Leber congenital amaurosis as the initial and essential manifestation in a Chinese patient with autoimmune polyglandular syndrome Type 1.

PURPOSE: Autoimmune polyglandular syndrome Type 1 (APS-1) is a rare autosomal recessive disorder caused by defects in the autoimmune regulator (AIRE) gene. Patients are generally diagnosed at ages between five and fifteen years when they exhibit three or more manifestations, most typically mucocutaneous candidiasis, autoimmune Addison's disease, and hypoparathyroidism. Our study aims to report the first case of a Chinese APS-1 patient, presented with LCA as the initial and essential clinical feature of this rare syndrome. METHODS: Detailed medical and family history were recorded for the patient. Also, the comprehensive ophthalmological examinations were conducted. Whole exome sequencing (WES) was applied to screen pathogenic variants. Sanger sequencing validation and segregation analysis were further performed for confirmation. RESULTS: A 3-year-old boy with severely impaired vision and initially referred as LCA. However, with a detailed history review, oral candidiasis, dental enamel hypoplasia, and nail candida infection were revealed. Moreover, genetic analysis revealed the homozygous c.769C>T (p.R257X) in AIRE gene (NM_000383.3) as the causative variant. CONCLUSION: We presented one case diagnosed with APS-1 based on clinical characteristics and genetic analysis. Our study demonstrated that LCA could serve as a warning sign for APS-1 and a potential trigger of early screening, which might prevent life-threatening complications.

Polyketone metabolites isolated from Rhodiola tibetica endohytic fungus Alternaria sp. HJT-Y7 and their SARS-CoV-2 virus inhibitory activitives.

Six new polyketone metabolites, compounds (1-6) and seven known polyketone compounds (7-13) were isolated from Rhodiola tibetica endophytic fungus Alternaria sp. The structural elucidation of five new polyketone metabolites were elucidated on the basis of spectroscopic including 2D NMR and HRMS and spectrometric analysis. Inhibition rate evaluation revealed that compounds 1(EC50 = 0.02 mM), 3(EC50 = 0.3 mM), 6(EC50 = 0.07 mM), 8(EC50 = 0.1 mM) and 9(EC50 = 0.04 mM) had inhibitory effect on the SARS-CoV-2 virus.

The VPS34 PI3K negatively regulates RAB-5 during endosome maturation.

The GTPase Rab5 and phosphatidylinositol-3 phosphate [PI(3)P] coordinately regulate endosome trafficking. Rab5 recruits Vps34, the class III phosphoinositide 3-kinase (PI3K), to generate PI(3)P and recruit PI(3)P-binding proteins. Loss of Rab5 and loss of Vps34 have opposite effects on endosome size, suggesting that our understanding of how Rab5 and PI(3)P cooperate is incomplete. Here, we report a novel regulatory loop whereby Caenorhabditis elegans VPS-34 inactivates RAB-5 via recruitment of the TBC-2 Rab GTPase-activating protein. We found that loss of VPS-34 caused a phenotype with large late endosomes, as with loss of TBC-2, and that Rab5 activity (mice have two Rab5 isoforms, Rab5a and Rab5b) is increased in Vps34-knockout mouse embryonic fibroblasts (Vps34 is also known as PIK3C3 in mammals). We found that VPS-34 is required for TBC-2 endosome localization and that the pleckstrin homology (PH) domain of TBC-2 bound PI(3)P. Deletion of the PH domain enhanced TBC-2 localization to endosomes in a VPS-34-dependent manner. Thus, PI(3)P binding of the PH domain might be permissive for another PI(3)P-regulated interaction that recruits TBC-2 to endosomes. Therefore, VPS-34 recruits TBC-2 to endosomes to inactivate RAB-5 to ensure the directionality of endosome maturation.

Amphiphilic Polycarbonates from Carborane-Installed Cyclic Carbonates as Potential Agents for Boron Neutron Capture Therapy.

Carboranes with rich boron content have showed significant applications in the field of boron neutron capture therapy. Biodegradable derivatives of carborane-conjugated polymers with well-defined structure and tunable loading of boron atoms are far less explored. Herein, a new family of amphiphilic carborane-conjugated polycarbonates was synthesized by ring-opening polymerization of a carborane-installed cyclic carbonate monomer. Catalyzed by TBD from a poly(ethylene glycol) macroinitiator, the polymerization proceeded to relatively high conversions (>65%), with low polydispersity in a certain range of molecular weight. The boron content was readily tuned by the feed ratio of the monomer and initiator. The resultant amphiphilic polycarbonates self-assembled in water into spherical nanoparticles of different sizes depending on the hydrophilic-to-hydrophobic ratio. It was demonstrated that larger nanoparticles (PN150) were more easily subjected to protein adsorption and captured by the liver, and smaller nanoparticles (PN50) were more likely to enter cancer cells and accumulate at the tumor site. PN50 with thermal neutron irradiation exhibited the highest therapeutic efficacy in vivo. The new synthetic method utilizing amphiphilic biodegradable boron-enriched polymers is useful for developing more-selective and -effective boron delivery systems for BNCT.

Lignocellulose degradation by the isolate of Streptomyces griseorubens JSD-1.

Streptomyces griseorubens JSD-1 is an isolate that can utilize lignocellulose (straw) as its sole carbon source for growth, and these lignocellulolytic genes involved in this biotransformation are expected to be crucial. However, little is known about the genetic basis related to this process. To further investigate the lignocellulose-degrading mechanisms, genome sequencing was carried out using MiSeq platform. After obtaining its draft genome, the key lignocellulolytic genes such as multicopper oxidase, exo-1, 4-ß-glucanase, endo-1,4-ß-glucanase, and ß-xylosidase were identified and characterized. Multiple sequence alignments were performed to find out the identities of these analyzed proteins to those of their similar species. Signal peptide cleavage sites were predicted by SignalP 4.1 to reflect the cellular localization of their mature proteins. Besides, predicted 3D structures of these proteins were modeled by Phyre2, which showed to be highly identical to the templates in the PDB database. Finally, quantitative real-time PCR revealed that expression levels of all analyzed enzymes were significantly and generally up-regulated during the whole cultivation, indicating that they all contributed to the biodegradation.

Safety and efficacy of a novel plastic stent coated with stone-dissolving agents for the treatment of biliary stones in a porcine model.

BACKGROUND AND STUDY AIM: We previously reported on a plastic stent that was coated with ethylenediaminetetraacetic acid (EDTA) and sodium cholate, which dissolved common bile duct (CBD) stones ex vivo. The aim of this study was to investigate the safety and efficacy of such stents on biliary stones in a live porcine model. METHODS: Stents without coating or with degradable membranes containing 0 % or 50 % EDTA and sodium cholate were inserted together with human CBD stones into the porcine CBD. Serum laboratory variables, histological examinations of the bile duct, and the weight change in stones were compared during and after stent placement for 6 months. RESULTS: A total of 16 pigs were included (5 no coating, 5 0 % coating, 6 50 % coating). Biliary stones showed decreased weight in all groups; however, stones in the group with 50 % coated stents showed a greater reduction in weight compared with the no coating and the 0 % coating groups (269 ±â€Š66 mg vs. 179 ±â€Š51 mg [P = 0.09]; 269 ±â€Š66 mg vs. 156 ±â€Š26 mg [P = 0.01], respectively). CONCLUSIONS: The plastic stent coated with 50 % agent enhanced CBD stone dissolution in vivo and may be a promising tool for patients with difficult biliary stones.

The effect of a novel drug-eluting plastic stent on biliary stone dissolution in an ex vivo bile perfusion model.

BACKGROUND: Temporary plastic stent insertion has been considered a safe and effective bridge therapy for difficult common bile duct (CBD) stones. Infusing chemicals to directly dissolve stones through the bile duct might also be effective. However, there are no studies on the efficacy of the combination of these 2 approaches. OBJECTIVE: To investigate the efficacy of a novel ethylenediaminetetraacetic acid (EDTA) and sodium cholate-eluting plastic stent on biliary stones. DESIGN: Ex vivo model by using different doses of active ingredient. SETTING AND INTERVENTIONS: An ex vivo bile duct model perfused with porcine bile was created. Stents coated with degradable membranes containing various concentrations of EDTA and sodium cholate were placed in the model with CBD stones. MAIN OUTCOME MEASUREMENTS: The change in the weight of stents and stones was measured every week during perfusion until the coated membranes were completely biodegraded. RESULTS: The time that the stents required to be fully degraded and the efficiency of stone dissolution were positively correlated with the percentage of EDTA and sodium cholate in the stent membrane. However, the 50% EDTA and sodium cholate stents achieved the greatest percentage of stone weight loss when the drugs were completely released. LIMITATIONS: Ex vivo study. CONCLUSIONS: The EDTA and sodium cholate-eluting plastic stent effectively dissolved CBD stones and has prospect in the therapy for patients with difficult CBD stones.

[Effects of Morinda officinalis polysaccharides on FN and FN-EDA of periodontal ligament fibroblasts in inflammatory microenvironment].

PURPOSE: To investigate the effect of Morinda officinalis polysaccharides(MOP) on the expression of fibronectin(FN) and fibronectin containing extra domain A(FN-EDA) in inflammatory periodontal ligament fibroblasts. METHODS: Thirty six rats were randomly divided into a control group(n=12) and a model group (n=24). The model group used orthodontic wire ligation to establish periodontitis. After three weeks, 6 rats from each group were selected and confirmed by Micro-CT to complete the modeling. The remaining rats in the model group were randomly divided into periodontitis group, normal saline(NS) group, and MOP group. In the MOP group, MOP (200 mg/kg for 3 d, 50 µL for 4 weeks) was injected into the palatal side of the left maxillary first molar of the rats. In the NS group, same volume of NS was injected, and no treatment was performed in the periodontitis group. The left maxillary tissue of rats were taken and the pathological changes of periodontal tissue were observed by H-E staining. The expression of FN and FN-EDA was detected by immunohistochemistry. Periodontal ligament fibroblasts were cultured in vitro, the effect of MOP on cell activity detected by CCK-8. The fourth generation cells were divided into control group, inflammation group (10 mg/mL lipopolysaccharide), and experimental group (12.5 µg/mL MOP, 12.5 µg/mL MOP+10 mg/mL lipopolysaccharide). The expression of FN and FN-EDA was detected by qRT-PCR and Western blot. The data were statistically analyzed using Prism 8.0 software package. RESULTS: In vivo experiments, the expression of FN-EDA in the MOP group was significantly lower than that in the periodontitis group and NS group(P＜0.05), and the infiltration of inflammatory cells was reduced. However, there was no significant difference in the expression of FN in each group. In vitro experiments, compared with the control group, the expression of FN-EDA mRNA and protein in the inflammation group was significantly increased(P＜0.000 1). MOP significantly reduced the expression of FN-EDA in inflammatory cells, but had no significant effect on FN expression. CONCLUSIONS: With increased expression of FN-EDA in inflammatory periodontal ligament tissues and cells, MOP may play a role in inhibiting inflammation by down-regulating FN-EDA.

The impact of arbuscular mycorrhizal fungi and endophytic bacteria on peanuts under the combined pollution of cadmium and microplastics.

It remains unclear how symbiotic microbes impact the growth of peanuts when they are exposed to the pollutants cadmium (Cd) and microplastics (MPs) simultaneously. This study aimed to investigate the effects of endophytic bacteria Bacillus velezens SC60 and arbuscular mycorrhizal fungus Rhizophagus irregularis on peanut growth and rhizosphere microbial communities in the presence of Cd at 40 (Cd40) or 80 (Cd80) mg kg-1 combined without MP or the presence of low-density polyethylene (LDPE) and poly butyleneadipate-co-terephthalate (PBAT). This study assessed soil indicators, plant parameters, and Cd accumulation indicators. Results showed that the application of R. irregularis and B. velezens significantly enhanced soil organic carbon and increased Cd content under the conditions of Cd80 and MPs co-pollution. R. irregularis and B. velezens treatment increased peanut absorption and the enrichment coefficient for Cd, with predominate concentrations localized in the peanut roots, especially under combined pollution by Cd and MPs. Under treatments with Cd40 and Cd80 combined with PBAT pollution, soil microbes Proteobacteria exhibited a higher relative abundance, while Actinobacteria showed a higher relative abundance under treatments with Cd40 and Cd80 combined with LDPE pollution. In conclusion, under the combined pollution conditions of MPs and Cd, the co-treatment of R. irregularis and B. velezens effectively immobilized Cd in peanut roots, impeding its translocation to the shoot.

Advantages of Totally Stapled Collard Over Circular Stapled Technique for Cervical Esophagectomy Anastomosis.

BACKGROUND: The quality of life between the totally stapled Collard (TSC) and circular stapled (CS) techniques from the patient's perspective has not been assessed. This longitudinal patient-reported outcome and objective data assessment study aimed to compare the effects of TSC vs CS for cervical anastomosis with minimally invasive esophagectomy (MIE) on the quality of life. METHODS: This single-center, retrospective study included patients with esophageal cancer who underwent MIE and cervical anastomosis between April 2019 and February 2021; of whom, 105 and 216 patients received TSC and CS anastomosis, respectively. The objective metrics were evaluated based on postoperative complications. Patient-reported outcomes instruments using the European Organization for Research and Treatment of Cancer modules were assessed preoperatively. The Quality of Life Questionnaire (QLQ) Core 30 and the QLQ-Oesophagus Module 18 assessed the quality of life. Mixed-effects models examined changes in questionnaire scores. RESULTS: The stenosis rate in the TSC group was significantly lower than that in the CS group. There were no significant differences in other postoperative complications between the groups. In the QLQ Core 30 scale, the TSC group had better emotional function, less fatigue, less appetite loss, and better function than the CS group, with significant differences in different time points between the groups. QLQ-Oesophagus Module 18 revealed that the TSC group had significantly less appetite loss, dysphagia, dry mouth, pain, and obstruction, and better eating and speech than the CS group. CONCLUSIONS: TSC has significant advantages over the CS technique in lowering postoperative symptom burden and improving quality of life for cervical anastomosis on patient-reported outcomes.

[Recombinant human bone morphogenetic protein 2/porous calcium phosphate cement/autologous bone and combination of platelet-rich plasma in repairing of large bone defects in rabbits by Masquelet technique].

Objective: To investigate the optimal mixing ratio of recombinant human bone morphogenetic protein 2 (rhBMP-2) with porous calcium phosphate cement (PCPC) and autologous bone as bone grafting material for the repair of large bone defects using Masquelet technique. The effect of platelet-rich plasma (PRP) on the healing of bone defects was evaluated under the optimal ratio of mixed bone. Methods: Fifty-four New Zealand White rabbits were taken to establish a 2 cm long bone defect model of the ulna and treated using the Masquelet technique. Two parts of the experiment were performed in the second phase of the Masquelet technique. First, 36 modeled experimental animals were randomly divided into 4 groups ( n=9) according to the mass ratio of autologous bone and rhBMP-2/PCPC. Group A: autologous bone (100%); group B: 25% autologous bone+75% rhBMP-2/PCPC; group C: 50% autologous bone+50% rhBMP-2/PCPC; group D: 75% autologous bone+25% rhBMP-2/PCPC. The animals were executed at 4, 8, and 12 weeks postoperatively for general observation, imaging observation, histological observation (HE staining), alkaline phosphatase (ALP) activity assay, and biomechanical assay (three-point bending test) were performed to assess the osteogenic ability and to determine the optimal mixing ratio. Then, 18 modeled experimental animals were randomly divided into 2 groups ( n=9). The control group was implanted with the optimal mixture ratio of autologous bone+rhBMP-2/PCPC, and the experimental group was implanted with the optimal mixture ratio of autologous bone+rhBMP-2/PCPC+autologous PRP. The same method was used to observe the above indexes at 4, 8, and 12 weeks postoperatively. Results: The bone healing process from callus formation to the cortical connection at the defected gap could be observed in each group after operation; new bone formation, bridging with the host bone, and bone remodeling to normal bone density were observed on imaging observation; new woven bone, new capillaries, bone marrow cavity, and other structures were observed on histological observation. The ALP activity of each group gradually increased with time ( P<0.05); the ALP activity of group A was significantly higher than that of the other 3 groups at each time point after operation, and of groups C and D than group B ( P<0.05); there was no significant difference between groups C and D ( P>0.05). Biomechanical assay showed that the maximum load in three-point bending test of each group increased gradually with time ( P<0.05), and the maximum loads of groups A and D were significantly higher than that of groups B and C at each time point after operation ( P<0.05), but there was no significant difference between groups A and D ( P>0.05). According to the above tests, the optimal mixing ratio was 75% autogenous bone+25% rhBMP-2/PCPC. The process of new bone formation in the experimental group and the control group was observed by gross observation, imaging examination, and histological observation, and the ability of bone formation in the experimental group was better than that in the control group. The ALP activity and maximum load increased gradually with time in both groups ( P<0.05); the ALP activity and maximum load in the experimental group were significantly higher than those in the control group at each time point after operation ( P<0.05), and the maximum load in the experimental group was also significantly higher than that in group A at 12 weeks after operation ( P<0.05). Conclusion: In the second phase of Masquelet technique, rhBMP-2/PCPC mixed with autologous bone to fill the bone defect can treat large bone defect of rabbit ulna, and it has the best osteogenic ability when the mixing ratio is 75% autologous bone+25% rhBMP-2/PCPC. The combination of PRP can improve the osteogenic ability of rhBMP-2/PCPC and autologous bone mixture.

Salivary microbiota analysis of patients with membranous nephropathy.

The oral microbiota are closely related to human health. Nonetheless, to the best of our knowledge, their relationship with membranous nephropathy (MN) remains unstudied. The saliva microbiota collected from 22 patients with MN and 15 healthy controls were analyzed by next­generation sequencing, and bioinformatics analysis of the 16S ribosomal RNA gene was subsequently carried out. The Chao1 and Shannon indices in patients with MN were higher than those in healthy controls. Analysis of similarities revealed that the oral microbiota in the patient group were significantly different from those in the healthy controls. At the genus level, the abundance of Alloprevotella, Granulicatella, Prevotella, Streptococcus and Prevotella_7 was markedly higher in patients with MN than in healthy controls. Six operational taxonomic units (OTUs; OTU5, OTU28, OTU9, OTU15, OTU33 and OTU38) were found to be markedly correlated with the clinical factors creatinine, proteinuria in 24 h, estimated glomerular filtration rate and systolic blood pressure. A total of 28 Kyoto Encyclopedia of Genes and Genomes pathways were obtained from the significant OTUs. The oral microbiota of patients with MN were investigated and it was found that OTU5, OTU28, OTU9, OTU15, OTU33 and OTU38 may be used as biomarkers. The present findings may assist in the diagnosis of patients with MN.

Effect of placement angle on the stability of loaded titanium microscrews: a microcomputed tomographic and biomechanical analysis.

INTRODUCTION: The aim of this study was to evaluate the impact of the placement angle on the stability of loaded microscrews. METHODS: Forty-eight microscrews were placed at 4 angles ( 30°, 50°, 70°, and 90°) into the tibiae of 12 beagles, loaded with a force of 2 N immediately, and maintained for 8 weeks. Microcomputed tomography and pullout tests were used for morphometric and biomechanical analyses, respectively. RESULTS: All microcomputed tomography parameters and the peak loads at extraction of the microscrews were influenced by the placement angles of the microscrews. The higher microcomputed tomography parameters and the peak load at extraction were measured at angles from 50° to 70°. Oblique and vertical placement angles resulted in reduced stability of the loaded microscrews (P <0.05). CONCLUSIONS: To achieve the best stability of microscrews, a placement angle of 50° to 70° is advisable.

Comparison of Chief Complaints and Patient-Reported Symptoms of Treatment-Naive Lung Cancer Patients Before Surgery.

BACKGROUND: Lung cancer patients without chief complaints have been increasingly identified by physical examination. This study aimed to profile and compare chief complaints with patient-reported symptoms of lung cancer patients before surgery. METHODS: Data were extracted from a multicenter, prospective longitudinal study (CN-PRO-Lung 1) in China from November 2017 to January 2020. A comparison between chief complaints and patient-reported symptoms was analyzed using the Chi-squared test. RESULTS: A total of 201 (50.8%) lung cancer patients without chief complaints were found by physical examination at admission, and 195 (49.2%) patients had chief complaints. The top 5 chief complaints were coughing (38.1%), expectoration (25.5%), chest pain (13.6%), hemoptysis (10.6%), and shortness of breath (5.3%). There were significantly more patients with chief complaints of coughing (38.1% vs 15.0%, P <0.001) and pain (20.5% vs 6.9%, P<0.001) than those with the same symptoms rated ≥4 via MD Anderson Symptom Inventory‒Lung Cancer (MDASI-LC). There were less patients with chief complaints of fatigue (1.8% vs 10.9%, P<0.001), nausea (0.3% vs 2.5%, P=0.006), and vomiting (0.3% vs 1.8%, p=0.032) than those with the same symptoms rated ≥4 via MDASI-LC. In patients without chief complaints, the five most common moderate to severe patient-reported symptoms were disturbed sleep (19.5%), distress (13.5%), dry mouth (13%), sadness (12%), and difficulty remembering (11.1%). CONCLUSION: Symptoms of lung cancer patients not included in the chief complaint could be identified via a patient-reported outcome instrument, suggesting the necessity of implementing the patient-reported outcome assessment before lung cancer surgery for better patient care.

A new species and key to known species of the genus Conophymacris Willemse, 1933 (Orthoptera, Acridoidea, Catantopidae, Podisminae) from China.

A new species in the genus Conophymacris Willemse, 1933 from Yunnan, China is described. The new species Conophymacris reni sp. nov. is similar to C. jiulongensis Zheng et al., 2009, but differs from latter in width of vertex between eyes of male equal to 2.8 width of frontal ridge between antennae, epiproct of male width longer than length, cercus of male apical part not wider, tegmina extending over the hind margin of first abdominal tergum, hind tibia all red, epiphallus ancorae small, lower than anterior projection, lophi not acute, width of subgenital plate shorter than its length and hind margin with 1 tooth in female. Type specimens are deposited in the Natural Museum of Hebei University, Baoding, Hebei, China.

Combination of SDF-1 and bFGF promotes bone marrow stem cell-mediated periodontal ligament regeneration.

Stromal cell derived factor-1 (SDF-1) and basic fibroblast growth factor (bFGF) were reported to induce the differentiation of bone marrow stem cells (BMSCs) into cells with characteristics of periodontal ligament fibroblasts. Thus SDF-1 and bFGF may play a positive role in BMSCs-mediated periodontal ligament regeneration. Here, the methylthiazolyldiphenyl tetrazolium bromide (MTT) assay was used to investigate the effect of scaffolds, SDF-1 and bFGF on BMSCs proliferation. RT-PCR and Western blot were used to evaluate gene and protein expression. Beagle dogs were used to establish an animal model of tooth reimplantation and to investigate the effects of scaffolds, BMSCs, SDF-1 and bFGF on periodontal ligament regeneration. X-ray images and micro computed tomography (micro CT) were used to assess morphological changes in replanted teeth and surrounding alveolar bone. H&E staining and Masson's staining were also performed. BMSCs from Beagle dogs growth on scaffolds consisted of dense structured collagens. SDF-1 and bFGF effectively promoted the differentiation of BMSCs into fibroblasts, periodontal membrane reconstruction, and cell proliferation in vitro. SDF-1 and bFGF also stimulated the expression of type I collagen (Col I), type III collagen (Col III), CXC family chemokine receptor 4 (CXCR4), and S100 calcium binding protein A4 (S100A4), and decreased the expression of alkaline phosphatase (ALP). In our experimental Beagle dog model of tooth extraction and replantation, application of SDF-1 and bFGF significantly elevated periodontal membrane reconstruction and thus supported the survival of replanted teeth. In conclusion, the findings from the present study demonstrated that SDF-1 and bFGF enhance the process of periodontal ligament reconstruction, and provide a basis and reference for the use of stem cell tissue engineering in promoting periodontal membrane regeneration.

Salivary microbial analysis of Chinese patients with immunoglobulin A nephropathy.

Microbiota plays an important role in immunoglobulin A (IgA) nephropathy (IgAN); however, the pathogenesis, early diagnosis, and treatment of IgAN remain unclear. The aim of the present study was to develop a preliminary model based on saliva­specific microbes and clinical indicators to facilitate the early diagnosis of IgAN and obtain insights into its treatment. The microbial profile of the saliva of 28 IgAN patients and 25 healthy control subjects was investigated using high­throughput sequencing and bioinformatics analyses of the V4 region in microbial 16S rRNA genes. IgAN patients and healthy subjects did not differ significantly in α­diversity indices (Chao1 and Shannon index) or phylum composition. At the genus level, however, Granulicatella was significantly less abundant in healthy individuals than in IgAN patients, while Prevotella and Veillonella were significantly more abundant in the healthy subjects than in IgAN patients (P<0.05 and P<0.01, respectively). Correlation analysis between biochemical indicators and operational taxonomic units (OTUs) revealed that the glomerular filtration rate was positively correlated with OTU86 and OTU287 at P<0.05, positively correlated with OTU165 at P<0.001, and negatively correlated with OTU455 at P<0.05. The serum creatinine index was negatively correlated with OTU287 at P<0.05 and negatively correlated with OTU165 at P<0.001. The pathological changes were positively correlated with OTU255 at P<0.05, OTU200 at P<0.01, and OTU455 and OTU75 at P<0.001, and negatively correlated with OTU86, OTU287, and OTU788 at P<0.05 and with OTU165 at P<0.01. The differences between Chinese IgAN patients and healthy subjects in terms of OTUs and biochemical indicators were analyzed and a mathematical model to facilitate the clinical diagnosis of IgAN was established.

Ion-assisted fabrication of neutral protein crosslinked sodium alginate nanogels.

Protein crosslinked nanogels which combine the merits of nanogels and the specific biological activity from protein have emerged as fascinating protein delivery systems. However, the fragility and low density of reactive group in proteins, especially low electric density of neutral proteins seriously limited the fabrication of protein crosslinked nanogels without affecting their bioactivities. Here, we demonstrated a facile ion-assisted method to fabricate neutral protein crosslinked nanogels. Oxidized sodium alginate (OSA) with aldehyde groups and low viscosity was successfully synthesized, which could reversibly form nanogels via addition and removal of divalent cation. Subsequently, hemoglobin and myoglobin were used as representative neutral proteins to fabricate stable protein crosslinked OSA nanogels under the assist of divalent cation followed by in situ Schiff base formation between OSA and proteins. The mild fabrication condition guaranteed the structural integrity and bioactivity of proteins in the obtained protein crosslinked nanogels. This ion-assisted method was expected to bring a new opportunity for fabricating versatile functional biohybrid nanogels systems.

Increased skin permeation efficiency of imperatorin via charged ultradeformable lipid vesicles for transdermal delivery.

AIM: The aim of this work was to develop a novel vesicular carrier, ultradeformable liposomes (UDLs), to expand the applications of the Chinese herbal medicine, imperatorin (IMP), and increase its transdermal delivery. METHODS: In this study, we prepared IMP-loaded UDLs using the thin-film hydration method and evaluated their encapsulation efficiency, vesicle deformability, skin permeation, and the amounts accumulated in different depths of the skin in vitro. The influence of different charged surfactants on the properties of the UDLs was also investigated. RESULTS: The results showed that the UDLs containing cationic surfactants had high entrapment efficiency (60.32%±2.82%), an acceptable particle size (82.4±0.65 nm), high elasticity, and prolonged drug release. The penetration rate of IMP in cationic-UDLs was 3.45-fold greater than that of IMP suspension, which was the highest value among the vesicular carriers. UDLs modified with cationic surfactant also showed higher fluorescence intensity in deeper regions of the epidermis. CONCLUSION: The results of our study suggest that cationic surfactant-modified UDLs could increase the transdermal flux, prolong the release of the drug, and serve as an effective dermal delivery system for IMP.

A facile way to prepare functionalized dextran nanogels for conjugation of hemoglobin.

Nanogels with several special advantages have been widely applied in protein delivery. However, biocompatible and biodegradable nanogels used for hemoglobin (Hb) delivery are far less explored. Herein, we developed a facile method to prepare functionalized dextran nanogels for conjugation of Hb. In situ cross-linked and aldehyde group functionalized nanogels (FNGs) were prepared from dextran-g-succinic anhydride-g-dopamine conjugate (Dex-SA-DA) assembly by simple pH adjustion and oxidization in water. Hb was further conjugated into the swelling FNGs by Schiff base reaction under mild condition. The obtained hemoglobin-loaded nanogels (HbNGs) exhibited high stability, oxygen affinity and good hemo-compatibility, suggesting the potential for oxygen carriers. We expected that the designed functionalized nanogels with high stability and loading capacity could bring a new opportunity for protein delivery.