A secreted bacterial protein protects bacteria from cationic antimicrobial peptides by entrapment in phase-separated droplets.

Mammalian hosts combat bacterial infections through the production of defensive cationic antimicrobial peptides (CAPs). These immune factors are capable of directly killing bacterial invaders; however, many pathogens have evolved resistance evasion mechanisms such as cell surface modification, CAP sequestration, degradation, or efflux. We have discovered that several pathogenic and commensal proteobacteria, including the urgent human threat Neisseria gonorrhoeae, secrete a protein (lactoferrin-binding protein B, LbpB) that contains a low-complexity anionic domain capable of inhibiting the antimicrobial activity of host CAPs. This study focuses on a cattle pathogen, Moraxella bovis, that expresses the largest anionic domain of the LbpB homologs. We used an exhaustive biophysical approach employing circular dichroism, biolayer interferometry, cross-linking mass spectrometry, microscopy, size-exclusion chromatography with multi-angle light scattering coupled to small-angle X-ray scattering (SEC-MALS-SAXS), and NMR to understand the mechanisms of LbpB-mediated protection against CAPs. We found that the anionic domain of this LbpB displays an α-helical secondary structure but lacks a rigid tertiary fold. The addition of antimicrobial peptides derived from lactoferrin (i.e. lactoferricin) to the anionic domain of LbpB or full-length LbpB results in the formation of phase-separated droplets of LbpB together with the antimicrobial peptides. The droplets displayed a low rate of diffusion, suggesting that CAPs become trapped inside and are no longer able to kill bacteria. Our data suggest that pathogens, like M. bovis, leverage anionic intrinsically disordered domains for the broad recognition and neutralization of antimicrobials via the formation of biomolecular condensates.

Numerical simulation of ultrawideband supercontinuum generation covering a 2-20 µm waveband in cascaded all-soft-glass fiber.

We designed a cascaded all-soft-glass fiber structure and simulate midinfrared 2-20 µm ultrawideband supercontinuum (SC) generation numerically. The cascaded fiber structure consists of a 1.5 m I n F 3 fiber, a 0.2 m chalcogenide photonic crystal fiber, and a 0.2 m tellurium-based chalcogenide photonic crystal fiber. Using a 2 µm pulse pumping this cascaded structure, the generated SC covering the wavelengths longer than 20 µm has been demonstrated theoretically. The 30 dB bandwidth reaches 20.87 µm from 1.44 to 22.31 µm. The effect of different pulse widths on SC generation is considered. With the increase of peak power and the decrease of pulse width, the energy of SC in the 15-20 µm waveband increases gradually. The mechanism of SC broadening process has also been analyzed. The SC generation of more than 20 µm in this cascade structure is caused by the self-phase modulation, soliton effects, four-wave mixing, and redshifted dispersive wave. This method demonstrates the possibility of generating ultrawide bandwidth SCs up to a 20 µm waveband by a commercial 2 µm pump source and all-fiber structure.

Decaying dynamics of harmonic mode-locking in a SESAM-based mode-locked fiber laser.

The entire decaying dynamics of harmonic mode-locking (HML) are studied utilizing the dispersive Fourier transform (DFT) technique in a SESAM-based mode-locked fiber laser. It is unveiled that the harmonic solitons do not disappear directly, but undergo transitional processes from the higher-order HML to the lower-order HML and then to the fundamental mode-locking (FML), and finally vanish. The "big corner" can also exist in the decaying process rather than just in the buildup process of HML, and there is at least one "big corner" during the decaying process between the consecutive multi-pulsing states. The energy stabilization phase (ESP) cannot be observed during every transitional process. A breathing behavior and a vibrating soliton molecule are observed in the decaying process from the 2nd HML to the FML and in the decaying process of the FML, respectively. Our work would enrich the understanding of HML behaviors and may contribute to the laser designs.

Bio-Inspired Hydrogel-Elastomer Actuator with Bidirectional Bending and Dynamic Structural Color.

In nature, some creatures can change their body shapes and surface colors simultaneously to respond to the external environments, which greatly inspired researchers in the development of color-tunable soft actuators. In this work, we present a facile method to prepare a smart hydrogel actuator that can bend bidirectionally and change color simultaneously, just like an octopus. The actuator is fabricated by elastomer/hydrogel bilayer and the hydrogel layer was decorated with thermoresponsive microgels as the photonic crystal blocks. Compared with the previously reported poly(N-isopropylacrylamide) hydrogel-based bilayer hydrogel actuators, which are generally limited to one-directional deformation, the elastomer/hydrogel bilayer actuator prepared in our work exhibits unique bidirectional bending behavior in accordance with the change of structural color. The bending degrees can be changed from -360° to 270° in response to solution temperatures ranging from 20 °C to 60 °C. At the same time, the surface color changes from red to green, and then to blue, covering the full visible light spectrum. The bending direction and degree of the hydrogel actuator can easily be adjusted by tuning the layer thickness ratio of the elastomer/hydrogel or the composition of the hydrogel. The color-tunable hydrogel-elastomer actuator reported in this work can achieve both programmable deformations and color-changing highly resembling the natural actuating behaviors of creatures.

High-efficiency mode-locked erbium-doped ZBLAN fiber laser around 2.8 µm by directly depositing Bi2S3 particles onto a cavity mirror.

Mid-infrared (MIR) pulsed lasers near a 3 µm waveband show great potential for the high absorption of water molecules and many important gas molecules. A passively Q-switched mode-locked (QSML) E r 3+-doped fluoride fiber laser with a low laser threshold and high slope efficiency around a 2.8 µm waveband is reported. The improvement is achieved by depositing bismuth sulfide (B i 2 S 3) particles onto the cavity mirror directly as a saturable absorber and using the cleaved end of the fluoride fiber as output directly. -QSML pulses begin to appear with the pump power of 280 mW. The repetition rate of the QSML pulses reaches a maximum of 33.59 kHz with the pump power of 540 mW. When the pump power is further increased, the output of the fiber laser switches from the QSML to the continuous-wave mode-locked operation with the repetition rate of 28.64 MHz and the slope efficiency of 12.2%. The results indicate that B i 2 S 3 is a promising modulator for the pulsed lasers near a 3 µm waveband, which paves the way for further development of various applications in MIR wavebands, including material processing, MIR frequency combs, and modern healthcare.

Case Report: Eosinophilic gastritis with pyloric stenosis in immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare X-linked recessive immunodeficiency caused by mutations in the forkhead box protein 3 (FOXP3) gene. IPEX is characterized by the onset of intractable diarrhea, type 1 diabetes mellitus (T1DM), and eczema in the early stages of life. The typical clinic triad for IPEX is not always seen. Here, we report a 15-year-old male patient with atypical IPEX syndrome complicated with severe eosinophilic gastritis (EG) and pyloric stenosis. The patient had noticeable eczema during the first year of life and had a history of food allergies. At the age of 3 years, the patient was diagnosed with EG, Helicobacter pylori (HP) infection, pyloric stenosis with recurrent vomiting, and failure to thrive. The patient did not respond to long-term symptomatic treatments in the following years, including methylprednisolone, proton pump inhibitors (PPI), L-glutamine and sodium gualenate granules, anti-HP therapy, and balloon dilation. At the age of 12 years, the patient received surgical interventions, including a laparoscopic jejunostomy feeding tube placement, gastrojejunal anastomosis bypass, and jejunal-jejunal end-to-side anastomosis. Intractable diarrhea and T1DM were not present in the patient. At the age of 14 years, the patient was diagnosed with IPEX syndrome due to a c.748-750del (p.Lys250del) mutation in the leucine zipper domain of the FOXP3 protein. The patient underwent matched sibling peripheral blood hematopoietic stem cell transplantation (HSCT) and showed good evolution after 3 months of HSCT. In summary, this case report provides information of unusual gastrointestinal findings in IPEX syndrome and highlights the need for increased awareness and early diagnosis of IPEX syndrome, which is vital for improving the patient's outcome.

Neuroprotective Effects of Curcumin against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in Cultured Primary Rat Astrocyte by Improving Mitochondrial Function and Regulating the ERK Signaling Pathway.

Objectives: Curcumin (Cur) is a natural polyphenol isolated from turmeric and has potent anti-inflammatory and antioxidant activities. This study aimed to explore the effects and possible mechanisms of curcumin on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in cultured rat astrocyte primary cells. Methods: After screening for effective doses, the cultured rat astrocyte primary cells were divided into three groups: control, OGD/R, and OGD/R + curcumin (10 µM, 20 µM, and 40 µM). Cell viability was detected using CCK8 assays. The level of malondialdehyde and superoxide dismutase activity was determined using commercial kits. The endothelial nitric oxide synthase and adenosine triphosphate concentrations were determined by enzyme-linked immunosorbent assay. The mRNA levels of the inflammatory indexes interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1ß were evaluated by quantitative reverse-transcription polymerase chain reaction. Annexin V-fluorescein isothiocyanate/propidium iodide was used to detect apoptosis. JC-1 was used to assess the mitochondrial membrane potential. The protein expression of apoptosis-related proteins (B-cell lymphoma-2 (Bcl-2), BCL-2-associated X (Bax), and cleaved caspase 3), mitochondria-related proteins (dynamin-related protein 1 (DRP1), phosphorylated DRP1 (p-DRP1), and mitofusin 2), and essential proteins of the extracellular signal-regulated kinase (ERK) signaling pathway (ERK1/2, p-ERK1/2) were analyzed by western blot. Results: Our data indicated that curcumin reversed OGD/R-induced cell viability loss, oxidative stress, inflammatory cytokine production, and cell apoptosis in a dose-dependent manner. Furthermore, curcumin attenuated OGD/R-induced mitochondrial dysfunction and ERK1/2 phosphorylation in a dose-dependent manner. Conclusions: Curcumin protected against OGD/R-induced injury in rat astrocyte primary cells through improving mitochondrial function and regulating the ERK signaling pathway.

Construction of AP003469.4-miRNAs-mRNAs ceRNA network to reveal potential biomarkers for hepatocellular carcinoma.

Studies have reported that the competing endogenous RNA (ceRNA) networks are related to disease progression and prognosis in patients with hepatocellular carcinoma (HCC). The roles and mechanisms of long-chain non-coding RNA AP003469.4 in HCC have remained unclear. Here, we explored the roles of AP003469.4 in HCC progression using bioinformatics, CCK-8, Transwell assay, etc. AP003469.4 targets miRNAs and these target genes were predicted by the LncBase Predicted v.2, miRDB, miRTarBase, and TargetScan databases. Then, AP003469.4-associated ceRNA network was constructed. Biological functions and mechanisms of differentially expressed genes in the ceRNA network were explored using GO and KEGG. Survival analysis and Cox regression analysis were used to screen prognostic genes and construct a prognostic risk model. The results revealed that AP003469.4, with the area under the curve of 0.9048, was highly expressed in HCC tissues. Increased expression of AP003469.4 was an independent risk factor for the dismal prognosis of HCC patients and was associated with the short overall and disease-free survival. Downregulation of AP003469.4 expression inhibited cell proliferation, cycle transition, invasion, and migration, and promoted cell apoptosis. There were 489 differentially expressed target genes in the ceRNA network, which were involved in several pathways, such as the MAPK signaling pathway, cell cycle, and p53 signaling pathway. The risk model was based on the DTYMK, ZFC3H1, CBX2, PKM, TTC26, ATG10, TAGLN2, CD3EAP, SHISA9, SLC1A5, KPNA2, SCML2, E2F7, and SMARCD1, which were the independent risk factors for poor prognosis of HCC patients. In general, interference with AP003469.4 expression might delay the progression of HCC. AP003469.4 related network could help to identify the hub target molecules in HCC progression, which might be candidate biomarkers for evaluating the prognosis of HCC patients.

Case report: Osteo-oto-hepato-enteric syndrome caused by UNC45A deficiency.

Background: Recently, UNC45 myosin chaperone A (UNC45A) deficiency was identified as a cause of osteo-oto-hepato-enteric syndrome (O2HE) characterized by congenital diarrhea, neonatal cholestasis, deafness, and bone fragility. To date, only a few O2HE cases have been reported in the literature. Case presentation: Here, we present a child from China diagnosed with O2HE with novel compound heterozygous variants in UNC45A. The patient suffered with neonatal jaundice, cholestasis, and intractable diarrhea after birth. Laboratory tests revealed highly elevated levels of total serum bilirubin (TB), direct bilirubin (DB), and total bile acid (TBA). The patient was managed with ursodeoxycholic acid (UDCA)-based treatments, and the clinical symptoms and abnormal liver functions were significantly relieved. The patient's hearing was normal, and no sign of bone fragility was observed. Exome sequencing (ES) identified novel compound heterozygote variants c.292C>T (p.Arg98Trp)/c.2534-2545del (p.Leu845-Met848del) in UNC45A, which were inherited from her mother and father, respectively. Both variants are predicted to be deleterious by in silico predictors. Conclusion: We present an O2HE child from China with novel compound heterozygous variants in UNC45A. Our patient's clinical manifestations were less severe than those of the previous reported cases, which expands the clinical spectrum of O2HE.

LPS-induced inflammatory response and apoptosis are mediated by Fra-1 upregulation and binding to YKL-40 in A549 cells.

Acute respiratory distress syndrome (ARDS) is a multifactorial syndrome that leads to increased morbidity and mortality in infants and children. The identification of novel biomarkers is critical for the treatment of ARDS. The present study aimed to investigate the effects of chitinase-3-like-1 protein (CHI3L1 or YKL-40) in an in vitro model of ARDS and to explore the potential underlying mechanisms. The in vitro model of ARDS was established in A549 alveolar epithelial type II cells, which were treated by lipopolysaccharide (LPS) to induce inflammation. Transfection was performed to alter YKL-40 expression. The mRNA and protein expression of YKL-40 was determined using reverse transcription-quantitative PCR and western blotting, respectively. Cell Counting Kit-8 and TUNEL assays were used to evaluate the cell viability and apoptosis, respectively. The production of cytokines was evaluated using specific ELISA kits. The relationship between YKL-40 and Fos-related antigen 1 (Fra-1) was verified using luciferase reporter and chromatin immunoprecipitation assays. The expression of the apoptotic proteins was detected using western blotting. The expression levels of YKL-40 and Fra-1 were increased in LPS-treated A549 cells. Higher levels of pro-inflammatory cytokines and induction of cell apoptosis were observed in LPS-treated A549 cells compared with the control. YKL-40 knockdown in LPS-treated A549 cells significantly decreased the production of pro-inflammatory cytokines and reduced cell apoptosis, whereas it concomitantly caused upregulation of Bax and downregulation of Bcl-2, cleaved caspase-3 and cleaved caspase-9. In addition, Fra-1 could directly bind to YKL-40 promoter and regulate its expression level. Overexpression of YKL-40 partly decreased the inhibitory effects of Fra-1 knockdown on the inflammatory response and induction of apoptosis. In summary, the findings from the present study indicated that Fra-1 could bind to YKL-40 and regulate its expression, whereas YKL-40 knockdown could further suppress LPS-induced inflammatory response and apoptosis in A549 cells. These data may provide novel evidence on the diagnosis and therapy of ARDS.

Programmable Color in a Free-Standing Photonic Microgel Film with Ultra-Fast Response.

In this work, a free-standing microgel film with programmable and angle-independent structural color is prepared via a simple but effective method. Dried poly(styrene-N-isopropylacrylamide-acrylic acid) (pStNIPAAmAA) microgels were stabilized by inter-microgel crosslinking, and thus, only microgels were used to build the optical hydrogel. The free-standing microgel film displayed tunable structural color by the swelling/deswelling of the microgels under external stimuli, such as temperature, pH, ionic strength, and organic solvent. Moreover, the structural color of the film is angle-independent for the disordered microgel arrays. It is worth noting that programmable color stripes which have the panther chameleon's ability to change skin color are successfully fabricated by patterning microgels with different thermoresponsivities. More importantly, the microgel film has an ultrafast response to temperature (1.41 s from 20 to 40 °C) and pH (2.24 s from pH 8.3 to pH 2.0), much faster than that of most optical materials reported in previous studies.

Development of a non-biased, high-throughput ELISA for the rapid evaluation of immunogenicity and cross-reactivity.

Traditional ELISA-based protein analysis has been predicated on the assumption that proteins bind randomly to the solid surface of the ELISA plate polymer (polystyrene or polyvinyl chloride). Random adherence to the plate ensures equal access to all faces of the protein, an important consideration when evaluating immunogenicity of polyclonal serum samples as well as when examining the cross-reactivity of immune serum against different antigenic variants of a protein. In this study we demonstrate that the soluble form of the surface lipoprotein transferrin binding protein B (TbpB) from three different bacterial pathogens (Neisseria meningitidis, Actinobacillus pleuropneumoniae, and Mannheimia haemolytica) bind the ELISA plate in a manner that consistently obscures the transferrin binding face of the proteins' N-lobe. In order to develop a non-biased ELISA where all faces of the protein are accessible, the strong interaction between biotin and avidin has been exploited by adding a biotin tag to these proteins during Escherichia coli-based cytoplasmic expression and utilizing streptavidin or neutravidin coated ELISA plates for protein capture and display. The use of avidin coated ELISA plates also allows for rapid purification of biotin-tagged proteins from crude E. coli lysates, removing the requirement of prior affinity purification of each protein to be included in the ELISA-based analyses. In proof of concept experiments we demonstrate the utility of this approach for evaluating immunogenicity and cross-reactivity of serum from mice and pigs immunized with TbpBs from human and porcine pathogens.

Proof of Concept for Prevention of Natural Colonization by Oral Needle-Free Administration of a Microparticle Vaccine.

There has been substantial interest in the development of needle-free vaccine administration that has led to a variety of approaches for delivery through the skin for induction of a systemic immune response. The mucosal administration of vaccines has inherently been needle-free, but the simple application of vaccines on the mucosal surface by itself does not lead to mucosal immunity. Since many important bacterial infections develop after initial colonization of the upper respiratory tract of the host, prevention of colonization could not only prevent infection but also eliminate the reservoir of pathogens that reside exclusively in that ecologic niche. This study was designed to provide proof of concept for a needle-free immunization approach that would reduce or eliminate colonization and prevent infection. In order to accomplish this a microparticle vaccine preparation was delivered just below the oral mucosal epithelial cell layer where it would lead to a robust immune response. A vaccine antigen (mutant transferrin binding protein B) shown to be capable of preventing infection in pigs was incorporated into a polyphosphazene microparticle preparation and delivered by a needle-free device to the oral sub-epithelial space of pigs. This vaccination regimen not only provided complete protection from infection after intranasal challenge by Glaesserella parasuis but also eliminated natural colonization by this bacterium. Notably, the complete prevention of natural colonization was dependent upon delivery of the microparticle preparation below the epithelial layer in the oral mucosa as intradermal or intramuscular delivery was not as effective at preventing natural colonization. This study also demonstrated that a primary immunization in the presence of maternal antibody limited the resulting antibody response but a robust antibody response after the second immunization indicated that maternal antibody did not prevent induction of B-cell memory.

Effects of rivastigmine hydrogen tartrate and donepezil hydrochloride on the cognitive function and mental behavior of patients with Alzheimer's disease.

The present study aimed to examine the effects of rivastigmine hydrogen tartrate and donepezil hydrochloride on the cognitive function and mental behavior of patients with Alzheimer's disease (AD). For this purpose, a total of 126 patients with AD admitted to Luoyang Central Hospital from January, 2018 to December, 2018 were enrolled. Patients were divided into different groups according to the treatment they selected. Patients treated with single-agent donepezil were separated into a monotherapy group (n=56), and patients receiving donepezil plus rivastigmine were placed in the combination group (n=70). Before and after treatment, the cognitive functions, mental behavior and quality of life of the patients in the two groups were respectively evaluated by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the Mini-Mental State Examination (MMSE), the Blessed-Roth Dementia Scale (BRDS) and the QOL-AD. In addition, the serum bradykinin level was detected by enzyme-linked immunosorbent assay. Following treatment, the MMSE score, BRDS, ADAS-Cog and QOL-AD scores were improved compared with those before treatment (P<0.05). However, following treatment, the 4 scores in the combination group were significantly higher than those in the monotherapy group (P<0.05). No significant differences were observed in the incidence of adverse reactions between the 2 groups (P>0.05). Following treatment, the bradykinin level in both groups was significantly decreased (P<0.05), although the decrease in the combination group was more significant than that in the monotherapy group (P<0.05). On the whole, the findings of the present study indicate that rivastigmine hydrogen tartrate used in combination with donepezil hydrochloride relieves the symptoms and improves the quality of life of patients with AD more effectively, which may be related to the reduction of the bradykinin level in these patients.

Apolipoprotein D alleviates glucocorticoid-induced osteogenesis suppression in bone marrow mesenchymal stem cells via the PI3K/Akt pathway.

BACKGROUND: To clarify the role of apolipoprotein D (Apod) in alleviating glucocorticoid-induced osteogenesis suppression in bone marrow mesenchymal stem cells (MSCs) via the PI3K/Akt pathway, thus influencing the progression of osteoporosis (OP). METHODS: Osteogenesis in MSCs was induced by dexamethasone (DEX) stimulation. Dynamic expressions of Apod in MSCs undergoing osteogenesis for different time points were determined by qRT-PCR. Relative levels of osteogenesis-associated genes, including ALP, RUNX2, and Osterix, in DEX-induced MSCs overexpressing Apod or not were examined. Moreover, the protein level of RUNX2, ALP, and Osterix; ALP activity; and mineralization ability influenced by Apod in osteogenic MSCs were assessed. At last, the potential influences of Apod on the PI3K/Akt pathway were identified through detecting the expression levels of PI3K and Akt in MSCs by Western blot. RESULTS: Apod was time-dependently upregulated in MSCs undergoing osteogenesis. DEX induction downregulated ALP, RUNX2, and Osterix and attenuated ALP activity and mineralization ability in MSCs undergoing osteogenesis, which were partially reversed by overexpression of Apod. In addition, Apod overexpression upregulated the reduced levels of PI3K and Akt in DEX-induced MSCs. CONCLUSION: Apod alleviates glucocorticoid-induced osteogenesis suppression in MSCs via the PI3K/Akt pathway, thus protecting the progression of OP.

Reducing Neuron Apoptosis in the Pontine Micturition Center by Nerve Root Transfer for Restoration of Micturition Function after Spinal Cord Injury.

OBJECTIVE: The rate of neuronal apoptosis increases after spinal cord injury (SCI). Anastomosing the normal nerve roots above the SCI level to the injured sacral nerve roots can enhance the functional recovery of neurons. Therefore, we evaluated the effect of sacral nerve root transfer after SCI on pontine neuronal survival. METHODS: Sprague-Dawley rats were randomly divided into three groups: Group A, reconstruction of afferent and efferent nerve pathways of the bladder after SCI; Group B, SCI only; and Group C, control group. We examined pontine neuronal morphology using hematoxylin and eosin (H&E) staining after SCI and nerve transfer. Bcl-2 and Bax protein expression changes in the pontine micturition center were quantified by immunohistochemistry. The number of apoptotic neurons was determined by TUNEL staining. We examined pontine neuronal apoptosis by transmission electron microscopy (TEM) at different time points. RESULTS: H&E staining demonstrated that the number of neurons had increased in Group A, but more cells in Group B displayed nuclear pyknosis, with the disappearance of the nucleus. Compared with Group B, Group A had significantly higher Bcl-2 expression, significantly lower Bax expression, and a significantly higher Bcl-2/Bax ratio. The number of apoptotic neurons and neuron bodies in Group A was significantly lower than that in Group B, as indicated by TUNEL staining and TEM. CONCLUSIONS: These findings demonstrate that lumbosacral nerve transfer can reduce neuronal apoptosis in the pontine micturition center and enhance functional recovery of neurons. This result further suggests that lumbosacral nerve transfer can be used as a new approach for reconstructing bladder function after spinal cord injury.

Syringic acid delivered via mPEG-PLGA-PLL nanoparticles enhances peripheral nerve regeneration effect.

Aim: To deliver syringic acid (SA) with a nanocarrier and enhance its function. Materials & methods: mPEG-PLGA-PLL (PEAL) nanoparticles were used to deliver SA. The characterization, storage stability, drug release, blood-compatibility and biocompatibility of SA-PEAL were detected by in vitro and in vivo assays. Cellular phenotypic experiments and rat sciatic nerve injury models were used to evaluate the function of SA-PEALs. Results: SA-PEAL had good storage stability, blood-compatibility and biocompatibility and could slowly release SA. SA-PEAL significantly enhanced the proliferation and migration ability of Schwann cells and function recovery of injured sciatic nerves. Conclusion: Our study provides an effective nano-delivery system for enhancing the neural repair function of SA and promoting further applications of SA.

Iron-Chelating Agent Can Maintain Bone Homeostasis Disrupted by Iron Overload by Upregulating Wnt/Beta-Catenin Signaling.

BACKGROUND: The incidence of osteoporotic fractures is increasing. In this study, we explored the activities of Wnt/ß-catenin signaling in bone tissues with iron accumulation. METHODS: We established rat bipedal walking models (RBWM), and a portion of our RBWM rats were intraperitoneally injected with ferric ammonium citrate, normal saline, and deferoxamine. Bone mineral density was measured with a small animal in vivo imaging system. The protein levels of ferritin, TRAP-5B, RANKL, and OPG in serum were measured by the enzyme-linked immunosorbent assay (ELISA). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to quantify the RNA and protein expression levels of certain regulators involved in Wnt/ß-catenin signaling in bone tissues. RESULTS: In the present study, we established a rat bipedal walking model containing 32 bipedal rats, which were randomly classified into four groups, termed as NS, FAC, FAC+NS, and FAC+DFO. Those three experimental groups with FAC injection had significantly lower bone mineral density (BMD) than the control group NS (P < 0.05). The disruption of bone homeostasis and downregulation of Wnt/ß-catenin signaling were also observed in the three groups with FAC injection. Moreover, after the injection of deferoxamine, those aberrations in samples with FAC injection seemed repaired as test results returning or getting close to normal ranges. CONCLUSION: The osteoporosis could be caused by iron overload, which reduced the bone mineral density by disrupting the homeostasis of bone formation and absorption and attenuating the Wnt/ß-catenin signaling in bone tissues. The deferoxamine had the potential to improve the bone health by reducing the accumulation of iron and increasing the bone mass, which might be a promising therapeutic solution for osteoporosis.

Study on the Formation of Glycine by Hydantoin and Its Kinetics.

The preparation of glycine by the hydantoin method is currently a relatively advanced process. The raw materials of this process are nontoxic, the operation process is simple and safe, the side reactions are few, and the yield of glycine is high. The core reaction of the hydantoin method is the hydrolysis of hydantoin. The hydrolysis is divided into two steps: first, hydantoin is hydrolyzed into hydantoin acid, and hydantoin acid is further hydrolyzed into glycine. At a temperature of 423.15 K, a molar ratio of sodium hydroxide to hydantoin of 1:3, and a total reaction time of 6 h, the conversion rate of hydantoin reached 100% and the yield of glycine reached 91%. At the same time, by calculating the hydrolysis kinetic parameters, the reaction was determined to be a first-order series reaction, and a kinetic model was established, which laid the foundation for the development of a green glycine process and a new reactor.

Clinical and molecular features of children with Beckwith-Wiedemann syndrome in China: a single-center retrospective cohort study.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a genetic overgrowth disorder with variable clinical features and cancer predisposition. In this study, we aim to characterize the clinical features and molecular defects of BWS patients in China. METHODS: Thirty-one patients with clinical suspicion of BWS were retrospectively recruited to the study from Shanghai Children's Hospital between January 2014 and December 2017. Clinical data, including demographics, clinical features, and molecular testing results were extracted and systematically analyzed. RESULTS: Twenty-one patients with a BWS score ≥ 4 (6, IQR 4, 7) were clinically diagnosed with BWS, and 10 children with a BWS score ≥ 2 and < 4 (2, IQR 2, 3) were clinically suspected BWS patients. The most common cardinal feature of clinically diagnosed patients was macroglossia (71.4%) followed by lateralized overgrowth (33.3%) and exomphalos (14.3%), and the major suggestive features were umbilical hernia and/or diastasis recti (65.0%) and ear creases or pits (61.9%). Among 10 clinically suspected BWS patients, macroglossia and lateralized overgrowth were observed in 3 (30%) and 2 (20%) patients, and umbilical hernia and/or diastasis recti occurred in 7 (70.0%) patients. Seven (33.3%) clinically diagnosed patients and 3 (30%) suspected patients were identified with loss of methylation at KCNQ1OT1:TSS differentially methylated region (DMR; IC2 LOM), 5 (23.8%) clinically diagnosed BWS patients were identified with gain of methylation at H19/IGF2:IG-DMR (IC1 GOM), and 1 (4.8%) clinically diagnosed BWS patients was identified with paternal uniparental isodisomy 11 (pUPD11). The phenotype-genotype correlation analysis showed no significant difference among patients with IC2 LOM, IC1 GOM, and pUPD11. CONCLUSIONS: The current study presents the first cohort study of BWS patients in mainland China. The clinical and molecular features of the patients are similar to those of other reported BWS patients in the Chinese population.