Multifunctional combined drug-loaded nanofibrous dressings with anti-inflammatory, antioxidant stress and microenvironment improvement for diabetic wounds.

The treatment of diabetic wounds remains a formidable clinical challenge worldwide. Because of persistent inflammatory reaction, excessive oxidative stress, cell dysfunction, poor blood microcirculation and other microvascular complications, diabetic wounds often fall into inflammatory circulation and are difficult to heal, making patients confront the risk of amputation. In this study, silver complex nanoparticles with Resina Draconis extract and Rhodiola rosea L. extract were loaded in situ onto thermoplastic polyurethane nanofibers to develop a multifunctional electrospun nanofiber wound dressing with excellent mechanical properties, superior water absorption and breathability, good coagulation promoting activity, strong antibacterial performance and antioxidant properties. This wound dressing could effectively enhance the migration and proliferation of fibroblasts, reduce the increased thickness of regenerated epidermis caused by diabetes, and the high expression and high lipid peroxidation levels of IL-1 ß, IL-6, TNF α, iNOS and MMP-9, and raise the low expression of VEGF, which shows great potential to accelerate the wound healing of diabetic mouse models. The wound healing rate reached about 87.92%, close to the non-diabetic group. Our findings suggest a breakthrough in diabetic wound care, offering a viable solution to a long-standing medical shackle.

A 2m-Range 711µW Body Channel Communication Transceiver Featuring Dynamically-Sampling Bias-Free Interface Front End.

Body Channel Communication (BCC) utilizes the body surface as a low-loss signal transmission medium, reducing the power consumption of wireless wearable devices. However, the effective communication range on the human body is limited in the state-of-the-art BCC transceivers, where the signal loss between the body surface and the BCC receiver remains one of the main bottlenecks. To reduce the interface loss, a high input impedance is desired by the BCC receiver, but the DC-biasing circuits decrease the input impedance. In this work, a dynamically-sampling IFE is proposed to eliminate the DC voltage bias, resulting in a 90kΩ high input impedance and a 94dB RF-IF conversion gain to reduce the interface loss in long-range BCC applications. The BCC transceiver chip is fabricated in 55nm CMOS process, taking a die area of 0.123mm2. Measured results show that the chip extends the BCC range to 2m for both the forward and backward paths, where the transmitter and receiver consume 711µW power in total.

IL-1 receptor antagonism reveals a yin-yang relationship between NFκB and interferon signaling in chronic lymphocytic leukemia.

Nuclear factor kappa B (NFκB) is a pathogenic factor in chronic lymphocytic leukemia (CLL) that is not addressed specifically by current therapies. NFκB is activated by inflammatory factors that stimulate toll-like receptors (TLRs) and receptors for interleukin-1 (IL-1) family members. IL-1 is considered a master regulator of inflammation, and IL-1 receptor signaling is inhibited by the IL-1 receptor antagonist anakinra. These considerations suggested that anakinra might have a role in the treatment of CLL. Consistent with this idea, anakinra inhibited spontaneous and TLR7-mediated activation of the canonical NFκB pathway in CLL cells in vitro. However, CLL cells exhibited only weak signaling responses to IL-1 itself, and anakinra was found to inhibit NFκB along with oxidative stress in an IL-1 receptor-independent manner. Anakinra was then administered with minimal toxicity to 11 previously untreated CLL patients in a phase I dose-escalation trial (NCT04691765). A stereotyped clinical response was observed in all patients. Anakinra lowered blood lymphocytes and lymph node sizes within the first month that were associated with downregulation of NFκB and oxidative stress in the leukemia cells. However, inhibition of NFκB was accompanied by upregulation of type 1 interferon (IFN) signaling, c-MYC-regulated genes and proteins, and loss of the initial clinical response. Anakinra increased IFN signaling and survival of CLL cells in vitro that were, respectively, phenocopied by mitochondrial antioxidants and reversed by IFN receptor blocking antibodies. These observations suggest that anakinra has activity in CLL and may be a useful adjunct for conventional therapies as long as compensatory IFN signaling is blocked at the same time.

Thick Glass High-Quality Cutting by Ultrafast Laser Bessel Beam Perforation-Assisted Separation.

The cutting of thick glass is extensively employed in aerospace, optical, and other fields. Although ultrafast laser Bessel beams are heavily used for glass cutting, the cutting thickness and cutting quality need to be further improved. In this research, the high-quality cutting of thick glass was realized for the first time using ultrafast laser perforation assisted by CO2 laser separation. Initially, an infrared picosecond laser Bessel beam was employed to ablate the soda-lime glass and generate a perforated structure. Subsequently, a CO2 laser was employed to induce crack propagation along the path of the perforated structure, resulting in the separation of the glass. This study investigates the influence of hole spacing, pulse energy, and the defocusing distance of the picosecond laser Bessel beam on the average surface roughness of the glass sample cutting surface. The optimal combination of cutting parameters for 6 mm thick glass results in a minimum surface roughness of 343 nm in the cross-section.

Neural Dielet 2.0: A 128-Channel 2mm×2mm Battery-Free Neural Dielet Merging Simultaneous Multi-Channel Transmission through Multi-Carrier Orthogonal Backscatter.

Miniaturization of wireless neural-recording systems enables minimally-invasive surgery and alleviates the rejection reactions for implanted brain-computer interface (BCI) applications. Simultaneous massive-channel recording capability is essential to investigate the behaviors and inter-connections in billions of neurons. In recent years, battery-free techniques based on wireless power transfer (WPT) and backscatter communication have reduced the sizes of neural-recording implants by battery eliminating and antenna sharing. However, the existing battery-free chips realize the multi-channel merging in the signal-acquisition circuits, which leads to large chip area, signal attenuation, insufficient channel number or low bandwidth, etc. In this work, we demonstrate a 2mm×2mm battery-free neural dielet, which merges 128 channels in the wireless part. The neural dielet is fabricated with 65nm CMOS process, and measured results show that: 1) The proposed multi-carrier orthogonal backscatter technique achieves a high data rate of 20.16Mb/s and an energy efficiency of 0.8pJ/bit. 2) A self-calibrated direct digital converter (SC-DDC) is proposed to fit the 128 channels in the 2mm×2mm die, and then the all-digital implementation achieves 0.02mm2 area and 9.87µW power per channel.

The gut microbiome promotes locomotion of Drosophila larvae via octopamine signaling.

The gut microbiome is a key partner of animals, influencing various aspects of their physiology and behaviors. Among the diverse behaviors regulated by the gut microbiome, locomotion is vital for survival and reproduction, although the underlying mechanisms remain unclear. Here, we reveal that the gut microbiome modulates the locomotor behavior of Drosophila larvae via a specific neuronal type in the brain. The crawling speed of germ-free (GF) larvae was significantly reduced compared to the conventionally reared larvae, while feeding and excretion behaviors were unaffected. Recolonization with Acetobacter and Lactobacillus can fully and partially rescue the locomotor defects in GF larvae, respectively, probably due to the highest abundance of Acetobacter as a symbiotic bacterium in the larval gut, followed by Lactobacillus. Moreover, the gut microbiome promoted larval locomotion, not by nutrition, but rather by enhancing the brain levels of tyrosine decarboxylase 2 (Tdc2), which is an enzyme that synthesizes octopamine (OA). Overexpression of Tdc2 rescued locomotion ability in GF larvae. These findings together demonstrate that the gut microbiome specifically modulates larval locomotor behavior through the OA signaling pathway, revealing a new mechanism underlying larval locomotion regulated by the gut microbiome.

The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis.

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Enhanced reproductive toxicity of photodegraded polylactic acid microplastics in zebrafish.

Microplastics are widely used due to their numerous advantages. However, they can have detrimental effects on marine ecosystems. When microplastics enter the ocean, they can be absorbed by marine organisms, leading to toxic effects. Additionally, the transformation of microplastics during natural degradation can alter their toxicity, necessitating further investigation. Polylactic acid (PLA) biodegradable plastics are commonly used, yet research on their toxicity, particularly their reproductive effects on aquatic organisms, remains limited. In this study, we conducted photodegradation of PLA using potassium persulfate as a catalyst to simulate natural degradation conditions. Our objective was to assess the reproductive toxicity of photodegraded PLA microplastics on zebrafish. The results revealed that photodegraded PLA exhibited elevated reproductive toxicity, resulting in abnormal oocyte differentiation, disruption of sexual hormone levels, and alterations in ovarian tissue metabolism. Metabolomics analysis indicated that both unphotodegraded PLA (UPLA) and photodegraded PLA (DPLA) disrupted oxidative stress homeostasis in zebrafish ovarian tissue by influencing pathways such as purine metabolism, phenylalanine metabolism, glutathione metabolism, and riboflavin metabolism. Furthermore, the DPLA treatment induced abnormal biosynthesis of taurocholic acid, which was not observed in the UPLA treatment group. Importantly, the DPLA treatment group exhibited more pronounced effects on offspring development compared to the UPLA treatment group, characterized by higher mortality rates, inhibition of embryo hatching, accelerated heart rates, and reduced larval body length. These findings underscore the varying levels of toxicity to zebrafish ovaries before and after PLA photodegradation, along with evidence of intergenerational toxicity.

A Self-Adaptive Dual-ILRO Clock-Recovery Technique for Two-Tone Battery-Free Crystal-Free Neural-Recording SoC.

Wireless implantable devices are widely used in medical treatment, which should meet clinical constraints such as longevity, miniaturization, and reliable communication. Wireless power transfer (WPT) can eliminate the battery to reduce system size and prolong device life, while it's challenging to generate a reliable clock without a crystal. In this work, we propose a self-adaptive dual-injection-locked-ring-oscillator (dual-ILRO) clock-recovery technique based on two-tone WPT and integrate it into a battery-free neural-recording SoC. The 2[Formula: see text]-order inter-modulation (IM2) component of the two WPT tones is extracted as a low-frequency reference for battery-free SoC, and the proposed self-adaptive dual-ILRO technique extends the lock range to ensure an anti-interference PVT-robust clock generation. The neural-recording SoC includes a low-noise signal acquisition unit, a power management unit, and a backscatter circuit to perform neural signal recording, wireless power harvesting, and neural data transmission. Benefiting from the 6.4 µW low power of the clock recovery circuit, the overall SoC power is cut down to 49.8 µW. In addition, the proposed clock-recovery technique enables both signal acquisition and uplink communication to perform as well as that synchronized by an ideal clock, i.e., an effective number of 9.6 bits and a bit error rate (BER) less than 4.8 × 10-7 in chip measurement. The SoC takes a die area of 2.05 mm 2, and an animal test is conducted in a Sprague-Dawley rat to validate the wireless neural-recording performance, compared to a crystal-synchronized commercial chip.

Exploring a multi-output temporal convolutional network driven encoder-decoder framework for ammonia nitrogen forecasting.

Artificial neural networks exhibit significant advantages in terms of learning capability and generalizability, and have been increasingly applied in water quality prediction. Through learning a compressed representation of the input data, the Encoder-Decoder (ED) structure not only could remove noise and redundancies, but also could efficiently capture the complex nonlinear relationships of meteorological and water quality factors. The novelty of this study lies in proposing a multi-output Temporal Convolutional Network based ED model (TCN-ED) to make ammonia nitrogen forecasts for the first time. The contribution of our study is indebted to systematically assessing the significance of combining the ED structure with advanced neural networks for making accurate and reliable water quality forecasts. The water quality gauge station located at Haihong village of an island in Shanghai City of China constituted the case study. The model input contained one hourly water quality factor and hourly meteorological factors of 32 observed stations, where each factor was traced back to the previous 24 h and each meteorological factor of 32 gauge stations was aggregated into one areal average factor. A total of 13,128 hourly water quality and meteorological data were divided into two datasets corresponding to model training and testing stages. The Long Short-Term Memory based ED (LSTM-ED), LSTM and TCN models were constructed for comparison purposes. The results demonstrated that the developed TCN-ED model can succeed in mimicking the complex dependence between ammonia nitrogen and water quality and meteorological factors, and provide more accurate ammonia nitrogen forecasts (1- up to 6-h-ahead) than the LSTM-ED, LSTM and TCN models. The TCN-ED model, in general, achieved higher accuracy, stability and reliability compared with the other models. Consequently, the improvement can facilitate river water quality forecasting and early warning, as well as benefit water pollution prevention in the interest of river environmental restoration and sustainability.

The combined toxic effects of polystyrene microplastics and different forms of arsenic on the zebrafish embryos (Danio rerio).

Microplastics have been widely studied for their ability to adsorb heavy metals. In the natural environment, arsenic exists in different forms and its toxicity depends mainly on its form and concentration. However, different forms of arsenic combined with microplastics have yet to be explored for their biological hazards. This study was conducted to reveal the adsorption mechanism of different forms of arsenic onto PSMP and to study the effects of PSMP on the tissue accumulation and developmental toxicity of different forms of arsenic in zebrafish larvae. As a result, the absorbing ability of PSMP for As(III) was 35 times higher than that of DMAs, in which hydrogen bonding plays an important role in the adsorption process. In addition, the adsorption kinetics of As(III) and DMAs on PSMP were in good agreement with the pseudo-second-order kinetic model. Furthermore, PSMP reduced the accumulation of As(III) early in zebrafish larvae development, thereby increasing hatching rates compared with the As(III)-treated group, whereas PSMP had no significant effect on DMAs accumulation in zebrafish larvae, but decreased hatching rates compared with the DMAs-treated group. In addition, except for the microplastic exposure group, the other treatment groups could lead to a decrease in the heart rate of zebrafish larvae. Both PSMP+As(III) and PSMP+DMAs exhibited aggravated oxidative stress compared with PSMP-treated group, but PSMP+As(III) caused more severe oxidative stress at later stages of zebrafish larvae development. Moreover, specific metabolic differences (e.g., AMP, IMP, and guanosine) were produced in the PSMP+As(III) exposure group, which would mainly affect purine metabolism and promoted specific metabolic disturbances. However, PSMP+DMAs exposure shared metabolic pathways altered by PSMP and DMAs, indicating an independent effect of these two chemicals. Taken together, our findings emphasized that the combined toxicity of PSMP and different forms of arsenic posed a health risk that cannot be ignored.

Design, Synthesis, and Antitumor Activities of Isomers of Artemisinin Dimer Derivatives.

In recent years, numerous studies have reported on the anti-tumor properties of artemisinin and its derivatives. However, the relationship between their artemisinin chirality and activity remains unknown. In this study, we synthesized a series of artemisinin dimer derivatives with three different chiral structures and tested their antiproliferative activity in MCF-7 and HepG2 cells using the CCK-8 assay. Interestingly, we discovered that artemisinin dimer derivatives with ß, ß and α, ß conformations at C-10 exhibited stronger anti-tumor activity than those with an α, α configuration in MCF-7 and HepG2 cells. Notably, compound 4 showed an activity of 0.06 µM in MCF-7 cells. This study demonstrates the relationship between the conformation and activity of artemisinin dimer derivatives, and these derivatives have the potential to be developed into anti-cancer drugs.

Exploring a similarity search-based data-driven framework for multi-step-ahead flood forecasting.

Due to a small proportion of observations, reliable and accurate flood forecasts for large floods present a fundamental challenge to artificial neural network models, especially when the forecast horizons exceed the flood concentration time of a river basin. This study proposed for the first time a Similarity search-based data-driven framework, and takes the advanced Temporal Convolutional Network based Encoder-Decoder model (S-TCNED) as an example for multi-step-ahead flood forecasting. A total of 5232 hourly hydrological data were divided into two datasets for model training and testing. The input sequence of the model included hourly flood flows of a hydrological station and rainfall data (traced back to the previous 32 h) of 15 gauge stations, and the output sequence stepped into 1- up to 16-hour-ahead flood forecasts. A conventional TCNED model was also built for comparison purposes. The results demonstrated that both TCNED and S-TCNED could make suitable multi-step-ahead flood forecasts, while the proposed S-TCNED model not only could effectively mimic the long-term rainfall-runoff relationship but also could provide more reliable and accurate forecasts of large floods than the TCNED model even in extreme weather conditions. There is a significant positive correlation between the mean sample label density improvement and the mean Nash-Sutcliffe Efficiency (NSE) improvement of the S-TCNED over the TCNED at the long forecast horizons (13 h up to 16 h). Based on the analysis of the sample label density, it is found that the similarity search largely improves the model performance by enabling the S-TCNED model to learn the development process of similar historical floods in a targeted manner. We conclude that the proposed S-TCNED model that converts and associates the previous rainfall-runoff sequence with the forecasting runoff sequence under a similar scenario can enhance the reliability and accuracy of flood forecasts while extending the length of forecast horizons.

Apple puree as a natural fructose source provides an effective alternative carbohydrate source for fuelling half-marathon running performance.

Carbohydrate supplementation during endurance exercise is known to improve performance, but the effects of food-based approaches in running exercise are understudied. Therefore, this study investigated the performance and gastrointestinal (GI) effects of a carbohydrate supplement containing a natural fructose source compared with a highly processed fructose source in a combined glucose-fructose supplement, during a half-marathon. Eleven trained runners (9 males, 2 females; age 32 ± 8 y, 89:53 ± 13:28 min half-marathon personal record) completed a familiarisation (8 miles) and two experimental trials (13.1 miles) on an outdoor running course, with blood and urine samples collected before and after the run. Subjective GI measures were made throughout the run. Carbohydrate was provided as a natural fructose source in the form of apple puree (AP) or highly processed crystalline fructose (GF) in a 2:1 glucose-to-fructose ratio (additional required glucose was provided through maltodextrin). Half-marathon performance was not different between carbohydrate sources (AP 89:52 ± 09:33 min, GF 88:44 ± 10:09 min; P = 0.684). There were no interaction effects for GI comfort (P = 0.305) or other GI symptoms (P ≥ 0.211). There were no differences between carbohydrate sources in ad libitum fluid intake (AP 409 ± 206 mL; GF 294 ± 149 mL; P = 0.094) or any other urinary (P ≥ 0.724), blood-based (P ≥ 0.215) or subjective (P ≥ 0.421) measures. Apple puree as a natural fructose source was equivalent to crystalline fructose in supporting half-marathon running performance without increasing GI symptoms.HighlightsResearch examining food-first and food-based approaches to carbohydrate supplementation and endurance running performance are limited. Therefore, this study aimed to compare carbohydrate supplements either containing a natural or highly processed fructose source as part of a glucose-fructose supplement on half-marathon running performance and gastrointestinal comfort in trained runners.Running performance (apple puree 89:52 ± 09:33 min vs. crystalline fructose 88:44 ± 10:09 min), gastrointestinal comfort and symptoms were not different between the two fructose sources.Apple puree can be effectively used as a carbohydrate source to fuel half-marathon running performance.

Nanoparticle-Based Photodynamic Inhibition of Candida albicans Biofilms with Interfering Quorum Sensing.

Biofilm formation is a critical event in the pathogenesis and virulence of fungal infections caused by Candida albicans, giving rise to about a 1000-fold increase in the resistance to antifungal agents. Although photodynamic treatment (PDT) has been excellently implicated in bacterial infections, studies on its potential against fungal infection through the clearance of fungal biofilm formation remain at its infancy stage. Here, we have designed photodynamic nanoparticles with different sizes, modifications, and the ability of generating reactive oxygen species (ROS) to examine their effects on inhibiting biofilm formation and destructing mature biofilms of C. albicans. We found that the nanoparticles modified with oligo-chitosan exhibited a better binding efficiency for planktonic cells, leading to stronger inhibitory efficacy of the filamentation and the early-stage biofilm formation. However, for mature biofilms, the nanoparticles with the smallest size (∼15 nm) showed the fastest penetration speed and a pronounced destructing effect albeit conferring the lowest ROS-producing capability. The inhibitory effect of photodynamic nanoparticles was dependent on the disruption of fungal quorum sensing (QS) by the upregulation of QS molecules, farnesol and tyrosol, mediated through the upregulation of ARO 8 and DPP 3 expression. Our findings provide a powerful strategy of nanoparticulate PDT to combat fungal infections through the inhibition of both hyphal and biofilm formation by disrupting QS.

Artificial Intelligence in the Prediction of Gastrointestinal Stromal Tumors on Endoscopic Ultrasonography Images: Development, Validation and Comparison with Endosonographers.

Background/Aims: The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. Methods: We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. Results: A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers. The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. Conclusions: We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.

A Wireless Headstage System Based on Neural-Recording Chip Featuring 315 nW Kickback-Reduction SAR ADC.

Wireless neural-recording instruments eliminate the bulky cables in multi-channel signal transmission, while the system size should be reduced to mitigate the impact on freely-moving animals. As the battery usually dominates the system size, the neural-recording chip should be low power to minimize the battery in long-termly monitoring. In general, a neural-recording chip consists of an analog front end (AFE) and an 8 bit -10 bit analog-to-digital converter (ADC), while it's challenging to design an ADC with an 8 -10 effective number of bits (ENOB) and sub- µ W power consumption due to the kickback noise. In this work, we propose a kickback-reduction technique for a successive-approximation-register (SAR) ADC based on neural-recording chip. Fabricated in 65 nm CMOS process, the proposed technique reduce the ADC power to 315 nW, resulting in an 8-channel neural-recording chip with 249 µW in total. Measured results show that the chip achieves an ADC ENOB of 9.73 bits, as well as an AFE gain of 43.3 dB and input-referred noise (IRN) of 9.68 µVrms in a bandwidth of 0.9 Hz -7.2 kHz. Combined with a BLE chip and a PCB antenna, the chip is implemented into a 2.6 g wireless headstage system (w/o battery), and an in-vivo demonstration is conducted on a male Sprague-Dawley rat with Parkinson's disease. The headstage system transfers the in-vivo neural signals to a commodity smartphone through BLE, and the miniature size induces little impact on freely-moving activities.

A Review of Generalized Zero-Shot Learning Methods.

Generalized zero-shot learning (GZSL) aims to train a model for classifying data samples under the condition that some output classes are unknown during supervised learning. To address this challenging task, GZSL leverages semantic information of the seen (source) and unseen (target) classes to bridge the gap between both seen and unseen classes. Since its introduction, many GZSL models have been formulated. In this review paper, we present a comprehensive review on GZSL. First, we provide an overview of GZSL including the problems and challenges. Then, we introduce a hierarchical categorization for the GZSL methods and discuss the representative methods in each category. In addition, we discuss the available benchmark data sets and applications of GZSL, along with a discussion on the research gaps and directions for future investigations.

Mechanisms of miR-29a-5p involvement in osteogenic phenotype transformation and cellular regulation of vascular smooth muscle and thus influencing calcification in VSMCs in chronic kidney disease.

Vascular calcification is one of the major complications of chronic kidney disease (CKD), which could be further accelerated by the osteogenic transition and apoptosis of smooth muscle cells, thereby advancing the progression of renal diseases and increasing the mortality rate of cardiovascular events. MicroRNA is a kind of key regulator in the phenotypic transition of vascular smooth muscle cells (VSMCs), but its role remains unclear in VSMCs. In this study, VSMCs were stimulated by platelet-derived growth factors - BB (PDGF-BB) in varying concentrations to establish the VSMC dysfunction models. The relative expression of miR-29a-5p was quantified via the quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation of VSMCs was determined via the BrdU method, analysis of cell cycle via flow cytometry, and the migration of VSMCs via Transwell assay. Expression of γ-secretase activating protein (GSAP) and markers of VSMC differentiation, including α-SMA, SM-22α, SMMHC and Calponin, was quantified via the Western blot. The targeting relationship between the 3'-UTR of miR-29a-5p and GSAP was validated through the dual-luciferase reporter gene assay. As a result, we found that PDGF-BB could trigger a decrease of miR-29a-5p in a time- and dose-dependent manner (P < 0.05). Overexpression of miR-29a-5p could curb the effect of PDGF-BB on the proliferation and migration of VSMCs while upregulating the expression of markers of differentiation (P < 0.05). In addition, the expression of GSAP was also affected by the negative regulation of miR-29a-5p, while the restoration of GSAP eliminated the effect of miR-29a-5p on the VSMCs partially (P < 0.05). Moreover, vascular calcification models were also established in the CKD rats, suggesting that the inhibition of GSAP could prevent PTH-induced vascular calcification in CKD rats. In conclusion, miR-29a-5p could inhibit the PDGF-BB-induced proliferation, migration and phenotypic transition of VSMCs via targeting GSAP. Thus, miR-29a-5p/GSAP might be a potential target for the treatment of vascular calcification.