 and ps396 in the cortex, which was accompanied by GSK-3β activation. The higher activated phenotype of microglia in the brain of the HFD group was typically evidenced by an increased average area of the cell body and reduced complexity of microglial processes. Immunoblotting showed that long-term HFD intake augmented the levels of inflammatory cytokines IL-6 in the hippocampus. These findings indicate that long-term HFD intake deteriorates cognitive dysfunctions, accompanied by Tau hyperphosphorylation, microglial activation, and inflammatory cytokine expression, and that the modifiable lifestyle factor contributes to the cognitive decline of senior citizens.

The detailed morphometry alterations of the human hippocampal formation (HF) for blind individuals are still understudied. 50 subjects were recruited from Yantai Affiliated Hospital of Binzhou Medical University, including 16 congenital blindness, 14 late blindness, and 20 sighted controls. Volume and shape analysis were conducted between the blind (congenital or late) and sighted groups to observe the (sub)regional alterations of the HF. No significant difference of the hippocampal volume was observed between the blind and sighted subjects. Rightward asymmetry of the hippocampal volume was found for both congenital and late blind individuals, while no significant hemispheric difference was observed for the sighted controls. Shape analysis showed that the superior and inferior parts of both the hippocampal head and tail expanded, while the medial and lateral parts constrained for the blind individuals as compared to the sighted controls. The morphometry alterations for the congenital blind and late blind individuals are nearly the same. Significant expansion of the superior part of the hippocampal tail for both congenital and late blind groups were observed for the left hippocampi after FDR correction. Current results suggest that the cross-model plastic may occur in both hemispheres of the HF to improve the navigation ability without the stimuli of visual cues, and the alteration is more prominent for the left hemisphere.

We present a novel top-push constrained feature learning (TFL) method for face identification. The idea is to learn low-rank approximations from raw intensity face images such that the squared distance between all faces of the same identity should be smaller than that of different identities by a margin. To this end, we formulate the learning process under the framework of generalized low-rank approximation of matrices (GLRAM) supervised with a top-push constraint. GLRAM operates on the matrix representation of images to seek low-dimensional and compact features, which improves the discriminative power of the features while reducing the time and space costs. The top-push constraint aims to optimize the face identification accuracy of the top-rank matching list, which makes the learned features more discriminative and compact, thus reducing the variability and ambiguity. Once the optimization is finished, the features are vectorized and used for similarity measurement. The effectiveness of TFL is verified on four publicly available face datasets.

ABSTRACT Bacterial persisters exhibit noninherited antibiotic tolerance and are linked to the recalcitrance of bacterial infections. It is very urgent but also challenging to develop antipersister strategies. Here, we report that 10-s freezing with liquid nitrogen dramatically enhances the bactericidal action of aminoglycoside antibiotics by 2 to 6 orders of magnitude against many Gram-negative pathogens, with weaker potentiation effects on Gram-positive bacteria. In particular, antibiotic-tolerant Escherichia coli and Pseudomonas aeruginosa persisters—which were prepared by treating exponential-phase cells with ampicillin, ofloxacin, the protonophore cyanide m-chlorophenyl hydrazone (CCCP), or bacteriostatic antibiotics—can be effectively killed. We demonstrated, as a proof of concept, that freezing potentiated the aminoglycosides' killing of P. aeruginosa persisters in a mouse acute skin wound model. Mechanistically, freezing dramatically increased the bacterial uptake of aminoglycosides regardless of the presence of CCCP, indicating that the effects are independent of the proton motive force (PMF). In line with these results, we found that the effects were linked to freezing-induced cell membrane damage and were attributable, at least partly, to the mechanosensitive ion channel MscL, which was able to directly mediate such freezing-enhanced aminoglycoside uptake. In view of these results, we propose that the freezing-induced aminoglycoside potentiation is achieved by freezing-induced cell membrane destabilization, which, in turn, activates the MscL channel, which is able to effectively take up aminoglycosides in a PMF-independent manner. Our work may pave the way for the development of antipersister strategies that utilize the same mechanism as freezing but do so without causing any injury to animal cells. IMPORTANCE Antibiotics have long been used to successfully kill bacterial pathogens, but antibiotic resistance/tolerance usually has led to the failure of antibiotic therapy, and it has become a severe threat to human health. How to improve the efficacy of existing antibiotics is of importance for combating antibiotic-resistant/tolerant pathogens. Here, we report that 10-s rapid freezing with liquid nitrogen dramatically enhanced the bactericidal action of aminoglycoside antibiotics by 2 to 6 orders of magnitude against many bacterial pathogens in vitro and also in a mouse skin wound model. In particular, such combined treatment was able to effectively kill persister cells of Escherichia coli and Pseudomonas aeruginosa, which are per se tolerant of conventional treatment with bactericidal antibiotics for several hours. We also demonstrated that freezing-induced aminoglycoside potentiation was apparently linked to freezing-induced cell membrane damage that may have activated the mechanosensitive ion channel MscL, which, in turn, was able to effectively uptake aminoglycoside antibiotics in a proton motive force-independent manner. Our report sheds light on the development of a new strategy against bacterial pathogens by combining existing antibiotics with a conventional physical treatment or with MscL agonists.

The crustal thicknesses and the Poisson's ratios under the seismic stations can be calculated by receiver function method with H-ҡ stacking effectively. But the stacking results are affected to some extent by the average crustal P-wave velocity. To eliminate this effect and get more accurate crustal structure along the Zhenkang–Luxi deep seismic sounding profile which lies in Yunnan Province, we calculate the receiver functions from the teleseismic events recorded by 11 temporary stations as well as 5 permanent ones along the profile and carry out the stacking with Vp obtained from the profile in this study. Our study shows that the crustal thicknesses along the Zhenkang–Luxi profile range from 34.8 km to 41.8 km with an average of 39 km. The crust is thicker in the middle part of the profile and thinner in both sides in general. Dramatic changes of crustal thickness about 3 km are detected across both the Lancangjiang fault and the Xiaojiang fault, which implies that these faults cut through the Moho. The lowest Poisson's ratio under the stations is 0.22 and the highest is 0.27 with the mean of 0.25, which is lower than the global average value 0.27 in the continental crust. It suggests that most of the crust along the profile lacks mafic component, but contains more felsic substance. The low Poisson's ratio also indicates that there is no satisfying condition for partial melting. We deduce that the material flow in the middle-lower crust in the southeastern margin of the Tibetan plateau may occur only in the north region of 24°N. Keywords: Receiver function, Crustal structure, Lancangjiang fault, Xiaojiang fault, Mid-lower crust flow

This paper presents a supervised feature learning method to learn discriminative and compact descriptors for drusen segmentation from retinal images. This method combines generalized low rank approximation of matrices with supervised manifold regularization to learn new features from image patches sampled from retinal images. The learned features are closely related to drusen and potentially free from information that is redundant in distinguishing drusen from background. The learned feature representations are then vectorized and used to train a support vector machine (SVM) classifier. Finally, the obtained SVM classifier is employed to classify the pixels in the test images as drusen or non-drusen. The performance of the proposed method is validated on the STARE and DRIVE databases, where it achieves an average sensitivity/specificity/accuracy of 90.03%/97.06%/96.92% and of 87.41%/94.93%/94.81%, respectively. We also experimentally compare the proposed method with the several representative state-of-the-art drusen segmentation techniques and find that it generates superior accuracy.

The quality control of drug products during manufacturing processes is important, particularly the presence of different polymorphic forms in active pharmaceutical ingredients (APIs) during production, which could affect the performance of the formulated products. The objective of this study was to investigate the phase transformation of fexofenadine hydrochloride (FXD) and its influence on the quality and performance of the drug. Water addition was key controlling factor for the polymorphic conversion from Form I to Form II (hydrate) during the wet granulation process of FXD. Water-induced phase transformation of FXD was studied and quantified with XRD and thermal analysis. When FXD was mixed with water, it rapidly converted to Form II, while the conversion is retarded when FXD is formulated with excipients. In addition, the conversion was totally inhibited when the water content was w/w. The relationship between phase transformation and water content was studied at the small scale, and it was also applicable for the scale-up during wet granulation. The effect of phase transition on the FXD tablet performance was investigated by evaluating granule characterization and dissolution behavior. It was shown that, during the transition, the dissolved FXD acted as a binder to improve the properties of granules, such as density and flowability. However, if the water was over added, it can lead to the incomplete release of the FXD during dissolution. In order to balance the quality attributes and the dissolution of granules, the phase transition of FXD and the water amount added should be controlled during wet granulation.

Celecoxib (CLX), a selective COX-2 inhibitor, is a biopharmaceutics classification system (BCS) class II drug with its bioavailability being limited by thepoor aqueoussolubility. The purpose of this study was to develop and optimize CLX nanocrystalline(CLX-NC) solid dispersion prepared by the wet medium millingtechnique combined with lyophilizationto enhance oral bioavailability. In formulation screening, the resulting CLX-NC usingpolyvinylpyrrolidone (PVP) VA64 and sodiumdodecyl sulfate (SDS) as combined stabilizers showed the minimum particle size and a satisfactory stability. The formulation and preparation processwere further optimized by central composite experimentaldesign with PVP VA64 concentration (X1), SDS concentration (X2) and milling times (X3) as independent factors and particle size (Y1), polydispersity index (PDI, Y2) and zeta potential (Y3) as response variables. The optimal condition was determined as a combination of 0.75% PVP VA64, 0.11% SDS with milling for 90 min.The particle size, PDI and zeta potential of optimized CLX-NC were found to be 152.4 ± 1.4 nm, 0.191 ± 0.012 and −34.4 ± 0.6 mV, respectively. The optimized formulation showed homogeneous rod-like morphology as observed by scanning electron microscopy and was in a crystalline state as determined by differential scanning calorimetry and powder X-ray diffraction. In a storage stability study, optimized CLX-NC exhibited an excellent physical stability during six months’ storage at both the refrigeration and room conditions. In vivo pharmacokinetic research in Sprague-Dawley ratsdisplayed that Cmax and AUC0−∞ of CLX-NC were increased by 2.9 and 3.1 fold, compared with physical mixture. In this study, the screening and optimizing strategy of CLX-NC formulation represents a commercially viable approach forenhancing the oral bioavailability of CLX.

Logo detection has gradually become a research hotspot in the field of computer vision and multimedia for its various applications, such as social media monitoring, intelligent transportation, and video advertising recommendation. Recent advances in this area are dominated by deep learning-based solutions, where many datasets, learning strategies, network architectures, and loss functions have been employed. This article reviews the advance in applying deep learning techniques to logo detection. First, we discuss a comprehensive account of public datasets designed to facilitate performance evaluation of logo detection algorithms, which tend to be more diverse, more challenging, and more reflective of real life. Next, we perform an in-depth analysis of the existing logo detection strategies and their strengths and weaknesses of each learning strategy. Subsequently, we summarize the applications of logo detection in various fields, from intelligent transportation and brand monitoring to copyright and trademark compliance. Finally, we analyze the potential challenges and present the future directions for the development of logo detection. This study aims better to inform readers about the current state of logo detection and encourage more researchers to get involved in logo detection. [ABSTRACT FROM AUTHOR]

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In orchards, detecting green apples can be challenging due to interference factors like similar fruit and background color, branch and leaf shading, and fruit overlap. To address this limitation, this paper presents a simple yet effective detection model based on improved YOLOv5, which can enhance the detection ability of green apples against a near-color background. Our contributions are twofold. Firstly, we added an attention mechanism to enhance the feature extraction network of the conventional YOLOv5. This modification focuses the network on green apple features and improves the detection performances on green apples. Secondly, we introduced the Focal Loss calculation method to the loss calculation of YOLOv5, to improve the model's results by controlling positive and negative sample weights as well as hard and easy to classify sample weights. Experimental results show that our model yields better results. While the base YOLOv5 model achieved an Average Precision (AP) of 86.3% and an Average Recall (AR) of 66.8% on the green apple dataset test, our improved YOLOv5 model reached an AP of 88.1% (a 1.8 percentage point improvement) and an AR of 69.1% (a 2.3 percentage point improvement). Our proposed model, therefore, significantly enhances detection efficiency. [ABSTRACT FROM AUTHOR]