Electrospun Biomimetic Periosteum Capable of Controlled Release of Multiple Agents for Programmed Promoting Bone Regeneration.

The effective repair of large bone defects remains a major challenge due to its limited self-healing capacity. Inspired by the structure and function of the natural periosteum, an electrospun biomimetic periosteum is constructed to programmatically promote bone regeneration using natural bone healing mechanisms. The biomimetic periosteum is composed of a bilayer with an asymmetric structure in which an aligned electrospun poly(ε-caprolactone)/gelatin/deferoxamine (PCL/GEL/DFO) layer mimics the outer fibrous layer of the periosteum, while a random coaxial electrospun PCL/GEL/aspirin (ASP) shell and PCL/silicon nanoparticles (SiNPs) core layer mimics the inner cambial layer. The bilayer controls the release of ASP, DFO, and SiNPs to precisely regulate the inflammatory, angiogenic, and osteogenic phases of bone repair. The random coaxial inner layer can effectively antioxidize, promoting cell recruitment, proliferation, differentiation, and mineralization, while the aligned outer layer can promote angiogenesis and prevent fibroblast infiltration. In particular, different stages of bone repair are modulated in a rat skull defect model to achieve faster and better bone regeneration. The proposed biomimetic periosteum is expected to be a promising candidate for bone defect healing.

Chitosan nonwoven fabric composited calcium alginate and adenosine diphosphate as a hemostatic bandage for acute bleeding wounds.

Acute bleeding following accidental injury is a leading cause of mortality. However, conventional hemostatic bandages impede wound healing by inducing excessive blood loss, dehydration, and adherence to granulation tissue. Strategies such as incorporating active hemostatic agents and implementing chemical modifications can augment the properties of these bandages. Nevertheless, the presence of remote thrombosis and initiators may pose risks to human health. Here, a hemostatic bandage was developed by physically combined chitosan nonwoven fabric, calcium alginate sponge, and adenosine diphosphate. The presented hemostatic bandage not only exhibits active and passive mechanisms for promoting clotting but also demonstrates excellent mechanical properties, breathability, ease of removal without causing damage to the wound bed or surrounding tissues, as well as maintaining an optimal moist environment conducive to wound healing. In vitro evaluation results indicated that the hemostatic bandage possesses favorable cytocompatibility with low levels of hemolysis. Furthermore, it effectively aggregates various blood cells while activating platelets synergistically to promote both extrinsic and intrinsic coagulation pathways. In an in vivo rat model study involving liver laceration and femoral artery injury scenarios, our developed hemostatic bandage demonstrated rapid clot formation capabilities along with reduced blood loss compared to commercially available fabrics.

Effect of soluble phosphate and bentonite amendments on lead and cadmium bioavailability and bioaccessibility in a contaminated soil.

Effect of commonly used heavy metal immobilizing agents on risks of soil heavy metals has not been well investigated. In this work, a contaminated acidic soil (total Cd = 8.05, total Pb = 261 mg kg-1) was amended with soluble phosphate (P: 160 mg kg-1) and bentonite (3 g kg-1) and incubated for 360 d. The soil was then added to mouse feed at 1:9 soil: feed ratio (weight) and fed to mouse for 10 days, after which the liver, kidney and bone Pb and Cd concentrations were measured. The amended soils were extracted with SBRC and PBET to assay bioaccessibility, and extracted with DTPA to assess the environmental availability. The amendments did not affect the DTPA-Pb/Cd significantly (p > 0.05), while the Cd bioaccessibility in the gastric phase of the SBRC assay was reduced from 90.0 to 20.4 % for the bentonite amended treatment (p < 0.05). Kidney Pb and Cd concentrations of the mice fed with feed containing phosphate spiked soil was 80.2 and 66.0 % lower than the control mice fed with unamended soil (CK), respectively. Significant linear correlations were found between DTPA-extractable concentration and kidney concentrations for Pb/Cd. The effect of amendment on Pb/Cd bioavailability differed between the results calculated with different endpoints. The phosphate amendment resulted in 82.7 and 34.3 % lower Pb RBA compared with the unamended soil calculated with kidney and kidney+liver+bone Pb concentrations, respectively, and 68.8 and 49.7 % lower Cd RBA than the control with kidney and kidney+liver concentrations, respectively. However, no significant effect was observed with both amendments when the RBA was calculated with liver or bone Pb/Cd concentrations, or on Pb RBA with kidney, liver or bone metal concentrations. Results indicate the complex effect of amendments on organ, tissue and overall health risk of soil Pb/Cd to animal/human.

Multi-crosslinked hydrogels with strong wet adhesion, self-healing, antibacterial property, reactive oxygen species scavenging activity, and on-demand removability for seawater-immersed wound healing.

In general, seawater-immersed wounds are associated with tissue necrosis, infection, prolonged healing period, and high mortality because of high salinity, hyperosmosis, and the presence of various pathogenic bacteria in seawater. However, current wound dressings can hardly achieve strong and stable wet adhesion and antibacterial properties, thus limiting their application to seawater-immersed wounds. Here a multifunctional hydrogel (OD/EPL@Fe) comprising catechol-modified oxidized hyaluronic acid (OD), ε-poly-L-lysine (EPL), and Fe3+ was prepared primarily through Schiff-base reaction, metal chelation, cation-π, and electrostatic interaction. The hydrogel with high wet adhesion (about 78 kPa) was achieved by combining the mussel-inspired strategy, dehydration effect, and cohesion enhancement, which is higher than that of commercial fibrin glues and cyanoacrylate glues. Meanwhile, the hydrogel can eliminate Marine bacteria (V. vulnificus and P. aeruginosa) and inhibit their biofilm formation. In addition, the hydrogel demonstrated injectability, self-healing, reactive oxygen species scavenging activity, photothermal effect, seawater isolation, on-demand removal, and hemostatic properties. In vivo results showed that the hydrogel had good adhesion to dynamic wounds in a rat neck full-thickness skin wound model. In particular, the hydrogel exhibited antibacterial, anti-inflammatory, and antioxidant properties in a rat seawater-immersed infected wound model and accelerated the reconstruction of skin structure and functions. The results demonstrated that the OD/EPL@Fe would be a potential wound dressing for seawater-immersed wound healing. STATEMENT OF SIGNIFICANCE: A multifunctional OD/EPL@Fe hydrogel has been prepared for the treatment of seawater-immersed wounds. The hydrogel with high wet adhesion was achieved by combining the mussel-inspired strategy, dehydration effect, and cohesion enhancement. The results revealed that the wet adhesion value of hydrogel was about eight times greater than commercial fibrin glues and 1.5 times greater than commercial cyanoacrylate glues. The hydrogel can be easily removed after being sprayed with deferoxamine mesylate. Notably, the inherent antimicrobial material of the hydrogel combined with the photothermal effect can eliminate marine bacteria and inhibit their biofilm formation. Moreover, the hydrogel can accelerate the healing of seawater-immersed infected wound on mice.

Effects of Various Cell Surface Engineering Reactions on the Biological Behavior of Mammalian Cells.

Cell surface engineering technologies can regulate cell function and behavior by modifying the cell surface. Previous studies have mainly focused on investigating the effects of cell surface engineering reactions and materials on cell activity. However, they do not comprehensively analyze other cellular processes. This study exploits covalent bonding, hydrophobic interactions, and electrostatic interactions to modify the macromolecules succinimide ester-methoxy polyethylene glycol (NHS-mPEG), distearoyl phosphoethanolamine-methoxy polyethylene glycol (DSPE-mPEG), and poly-L-lysine (PLL), respectively, on the cell surface. This work systematically investigates the effects of the three surface engineering reactions on the behavior of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts, including viability, growth, proliferation, cell cycle, adhesion, and migration. The results reveals that the PLL modification method notably affects cell viability and G2/M arrest and has a short modification duration. However, the DSPE-mPEG and NHS-mPEG modification methods have little effect on cell viability and proliferation but have a prolonged modification duration. Moreover, the DSPE-mPEG modification method highly affects cell adherence. Further, the NHS-mPEG modification method can significantly improve the migration ability of HUVECs by reducing the area of focal adhesions. The findings of this study will contribute to the application of cell surface engineering technology in the biomedical field.

Unveiling the visible-light-driven photodegradation pathway and products toxicity of tetracycline in the system of Pt/BiVO4 nanosheets.

The antibiotics pollution has currently captured increasing concerns due to its potential hazards to the environment and human health. The development of efficient and viable techniques for the removal of antibiotics is one of the research hotspots in fields of wastewater treatment and pharmaceutical industry. Although the photodegradation of antibiotics is widely studied, the evolution and toxicity of degradation intermediates have been rarely documented. Herein, Pt nanoparticles (NPs) decorated BiVO4 nanosheets (Pt/BiVO4 NSs) that exhibit excellent tetracycline (TC) photodegradation activity and stability have been prepared. Especially, the TC degradation efficiency reaches ca. 88.5% after 60 min under visible light irradiation, which is superior to most of the metal loaded two-dimensional photocatalysts reported hitherto. The excellent photocatalytic activity is attributable to the enhanced light absorption capacity and charge separation efficiency in Pt/BiVO4 NSs. h+, •O2- and •OH are the main active species for TC degradation, resulting in three possible degradation pathways. Furthermore, we first verify that TC solutions treated by Pt/BiVO4 NSs are harmless to Escherichia coli K-12 and various bacteria in natural rivers, which would not stimulate Escherichia coli to produce antibiotics resistance genes (ARGs). This work develops an environmentally friendly photodegradation strategy using Pt/BiVO4 NSs with potentials for efficient remediation of antibiotics pollution in wastewater.

Complicated Hereditary Spastic Paraplegia Caused by SERAC1 Variants in a Chinese Family.

BACKGROUND: The serine active site-containing protein 1 (SERAC1) biallelic variant usually causes MEGDEL syndrome, clinically characterized by increased excretion of 3-methylglutaconic in the urine, muscle hypotonia, sensorineural deafness, and Leigh-like lesions on brain MRI scans. In this study, we present a case from a Chinese family with disordered metabolism and dystonia owing to SERAC1 variants; the clinical phenotypes of the proband were different from those of MEGDEL syndrome but were similar to those juvenile-onset complicated hereditary spastic paraplegia. Thus, in this study, we aimed to confirm the relationship between SERAC1 variants and complicated hereditary spastic paraplegia. METHODS: MRI and laboratory tests, including gas chromatography/mass spectrometry (GC/MS), were carried out for the proband. Whole-exome sequencing was used to detect the candidate SERAC1 variants. Variants were verified using Sanger sequencing. Various software programs (PolyPhen-2, MutationTaster, PROVEAN, and SIFT) were used to predict the pathogenicity of novel variants. RESULTS: Brain MRI scans showed a symmetric flake abnormal signal shadow in the bilateral basal ganglia in T2-weighted image (T2WI) and fluid-attenuated inversion recovery (FLAIR) analyses. The excretion of 3-methylglutaconic acid was found to be increased in our GC/MS analysis. Whole-exome sequencing showed novel compound heterozygous variants, including a novel c.1495A>G (p.Met499Val) variant in exon 14 of SERAC1 inherited from the father and a novel c.721_722delAG (p.Leu242fs) variant in exon 8 inherited from the mother. The pathogenicity prediction results showed that these two variants were deleterious. CONCLUSIONS: This study presented a patient with complicated hereditary spastic paraplegia caused by SERAC1 variants. These findings expand the number of known SERAC1 variants and the phenotypic spectrum associated with SERAC1 deficiency. This study may contribute to counseling and prevention of hereditary diseases through prenatal.

[Analysis of gene variant in a Chinese child affected with dihydropyrimidinase deficiency].

OBJECTIVE: To analyze the molecular etiology of a Chinese child affected with dihydropyrimidinase deficiency. METHODS: Genomic DNA was extracted from peripheral blood samples of the family members. Pathogenic variant was determined by whole exome sequencing and verified by Sanger sequencing. RESULTS: The child was found to harbor homozygous c.905G>A (p.Arg302Gln) variants in exon 5 of the DPYS gene, for which her parents were both heterozygous carriers. CONCLUSION: The homozygous c.905G>A (p.Arg302Gln) variants of the DPYS gene probably underlies the dihydropyrimidinase deficiency in the child. Above result has enabled genetic counseling and prenatal diagnosis for this family.

In situ immobilization of ultra-fine Ag NPs onto magnetic Ag@RF@Fe3O4 core-satellite nanocomposites for the rapid catalytic reduction of nitrophenols.

Novel magnetic Ag@RF@Fe3O4 core-satellite (MCS) nanocomposites were prepared through in situ photoreduction upon bridging Fe(III) and Ag+ via hydroxyl groups in resorcinol formaldehyde (RF) resin by virtue of the coordination effect. The catalytic activity of MCS nanocomposites was evaluated based on catalytic 4-nitrophenol (4-NP) reduction with NaBH4 as the reducing agent. It was noteworthy that the MCS-3 was beneficial to obtain a superior reaction rate constant of 2.27 min-1 and a TOF up to 72.7 h-1. Moreover, the MCS could be easily recovered by applying an external magnetic field and was reused for five times without significantly decrease in catalytic activity. Kinetic and thermodynamic study revealed that catalytic 4-NP reduction using MCS nanocatalysts obeyed the Langmuir-Hinshelwood mechanism and was controlled by the diffusion rate of substrates. Overall, the immobilization of ultra-fine Ag nanoparticles and the extremely negative potentials around MCS nanocomposites, which were effective for the diffusion of reactants, synergistically accelerated the catalytic reduction reactions.

Rapid screening of MMACHC gene mutations by high-resolution melting curve analysis.

BACKGROUND: Cobalamin (cbl) C is a treatable rare hereditary disorder of cbl metabolism with autosomal recessive inheritance. It is the most common organic acidemia, manifested as methylmalonic academia combined with homocysteinemia. Early screening and diagnosis are important. The mutation spectrum of the MMACHC gene causing cblC varies among populations. The mutation spectrum in Chinese population is notably different from that in other populations. METHODS: A PCR followed by high-resolution melting curve analysis (PCR-HRM) method covering all coding exons of MMACHC gene was designed to verify 14 pathogenic MMACHC gene variants found in patients with cblC, including all common mutations in Chinese patients with cblC. RESULT: By PCR-HRM analysis, 14 pathogenic variants of MMACHC showed distinctly different melting curves, which were consistent with Sanger sequencing. The homozygous type of the most common mutation c.609G > A (p.Trp203Ter) can also be analyzed by specially designed PCR-HRM. CONCLUSION: The established PCR-HRM method for screening common pathogenic MMACHC variants in Chinese patients with cblC has the advantages of high accuracy, high throughput, low cost, and high speed. It is suitable for the large-sample screening of suspected children with methylmalonic acidemia and carriers in population.

[Genetic analysis of one family with congenital limb malformations].

OBJECTIVE: To detect potential mutation in a Chinese pedigree affected with congenital limb malformations. METHODS: Clinical data was collected. Genomic DNA was extracted from peripheral blood samples of family members. The zone of polarizing activity regulatory sequence (ZRS) were amplified by PCR and subjected to direct sequencing. RESULTS: Among the 13 individuals in this pedigree, there were 4 PPD patients, who were characterized by varying degrees of deformity. The female patients suffered triphalangeal thumb and preaxial polydactyly, while the male patients only had preaxial polydactyly. Only one patient had foot involvement. TA heterogeneous mutations was discovered in the ZRS (105C>G) in all patients, the same mutation was not detected in 2 healthy family members. CONCLUSION: The inheritance pattern of PPD was autosomal dominant inheritance. There was a significant variability of symptoms among family patients. The heterozygous mutation of the ZRS (105C>G) probably underlie the disease.

Mixed phase nano-CdS supported on activated biomass carbon as efficient visible light-driven photocatalysts.

Semiconductors are promising photocatalysts for the use of sunlight in energy conversion and environmental remediation. To this end, various synthetic pathways have been proposed to increase their photocatalytic efficiency, catalytic stability, recycle, and reuse. In this work, mixed phase CdS nanoparticles were loaded on the surface of activated biomass carbons to prepare composite photocatalysts via hydrothermal syntheses, which were further applied to photocatalytic degradation of rhodamine B (RhB) under visible irradiation. The composite photocatalysts displayed considerable specific surface area (up to 672 m2 g-1) and suitable band gap energy of ca. 2.1 eV. Due to the excellent light adsorption ability and chemical stability, these composite photocatalysts exhibited excellent photocatalytic capacity toward RhB degradation under visible irradiation. Moreover, the photocatalytic stability was also demonstrated by cyclic experiments, by which the composite photocatalysts retained over 80% of the initial catalytic activity after 4 consecutive runs.

Mutation spectrum of MMACHC in Chinese pediatric patients with cobalamin C disease: A case series and literature review.

Cobalamin (cbl) C disease is a rare autosomal recessive inheritance disease, which is the most common cobalamin metabolic disorder. Its clinical phenotype involves multiple systems with varying degrees of severity, where in mild cases can be asymptomatic for many years, whereas severe cases may cause death during the neonatal period. The disease is caused by mutations in the MMACHC gene located on chromosome 1p34.1 that contains 5 exons; among which, exons 1-4 have an 849 bp coding sequence that encodes a protein containing 282 amino acids. Through clinical physical examination and laboratory tests, especially blood and urine screening, we found 28 cblC pediatric patients with clinical manifestations, such as mental retardation, motor development delay, epilepsy, metabolic acidosis, vomiting and diarrhea. By Sanger sequencing, we found homozygous or compound heterozygous mutations of MMACHC in 27 of the patients, and single heterozygous mutation of MMACHC in one of them. The c.609G > A, c.658-660delAAG, c.80A > G and c.482G > A mutations accounted for 43.64% (24/55), 10.91% (6/55), 9.09% (5/55) and 7.27% (4/55) of all the mutations, respectively. This spectrum finding is basically consistent with the previously reported data in Chinese patients. The most common c.609G > A mutation may likely lead to early-onset cblC disease. In previous literature involving a large sample of Caucasian cblC cases, the mutation spectrum of MMACHC gene is almost completely different from that of the Chinese population. The most common mutations in the Caucasian population were c.271dupA, c.394C > T and c.331C > T, which account for 48.05% (542/1128), 13.65% (154/1128) and 7.36% (83/1128) of all the mutant alleles, respectively. The c.271dupA mutation and c.331C > T mutation were mainly associated with early-onset cblC in children less than 1 year old, whilst the c.394C > T mutation was mainly associated with late-onset cblC patients characterised by isolated acute nervous system abnormalities. We also analysed the cause behind the different mutation spectrum of MMACHC gene between the Chinese and Caucasian populations.

Clinical diagnosis and mutation analysis of four Chinese families with succinic semialdehyde dehydrogenase deficiency.

BACKGROUND: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessively-inherited defect of γ-aminobutyric acid (GABA) metabolism. The absence of SSADH, which is encoded by aldehyde dehydrogenase family 5 member A1 (ALDH5A1) gene, leads to the accumulation of GABA and γ-hydroxybutyric acid (GHB). Few cases with SSADH deficiency were reported in China. CASE PRESENTATION: In this study, four Chinese patients were diagnosed with SSADH deficiency in Tianjin Children's Hospital. We conducted a multidimensional analysis with magnetic resonance imaging (MRI) of the head, semi quantitative detection of urine organic acid using gas chromatography-mass spectrometry, and analysis of ALDH5A1 gene mutations. Two of the patients were admitted to the hospital due to convulsions, and all patients were associated with developmental delay. Cerebral MRI showed symmetrical hyperintense signal of bilateral globus pallidus and basal ganglia in patient 1; hyperintensity of bilateral frontal-parietal lobe, widened ventricle and sulci in patient 2; and widened ventricle and sulci in patient 4. Electroencephalogram (EEG) revealed the background activity of epilepsy in patient 1 and the disappearance of sleep spindle in patient 2. Urine organic acid analysis revealed elevated GHB in all the patients. Mutational analysis, which was performed by sequencing the 10 exons and flanking the intronic regions of ALDH5A1 gene for all the patients, revealed mutations at five sites. Two cases had homozygous mutations with c.1529C > T and c.800 T > G respectively, whereas the remaining two had different compound heterozygous mutations including c.527G > A/c.691G > A and c.1344-2delA/c.1529C > T. Although these four mutations have been described previously, the homozygous mutation of c.800 T > G in ALDH5A1 gene is a novel discovery. CONCLUSION: SSADH deficiency is diagnosed based on the elevated GHB and 4, 5DHHA by urinary organic acid analysis. We describe a novel mutation p.V267G (c.800 T > G) located in the NAD binding domain, which is possibly crucial for this disease's severity. Our study expands the mutation spectrum of ALDH5A1 and highlights the importance of molecular genetic evaluation in patients with SSADH deficiency.

Assessment of tea garden soils at An'xi County in southeast China reveals a mild threat from contamination of potentially harmful elements.

An extensive study of the spatial distribution characteristics of potentially harmful elements (PHEs) in tea (Camellia sinensis (L.) O. Kuntze) garden soils and ecological risk assessment at An'xi County, the birthplace of oolong tea in China, was implemented. A total of 78 soil samples were examined to determine the concentration of five PHEs (As, Cd, Cr, Hg and Pb), soil organic matter and pH by using geostatistical approaches combined with geographical information system analysis. All PHEs presented in the study area were slightly higher than their background values for provincial and national standards except Cr. Moreover, ecological risk assessment of PHEs in the tea garden soils at An'xi County was performed by means of the Håkanson method. The average ecological potential risk index (Er) of the five PHEs followed a descending order of Cd > Hg > Pb > As > Cr, and suggested a moderate ecological risk in the study area.

[Identification of ALDH5A1 gene mutations in a Chinese family affected with succinic semialdehyde dehydrogenase deficiency].

OBJECTIVE: To detect potential mutation in a Chinese family affected with succinic semialdehyde dehydrogenase deficiency. METHODS: Genomic DNA was extracted from the peripheral blood samples of the proband, her family members and 100 healthy controls. All exons and flanking intronic regions of the ALDH5A1 gene were amplified by PCR and subjected to direct sequencing. RESULTS: The proband was found to have compound heterozygous mutations of the ALDH5A1 gene, namely c.398_399delAA (p.N134X) and c.638G>T (p.R213L), for which her parents were both heterozygous carriers. The same mutations were not found among the 100 healthy controls. CONCLUSION: The novel mutations of the ALDH5A1 gene probably underlie the pathogenesis of the disease in the infant, which also enriched the mutation spectrum of the ALDH5A1 gene.

Photodegradation of Rhodamine B over Biomass-Derived Activated Carbon Supported CdS Nanomaterials under Visible Irradiation.

A family of new composite materials was successfully prepared through the deposition of as-synthesized CdS nanomaterials on lotus-seedpod-derived activated carbon (SAC). The SAC supports derived at different activation temperatures exhibited considerably large surface areas and various microstructures that were of great importance in enhancing photocatalytic performance of CdS@SAC composite materials toward the photodegradation of rhodamine B (RhB) under visible irradiation. The best-performing CdS@SAC-800 showed excellent photocatalytic activity with a rate constant of ca. 2.40 × 10-2 min-1, which was approximately 13 times higher than that of the CdS nanomaterials. Moreover, the estimated band gap energy of CdS@SAC-800 was significantly lowered down to 1.99 eV compared to that of the CdS precursor (2.22 eV), which suggested considerable strength of interface contact between the CdS and SAC support, as well as efficient light harvesting capacity of the composite material. Further photocatalytic study indicated that the SAC supports enhanced the separation of photogenerated electrons and holes in this system. Improved photocatalytic activity of the composite materials was largely due to the increased generation of catalytically active species such as h+, OH•, [Formula: see text] etc. This work provided a facile and low-cost pathway to fabricate photocatalysts for viable degradation of organic dye molecules.