Vitamin D accelerates the subdural hematoma clearance through improving the meningeal lymphatic vessel function.

Subdural hematoma (SDH) drains into the extracranial lymphatic system through the meningeal lymphatic vessels (mLVs) but the formation of SDH impairs mLVs. Because vitamin D (Vit D) can protect the endothelial cells, we hypothesized that Vit D may enhance the SDH clearance. SDH was induced in Sprague-Dawley rats and treated with Vit D or vehicle. Hematoma volume in each group was measured by H&E staining and hemoglobin quantification. Evans blue (EB) quantification and red blood cells injection were used to evaluated the drainage of mLVs. Western blot analysis and immunofluorescence were conducted to assess the expression of lymphatic protein markers. We also examined the inflammatory factors levels in subdural space by ELISA. Vit D treatment significantly reduced SDH volume and improved the drainage of SDH to cervical lymph nodes. The structure of mLVs in SDH rats were protected by Vit D, and the expressions of LYVE1, PROX1, FOXC2, and VE-cadherin were increased after Vit D treatment. The TNF-α, IL-6, and IL-8 levels were reduced in Vit D group. In vitro, Vit D also increased the VE-cadherin expression levels under inflammation. Vit D protects the structure of mLVs and enhances the absorption of SDH, partly by the anti-inflammatory effect of Vit D.

Mutagenesis-Derived Resistance to Black Point in Wheat.

Black point, a severe global wheat disease, necessitates deploying resistant cultivars for effective control. However, susceptibility remains prevalent among most wheat cultivars. Identifying new sources of resistance and understanding their mechanisms are crucial for breeding resistant cultivars. This study pinpointed black point resistance in an ethyl methane sulfonate (EMS)-mutagenized wheat population of Wanyuanbai 1 (WYB) and analyzed resistant mutants using RNA-Seq. The findings revealed the following: (i) wyb-18, among 10,008 EMS-mutagenized lines, exhibited robust resistance with significantly lower black point incidence under artificial Bipolaris sorokiniana inoculation in 2020 and 2021 (average incidence of 5.2% over 2 years), markedly reduced compared with WYB (50.9%). (ii) wyb-18 kernels displayed black point symptoms at 12 days after inoculation (dai), 3 days later than WYB. At 15 dai, wyb-18 kernels had isolated black spots, unlike WYB kernels, where the entire embryo turned black. (iii) wyb-18 showed heightened antioxidant enzyme activity, including peroxidase, catalase, and superoxide dismutase. (iv) Analysis of 543 differentially expressed genes between wyb-18 and WYB at 9 dai identified enrichment in the MAPK signaling pathway through KEGG analysis. Ten genes in this pathway exhibited upregulated expression, while one was downregulated in wyb-18. Among these genes, PR1, WRKY11, SAPK5, and TraesCS1A02G326800 (chitin recognition protein) consistently showed upregulation in wyb-18, making them potential candidates for black point resistance. These results offer valuable germplasm resources for breeding and novel insights into the mechanisms of black point resistance.

Antiviral RNA interference in disease vector (Asian longhorned) ticks.

Disease vectors such as mosquitoes and ticks play a major role in the emergence and re-emergence of human and animal viral pathogens. Compared to mosquitoes, however, much less is known about the antiviral responses of ticks. Here we showed that Asian longhorned ticks (Haemaphysalis longicornis) produced predominantly 22-nucleotide virus-derived siRNAs (vsiRNAs) in response to severe fever with thrombocytopenia syndrome virus (SFTSV, an emerging tick-borne virus), Nodamura virus (NoV), or Sindbis virus (SINV) acquired by blood feeding. Notably, experimental acquisition of NoV and SINV by intrathoracic injection also initiated viral replication and triggered the production of vsiRNAs in H. longicornis. We demonstrated that a mutant NoV deficient in expressing its viral suppressor of RNAi (VSR) replicated to significantly lower levels than wildtype NoV in H. longicornis, but accumulated to higher levels after knockdown of the tick Dicer2-like protein identified by phylogeny comparison. Moreover, the expression of a panel of known animal VSRs in cis from the genome of SINV drastically enhanced the accumulation of the recombinant viruses. This study establishes a novel model for virus-vector-mouse experiments with longhorned ticks and provides the first in vivo evidence for an antiviral function of the RNAi response in ticks. Interestingly, comparing the accumulation levels of SINV recombinants expressing green fluorescent protein or SFTSV proteins identified the viral non-structural protein as a putative VSR. Elucidating the function of ticks' antiviral RNAi pathway in vivo is critical to understand the virus-host interaction and the control of tick-borne viral pathogens.

Integrative mRNA-miRNA interaction analysis associated with the immune response of Strongylocentrotus intermedius to Vibrio harveyi infection.

Strongylocentrotus intermedius is one of the most economically valuable sea urchin species in China and has experienced mass mortality owing to outbreaks of bacterial diseases such as black mouth disease. This has caused serious economic losses to the sea urchin farming industry. To investigate the immune response mechanism of S. intermedius with different tube feet colors in response to Vibrio harveyi infection, we examined the different tube feet-colored S. intermedius under V. harveyi challenge and compared their transcriptome and microRNA (miRNA) profiles using RNA-Seq. We obtained 1813 differentially expressed genes (DEGs), 28 DE miRNAs, and 303 DE miRNA-DEG pairs in different tube feet-colored S. intermedius under V. harveyi challenge. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the most significant DEGs were associated with the Notch signaling and phagosome pathways. The target genes of immune-related miRNAs (miR-71, miR-184, miR-193) and genes (CALM1, SPSB4, DMBT, CSRP1) in S. intermedius were predicted and validated. This study provides insight into the molecular mechanisms that regulate genes involved in the immune response of S. intermedius infected with V. harveyi.

Quantitative trait loci for resistance to black point caused by Bipolaris sorokiniana in bread wheat.

Black point disease is a serious concern in wheat production worldwide. In this study, we aimed to identify the major quantitative trait loci (QTL) for resistance to black point caused by Bipolaris sorokiniana and develop molecular markers for marker-assisted selection (MAS). A recombinant inbred line (RIL) population derived from a cross between PZSCL6 (highly susceptible) and Yuyou1 (moderately resistant) was evaluated for black point resistance at four locations under artificial inoculation with B. sorokiniana. Thirty resistant and 30 susceptible RILs were selected to form resistant and susceptible bulks, respectively, which were genotyped by the wheat 660 K SNP array. Two hundred and four single-nucleotide polymorphisms (SNPs) were identified, among which 41(20.7%), 34 (17.2%), 22 (11.1%), and 22 (11.1%) were located on chromosomes 5A, 5B, 4B, and 5D, respectively. The genetic linkage map for the RIL population was constructed using 150 polymorphic SSR and dCAPS markers. Finally, five QTL were detected on chromosomes 5A, 5B, and 5D, designated QBB.hau-5A, QBB.hau-5B.1, QBB.hau-5B.2, QBB.hau-5D.1, and QBB.hau-5D.2, respectively. All resistance alleles were contributed by the resistant parent Yuyou1. QBB.hau-5D.1 is likely to be a new locus for black point resistance. The markers Xwmc654 and Xgwm174 linked to QBB.hau-5A and QBB.hau-5D.1, respectively, have potential utility in MAS-based breeding. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01356-6.

Association between preadmission low-density lipoprotein cholesterol concentration and risk of large intracerebral hemorrhage: Results from the Kailuan study.

BACKGROUND: To examine the association between low-density lipoprotein cholesterol (LDL-C) concentrations and the risk of a large hematoma volume after intracerebral hemorrhage (ICH). METHODS: Patients from the Kailuan study (Tangshan, China) who were hospitalized with ICH during 2006 and 2020 were included in this study. The concentration of lipid concentrations, hematoma volume and other clinical characteristics were retrospectively collected and analyzed. Hematoma volumes were measured on the first available brain scan using the ABC/2 method. LDL-C concentrations were obtained from the last physical examination before the occurrence of ICH. LDL-C concentration was categorized into four groups in accordance with the quartiles. Logistic regression was used to assess the association between LDL-C concentrations and the risk of a large hematoma volume of ≥30 ml. A generalized linear regression model was used to analyze the dose-response relationship between LDL-C concentration and hematoma volume. RESULTS: A total of 836 patients with ICH were evaluated. In the Multivariate logistic regression, compared to the second quartile of LDL_C, the first quartile of LDL_C had a significantly higher risk of a large hematoma volume (OR 2.49 [95% CI 1.54-4.01]), and the higher quartile of LDL_C is not associated with higher odds of large hematoma volume. In the generalized linear regression model, the adjusted ß for the association between LDL-C concentration and hematoma volume was 9.46 (95% confidence interval 2.87-16.04), whereas higher LDL-C concentration was not associated with a large hematoma volume. CONCLUSIONS: This study confirmed that low LDL-C concentrations prior to ICH are associated with a higher risk of a large hematoma volume.

The inflammatory cellular feature in the peripheral blood of chronic subdural hematoma patients.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common neurosurgical disease with an increasing incidence. The absorption route of CSDH is not clear. Whether inflammatory factors enter the peripheral blood and cause systemic reactions is unknown. METHODS: We screened 105 CSDH patients and 105 control individuals. Their clinical characteristics and blood routine results were collected and compared. The blood routine changes of CSDH patients before and after treatment were compared. Age-stratified analysis was performed due to age may affect the inflammatory markers. RESULTS: The white blood cell count, absolute neutrophil count, neutrophil percentage, neutrophil-lymphocyte count ratio (NLR), and platelet to lymphocyte count ratio (PLR) of CSDH patients before treatment were within the normal range, while were significantly higher than the control individuals (p < 0.001). The absolute lymphocyte count and lymphocyte percentage of control individuals were higher than those of patients (p < 0.001). The inflammatory cells in patients of different age groups were similar. After the patient was cured, the white blood cell count, the absolute value and percentage of neutrophils decreased (p < 0.05), while the number of monocytes increased. CONCLUSIONS: CSDH caused slight systemic inflammatory responses in the peripheral blood, implying that there is a non-hematologic route for the absorption of hematoma.

A National Network of Safe Havens: Scottish Perspective.

For over a decade, Scotland has implemented and operationalized a system of Safe Havens, which provides secure analytics platforms for researchers to access linked, deidentified electronic health records (EHRs) while managing the risk of unauthorized reidentification. In this paper, a perspective is provided on the state-of-the-art Scottish Safe Haven network, including its evolution, to define the key activities required to scale the Scottish Safe Haven network's capability to facilitate research and health care improvement initiatives. A set of processes related to EHR data and their delivery in Scotland have been discussed. An interview with each Safe Haven was conducted to understand their services in detail, as well as their commonalities. The results show how Safe Havens in Scotland have protected privacy while facilitating the reuse of the EHR data. This study provides a common definition of a Safe Haven and promotes a consistent understanding among the Scottish Safe Haven network and the clinical and academic research community. We conclude by identifying areas where efficiencies across the network can be made to meet the needs of population-level studies at scale.

Study on site selection of municipal solid waste incineration plant based on swarm optimization algorithm.

In this paper, based on an improved swarm optimization algorithm, a new site selection model of a municipal solid waste (MSW) incineration plant is proposed. First, the whale optimization algorithm and particle swarm optimization algorithm are combined according to certain rules to improve the performance of the hybrid algorithm. Through a verification of the single and multi-peak functions, the results show that the algorithm achieves a good performance. The location model of the MSW incineration plant is based on many factors, including the economy, environmental protection, population scale, and operation cost. Finally, based on a sample analysis, a new location model of an MSW incineration plant is used to select the location of an Anshan MSW incineration plant, and a reasonable location is obtained.

Cell type-specific evaluation of ADGRG1/GPR56 function in developmental central nervous system myelination.

Myelination of axons in the central nervous system (CNS) is a concerted effort between many cell types, resulting in significant cross-talk and communication among cells. Adhesion G protein-coupled receptor ADGRG1 (GPR56) is expressed in all major glial cells and regulates a wide variety of physiological processes by mediating cell-cell and cell-matrix communications. Previous literature has demonstrated the requirement of ADGRG1 in oligodendrocyte precursor cells (OPCs) during developmental myelination. However, it is unknown if ADGRG1 is responsible for myelin formation in a cell-type-specific manner. To that end, here we profiled myelin status in response to deletion of Adgrg1 specifically in OPCs, microglia, astrocytes, and neurons. Interestingly, we find that knocking out Adgrg1 in OPCs significantly decreases OPC proliferation and reduced number of myelinated axons. However, deleting Adgrg1 in microglia, astrocytes, and neurons does not impact developmental myelination. These data support an autonomous functional role for Adgrg1 in OPCs related to myelination.

Dexamethasone enhances the efficacy of atorvastatin in inhibiting excessively inflammation-induced abnormal angiogenesis by regulating macrophages.

BACKGROUND: We have recently showed that atorvastatin (ATO) combined with low dose of dexamethasone (DEX) was more efficacious in treating patients with chronic subdural haematoma (CSDH) than ATO monotherapy. This study was designed to investigate the underlying mechanisms of the improved efficacy of this combined therapy. METHODS: Mass spectrometry was performed to quantitatively detect drugs in haematoma fluids and serum samples from CSDH patients and also in cultured macrophages after treatment with either ATO alone or in combination with DEX. The differentiation and apoptosis of macrophages were evaluated using flow cytometry. The expression of cytokines, chemokines and angiogenesis-related proteins was evaluated using proteome profile arrays, immunoblots and ELISA, respectively. RESULTS: ATO was detected in haematoma fluids and serum samples, whose levels were increased significantly in samples collected from patients treated with both ATO and DEX. ATO was also increased in cultured macrophages treated with ATO and DEX. The numbers of M1-polarized macrophages were higher than the M2 phenotype in the haematoma fluids of patients. Cultured macrophages treated with ATO and DEX had reduced numbers of M1-polarized macrophages, increased numbers of M2-polarized macrophages as compared to monotherapies, and decreased rate of apoptosis induced by high-dose DEX. DEX enhanced the anti-inflammatory and anti-angiogenic activity of ATO by suppressing VEGFA and other inflammatory angiogenic factors. Consistent with the finding, patients responded well to the drug treatments had lower serum levels of VEGFA. CONCLUSIONS: We have shown for the first time that ATO given orally was detected in CSDH haematoma fluids. DEX enhances the anti-inflammatory and anti-angiogenic effects of ATO, primarily by increasing the presence of ATO in haematoma and macrophages and by regulating the functions of macrophages.

Effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia: a multicenter study in Hubei Province, China. / çª’æ¯æ–°ç”Ÿå„¿ç³–ä»£è°¢ç´Šä¹±å¯¹è¿‘æœŸé¢„åŽçš„å½±å“ï¼šä¸€é¡¹æ¹–åŒ—çœå¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia. METHODS: A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%, P<0.05) or with severe asphyxia (19.8% vs 8.1%, P<0.05) or hypothermia therapy (4.8% vs 1.5%, P<0.05), as well as a significantly higher incidence rate of disorder of glucose metabolism (18.8% vs 12.5%, P<0.05). Compared with the good prognosis group, the poor prognosis group had a significantly higher incidence rate of disorder of glucose metabolism at 1, 2, and 6 hours after birth (P<0.05). The multivariate logistic regression analysis showed that recurrent hyperglycemia (adjusted odds ratio=2.380, 95% confidence interval: 1.275-4.442, P<0.05) was an independent risk factor for poor prognosis in neonates with asphyxia. CONCLUSIONS: Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.

Low-temperature laminar flow ward for the treatment of multidrug resistance Acinetobacter baumannii pneumonia.

This study was designed to investigate the effect of low-temperature laminar flow ward (LTLFW) on the Acinetobacter baumannii pneumonia (MDR-ABP) in neurosurgical intensive care unit (NICU) patients. We evaluated whether patients in a LTLFW had significantly improved clinical outcomes as compared to those in nonconstant-temperature NICU (room temperature). The association of temperature with the prevalence of ABP and A. baumannii isolates (ABI) found in NICU patients was specifically investigated. In vitro microbiological experiments were conducted to measure the proliferation, antibiotic sensitivity, and genomic profiles of A. baumannii (AB) that grew in variable temperatures. MDR-ABP patients in LTLFW had significantly improved outcomes than those in the room temperature NICU. In addition, the numbers of ABI were positively associated with mean ambient outdoor temperatures (P = 0.002), with the incidence of ABP and average numbers of ABI among NICU patients being substantially lower in the winter as compared to other seasons. However, there were no significant seasonal variations in the other strains of the top five bacteria. Consistent with these clinical observations, AB growing at 20°C and 25°C had significantly reduced viability and antibiotic resistance compared to those growing at 35°C. The expression of genes related to AB survival ability, drug resistance, and virulence also differed between AB growing at 20°C and those at 35°C. LTLFW is effective in promoting the recovery of MDR-ABP patients because low temperatures reduced the density and virulence of AB and enhanced the efficacy of antibiotics, likely at the genetic level.

Molecular immune mechanisms of HPV-infected HaCaT cells in vitro based on toll-like receptors signaling pathway.

OBJECTIVE: To explore the molecular immune mechanism of HPV-infected HaCaT cells in vitro based on TLRs signaling pathway by analyzing the effects of interfering TLRs on inflammatory and immune factors in the signaling pathway. METHODS: FCM was used to analyze the proportion of Th1, Th2, Th17, and Treg cells in blood samples. HPV-infected HaCaT cells were divided into five groups: A, B, C, D, and E. Group A added TLR3 antagonist, group B added TLR9 antagonist, group C added equivalent saline, group D added IRF3 agonist, and group E added IRF3 inhibitor. Immunohistochemistry was used to analyze the expression of TLR3 and TLR9 in HaCaT cell model; ELISA was used to analyze the expression of inflammatory factors IL-2, TNF-a, and IFN-beta; WB was used to analyze the expression of TRAF3, IKK epsilon, and TBK1; RT-PCR was used to analyze the expression of IRF3 and IRF7 in each cell model. RESULTS: The proportion of blood immune cells in patients with HPV infection was Th1, Th17, Th2, and Treg, with statistical significance (P < .05); the expression of TLR3 and TLR9 in HPV-infected cells was higher than that in negative control group, with statistical significance (P < .05); TLR3 was higher than TLR9, with no significant difference (P > .05); the expression of IL-2, TNF-alpha, IFN-beta in each group, TLR3, and TLR9 was higher than that in negative control group (P < .05). The expression of TRAF3, IKK epsilon, and TBK1 in the control group was higher than that in the TLR3 and TLR9 inhibitor groups, and the expression of IRF3 and IRF7 in the TLR9 inhibitor group was higher than that in the TLR3 inhibitor group (P < .05); the expression of IRF3 and IRF7 in the TLR3i and TLR9i inhibitor groups was lower than that in the TLR3 inhibitor group (P < .05). Compared with the control group, IRF3a group was higher than the control group, IRF3i group was lower than the control group, the difference was statistically significant (P < .05). CONCLUSION: TLR3 and TLR9, the key factors of TLRs, are highly expressed in HaCaT cells infected with HPV. Through TLRs-IKK-e-IRFs-IFN signaling pathway, they can induce high expression of inflammatory factors, IKK-e, IRFs, and IFN, and improve immunity.

Effects of Selenium Species on the Belousov-Zhabotinsky Reaction.

The effects of selenium species on the Belousov-Zhabotinsky (B-Z) reaction were investigated by adding them to the system before and during oscillation. When selenium species were added into the system before oscillation, sodium selenite prolonged the induction period, whose effect was strong as sodium selenite could consume malonic acid to prohibit the accumulation of bromomalonic acid. For selenomethionine and selenocystine, their effects were derived from their reaction with •CH2COOH and •Br2- producing a radical cation of selenoamino acids, which prohibited the accumulation of bromomalonic acid. Here, the selenium atoms in selenoamino acids, as reactive centers, took part in the redox reaction. As a result, the induction period was prolonged. However, as a diselenide, selenocystine can reduce bromate in acidic medium, which led to shortening of the induction period. Therefore, the effect of selenocystine on the induction period was the result of two opposite effects. Nanoselenium shortened the induction period in a certain concentration range because bromate was directly reduced by nanoselenium and the accumulation of bromomalonic acid was promoted. Furthermore, the dose perturbation effect was investigated by the injection of nanoselenium during oscillation. It was found that the amplitude was increased or decreased in a dose-dependent fashion when nanoselenium was injected at peak or trough of the time-dependent redox potential curve.

Amphiphilic Drug Conjugates as Nanomedicines for Combined Cancer Therapy.

Chemotherapy suffers from some limitations such as poor bioavailability, rapid clearance from blood, poor cellular uptake, low tumor accumulation, severe side effects on healthy tissues and most importantly multidrug resistance (MDR) in cancer cells. Nowadays, a series of smart drug delivery system (DDS) based on amphiphilic drug conjugates (ADCs) has been developed to solve these issues, including polymer-drug conjugate (PDC), phospholipid-mimicking prodrugs, peptide-drug conjugates (PepDCs), pure nanodrug (PND), amphiphilic drug-drug conjugate (ADDC), and Janus drug-drug conjugate (JDDC). These ADCs can self-assemble into nanoparticles (NPs) or microbubbles (MBs) for targeted drug delivery by minimizing the net amount of excipients, realizing great goals, such as stealth behavior and physical integrity, high drug loading content, no premature leakage, long blood circulation time, fixed drug combination, and controlled drug-release kinetics. Besides, these self-assembled systems can be further used to load additional therapeutic agents and imaging contrast agents for combined therapy, personalized monitoring of in vivo tumor targeting, and the pharmacokinetics of drugs for predicting the therapeutic outcome. In this review, we will summarize the latest progress in the development of ADCs based combination chemotherapy and discuss the important roles for overcoming the tumor MDR.

Non-Intrusive Cable Fault Diagnosis Based on Inductive Directional Coupling.

This paper presents and applies an inductive directional coupling technology based on spread spectrum time domain reflectometry (SSTDR) for non-intrusive power cable fault diagnosis. Different from existing capacitive coupling approaches with large signal attenuation, an inductive coupling approach with a capacitive trapper is proposed to restrict the detection signal from transmitting to power source and to eliminate the effect of the power source impedance mismatch. The development, analysis, and implementation of the proposed approach are discussed in detail. A series of simulations and experiments on cables with different fault modes are conducted, along with comparison of existing capacitive coupling, to verify and demonstrate the effectiveness of the proposed method.

Phase offset method of ptychographic contrast reversal correction.

The contrast transfer function of direct ptychography methods such as the single side band (SSB) method are single signed, yet these methods still sometimes exhibit contrast reversals, most often where the projected potentials are strong. In thicker samples central focusing often provides the best ptychographic contrast as this leads to defocus variations within the sample canceling out. However focusing away from the entrance surface is often undesirable as this degrades the annular dark field (ADF) signal. Here we discuss how phase wrap asymptotes in the frequency response of SSB ptychography give rise to contrast reversals, without the need for dynamical scattering, and how these can be counteracted by manipulating the phases such that the asymptotes are either shifted to higher frequencies or damped via amplitude modulation. This is what enables post collection defocus correction of contrast reversals. However, the phase offset method of counteracting contrast reversals we introduce here is generally found to be superior to post collection application of defocus, with greater reliability and generally stronger contrast. Importantly, the phase offset method also works for thin and thick samples where central focusing does not. Finally, the independence of the method from focus is useful for optical sectioning involving ptychography, improving interpretability by better disentangling the effects of strong potentials and focus.

Biofabrication of biomimetic undulating microtopography at the dermal-epidermal junction and its effects on the growth and differentiation of epidermal cells.

The undulating microtopography located at the junction of the dermis and epidermis of the native skin is called rete ridges (RRs), which plays an important role in enhancing keratinocyte function, improving skin structure and stability, and providing three-dimensional (3D) microenvironment for skin cells. Despite some progress in recent years, most currently designed and manufactured tissue-engineered skin models still cannot replicate the RRs, resulting in a lack of biological signals in the manufactured skin models. In this study, a composite manufacturing method including electrospinning, 3D printing, and functional coating was developed to produce the epidermal models with RRs. Polycaprolactone (PCL) nanofibers were firstly electrospun to mimic the extracellular matrix environment and be responsible for cell attachment. PCL microfibers were then printed onto top of the PCL nanofibers layer by 3D printing to quickly prepare undulating microtopography and finally the entire structures were dip-coated with gelatin hydrogel to form a functional coating layer. The morphology, chemical composition, and structural properties of the fabricated models were studied. The results proved that the multi-process composite fabricated models were suitable for skin tissue engineering. Live and dead staining, cell counting kit-8 (CCK-8) as well as histology (haematoxylin and eosin (HE) methodology) and immunofluorescence (primary and secondary antibodies combination assay) were used to investigate the viability, metabolic activity, and differentiation of skin cells forin vitroculturing.In vitroresults showed that each model had high cell viability, good proliferation, and the expression of differentiation marker. It was worth noting that the sizes of the RRs affected the cell growth status of the epidermal models. In addition, the unique undulation characteristics of the epidermal-dermal junction can be reproduced in the developed epidermal models. Overall, thesein vitrohuman epidermal models can provide valuable reference for skin transplantation, screening and safety evaluation of drugs and cosmetics.

Scaffold-Based Poly(Vinylidene Fluoride) and Its Copolymers: Materials, Fabrication Methods, Applications, and Perspectives.

Tissue engineering involves implanting grafts into damaged tissue sites to guide and stimulate the formation of new tissue, which is an important strategy in the field of tissue defect treatment. Scaffolds prepared in vitro meet this requirement and are able to provide a biochemical microenvironment for cell growth, adhesion, and tissue formation. Scaffolds made of piezoelectric materials can apply electrical stimulation to the tissue without an external power source, speeding up the tissue repair process. Among piezoelectric polymers, poly(vinylidene fluoride) (PVDF) and its copolymers have the largest piezoelectric coefficients and are widely used in biomedical fields, including implanted sensors, drug delivery, and tissue repair. This paper provides a comprehensive overview of PVDF and its copolymers and fillers for manufacturing scaffolds as well as the roles in improving piezoelectric output, bioactivity, and mechanical properties. Then, common fabrication methods are outlined such as 3D printing, electrospinning, solvent casting, and phase separation. In addition, the applications and mechanisms of scaffold-based PVDF in tissue engineering are introduced, such as bone, nerve, muscle, skin, and blood vessel. Finally, challenges, perspectives, and strategies of scaffold-based PVDF and its copolymers in the future are discussed.