Sex Differences in Prognosis of Childhood Arterial Ischemic Stroke: Results From Chinese Pediatric Ischemic Stroke Registry Multicenter Registry.

BACKGROUND: Current studies on the impact of sex in the prognosis of childhood arterial ischemic stroke (AIS) are limited. We aimed to explore the sex differences in outcomes in patients with childhood AIS. METHODS: A retrospective analysis was conducted using the prospective data from the Chinese Pediatric Ischemic Stroke Registry. Baseline characteristics between sexes were compared in the total population cohort, propensity score (PS)-matched cohort, and inverse probability of treatment weighting cohort. Multivariate logistic regression and ordinal regression were used to analyze the association of sex with outcomes. Mixed-effects regression model was applied to further analyze the improvement in pediatric modified Rankin Scale (mRS) scores between sexes from 90 days to one year. Survival analysis was used to estimate the recurrence rates during the follow-up period. RESULTS: A total of 468 patients were finally included. Multivariate logistic regression showed that there were no significant differences between females and males in achieving favorable outcome (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.63 to 1.72), functional independence (OR 0.98, 95% CI 0.59 to 1.63), or shift to worse pediatric mRS scores (OR 0.83, 95% CI 0.59 to 1.17) at 90-day. Mixed-effects regression and survival analysis indicated that females and males exhibited comparable functional recovery from 90 days to one year and had similar recurrent risk during the follow-up period. CONCLUSIONS: This nationally-representative observational study indicated that both male and female pediatric patients with AIS exhibited comparable similar clinical outcomes at 90 days, as well as similar improvements and risks of recurrence during the follow-up period.

circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models.

Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.

Dithiophosphinylation of Allenyl Acetates: Access to 1,2-Bis(diphenylphosphino)ethane-Type Bidentate Ligands.

1,2-Bis(diphenylphosphino)ethanes (DPPEs) are versatile and immensely important ligands in transition metal catalysts. Here we report the dithiophosphinylation of readily available allenyl acetates to give DPPEs in high yields and regioselectivity. This protocol features a broad substrate scope and mild conditions, avoiding the use of transition metals and air-sensitive sources of phosphorus. Mechanism studies indicate that the reaction was accomplished via an SN2'-type addition-elimination followed by a 1,4-addition step.

(Z, Z, Z)-3,6,9-Nonadecadiene, a potential inhibitor of sex pheromone of Grey Tea Geometrid (Lepidoptera: Geometridae): electroantennogram test, wind tunnel, and in silico study.

Sex pheromone analogs have high structural similarity to sex pheromone components. They also play a role in studying many agricultural pests. In our study, (Z, Z, Z)-3,6,9-nonadecadiene (Z3Z6Z9-19:Hy) was successfully synthesized, which is an analogue to 1 of 2 sex pheromone components of Ectropis grisescens Warren (Z, Z, Z)-3,6,9-octadecatriene (Z3Z6Z9-18:Hy), and it showed potential inhibition in experiments. In the electroantennogram test, Z3Z6Z9-19:Hy showed a dose-dependent response, and only measured half the response of Z3Z9-6,7-epo-18:Hy. However, the compound significantly reduced positive response of E. grisescens males by up to 70% in the Y-tube olfactometer. Furthermore, in the wind tunnel, it significantly inhibited all types of behavioral responses. The percentage of moths contacting the pheromone odor source was reduced even at the lowest dose tested. In silico study afterward, molecular docking results showed affinity between Z3Z6Z9-19:Hy and sensory neuron membrane protein 1. Our study revealed the potential of Z3Z6Z9-19:Hy as a sex pheromone inhibitor, which would provide new tools for monitoring and mating disruption of E. grisescens.

Unlocking the potential of senescence-related gene signature as a diagnostic and prognostic biomarker in sepsis: insights from meta-analyses, single-cell RNA sequencing, and in vitro experiments.

Cellular senescence is closely associated with the pathogenesis of sepsis. However, the diagnostic and prognostic value of senescence-related genes remain unclear. In this study, 866 senescence-related genes were collected from CellAge. The training cohort, GSE65682, which included 42 control and 760 sepsis samples, was obtained from the Gene Expression Omnibus (GEO). Feature selection was performed using gene expression difference detection, LASSO analysis, random forest, and Cox regression. TGFBI and MAD1L1 were ultimately selected for inclusion in the multivariate Cox regression model. Clustering based on the expressions of TGFBI and MAD1L1 was significantly associated with sepsis characteristics and prognoses (all P < 0.05). The risk signature served as a reliable prognostic predictor across the GSE65682, GSE95233, and GSE4607 cohorts (pooled hazard ratio = 4.27; 95% confidence interval [CI] = 1.63-11.17). Furthermore, it also served as a robust classifier to distinguish sepsis samples from control cases across 14 cohorts (pooled odds ratio = 5.88; 95% CI = 3.54-9.77). Single-cell RNA sequencing analyses from five healthy controls and four sepsis subjects indicated that the risk signature could reflect the senescence statuses of monocytes and B cells; this finding was then experimentally validated in THP-1 and IM-9 cells in vitro (both P < 0.05). In all, a senescence-related gene signature was developed as a prognostic and diagnostic biomarker for sepsis, providing cut-in points to uncover underlying mechanisms and a promising clinical tool to support precision medicine.

Ambient Degradation Anisotropy and Mechanism of van der Waals Ferroelectric NbOI2.

The spontaneous centrosymmetry-breaking and robust room-temperature ferroelectricity in niobium oxide dihalides spurs a flurry of explorations into its promising second-order nonlinear optical properties, and promises potential applications in nonvolatile electro-optical and optoelectronic devices. However, the ambient stability of the niobium oxide dihalides remains questionable, which overshadows their future development. In this work, the chemical degradation of NbOI2 is comprehensively investigated using combined chemical and optical microscopies in conjunction with spectroscopies. We unveil the highly anisotropic degradation kinetics of NbOI2 driven by the hydrolysis process of the unstable dangling iodine bonds dominantly on the (010) facet and progressing along the c axis. Knowing its degradation mechanism, the NbOI2 flake can then be stabilized by the hexagonal boron nitride encapsulation, which isolates the air moisture. These findings provide direct insights into the ambient instability of NbOI2, and they deliver possible solutions to circumvent this issue, which are essential for its practical integration in photonic and electronic devices.

Effective Long Afterglow Amplification Induced by Surface Coordination Interaction.

Long-persistent luminescent (LPL) materials have attracted considerable research interest due to their extensive applications and outstanding afterglow performance. However, the performance of red LPL materials lags behind that of green and blue materials. Therefore, it is crucial to explore novel red LPL materials. This study introduces a straightforward and viable strategy for organic-inorganic hybrids, wherein the organic ligand 1,3,6,8-Tetrakis(4-carboxyphenyl)pyrene (TCPP) is coordinated to the surface of a red persistent phosphor Sr0.75 Ca0.25 S:Eu2+ (R) through a one-step method. TCPP serves as an antenna, facilitating the transfer of absorbed light energy to R via triplet energy transfer (TET). Notably, the initial afterglow intensity and luminance of R increase by twofold and onefold, respectively, and the afterglow duration extends from 9 to 17 min. Furthermore, this study involves the preparation of a highly flexible film by mixing R@TCPP with high-density polyethylene (HDPE) to create a sound-controlled afterglow lamp. This innovative approach holds promising application prospects in flexible large-area luminescence, flexible wearables, and low-vision lighting.

Unconventional polarization fatigue in van der Waals layered ferroelectric ionic conductor CuInP2S6.

Recent progress in two-dimensional ferroelectrics greatly expands the versatility and tunability in van der Waals heterostructure based electronics. However, the switching endurance issue that widely plagues conventional ferroelectrics in practical applications is hitherto unexplored for van der Waals layered ferroelectrics. Herein, we report the observation of unusual polarization fatigue behaviors in van der Waals layered CuInP2S6, which also possesses finite ionic conductivity at room temperature. The strong intertwinement of the short-range polarization switching and long-range ionic movement in conjunction with the van der Waals layered structure gives rise to unique morphological and polarization evolutions under repetitive electric cycles. With the help of concerted chemical, structural, lattice vibrational and dielectric analyses, we unravel the critical role of the synergy of ionic migration and surface oxidation on the anomalous polarization enhancement and the eventual polarization degradation. This work provides a general insight into the polarization fatigue characteristics in ionically-active van der Waals ferroelectrics and delivers potential solutions for the realization of fatigue-free capacitors.

Embracing Large Natural Data: Enhancing Medical Image Analysis via Cross-domain Fine-tuning.

With the rapid advancements of big data and computer vision, many large-scale natural visual datasets are proposed, such as ImageNet-21K, LAION-400M, and LAION-2B. These large-scale datasets significantly improve the robustness and accuracy of models in the natural vision domain. However, the field of medical images continues to face limitations due to relatively small-scale datasets. In this paper, we propose a novel method to enhance medical image analysis across domains by leveraging pre-trained models on large natural datasets. Specifically, a Cross-Domain Transfer Module (CDTM) is proposed to transfer natural vision domain features to the medical image domain, facilitating efficient fine-tuning of models pre-trained on large datasets. In addition, we design a Staged Fine-Tuning (SFT) strategy in conjunction with CDTM to further improve the model performance. Experimental results demonstrate that our method achieves state-of-the-art performance on multiple medical image datasets through efficient fine-tuning of models pre-trained on large natural datasets. The code is available at https://github.com/qklee-lz/CDTM.

The effect of nebulized heparin on clinical outcomes in mechanically ventilated patients: a meta-analysis and review of the literature.

OBJECTIVE: To determine the relationship between use of nebulized heparin and clinical outcomes in mechanically ventilated patients. METHODS: The Medline, Embase, Web of Science, Cochrane Library, and PubMed databases were searched for relevant randomized controlled trials (RCTs), published between database inception and May 2022. Primary outcomes were intensive care unit (ICU) length of stay and in-hospital mortality; secondary outcomes included duration of mechanical ventilation, ventilator-free days (VFDs) in 28 days, and length of hospitalization. The study protocol was registered on PROSPERO (registration No: CRD42022345533). RESULTS: A total of eight RCTs (651 patients) were included. Nebulized heparin was associated with reduced ICU length of stay (six studies; mean difference [MD] -1.10, 95% confidence interval [CI] -1.87, -0.33, I2 = 76%), reduced duration of mechanical ventilation (two studies; MD -2.63, 95% CI -3.68, -1.58, I2 = 92%) and increased VFDs in 28 days (two studies; MD 4.22, 95% CI 1.10, 7.35, I2 = 18%), without increased incidence of adverse events, such as bleeding; but was not associated with a reduction in length of hospitalization (three studies; MD -1.00, 95% CI -2.90, -0.90, I2 = 0%) or in-hospital mortality (five studies; odds ratio 1.10, 95% CI 0.69, 1.77, I2 = 0%). CONCLUSION: Nebulized heparin reduces ICU length of stay and duration of mechanical ventilation in mechanically ventilated patients, but has no effect on length of hospitalization or mortality.

Construction of Ag-TiO2 Hierarchical Micro-/Nanostructures on a Ti Plate for Photocatalysts via Femtosecond Laser Hybrid Technology.

Titanium dioxide photocatalysts can break down pollutants using natural light. They possess notable light stability, chemical stability, and catalytic effects, thus leading to extensive research worldwide. However, the limited light absorption range of titanium dioxide and their inefficiencies in generating and transporting photogenerated carriers hinder the enhancement of their photocatalytic performance. In this study, we employ a femtosecond laser composite processing method to create an Ag-TiO2 nanoplate composite catalyst. This method doubles the catalytic efficiency compared with the structure processed solely with the femtosecond laser. The resulting Ag-TiO2 nanoplate composite catalysts show significant promise for addressing environmental and energy challenges, including the photodegradation of organic pollutants.

P-MSC-derived extracellular vesicles facilitate diabetic wound healing via miR-145-5p/ CDKN1A-mediated functional improvements of high glucose-induced senescent fibroblasts.

Background: Persistent hyperglycaemia in diabetes causes functional abnormalities of human dermal fibroblasts (HDFs), partially leading to delayed skin wound healing. Extracellular vesicles (EVs) containing multiple pro-healing microRNAs (miRNAs) have been shown to exert therapeutic effects on diabetic wound healing. The present study aimed to observe the effects of EVs derived from placental mesenchymal stem cells (P-MSC-EVs) on diabetic wound healing and high glucose (HG)-induced senescent fibroblasts and to explore the underlying mechanisms. Methods: P-MSC-EVs were isolated by differential ultracentrifugation and locally injected into the full-thickness skin wounds of diabetic mice, to observe the beneficial effects on wound healing in vivo by measuring wound closure rates and histological analysis. Next, a series of assays were conducted to evaluate the effects of low (2.28 x 1010 particles/ml) and high (4.56 x 1010 particles/ml) concentrations of P-MSC-EVs on the senescence, proliferation, migration, and apoptosis of HG-induced senescent HDFs in vitro. Then, miRNA microarrays and real-time quantitative PCR (RT-qPCR) were carried out to detect the differentially expressed miRNAs in HDFs after EVs treatment. Specific RNA inhibitors, miRNA mimics, and small interfering RNA (siRNA) were used to evaluate the role of a candidate miRNA and its target genes in P-MSC-EV-induced improvements in the function of HG-induced senescent HDFs. Results: Local injection of P-MSC-EVs into diabetic wounds accelerated wound closure and reduced scar widths, with better-organized collagen deposition and decreased p16INK4a expression. In vitro, P-MSC-EVs enhanced the antisenescence, proliferation, migration, and antiapoptotic abilities of HG-induced senescent fibroblasts in a dose-dependent manner. MiR-145-5p was found to be highly enriched in P-MSC-EVs. MiR-145-5p inhibitors effectively attenuated the P-MSC-EV-induced functional improvements of senescent fibroblasts. MiR-145-5p mimics simulated the effects of P-MSC-EVs on functional improvements of fibroblasts by suppressing the expression of cyclin-dependent kinase inhibitor 1A and activating the extracellular signal regulated kinase (Erk)/protein kinase B (Akt) signaling pathway. Furthermore, local application of miR-145-5p agomir mimicked the effects of P-MSC-EVs on wound healing. Conclusions: These results suggest that P-MSC-EVs accelerate diabetic wound healing by improving the function of senescent fibroblasts through the transfer of miR-145-5p, which targets cyclin-dependent kinase inhibitor 1A to activate the Erk/Akt signaling pathway. P-MSC-EVs are promising therapeutic candidates for diabetic wound treatment.

Palladium-Catalyzed Modular Assembly of P-Stereogenic and Axially Chiral Phosphinooxazoles (PHOX) Ligands by C-P Bond Cleavage/Intermolecular C(sp2)-H Bond Functionalization.

Chiral P,N-ligands are of great interest and importance in the fields of metal-catalyzed enantioselective transformations and have found numerous applications spanning drug and polymer synthesis. Here, modular assembly of diverse P-stereogenic and axially chiral phosphinooxazoles ligands is achieved through palladium-catalyzed asymmetric cleavage of C-P bond/intermolecular C-H bond functionalization in high atroposelectivities and diastereoselectivities of up to >99% ee and >25:1 dr. This protocol features broad substrate scope and provides an avenue for facile construction of new P-stereogenic and axially chiral phosphinooxazoles ligands directly from the phosphonium salts and benzoxazoles/benzothiazoles. Evaluation of the synthesized P-stereogenic and axially chiral phosphinooxazoles ligands in two model catalytic asymmetric reactions illustrates the potential of our strategy to access valuable chiral molecules.

Diversity-oriented synthesis of P-stereogenic and axially chiral monodentate biaryl phosphines enabled by C-P bond cleavage.

Chiral monodentate biaryl phosphines (MOPs) have attracted intense attention as chiral ligands over the past decades. However, the creation of structurally diverse chiral MOPs with both P- and axial chirality is still in high demand but challenging. Here, we show a distinct strategy for diversity-oriented synthesis of structurally diverse MOPs containing both P- and axial chirality enabled by enantioselective C-P bond cleavage. The key chiral PdII intermediates, generated through the stereoselective oxidative addition of C-P bond, could be trapped by alkynes, R3Si-Bpin, diboron esters or reduced by H2O/B2pin2, leading to enantioenriched structurally diverse MOPs in excellent diastereo- and enantioselectivities. Based on the outstanding properties of the parent scaffolds, the P- and axially chiral monodentate biaryl phosphines serve as excellent catalysts in asymmetric [3 + 2] annulation of MBH carbonate affording the chiral functionalized bicyclic imide.

First report of Meloidogyne javanica infecting Bletilla striata in Yunnan, China.

Bletilla striata (Thunb. ex Murray) Rchb. F. (Orchidaceae) is an endangered traditional Chinese medicinal plant and has been traditionally used for hemostasis and detumescence in China (Wang et al. 2022). In March of 2021, during a field survey in Xuanwei city, Yunnan province, China, some B. striata plants with symptoms of plant dwarfing and leaf yellowing were observed. Roots of diseased plants presented numerous galls, typical symptoms of root-knot nematodes (RKNs) infection. The diseased area was approximately 66667 m2, showing a patchy disease distribution pattern. To identify the species of RKNs, females and eggs were isolated from galled tissue, and second-stage juveniles (J2s) were collected from eggs hatched. Nematodes were identified through comprehensive morphological and molecular methods. The perineal pattern of females is round to ovoid with a flat or moderately high dorsal arch and has two conspicuous lateral line striae. Morphological measurements of females (n=20) included body length (L) = 702.9 ± 70.8 (556.2-780.2) µm, body width (BW) = 404.1 ± 48.5 (327.5-470.1) µm, stylet length = 15.5 ± 2.2 (12.3-18.6) µm, distance from base of stylet to dorsal esophageal gland opening (DGO) = 3.7 ± 0.8 (2.1-4.9) µm. The morphometrics of J2s (n=20), L = 438.4 ± 22.6 (354.1-464.8) µm, BW = 17.4 ± 2.0 (12.9-20.8) µm, stylet length = 13.5 ± 0.4 (13.0-14.2) µm, DGO = 3.2 ± 0.6 (2.6-4.7) µm, and hyaline tail terminus = 12.3 ± 1.9 (9.6-15.7) µm. These morphological characteristics were similar to the original descriptions of Meloidogyne javanica (Rammah and Hirschmann 1990). DNA extraction was done 60 times, each from a different single females following the method of Yang et al. (2020). Amplification of ITS1-5.8S-ITS2 region of rDNA and the coxI region of mtDNA was done by using primers 18S/26S (5'-TTGATTACGTCCCTGCCCTTT-3'/5'-TTTCACTCGCCGTTACTAAGG-3') (Vrain et al. 1992) and cox1F/cox1R (5'-TGGTCATCCTGAAGTTTATG-3'/5'-CTACAACATAATAAGTATCATG-3') (Trinh et al. 2019) respectively. The PCR amplification program followed the method described by Yang et al. (2021). The ITS1-5.8S-ITS2 gene sequence (768 bp, GenBank Accession No. OQ091922) showed 99.35-100% identical to the known sequences of M. javanica (GenBank Accession Nos. KX646187, MW672262, KJ739710, KP901063, MK390613). The coxI gene sequence (410 bp, OQ080070) showed 99.75%-100% identical to the known sequences of M. javanica (OP646645, MZ542457, KP202352, KU372169, KU372170). Furthermore, M. javanica species-specific primers Fjav/Rjav (5'-GGTGCGCGATTGAACTGAGC-3'/5'-CAGGCCCTTCAGTGGAACTATAC-3') were used for PCR amplification. An expected fragment of approximately 670 bp was obtained, which was identical to that previously reported for M. javanica (Zijlstra et al. 2000). To verify pathogenicity of this nematode on B. striata, six 1.6-year-old tissue culture seedings of B. striata were maintained in 10-cm-diameter × 9-cm-high plastic pots containing a sterilized mixed soil (humus soil: laterite soil: perlite=3:1:1), and each plant was inoculated with 1000 J2s hatched from eggs of M. javanica. Three non-inoculated B. striata were used as the negative controls. All plants were placed in a greenhouse at approximately 14～26 ℃. After 90 days, the inoculated plants presented symptoms of leaf yellowing, and the roots with root knots identical to those observed in the fields. The root gall rating was 2 according to the 0-5 RKNs rating scale (Anwar and McKenry, 2002) and the reproductive factor (RF= final population/initial population) was 1.6. No symptoms or nematodes were observed on control plants. The nematode was reisolated and identified as M. javanica by morphological and molecular methods as above. To our knowledge, this is the first report of infection of M. javanica on B. striata. The infection of this economically important medicinal plant with M. javanica could pose a great threat to B. striata production in China, and further research will be necessary to develop control strategies.

Enzalutamide combination with Arsenic trioxide suppresses the progression of castration-resistant prostate cancer.

The study aimed to investigate the anti-tumor effects and underlying mechanisms of Enzalutamide (ENZ) and Arsenic trioxide (ATO) co-treatment on castration-resistant prostate cancer (CRPC). The effects on C4-2B cells were initially evaluated by colony formation assay, FACS analysis, and DNA fragmentation detection. Bioinformatics methods including mRNA-sequencing and gene enrichment analysis were used to screen the underlying target genes and pathways related to their actions. Western blot was employed to assess the expression levels of protein-related angiogenesis, apoptosis, DNA repair, and the screened genes. Finally, the effects were further verified in subcutaneous tumor models and tissue sections from the xenografts. It was found that not only could ENZ combination with ATO significantly inhibit cell proliferation and angiogenesis, but also induce cell arrest and apoptosis in C4-2B cells. In addition, interruption of the DNA damage repair-related pathways also occurred as a result of their combined effects. Western blot analysis further suggested that proteins involved in these pathways, especially P-ATR and P-CHEK1 were significantly reduced. In addition, their combination also inhibited the tumor growth of xenografts. Altogether, ENZ combination with ATO synergistically improved the therapeutic effects and suppressed CRPC progression through regulation of the ATR-CHEK1-CDC25C pathway.

Stereogenic-at-Cobalt(III) Complex Catalyzed Halocyclization of Alkynes: Enantioselective Access to Axially Chiral ortho-Halo-C2-indoles.

Here, we report an anionic stereogenic-at-cobalt(III) complex catalysis strategy for the enantioselective halocyclization of ortho-alkynylanilines using N-halosuccinimide (NXS) as the halogen source. This protocol provides a distinct atroposelective approach to access the axially chiral ortho-halo-C2-indole skeletons in excellent yields with good to high enantioselectivities (up to 99% yield, 99:1 er).

Identification and Validation of a m5C RNA Modification-Related Gene Signature for Predicting Prognosis and Immunotherapeutic Efficiency of Gastric Cancer.

Background: 5-methylcytosine (m5C) is a major site of RNA methylation modification, and its abnormal modification is associated with the development of gastric cancer (GC). This study aimed to explore the value of m5C-related genes on the prognosis of GC patients through bioinformatics. Methods: First, m5C-related genes were obtained by nonnegative matrix factorization (NMF) analysis and differentially expressed analysis. The m5C-related model was established and validated in distinct datasets. Moreover, a differential analysis of risk scores according to clinical characteristics was performed. The enrichment analysis was carried out to elucidate the underlying molecular mechanisms. Furthermore, we calculated the differences in immunotherapy and chemotherapy sensitivity between the high- and low-risk groups. Finally, we validated the expression levels of identified model genes by quantitative real-time polymerase chain reaction (qRT-PCR). Results: A total of five m5C-related subtypes of GC patients in the TCGA database were identified. The m5C-related model was constructed based on APOD, ASCL2, MFAP2, and CREB3L3. Functional enrichment revealed that the m5C-related model might involve in the cell cycle and cell adhesion. Moreover, the high-risk group had a higher abundance of stromal and immune cells in malignant tumor tissues and a lower tumor purity than the low-risk group. The patients in the high-risk group were more sensitive to chemotherapy and had better sensitivity to CTLA4 inhibitors. Furthermore, qRT-PCR results from our specimens verified an over-expression of ASCL2, CREB3L3, and MFAP2 in the cancer cells compared with the normal cells. Conclusion: A total of five GC subtypes were identified, and a risk model was constructed based on m5C modification.

MiR146a-loaded engineered exosomes released from silk fibroin patch promote diabetic wound healing by targeting IRAK1.

Unhealable diabetic wounds need to be addressed with the help of newer, more efficacious strategies. Exosomes combined with biomaterials for sustained delivery of therapeutic agents are expected to bring new hope for chronic wound treatment. Here, the engineered exosomes modified for efficiently loading miR146a and attaching to silk fibroin patch (SFP) were demonstrated to promote diabetic wound healing. Silk fibroin binding peptide (SFBP) was screened through phage display, and SFBP-Gluc-MS2 (SGM) and pac-miR146a-pac fusion protein were constructed. The designed exosomes (SGM-Exos, miR146a-Exos, and SGM-miR146a-Exos) were isolated from the engineered placental mesenchymal stem cells (PMSCs) transduced with SGM or/and pac-miR146a-pac protein. Gluc signals indicated SGM-Exo@SFP markedly increased the binding rate and the stability of SGM-Exo. Moreover, the loading efficiency of miR146a in SGM-miR146a-Exos was ten-fold higher than that in miR146a-Exos. Superior to untreated, SGM-miR146a-Exo-only treated, and SFP-only treated groups, SGM-miR146a-Exo@SFP drived wound healing associated with less inflammation, collagen deposition, and neovascularization. The transcriptomics analysis suggested anti-inflammatory and regenerative effects with SGM-miR146a-Exo@SFP treatment. Here, we show efficient exosome@biomaterial-based miRNA delivery systems for regenerative medicine and tissue engineering.

Enabling Long-Lived Polymeric Room Temperature Phosphorescence Material in Abominable Solvent.

Long-lived polymeric room temperature phosphorescence (RTP) materials have drawn more attention due to their convenient preparation process and equally efficient phosphorescence performance in recent years. As the polymer matrix is sensitive to air and humidity, some non-covalent interactions in the matrix are easily decomposed in water or air, which means that it is difficult for this material to be stored stably for a long time in the atmospheric environment or under harsh conditions. In this work, polymer powder mBPipQ contains aromatic and piperidine rings that are designed and synthesized successfully. Then the polymer is uniformly dispersed into epoxy resin matrix to form long-lived polymeric RTP material with efficient afterglow properties. The stiff backbone structure of mBPip and dense molecular arrangement of epoxy resin provide a rigid environment to stabilize triplet excitons, the RTP performance is greatly enhanced. The lifetime of mBPipQ in epoxy resin is 2 times higher than that of small molecule chromophore in that one. Interestingly, after soaking in strong acid or alkali solution for 10 days, the material can still emit stable and efficient long-lived phosphorescence. It is thanks to the hard matrix after full curing, which can provide a protective layer to prevent external quenchers from interfering with phosphorescence emission. Utilizing the efficient phosphorescence emission and excellent abominable-solvent resistance of this RTP material, multilevel information encryption has been successfully demonstrated. This work broadens the application scope of polymeric RTP materials in harsh environments and provides a new idea for achieving efficient RTP emission.