Early short-term hypoxia promotes epidermal cell migration by activating the CCL2-ERK1/2 pathway and epithelial-mesenchymal transition during wound healing.

Background: Due to vasculature injury and increased oxygen consumption, the early wound microenvironment is typically in a hypoxic state. We observed enhanced cell migration ability under early short-term hypoxia. CCL2 belongs to the CC chemokine family and was found to be increased in early hypoxic wounds and enriched in the extracellular signal-regulated kinase (ERK)1/2 pathway in our previous study. However, the underlying mechanism through which the CCL2-ERK1/2 pathway regulates wound healing under early short-term hypoxia remains unclear. Activation of epithelial-mesenchymal transition (EMT) is a key process in cancer cell metastasis, during which epithelial cells acquire the characteristics of mesenchymal cells and enhance cell motility and migration ability. However, the relationship between epithelial cell migration and EMT under early short-term hypoxia has yet to be explored. Methods: HaCaT cells were cultured to verify the effect of early short-term hypoxia on migration through cell scratch assays. Lentiviruses with silenced or overexpressed CCL2 were used to explore the relationship between CCL2 and migration under short-term hypoxia. An acute full-thickness cutaneous wound rat model was established with the application of an ERK inhibitor to reveal the hidden role of the ERK1/2 pathway in the early stage of wound healing. The EMT process was verified in all the above experiments through western blotting. Results: In our study, we found that short-term hypoxia promoted cell migration. Mechanistically, hypoxia promoted cell migration through mediating CCL2. Overexpression of CCL2 via lentivirus promoted cell migration, while silencing CCL2 via lentivirus inhibited cell migration and the production of related downstream proteins. In addition, we found that CCL2 was enriched in the ERK1/2 pathway, and the application of an ERK inhibitor in vivo and in vitro verified the upstream and downstream relationships between the CCL2 pathway and ERK1/2. Western blot results both in vivo and in vitro demonstrated that early short-term hypoxia promotes epidermal cell migration by activating the CCL2-ERK1/2 pathway and EMT during wound healing. Conclusions: Our work demonstrated that hypoxia in the early stage serves as a stimulus for triggering wound healing through activating the CCL2-ERK1/2 pathway and EMT, which promote epidermal cell migration and accelerate wound closure. These findings provide additional detailed insights into the mechanism of wound healing and new targets for clinical treatment.

Engineering an Almost All-Waterborne System for Transparent yet Superhydrophobic Surfaces with High Liquid Impalement Resistance.

Realistically, green manufacturing of transparent superhydrophobic surfaces (SHSs) and high liquid impalement resistance for outdoor engineering are very necessary but pretty challenging. To address this, an almost all-waterborne system composed of synthesized partially open-cage fluorinated polyhedral oligomeric silsesquioxane bearing a pair of -OH (poc-FPOSS-2OH), silica sol, and resin precursor is engineered. The transparent SHSs facilely formed by this system are featured with the exclusive presence of wrapped silica nanoparticle (SiNP) dendritic networks at solid-gas interfaces. The wrapped SiNP dendritic networks have a small aggregation size and low distribution depth, making SHSs highly transparent. The Si-O polymeric wrappers render mechanical flexibility to SiNP dendritic networks and thus enable transparent SHSs to resist high-speed water jet impinging with a Weber number of ≥19 800 in conjunction with the extremely low-surface-energy poc-FPOSS-2OH, which is the highest liquid impalement resistance so far among waterborne SHSs, and can rival the state-of-the-art solventborne SHSs.

[Screening of pathogenic molecular markers of Staphylococcus aureus in children based on whole genome sequencing technology]. / åŸºäºŽå ¨åŸºå› ç»„æµ‹åºæŠ€æœ¯ç­›é€‰å„¿ç«¥é‡‘é»„è‰²è‘¡è„çƒèŒçš„è‡´ç— ç›¸å ³åˆ†å­æ ‡å¿—ç‰©.

OBJECTIVES: To explore the molecular characteristics of Staphylococcus aureus (S. aureus) in children, and to compare the molecular characteristics of different types of strains (infection and colonization strains) so as to reveal pathogenic molecular markers of S. aureus. METHODS: A cross-sectional study design was used to conduct nasopharyngeal swab sampling from healthy children in the community and clinical samples from infected children in the hospital. Whole genome sequencing was used to detect antibiotic resistance genes and virulence genes. A random forest method to used to screen pathogenic markers. RESULTS: A total of 512 S. aureus strains were detected, including 272 infection strains and 240 colonization strains. For virulence genes, the carrying rates of enterotoxin genes (seb and sep), extracellular enzyme coding genes (splA, splB, splE and edinC), leukocytotoxin genes (lukD, lukE, lukF-PV and lukS-PV) and epidermal exfoliating genes (eta and etb) in infection strains were higher than those in colonization strains. But the carrying rates of enterotoxin genes (sec, sec3, seg, seh, sei, sel, sem, sen, seo and seu) were lower in infection strains than in colonization strains (P<0.05). For antibiotic resistance genes, the carrying rates of lnuA, lnuG, aadD, tetK and dfrG were significantly higher in infection strains than in colonization strains (P<0.05). The accuracy of cross-validation of the random forest model for screening pathogenic markers of S. aureus before and after screening was 69% and 68%, respectively, and the area under the curve was 0.75 and 0.70, respectively. The random forest model finally screened out 16 pathogenic markers (sem, etb, splE, sep, ser, mecA, lnuA, sea, blaZ, cat(pC233), blaTEm-1A, aph(3')-III, ermB, ermA, ant(9)-Ia and ant(6)-Ia). The top five variables in the variable importance ranking were sem (OR=0.40), etb (OR=3.95), splE (OR=1.68), sep (OR=3.97), and ser (OR=1.68). CONCLUSIONS: The random forest model can screen out pathogenic markers of S. aureus and exhibits a superior predictive performance, providing genetic evidence for tracing highly pathogenic S. aureus and conducting precise targeted interventions.

[Dose-response relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children]. / 幼儿园儿童年龄与肺炎链球菌疫苗覆盖率间的剂量-ååº”å ³ç³».

OBJECTIVES: To investigate the potential relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children, and to provide a basis for guiding vaccination and developing new protein vaccines. METHODS: The stratified cluster random sampling method was used to select 1 830 healthy children from six kindergartens in Shunde District, Foshan City, China, and nasopharyngeal swabs were collected for the isolation and identification of Streptococcus pneumoniae. The logistic regression model based on restricted cubic spline was used to analyze the dose-response relationship between age and Streptococcus pneumoniae vaccination coverage. RESULTS: The rate of nasal Streptococcus pneumoniae carriage was 22.46% (411/1 830) among the kindergarten children, with the predominant serotypes of 6B, 19F, 15A, 23A, 34, and 23F. The coverage rates of 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) were 53.0% and 57.9%, respectively, and there was a significant non-linear dose-response relationship between age and the coverage rates of PCV10 and PCV13 (P<0.05), with a higher coverage rate of PCV10 (88.0%) and PCV13 (91.1%) in the children aged 2 years. There was a significant non-linear dose-response relationship between age and the coverage rates of pilus islet 1 (PI-1) and pilus islet 2 (PI-2) (P<0.05), with a lower vaccination coverage rate for PI-1 (37.7%) and PI-2 (16.1%). The coverage rates of PI-1 (13.0%-58.5%) and PI-2 (6.0%-29.4%) were lower in all age groups. The virulence genes lytA (99.5%) and ply (99.0%) associated with candidate protein vaccines showed higher vaccination coverage rates. CONCLUSIONS: There is a significant non-linear dose-response relationship between the age of kindergarten children and the coverage rates of PCV10 and PCV13 serotypes, and kindergarten children aged 2 years have a relatively high coverage rate of PCV. The high prevalence of the virulence genes lytA and ply shows that they are expected to become candidate virulence factors for the development of a new generation of recombinant protein vaccines.

DNMT3A-mediated epigenetic silencing of SOX17 contributes to endothelial cell migration and fibroblast activation in wound healing.

BACKGROUND: Wound healing, especially impaired chronic wound healing, poses a tremendous challenge for modern medicine. Understanding the molecular mechanisms underlying wound healing is essential to the development of novel therapeutic strategies. METHODS: A wound-healing mouse model was established to analyze histopathological alterations during wound healing, and the expression of SRY-box transcription factor 17 (SOX17), DNA methyltransferase 3 alpha (DNMT3A), and a specific fibroblast marker S100 calcium-binding protein A4 (S100A4) in wound skin tissues was tested by immunofluorescence (IF) assay. Cell proliferation and migration were evaluated using 5-ethynyl-2'-deoxyuridine (EdU) and Transwell migration assays. RT-qPCR and western blotting were used to measure RNA and protein expression. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the secretion of transforming growth factor-beta (TGF-ß). Chromatin immunoprecipitation followed by qPCR (ChIP-qPCR) and DNA pull-down assays were performed to confirm the interaction between DNMT3A and the CpG island of the SOX17 promoter. Promoter methylation was examined by pyrosequencing. RESULTS: SOX17 and DNMT3A expression were regularly regulated during the different phases of wound healing. SOX17 knockdown promoted HUVEC migration and the production and release of TGF-ß. Through establishing an endothelial cells-fibroblasts co-culture model, we found that SOX17 knockdown in HUVECs activated HFF-1 fibroblasts, which expressed α-smooth muscle actin (α-SMA) and type I collagen (COL1). DNMT3A overexpression reduces SOX17 mRNA levels. ChIP-qPCR and DNA pull-down assays verified the interaction between DNMT3A and CpG island in the SOX17 promoter region. Pyrosequencing confirmed that DNMT3A overexpression increased the methylation level of the SOX17 promoter. CONCLUSION: DNMT3A-mediated downregulation of SOX17 facilitates wound healing by promoting endothelial cell migration and fibroblast activation.

Regeneration of Activated Sludge into SiO2-Decorated Heteroatom-Doped Porous Carbon as Advanced Electrodes for Li-S Batteries.

The regeneration of harmful activated sludge into an energy source is an important strategy for municipal sludge treatment and recycling. Herein, SiO2-modified N,S auto-doped porous carbon (NSC@SiO2) with high conductivity (70 S m-1) is successfully obtained through a simple calcination method of the activated sludge from wastewater treatment. Further, P-doped NSC@SiO2 (NSPC@SiO2) is designed to achieve a higher surface area (891 m2 g-1 vs 624 m2 g-1), a larger pore volume (0.87 cm3 g-1 vs 0.08 cm3 g-1), and more carbon defects. Due to its special structure, NSPC@SiO2 is used as a sulfur host of lithium-sulfur batteries. The results of polysulfide adsorption experiments, S 2p X-ray photoelectron spectra (XPS), Li2S nucleation experiments, polysulfide symmetric cells, measurement of the galvanostatic intermittent titration (GITT), polarization voltage difference, lithium-ion diffusion rate, and Tafel slope verified that NSPC@SiO2 greatly improved the adsorption capacity of polysulfides, lowered the barrier to Li2S formation and the internal resistances of cells, and accelerated Li+ ion diffusion and the reaction kinetics of polysulfide conversion, resulting in the excellent performance of polysulfide capture and superior rate performance and cyclic stability. By comparing NSPC@SiO2 with NSC@SiO2, a higher initial capacity (1377 mAh g-1 vs 1150 mAh g-1 at 0.1C), better rate capacity (912 mAh g-1 vs 719 mAh g-1 at 2C), and low capacity decay (0.094% per cycle within 200 cycles) are obtained. Our work provides direction for the treatment, disposal, and resource utilization of activated sludge.

Nasopharyngeal aspirates in children with severe community-acquired pneumonia collected within 3 days before bronchoscopy can partially reflect the pathogens in bronchoalveolar lavage fluids.

BACKGROUND: There is little evidence about consistency between nasopharyngeal and pulmonary pathogens in children with severe pneumonia. This study aims to compare the difference of pathogens between nasopharyngeal aspirates (NPAs) collected before bronchoscopy and bronchoalveolar lavage fluids (BALFs) in children with severe community-acquired pneumonia (SCAP). METHODS: NPAs and BALFs were collected form pediatric SCAP cases hospitalized from January 2018 to March 2019. NPAs were colleced within 3 days before bronchoscopy. Samples were detected by direct immunofluorescence assay (DFA) for seven respiratory viruses and by routine bacterial culture in the clinical microbiology laboratory. Respiratory syncytial virus (RSV), Adenovirus (ADV), Influenza virus types A, B (IV-A and IV-B), Parainfluenza virus 1-3 (PIV1-3) were detected with a commercial assay. The virological and bacteriological detention results of NPAs were compared with the results of BALFs. RESULTS: In total 204 cases with mean age of 3.4 ± 2.8 years (IQR, 1 month-14 years) were included in the study. Both NPA and BALF were collected from those cases. The positive rates of pathogen in NPAs and BALFs were 25.0% (51/204) and 36.7% (75/204), respectively (x2 = 6.614, P = 0.010). Respiratory viruses were found in 16.1% (33/204) from NPAs and 32.3% (66/204) from BALFs (x2 = 14.524, P < 0.001). RSV and ADV were the two most frequent detected viruses in NPAs and BALFs. High consistentcy of pathogens between NPAs and BALFs was observed, and 96.9% (32/33) viruses detected in NPAs were also found in BALFs. While bacteria were isolated from 12.7% (26/204) and 10.7% (22/204) of the two kinds of samples, respectively (x2 = 0.378, P = 0.539). In addition, Haemophilus influenzae (HI) was the dominant germ in both samples. CONCLUSION: The DFA method used to detect seven respiratory viruses from NPAs collected within 3 days before bronchoscopy can partially reflect the pathogens in the lungs in children with SCAP.

Autophagy promotes directed migration of HUVEC in response to electric fields through the ROS/SIRT1/FOXO1 pathway.

Endogenous electric fields (EFs) have been confirmed to facilitate angiogenesis through guiding directional migration of endothelial cells (ECs), but the underlying mechanisms remain obscure. Recent studies suggest that the directed migration of ECs in angiogenesis is correlated with autophagy, and the latter of which could be augmented by EFs. We hypothesize that autophagy may participate in the EFs-guided migration of ECs during angiogenesis. Herein, we showed that EFs induced human umbilical vein endothelial cells (HUVEC) migration toward the cathode with enhanced autophagy. Genetic ablation of autophagy by silencing the autophagy-related gene (Atg) 5 abolished the EFs-directed migration of HUVEC, indicating that autophagy is definitely required for EFs-guided migration of cells. Mechanistically, we identified the intracellular reactive oxygen species (ROS) as a crucial mediator in EFs-triggered autophagy through augmenting the silencing information regulator 2 related enzyme1 (SIRT1)/forkhead box protein O1 (FOXO1) signaling. Either ROS scavenging or SIRT1 knockdown eliminated the EFs-triggered autophagy in HUVEC. Further study showed that SIRT1 promoted FOXO1 deacetylation, facilitating its nuclear accumulation and transcriptional activity, and thereby activating autophagy in EFs-treated HUVECs. In conclusion, our study demonstrated a pivotal role for autophagy in EFs-induced directed migration of HUVECs through the ROS/SIRT1/FOXO1 pathway, and provided a novel theoretical foundation for angiogenesis.

Co-carriage of Streptococcus pneumoniae and Moraxella catarrhalis among preschool children and its influencing factors. / å­¦é¾„å‰å„¿ç«¥è‚ºç‚Žé“¾çƒèŒå’Œå¡ä»–èŽ«æ‹‰èŒæºå¸¦çŠ¶æ€åŠå½±å“å› ç´ åˆ†æž.

OBJECTIVES: To investigate the carriage status of Streptococcus pneumoniae (S.pneumoniae) and Moraxella catarrhalis (M. catarrhalis) in preschool children and the influencing factors for the carriage status. METHODS: The stratified cluster sampling method was used to select 2 031 healthy children from seven kindergartens in Shunde District of Foshan in Guangdong, China. Nasal swabs were collected from all children for the isolation and identification of S. pneumoniae and M. catarrhalis. The carriage status of S. pneumoniae and M. catarrhalis was analyzed in terms of its association with demographic features and hospital- and community-related factors. RESULTS: The carriage rates of S. pneumoniae and M. catarrhalis were 21.81% and 52.44%, respectively among the children. The co-carriage rate of S. pneumoniae and M. catarrhalis was 14.87%. The correspondence analysis showed that the factors such as lower grade, non-local registered residence, living in rural areas, small living area, history of respiratory tract infection but no history of antibiotic use, allergic skin diseases, and no hospital-related exposure history were significantly associated with the co-carriage of S. pneumoniae and M. catarrhalis among the children (P<0.05). CONCLUSIONS: Co-carriage of S. pneumoniae and M. catarrhalis can be observed in preschool children. Young age, poor living environment, a history of respiratory tract infection but no history of antibiotic use, allergic skin diseases, and no hospital-related exposure history are important risk factors for the co-carriage of S. pneumoniae and M. catarrhalis in preschool children.

Activation of locus coeruleus-spinal cord noradrenergic neurons alleviates neuropathic pain in mice via reducing neuroinflammation from astrocytes and microglia in spinal dorsal horn.

BACKGROUND: The noradrenergic neurons of locus coeruleus (LC) project to the spinal dorsal horn (SDH), and release norepinephrine (NE) to inhibit pain transmission. However, its effect on pathological pain and the cellular mechanism in the SDH remains unclear. This study aimed to explore the analgesic effects and the anti-neuroinflammation mechanism of LC-spinal cord noradrenergic pathway (LC:SC) in neuropathic pain (NP) mice with sciatic chronic constriction injury. METHODS: The Designer Receptors Exclusively Activated by Designer Drugs (DREADD) was used to selectively activate LC:SC. Noradrenergic neuron-specific retro-adeno-associated virus was injected to the spinal cord. Pain threshold, LC and wide dynamic range (WDR) neuron firing, neuroinflammation (microglia and astrocyte activation, cytokine expression), and α2AR expression in SDH were evaluated. RESULTS: Activation of LC:SC with DREADD increased the mechanical and thermal nociceptive thresholds and reduced the WDR neuron firing. LC:SC activation (daily, 7 days) downregulated TNF-α and IL-1ß expression, upregulated IL-4 and IL-10 expression in SDH, and inhibited microglia and astrocytes activation in NP mice. Immunofluorescence double staining confirmed that LC:SC activation decreased the expression of cytokines in microglia of the SDH. In addition, the effects of LC:SC activation could be reversed by intrathecal injection of yohimbine. Immunofluorescence of SDH showed that NE receptor α2B-AR was highly expressed in microglia in CCI mice. CONCLUSION: These findings indicate that selective activation of LC:SC alleviates NP in mice by increasing the release of NE and reducing neuroinflammation of astrocytes and microglia in SDH.

Multivariate Strategy Preparation of Nanoscale Ru-Doped Metal-Organic Frameworks with Boosted Photoactivity for Bioimaging and Reactive Oxygen Species Generation.

How to incorporate chromophores into MOFs is a key for the development of multifunctional photoactive systems. The poor internalization by cancer cells and low efficiency of ROS generation hamper the potential clinic application of Ru-based molecular agents. In this work, a nanoscale Ru-doped metal-organic framework Hf-UiO-Ru (Hf-Ru) with framework-boosted photoactivities was prepared via a multivariate strategy for use in bioimaging and ROS generation. The as-synthesized Hf-Ru nanocrystals not only maintain the well regular morphology and crystal structure in comparison with that of the Hf-UiO-66 prototype but also give an oxygen-independent emission with a much longer lifetime, higher quantum yield, and stronger ROS generation than molecular Ru(dcbpy)3. Additionally, the enhanced cellular uptake and high brightness in fluorescence and CT imaging of Hf-Ru nanocrystals have also been well studied in vitro. This multivariate strategy may be utilized as a general paradigm to develop a photoactive nanosystem for bioimaging and cancer treatment.

Clinical and molecular characteristics of Wiskott-Aldrich Syndrome in five unrelated Chinese families.

Wiskott-Aldrich syndrome (WAS) also called the eczema-thrombocytopenia-immunodeficiency syndrome is a primary immunodeficiency disease with X-linked recessive inheritance caused by mutations in the WAS protein (WASp) gene and characterized by thrombocytopenia with reduced platelet volume, eczema, immunodeficiency, and increased risk of malignant tumours. The mutations will lead to separate WAS severity which can be typical severe 'classical' WAS or less severe 'non-classical' WAS. This article will review and analyse clinical and immune characteristics of five unrelated Chinese families harbouring classical and non-classical WAS. The expression of WASp was detected in the peripheral blood monocytes (PBMC) by flow cytometry, and five mutations were found by WAS gene sequencing, one of which had not been reported in the literature, namely frameshift mutation c.1240_1247delCCACTCCC (p. P414Sfs*41).

Transmission risk and resistance characteristics of Streptococcus pneumoniae among preschool children in Foshan / 中国学校卫生

Objective@#To understand the homology and resistance characteristics of Streptococcus pneumoniae (S. pneumoniae) in healthy preschool children, so as to provide basis for disease transmission prevention and rational use of antibiotics.@*Methods@#Stratified cluster random sampling method was used to sample 1 829 healthy children from six kindergartens in Shunde District, Foshan City. Nasal swabs were taken and tested for S. pneumoniae. Multi locus sequence typing was used for homology analysis. The Chi squared test and random forest analysis were used to explore the resistance characteristics.@*Results@#The nasal carriage rate of S. pneumoniae and multidrug resistant S. pneumoniae (MDRSP) in children were 22.5%(412/1 829) and 21.3%(390/1 829), respectively. Homology analysis in sequence types showed that the total homology rates of 6 kindergartens were 93.5%(87/93), 91.1% (72/79), 89.2%(58/65), 88.9%(64/72), 86.2%(50/58), 77.8%(35/45), respectively. It was found that the highest homology rate was 82.8% (48/58) within class and 93.1% (81/87) between classes. S. pneumoniae was mainly resistant to azithromycin (97.1%, 400/412), erythromycin (92.0%, 379/412) and tetracycline (91.5%, 377/412). The dominant multidrug resistance pattern of MDRSP isolates was not sensitive to azithromycin, erythromycin, cotrimoxazole, tetracycline and clindamycin. Random forest analysis indicated that the important phenotypic markers associated with MDRSP were resistance to azithromycin, cotrimoxazole, tetracycline, clindamycin and erythromycin(MDG=8.94, 6.92, 5.80, 4.84, 2.58).@*Conclusion@#The risk of cross transmission of S. pneumoniae among preschool children is high, and direct contact is the main way of transmission. Consequently, kindergartens and health departments should take effective measures to effectively prevent and block the spread of Streptococcus pneumoniae.

Intracellular Enzyme-Responsive Profluorophore and Prodrug Nanoparticles for Tumor-Specific Imaging and Precise Chemotherapy.

Responsive drug delivery systems possess great potential in disease diagnosis and treatment. Herein, we develop an activatable prodrug and fluorescence imaging material by engineering the endogenous NAD(P)H:quinone oxidoreductase-1 (NQO1) responsive linker. The as-prepared nanomaterials possess the NQO1-switched drug release and fluorescence enablement, which realizes the tumor-specific chemotherapy and imaging in living mice. The enzyme-sensitive prodrug nanoparticles exhibit selectively potent anticancer performance to NQO1-positive cancer and ignorable off-target toxicity. This work provides an alternative strategy for constructing smart prodrug nanoplatforms with precision, selectivity, and practicability for advanced cancer imaging and therapy.

Efficacy of Low-Dose rhGM-CSF Treatment in a Patient With Severe Congenital Neutropenia Due to CSF3R Deficiency: Case Report of a Novel Biallelic CSF3R Mutation and Literature Review.

This study reports the clinical manifestations, genetics, and efficacy of treatment with the efficacy of recombinant human granulocyte macrophage colony-stimulating factor (rhGM-GSF) of a 2-year-old female patient with severe congenital neutropenia (SCN) type 7 (SCN7) caused by novel biallelic mutations in the colony-stimulating factor 3 receptor (CSF3R) gene. Genetic diagnosis of the patient was performed by whole-exome and Sanger sequencing. Expression of the CSF3R gene in the peripheral neutrophils of the patient was detected by real-time PCR and Western blotting. The patient presented with recurrent suppurative tonsillitis and decreased absolute neutrophil count <0.5 × 109/L. Novel heterozygous mutations were found to be inherited from each parent (maternal c.690delC [p.met231Cysfs*32] and paternal c.64+5G>A). The patient's neutrophils had lower CSF3R mRNA and protein levels than those of the parents. Low-dose rhGM-CSF (3 µg/kg/day once a week) prevented recurrent infection in the patient. These results demonstrate that the clinical manifestations of SCN7 with biallelic CSF3R mutations and downregulated CSF3R can be effectively treated with rhGM-CSF.

Structural diversity of nanoscale zirconium porphyrin MOFs and their photoactivities and biological performances.

Photoactive MOF-based delivery systems are highly attractive for photodynamic therapy (PDT), but the fundamental interplay among structural parameters and photoactivity and biological properties of these MOFs remains unclear. Herein, porphyrinic MOF isomers (TCPP-MOFs), constructing using the same building blocks into distinct topologies, have been selected as ideal models to understand this problem. Both the intramolecular distances and molecular polarization within TCPP-MOFs isomers collectively contribute to the photoactivity of generating reactive oxygen species. Remarkably, the morphology-determined endocytic pathways and cytotoxicity, as well as good biocompatibility have been confirmed for TCPP-MOF isomers without any chemical modification for the first time. Besides the topology-dependent photoactive regulation, this work also provides in-depth insights into the biological effect from the MOF nanoparticles with controllable structural factors, benefiting further in vivo applications and clinical transformation.

Defect Engineering of Nanoscale Hf-Based Metal-Organic Frameworks for Highly Efficient Iodine Capture.

With the rapid development of the nuclear industry, how to deal with radioactive iodine waste in a timely and effective manner has become an important issue to be solved urgently. Herein, the defect-engineering strategy has been applied to develop a metal-organic framework (MOF)-based solid adsorbent by using the classical UiO-type Hf-UiO-66 as an example. After simple acid treatment, the produced defect-containing Hf-UiO-66 (DHUN) not only retains its topological structure, high crystallization, and regular shape but also shows a great increase in the Brunauer-Emmett-Teller value and pore size in comparison with the original Hf-UiO (HUN). These formed defects within DHUN have been demonstrated to be important for the great enhancement of the iodine capture and following application in computed tomography imaging in vitro. This present work gives a new insight into the control and formation of defect sites, and this simple and efficient defect-engineering strategy also shows great promise for the development of novel solid adsorbents and other functional MOF materials.

Merocyanine-paclitaxel conjugates for photothermal induced chemotherapy.

Small molecular nanomedicines that integrate the flexibility of self-assembly strategies and the advantages of a precise molecular structure, a high drug content and controlled drug release are effective diagnostic and therapeutic modalities. Herein, merocyanine-paclitaxel conjugates (MC-PTX) were developed and fabricated by using the degradable ester bonds as the linker. The as-prepared MC-PTX could self-assemble into nanoparticles (MC-PTX NPs) using the non-covalent molecular interaction via the nanoprecipitation method. MC-PTX NPs possess a favorable biological stability and can efficiently release the paclitaxel (PTX) activated by the heat of the photoactive material merocyanine under light illumination, as monitored using dynamic light scattering. The obtained MC-PTX NPs could be endocytosed into cancer cells and release PTX under laser irradiation in the cytoplasm, thus eliciting a satisfactory anticancer effect. Photothermal triggered degradation upon light illumination could enhance the chemotherapeutic efficacy of paclitaxel. The fluorescent nature of the NPs could visualize the internalization process. We believe that this robust nanomedicine offers a novel strategy to facilitate clinical translation for use as a small molecular chemotherapy nanomedicine.

Intravenous lidocaine alleviates postherpetic neuralgia in rats via regulation of neuroinflammation of microglia and astrocytes.

This study aimed to explore the effects and possible mechanisms of intravenous lidocaine in postherpetic neuralgia (PHN) rats. Mechanical withdrawal thresholds and thermal withdrawal latencies were measured. Open field test, elevated plus maze test, and tail suspension test were used to assess anxiety- and depressive-like behaviors. Microglia and astrocytes in spinal dorsal horn (SDH), prefrontal cortex (PFC), anterior cingulate cortex (ACC), and hippocampus were analyzed. The expression of TNF-α, IL-1ß, and IL-4 in SDH and serum were evaluated. Intravenous lidocaine alleviated mechanical allodynia and thermal hypoalgesia, downregulated the expression of TNF-α and IL-1ß, and inhibited the activation of microglia and astrocytes in SDH. In addition, it reduced the activation of astrocyte but not microglia in PFC, ACC, and hippocampus. Intravenous lidocaine may relieve PHN by inhibiting the activation of microglia and astrocyte in SDH or by reducing the neuroinflammation and astrocyte activation in PFC, ACC, and hippocampus.

Interconnected NiCo2O4 nanosheet arrays grown on carbon cloth as a host, adsorber and catalyst for sulfur species enabling high-performance Li-S batteries.

Li-S batteries are a promising next-generation electrochemical energy-storage system due to their high energy density, as well as the abundance and low cost of sulfur. However, the low conductivity of sulfur and Li2S/Li2S2, as well as the dissolution and shuttling of intermediate lithium polysulfides, is a great challenge for high-performance Li-S batteries. Herein, interconnected NiCo2O4 nanosheet arrays grown on carbon cloth (CC) are applied as the cathode (S/NiCo2O4/CC) in Li-S batteries for accommodating sulfur. The obtained cathode shows high conductivity, high dispersion of sulfur species and excellent polysulfide adsorption and catalytic properties. As a result, significantly higher specific capacity (1480 vs. 1048 mA h g-1 at 0.1C) and greatly enhanced rate performance (624 vs. 215 mA h g-1 at 2C) are obtained for the S/NiCo2O4/CC cathode in comparison to S/CC. Further, the S/NiCo2O4/CC cathode demonstrates a low capacity decay of 0.060% per cycle over 400 cycles at 0.5C.