Search

Monitoring patient safety during clinical trials is a critical component throughout the drug development life-cycle. Pharmaceutical sponsors must work proactively and collaboratively with all stakeholders to ensure a systematic approach to safety monitoring. The regulatory landscape has evolved with increased requirements for risk management plans, risk evaluation and minimization strategies. As the industry transitions from passive to active safety surveillance activities, there will be greater demand for more comprehensive and innovative approaches that apply quantitative methods to accumulating data from all sources, ranging from the discovery and preclinical through clinical and post-approval stages. Statistical methods, especially those based on the Bayesian framework, are important tools to help provide objectivity and rigor to the safety monitoring process. [ABSTRACT FROM AUTHOR]

In this paper, a method for augmenting samples of side-scan sonar seafloor sediment images based on CBAM-BCEL1-INGAN is proposed, aiming to address the difficulties in acquiring and labeling datasets, as well as the insufficient diversity and quantity of data samples. Firstly, a Convolutional Block Attention Module (CBAM) is integrated into the residual blocks of the INGAN generator to enhance the learning of specific attributes and improve the quality of the generated images. Secondly, a BCEL1 loss function (combining binary cross-entropy and L1 loss functions) is introduced into the discriminator, enabling it to focus on both global image consistency and finer distinctions for better generation results. Finally, augmented samples are input into an AlexNet classifier to verify their authenticity. Experimental results demonstrate the excellent performance of the method in generating images of coarse sand, gravel, and bedrock, as evidenced by significant improvements in the Frechet Inception Distance (FID) and Inception Score (IS). The introduction of the CBAM and BCEL1 loss function notably enhances the quality and details of the generated images. Moreover, classification experiments using the AlexNet classifier show an increase in the recognition rate from 90.5% using only INGAN-generated images of bedrock to 97.3% using images augmented using our method, marking a 6.8% improvement. Additionally, the classification accuracy of bedrock-type matrices is improved by 5.2% when images enhanced using the method presented in this paper are added to the training set, which is 2.7% higher than that of the simple method amplification. This validates the effectiveness of our method in the task of generating seafloor sediment images, partially alleviating the scarcity of side-scan sonar seafloor sediment image data.

The lateral root (LR) is an essential component of the plant root system, performing important functions for nutrient and water uptake in plants and playing a pivotal role in cereal crop productivity. Nitrate (NO 3 - ) is an essential nutrient for plants. In this study, wheat plants were grown in 1/2 strength Hoagland's solution containing 5 mM NO 3 - (check; CK), 0.1 mM NO 3 plus 60 mg/L 2,3,5-triiodobenzoic acid (TIBA) (LNT). The results showed that LN increased the LR number significantly at 48 h after treatment compared with CK, while not increasing the root biomass, and LNT significantly decreased the LR number and root biomass. The transcriptomic analysis showed that LN induced the expression of genes related to root IAA synthesis and transport and cell wall remodeling, and it was suppressed in the LNT conditions. A physiological assay revealed that the LN conditions increased the activity of IAA biosynthesis-related enzymes, the concentrations of tryptophan and IAA, and the activity of cell wall remodeling enzymes in the roots, whereas the content of polysaccharides in the LRP cell wall was significantly decreased compared with the control. Fourier-transform infrared spectroscopy and atomic microscopy revealed that the content of cell wall polysaccharides decreased and the cell wall elasticity of LR primordia (LRP) increased under the LN conditions. The effects of LN on IAA synthesis and polar transport, cell wall remodeling, and LR development were abolished when TIBA was applied. Our findings indicate that NO - (low NO 3 - ; LN), or 0.1 mM NO 3 - plus 60 mg/L 2,3,5-triiodobenzoic acid (TIBA) (LNT). The results showed that LN increased the LR number significantly at 48 h after treatment compared with CK, while not increasing the root biomass, and LNT significantly decreased the LR number and root biomass. The transcriptomic analysis showed that LN induced the expression of genes related to root IAA synthesis and transport and cell wall remodeling, and it was suppressed in the LNT conditions. A physiological assay revealed that the LN conditions increased the activity of IAA biosynthesis-related enzymes, the concentrations of tryptophan and IAA, and the activity of cell wall remodeling enzymes in the roots, whereas the content of polysaccharides in the LRP cell wall was significantly decreased compared with the control. Fourier-transform infrared spectroscopy and atomic microscopy revealed that the content of cell wall polysaccharides decreased and the cell wall elasticity of LR primordia (LRP) increased under the LN conditions. The effects of LN on IAA synthesis and polar transport, cell wall remodeling, and LR development were abolished when TIBA was applied. Our findings indicate that NO 3 - starvation may improve auxin homeostasis and the biological properties of the LRP cell wall and thus promote LR initiation, while TIBA addition dampens the effects of LN on auxin signaling, gene expression, physiological processes, and the root architecture.

The continuous worsening of the natural surroundings requires accelerating the exploration of green energy technology. Utilising ambient vibration to power electronic equipment constitutes an important measure to address the power crisis. Vibration power is widely dispersed in the surroundings, such as mechanical vibration, acoustic vibration, wind vibration, and water wave vibration. Collecting vibration energy is one of the research hotspots in the field of energy. Meanwhile, it is also an important way to solve the energy crisis. This paper illustrates the working principles and recent research progress of five known methods of vibrational energy harvesting, namely, electromagnetic, piezoelectric, friction electric, electrostatic, and magnetostrictive vibrational energy harvesters. The strengths and weaknesses of each method are summarised. At the end of the article, the future trends of micro-nano vibrational energy collectors are envisioned.

Triple-negative breast cancer (TNBC) has been considered a huge clinical unmet need due to its aggressive progression and highly frequent metastasis. mRNA therapeutics supply a potential and versatile immunotherapy of oncology treatment. Here, we developed α-lactalbumin mRNA-lipid nanoparticles (α-LNP) as a potential therapeutical strategy for TNBC. The α-LNP induced the specific IgG antibodies and activated IFN γ-secreting-T cells in vivo. Additionally, the safety of α-LNP also had been demonstrated in vivo. When vaccinated prior to tumor implantation, α-LNP showed a preventive effect against 4T1 tumor growth and extended the survival of the tumor model by activating the memory immune responses. Furthermore, α-LNP administration in combination with surgical removal of neoplasm effectively inhibited the progression and metastasis in the TNBC model. Taken together, our results indicate that the α-LNP vaccine is a promising novel treatment for both therapeutics and prophylactics in TNBC.

Sinomenine hydrochloride is an excellent drug with anti-inflammatory, antioxidant, immune-regulatory, and other functions. Atopic dermatitis is an inherited allergic inflammation that causes itchiness, redness, and swelling in the affected area, which can have a significant impact on the life of the patient. There are many therapeutic methods for atopic dermatitis, and sinomenine with immunomodulatory activity might be effective in the treatment of atopic dermatitis. In this study, the atopic dermatitis model was established in experimental mice, and physical experiments were carried out on the mice. In the experiment, sinomenine hydrochloride liposomes-in-hydrogel as a new preparation was selected for delivery. In this case, liposomes were dispersed in the colloidal hydrogel on a mesoscopic scale and could provide specific transfer properties. The results showed that the sinomenine hydrochloride-loaded liposomes-in-hydrogel system could effectively inhibit atopic dermatitis.

Plant-derived PA10T is regarded as one of the most promising semi-aromatic polyamides; however, shortcomings, including low dimensional accuracy, high moisture absorption, and relatively high dielectric constant and loss, have impeded its extensive utilization. Polymer blending is a versatile and cost-effective method to fabricate new polymeric materials with excellent comprehensive performance. In this study, various ratios of PA10T/PPO blends were fabricated via melt blending with the addition of a SEBS-g-MAH compatibilizer. Molau test and scanning electron microscopy (SEM) were employed to study the influence of SEBS-g-MAH on the compatibility of PA10T and PPO. These studies indicated that SEBS-g-MAH effectively refines the domain size of the dispersed PPO phase and improves the dispersion stability of PPO particles within a hexafluoroisopropanol solvent. This result was attributed to the in situ formation of the SEBS-g-PA10T copolymer, which serves as a compatibilizer. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) results showed that the melting-crystallization behavior and thermal stability of blends closely resembled that of pure PA10T. Dynamic mechanical analysis (DMA) revealed that as the PPO content increased, there was a decrease in the glass transition temperature and storage modulus of PA10T. The water absorption rate, injection molding shrinkage, dielectric properties, and mechanical strength of blends were also systematically investigated. As the PPO content increased from 10% to 40%, the dielectric loss at 2.5 GHz decreased significantly from 0.00866 to 0.00572, while the notched Izod impact strength increased from 7.9 kJ/m 2 to 13.7 kJ/m 2 .

The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and paracrine pathways. Male fertility hinges on the availability of testosterone, a cornerstone of spermatogenesis, while follicle-stimulating hormone (FSH) signaling is indispensable for the proliferation, differentiation, and proper functioning of Sertoli and germ cells. This review covers the research on how androgens, FSH, and other hormones support processes crucial for male fertility in the testis and reproductive tract. These hormones are regulated by the hypothalamic-pituitary-gonad (HPG) axis, which is either quiescent or activated at different stages of the life course, and the regulation of the axis is crucial for the development and normal function of the male reproductive system. Hormonal imbalances, whether due to genetic predispositions or environmental influences, leading to hypogonadism or hypergonadism, can precipitate reproductive disorders. Investigating the regulatory network and molecular mechanisms involved in testicular development and spermatogenesis is instrumental in developing new therapeutic methods, drugs, and male hormonal contraceptives.

Based on the decorrelation calculation of diffusion ultrasound in time-frequency domain, this paper discusses the repeatability and potential significance of Disturbance Sensitive Zone (DSZ) in time-frequency domain. The experimental study of Barely Visible Impact Damage (BVID) on Carbon Fiber Reinforced Polymer (CFRP) is carried out. The decorrelation coefficients of time, frequency, and time-frequency domains and DSZ are calculated and compared. It has been observed that the sensitivity of the scattered wave disturbance caused by impact damage is non-uniformly distributed in both the time and frequency domains. This is evident from the non-uniform distribution of the decorrelation coefficient in time-domain and frequency-domain decorrelation calculations. Further, the decorrelation calculation in the time-frequency domain can show the distribution of the sensitivity of the scattered wave disturbance in the time domain and frequency domain. The decorrelation coefficients in time, frequency, and time-frequency domains increase monotonically with the number of impacts. In addition, in the time-frequency domain decorrelation calculation results, stable and repetitive DSZ are observed, which means that the specific frequency component of the scattered wave is extremely sensitive to the damage evolution of the impact region at a specific time. Finally, the DSZ obtained from the first 15 impacts is used to improve the decorrelation calculation in the 16-th to 20-th impact. The results show that the increment rate of the improved decorrelation coefficient is 10.22%. This study reveals that the diffusion ultrasonic decorrelation calculation improved by DSZ makes it feasible to evaluate early-stage damage caused by BVID.

Tumor necrosis factor-α-induced protein 8-like 3 (TNFAIP8L3 or TIPE3) functions as a transfer protein for lipid second messengers. TIPE3 is highly upregulated in several human cancers and has been established to significantly promote tumor cell proliferation, migration, and invasion and inhibit the apoptosis of cancer cells. Thus, inhibiting the function of TIPE3 is expected to be an effective strategy against cancer. The advancement of artificial intelligence (AI)-driven drug development has recently invigorated research in anti-cancer drug development. In this work, we incorporated DFCNN, Autodock Vina docking, DeepBindBC, MD, and metadynamics to efficiently identify inhibitors of TIPE3 from a ZINC compound dataset. Six potential candidates were selected for further experimental study to validate their anti-tumor activity. Among these, three small-molecule compounds (K784-8160, E745-0011, and 7238-1516) showed significant anti-tumor activity in vitro, leading to reduced tumor cell viability, proliferation, and migration and enhanced apoptotic tumor cell death. Notably, E745-0011 and 7238-1516 exhibited selective cytotoxicity toward tumor cells with high TIPE3 expression while having little or no effect on normal human cells or tumor cells with low TIPE3 expression. A molecular docking analysis further supported their interactions with TIPE3, highlighting hydrophobic interactions and their shared interaction residues and offering insights for designing more effective inhibitors. Taken together, this work demonstrates the feasibility of incorporating deep learning and MD simulations in virtual drug screening and provides inhibitors with significant potential for anti-cancer drug development against TIPE3-.

Orthobunyavirus is the largest and most diverse genus in the family Peribunyaviridae. Orthobunyaviruses are widely distributed globally and pose threats to human and animal health. Ebinur Lake virus (EBIV) is a newly classified Orthobunyavirus detected in China, Russia, and Kenya. This study explored the antiviral effects of two broad-spectrum antiviral drugs, favipiravir and ribavirin, in a BALB/c mouse model. Favipiravir significantly improved the clinical symptoms of infected mice, reduced viral titer and RNA copies in serum, and extended overall survival. The median survival times of mice in the vehicle- and favipiravir-treated groups were 5 and 7 days, respectively. Favipiravir significantly reduced virus titers 10- to 100-fold in sera at all three time points compared to vehicle-treated mice. And favipiravir treatment effectively reduced the virus copies by approximately 10-fold across the three time points, relative to vehicle-treated mice. The findings expand the antiviral spectrum of favipiravir for orthobunyaviruses in vivo., Competing Interests: The authors declare no conflicts of interest.

In this paper, berberine hydrochloride-loaded liposomes-in-gel were designed and developed to investigate their antioxidant properties and therapeutic effects on the eczema model of the mouse. Berberine hydrochloride-liposomes (BBH-L) as the nanoparticles were prepared by the thin-film hydration method and then dispersed BBH-L evenly in the gel matrix to prepare the berberine hydrochloride liposomes-gel (BBH-L-Gel) by the natural swelling method. Their antioxidant capacity was investigated by the free radical scavenging ability on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and H 2 O 2 and the inhibition of lipid peroxides malondialdehyde (MDA). An eczema model was established, and the efficacy of the eczema treatment was preliminarily evaluated using ear swelling, the spleen index, and pathological sections as indicators. The results indicate that the entrapment efficiency of BBH-L prepared by the thin-film hydration method was 78.56% ± 0.7%, with a particle size of 155.4 ± 9.3 nm. For BBH-L-Gel, the viscosity and pH were 18.16 ± 6.34 m Pas and 7.32 ± 0.08, respectively. The cumulative release in the unit area of the in vitro transdermal study was 85.01 ± 4.53 μg/cm 2 . BBH-L-Gel had a good scavenging capacity on DPPH and H 2 O 2 , and it could effectively inhibit the production of hepatic lipid peroxides MDA in the concentration range of 0.4-2.0 mg/mL. The topical application of BBH-L-Gel could effectively alleviate eczema symptoms and reduce oxidative stress injury in mice. This study demonstrates that BBH-L-Gel has good skin permeability, excellent sustained release, and antioxidant capabilities. They can effectively alleviate the itching, inflammation, and allergic symptoms caused by eczema, providing a new strategy for clinical applications in eczema treatment.

Silver (Ag) nanowires, as an important one-dimensional (1D) nanomaterial, have garnered wide attention, owing to their applications in electronics, optoelectronics, sensors, and other fields. In this study, an alternative hydrothermal route was developed to synthesize Ag nanowires via modified reduction of Ag + . Silver sulfamate plays an important role in the formation of Ag nanowires via controlled release of free Ag + . Results of controlled experiments and characterizations such as UV-vis spectroscopy, FTIR, XPS, and 1 H NMR revealed that sulfamic acid does not function as a reductant, supporting by the generation of free Ag + instead of Ag nanostructures in hydrothermally treated silver sulfamate solution. The initial reduction of Ag + was induced by the combination of poly (vinylpyrrolidone) (PVP) end group and degradation products. This phenomenon was supported by abundant free Ag + in the mixed preheated silver sulfamatic and preheated PVP aqueous solutions, indicating a second and distinct Ag + autocatalytic reduction. Thus, the roles of different reagents and Ag + reduction must be studied for nanomaterial syntheses.

To identify suitable potassium fertilizers for grape ( Vitis vinifera L.) production and study their mechanism of action, the effects of four potassium-containing fertilizers (complex fertilizer, potassium nitrate, potassium sulfate, and potassium dihydrogen phosphate) on sugar and organic acid metabolism in grape fruits were investigated. Potassium-containing fertilizers increased the activity of sugar and organic acid metabolism-related enzymes at all stages of grape fruit development. During the later stages of fruit development, potassium-containing fertilizers increased the total soluble solid content and the sugar content of the different sugar fractions and decreased the titratable acid content and organic acid content of the different organic acid fractions. At the ripening stage of grape fruit, compared with the control, complex fertilizer, potassium nitrate, potassium sulfate, and potassium dihydrogen phosphate increased the total soluble solid content by 1.5, 1.2, 3.5, and 3.4 percentage points, decreased the titratable acid content by 0.09, 0.06, 0.18, and 0.17 percentage points, respectively, and also increased the total potassium content in grape fruits to a certain degree. Transcriptome analysis of the differentially expressed genes (DEGs) in the berries showed that applying potassium-containing fertilizers enriched the genes in pathways involved in fruit quality, namely, carbon metabolism, carbon fixation in photosynthetic organisms, glycolysis and gluconeogenesis, and fructose and mannose metabolism. Potassium-containing fertilizers affected the expression levels of genes regulating sugar metabolism and potassium ion uptake and transport. Overall, potassium-containing fertilizers can promote sugar accumulation and reduce acid accumulation in grape fruits, and potassium sulfate and potassium dihydrogen phosphate had the best effects among the fertilizers tested.

Graphene and its derivatives have been confirmed to be among the best fillers for rubber due to their excellent properties, such as high mechanical strength, improved interface interaction, and strain-induced crystallization capabilities. Graphene rubber materials can be widely used in tires, shoes, high-barrier conductive seals, electromagnetic shielding seals, shock absorbers, etc. In order to reduce the graphene loading and endow more desirable functions to rubber materials, graphene-based hybrid fillers are extensively employed, which can effectively enhance the performance of rubber composites. This review briefly summarizes the recent research on rubber composites with graphene-based hybrid fillers consisting of carbon black, silica, carbon nanotubes, metal oxide, and one-dimensional nanowires. The preparation methods, performance improvements, and applications of different graphene-based hybrid fillers/rubber composites have been investigated. This study also focuses on methods that can ensure the effectiveness of graphene hybrid fillers in reinforcing rubber composites. Furthermore, the enhanced mechanism of graphene- and graphene derivative-based hybrid fillers in rubber composites is investigated to provide a foundation for future studies.

Coastal levees play a role in protecting coastal areas from storm surges and high waves, and they provide important input information for inundation damage simulations. However, coastal levee data with uniformity and sufficient accuracy for inundation simulations are not always well developed. Against this background, this study proposed a method to extract coastal levees by inputting high spatial resolution optical satellite image products (RGB images, digital surface models (DSMs), and slope images that can be generated from DSM images), which have high data availability at the locations and times required for simulation, into a deep learning model. The model is based on U-Net, and post-processing for noise removal was introduced to further improve its accuracy. We also proposed a method to calculate levee height using a local maximum filter by giving DSM values to the extracted levee pixels. The validation was conducted in the coastal area of Ibaraki Prefecture in Japan as a test area. The levee mask images for training were manually created by combining these data with satellite images and Google Street View, because the levee GIS data created by the Ibaraki Prefectural Government were incomplete in some parts. First, the deep learning models were compared and evaluated, and it was shown that U-Net was more accurate than Pix2Pix and BBS-Net in identifying levees. Next, three cases of input images were evaluated: (Case 1) RGB image only, (Case 2) RGB and DSM images, and (Case 3) RGB, DSM, and slope images. Case 3 was found to be the most accurate, with an average Matthews correlation coefficient of 0.674. The effectiveness of noise removal post-processing was also demonstrated. In addition, an example of the calculation of levee heights was presented and evaluated for validity. In conclusion, this method was shown to be effective in extracting coastal levees. The evaluation of generalizability and use in actual inundation simulations are future tasks.

Due to the increasing trend of delayed childbirth, the age-related decline in male reproductive function has become a widely recognized issue. Sertoli cells (SCs) play a vital role in creating the necessary microenvironment for spermatogenesis in the testis. However, the mechanism underlying Sertoli cell aging is still unclear. In this study, senescent Sertoli cells showed a substantial upregulation of miR-143-3p expression. miR-143-3p was found to limit Sertoli cell proliferation, promote cellular senescence, and cause blood-testis barrier (BTB) dysfunction by targeting ubiquitin-conjugating enzyme E2 E3 (UBE2E3). Additionally, the TGF-β receptor inhibitor SB431542 showed potential in alleviating age-related BTB dysfunction, rescuing testicular atrophy, and reversing the reduction in germ cell numbers by negatively regulating miR-143-3p . These findings clarified the regulatory pathways underlying Sertoli cell senescence and suggested a promising therapeutic approach to restore BTB function, alleviate Sertoli cell senescence, and improve reproductive outcomes for individuals facing fertility challenges.

Ammonium (NH 4 + ) toxicity is ubiquitous in plants. To investigate the underlying mechanisms of this toxicity and bicarbonate (HCO 3 - )-dependent alleviation, wheat plants were hydroponically cultivated in half-strength Hoagland nutrient solution containing 7.5 mM NO 3 - (AC). Transcriptomic analysis revealed that compared to CK, SA treatment at 48 h significantly upregulated the expression of genes encoding fermentation enzymes (pyruvate decarboxylase (PDC), alcohol dehydrogenase (ADH), and lactate dehydrogenase (LDH)) and oxygen consumption enzymes (respiratory burst oxidase homologs, dioxygenases, and alternative oxidases), downregulated the expression of genes encoding oxygen transporters (PIP-type aquaporins, non-symbiotic hemoglobins), and those involved in energy metabolism, including tricarboxylic acid (TCA) cycle enzymes and ATP synthases, but upregulated the glycolytic enzymes in the roots and downregulated the expression of genes involved in the cell cycle and elongation. The physiological assay showed that SA treatment significantly increased PDC, ADH, and LDH activity by 36.69%, 43.66%, and 61.60%, respectively; root ethanol concentration by 62.95%; and lactate efflux by 23.20%, and significantly decreased the concentrations of pyruvate and most TCA cycle intermediates, the complex V activity, ATP content, and ATP/ADP ratio. As a consequence, SA significantly inhibited root growth. AC treatment reversed the changes caused by SA and alleviated the inhibition of root growth. In conclusion, NH 4 + (SA), or 7.5 mM NH 4 + + 3 mM HCO 3 - (AC). Transcriptomic analysis revealed that compared to CK, SA treatment at 48 h significantly upregulated the expression of genes encoding fermentation enzymes (pyruvate decarboxylase (PDC), alcohol dehydrogenase (ADH), and lactate dehydrogenase (LDH)) and oxygen consumption enzymes (respiratory burst oxidase homologs, dioxygenases, and alternative oxidases), downregulated the expression of genes encoding oxygen transporters (PIP-type aquaporins, non-symbiotic hemoglobins), and those involved in energy metabolism, including tricarboxylic acid (TCA) cycle enzymes and ATP synthases, but upregulated the glycolytic enzymes in the roots and downregulated the expression of genes involved in the cell cycle and elongation. The physiological assay showed that SA treatment significantly increased PDC, ADH, and LDH activity by 36.69%, 43.66%, and 61.60%, respectively; root ethanol concentration by 62.95%; and lactate efflux by 23.20%, and significantly decreased the concentrations of pyruvate and most TCA cycle intermediates, the complex V activity, ATP content, and ATP/ADP ratio. As a consequence, SA significantly inhibited root growth. AC treatment reversed the changes caused by SA and alleviated the inhibition of root growth. In conclusion, NH 4 + treatment alone may cause hypoxic stress in the roots, inhibit energy generation, suppress cell division and elongation, and ultimately inhibit root growth, and adding HCO 3 - remarkably alleviates the NH 4 + -induced inhibitory effects on root growth largely by attenuating the hypoxic stress.

The profound impacts of severe air pollution on human health, ecological balance, and economic stability are undeniable. Precise air quality forecasting stands as a crucial necessity, enabling governmental bodies and vulnerable communities to proactively take essential measures to reduce exposure to detrimental pollutants. Previous research has primarily focused on predicting air quality using only time-series data. However, the importance of remote-sensing image data has received limited attention. This paper proposes a new multi-modal deep-learning model, Res-GCN, which integrates high spatial resolution remote-sensing images and time-series air quality data from multiple stations to forecast future air quality. Res-GCN employs two deep-learning networks, one utilizing the residual network to extract hidden visual information from remote-sensing images, and another using a dynamic spatio-temporal graph convolution network to capture spatio-temporal information from time-series data. By extracting features from two different modalities, improved predictive performance can be achieved. To demonstrate the effectiveness of the proposed model, experiments were conducted on two real-world datasets. The results show that the Res-GCN model effectively extracts multi-modal features, significantly enhancing the accuracy of multi-step predictions. Compared to the best-performing baseline model, the multi-step prediction's mean absolute error, root mean square error, and mean absolute percentage error increased by approximately 6%, 7%, and 7%, respectively.

Diabetes patients need to monitor blood glucose all year round. In this article, a novel scheme is proposed for blood glucose detection. The proposed sensor is based on a U-shaped microfiber prepared using hydrogen-oxygen flame-heating technology, and then 3-aminopropyltriethoxysilane (APTES) and glucose oxidase (GOD) are successively coated on the surface of the U-shaped microfiber via a coating technique. The glucose reacts with the GOD of the sensor surface to produce gluconic acid, which changes the effective refractive index and then shifts the interference wavelength. The structure and morphology of the sensor were characterized via scanning electron microscope (SEM) and confocal laser microscopy (CLM). The experimental results show that the sensitivity of the sensor is as high as 5.73 nm/(mg/mL). Compared with the glucose sensor composed of the same material, the sensitivity of the sensor increased by 329%. The proposed sensor has a broad application prospect in blood glucose detection of diabetic patients due to the advantages of miniaturization, high sensitivity, and good stability.

Medium additives have been shown to affect the synthesis of active products in fungi. This study investigated the effects of corn stalk, poplar sawdust, Tween-80, and oleic acid on mycelial biomass and physicochemical properties, as well as the bioactivity of polysaccharides, including exopolysaccharides (EPS) and intracellular polysaccharides (IPS), in the submerged culture of Bjerkandera fumosa . Results showed that the addition of corn stalk or poplar sawdust increased the production of EPS but decreased the production of IPS; Tween-80 had less effect on the production of EPS and IPS; and oleic acid stimulated polysaccharide production significantly. Polysaccharide property analysis showed that the addition of corn stalk or poplar sawdust promoted the production of high-molecular-weight components in polysaccharides and changed the monosaccharide composition of polysaccharides, as well as increased the mannose, glucuronic acid, and xylose contents of IPS. Tween-80 and oleic acid also changed the molecular weight distribution of polysaccharides but only slightly affected the composition of monosaccharides. The bioactivity assay indicated that the polysaccharides obtained by adding corn stalk possessed high hydroxyl radical scavenging and antitumor activities. The effect of poplar sawdust was slightly weaker than that of corn stalk. EPS and IPS obtained from a culture with Tween-80 and oleic acid possessed low antioxidant activity. Moreover, their antitumor activity was improved and lost, respectively. The results obtained in this work are useful for improving the understanding of the optimization and regulation of bioactive polysaccharide production in the submerged culture of B. fumosa .

With the continuous expansion of the application range of gob-side entry retaining technology, the depth, height, and advancing speed of coal seams also increase, which brings great problems to the stability control of surrounding rock structures of gob-side entry retaining. As one of the main bearing structures of the surrounding rock, the stability of the roadway-side support body is a key factor for the success of gob-side entry retaining. In order to study the deformation characteristics and instability mechanism of roadway-side support body, based on the roadway-side support materials of gob-side entry retaining, the dynamic expansion test of back-filling concrete cracks under uniaxial compression was carried out. The YOLOv5 algorithm was applied to establish the fine identification and quantitative characterization method of macroscopic cracks of the samples, and the dynamic expansion rule of roadway-side support body cracks and its dimensional effect were revealed by combining the fractal theory. The results show that the F1 value and average precision mean of the intelligent dynamic crack identification model reached 75% and 71%, respectively, the GIoU loss value tends to fit around 0.038, and the model reached the overall optimal solution. During the uniaxial compression process, micro cracks on the surface of the back-filling concrete first initiated at the end, and after reaching the yield stress, the macroscopic cracks developed significantly. Moreover, several secondary cracks expanded, pooled, and connected from the middle of the specimen to the two ends, inducing the overall instability of the specimen. The surface crack expansion rate, density, and fractal dimension all show stage change characteristics with the increase in stress, and the main crack expansion rate has obvious precursor characteristics. With the increase in the size, the decrease in crack density after back-filling concrete failures gradually decreases from 93.19% to 4.08%, the surface crack network develops from complex to simple, and the failure mode transits from tensile failure to shear failure. The above research results provide a basic experimental basis for design optimization and instability prediction of a roadway-side support body for engineering-scale applications.

(1) Background: The aim of our research was to systematically review papers specifically focused on the hepatocellular carcinoma (HCC) diagnostic performance of DL methods based on medical images. (2) Materials: To identify related studies, a comprehensive search was conducted in prominent databases, including Embase, IEEE, PubMed, Web of Science, and the Cochrane Library. The search was limited to studies published before 3 July 2023. The inclusion criteria consisted of studies that either developed or utilized DL methods to diagnose HCC using medical images. To extract data, binary information on diagnostic accuracy was collected to determine the outcomes of interest, namely, the sensitivity, specificity, and area under the curve (AUC). (3) Results: Among the forty-eight initially identified eligible studies, thirty studies were included in the meta-analysis. The pooled sensitivity was 89% (95% CI: 87-91), the specificity was 90% (95% CI: 87-92), and the AUC was 0.95 (95% CI: 0.93-0.97). Analyses of subgroups based on medical image methods (contrast-enhanced and non-contrast-enhanced images), imaging modalities (ultrasound, magnetic resonance imaging, and computed tomography), and comparisons between DL methods and clinicians consistently showed the acceptable diagnostic performance of DL models. The publication bias and high heterogeneity observed between studies and subgroups can potentially result in an overestimation of the diagnostic accuracy of DL methods in medical imaging. (4) Conclusions: To improve future studies, it would be advantageous to establish more rigorous reporting standards that specifically address the challenges associated with DL research in this particular field.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Although immunotherapy is effective for some patients, most find it difficult to benefit from it. This study aims to explore the impact of specific immune pathways and their regulated molecular mechanisms in TNBC. The gene expression data of breast cancer patients were obtained from the TCGA and METABRIC databases. Gene set variation analysis (GSVA) revealed specific upregulation or abnormal expression of immunodeficiency pathways in TNBC patients. Multi-omics data showed significant differential expression of Primary Immunodeficiency Genes (PIDGs) in TNBC patients, who are prone to genomic-level variations. Consensus clustering was used in two datasets to classify patients into two distinct molecular subtypes based on PIDGs expression patterns, with each displaying different biological features and immune landscapes. To further explore the prognostic characteristics of PIDGs-regulated molecules, we constructed a four-gene prognostic PIDG score model and a nomogram using least absolute shrinkage and selection operator (LASSO) regression analysis in combination with clinicopathological parameters. The PIDG score was closely associated with the immune therapy and drug sensitivity of TNBC patients, providing potential guidance for clinical treatment. Particularly noteworthy is the close association of this scoring with RNA modifications; patients with different scores also exhibited different mutation landscapes. This study offers new insights for the clinical treatment of TNBC and for identifying novel prognostic markers and therapeutic targets in TNBC.

Recently, piezoresistive sensors made by 3D printing have gained considerable interest in the field of wearable electronics due to their ultralight nature, high compressibility, robustness, and excellent electromechanical properties. In this work, building on previous results on the Selective Laser Sintering (SLS) of porous systems based on thermoplastic polyurethane (TPU) and graphene (GE)/carbon nanotubes (MWCNT) as carbon conductive fillers, the effect of variables such as thickness, diameter, and porosity of 3D printed disks is thoroughly studied with the aim of optimizing their piezoresistive performance. The resulting system is a disk with a diameter of 13 mm and a thickness of 0.3 mm endowed with optimal reproducibility, sensitivity, and linearity of the electrical signal. Dynamic compressive strength tests conducted on the proposed 3D printed sensors reveal a linear piezoresistive response in the range of 0.1-2 N compressive load. In addition, the optimized system is characterized at a high load frequency (2 Hz), and the stability and sensitivity of the electrical signal are evaluated. Finally, an application test demonstrates the ability of this system to be used as a real-time wearable pressure sensor for applications in prosthetics, consumer products, and personalized health-monitoring systems.

The yellowing of leaves due to iron deficiency is a prevalent issue in peach production. Although the capacity of exogenous melatonin (MT) to promote iron uptake in peach plants has been demonstrated, its underlying mechanism remains ambiguous. This investigation was carried out to further study the effects of exogenous MT on the iron absorption and transport mechanisms of peach ( Prunus persica ) plants under iron-deficient conditions through transcriptome sequencing. Under both iron-deficient and iron-supplied conditions, MT increased the content of photosynthetic pigments in peach leaves and decreased the concentrations of pectin, hemicellulose, cell wall iron, pectin iron, and hemicellulose iron in peach plants to a certain extent. These effects stemmed from the inhibitory effect of MT on the polygalacturonase (PG), cellulase (Cx), phenylalanine ammonia-lyase (PAL), and cinnamoyl-coenzyme A reductase (CCR) activities, as well as the promotional effect of MT on the cinnamic acid-4-hydroxylase (C4H) activity, facilitating the reactivation of cell wall component iron. Additionally, MT increased the ferric-chelate reductase (FCR) activity and the contents of total and active iron in various organs of peach plants under iron-deficient and iron-supplied conditions. Transcriptome analysis revealed that the differentially expressed genes (DEGs) linked to iron metabolism in MT-treated peach plants were primarily enriched in the aminoacyl-tRNA biosynthesis pathway under iron-deficient conditions. Furthermore, MT influenced the expression levels of these DEGs, regulating cell wall metabolism, lignin metabolism, and iron translocation within peach plants. Overall, the application of exogenous MT promotes the reactivation and reutilization of iron in peach plants.

Genetic polymorphisms in ATP-binding cassette subfamily B member 1 ( ABCB1 , also known as MDR1 ) have been reported to be possibly associated with the regulation of response to antiseizure medications. The aim of this study was to investigate the association of ABCB1 polymorphisms with the efficacy of and adverse drug reactions to valproic acid among Chinese children with epilepsy. A total of 170 children from southern China with epilepsy treated with valproic acid for more than one year were recruited, including 61 patients with persistent seizures and 109 patients who were seizure-free. Two single nucleotide polymorphisms of ABCB1 , rs1128503 and rs3789243, were genotyped using the Sequenom MassArray system. The two single nucleotide polymorphisms of ABCB1 were found to be significantly associated with treatment outcomes of valproic acid in children with epilepsy. Carriers with the TT genotype of ABCB1 rs1128503 were more inclined to exhibit persistent seizures after treatment with valproic acid ( p = 0.013). The CC genotype of rs3789243 was observed to be a potential protective factor for valproic acid-induced gastrointestinal adverse drug reactions ( p = 0.018), but possibly increased the risk of valproic acid-induced cutaneous adverse drug reactions ( p = 0.011). In contrast, the CT genotype of rs3789243 was associated with a lower risk of valproic acid-induced cutaneous adverse drug reactions ( p = 0.011). Haplotype analysis showed that CC haplotype carriers tended to respond better to valproic acid treatment ( p = 0.009). Additionally, no significant association was found between ABCB1 polymorphisms and serum concentrations of valproic acid. This study revealed that the polymorphisms and haplotypes of the ABCB1 gene might be associated with the treatment outcomes of valproic acid in Chinese children with epilepsy.

When the skin is overexposed to ultraviolet rays, free radicals will accumulate in the skin, causing lipid damage and even inducing photoaging of the skin. Combination therapy with antioxidant drugs is a good choice for topical treatment of skin photoaging due to its special physiological structure. In this paper, shikonin was encapsulated in β-cyclodextrin (SH-β-CD) by the precipitation crystallization method, which delayed the release of the drug and increased drug solubility. The average diameter of SH-β-CD was 203.0 ± 21.27 nm with a zeta potential of -14.4 ± 0.5 mV. The encapsulation efficiency (EE%) was 65.9 ± 7.13%. The results of the in vitro permeation across the dialysis membrane and ex vivo transdermal release rates were 52.98 ± 1.21% and 88.25 ± 3.26%, respectively. In vitro antioxidant and antilipid peroxidation model assay revealed the antioxidant potential of SH and SH-β-CD. In the mice model of skin photoaging, SH and SH-β-CD had a recovery effect on the skin damage of mice, which could significantly increase the superoxide dismutase (SOD) activity in the skin. Briefly, SH-β-CD had an obvious therapeutic effect on the skin photoaging of mice caused by UV, and it is promising in skin disease treatment and skin care.

In this study, we investigated the effect of exogenous melatonin (MT) on cell wall metabolism leading to Chinese plum ( Prunus salicina Lindl.) fruit softening. Exogenous MT treatment increased the endogenous MT content in plum fruits before fruit ripening. However, in mature plum fruits, exogenous MT treatment decreased the fruit hardness, pulp hardness, fruit elasticity, contents of ion-bound pectin, covalently-bound pectin, hemicellulose, and cellulose, and activities of xyloglucan endotransglycosylase/hydrolase and endo-β-1,4-glucanase, and increased the water-soluble pectin content, and activities of pectin methyl esterase, pectin lyase, polygalacturonase, β-galactopyranosidase, and α-L-arabinofuranosidase. Transcriptome analysis revealed that the differentially expressed genes (DEGs) associated with cell wall metabolism in the exogenous MT-treated plum fruits were mainly enriched in the pentose and glucuronate interconversions, phenylpropanoid biosynthesis, cyanoamino acid metabolism, and galactose metabolism pathways. Analysis of these DEGs revealed that exogenous MT treatment affected the expression of genes regulating the cell wall metabolism. Overall, exogenous MT treatment promotes the fruit softening of Chinese plum.

Flavonoids have anti-inflammatory, antioxidative, and anticarcinogenic effects. Breeding rice varieties rich in flavonoids can prevent chronic diseases such as cancer and cardio-cerebrovascular diseases. However, most of the genes reported are known to regulate flavonoid content in leaves or seedlings. To further elucidate the genetic basis of flavonoid content in rice grains and identify germplasm rich in flavonoids in grains, a set of rice core collections containing 633 accessions from 32 countries was used to determine total flavonoid content (TFC) in brown rice. We identified ten excellent germplasms with TFC exceeding 300 mg/100 g. Using a compressed mixed linear model, a total of 53 quantitative trait loci (QTLs) were detected through a genome-wide association study (GWAS). By combining linkage disequilibrium (LD) analysis, location of significant single nucleotide polymorphisms (SNPs), gene expression, and haplotype analysis, eight candidate genes were identified from two important QTLs ( qTFC1-6 and qTFC9-7 ), among which LOC_Os01g59440 and LOC_Os09g24260 are the most likely candidate genes. We also analyzed the geographic distribution and breeding utilization of favorable haplotypes of the two genes. Our findings provide insights into the genetic basis of TFC in brown rice and could facilitate the breeding of flavonoid-rich varieties, which may be a prevention and adjuvant treatment for cancer and cardio-cerebrovascular diseases.

Cutaneous eczema is a kind of skin disease is characterized by inflammation. The main manifestations are various types of dermatitis, eczema, and urticaria. There are usually complications such as erythema, blisters, and epidermal peeling. The quercetin might have a therapeutic effect on cutaneous eczema due to its favorable antioxidant activity and anti-inflammatory effects. Currently, there are few studies on transdermal administration of antioxidant drugs for the treatment of cutaneous eczema. The aim of this study was to prepare quercetin-containing liposomes-in-gel (QU-LG), its antioxidant properties were evaluated, and it was used in the skin of mice suffering from dermal eczema to see if it had preventive and therapeutic effects in an attempt to make it a new option for the treatment of cutaneous eczema. QU-LG was prepared by the injection method to form the quercetin-containing liposomes (QU-L) and evenly dispersed in the natural dissolution of carboxymethylcellulose sodium (1%, CMC-Na). The release of QU-LG across the dialysis membranes was up to 30% and clearance of 1,1-diphenyl-2-picrylhydrazyl (DPPH) was 65.16 ± 3.513%. In anti-oxidation assay QU-LG inhibited malondialdehyde (MDA) production in liver better than the commercially available drug dexamethasone acetate cream. Compared with untreated mice, mice treated with QU-LG showed a statistically significant reduction in dermatopathologic symptoms. The results suggested that QU-LG had good antioxidant activity in vivo and in vitro and could be used for the prevention and treatment of cutaneous eczema.

Due to their lack of pollution and long replacement cycles, piezoelectric energy harvesters have gained increasing attention as emerging power generation devices. However, achieving effective energy harvesting in ultra-low-frequency (<1 Hz) rotational environments remains a challenge. Therefore, a novel rotational energy harvester (REH) with a double-frequency up-conversion mechanism was proposed in this study. It consisted of a hollow cylindrical shell with multiple piezoelectric beams and a ring-shaped slider with multiple paddles. During operation, the relative rotation between the slider and the shell induced the paddles on the slider to strike the piezoelectric beams inside the shell, thereby causing the piezoelectric beams to undergo self-excited oscillation and converting mechanical energy into electrical energy through the piezoelectric effect. Additionally, by adjusting the number of paddles and piezoelectric beams, the frequency of the piezoelectric beam struck by the paddles within one rotation cycle could be increased, further enhancing the output performance of the REH. To validate the output performance of the proposed REH, a prototype was fabricated, and the relationship between the device's output performance and parameters such as the number of paddles, system rotation speed, and device installation eccentricity was studied. The results showed that the designed REH achieved a single piezoelectric beam output power of up to 2.268 mW, while the REH with three piezoelectric beams reached an output power of 5.392 mW, with a high power density of 4.02 μW/(cm 3 Hz) under a rotational excitation of 0.42 Hz, demonstrating excellent energy-harvesting characteristics.

Aluminum alloy adhesive bonding joint widely appears in many industrial products. Improving the mechanical performances of aluminum alloy bonding joints has been attracting much effort. To acquire more excellent bonding strength, this paper focused on the effects of different surface treatments, including laser ablation and milling superposed by phosphoric acid anodizing (PAA). The treated surfaces were characterized by roughness and contact angle, and the effects of the geometric parameters of microstructures on wettability, failure mode, and shear strength were examined. The results indicate that those surfaces where the spacing is smaller than the diameter present a hydrophilic property and the corresponding specimens are mainly subject to cohesive failure, and vice versa. Additionally, laser ablation with a properly designed dimple pattern can greatly improve the bonding strength, and the maximum average shear strength of specimens with a thickness of 50 μm reaches 32.82 MPa, which is an increase of 28.15% compared with the original milling specimen. Moreover, fabricating groove or grid patterns on the surfaces and applying PAA treatment can also significantly enhance the bonding strength, reaching up to 36.28 MPa.

Aroma is an important aspect of wine quality and consumer appreciation. The volatile organic compounds (VOCs) and olfactory profiles of Merlot dry red wines from the Eastern Foothill of Helan Mountain (EFHM) were analyzed using gas chromatography-mass spectrometry and quantitative descriptive analysis. The results showed that Merlot wines from EFHM were characterized by intense flavors of drupe and tropical fruits compared with the Gansu region. Nineteen VOCs were defined as essential compounds contributing to the aroma characteristics of the Merlot wines through gas chromatography-olfactometry/mass spectrometry and odor activity value analysis. Predominantly, geranyl isovalerate, which contributed to the herbal odors of the Merlot wines, was detected in the grape wine of EFHM for the first time. The addition experiment revealed that geranyl isovalerate influenced the aroma quality of wine by increasing herbal odors and enhancing the olfactory intensities of tropical fruits. These results are helpful for further understanding the aroma of Merlot wines from EFHM and improving the quality of wine aromas.

Copper (Cu)-based antimicrobial compounds (CBACs) have been widely used to control phytopathogens for nearly fourteen decades. Since the first commercialized Bordeaux mixture was introduced, CBACs have been gradually developed from highly to slightly soluble reagents and from inorganic to synthetic organic, with nanomaterials being a recent development. Traditionally, slightly soluble CBACs form a physical film on the surface of plant tissues, separating the micro-organisms from the host, then release divalent or monovalent copper ions (Cu 2+ or Cu + ) to construct a secondary layer of protection which inhibits the growth of pathogens. Recent progress has demonstrated that the release of a low concentration of Cu 2+ may elicit immune responses in plants. This supports a triple-tiered protection role of CBACs: break contact, inhibit microorganisms, and stimulate host immunity. This spatial defense system, which is integrated both inside and outside the plant cell, provides long-lasting and broad-spectrum protection, even against emergent copper-resistant strains. Here, we review recent findings and highlight the perspectives underlying mitigation strategies for the sustainable utilization of CBACs.

This study aimed to explore the applicability of DNA barcoding for assessing the authenticity of caviar on the Chinese market. A set of universal COI primers and two sets of designed primers based on COI and D-loop genes were used to identify maternal species of samples from 21 batches of caviar. The results showed that the PCR products from three sets of primers had more than 98% similarity to the sequences in database. The COI gene could not distinguish sturgeons with closed genetic relationships, while D-loop gene could effectively improve the accuracy of DNA barcoding and was more suitable to the identification of interspecific sturgeon than the COI gene. The neighbor-joining dendrogram further confirmed the applicability and accuracy of COI and D-loop genes in identifying maternal relatives of caviar ( Acipenser baerii / Acipenser gueldenstaedtii / Acipenser schrenckii / Huso dauricus / Huso huso) . Despite the limitations of mitochondrial DNA in identifying hybrid sturgeon species, the presence of counterfeit caviar of non-sturgeon ingredients could be excluded. All the caviar samples were identified successfully as sturgeon species, but the mislabeling rate of species was 33.4%, indicating that there were illegal phenomena such as disorderly labeling, mislabeling, and adulteration on the market.

Food protein-derived antihypertensive peptides are a representative type of bioactive peptides. Several models based on partial least squares regression have been constructed to delineate the relationship between the structure and activity of the peptides. Machine-learning-based models have been applied in broad areas, which also indicates their potential to be incorporated into the field of bioactive peptides. In this study, a long short-term memory (LSTM) algorithm-based deep learning model was constructed, which could predict the IC 50 value of the peptide in inhibiting ACE activity. In addition to the test dataset, the model was also validated using randomly synthesized peptides. The LSTM-based model constructed in this study provides an efficient and simplified method for screening antihypertensive peptides from food proteins.

Monocytes are highly plastic innate immune cells that display significant heterogeneity during homeostasis, inflammation, and tumorigenesis. Tumor-induced systemic and local microenvironmental changes influence the phenotype, differentiation, and distribution of monocytes. Meanwhile, monocytes and their related cell subsets perform an important regulatory role in the development of many cancers by affecting tumor growth or metastasis. Thanks to recent advances in single-cell technologies, the nature of monocyte heterogeneity and subset-specific functions have become increasingly clear, making it possible to systematically analyze subset-specific roles of monocytes in tumorigenesis. In this review, we discuss recent discoveries related to monocytes and tumorigenesis, and new strategies for tumor biomarker identification and anti-tumor immunotherapy.

Polyvinyl alcohol is the most commercially water-soluble biodegradable polymer, and it is in use for a wide range of applications. It shows good compatibility with most inorganic/organic fillers, and enhanced composites may be prepared without the need to introduce coupling agents and interfacial modifiers. The patented high amorphous polyvinyl alcohol (HAVOH), commercialized with the trade name G-Polymer, can be easily dispersed in water and melt processed. HAVOH is particularly suitable for extrusion and can be used as a matrix to disperse nanocomposites with different properties. In this work, the optimization of the synthesis and characterization of HAVOH/reduced graphene oxide (rGO) nanocomposite obtained by the solution blending process of HAVOH and Graphene Oxide (GO) water solutions and 'in situ' reduction of GO is studied. The produced nanocomposite presents a low percolation threshold (~1.7 wt%) and high electrical conductivity (up to 11 S/m) due to the uniform dispersion in the polymer matrix as a result of the solution blending process and the good reduction level of GO. In consideration of HAVOH processability, the conductivity obtained by using rGO as filler, and the low percolation threshold, the nanocomposite presented here is a good candidate for the 3D printing of a conductive structure.

In this study, a method for double-beam quantum cascade laser absorption spectroscopy (DB-QCLAS) was developed. Two mid-infrared distributed feedback quantum cascade laser beams were coupled in an optical cavity for the monitoring of NO and NO 2 (NO at 5.26 μm; NO 2 at 6.13 μm). Appropriate lines in the absorption spectra were selected, and the influence of common gases in the atmosphere, such as H 2 O and CO 2 , was avoided. By analyzing the spectral lines under different pressure conditions, the appropriate measurement pressure of 111 mbar was selected. Under this pressure, the interference between adjacent spectral lines could be effectively distinguished. The experimental results show that the standard deviations for NO and NO 2 were 1.57 ppm and 2.67 ppm, respectively. Moreover, in order to improve the feasibility of this technology for detecting chemical reactions between NO and O 2 , the standard gases of NO and O 2 were used to fill the cavity. A chemical reaction instantaneously began, and the concentrations of the two gases were immediately changed. Through this experiment, we hope to develop new ideas for the accurate and rapid analysis of the process of NOx conversion and to lay a foundation for a deeper understanding of the chemical changes in atmospheric environments.

A sensitive and selective electrochemical dopamine (DA) sensor has been developed using gold nanoparticles decorated marimo-like graphene (Au NP/MG) as a modifier of the glassy carbon electrode (GCE). Marimo-like graphene (MG) was prepared by partial exfoliation on the mesocarbon microbeads (MCMB) through molten KOH intercalation. Characterization via transmission electron microscopy confirmed that the surface of MG is composed of multi-layer graphene nanowalls. The graphene nanowalls structure of MG provided abundant surface area and electroactive sites. Electrochemical properties of Au NP/MG/GCE electrode were investigated by cyclic voltammetry and differential pulse voltammetry techniques. The electrode exhibited high electrochemical activity towards DA oxidation. The oxidation peak current increased linearly in proportion to the DA concentration in a range from 0.02 to 10 μM with a detection limit of 0.016 μM. The detection selectivity was carried out with the presence of 20 μM uric acid in goat serum real samples. This study demonstrated a promising method to fabricate DA sensor-based on MCMB derivatives as electrochemical modifiers., Competing Interests: The authors declare no conflict of interest.

At present, the majority of sparse-aperture telescopes (SATs) are unable to observe moving targets. In this paper, we describe the construction of and present the results obtained using a Fizeau directly-imaging sparse-aperture telescope (FDISAT) that permits pointing and the tracking of moving targets. The telescope comprises three sub-apertures, each of which is equipped with a Risley prism system that permits a maximum tracking range of 5° and has independent boresight adjustment capability. On targets in various positions, experiments with pointing and tracking are conducted. The maximum root-mean-square error (RMSE) of pointing in the sub-apertures was found to be 8.22 arcsec. When considering a target moving at 0.01°/s for approximately 320 s, the maximum RMSE of tracking in the sub-apertures was found to be 4.23 arcsec. The images obtained from the focal plane detector exhibit clear interference fringes while tracking. The experimental results demonstrate that the system can effectively track moving targets, providing a method for SAT observation of moving targets.

The vacuum degree is the key parameter reflecting the quality and performance of vacuum glass. This investigation proposed a novel method, based on digital holography, to detect the vacuum degree of vacuum glass. The detection system was composed of an optical pressure sensor, a Mach-Zehnder interferometer and software. The results showed that the deformation of monocrystalline silicon film in an optical pressure sensor could respond to the attenuation of the vacuum degree of vacuum glass. Using 239 groups of experimental data, pressure differences were shown to have a good linear relationship with the optical pressure sensor's deformations; pressure differences were linearly fitted to obtain the numerical relationship between pressure difference and deformation and to calculate the vacuum degree of the vacuum glass. Measuring the vacuum degree of vacuum glass under three different conditions proved that the digital holographic detection system could measure the vacuum degree of vacuum glass quickly and accurately. The optical pressure sensor's deformation measuring range was less than 4.5 μm, the measuring range of the corresponding pressure difference was less than 2600 pa, and the measuring accuracy's order of magnitude was 10 pa. This method has potential market applications.

Global warming caused by carbon emissions is an environmental issue of great concern to all sectors. Dynamic monitoring of the spatiotemporal evolution of urban carbon emissions is an important link to achieve the regional "double carbon" goal. Using 14 cities (prefectures) in Hunan Province as an example, based on the data of carbon emissions generated by land use and human production and life, and on the basis of estimating the carbon emissions in Hunan Province from 2000 to 2020 using the carbon emission coefficient method, this paper uses the Exploratory Spatial-Temporal Data Analysis (ESTDA) framework to analyze the dynamic characteristics of the spatiotemporal pattern of carbon emissions in Hunan Province from 2000 to 2020 through the Local Indicators of Spatial Association (LISA) time path, spatiotemporal transition, and the standard deviation ellipse model. The driving mechanism and spatiotemporal heterogeneity of urban carbon emissions were studied by using the geographically and temporally weighted regression model (GTWR). The results showed that: (1) In the last 20 years, the urban carbon emissions of Hunan Province have had a significant positive spatial correlation, and the spatial convergence shows a trend of first increasing and then decreasing. Therefore, priority should be given to this relevance when formulating carbon emission reduction policies in the future. (2) The center of carbon emission has been distributed between 112°15'57″~112°25'43″ E and 27°43'13″~27°49'21″ N, and the center of gravity has shifted to the southwest. The spatial distribution has changed from the "northwest-southeast" pattern to the "north-south" pattern. Cities in western and southern Hunan are the key areas of carbon emission reduction in the future. (3) Based on LISA analysis results, urban carbon emissions of Hunan from 2000 to 2020 have a strong path dependence in spatial distribution, the local spatial structure has strong stability and integration, and the carbon emissions of each city are affected by the neighborhood space. It is necessary to give full play to the synergistic emission reduction effect among regions and avoid the closure of inter-city emission reduction policies. (4) Economic development level and ecological environment have negative impacts on carbon emissions, and the population, industrial structure, technological progress, per capita energy consumption, and land use have a positive impact on carbon emissions. The regression coefficients are heterogeneous in time and space. The actual situation of each region should be fully considered to formulate differentiated emission reduction policies. The research results can provide reference for the green and low-carbon sustainable development of Hunan Province and the formulation of differentiated emission reduction policies, and provide reference for other similar cities in central China.

Although previous studies have presented that fine particulate matter (PM2.5) regulates liver enzyme levels in the development of liver diseases, the evidence regarding the relationship between PM2.5 exposure and liver enzyme is not robust. We further aimed to conduct a systematic review and meta-analysis of observational studies to summarize the recent evidence on the effects of PM2.5 on liver enzyme in humans. In the meta-analysis, we retrieved online databases including PubMed and Web of Science database from 1982 up to 2022. A random-effects model was applied to evaluate the correlation between PM2.5 and liver enzyme level. A total of 10 studies fulfilled the inclusion criteria, including five prospective cohort studies, two cross-sectional studies, two longitudinal studies, and one time-series analysis. Each 10 μg/m 3 increase in PM2.5 concentration was significantly correlated with a 4.45% increase in alanine aminotransferase (ALT) level (95% CI: 0.51-8.38%, p = 0.03), a 3.99% increase in aspartate transferase (AST) level (95% CI: 0.88-7.10%, p = 0.01), and a 2.91% increase in gamma-glutamyl transferase (GGT) level (95% CI: 1.18-4.64%, p < 0.001), but this significant association was not observed in alkaline phosphatase (ALP). Subgroup analysis revealed that PM2.5 has a significant correlation with ALT (5.07%, 95% CI: 0.81-9.33%), AST (4.11%, 95% CI: 0.74-7.48%), and GGT (2.74%, 95% CI: 1.09-4.38%) in Asia. Our meta-analysis showed that increments in PM2.5 exposure were significantly associated with a higher level of ALT, AST, and GGT. In addition, investigations into liver enzyme subtypes and specific chemical components of PM2.5 are important directions for future research.

In this study, the influences of long-term soil drought with three levels [soil-relative water content ( SRWC ) (75 ± 5)%, as the control; SRWC (55 ± 5)%, mild drought; SRWC (45 ± 5)%, severe drought] were investigated on sucrose-starch metabolism in sweet potato tuberous roots (TRs) by pot experiment. Compared to the control, drought stress increased soluble sugar and sucrose content by 4-60% and 9-75%, respectively, but reduced starch accumulation by 30-66% through decreasing the starch accumulate rate in TRs. In the drought-treated TRs, the inhibition of sucrose decomposition was attributed to the reduced activities of acid invertase (AI) and alkaline invertase (AKI) and the IbA-INV3 expression, rather than sucrose synthase (SuSy), consequently leading to the increased sucrose content in TRs. In addition, starch synthesis was inhibited mainly by reducing ADP-glucose pyrophosphorylase (AGPase), granular starch synthase (GBSS) and starch branching enzyme (SBE) activities in TRs under drought stress, and AGPase was the rate-limiting enzyme. Furthermore, soil drought remarkably up-regulated the IbSWEET11 , IbSWEET605 , and IbSUT4 expressions in Jishu 26 TRs, while it down-regulated or had no significant differences in Xushu 32 and Ningzishu 1 TRs. These results suggested that the sucrose-loading capability in Jishu 26 TRs were stronger than that in Xushu 32 and Ningzishu 1 TRs. Moreover, IbA-INV3 , IbAGPS1 , IbAGPS2 , IbGBSSI and IbSBEII play important roles in different drought-tolerant cultivars under drought stress.

Osteosarcoma (OS) is a primary malignant tumor of bone. Chemotherapy is one of the crucial approaches to prevent its metastasis and improve prognosis. Despite continuous improvements in the clinical treatment of OS, tumor resistance and metastasis remain dominant clinical challenges. Macropinocytosis, a form of non-selective nutrient endocytosis, has received increasing attention as a novel target for cancer therapy, yet its role in OS cells remains obscure. Benzethonium chloride (BZN) is an FDA-approved antiseptic and bactericide with broad-spectrum anticancer effects. Here, we described that BZN suppressed the proliferation, migration, and invasion of OS cells in vitro and in vivo, but simultaneously promoted the massive accumulation of cytoplasmic vacuoles as well. Mechanistically, BZN repressed the ERK1/2 signaling pathway, and the ERK1/2 activator partially neutralized the inhibitory effect of BZN on OS cells. Subsequently, we demonstrated that vacuoles originated from macropinocytosis and indicated that OS cells might employ macropinocytosis as a compensatory survival mechanism in response to BZN. Remarkably, macropinocytosis inhibitors enhanced the anti-OS effect of BZN in vitro and in vivo. In conclusion, our results suggest that BZN may inhibit OS cells by repressing the ERK1/2 signaling pathway and propose a potential strategy to enhance the BZN-induced inhibitory effect by suppressing macropinocytosis.

High dietary intake of β-cryptoxanthin (BCX, an oxygenated provitamin A carotenoid) is associated with a lower risk of lung disease in smokers. BCX can be cleaved by β-carotene-15,15'-oxygenase (BCO1) and β-carotene-9',10'-oxygenase (BCO2) to produce retinol and apo-10'-carotenoids. We investigated whether BCX has protective effects against cigarette smoke (CS)-induced lung injury, dependent or independent of BCO1/BCO2 and their metabolites. Both BCO1 -/- /BCO2 -/- double knockout mice (DKO) and wild type (WT) littermates were supplemented with BCX 14 days and then exposed to CS for an additional 14 days. CS exposure significantly induced macrophage and neutrophil infiltration in the lung tissues of mice, regardless of genotypes, compared to the non-exposed littermates. BCX treatment significantly inhibited CS-induced inflammatory cell infiltration, hyperplasia in the bronchial epithelium, and enlarged alveolar airspaces in both WT and DKO mice, regardless of sex. The protective effects of BCX were associated with lower expression of IL-6, TNF-α, and matrix metalloproteinases-2 and -9. BCX treatment led to a significant increase in hepatic BCX levels in DKO mice, but not in WT mice, which had significant increase in hepatic retinol concentration. No apo-10'-carotenoids were detected in any of the groups. In vitro BCX, at comparable doses of 3-OH-β-apo-10'-carotenal, was effective at inhibiting the lipopolysaccharide-induced inflammatory response in a human bronchial epithelial cell line. These data indicate that BCX can serve as an effective protective agent against CS-induced lung lesions in the absence of carotenoid cleavage enzymes.

Inadequate potassium (K) availability is a common abiotic stress that limits the growth and quality of fruit trees. Few studies have investigated the physiological and molecular responses of grapes at different potassium levels. In this study, an integrated approach was developed for grapevines grown at four different potassium fertilization levels [0 (K0-CK), 150 (K150), 300 (K300), and 450 (K450) g/plant] in combination with metabolite measurements and transcript analysis. The results showed that different K levels affected the accumulation of sugars and anthocyanins in the fruit. At 78 days after bloom (DAB), the K150, K300, and K450 treatments increased soluble sugar content by 37.39%, 31.10% and 32.59%, respectively, and anthocyanin content by 49.78%, 24.10%, and 13.06%, respectively, compared to K0. Weighted gene co-expression network analysis (WGCNA) of DEGs identified a network of 11 grapevines involved. During fruit development, potassium application promoted the accumulation of anthocyanins and sugars in fruit by regulating the up-regulation of GST , AT , UFGT and SPS , HT , PK gene expressions. These results suggest that potassium deficiency inhibits anthocyanin and sugar metabolism. In addition, it promotes the up-regulation of KUP expression, which is the main cause of K accumulation in fruits. Together, our data revealed the molecular mechanism in response to different K levels during fruit quality formation and provides the scientific foundation for the improvement of fruit quality by adding K fertilizer., Competing Interests: The authors declare no conflict of interest.