Decreased GATA3 levels cause changed mouse cutaneous innate lymphoid cell fate, facilitating hair follicle recycling.

In mice, skin-resident type 2 innate lymphoid cells (ILC2s) exhibit some ILC3-like characteristics. However, the underlying mechanism remains elusive. Here, we observed lower expression of the ILC2 master regulator GATA3 specifically in cutaneous ILC2s (cILC2s) compared with canonical ILC2s, in line with its functionally divergent role in transcriptional control in cILC2s. Decreased levels of GATA3 enabled the expansion of RORγt fate-mapped (RORγtfm+) cILC2s after postnatal days, displaying certain similarities to ILC3s. Single-cell trajectory analysis showed a sequential promotion of the RORγtfm+ cILC2 divergency by RORγt and GATA3. Notably, during hair follicle recycling, these RORγtfm+ cILC2s accumulated around the hair follicle dermal papilla (DP) region to facilitate the process. Mechanistically, we found that GATA3-mediated integrin α3ß1 upregulation on RORγtfm+ cILC2s was required for their positioning around the DP. Overall, our study demonstrates a distinct regulatory role of GATA3 in cILC2s, particularly in promoting the divergence of RORγtfm+ cILC2s to facilitate hair follicle recycling.

Association of serum 25-hydroxyvitamin D levels with aggressiveness of papillary thyroid cancer.

Objective: Serum 25-hydroxyvitamin D (25(OH)D) deficiency has been known to be associated with the risk and mortality of several cancers. However, the role of 25(OH)D in papillary thyroid cancer (PTC) remains controversial. This study aimed to investigate the association between 25(OH)D and clinicopathologic features of PTC. Methods: Patients who underwent thyroidectomy were retrospectively reviewed. Serum 25(OH)D levels were measured within a week prior to surgery. The patients were categorized into four quartiles according to season-specific 25(OH)D levels. The association between 25(OH)D levels and clinicopathologic features of PTC was analyzed. Results: A total of 2932 patients were enrolled in the study. The 25(OH)D levels were significantly higher in patients with lymph node metastasis (LNM; P < 0.001), lateral LNM (P < 0.001), and multifocal tumors (P < 0.001). Compared to the first quartile (Q1) of 25(OH)D level, the third quartile (Q3) and the fourth quartile (Q4) showed an unadjusted OR of 1.36 (95% CI: 1.09-1.69; P = 0.006) and 1.76 (95% CI: 1.42-2.19; P < 0.001) for LNM (P for trend < 0.001), respectively. An increased risk of multifocal tumors was strongly associated with high 25(OH)D concentration (P for trend <0.001). Similar results were obtained after adjusting for confounding factors. Conclusion: High 25(OH)D levels are associated with aggressive features of PTC, such as lymph node metastasis and multifocality.

Layered GelMA/PEGDA Hydrogel Microneedle Patch as an Intradermal Delivery System for Hypertrophic Scar Treatment.

Hypertrophic scar (HS) is an unfavorable skin disorder that typically develops after trauma, burn injury, or surgical procedures and causes numerous physical and psychological issues in patients. Currently, intralesional multi-injection of corticosteroid, particularly compound betamethasone (CB), is one of the most prevalent treatments for HS. However, injection administration could result in severe pain and dose-related side effects. Additionally, the vacuum therapeutic efficacy of this treatment relies on the level of expertise of the healthcare professional. To overcome the limitations of conventional injections, a new method that is convenient, painless, and self-administrable is urgently required. In this study, we developed a methacrylate gelatin (GelMA)/polyethylene glycol diacrylate (PEGDA) double-network hydrogel microneedle patch loaded with CB (CB-HMNP) as an intradermal delivery system for HS treatment. The double-network structure conferred the CB-HMNP with sufficient mechanical properties to successfully penetrate scar tissue while also helping to regulate the drug's sustained release rate. Subsequently, we confirmed that the CB-HMNP had a pronounced inhibitory effect on human HS fibroblasts (hHSFs), whereas drug-free HMNPs had no effect on hHSFs, indicating its high biocompatibility. In order to assess the therapeutic efficacy of CB-HMNPs, HS models of New Zealand rabbit ears were developed. The administration of CB-HMNP three times significantly decreased the scar elevation index (SEI), collagen I/III, and transforming growth factor-ß1 (TGF-ß1) protein. Therefore, the CB-HMNP may offer an administration pathway for the treatment of HS that is less painful, more convenient, less invasive, and sustain-released.

UCA1 executes an oncogenic role in pancreatic cancer by regulating miR-582-5p/BRCC3.

Background: As a fatal disease, the mechanism of pancreatic cancer is unclear. Urothelial carcinoma antigen 1(UCA1), a long noncoding RNA (lncRNA) that was first reported in bladder cancer, acts as an oncogene. However, the regulatory role and mechanism of UCA1 in pancreatic cancer remain unknown. This study aims to investigate the expression level and prognostic value of UCA1 in pancreatic cancer tissues, the effects and mechanism of UCA1 in regulating cell proliferation, apoptosis and metastasis. Methods: UCA1 expression levels in tissues were detected by in situ hybridization (ISH) and the prognostic value was evaluated by univariate and multivariate survival analysis. For in vitro experiments, proliferation was evaluated by a cell count kit assay, Edu experiments, and a clone formation assay. Apoptosis was evaluated by fluorescence-activated cell sorting flow-cytometry. Cell migration and invasion capacities were detected by wound healing and transwell assays. Western blots were performed to detect apoptotic associated molecules and epithelial-mesenchymal transition (EMT) markers. For the in vivo experiment, subcutaneous transplantation models of pancreatic cancer in nude mice were established to observe the tumor growth. The regulatory mechanism of UCA1 was explored by proteomics, bioinformatic analysis, luciferase reporter assays, and rescue experiments. Results: ISH staining revealed that UCA1 levels between cancer tissues (n=94) and tumor-adjacent tissues (n=73) did not show significant differences. Survival analysis indicated that high expression of UCA1 was an unfavorable prognosis factor for pancreatic cancer. Downregulation of UCA1 by siRNA significantly inhibited cell proliferation, decreased the capacities of cell migration and invasion, induced cell apoptosis, and inhibited EMT. Furthermore, we demonstrated that UCA1 positively regulated the expression of BRCC3 by inhibiting miR-582-5p. Rescue experiments indicated that either inhibiting the expression of miR-582-5p or enhancing expression of BRCC3 could partly attenuate the antitumor effects of downregulation of UCA1. Conclusion: UCA1 acted as an oncogene in pancreatic cancer by partly regulating miR-582-5p/BRCC3, which could be a new therapeutic target for pancreatic cancer.

3D light-curing printing to construct versatile octopus-bionic patches.

Reliable, fast and switchable gluing modes are critically important in medical adhesives and intelligent climbing robot applications. The octopus-bionic patch has attracted the attention of many scholars. The suction cup structure of the octopus achieves adhesion through differential pressure, showing strong adhesion in both dry and wet environments. However, the construction of the octopus-bionic patch remains limited in terms of adaptability, personalization and mass production. Herein, a composite hydrogel consisting of gelatin methacryloyl (GelMA), polyethylene glycol diacrylate (PEGDA) and acrylamide (AAM) was developed, and a structure mimicking the octopus sucker was constructed by digital light processing (DLP). The obtained octopus-bionic patch has strong adhesion, good biocompatibility and multi-functionality. Compared with the template method in most studies, the octopus-bionic patch constructed by the DLP printing method has the advantages of customizability and low cost. In addition, the DLP printing method endows the patch surface with an octopus-like groove structure for a better bionic effect.

Free-standing two-dimensional sheets of polymer-linked nanoparticles.

Here, we report a simple and general approach to fabricate free-standing two-dimensional (2D) sheets of nanoparticles by the simultaneous self-assembly of hydrophobic nanoparticles and hydrophilic polymers at the liquid-liquid interface. The nanoparticle-polymer interaction at the interface generates well-defined 2D sheets of densely packed nanoparticles with a lateral dimension of tens of micrometers. The nanosheets transferred in water are stable over months without any additional cross-linking step. The method is applicable for a broad range of nanoparticles including oxide, semiconductor, and metal nanoparticles as well as functional polymers.

Active constituent of Polygala tenuifolia attenuates cognitive deficits by rescuing hippocampal neurogenesis in APP/PS1 transgenic mice.

BACKGROUND: Alzheimer's disease (AD) is the most common dementia worldwide, and there is still no satisfactory drug or therapeutic strategy. Polygala tenuifolia is a traditional Chinese medicine with multiple neuroprotective effects. In present study, we investigated the effects of three active constituents [3,6'-disinapoyl sucrose (DISS), onjisaponin B (OB) and tenuifolin (TEN)] of Polygala tenuifolia (PT) on the proliferation and differentiation of neural stem cells (NSCs) to identify the potential active constituent of PT promoting hippocampal neurogenesis. METHODS: NSCs were isolated from hippocampi of newborn C57BL/6 mice, and transfected with mutant amyloid precursor protein (APP) gene to establish an AD cell model (APP-NSCs). 3-(4,5- Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were performed, and the proliferation and differentiation of NSCs were assessed by neurosphere formation assay, 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and immunofluorescence (IF) staining analysis. APP/PS1 transgenic mice were administrated with the potential active constituent DISS for 4 weeks. Morris water maze (MWM), Nissl staining assay and IF staining assays were carried out to evaluate the cognitive function, neural damages and hippocampal neurogenesis, respectively. RESULTS: DISS exerted the optimal ability to strengthen APP-NSCs proliferation and neuronal differentiation, followed by OB and TEN. Furthermore, DISS treatment for 4 weeks strikingly rescued the cognitive deficits, neuronal injures, and neurogenesis disorder in adult APP/PS1 transgenic mice. CONCLUSIONS: Our findings demonstrated that DISS is the constituent of PT that triggers the most potent increase of hippocampal neurogenesis in our mouse model of AD.

Application of comprehensive u nit-based safety program model in the inter-hospital transfer of patients with critical diseases: a retrospective controlled study.

BACKGROUND: To explore the effect of applying a comprehensive unit-based safety program (CUSP) in the intrahospital transfer of patients with critical diseases. METHODS: A total of 426 critically ill patients in the first affiliated Hospital of Anhui Medical University from August 2018 to February 2019 were divided into two groups according to the time of admission. Overall, 202 patients in the control group were treated with the routine transfer method, and 224 patients in the observational group were treated with the transfer method based on the CUSP model. The safety culture assessment data of medical staff, the occurrence rate of adverse events and related causes, the time of transfer, and the satisfaction of patients' relatives to the transfer process were compared before and after implementation of the transfer model between the two groups. RESULTS: Before and after the implementation of the CUSP mode transfer program, there were significant differences in the scores of all dimensions of the safety culture assessment of medical staff (P < 0.05), and the occurrence rate of adverse events and the causes in the observational group were significantly lower than those in the control group (disease-related, staff-related, equipment-related, environment-related) (P < 0.05). The transfer time for Computed Tomography (CT), Magnetic Resonance Imaging (MRI), operating room, and the interventional room was significantly shorter in the observational group than that in the control group (P < 0.05), while the satisfaction of relatives to the transfer process was significantly higher than those in the control group (P < 0.05). CONCLUSION: The implementation of CUSP model for the intrahospital transfer of critically ill patients can significantly shorten the in-hospital transfer time, improve the attitude of medical staff towards safety, reduce the occurrence rate of adverse events, and improve the satisfaction of patients' relatives to the transfer process.

Janus Nanosheets with Face-Selective Molecular Recognition Properties from DNA-Peptide Conjugates.

Chemical and functional anisotropy in Janus materials offer intriguing possibilities for constructing complex nanostructures and regulating chemical and biological reactions. Here, the authors report the fabrication of Janus nanosheets from molecular building blocks composed of two information-carrying biopolymers, DNA and peptides. Experimental and structural modeling studies reveal that DNA-peptide diblock conjugates assemble into Janus nanosheets with distinct DNA and peptide faces. The surprising level of structural control is attributed to the exclusive parallel ß-sheet formation of phenylalanine-rich peptides. This approach is extended to triblock DNA1-peptide-DNA2 conjugates, which assemble into nanosheets presenting two different DNA on opposite faces. The Janus nanosheets with independently addressable faces are utilized to organize an enzyme pair for concerted enzymatic reactions, where enhanced catalytic activities are observed. These results demonstrate that the predictable and designable peptide interaction is a promising tool for creating Janus nanostructures with regio-selective and sequence-specific molecular recognition properties.

Peptide-Driven Shape Control of Low-Dimensional DNA Nanostructures.

We report the rational design and fabrication of unusual low-dimensional DNA nanostructures through programmable and sequence-specific peptide interactions. Dual-bioactive block copolymers composed of DNA and amino acid-based polymers (DNA-b-poly(amino acid)) were synthesized by coupling oligonucleotides to phenylalanine (Phe)-based polymers. Unlike prototypical DNA block copolymers, which typically form simple spherical micelles, DNA-b-poly(amino acid) assemble into various low-dimensional structures such as nanofibers, ribbons, and sheets through controllable amino acid interactions. Moreover, DNA-b-poly(amino acid) assemblies can undergo protease-induced fiber-to-sheet shape transformations, where the morphology change is dictated by the type of enzymes and amino acid sequences. The peptide-based self-assembly reported here provides a programmable approach to fabricate dynamic DNA assemblies with diverse and unusual low-dimensional structures.

Dynamic Nanostructures from DNA-Coupled Molecules, Polymers, and Nanoparticles.

Dynamic and reconfigurable systems that can sense and react to physical and chemical signals are ubiquitous in nature and are of great interest in diverse areas of science and technology. DNA is a powerful tool for fabricating such smart materials and devices due to its programmable and responsive molecular recognition properties. For the past couple of decades, DNA-based self-assembly is actively explored to fabricate various DNA-organic and DNA-inorganic hybrid nanostructures with high-precision structural control. Building upon past development, researchers have recently begun to design and assemble dynamic nanostructures that can undergo an on-demand transformation in the structure, properties, and motion in response to various external stimuli. In this Review, recent advances in dynamic DNA nanostructures, focusing on hybrid structures fabricated from DNA-conjugated molecules, polymers, and nanoparticles, are introduced, and their potential applications and future perspectives are discussed.

DNA-Grafted Poly(acrylic acid) for One-Step DNA Functionalization of Iron Oxide Nanoparticles.

Here, we report one-step DNA functionalization of hydrophobic iron oxide nanoparticles (IONPs) using DNA-grafted poly(acrylic acid) (PAA- g-DNA). PAA- g-DNA was synthesized by coupling PAA to amine-modified oligonucleotides via solid-phase amide chemistry, which yielded PAA grafted with multiple DNA strands with high graft efficiencies. Synthesized PAA- g-DNA was utilized as a phase-transfer and DNA functionalization agent for hydrophobic IONPs, taking advantage of unreacted carboxylic acid groups. The resulting DNA-modified IONPs were well dispersed in aqueous solutions and possessed DNA binding properties characteristic of polyvalent DNA nanostructures, showing that this approach provides a simple one-step method for DNA functionalization of hydrophobic IONPs.

Multimodal Shape Transformation of Dual-Responsive DNA Block Copolymers.

Herein, we report the self-assembly and multimodal shape transformation of dual-responsive DNA di- and triblock copolymers. Dual-responsive DNA diblock copolymer was synthesized by coupling a thermoresponsive polymer, poly(N-isopropylacrylamide (PNIPAM), and an oligonucleotide. DNA-b-PNIPAM possesses thermoresponsive properties of PNIPAM as well as molecular recognition properties of DNA. Thus, they undergo reversible temperature-triggered transition at lower critical solution temperature (LCST) between molecular DNA and polymer micelles with high density DNA corona. The hybridization of DNA-b-PNIPAM and DNA-modified nanoparticles generates functional nanoparticles showing unique temperature-dependent aggregation and disaggregation behaviors due to the dual-responsive nature of DNA-b-PNIPAM. DNA triblock copolymers of DNA-b-PNIPAM-b-PMA were synthesized by introducing a hydrophobic block, poly(methyl acrylate) (PMA), to DNA/PNIPAM block copolymers, which form spherical micelles at room temperature. They are capable of nanoscale shape transformation through the combination of thermal trigger and DNA binding. DNA-b-PNIPAM-b-PMA micelles undergo sphere-to-cylinder shape changes above LCST due to the conformational change of PNIPAM. The shape change is reversible, and fast cylinder-to-sphere transition occurs when the temperature is lowered below LCST. The low temperature spherical morphology can also be accessed while keeping the temperature above LCST by introducing complementary DNA strands with single stranded overhang regions. These results demonstrate the multidimensional shape changing capability of DNA-b-PNIPAM-b-PMA enabled by the dual-responsive property.

Over-expression of CYP78A98, a cytochrome P450 gene from Jatropha curcas L, increases seed size of transgenic tobacco

Background: Jatropha curcas L. (further referred to as Jatropha), as a rapidly emerging biofuel crop, has attracted worldwide interest. However, Jatropha is still an undomesticated plant, the true potential of this shrub has not yet been fully realized. To explore the potential of Jatropha, breeding and domestication are needed. Seed size is one of the most important traits of seed yield and has been selected since the beginning of agriculture. Increasing the seed size is a main goal of Jatropha domestication for increasing the seed yield, but the genetic regulation of seed size in Jatropha has not been fully understood. Results: We cloned CYP78A98 gene from Jatropha,a homologue of CYP78A5 in Arabidopsis.Wefound that CYP78A98 was highly expressed in male flower, female flower, stem apex, leaf and developing seed. However, its transcripts were hardly detected in root and stem. CYP78A98 protein localized in endoplasmic reticulum (ER) and the hydrophobic domain at the N-terminus was essential for the correct protein localization. Furthermore, INNER NO OUTER promoter (pINO) drove specific overexpression of CYP78A98 in transgenic tobacco seeds resulted in increased seed size and weight, as well as improved seed protein and fatty acid content. Conclusions: The results indicated that CYP78A98 played a role in Jatropha seed size control. This may help us to better understand the genetic regulation of Jatropha seed development, and accelerate the breeding progress of Jatropha.

A novel chloroplastic isopentenyl diphosphate isomerase gene from Jatropha curcas: Cloning, characterization and subcellular localization

Background Jatropha curcas is a rich reservoir of pharmaceutically active terpenoids. More than 25 terpenoids have been isolated from this plant, and their activities are anti-bacterial, anti-fungal, anti-cancer, insecticidal, rodenticidal, cytotoxic and molluscicidal. But not much is known about the pathway involved in the biosynthesis of terpenoids. The present investigation describes the cloning, characterization and subcellular localization of isopentenyl diphosphate isomerase (IPI) gene from J. curcas. IPI is one of the rate limiting enzymes in the biosynthesis of terpenoids, catalyzing the crucial interconversion of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Results A full-length JcIPI cDNA consisting of 1355 bp was cloned. It encoded a protein of 305 amino acids. Analysis of deduced amino acid sequence predicted the presence of conserved active sites, metal binding sites and the NUDIX motif, which were consistent with other IPIs. Phylogenetic analysis indicated a significant evolutionary relatedness with Ricinus communis. Southern blot analysis showed the presence of an IPI multigene family in J. curcas. Comparative expression analysis of tissue specific JcIPI demonstrated the highest transcript level in flowers. Abiotic factors could induce the expression of JcIPI. Subcellular distribution showed that JcIPI was localized in chloroplasts. Conclusion This is the first report of cloning and characterization of IPI from J. curcas. Our study will be of significant interest to understanding the regulatory role of IPI in the biosynthesis of terpenoids, although its function still needs further confirmation.