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Cell sheets combined with electrospun fibrous mats represent an attractive approach for the repair and regeneration of injured tissues. However, the conventional dense electrospun mats as supportive substrates in forming "cell sheet on fiber mat" complexes suffer from problems of limiting the cellular function and eliciting a host response upon implantation. To give full play to the role of electrospun biomimicking fibers in forming quality cell sheets, this study proposed to develop a cell-fiber integrated sheet (CFIS) featuring a spatially homogeneous distribution of cells within the fiber structure by using a low-density fibrous network for cell sheet formation. A low-density electrospun polycaprolactone (PCL) fibrous network at a density of 103.8 ± 16.3 μg cm

The prediction of crop yield plays a crucial role in national economic development, encompassing grain storage, processing, and grain price trends. Employing multiple sensors to acquire remote sensing data and utilizing machine learning algorithms can enable accurate, fast, and nondestructive yield prediction for maize crops. However, current research heavily relies on single-type remote sensing data and traditional machine learning methods, resulting in the limited robustness of yield prediction models. To address these limitations, this study introduces a field-scale maize yield prediction model named the convolutional neural network–attention–long short-term memory network (CNN-attention-LSTM) model, which utilizes multimodal remote sensing data collected by multispectral and light detection and ranging (LIDAR) sensors mounted on unmanned aerial vehicles (UAVs). The model incorporates meteorological data throughout the crop reproductive stages and employs the normalized difference vegetation index (NDVI), normalized difference red edge (NDRE), soil-adjusted vegetation index (SAVI), and enhanced vegetation index (EVI) for the initial part of the vegetative stage (initial part of the V period), the later part of the vegetative stage (later part of the V period), the reproductive stage (R period), and the maturity stage (M period), along with LIDAR data for Point75–100 in the later part of the V period, Point80–100 in the R period, and Point50–100 in the M period, complemented by corresponding meteorological data as inputs. The resulting yield estimation demonstrates exceptional performance, with an R2 value of 0.78 and an rRMSE of 8.27%. These results surpass previous research and validate the effectiveness of multimodal data in enhancing yield prediction models. Furthermore, to assess the superiority of the proposed model, four machine learning algorithms—multiple linear regression (MLR), random forest regression (RF), support vector machine (SVM), and backpropagation (BP)—are compared to the CNN-attention-LSTM model through experimental analysis. The outcomes indicate that all alternative models exhibit inferior prediction accuracy compared to the CNN-attention-LSTM model. Across the test dataset within the study area, the R2 values for various nitrogen fertilizer levels consistently exceed 0.75, illustrating the robustness of the proposed model. This study introduces a novel approach for assessing maize crop yield and provides valuable insights for estimating the yield of other crops.

Zn metal is thermodynamically unstable in aqueous electrolytes, which induces dendrite growth and ongoing parasitic reactions at the interface during the plating process and even during shelf time, resulting in rapid battery failure and hindering the practical application of aqueous Zn ion batteries. In this work, glycine, a common multifunctional additive, is utilized to modulate the solvation shell structure and enhance the interfacial stability to guard the reversibility and stability of the Zn anode. Apart from partially replacing the original SO

In response to central nervous system (CNS) injury, astrocytes go through a series of alterations, referred to as reactive astrogliosis, ranging from changes in gene expression and cell hypertrophy to permanent astrocyte borders around stromal cell scars in CNS lesions. The mechanisms underlying injury-induced reactive astrocytes in the adult CNS have been extensively studied. However, little is known about injury-induced reactive astrocytes during early postnatal development. Astrocytes in the mouse cortex are mainly produced through local proliferation during the first 2 weeks after birth. Here we show that Sox2, a transcription factor critical for stem cells and brain development, is expressed in the early postnatal astrocytes and its expression level was increased in reactive astrocytes after traumatic brain injury (TBI) at postnatal day (P) 7 in the cortex. Using a tamoxifen-induced hGFAP-CreERT2; Sox2

Purpose Adequate pulmonary function is important for patients undergoing surgical resection of esophageal cancer, especially those that received neoadjuvant therapy. However, it is unknown if pre-operative radiation affects pulmonary function differently compared to chemotherapy. The purpose of this study was to compare changes in pulmonary function between patients undergoing minimally invasive esophagectomy (MIE) who received neoadjuvant chemotherapy or chemoradiotherapy. Methods Between March 2017 and March 2018, esophageal cancer patients requiring neoadjuvant therapy were prospectively enrolled and randomly assigned to receive chemotherapy (CT) or chemoradiotherapy (CRT) before MIE. All patients received pulmonary function testing before and after the neoadjuvant therapy. Changes in pulmonary function, operative data, and pulmonary complications were compared between the 2 groups. Results A total of 71 patients were randomized and underwent MIE after receiving CT (n = 34) or CRT (n = 37). Baseline clinical characteristics were comparable between the 2 groups. The CRT group experienced a greater decrease of forced expiratory volume at 1 s (FEV1) (2.66 to 2.18 L, p = 0.023) and diffusion capacity of the lung for carbon monoxide divided by the mean alveolar volume (DLCO/Va) (17.3%, p 1 2.53 to 2.41 L; DLCO/Va 4.8%). The incidence of pulmonary complications was higher in the CRT group (13.51 vs. 8.82%), but the difference was not significant (p = 0.532). Conclusions Preoperative CRT affects pulmonary function more than CT alone, but does not increase the risk of pulmonary complications in patients undergoing MIE.

This study is aimed at the special working conditions of seeding on sloping land, combining advanced precision seeding technology and the structure of rotary hole filling corn precision metering device seed rowers at home and abroad, and studying soil entry characteristics, the characteristics of soil particles and the seed transport pattern in the puncture process, in order to improve the seed dispersal qualified index and reduce the coefficient of variation in the process of seeding. The simulation test of the cavity-tying device was carried out using the MBD–DEM coupling method, and it can be seen that the rocker bending angle is 120° when the force is the largest; at this time the rocker and the soil force is the largest, indicating the best effect on soil particle separation and the fastest movement speed. The single-factor test determined that the operating speed of the seed rower ranged from 0.8 to 1.2 m/s, the spring preload force of the seed rower ranged from 5.5 to 25 N, and the operating slope angle of the seed rower ranged from 8° to 16°. The optimal structure and parameter characteristics of the rotary hole filling corn precision metering device were determined with a multi-factor test, and it was proven that the rotary hole filling corn precision metering device has better performance and a higher seed rowing quality, with the qualified index reaching 96.2%. This study can provide a reference for the research of corn precision seeders, enrich the form of corn precision seeders, and effectively improve the level of corn mechanized seeding.

Hypothalamic defects characterized by metabolic disorders influence the progression of Alzheimer’s disease (AD). Recent studies have proposed that tanycytes, radial glial-like cells lining the third ventricle wall, participate in energy homeostasis regulation as an important player. However, the role of tanycytes in neurodegenerative diseases such as AD is unclear. Our ongoing research aims to investigate morphological and functional changes in tanycytes in an APP/PS1 mouse model of AD. Considering the spatial distribution of hypothalamic nuclei, we focused on middle region (from bregma − 1.5 to − 2.1 mm) of the mediobasal hypothalamus. By vimentin immunostaining, we found both internal and external ME areas occupied by vimentin-positive processes displayed a significant reduction in 12-month-old APP/PS1 mice compared with WT controls. Administration of Evans blue revealed normal barrier function of the ME–ARH interface and impaired fasting-induced remodeling of the blood–hypothalamic barrier, suggesting an attenuated ability of blood-borne molecules to enter the ARH. Moreover, in 5- and 12-month-old APP/PS1 mice, tanycytes exhibited a similar expression pattern of the zonula occludins-1 (ZO-1) tight-junction complex relative to age-matched control littermates. Interestingly, although random and actual food intake was similar among 5- and 12-month-old APP/PS1 and WT mice, fasting blood glucose and rebound feeding was significantly higher in 12-month-old APP/PS1 mice than WT mice. We also detected more c-Fos immunoreactive neurons in the ARH and more areas of ARH occupied by tanycytic processes in 12-month-old APP/PS1 mice, providing more anatomical evidence for tanycyte–neuron communication in the ARH. These results uncovered changes in morphology and barrier function of tanycytes in APP/PS1 mice, which may be associated with abnormal hypothalamic glucose metabolism.

Eutectic In-48Sn was considered a promising candidate for low-temperature solder due to its low melting point and excellent mechanical properties. Both Cu2(In,Sn) and Cu(In,Sn)2 formation were observed at the In-48Sn/Cu interface after 160 °C soldering. However, traditional mechanical polishing produces many defects at the In-48Sn/Cu interface, which may affect the accuracy of interfacial reaction investigations. In this study, cryogenic broad Ar+ beam ion milling was used to investigate the interfacial reaction between In-48Sn and Cu during soldering. The phase Cu6(Sn,In)5 was confirmed as the only intermetallic compound formed during 150 °C soldering, while Cu(In,Sn)2 formation was proven to be caused by room-temperature aging after soldering. Both the Cu6(Sn,In)5 and Cu(In,Sn)2 phases were confirmed by EPMA quantitative analysis and TEM selected area electron diffraction. The microstructure evolution and growth mechanism of Cu6(Sn,In)5 during soldering were proposed. In addition, the Young’s modulus and hardness of Cu6(Sn,In)5 were determined to be 119.04 ± 3.94 GPa and 6.28 ± 0.13 GPa, respectively, suggesting that the doping of In in Cu6(Sn,In)5 has almost no effect on Young’s modulus and hardness.

Although water table recessions associated with seasonal freezing have been widely reported, the conditions that groundwater could respond to seasonal freezing are poorly known. Based on 30 records of winter-time water table recessions reported in the literature, we find the mean water table recession increases from sand to loam to silt to clay. To obtain a quantitative understanding of the conditions of freezing-induced groundwater migration and the role of soil texture, we construct a one-dimensional SHAW model with a dynamic water table that could respond to winter-time atmospheric conditions. By simulating freezing-induced groundwater migration under a series of pre-freezing water table depths, soil textures and freezing indices, we find the extinction depth of freezing-induced groundwater migration, i.e., the limit water table depth beyond which there is negligible freezing-induced groundwater flow, increases from coarse to fine soils and increases with freezing index. Moreover, we find there is a good linear relationship between the distance from the freezing front to the water table corresponding to the extinction depth of freezing-induced groundwater migration and the distance from the land surface to the water table corresponding to the extinction depth of evaporation-induced groundwater migration for different soils. To demonstrate the importance of defining extinction depth, we also show the overestimation of freezing-induced water gain in the frozen zone by the widely used fixed water table condition when the water table depth is shallower than the extinction depth. This study has implications for future hydrologic and engineering studies in critical zones with a cold climate.

OX2 (X=halogen) molecules was studied theoretically. Calculation results show that delocalized [Formula: see text] bonds exist in their electronic structures and O atoms adopt the sp2 type of hybridization, which violates the prediction of the valence shell electron pair repulsion theory of sp3 type. Delocalization stabilization energy is proposed to measure the contribution of delocalized [Formula: see text] bond to energy decrease and proves to bring extra-stability to the molecule. These phenomena can be summarized as a kind of coordinating effect.

Ultraviolet (UV) irradiation causes 90% of photodamage to skin and long-term exposure to UV irradiation is the largest threat to skin health. To study the mechanism of UV-induced photodamage and the repair of sunburnt skin, the key problem to solve is how to non-destructively and continuously evaluate UV-induced photodamage to skin. In this study, a method to quantitatively analyze the structural and tissue optical parameters of artificial skin (AS) using optical coherence tomography (OCT) was proposed as a way to non-destructively and continuously evaluate the effect of photodamage. AS surface roughness was achieved based on the characteristic peaks of the intensity signal of the OCT images, and this was the basis for quantifying AS cuticle thickness using Dijkstra’s algorithm. Local texture features within the AS were obtained through the gray-level co-occurrence matrix method. A modified depth-resolved algorithm was used to quantify the 3D scattering coefficient distribution within AS based on a single-scattering model. A multiparameter assessment of AS photodamage was carried out, and the results were compared with the MTT experiment results and H&E staining. The results of the UV photodamage experiments showed that the cuticle of the photodamaged model was thicker (56.5%) and had greater surface roughness (14.4%) compared with the normal cultured AS. The angular second moment was greater and the correlation was smaller, which was in agreement with the results of the H&E staining microscopy. The angular second moment and correlation showed a good linear relationship with the UV irradiation dose, illustrating the potential of OCT in measuring internal structural damage. The tissue scattering coefficient of AS correlated well with the MTT results, which can be used to quantify the damage to the bioactivity. The experimental results also demonstrate the anti-photodamage efficacy of the vitamin C factor. Quantitative analysis of structural and tissue optical parameters of AS by OCT enables the non-destructive and continuous detection of AS photodamage in multiple dimensions.

AimsThe distribution of residual esophageal squamous cell carcinoma (ESCC) in the esophageal wall and resected lymph nodes was evaluated after neoadjuvant chemoimmunotherapy (nICT).Methods and resultsClinical data were collected from 137 ESCC patients who underwent anti-programmed death 1 therapy and esophagectomy. Ninety (65.7%) achieved an major pathological response (MPR) in the esophageal wall, and 27 (19.7%) achieved an MPR in the lymph nodes. Pathologically complete response (pCR, ypT0N0) was observed in 26 patients (19%). Residual tumors located in the mucosa and/or submucosa were found in 94.6% of nonpCR patients. In the minor responders, 97.8% had residual tumor >10% in the mucosa or submucosa. A preferential regression direction toward the lumen was found in 76.4% of prepT2 nonpCR patients, or 60.7% of prepT3-4a nonpCR patients. The correlation between pCR in the esophageal wall and in lymph nodes was not significant (P=0.143). Among 19 patients with pCR in resected recurrent laryngeal nerve (RLN) lymph nodes, 31.6% had residual tumor cells in other resected lymph nodes. A significant correlation was found between ypT/ypN downstaging and tumor regression grade (PConclusionsAfter nICT for ESCC, residual tumors were frequently found in the mucosa or submucosa, with relatively high responsiveness of the invasive front and a significant correlation with downstaging, which may help clinicians make appropriate decisions about postoperative treatment and surveillance. The differences in pCR status in primary tumors, resected lymph nodes, and RLN lymph nodes indicated the importance of assessing regression changes in all resected lymph nodes during clinical practice.

The 5-year survival rate for patients with oral squamous cell carcinomas (SCC), including tongue SCC, has not significantly improved over the last several decades. Oral potentially malignant disorders (OPMD), including oral dysplasias, are oral epithelial disorders that can develop into oral SCCs. To identify molecular characteristics that might predict conversion of OPMDs to SCCs and guide treatment plans, we performed global transcriptomic analysis of human tongue OPMD (n = 9) and tongue SCC (n = 11) samples with paired normal margin tissue from patients treated at Weill Cornell Medicine. Compared to margin tissue, SCCs showed more transcript changes than OPMDs. OPMDs and SCCs shared some altered transcripts, but these changes were generally greater in SCCs than OPMDs. Both OPMDs and SCCs showed altered signaling pathways related to cell migration, basement membrane disruption, and metastasis. We suggest that OPMDs are on the path toward malignant transformation. Based on patterns of gene expression, both OPMD and tongue SCC samples can be categorized into subclasses (mesenchymal, classical, basal, and atypical) similar to those seen in human head and neck SCC (HNSCC). These subclasses of OPMDs have the potential to be used to stratify patient prognoses and therapeutic options for tongue OPMDs. Lastly, we identified a gene set (ELF5; RPTN; IGSF10; CRMP1; HTR3A) whose transcript changes have the power to classify OPMDs and SCCs and developed a Firth logistic regression model using the changes in these transcripts relative to paired normal tissue to validate pathological diagnosis and potentially predict the likelihood of an OPMD developing into SCC, as data sets become available.

Camellia sinensis var. Assamica cv. Duntsa (C.duntsa), a valuable Theaceae from Hunan Province, has been looked at as a precious tea resource by local farmers because of its economic and ecological value. Genomics study on C.duntsa is essential for the domestication and enhancement of tea tree varieties. In the present study, we used a hybrid approach based on Illumina and PacBio data to sequence and assemble the mitochondrial genome of C.duntsa. The mitochondrial genome of C.duntsa was estimated to be 1,081,996 base pairs (bp) and eighty-one genes consisting of one pseudogene, three ribosomal RNA (rRNA) genes, thirty transfer RNA (tRNA) genes, and forty-seven protein-coding genes (PCGs). Tetramer repetitions made up 43.90% of simple sequence repeats (SSRs). The codon usage bias of the Theaceae mitochondrial gene atp9 was altered by mutation, but the codon usage of other genes was shaped by natural selection. Besides, there are eighteen gene-containing homologous regions between the chloroplast and mitochondrial genomes of C. duntsa.Some genomes including atp8, cox1, cox3, nad7, nad9, rpl16, rpl2, rps19, rps4, and sdh4 are absent in the mitochondrial genome of several Theaceae plant. However, C. duntsa maintains these genes integrity and functionality. Another gene, rps16, is either lacking from the mitochondrial genome of C. duntsa or is present as a pseudogene. C. duntsa and C. sinensis (OM809792) are very similar, as shown by a collinear match across four species of Theaceae; the most conservative genes are nad5, atp9, cox2, rps3, trnA-TGC, trnI-GAT, rrn18, trnV-GAC, and ccmFN. Similarly, the genome’s phylogenetic trees revealed that C. duntsa was the sister species to C. sinensis. The results confirmed that the C. duntsa and C. sinensis (OM809792) mitochondrial genome underwent gene rearrangement.In general, our results shows that genomic information from organelles can help us understand plant phylogeny and can also be used to make molecular markers and study how genetic traits change over time. Our research will contribute to the population genetics and evolution of tea plant.

Since circCDR1 was abnormally expressed in esophageal squamous cell cancer (ESCC), the current study explored whether circCDR1 affected ESCC. Detailedly, circCDR1 expression in ESCC and linear isoform and stability of circCDR1 were detected by RT-qPCR. The location of circCDR1 was detected by fluorescence in situ hybridization (FISH). After transfection, the cell biological functions were detected by wound-healing, CCK-8, colony formation, and flow cytometry assays. The target of circCDR1 was predicted by bioinformatics, FISH, RNA pull-down, and dual-luciferase reporter assays. The correlation between circCDR1 and miR-1290 was analyzed by Pearson’s correlation analysis. A subcutaneous-xenotransplant tumor model in BALB/c nude mice was established and the levels of circCDR1, miR-1290, and apoptosis/metastasis/proliferation-related factors in the cancer cells and tissues were detected by immunohistochemical analysis, western blot, or RT-qPCR. As a result, circCDR1 was low-expressed in ESCC tissues and cells, while miR-1290 was high-expressed. CircCDR1 was regulated and was negatively correlated with miR-1290. CircCDR1, located in cytoplasm, inhibited the viability, proliferation, migration, and invasion of the cancer cells and the expressions of Bcl-2, N-cadherin, and Vimentin, but enhanced cell apoptosis and the expressions of C caspase-3, Bax, E-cadherin, IGFBP4, LHX6 and NFIX. In vivo, circCDR1 promoted xenotransplanted tumor weight and volume, and the expressions of C caspase-3 and Bax yet suppressed the levels of Bcl-2, miR-1290, and Ki-67 in tumor tissues. The effects of circCDR1 on both cancer cells and tissues were opposite to and reversed by miR-1290 mimic. Collectively, circCDR1 sponged miR-1290 to regulate the progression of ESCC both in vitro and in vivo.

Maintaining proteostasis in the endoplasmic reticulum (ER) is critical for cell viability and plant survival under adverse conditions. The unfolded protein response (UPR) pathways interact with reactive oxygen species (ROS) to precisely trigger adaptive outputs or cell death under ER stress with varying degrees. However, little information is known about the relationship between UPR signalling and ROS regulation. Here, Arabidopsis GOLGI ANTI-APOPTOTIC PROTEIN1 (GAAP1)-GAAP4 were found to play redundant positive roles under ER stress. Genetic analysis showed that GAAP4 played a role in INOSITOL-REQUIRING ENZYME (IRE1)-dependent and -independent pathways. In addition, GAAPs played negative roles to activate the adaptive UPR under conditions of stress. Quantitative biochemical analysis showed that mutations in GAAP genes decreased the oxidised glutathione content and altered the pattern of ROS and glutathione in early ER stress. When plants were challenged with unmitigated ER stress, mutations in GAAP advanced ROS accumulation, which was associated with a decline in adaptive UPR. These data indicated that GAAPs resist cell death by regulating glutathione content to inhibit ROS accumulation and maintain UPR during ER stress. They provide a basis for further analysis of the regulation of cell fate decision under ER stress.

There is controversy regarding the long-term prognosis and short-term postoperative complications of different surgical strategies for proximal gastric cancer (PGC).We searched for articles published in Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science between January 1, 1990, and February 1, 2021. We screened out the literature comparing different surgical strategies. We then evaluated the long-term and short-term outcome of different surgical strategies using a network meta-analysis, which summarizes the hazard ratio, odds ratio, mean difference, and 95% confidence interval.There were no significant differences between different surgical strategies for 5-year overall survival (OS), anastomotic leakage, or weight loss after 1 year. Compared with total gastrectomy with Roux-en-Y reconstruction (TG-RY) and proximal gastrectomy with double tract reconstruction (PG-DTR), the proximal gastrectomy with esophagogastrostomy (PG-EG) strategy significantly increased the incidence of reflux esophagitis; and the operation time and blood loss of the PG-EG strategy were significantly less than those of the other surgical strategies. The anastomotic stenosis rates of the PG-EG and proximal gastrectomy with jejunum interstitial (PG-JI) strategies were significantly higher than those of TG-RY and PG-DTR; the hemoglobin level after 1 year for the PG-DTR strategy was significantly higher than that of the TG-RY strategy.Our comprehensive literature research found that different surgical strategies had no significant difference in the long-term survival of PGC, but the incidence of reflux esophagitis and anastomotic stenosis after PG-DTR and TG-RY was significantly reduced.

The surface morphology of the zinc-metal electrode was modulated using different levels of physical polishing treatment. Modulating the surface scratches homogenized the deposition electric field and reduced the local current density. A reasonable surface treatment could limit the "tip effect" and bring homogeneous plating and stripping of the Zn electrode.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a gland-forming malignancy arising in the pancreas. It is estimated that in developed countries the incidence of PDAC will continue to rise, and PDAC is now the fourth leading cause of cancer-related deaths in the USA. The mortality of PDAC patients closely parallels the incidence rate, as this malignancy generally remains asymptomatic until it reaches an advanced stage. Summary: The poor prognosis results from the aggressive nature of the tumor, late detection, and resistance to chemotherapy and radiotherapy. Retinoids, vitamin A (retinol) and its metabolites, such as retinoic acid (RA), play critical roles in important biological functions, including cell growth and differentiation, development, metabolism, and immunity. The actions of retinoids in maintaining normal pancreatic functions have generated considerable research interest from investigators interested in understanding and treating PDAC. Altered expression of retinoid receptors and other RA signaling pathway genes in human cancers offers opportunities for target discovery, drug design, and personalized medicine for distinct molecular retinoid subtypes. Key Messages: The goals of this review are to explore the potential activities of retinoids in the pancreas, to assess the evidence that retinoid functions become dysregulated in PDAC, and to describe the actions of retinoids in new therapies developed to increase patient survival.

Uncertain time series analysis has been developed for studying the imprecise observations. In this paper, we propose a nonlinear model called uncertain max-autoregressive (UMAR) model. The unknown parameters in model are estimated by the least squares estimation. Then the residual analysis is presented. In many cases, there are some outliers in the time series due to short-term change in the underlying process. The UMAR model offers an alternative for detecting outliers in the imprecise observations. Based on the previous theoretical results, the UMAR model is used to forecast the future. Finally, an example suggests that the new proposed time series model works well compared to the uncertain autoregressive (UAR) model.

The ligand exchange technique is a common method for postsynthesis isoreticular structures of metal–organic frameworks (MOFs). Here, an interesting framework transformation after linker exchange wa...

Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a secretory serine protease that plays multiple biological functions in the regulation of physiological and pathological processes. PCSK9 inhibitors decrease the circulating LDL-cholesterol level with well-known preventive and therapeutic effects on atherosclerosis (AS). Still, increasing evidence shows that the direct impact of PCSK9 on the vascular wall also plays an important role in atherosclerotic progression. Compared with other vascular cells, a large proportion of PCSK9 is originated from vascular smooth muscle cells (VSMC). Therefore, defining the effect of VSMC-derived PCSK9 on response changes, such as phenotypic switch, apoptosis, autophagy, inflammation, foam cell formation, and calcification of VSMC, helps us better understand the “pleiotropic” effects of VSMC on the atherosclerotic process. In addition, our understanding of the mechanisms of PCSK9 controlling VSMC functions in vivo is far from enough. This review aims to holistically evaluate and analyze the current state of our knowledge regarding PCSK9 actions affecting VSMC functions and its mechanism in atherosclerotic lesion development. A mechanistic understanding of PCSK9 effects on VSMC will further underpin the success of a new therapeutic strategy targeting AS.