Diabetic wound healing is one of the major challenges in the biomedical fields. The conventional single drug treatments have unsatisfactory efficacy, and the drug delivery effectiveness is restricted by the penetration depth. Herein, we develop a magnesium organic framework-based microneedle patch (denoted as MN-MOF-GO-Ag) that can realize transdermal delivery and combination therapy for diabetic wound healing. Multifunctional magnesium organic frameworks (Mg-MOFs) are mixed with poly­(γ-glutamic acid) (γ-PGA) hydrogel and loaded into the tips of MN-MOF-GO-Ag, which slowly releases Mg2+ and gallic acid in the deep layer of the dermis. The released Mg2+ induces cell migration and endothelial tubulogenesis, while gallic acid, a reactive oxygen species-scavenger, promotes antioxidation. Besides, the backing layer of MN-MOF-GO-Ag is made of γ-PGA hydrogel and graphene oxide-silver nanocomposites (GO-Ag) which further enables excellent antibacterial effects for accelerating wound healing. The therapeutic effects of MN-MOF-GO-Ag on wound healing are demonstrated with the full-thickness cutaneous wounds of a diabetic mouse model. The significant improvement of wound healing is achieved for mice treated with MN-MOF-GO-Ag.

BackgroundThree first-line antituberculosis drugs, isoniazid, rifampicin and pyrazinamide, may induce liver injury, especially isoniazid. This antituberculosis drug-induced liver injury (ATLI) ranges from a mild to severe form, and the associated mortality cases are not rare. In the past decade, many investigations have focused the association between drug-metabolising enzyme (DME) gene polymorphisms and risk for ATLI; however, these studies have yielded contradictory results.MethodsPubMed, EMBASE, ISI web of science and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between polymorphisms from 4 DME genes (NAT2, CYP2E1, GSTM1 and GSTT1) and susceptibility to ATLI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Heterogeneity among articles and their publication bias were also tested.Results38 studies involving 2,225 patients and 4,906 controls were included. Overall, significantly increased ATLI risk was associated with slow NAT2 genotype and GSTM1 null genotype when all studies were pooled into the meta-analysis. Significantly increased risk was also found for CYP2E1*1A in East Asians when stratified by ethnicity. However, no significant results were observed for GSTT1.ConclusionsOur results demonstrated that slow NAT2 genotype, CYP2E1*1A and GSTM1 null have a modest effect on genetic susceptibility to ATLI.

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Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stromal cells that have a critical role in the maintenance of skeletal tissues such as bone, cartilage, and the fat in bone marrow. In addition to providing microenvironmental support for hematopoietic processes, BM-MSCs can differentiate into various mesodermal lineages including osteoblast/osteocyte, chondrocyte, and adipocyte that are crucial for bone metabolism. While BM-MSCs have high cell-to-cell heterogeneity in gene expression, the cell subtypes that contribute to this heterogeneity in vivo in humans have not been characterized. To investigate the transcriptional diversity of BM-MSCs, we applied single-cell RNA sequencing (scRNA-seq) on freshly isolated CD271 + BM-derived mononuclear cells (BM-MNCs) from two human subjects. We successfully identified LEPR hi CD45 low BM-MSCs within the CD271 + BM-MNC population, and further codified the BM-MSCs into distinct subpopulations corresponding to the osteogenic, chondrogenic, and adipogenic differentiation trajectories, as well as terminal-stage quiescent cells. Biological functional annotations of the transcriptomes suggest that osteoblast precursors induce angiogenesis coupled with osteogenesis, and chondrocyte precursors have the potential to differentiate into myocytes. We also discovered transcripts for several clusters of differentiation (CD) markers that were either highly expressed (e.g., CD167b, CD91, CD130 and CD118) or absent (e.g., CD74, CD217, CD148 and CD68) in BM-MSCs, representing potential novel markers for human BM-MSC purification. This study is the first systematic in vivo dissection of human BM-MSCs cell subtypes at the single-cell resolution, revealing an insight into the extent of their cellular heterogeneity and roles in maintaining bone homeostasis.

Directly using solar energy to realize photocatalytic reduction of CO2to hydrocarbon fuels is an effective tactics to solve the energy crisis and carbon emission. Although graphite carbon nitride (g‐C3N4) has been widely studied as a star photocatalyst for CO2reduction, the extremely fast charge recombination rate seriously limits its performance. Loading suitable co‐catalysts to construct an effective junction is considered an efficient way to solve this issue and promote photocatalytic performance. In this work, metallic molybdenum dioxide (MoO2) is dispersed on g‐C3N4nanosheets to construct a Schottky junction photocatalyst. The Schottky junction between MoO2and g‐C3N4induces efficient charge separation and transfer. As a result, the optimal MoO2/g‐C3N4Schottky junction photocatalyst exhibits a 15 times higher CH4yield and five times higher CO yield compared with pure g‐C3N4. This article provides a new route to construct a Schottky junction for boosting photocatalytic activity.

An optical probe based on colorimetric and ratiometric as well as chemiluminometric signal outputs is developed for the specific detection of hydrazine. On the basis of a Gabriel-type reaction, hydrazinolysis of a simple probe CF (4-phtalamide-N-(4'-methylcoumarin) naphthalimide) produces both the fluorescence of 7-amino-4-methylcoumarin with the max emission wavelength changed from 480 to 420 nm (along with a color change from yellow to transparent) and the luminol chemiluminescence activated by H2O2 with a max emission wavelength at 450 nm. The experimental detection limit of hydrazine is 3.2 ppb (0.1 μM). Selectivity experiments proved CF has excellent selectivity to hydrazine over other interfering substances. Probe CF was also successfully applied in the vapor hydrazine detection over other interfering volatile analytes. Furthermore, the probe CF loaded thin-layer chromatography (TLC) plate for vapor hydrazine detection limit is 5.4 mg/m(3) which is well below the half lethal dose of hydrazine gas for mice (LC50(mice), 330 mg/m(3)) and National Institute of Occupational Safety and Health's immediately dangerous to life or health limit (NIOSHIDLH, 66 mg/m(3)). With H2O2, only hydrazinolysis product luminol can be lighted at 450 nm, other species have no signal. Probe CF can also be used for the detection of hydrazine in HeLa cells.

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