An extra-erythrocyte role of haemoglobin body in chondrocyte hypoxia adaption.

Although haemoglobin is a known carrier of oxygen in erythrocytes that functions to transport oxygen over a long range, its physiological roles outside erythrocytes are largely elusive1,2. Here we found that chondrocytes produced massive amounts of haemoglobin to form eosin-positive bodies in their cytoplasm. The haemoglobin body (Hedy) is a membraneless condensate characterized by phase separation. Production of haemoglobin in chondrocytes is controlled by hypoxia and is dependent on KLF1 rather than the HIF1/2α pathway. Deletion of haemoglobin in chondrocytes leads to Hedy loss along with severe hypoxia, enhanced glycolysis and extensive cell death in the centre of cartilaginous tissue, which is attributed to the loss of the Hedy-controlled oxygen supply under hypoxic conditions. These results demonstrate an extra-erythrocyte role of haemoglobin in chondrocytes, and uncover a heretofore unrecognized mechanism in which chondrocytes survive a hypoxic environment through Hedy.

Characterization of GSDME in amphioxus provides insights into the functional evolution of GSDM-mediated pyroptosis.

Members of the gasdermin (GSDM) family are pore-forming effectors that cause membrane permeabilization and pyroptosis, a lytic proinflammatory type of cell death. To reveal the functional evolution of GSDM-mediated pyroptosis at the transition from invertebrates to vertebrates, we conducted functional characterization of amphioxus GSDME (BbGSDME) and found that it can be cleaved by distinct caspase homologs, yielding the N253 and N304 termini with distinct functions. The N253 fragment binds to cell membrane, triggers pyroptosis, and inhibits bacterial growth, while the N304 performs negative regulation of N253-mediated cell death. Moreover, BbGSDME is associated with bacteria-induced tissue necrosis and transcriptionally regulated by BbIRF1/8 in amphioxus. Interestingly, several amino acids that are evolutionarily conserved were found to be important for the function of both BbGSDME and HsGSDME, shedding new lights on the functional regulation of GSDM-mediated inflammation.

Ablation of Argonaute 2 in Schwann cells accelerates the progression of diabetic peripheral neuropathy.

Schwann cells (SCs) form myelin and provide metabolic support for axons, and are essential for normal nerve function. Identification of key molecules specific to SCs and nerve fibers may provide new therapeutic targets for diabetic peripheral neuropathy (DPN). Argonaute2 (Ago2) is a key molecular player that mediates the activity of miRNA-guided mRNA cleavage and miRNA stability. Our study found that Ago2 knockout (Ago2-KO) in proteolipid protein (PLP) lineage SCs in mice resulted in a significant reduction of nerve conduction velocities and impairments of thermal and mechanical sensitivities. Histopathological data revealed that Ago2-KO significantly induced demyelination and neurodegeneration. When DPN was induced in both wild-type and Ago2-KO mice, Ago2-KO mice exhibited further decreased myelin thickness and exacerbated neurological outcomes compared with wild-type mice. Deep sequencing analysis of Ago2 immunoprecipitated complexes showed that deregulated miR-206 in Ago2-KO mice is highly related to mitochondrial function. In vitro data showed that knockdown of miR-200 induced mitochondrial dysfunction and apoptosis in SCs. Together, our data suggest that Ago2 in SCs is essential to maintain peripheral nerve function while ablation of Ago2 in SCs exacerbates SC dysfunction and neuronal degeneration in DPN. These findings provide new insight into the molecular mechanisms of DPN.

Cerebellar connectome alterations and associated genetic signatures in multiple sclerosis and neuromyelitis optica spectrum disorder.

BACKGROUND: The cerebellum plays key roles in the pathology of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), but the way in which these conditions affect how the cerebellum communicates with the rest of the brain (its connectome) and associated genetic correlates remains largely unknown. METHODS: Combining multimodal MRI data from 208 MS patients, 200 NMOSD patients and 228 healthy controls and brain-wide transcriptional data, this study characterized convergent and divergent alterations in within-cerebellar and cerebello-cerebral morphological and functional connectivity in MS and NMOSD, and further explored the association between the connectivity alterations and gene expression profiles. RESULTS: Despite numerous common alterations in the two conditions, diagnosis-specific increases in cerebellar morphological connectivity were found in MS within the cerebellar secondary motor module, and in NMOSD between cerebellar primary motor module and cerebral motor- and sensory-related areas. Both diseases also exhibited decreased functional connectivity between cerebellar motor modules and cerebral association cortices with MS-specific decreases within cerebellar secondary motor module and NMOSD-specific decreases between cerebellar motor modules and cerebral limbic and default-mode regions. Transcriptional data explained > 37.5% variance of the cerebellar functional alterations in MS with the most correlated genes enriched in signaling and ion transport-related processes and preferentially located in excitatory and inhibitory neurons. For NMOSD, similar results were found but with the most correlated genes also preferentially located in astrocytes and microglia. Finally, we showed that cerebellar connectivity can help distinguish the three groups from each other with morphological connectivity as predominant features for differentiating the patients from controls while functional connectivity for discriminating the two diseases. CONCLUSIONS: We demonstrate convergent and divergent cerebellar connectome alterations and associated transcriptomic signatures between MS and NMOSD, providing insight into shared and unique neurobiological mechanisms underlying these two diseases.

Low-Temperature Preparation of High-Quality Perovskite Polycrystalline Films via Crystallization Kinetics Engineering.

Preparation of lead halide perovskite polycrystalline films at a low annealing temperature is highly restricted by their intrinsically large crystallization activation energy, which hinders the conversion of the precursors/intermediates to perovskites and yields as-prepared polycrystals with tiny grain sizes and terrible crystal quality. Herein, we demonstrate through in-situ, real-time spectroscopic studies that both the nucleation and crystal growth kinetics can be improved without the need for a high annealing temperature by treating the film with thiourea, as accounted for by the reduced activation energy. As a consequence, the thiourea-treated perovskite polycrystalline film exhibits larger grain sizes and greater crystallinity than the untreated one. More importantly, owing to the synergistic effect of the promoted crystallization kinetics and the passivation of surface defects, the low-temperature prepared films treated with thiourea even present more prominent photophysical properties than those fabricated by using the conventional high-temperature method. The strategy of crystallization kinetics engineering proposed in this work paves the way for fabricating high-quality perovskite polycrystalline films in a low-temperature manner.

Association between ambient air pollutants and birthweight of singletons following assisted reproductive technologies.

OBJECTIVE: To investigate the associations between exposure to ambient air pollutants and birthweight following ART treatment. DESIGN: Retrospective cohort study. METHODS: We included 11,599 singletons derived from fresh cycles or frozen-thawed embryo transfer (FET) cycles between Jan 2013 and Dec 2019. Exposure to six air pollutants (SO2, NO2, CO, O3, PM2.5, and PM10) at patients` residences and the clinic site were estimated using the inverse distance weighting interpolation method based on data obtained from monitor sites. The daily mean levels of pollutants were estimated in potential exposure windows (the period from three months before treatment to oocyte retrieval, the period of ovarian stimulation, the period of in vitro culture, the period from embryo transfer to hCG test, the period of entire pregnancy, the 1st, 2nd, and 3rd trimester) were calculated. Generalized additive models adjusted for confounders including maternal age, BMI, and parity were used to evaluate the association between exposures and birthweight. Interaction of exposures and ART-associated factors, such as supraphysiologic estradiol and frozen-thawed, were explored in an XGboost model. MAIN OUTCOME MEASURES: Birthweight and z-score of singletons. RESULTS: In fresh cycles, O3 exposure during the period from three months before treatment to oocyte retrieval and SO2 exposure during in vitro culture at the ART clinic showed a linear association with birthweight (7.24, 95% CI: 1.18-13.31 g per 10 µg/m3 increase in O3; 25.92, 95% CI: 8.26-43.58 g per 10 µg/m3 increase in SO2, respectively). For patients receiving single blastocyst transfer with exposures below the China standard of 20 µg/m3, an increase of 10 µg/m3 in SO2 was associated with a 61.52 (95% CI: 1.13-121.91) g increase in birthweight. In FET cycles, no significant association was found between air pollution and birthweight. XGboost model did not reveal a strong interaction between the exposures and ART-related factors, except for the interactions between O3 exposure and BMI. However, none of the interactions reached a higher rank of importance. CONCLUSIONS: Air pollution exposure during ART treatment may affect the birthweight of the offspring.

Defect management by a cesium fluoride-modified electron transport layer promotes perovskite solar cells.

SnO2 is a candidate material for electron transport layers (ETLs) in perovskite solar cells (PSCs). However, a large number of defects at the SnO2/perovskite interface lead to notable non-radiative interfacial recombination. Moreover, the energy level arrangement between SnO2/perovskite does not match well. In this study, a SnO2/CsF-SnO2 double-layer ETL was prepared by doping CsF into SnO2, effectively passivating the defects of the SnO2 ETL and SnO2/perovskite interface. The formation of a good energy level arrangement with the perovskite layer reduces the interface non-radiative recombination and improves the performance of the interface charge extraction. The photoelectric conversion efficiency of the optimal CsF-modified PSC reached 22.18%, owing to the significant increase in the open-circuit voltage to 1.180 V.

Polyethylene glycol recombinant human growth hormone in Chinese prepubertal slow-growing short children: doses reported in a multicenter real-world study.

BACKGROUND: To evaluate the effectiveness of individualized-dose polyethylene glycol recombinant human growth hormone (PEG-rhGH) for short stature. METHODS: This real-world study enrolled children with short stature in 19 hospitals throughout China. They were treated with PEG-rhGH for 6 months. The starting dosage ranged from 0.10 to 0.20 mg/kg/week. The primary outcome was the change in height standard deviation score (ΔHt SDS). RESULTS: Five hundred and ten patients were included and grouped based on dosage as A (0.10-0.14 mg/kg/week), B (0.15-0.16 mg/kg/week), C (0.17-0.19 mg/kg/week), and D (0.20 mg/kg/week). The mean 6-month ΔHt SDS for the total cohort was 0.49 ± 0.27, and the means differed among the four dose groups (P = 0.002). The ΔHt SDS was lower in group A than in groups B (LSM difference [95%CI], -0.09 [-0.17, -0.01]), C (LSM difference [95%CI], -0.10 [-0.18, -0.02]), and D (LSM difference [95%CI], -0.13 [-0.21, -0.05]) after adjusting baseline covariates. There were no significant differences among groups B, C, and D. When the baseline IGF-1 was < -2 SDS or > 0 SDS, the △Ht SDS was not different among the four groups (P = 0.931 and P = 0.400). In children with baseline IGF-1 SDS of -2 ~ 0 SDS, a higher dosage was associated with a better treatment effect (P = 0.003), and the △Ht SDS was lower in older children than in younger ones (P < 0.001). CONCLUSIONS: PEG-rhGH could effectively increase height in prepubertal short children. When the baseline IGF-1 was < -2 SDS, 0.10 mg/kg/week could be a starting dose. In other IGF-1 statuses, 0.15-0.20 mg/kg/week might be preferred. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03249480 , retrospectively registered.

Spectral-Free Double Light Detection of DNA Based on a Porous Silicon Bragg Mirror.

To improve the detection sensitivity of a porous silicon optical biosensor in the real-time detection of biomolecules, a non-spectral porous silicon optical biosensor technology, based on dual-signal light detection, is proposed. Double-light detection is a combination of refractive index change detection and fluorescence change detection. It uses quantum dots to label probe molecules to detect target molecules. In the double-signal-light detection method, the first detection-signal light is the detection light that is reflected from the surface of the porous silicon Bragg mirror. The wavelength of the detection light is the same as the wavelength of the photonic band gap edge of the porous silicon Bragg mirror. CdSe/ZnS quantum dots are used to label the probe DNA and hybridize it with the target DNA molecules in the pores of porous silicon to improve its effective refractive index and enhance the detection-reflection light. The second detection-signal light is fluorescence, which is generated by the quantum dots in the reactant that are excited by light of a certain wavelength. The Bragg mirror structure further enhances the fluorescence signal. A digital microscope is used to simultaneously receive the digital image of two kinds of signal light superimposed on the surface of porous silicon, and the corresponding algorithm is used to calculate the change in the average grey value before and after the hybridization reaction to calculate the concentration of the DNA molecules. The detection limit of the DNA molecules was 0.42 pM. This method can not only detect target DNA by hybridization, but also detect antigen by immune reaction or parallel biochip detection for a porous silicon biosensor.

lncRNA BSG-AS1 is hypoxia-responsive and promotes hepatocellular carcinoma by enhancing BSG mRNA stability.

Emerging evidence indicates that aberrant changes of lncRNAs expression induced by hypoxia participate in the development of HCC. The present study aimed to identify novel hypoxia-responsive lncRNAs and reveal its role and mechanism in HCC. Hypoxia exposure in HCC tissues was comprehensively estimated based on public data using multiple hypoxia gene signatures. Huh7 cells were treated with hypoxia and RNA-seq was performed. Then we analyzed the changes of lncRNAs in HCC tissues and cells exposed to hypoxia. We found that lncRNA BSG-AS1 was highly expressed in tissues with high hypoxia score. Then we verified the response of lncRNA BSG-AS1 to hypoxia in the cell hypoxia model in vitro. Through functional phenotypic analysis, we found that lncRNA BSG-AS1 can mediate the promoting effect of hypoxia on the proliferation and migration in HCC cells. RNA-seq was used to find the downstream target genes of lncRNA BSG-AS1. Sequencing data and wet experiments showed that mRNA of BSG decreased after knockout of lncRNA BSG-AS1, and mediated the promotive effect of lncRNA BSG-AS1 on proliferation and migration in HCC cells. The mechanism is that lncRNA BSG-AS1 can enhance the stability of BSG mRNA as antisense lncRNA. Finally, the data based on the public cohort and the cohort we collected suggested that the overexpression of lncRNA BSG-AS1 and BSG are related to the poor prognosis. In conclusion, lncRNA BSG-AS1 is a novel hypoxia-responsive lncRNA. LncRNA BSG-AS1 can positively regulate BSG, by maintaining the mRNA stability of BSG, thus promoting the proliferation and migration of HCC. High expression of lncRNA BSG-AS1 and BSG are risk factors for prognosis.

Effects of Different Land Use Types on Active Autotrophic Ammonia and Nitrite Oxidizers in Cinnamon Soils.

Land use types with different disturbance gradients show many variations in soil properties, but the effects of different land use types on soil nitrifying communities and their ecological implications remain poorly understood. Using 13CO2-DNA-based stable isotope probing (DNA-SIP), we examined the relative importance and active community composition of ammonia-oxidizing archaea (AOA) and bacteria (AOB) and nitrite-oxidizing bacteria (NOB) in soils under three land use types, forest, cropland, and greenhouse vegetable soil, representing three interference gradients. Soil net nitrification rate was in the order forest soil > cropland soil > greenhouse vegetable soil. DNA-SIP showed that active AOA outcompeted AOB in the forest soil, whereas AOB outperformed AOA in the cropland and greenhouse vegetable soils. Cropland soil was richer in NOB than in AOA and AOB. Phylogenetic analysis revealed that ammonia oxidation in the forest soil was predominantly catalyzed by the AOA Nitrosocosmicus franklandus cluster within the group 1.1b lineage. The 13C-labeled AOB were overwhelmingly dominated by Nitrosospira cluster 3 in the cropland soil. The active AOB Nitrosococcus watsonii lineage was observed in the greenhouse vegetable soil, and it played an important role in nitrification. Active NOB communities were closely affiliated with Nitrospira in the forest and cropland soils, and with Nitrolancea and Nitrococcus in the greenhouse vegetable soil. Canonical correlation analysis showed that soil pH and organic matter content significantly affected the active nitrifier community composition. These results suggest that land use types with different disturbance gradients alter the distribution of active nitrifier communities by affecting soil physicochemical properties. IMPORTANCE Nitrification plays an important role in the soil N cycle, and land use management has a profound effect on soil nitrifiers. It is unclear how different gradients of land use affect active ammonia-oxidizing archaea and bacteria and nitrite-oxidizing bacteria. Our research is significant because we determined the response of nitrifiers to human disturbance, which will greatly improve our understanding of the niche of nitrifiers and the differences in their physiology.

Long noncoding RNA mediates stroke-induced neurogenesis.

Neurogenesis contributes to poststroke recovery. Long noncoding RNAs (lncRNAs) participate in the regulation of stem cell self-renewal and differentiation. However, the role of lncRNAs in stroke-induced neurogenesis remains unknown. In this study, we found that H19 was the most highly upregulated lncRNA in neural stem cells (NSCs) of the subventricular zone (SVZ) of rats subjected to focal cerebral ischemia. Deletion of H19 suppressed cell proliferation, promoted cell death, and blocked NSC differentiation. RNA sequencing analysis revealed that genes deregulated by H19 knockdown were those that are involved in transcription, apoptosis, proliferation, cell cycle, and response to hypoxia. H19 knockdown significantly increased the transcription of cell cycle-related genes including p27, whereas overexpression of H19 substantially reduced expression of these genes through the interaction with chromatin remodeling proteins EZH2 and SUZ12. Moreover, H19 regulated neurogenesis-related miRNAs. Inactivation of H19 in NSCs of ischemic rats attenuated spontaneous functional recovery after stroke. Collectively, our data provide novel insights into the epigenetic regulation of lncRNAs in stroke-induced neurogenesis.

Brain structural and functional alterations in MOG antibody disease.

BACKGROUND: The impact of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) on brain structure and function is unknown. OBJECTIVES: The aim of this study was to study the multimodal brain MRI alterations in MOGAD and to investigate their clinical significance. METHODS: A total of 17 MOGAD, 20 aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders (AQP4 + NMOSD), and 28 healthy controls (HC) were prospectively recruited. Voxel-wise gray matter (GM) volume, fractional anisotropy (FA), mean diffusivity (MD), and degree centrality (DC) were compared between groups. Clinical associations and differential diagnosis were determined using partial correlation and stepwise logistic regression. RESULTS: In comparison with HC, MOGAD had GM atrophy in frontal and temporal lobe, insula, thalamus, and hippocampus, and WM fiber disruption in optic radiation and anterior/posterior corona radiata; DC decreased in cerebellum and increased in temporal lobe. Compared to AQP4 + NMOSD, MOGAD presented lower GM volume in postcentral gyrus and decreased DC in cerebellum. Hippocampus/parahippocampus atrophy associated with Expanded Disability Status Scale (R = -0.55, p = 0.04) and California Verbal Learning Test (R = 0.62, p = 0.031). The differentiation of MOGAD from AQP4 + NMOSD achieved an accuracy of 95% using FA in splenium of corpus callosum and DC in occipital gyrus. CONCLUSION: Distinct structural and functional alterations were identified in MOGAD. Hippocampus/parahippocampus atrophy associated with clinical disability and cognitive impairment.

Achieving Molecular Fluorescent Conversion from Aggregation-Caused Quenching to Aggregation-Induced Emission by Positional Isomerization.

In this work, we synthesized a pair of positional isomers by attaching a small electron-donating pyrrolidinyl group at ortho- and para-positions of a conjugated core. These isomers exhibited totally different fluorescent properties. PDB2 exhibited obvious aggregation-induced emission properties. In contrast, PDB4 showed the traditional aggregation-caused quenching effect. Their different fluorescent properties were investigated by absorption spectroscopy, fluorescence spectroscopy, density functional theory calculations and single-crystal structural analysis. These results indicated that the substituent position of the pyrrolidinyl groups affects the twisted degree of the isomers, which further induces different molecular packing modes, thus resulting in different fluorescent properties of these two isomers. This molecular design concept provided a new accurate strategy for designing new aggregation-induced emission luminogens.

Ischemic Cerebral Endothelial Cell-Derived Exosomes Promote Axonal Growth.

BACKGROUND AND PURPOSE: Cerebral endothelial cells (CECs) and axons of neurons interact to maintain vascular and neuronal homeostasis and axonal remodeling in normal and ischemic brain, respectively. However, the role of exosomes in the interaction of CECs and axons in brain under normal conditions and after stroke is unknown. METHODS: Exosomes were isolated from CECs of nonischemic rats and is chemic rats (nCEC-exos and isCEC-exos), respectively. A multicompartmental cell culture system was used to separate axons from neuronal cell bodies. RESULTS: Axonal application of nCEC-exos promotes axonal growth of cortical neurons, whereas isCEC-exos further enhance axonal growth than nCEC-exos. Ultrastructural analysis revealed that CEC-exos applied into distal axons were internalized by axons and reached to their parent somata. Bioinformatic analysis revealed that both nCEC-exos and isCEC-exos contain abundant mature miRNAs; however, isCEC-exos exhibit more robust elevation of select miRNAs than nCEC-exos. Mechanistically, axonal application of nCEC-exos and isCEC-exos significantly elevated miRNAs and reduced proteins in distal axons and their parent somata that are involved in inhibiting axonal outgrowth. Blockage of axonal transport suppressed isCEC-exo-altered miRNAs and proteins in somata but not in distal axons. CONCLUSIONS: nCEC-exos and isCEC-exos facilitate axonal growth by altering miRNAs and their target protein profiles in recipient neurons.

An AMPK/Axin1-Rac1 signaling pathway mediates contraction-regulated glucose uptake in skeletal muscle cells.

Contraction stimulates skeletal muscle glucose uptake predominantly through activation of AMP-activated protein kinase (AMPK) and Rac1. However, the molecular details of how contraction activates these signaling proteins are not clear. Recently, Axin1 has been shown to form a complex with AMPK and liver kinase B1 during glucose starvation-dependent activation of AMPK. Here, we demonstrate that electrical pulse-stimulated (EPS) contraction of C2C12 myotubes or treadmill exercise of C57BL/6 mice enhanced reciprocal coimmunoprecipitation of Axin1 and AMPK from myotube lysates or gastrocnemius muscle tissue. Interestingly, EPS or exercise upregulated total cellular Axin1 levels in an AMPK-dependent manner in C2C12 myotubes and gastrocnemius mouse muscle, respectively. Also, direct activation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleotide treatment of C2C12 myotubes or gastrocnemius muscle elevated Axin1 protein levels. On the other hand, siRNA-mediated Axin1 knockdown lessened activation of AMPK in contracted myotubes. Further, AMPK inhibition with compound C or siRNA-mediated knockdown of AMPK or Axin1 blocked contraction-induced GTP loading of Rac1, p21-activated kinase phosphorylation, and contraction-stimulated glucose uptake. In summary, our results suggest that an AMPK/Axin1-Rac1 signaling pathway mediates contraction-stimulated skeletal muscle glucose uptake.

Ablation of the microRNA-17-92 cluster in neural stem cells diminishes adult hippocampal neurogenesis and cognitive function.

Impairment of adult neurogenesis in the hippocampus causes cognitive deficits; however, the underlying molecular mechanisms have not been fully elucidated. microRNAs (miRNAs) regulate neural stem cell (NSC) function. With the use of a transgenic mouse line with conditional ablation of the miR-17-92 cluster in nestin lineage NSCs, we tested the hypothesis that the miR-17-92 cluster regulates adult neurogenesis and cognitive function in vivo. Compared with wild-type mice, ablation of the miR-17-92 cluster significantly reduced the number of proliferating NSCs and neuroblasts and neuronal differentiation in the dentate gyrus (DG) of the hippocampus and significantly impaired hippocampal-dependent learning and memory, as assayed by social recognition memory, novel object recognition, and Morris water-maze tests. Statistical analysis showed a highly significant correlation between newly generated neuroblasts in the DG and cognition deficits in miR-17-92 knockout (KO) mice. Western blot analysis showed that conditional KO of the miR-17-92 cluster significantly increased and reduced a cytoskeleton-associated protein, Enigma homolog 1 (ENH1), and its downstream transcription factor, inhibitor of differentiation 1 (ID1), respectively, as well as increased phosphatase and tensin homolog gene. These proteins are related to neuronal differentiation. Our study demonstrates that the miR-17-92 cluster in NSCs is critical for cognitive and behavioral function and regulates neurogenesis and that the miR-17-92 cluster may target ENH1/ID1 signaling.-Pan, W. L., Chopp, M., Fan, B., Zhang, R., Wang, X., Hu, J., Zhang, X. M., Zhang, Z. G., Liu, X. S. Ablation of the microRNA-17-92 cluster in neural stem cells diminishes adult hippocampal neurogenesis and cognitive function.

Final adult height of children with idiopathic short stature: a multicenter study on GH therapy alone started during peri-puberty.

BACKGROUND: To evaluate the efficacy of GH in improving FAH in ISS children in a multicenter study. METHODS: A real-world observation was carried out. Children with ISS in seven hospitals in China were enrolled. The height gains standard deviation score and the height gain over the target height were evaluated. RESULTS: There were 344 ISS patients (217 boys and 127 girls). The baseline average age of boys and girls was 12.7 and 11.7 years, with bone age of 11.7 and 10.1 years, respectively. The baseline height SDS of boys and girls was - 3.07 and - 2.74, and the FAH SDS was - 1.91 and - 1.38, respectively. Compared with the baseline height SDS, the FAH SDS was significantly increased in both boys and girls (both P = 0.0000). The FAH SDS was the highest (gain by 1.54 SD) in the ≥2y treatment course group. Two hundred eighteen patients (218/344, 63.4%) had a FAH SDS > - 2 SD. Among these patients, girls in the 1-2y treatment course group and ≥ 2y group had a FAH SDS higher than TH SDS. Even in the control group, a spontaneous catch-up growth of 1.16 SD was observed. A multivariate linear regression model was used to analyze the results, with FAH SDS as the dependent variable. It was found that the treatment course and baseline height SDS in the boys' model were statistically significant (P < 0.05), whereas the baseline height SDS and baseline bone age significantly affected the girls' FAH SDS (P < 0.05). CONCLUSIONS: Both girls and boys of ISS improved FAH by GH therapy even if treatments begin over 10 years old and majority of them reached TH. Some peri-puberty ISS will have a spontaneous height gain. We recommend the course of GH treatment more than 2 years for girls, and longer courses for boys.

Investigating the biomechanical function of the plate-type external fixator in the treatment of tibial fractures: a biomechanical study.

BACKGROUND: The design of an external fixator with the optimal biomechanical function and the lowest profile has been highly pursued, as fracture healing is dependent on the stability and durability of fixation, and a low profile is more desired by patients. The plate-type external fixator, a novel prototype of an external tibial fixation device, is a low profile construct. However, its biomechanical properties remain unclear. The objective of this study was to investigate the stiffness and strength of the plate-type external fixator and the unilateral external fixator. We hypothesized that the plate-type external fixator could provide higher stiffness while retaining sufficient strength. METHODS: Fifty-four cadaver tibias underwent a standardized midshaft osteotomy to create a fracture gap model to simulate a comminuted diaphyseal fracture. All specimens were randomly divided into three groups of eighteen specimens each and stabilized with either a unilateral external fixator or two configurations of the plate-type external fixator. Six specimens of each configuration were tested to determine fixation stiffness in axial compression, four-point bending, and torsion, respectively. Afterwards, dynamic loading until failure was performed in each loading mode to determine the construct strength and failure mode. RESULTS: The plate-type external fixator provided higher stiffness and strength than the traditional unilateral external fixator. The highest biomechanics were observed for the classical plate-type external fixator, closely followed by the extended plate-type external fixator. CONCLUSIONS: The plate-type external fixator is stiffer and stronger than the traditional unilateral external fixator under axial compression, four-point bending and torsion loading conditions.

Design and Synthesis of a Novel NIR Celecoxib-Based Fluorescent Probe for Cyclooxygenase-2 Targeted Bioimaging in Tumor Cells.

Cyclooxygenase-2 (COX-2) imaging agents are potent tools for early cancer diagnosis. Almost all of the COX2 imaging agents using celecoxib as backbone were chemically modified in the position of N-atom in the sulfonamide group. Herein, a novel COX-2 probe (CCY-5) with high targeting ability and a near-infrared wavelength (achieved by attaching a CY-5 dye on the pyrazole ring of celecoxib using a migration strategy) was evaluated for its ability to probe COX-2 in human cancer cells. CCY-5 is expected to have high binding affinity for COX-2 based on molecular docking and enzyme inhibition assay. Meanwhile, CCY-5 caused stronger fluorescence imaging of COX-2 overexpressing cancer cells (Hela and SCC-9 cells) than that of normal cell lines (RAW 264.7 cells). Lipopolysaccharide (LPS) treated RAW264.7 cells revealed an enhanced fluorescence as LPS was known to induce COX-2 in these cells. In inhibitory studies, a markedly reduced fluorescence intensity was observed in cancer cells, when they were co-treated with a COX-2 inhibitor celecoxib. Therefore, CCY-5 may be a selective bioimaging agent for cancer cells overexpressing COX-2 and could be useful as a good monitoring candidate for effective diagnosis and therapy in cancer treatment.