Nitrided Rhodium Nanoclusters with Optimized Water Bonding and Splitting Effects for pH-Universal H2-Production.

The nitridation of noble metals-based catalysts to further enhance their hydrogen evolution reaction (HER) kinetics in neutral and alkaline conditions would be an effective strategy for developing high-performance wide pH HER catalysts. Herein, a facile molten urea method is employed to construct the nitrided Rh nanoclusters (RhxN) supported on N-doped carbon (RhxN-NC). The uniformly distributed RhxN clusters exhibited optimized water bonding and splitting effects, therefore resulting in excellent pH-universal HER performance. The optimized RhxN-NC catalyst only requires 8, 12, and 109 mV overpotentials to reach the current density of 10 mA cm-2 in 0.5 M H2SO4, 1.0 M KOH, and 1.0 M PBS electrolytes, respectively. The spectroscopic characterizations and theoretical calculation further confirm the vital role of Rh-N moieties in RhxN clusters in improving the transfer of electrons and facilitating the generation of H2. This work not only provides a suitable nitridation method for noble metal species in mild conditions but also makes a breakthrough in synthesizing noble metal nitrides-based electrocatalysts to achieve an exceptional wide-pH HER performance and other catalysis.

Engineering Zinc-Organic Frameworks-Based Artificial Carbonic Anhydrase with Ultrafast Biomimetic Centers for Efficient Hydration Reactions.

Constructing effective and robust biocatalysts with carbonic anhydrase (CA)-mimetic activities offers an alternative and promising pathway for diverse CO2-related catalytic applications. However, there is very limited success has been achieved in controllably synthesizing CA-mimetic biocatalysts. Here, inspired by the 3D coordination environments of CAs, this study reports on the design of an ultrafast ZnN3-OH2 center via tuning the 3D coordination structures and mesoporous defects in a zinc-dipyrazolate framework to serve as new, efficient, and robust CA-mimetic biocatalysts (CABs) to catalyze the hydration reactions. Owing to the structural advantages and high similarity with the active center of natural CAs, the double-walled CAB with mesoporous defects displays superior CA-like reaction kinetics in p-NPA hydrolysis (V0 = 445.16 nM s-1, Vmax = 3.83 µM s-1, turnover number: 5.97 × 10-3 s-1), which surpasses the by-far-reported metal-organic frameworks-based biocatalysts. This work offers essential guidance in tuning 3D coordination environments in artificial enzymes and proposes a new strategy to create high-performance CA-mimetic biocatalysts for broad applications, such as CO2 hydration/capture, CO2 sensing, and abundant hydrolytic reactions.

SUGP2 p.(Arg639Gln) variant is involved in the pathogenesis of hemochromatosis via the CIRBP/BMPER signaling pathway.

Pathogenic variants in HFE and non-HFE genes have been identified in hemochromatosis in different patient populations, but there are still a certain number of patients with unexplained primary iron overload. We recently identified in Chinese patients a recurrent p.(Arg639Gln) variant in SURP and G-patch domain containing 2 (SUGP2), a potential mRNA splicing-related factor. However, the target gene of SUGP2 and affected iron-regulating pathway remains unknown. We aimed to investigate the pathogenicity and underlying mechanism of this variant in hemochromatosis. RNA-seq analysis revealed that SUGP2 knockdown caused abnormal alternative splicing of CIRBP pre-mRNA, resulting in an increased normal splicing form of CIRBP V1, which in turn increased the expression of BMPER by enhancing its mRNA stability and translation. Furthermore, RNA-protein pull-down and RNA immunoprecipitation assays revealed that SUGP2 inhibited splicing of CIRBP pre-mRNA by a splice site variant at CIRBP c.492 and was more susceptible to CIRBP c.492 C/C genotype. Cells transfected with SUGP2 p.(Arg639Gln) vector showed up-regulation of CIRBP V1 and BMPER expression and down-regulation of pSMAD1/5 and HAMP expression. CRISPR-Cas9 mediated SUGP2 p.(Arg622Gln) knock-in mice showed increased iron accumulation in the liver, higher total serum iron, and decreased serum hepcidin level. A total of 10 of 54 patients with hemochromatosis (18.5%) harbored the SUGP2 p.(Arg639Gln) variant and carried CIRBP c.492 C/C genotype, and had increased BMPER expression in the liver. Altogether, the SUGP2 p.(Arg639Gln) variant down-regulates hepcidin expression through the SUGP2/CIRBP/BMPER axis, which may represent a novel pathogenic factor for hemochromatosis.

Influence on the temporomandibular joint induced by mandibular malpositioning caused by vertical dimension elevation and occlusal loss in adult rats: An imaging, histological and immunohistochemical study.

BACKGROUND: Mandibular malpositioning may result in an abnormal concentration of stresses within the temporomandibular joint (TMJ) in adult rats, which may further lead to a series of pathological changes, such as articular cartilage wear, subchondral bone sclerosis and osteophyte formation. However, the pathological and adaptive changes in condylar cartilage caused by different stress distributions are still controversial. OBJECTIVE: The aim of this study was to observe the effect of sagittal changes in mandibular position on condylar cartilage by changing the occlusal vertical dimension (OVD) in adult rats. METHODS: Fifteen-week-old female rats were divided into three groups: control (CON), increased OVD (iOVD) and loss of occlusion (LO) groups. An occlusal plate and tooth extraction were used to establish the animal model. TMJ samples of the experimental and CON groups were observed and investigated by bone morphological, histomorphological and immunohistochemical staining analyses at 3 days, 1 week, 2 weeks, 4 weeks and 8 weeks. Weight curves were plotted. RESULTS: Micro-computed tomography showed that, compared with the CON group, cartilage destruction followed by repair occurred in both experimental groups, which was similar to the trend observed in haematoxylin-eosin staining. All experimental results for the iOVD group showed an approximately similar time trend. Compared with the iOVD group, the toluidine blue and immunohistochemical staining results in the LO group showed no obvious change trend over time. CONCLUSION: Compared with occlusal loss, an increase in OVD caused faster and more severe damage to condylar cartilage, and subchondral bone repair occurred later.

[Highly polar chemical constituents from whole herb of Scindapsus officinalis].

Macroporous resin column chromatography, MCI medium pressure column chromatography, and semi-preparative high performance liquid chromatography were employed to isolate the chemical components from the aqueous extract of the whole herb of Scindapsus officinalis. The structures of the compounds were identified based on the physical and chemical properties and the spectroscopic data. Ten compounds were isolated from the aqueous extract and identified as 3,4-dihydroxyphenylethyl-8-O-[ß-D-apiofuranosyl-(1→4)]-ß-D-glucopyranoside(1), alternamide B(2), 3,4-dihydroxyphenylethyl-O-ß-D-glucopyranoside(3), 1-(4-hydroxy)-phenylethyl-ß-D-galactopyranoside(4), 3,4-dihydroxyphenylethyl-8-O-[ß-D-apiofuranosyl-(1→2)]-ß-D-glucopyranoside(5), hydroxytyrosol-4-O-ß-D-glucopyranoside(6), 3,5-dihydroxyphenylethyl-3-O-ß-D-glucopyranoside(7), salidroside(8), dihydroisoquinolone(9), and 4-methoxybenzenepropanol-3-O-ß-D-glucopyranoside(10). Among them, compound 1 was a new one, and compounds 2-10 were obtained from S. officinalis for the first time. The RAW264.7 cells were exposed to lipopolysaccharide for the mode-ling of inflammation, and the cells were then used to examine anti-inflammatory activities of the compounds. The results showed that compounds 6 and 7 had strong anti-inflammatory activities, while compounds 1, 2, and 5 had moderate anti-inflammatory activities.

Spiky Artificial Peroxidases with V-O-Fe Pair Sites for Combating Antibiotic-Resistant Pathogens.

With the sharp rise of antibiotic-resistant pathogens worldwide, it is of enormous importance to create new strategies for combating pathogenic bacteria. Here, we create an iron oxide-based spiky artificial peroxidase (POD) with V-O-Fe pair sites (V-Fe2 O3 ) for combating methicillin-resistant Staphylococcus aureus (MRSA). The experimental studies and theoretical calculations demonstrate that the V-Fe2 O3 can achieve the localized "capture and killing" bifunction from the spiky morphology and massive reactive oxygen species (ROS) production. The V-Fe2 O3 can reach nearly 100 % bacterial inhibition over a long period by efficiently oxidizing the lipid membrane. Our wound disinfection results identify that the V-Fe2 O3 can not only efficiently eliminate MRSA and their biofilm but also accelerate wound recovery without causing noticeable inflammation and toxicity. This work offers essential insights into the critical roles of V-O-Fe pair sites and localized "capture and killing" in biocatalytic disinfection and provides a promising pathway for the de novo design of efficient artificial peroxidases.

Interfacial Ir-V Direct Metal Bonding Enhanced Hydrogen Evolution Activity in Vanadium Oxides Supported Catalysts.

Tuning the interfacial structure of metal oxide substrates is an essential strategy to induce electronic structure reconstruction of supported catalysts, which is of great importance in optimizing their catalytic activities. Herein, vanadium oxides-supported Ir catalysts (Ir-V2O3, Ir-VO2, and Ir-V2O5) with different interfacial bonding environments (Ir-V, Ir-Obri, and Ir-O, respectively) were investigated for hydrogen evolution reaction (HER). The regulating mechanism of the influence of different interfacial bonding environments on HER activity was investigated by both experimental results and computational evidence. Benefiting from the unique advantages of interfacial Ir-V direct metal bonds in Ir-V2O3, including enhanced electron transfer and electron donation ability, an optimized HER performance can be obtained with lowest overpotentials of 16 and 26 mV at 10 mA cm-2, high mass activities of 11.24 and 6.66 A mg-1, and turnover frequency values of 11.20 and 6.63 s-1, in acidic and alkaline conditions respectively. Furthermore, the assembled Ir-V2O3||RuO2 anion exchange membrane (AEM) electrolyzer requires only 1.92 V to achieve a high current density of 500 mA cm-2 and realizes long-term stability. This study provides essential insights into the regulating mechanism of interfacial chemical bonding in electrocatalysts and offers a new pathway to design noble metal catalysts for different applications.

Copper-containing titanium alloys promote the coupling of osteogenesis and angiogenesis by releasing copper ions.

Previous investigations have reported on the ability of copper (Cu)-bearing biomaterials to accelerate vascular formation and bone regeneration. However, few studies have explored the effects of Cu-bearing materials on the interactions between angiogenesis and osteogenesis. Therefore, in this study, we prepared Cu-containing alloys using selective laser melting (SLM) technology and investigated the impact of preosteoblasts seeded on Ti6Al4V-4.5Cu alloy on angiogenesis. Our results indicated that Ti6Al4V-4.5Cu alloys increased the expression of proangiogenic genes and proteins in preosteoblasts, which further stimulated vascular formation in endothelial cells. Besides, we discovered that the biological effects of the Ti6Al4V-4.5Cu alloy were partly attributed to the release of Cu ions. In short, our research demonstrated the ability of Ti6Al4V-4.5Cu alloys to promote the coupling of angiogenesis and osteogenesis by releasing Cu ions.

Molybdenum Oxycarbide Supported Rh-Clusters with Modulated Interstitial C-O Microenvironments for Promoting Hydrogen Evolution.

Tuning the microenvironment and electronic structure of support materials is essential strategy to induce electron transfer between supports and active centers, which is of great importance in optimizing catalytic kinetics. In this study, the molybdenum oxycarbide supported Rh-clusters are synthesized with modulated interstitial C-O microenvironments (Rh/MoOC) for promoting efficient hydrogen evolution in water splitting. Both electronic structure characterizations and theoretical calculations uncover the apparent charge transfer from Rh to MoOC, which optimizes the d-band center, H2 O adsorption energy, and hydrogen binding energy, thus enhancing its intrinsic hydrogen-evolving activities. In addition, the co-occurrence of interstitial C and O atoms in MoOC supports plays a vital role in the dissociation reaction of water during the hydrogen-evolving process. Impressively, the Rh/MoOC exhibits excellent hydrogen-evolving activities in terms of exceptional turnover frequency values (11.4 and 39.41 H2 s-1 in alkaline and acidic media) and mass activities (21.3 and 73.87 A mg-1 in alkaline and acidic media) at an overpotential of 100 mV, which is more than 40 times higher than that of the benchmark commercial Rh/C catalysts. This work sheds new light on designing water dissociation materials that surpasses most of the reported catalysts.

Synchronized triple-wavelength fiber lasers at 1, 1.55, and 1.9†µm.

Synchronized lasers working at different wavelengths are of great significance for numerous applications, such as high-energy femtosecond pulse emission, Raman microscopy, and precise timing distribution. Here, we report synchronized triple-wavelength fiber lasers working at 1, 1.55, and 1.9 µm, respectively, by combining the coupling and injection configurations. The laser system consists of three fiber resonators gained by ytterbium-doped fiber, erbium-doped fiber, and thulium-doped fiber, respectively. Ultrafast optical pulses formed in these resonators are obtained by passive mode-locking with the use of a carbon-nanotube saturable absorber. A maximum cavity mismatch of ∼1.4 mm is reached by the synchronized triple-wavelength fiber lasers in the synchronization regime by finely tuning the variable optical delay lines incorporated in the fiber cavities. In addition, we investigate the synchronization characteristics of a non-polarization-maintaining fiber laser in an injection configuration. Our results provide a new, to the best of our knowledge, perspective on multi-color synchronized ultrafast lasers with broad spectral coverage, high compactness, and a tunable repetition rate.

A Semiconductor Biohybrid System for Photo-Synergetic Enhancement of Biological Hydrogen Production.

CdS nanoparticles were introduced on E. coli cells to construct a hydrogen generating biohybrid system via the biointerface of tannic acid-Fe complex. This hybrid system promotes good biological activity in a high salinity environment. Under light illumination, the as-synthesized biohybrid system achieves a 32.44 % enhancement of hydrogen production in seawater through a synergistic effect.

High level of tumor marker CA19-9 returned to normal after cholecystectomy in calculous cholecystitis patients.

BACKGROUND: High serum CA19-9 is usually caused by pancreaticobiliary malignancies, but it has also been found in a tiny minority of calculous cholecystitis patients. AIMS: To clarify the relationship between calculous cholecystitis and serum CA19-9. METHODS: Clinical data of calculous cholecystitis patients with high serum CA19-9 (high group, n = 20) and normal serum CA19-9 (normal group, n = 40) who underwent cholecystectomy were analyzed. Serum CA19-9 of high group were followed-up and gallbladder specimens were analyzed by immunohistochemistry. RESULTS: Serum CA19-9 in the high group ranged from 105 to 1635 U/ml, of which 30% exceeded 1000 U/ml. Follow-up results showed that 20 patient's serum CA19-9 returned to normal after cholecystectomy, including 4 closely followed-up patients whose serum CA19-9 recovered within one month. Immunohistochemical results revealed that CA19-9 was mildly positive only in mucosal epithelial cells in the normal group, but positive in mucosal epithelial cells, vascular endothelial cells, and intercellular substances in the high group, accounting for high serum CA19-9. CONCLUSION: Serum CA19-9 is proved to be associated with calculous cholecystitis for the first time, so that clinicians should consider calculous cholecystitis associated CA19-9 elevation in the clinic practice besides other CA19-9 related diseases.

Pro-carcinogenic actions of miR-155/FOXO3a in colorectal cancer development.

Colorectal cancer (CRC) ranks third in cancer incidence and second in cancer mortality globally. MicroRNAs (miRNAs) are promising biomarkers and therapeutic targets for CRC diagnosis and treatment. The miR-155 is reported to induce radiation resistance in CRC. In this study, we aimed to further clarify the role and underlying mechanism of the miR-155 in CRC cell malignancy. We found that miR-155 was significantly up-regulated in CRC tissues. The results of loss-of-function experiments revealed that miR-155 deficiency suppressed the proliferative capacity, invasion, and migration of CRC cells. Moreover, the downstream target genes of miR-155 were screened, and miR-155 was demonstrated to directly bind to FOXO3a in CRC cells to negatively regulate FOXO3a expression. FOXO3a was downregulated in CRC tissues and the expression of FOXO3a and miR-155 was in negative correlation in CRC tissues. FOXO3a overexpression alone was revealed to inhibit CRC cell growth, migration and invasion. Additionally, rescue assays showed that FOXO3a silencing significantly reversed the inhibitory effect of miR-155 deficiency on CRC cell malignant behaviors. In conclusion, miR-155 induces malignant phenotypes of CRC cells including cell proliferation, migration and invasion by targeting FOXO3a, which might provide clues for the targeted therapy of CRC.

Accuracy of 2 direct digital scanning techniques-intraoral scanning and stereophotogrammetry-for complete arch implant-supported fixed prostheses: A prospective study.

STATEMENT OF PROBLEM: Conventional impression techniques for complete arch implant-supported prostheses are technique-sensitive. Stereophotogrammetry (SPG) and intraoral scanning (IOS) may offer an alternative to conventional impression making. PURPOSE: The purpose of this prospective study was to compare the accuracy of IOS and SPG for complete arch implant scans and to evaluate the passive fit of frameworks fabricated with SPG. MATERIAL AND METHODS: Laboratory scanning of gypsum casts, SPG, and IOS were performed for all participants. The data regarding the abutment platform were superimposed to calculate the 3D deviation of SPG and IOS compared with that of laboratory scanning as an evaluation of accuracy. The effect of implant position and number on accuracy was analyzed. The more accurate technique between SPG and IOS was used to fabricate the titanium frameworks, as was laboratory scanning. The passive fit of the frameworks was assessed by clinical examination, the Sheffield test, and panoramic radiography. RESULTS: Seventeen participants (21 arches, 120 implants) were included. The accuracy of SPG ranged from 2.70 µm to 92.80 µm, with a median (Q1, Q3) of 17.00 (11.68, 22.50) µm, which was significantly more accurate than that of IOS, ranging from 21.30 µm to 815.60 µm, with a median (Q1, Q3) of 48.95 (34.78, 75.88) µm. No significant correlation was found between position or number of implants and 3D deviation in the SPG group. A weak positive correlation was found between implant number and 3D deviation in the IOS group. SPG and laboratory scanning were used to fabricate titanium frameworks. The passive fit between the frameworks and abutment platforms was confirmed. CONCLUSIONS: SPG, which was not affected by position or number of implants, was more accurate than IOS and comparable with laboratory scanning. The frameworks fabricated based on SPG and laboratory scanning were comparable in their passive fit. The SPG technique may be an alternative to laboratory scanning for complete arch implant scans.

A completely digital workflow aided by cone beam computed tomography scanning to maintain jaw relationships for implant-supported fixed complete dentures: A clinical study.

STATEMENT OF PROBLEM: The conventional workflow for the fabrication of implant-supported fixed complete dentures (IFCDs) is complex and makes it impossible to maintain jaw relationships. A fully digital workflow might solve this problem. PURPOSE: The purpose of this clinical study was to develop a completely digital workflow aided by a cone beam computed tomography (CBCT) scan for the fabrication of IFCDs and to evaluate the accuracy of this workflow with regard to the maintenance of jaw relationships. MATERIAL AND METHODS: All participants received a preoperative CBCT scan while wearing radiographic diagnosis dentures and occluding in the maximum intercuspal position. After the implant surgery, CBCT scanning, intraoral scanning, and stereophotogrammetry were performed to identify jaw anatomy, soft tissue, and the 3-dimensional (3D) locations of the implants, respectively. Then, all data were merged to transfer jaw relationships and generate digital casts to fabricate interim prostheses. A posttreatment CBCT scan was performed while the participants were wearing the interim prostheses and occluding in the maximum intercuspal position. The preoperative and postoperative jaw relationships were compared by CBCT cephalometric analysis. A meaningful and unacceptable difference was defined as 0.8 degrees and 2.4 degrees, respectively. RESULTS: Six participants (6 jaw relationships, 9 arches, and 58 implants) were included. All interim prostheses were stable and achieved symmetric occlusion after only minimal adjustment. A total of 18 angles were measured. Three angles revealed a meaningful minimal difference, and 1 angle revealed an unacceptable minimal difference. No prosthodontic complications were reported during the study. CONCLUSIONS: A completely digital workflow for fabricating IFCDs achieved sufficient accuracy for the maintenance of jaw relationships throughout the treatment.

Integrative metabolomic characterisation identifies altered portal vein serum metabolome contributing to human hepatocellular carcinoma.

OBJECTIVE: Altered metabolites are important for the tumourigenicity of hepatocellular carcinoma (HCC). We performed integrative metabolomics analysis of the metabolites changes in portal venous blood and in comparison with the metabolites changes in liver tissues and stool samples of HCC patients and healthy liver donors. DESIGN: Serum (portal and central vein), liver tissue (HCC tumour and adjacent non-tumour, normal liver) and stool samples were collected from 102 subjects (52 HCC patients and 50 healthy controls) in the discovery cohort; and 100 subjects (50 HCC patients and 50 healthy controls) in an independent validation cohort. Untargeted metabolomic profiling was performed using high-performance liquid chromatography-mass spectrometry. The function of candidate metabolites was validated in hepatocyte cell lines. RESULTS: Detailed metabolomic evaluation showed distinct clusters of metabolites in serum, liver tissue and stool samples from patients with HCC and control individuals (p<0.001). HCC patients had significantly higher levels of portal vein serum and HCC tissue metabolites of DL-3-phenyllactic acid, L-tryptophan, glycocholic acid and 1-methylnicotinamide than healthy controls, which were associated with impaired liver function and poor survival. On the other hand, HCC patients had lower levels of linoleic acid and phenol in portal vein and stool samples than healthy controls. Linoleic acid and phenol significantly inhibited HCC proliferation, inferring their anti-HCC function as protective metabolites. CONCLUSIONS: The integrative metabolome analysis of serum, tissue and stool metabolites revealed unreported metabolic alterations in HCC patients. In portal vein, we identified elevated and depleted metabolites signifying that they might play a role in HCC development.

Gene expression profiles provide insights into the survival strategies in deep-sea mussel (Bathymodiolus platifrons) of different developmental stages.

BACKGROUND: Deep-sea mussels living in the cold seeps with enormous biomass act as the primary consumers. They are well adapted to the extreme environment where light is absent, and hydrogen sulfide, methane, and other hydrocarbon-rich fluid seepage occur. Despite previous studies on diversity, role, evolution, and symbiosis, the changing adaptation patterns during different developmental stages of the deep-sea mussels remain largely unknown. RESULTS: The deep-sea mussels (Bathymodiolus platifrons) of two developmental stages were collected from the cold seep during the ocean voyage. The gills, mantles, and adductor muscles of these mussels were used for the Illumina sequencing. A total of 135 Gb data were obtained, and subsequently, 46,376 unigenes were generated using de-novo assembly strategy. According to the gene expression analysis, amounts of genes were most actively expressed in the gills, especially genes involved in environmental information processing. Genes encoding Toll-like receptors and sulfate transporters were up-regulated in gills, indicating that the gill acts as both intermedium and protective screen in the deep-sea mussel. Lysosomal enzymes and solute carrier responsible for nutrients absorption were up-regulated in the older mussel, while genes related to toxin resistance and autophagy were up-regulated in the younger one, suggesting that the older mussel might be in a vigorous stage while the younger mussel was still paying efforts in survival and adaptation. CONCLUSIONS: In general, our study suggested that the adaptation capacity might be formed gradually during the development of deep-sea mussels, in which the gill and the symbionts play essential roles.

Prognostic value of hemoglobin combined with Geriatric Nutritional Risk Index scores in patients undergoing postoperative radiotherapy for esophageal squamous cell carcinoma.

Aims: To investigate the prognostic value of hemoglobin combined with geriatric nutritional risk index (GNRI) scores in patients undergoing postoperative radiotherapy for esophageal squamous cell carcinoma (ESCC). Patients & methods: Patients who underwent esophagectomy and postoperative radiotherapy were included in this retrospective study. Their preoperative hemoglobin and GNRI were collected to establish hemoglobin-GNRI (H-GNRI) scores, and their association with OS was evaluated. Results: Patients with high H-GNRI scores had better prognosis than those with low scores (p < 0.001). Differentiation (p = 0.001), T classification (p = 0.010), N classification (p = 0.001) and H-GNRI score (p = 0.018) were independent prognostic factors for all patients. Conclusion: H-GNRI score is an independent prognostic factor for the survival of patients with ESCC managed by surgery and postoperative radiotherapy.

Effects of metformin on the osteogenesis of alveolar BMSCs from diabetic patients and implant osseointegration in rats.

OBJECTIVES: This study aimed to explore the effects of metformin on osteogenic differentiation of alveolar bone marrow mesenchymal stem cells (BMSCs) from type-2 diabetes mellitus (T2DM) patients (DM-BMSCs) and implant osseointegration in rats, screen the optimal concentration, and investigate whether metformin could protect against the adverse impact of T2DM on BMSC osteogenic capacity. SUBJECTS AND METHODS: Different concentrations of metformin were administered to human-derived BMSCs and Wistar rats receiving implants. ALP detection, alizarin red staining, real-time RT-PCR and Western blotting were performed to detect osteogenesis and investigate the mechanism. Toluidine blue staining was performed to analyse bone-implant contact in rats. RESULTS: Metformin increased implant osseointegration in a rat model and promoted the osteogenic capacity of DM-BMSCs via the AMPK/BMP/Smad signalling pathway, and 125 µM was the optimal concentration; however, concentrations over 200 µM, metformin showed an inhibitory effect on DM-BMSCs. Additionally, metformin at the optimal concentration (125 µM) identified in this study could compensate for the negative impacts of T2DM on the osteogenic differentiation of BMSCs. CONCLUSIONS: Metformin can promote the osteogenesis of BMSCs from T2DM patients and osseointegration in rats, and it might be an effective drug for increasing the success rate of T2DM-associated implants.

Plasma Metabolomic Profiling of Patients Recovered From Coronavirus Disease 2019 (COVID-19) With Pulmonary Sequelae 3 Months After Discharge.

BACKGROUND: Elucidation of the molecular mechanisms involved in the pathogenesis of coronavirus disease 2019 (COVID-19) may help to discover therapeutic targets. METHODS: To determine the metabolomic profile of circulating plasma from COVID-19 survivors with pulmonary sequelae 3 months after discharge, a random, outcome-stratified case-control sample was analyzed. We enrolled 103 recovered COVID-19 patients as well as 27 healthy donors, and performed pulmonary function tests, computerized tomography (CT) scans, laboratory examinations, and liquid chromatography-mass spectrometry. RESULTS: Plasma metabolite profiles of COVID-19 survivors with abnormal pulmonary function were different from those of healthy donors or subjects with normal pulmonary function. These alterations were associated with disease severity and mainly involved amino acid and glycerophospholipid metabolic pathways. Furthermore, increased levels of triacylglycerols, phosphatidylcholines, prostaglandin E2, arginine, and decreased levels of betain and adenosine were associated with pulmonary CO diffusing capacity and total lung capacity. The global plasma metabolomic profile differed between subjects with abnormal and normal pulmonary function. CONCLUSIONS: Further metabolite-based analysis may help to identify the mechanisms underlying pulmonary dysfunction in COVID-19 survivors, and provide potential therapeutic targets in the future.