Integrated Metabolome and Transcriptome Analysis of Gibberellins Mediated the Circadian Rhythm of Leaf Elongation by Regulating Lignin Synthesis in Maize.

Plant growth exhibits rhythmic characteristics, and gibberellins (GAs) are involved in regulating cell growth, but it is still unclear how GAs crosstalk with circadian rhythm to regulate cell elongation. The study analyzed growth characteristics of wild-type (WT), zmga3ox and zmga3ox with GA3 seedlings. We integrated metabolomes and transcriptomes to study the interaction between GAs and circadian rhythm in mediating leaf elongation. The rates of leaf growth were higher in WT than zmga3ox, and zmga3ox cell length was shorter when proliferated in darkness than light, and GA3 restored zmga3ox leaf growth. The differentially expressed genes (DEGs) between WT and zmga3ox were mainly enriched in hormone signaling and cell wall synthesis, while DEGs in zmga3ox were restored to WT by GA3. Moreover, the number of circadian DEGs that reached the peak expression in darkness was more than light, and the upregulated circadian DEGs were mainly enriched in cell wall synthesis. The differentially accumulated metabolites (DAMs) were mainly attributed to flavonoids and phenolic acid. Twenty-two DAMs showed rhythmic accumulation, especially enriched in lignin synthesis. The circadian DEGs ZmMYBr41/87 and ZmHB34/70 were identified as regulators of ZmHCT8 and ZmBM1, which were enzymes in lignin synthesis. Furthermore, GAs regulated ZmMYBr41/87 and ZmHB34/70 to modulate lignin biosynthesis for mediating leaf rhythmic growth.

[Anti-arthritic-related metal bioavailability for optimal compatibility ratio of Aconiti Radix Cocta and Paeoniae Radix Alba].

Trace metals deficiency or excess are associated with the etiology and pathogenesis of rheumatoid arthritis(RA). Aconiti Radix Cocta(A) and Paeoniae Radix Alba(B) are commonly used together for the treatment of RA. In this study, we aim to determine anti-arthritic-related metal bioavailability in the compatibility of herb A and B for avoiding metal deficiency or excess, and optimize the combination ratio of herb A and B, accordingly. Anti-arthritic-related metal bioaccessibility were evaluated by in vitro simulator of all gastrointestinal tract(including mouth, stomach, small and large intestines), and the roles of gastrointestinal digestive enzymes and intestinal microflora were investigated. Anti-arthritic-related metal bioavailability was assessed by the affinity adsorption with liposomes. The results indicated that compatibility proportion of corresponding herbal plants, gastrointestinal digestion and microbial metabolic, which could affect metal digestion and absorption. The optimal compatibility proportion of 1 A∶1 B is recommended, according to the dose of anti-arthritic-related metal bioavailability, which is often chosen for clinical practice of RA therapy. Thus, anti-arthritic-related metal bioavailability might be the key active substances for RA treatment.

Zwitterionic PMCP-Modified Polycaprolactone Surface for Tissue Engineering: Antifouling, Cell Adhesion Promotion, and Osteogenic Differentiation Properties.

Biodegradable polycaprolactone (PCL) has been widely applied as a scaffold material in tissue engineering. However, the PCL surface is hydrophobic and adsorbs nonspecific proteins. Some traditional antifouling modifications using hydrophilic moieties have been successful but inhibit cell adhesion, which is not ideal for tissue engineering. The PCL surface is modified with bioinspired zwitterionic poly[2-(methacryloyloxy)ethyl choline phosphate] (PMCP) via surface-initiated atom transfer radical polymerization to improve cell adhesion through the unique interaction between choline phosphate (CP, on PMCP) and phosphate choline (PC, on cell membranes). The hydrophilicity of the PCL surface is significantly enhanced after surface modification. The PCL-PMCP surface reduces nonspecific protein adsorption (e.g., up to 91.7% for bovine serum albumin) due to the zwitterionic property of PMCP. The adhesion and proliferation of bone marrow mesenchymal stem cells on the modified surface is remarkably improved, and osteogenic differentiation signs are detected, even without adding any osteogenesis-inducing supplements. Moreover, the PCL-PMCP films are more stable at the early stage of degradation. Therefore, the PMCP-functionalized PCL surface promotes cell adhesion and osteogenic differentiation, with an antifouling background, and exhibits great potential in tissue engineering.

Consequences of orthodontic treatment in malocclusion patients: clinical and microbial effects in adults and children.

BACKGROUND: Malocclusion is a common disease of oral and maxillofacial region. The study was aimed to investigate levels changes of periodontal pathogens in malocclusion patients before, during and after orthodontic treatments, and to confirm the difference between adults and children. METHOD: One hundred and eight malocclusion patients (46 adults and 62 children at the school-age) were randomly selected and received orthodontic treatment with fixed orthodontic appliances. Subgingival plaques were Porphyromonas gingivalis (P.gingivalis), Fusobacterium nucleatum (F. nucleatum), Prevotella intermedia (P. intermedia) and Tannerella forsythensis (T. forsythensis) collected from the observed regions before and after treatment. Clinical indexes, including plaque index (PLI), gingival index (GI), sulcus bleeding index (SBI), probing depth (PD) and attachment loss (AL) of observed teeth were examined. RESULTS: The detection rates of P.gingivalis, F. nucleatum, P. intermedia and T. forsythensis increased from baseline to the third month without significant difference, and then returned to pretreatment levels 12 month after applying fixed orthodontic appliances. Adults' percentage contents of P.gingivalis, F. nucleatum, P. intermedia and T. forsythensis were significantly higher than those of children at baseline and the first month, but not obvious at the third month. PLI and SBI were increased from baseline to the first and to the third month both in adults and children groups. Besides, PD were increased from baseline to first month, followed by a downward trend in the third month; however, all patients were failed to detect with AL. CONCLUSIONS: Periodontal and microbiological statuses of malocclusion patients may be influenced by fixed orthodontic appliances in both adults and children, more significant in children than in adults. Some microbiological indexes have synchronous trend with the clinical indexes. Long-term efficacy of fixed orthodontic appliances for malocclusion should be confirmed by future researches.

Efficacy of dexmedetomidine on postoperative shivering: a meta-analysis of clinical trials.

PURPOSE: Shivering is a frequent complication in the postoperative period. The aim of the current meta-analysis was to assess the efficacy of dexmedetomidine on postoperative shivering. METHODS: Two researchers independently searched PubMed, EMBASE and the Cochrane Central Register of Controlled Trials for controlled clinical trials. The meta-analysis was performed by Review Manager. RESULTS: Thirty-nine trials with 2,478 patients were included in this meta-analysis. Dexmedetomidine reduced postoperative shivering compared with placebo (risk ratio [RR] = 0.26; 95% confidence interval [CI]: 0.20 to 0.34), with a minimum effective dose of 0.5 µg·kg(-1) (RR = 0.36; 95% CI: 0.21 to 0.60). The anti-shivering effect can be achieved both intravenously and epidurally when administered within two hours prior to the end of surgery. The efficacy of dexmedetomidine was similar to widely used anti-shivering agents, such as fentanyl, meperidine, tramadol, clonidine and so on; however, dexmedetomidine may increase the incidence of sedation, hypotension, bradycardia and dry mouth. CONCLUSIONS: The present meta-analysis indicates that dexmedetomidine shows superiority over placebo, but not over other anti-shivering agents. Therefore, considering its high price and potential adverse events, dexmedetomidine may not be appropriate solely for the purpose of the prevention of postoperative shivering.

Constituting fully integrated visual analysis system for Cu(II) on TiO2/cellulose paper.

As a cheap and abundant porous material, cellulose filter paper was used to immobilize nano-TiO2 and denoted as TiO2/cellulose paper (TCP). With high adsorption capacity for Cu(II) (more than 1.65 mg), TCP was used as an adsorbent, photocatalyst, and colorimetric sensor at the same time. Under the optimum adsorption conditions, i.e., pH 6.5 and 25 °C, the adsorption ratio of Cu(II) was higher than 96.1%. Humic substances from the matrix could be enriched onto TCP but the interference of their colors on colorimetric detection could be eliminated by the photodegradation. In the presence of hydroxylamine, neocuproine, as a selective indicator, was added onto TCP, and a visual color change from white to orange was generated. The concentration of Cu(II) was quantified by the color intensity images using image processing software. This fully integrated visual analysis system was successfully applied for the detection of Cu(II) in 10.0 L of drinking water and seawater with a preconcentration factor of 10(4). The log-linear calibration curve for Cu(II) was in the range of 0.5-50.0 µg L(-1) with a determination coefficient (R(2)) of 0.985 and its detection limit was 0.073 µg L(-1).

Ischemic preconditioning reduces transplanted submandibular gland injury.

BACKGROUND: Ischemic preconditioning (IPC) can reduce ischemia/reperfusion (I/R) injury in multiple organs and species. However, the effect of IPC on transplanted submandibular glands remains unknown. We explored the protection of IPC in transplanted submandibular glands in the rabbit and the underlying mechanism. METHODS: IPC was performed by clamping the lingual artery for 10 min, with 10 min of reperfusion before transplantation. Male rabbits were randomly divided into control, transplantation, and IPC groups (n = 6 each). Saliva secretion, oxidative stress, pro-inflammatory cytokine levels, and apoptosis-related protein levels were determined at 1, 12, and 24 h after reperfusion. RESULTS: Salivary flow was significantly increased at 12 h and decreased at 24 h in the transplanted glands. IPC treatment prevented the reduced saliva secretion at 24 h after reperfusion (P < 0.01). The mRNA levels of tumor necrosis factor-α, interleukin-1ß, and reactive oxygen species, as well as malondialodehyde (MDA) and myeloperoxidase activity, were significantly increased and superoxide dismutase activity was decreased in the transplanted glands. However, these changes were all attenuated with IPC treatment (all P < 0.05). Also, acinar cell apoptosis and Bax protein expression were decreased and Bcl-2 protein expression was increased in the IPC-treated glands at 1 and 12 h after reperfusion (all P < 0.05). CONCLUSIONS: IPC protects the secretory function of transplanted submandibular gland in the rabbit by reducing the inflammatory response, attenuating oxidative stress, and an anti-apoptosis process.

[Construction and functional characterization of a monocistronic replicon based on the HCV genotype 2a promotor].

To construct a hepatitis C virus (HCV) genotype 2a monocistronic replicon and investigate its replication capabilities in the human hepatocarcinoma cell lines, Huh7.5 and Huh7.1, in order to determine its potential as a molecular tool for future in vitro studies of HCV replication and selection studies for putative anti-HCV drugs. Site-directed mutagenesis was used to delete the Core-E1-E2-p7-NS2 fragment (about 3090 bp) from plasmid pJ6JFH1BlaRL. The resultant trianglepJ6JFH1BlaRL plasmid was digested with AgeI and AvrII to release the cDNA fragment (hereafter, referred to as fragment L) containing partial 5'-untranslated region (UTR), the first 12 amino acid (aa) of HCV Core coding sequence, full-length coding sequences for the blasticidin-resistance gene, Renilla luciferase, foot-and-mouth disease virus (FMDV) 2a antiprotease and ubiquitin, and partial coding sequence for HCV NS3. To generate the monocistronic replicon, pSGRmJFH1BlaRL, fragment L was ligated into the pSGR-JFH1 vector that had been digested with AgeI and AvrII to remove the partial 5'-UTR, the first 19 aa of HCV Core coding sequence, the full-length coding sequence for the neomycin phosphotransferase II gene, the internal ribosomal entry site from encephalomyocarditis virus, and partial HCV NS3 coding sequence. A replication-defective mutant replicon, pSGRmJFH1BlaRL/GND, was constructed by a similar procedure using the pSGR-JFH1/GND vector. Fragment L was confirmed in both constructs by sequencing. Replicon RNAs were prepared from XbaI-linearized plasmid DNA templates with Invitrogen's T7 MEGAscript kit, and were purified by DNase I treatment and LiCl precipitation. RNAs were quanti?ed by optical density, and the quality and concentration were con?rmed by agarose gel electrophoresis. Replicon RNAs were transfected into Huh7.5 and Huh7.1 cells using Invitrogen's DMRIE-C transfection reagent at a ratio of 5 mug of lipid to 1mug of RNA. Time course assay of Renilla luciferase activity indicated the replicon's replication function. The pSGRmJFH1BlaRL monocistronic replicon and pSGRmJFH1BlaRL/GND replication-defective mutant replicon were successfully constructed. The pSGRmJFH1BlaRL replicon was replication-proficient in Huh7.5 and Huh7.1 cells, with replication peaking at 72 hours post-transfection and decreasing after 96 hours. No replication was detected at any time point post-transfection for the defective mutant replicon. A monocistronic replicon of HCV genotype 2a was constructed and shown to be replication-proficient in human hepatocarcinoma cell lines.

[Clinical effect of digital impression combined with all-ceramic denture on restoration of 60 patients with dental defects].

PURPOSE: To analyze the clinical effect of digital impression combined with all-ceramic denture restoration on patients with dental defects. METHODS: A study was conducted on 120 patients with dental defects admitted to Dongfeng Stomatological Hospital from June 2018 to June 2020. The two groups of patients were randomly divided into digital imprinting modules and silicone rubber imprinting modules using a random number table method. There were 60 cases in each group. The silicone rubber imprint module used traditional silicone impression combined with all-ceramic denture restoration, while the digital imprint module used digital impression combined with all-ceramic denture restoration.The clinical efficacy of the two groups was observed. Gingival index (GI), periodontal index (PI) before dental restoration, during dental restoration and 6 monthes after dental restoration were compared. The adjacent surface contact conditions, occlusion and adverse reactions of the two groups were compared. SPSS 22.0 software package was used for statistical analysis. RESULTS: The two groups of patients selected grade A and grade B for the evaluation of the restoration when the restoration was completed. The number of patients who chose grade A for the digital imprint module was more than that of the silicone rubber imprint module,but there was no significant difference(P＞0.05). Six months after the tooth was worn, GI and PI indexes of the two groups of patients increased. GI and PI indexes of the silicone rubber stamping module were significantly higher than those of the digital stamping module(P＜0.05). When dental restoration was completed and 6 months after the tooth was replaced, the pass rate of contact between the adjacent surfaces of the imprinting module patients was significantly higher than that of the silicone rubber imprinting module(P＜0.05). When dental restoration was completed, the occlusion of the digital imprinting module patients was significantly better than that of the silicone rubber imprinting module(P＜0.05). Six months after wearing the denture, there was no significant difference in occlusion between the two groups of patients(P＞0.05). When dental models of the two groups of patients were taken, the incidence of adverse reactions in patients with digital imprints was significantly lower than that of silicone rubber imprints(P＜0.05). CONCLUSIONS: The use of digital impressions combined with all-ceramic restorations to repair patients with dental defects can effectively improve the treatment effect, improve prognostic GI and PI indexes of the patients, increase the pass rate of the adjacent surface contact and occlusion of the tooth, and reduce the process of dental restoration. The incidence of adverse reactions are minimal, with good prognostic effects. It is worthy of clinical application.

Oral and maxillofacial pain as the first sign of metastasis of an occult primary tumour: A fifteen-year retrospective study.

BACKGROUND: Metastatic adenocarcinoma of the jaw (MAJ) is a rare disease that accounts for 1%-3% of all oral and maxillofacial malignant tumours. Oral and maxillofacial pain may be the first symptom of metastatic spread of an occult primary tumour. Therefore, early identification of oral and maxillofacial pain by dental professionals is critical. AIM: To explore the clinical and computerized tomography (CT) features of MAJ with oral and maxillofacial pain as the first symptom. METHODS: The medical records of all patients who were treated in our hospital between January 2006 and February 2020, and diagnosed with MAJ with oral and maxillofacial pain as the first symptom, were reviewed retrospectively. Clinical data were collected on age, sex, medical history, clinical manifestations, site of metastasis, and site of the primary lesion. CT features were analysed in detail, and a radiological classification scheme comprising five types: Osteolytic, osteoblastic, mixed, cystic, and alveolar bone resorption was proposed. RESULTS: The primary sites of MAJ were the lungs (n = 6), liver (n = 4), kidneys (n = 2), prostate (n = 1), and gastric cardia (n = 1). Five tumours were classified as the osteolytic type, all with a permeative margin (100%, P < 0.05), and three were classified as the mixed type, mostly with a moth-eaten margin (80%, P < 0.05). The cystic (n = 3) and alveolar bone resorption (n = 1) types had geographic margins, and the osteoblastic type (n = 1) had sclerotic margins. Moreover, nine tumours showed periosteal reaction and five showed a localised soft tissue mass, while the occurrence of jaw expansion was relatively rare. CONCLUSION: MAJ has complex clinical and CT features. Oral and maxillofacial pain may be the first sign of a primary tumour affecting other sites.

Immunotherapy combining tumor and endothelium cell lysis with immune enforcement by recombinant MIP-3α Newcastle disease virus in a vessel-targeting liposome enhances antitumor immunity.

BACKGROUND: Several agents for oncolytic immunotherapy have been approved for clinical use, but monotherapy is modest for most oncolytic agents. The combination of several therapeutic strategies through recombinant and nanotechnology to engineer multifunctional oncolytic viruses for oncolytic immunotherapy is a promising strategy. METHODS: An endothelium-targeting iRGD-liposome encapsulating a recombinant Newcastle disease virus (NDV), which expresses the dendritic cell (DC) chemokine MIP-3α (iNDV3α-LP), and three control liposomes were constructed. MIP-3α, HMGB1, IgG, and ATP were detected by western blotting or ELISA. The chemotaxis of DCs was examined by Transwell chambers. The phenotypes of the immune cells were analyzed by flow cytometry. The antitumor efficiency was investigated in B16 and 4T1 tumor-bearing mice. Immunofluorescence and immunohistochemistry were used to observe the localization of liposomes, molecular expression and angiogenesis. Synergistic index was calculated using the data of tumor volume, tumor angiogenesis and tumor-infiltrating lymphocytes. RESULTS: Compared with NDV-LP, treatment with iNDV3α-LP and NDV3α-LP induced stronger virus replication and cell lysis in B16 and 4T1 tumor cells and human umbilical vein endothelial cells (HUVECs) with the best response observed following iNDV3α-LP treatment. B16 and 4T1 cells treated with iNDV3α-LP produced more damage-associated molecular pattern molecules, including secreted HMGB1, ATP, and calreticulin. Moreover, iNDV3α-LP specifically bound to αvß3-expressing 4T1 cells and HUVECs and to tumor neovasculature. Tumor growth was significantly suppressed, and survival was longer in iNDV3α-LP-treated B16-bearing and 4T1-bearing mice. A mechanism study showed that iNDV3α-LP treatment initiated the strongest tumor-specific cellular and humoral immune response. Moreover, iNDV3α-LP treatment could significantly suppress tumor angiogenesis and reverse the tumor immune suppressive microenvironment in both B16-bearing and 4T1-bearing mice. CONCLUSIONS: In this study, iNDV3α-LP had several functions, such as tumor and vessel lysis, MIP-3α immunotherapy, and binding to αvß3-expressing tumor and its neovasculature. iNDV3α-LP treatment significantly suppressed tumor angiogenesis and reversed the tumor immunosuppressive microenvironment. These findings offer a strong rationale for further clinical investigation into a combination strategy for oncolytic immunotherapy, such as the formulation iNDV3α-LP in this study.

Low-toxic, fluorescent labeled and size-controlled graphene oxide quantum dots@polystyrene nanospheres as reference material for quantitative determination and in vivo tracing.

Polystyrene (PS) is selected as a representative nanoplastic and persistent pollutant for its difficult degradation and wide application. The environmental risk assessment of PS is obstructed by the toxic dye-based fluorescent PS, which false positives could be induced by the leakage of dye. For high biocompatibility, low toxicity, hydrophilicity, good water dispersibility, strong fluorescent stability, graphene oxide quantum dots (o-CQDs) are selected and embedded into PS microspheres, i.e., o-CQDs@PS, by microemulsion polymerization and denoted as CPS. Meanwhile, the sizes of CPS, e.g., 100, 150, and 200 nm, could be controlled by optimizing the type and number of water-soluble initiators. The anti-interference, low toxicity, and in vivo fluorescent tracing of CPS are proven by the coexistence of metals (including Fe2+, Fe3+, K+, Ba2+, Al3+, Zn2+, Mg2+, Ca2+, and Na+) on the fluorescence intensity of CPS, the growth of Chlorella pyrenoidosa and Artemia cysts as aquatic phytoplankton and zooplankton cultured with CPS, and the transfer of CPS from water into brine shrimp. In the concentration range of 0.1-100 mg/L, CPS can be quantitatively determined, which is suitable for coastal water and wastewater treatment plants. Therefore, CPS with standard size is suitable as reference material of PS.

Speciation analysis of silver nanoparticles and silver ions in antibacterial products and environmental waters via cloud point extraction-based separation.

The rapid growth in commercial use of silver nanoparticles (AgNPs) will inevitably increase silver exposure in the environment and the general population. As the fate and toxic effects of AgNPs is related to the Ag(+) released from AgNPs and the transformation of Ag(+) into AgNPs, it is of great importance to develop methods for speciation analysis of AgNPs and Ag(+). This study reports the use of Triton X-114-based cloud point extraction as an efficient separation approach for the speciation analysis of AgNPs and Ag(+) in antibacterial products and environmental waters. AgNPs were quantified by determining the Ag content in the Triton X-114-rich phase with inductively coupled plasma mass spectrometry (ICPMS) after microwave digestion. The concentration of total Ag(+), which consists of the AgNP adsorbed, the matrix associated, and the freely dissolved, was obtained by subtracting the AgNP content from the total silver content that was determined by ICPMS after digestion. The limits of quantification (S/N = 10) for antibacterial products were 0.4 µg/kg and 0.2 µg/kg for AgNPs and total silver, respectively. The reliable quantification limit was 3 µg/kg for total Ag(+). The presence of Ag(+) at concentrations up to 2-fold that of AgNPs caused no effects on the determination of AgNPs. In the cloud point extraction of AgNPs in antibacterial products, the spiked recoveries of AgNPs were in the range of 71.7-103% while the extraction efficiencies of Ag(+) were in the range of 1.2-10%. The possible coextracted other silver containing nanoparticles in the cloud point extraction of AgNPs were distinguished by transmission electron microscopy (TEM), scanning electron microscopy (SEM)- energy dispersive spectroscopy (EDS), and UV-vis spectrum. Real sample analysis indicated that even though the manufacturers claimed nanosilver products, AgNPs were detected only in three of the six tested antibacterial products.

[A finite element study of the influence of upper lip pressure on the development of maxilla after cleft lip surgery].

PURPOSE: To explore the mechanism of upper lip pressure on maxilla after cleft lip surgery. METHODS: ANSYS 17.0 software was used to add the upper lip soft tissue to the finite element model of maxilla with cleft palate, and the material properties was assigned to form a three-dimensional finite element model of maxilla with upper lip. The upper lip pressure was applied to the model and force analysis was performed in 2 groups. In the experimental group, upper lip pressure with cleft lip surgery was applied; in the control group, upper lip pressure in normal children of the same age was applied. RESULTS: Maxillary deformation in the experimental group was greater than that in the control group. Maxillary deformation occurred in three-dimensional direction, which was mainly in Z axis, followed by X axis and Y axis. The anterior segment of alveolar process was the most obvious，and from the anterior to the posterior, the change trend was gradually decreased. CONCLUSIONS: Maxillary growth is inhibited in three-dimensional direction,which is mainly sagittal growth inhibition,followed by transverse and vertical growth. The inhibition gradually decreases from anterior to posterior.

Decellularized gastric matrix as a mesh for gastric perforation repair.

The development of novel materials with effective defect-repairing properties will help avoid subtotal gastrectomy in patients with large gastric perforations. We prepared perfused decellularized gastric matrix (PDGM) and analyzed its components, spatial structure, biomechanics, cytotoxicity, and histocompatibility to validate its efficacy in the repair of gastric perforation. PDGM retained large amounts of gastric extracellular matrix, while residual glandular cells and muscle fibers were not found. The spatial structure of the tissue was well preserved, while the DNA and glycosaminoglycan contents were significantly decreased compared with normal gastric tissue (p < .01). There was no obvious deformation of the spatial structure and tissue elasticity of PDGM after sterilization by Cobalt-60 irradiation. The PDGM had good histocompatibility. PDGM was then used to repair a rat gastric perforation model. Radiography of the upper gastrointestinal tract at 24 hr postoperatively revealed no contrast agent leakage. There was evidence of early fibroblast proliferation, which was complicated by capillary regeneration. The hyperplastic gastric gland was slightly disarranged after repair. Defects of the muscular layer also healed a little with the regeneration process. PDGM is a nontoxic biocompatible biological mesh that may be useful for repairing relatively large gastric defects.

Biomimicking Dual-Responsive Extracellular Matrix Restoring Extracellular Balance through the Na/K-ATPase Pathway.

Biomedical implant mimicking the physiological extracellular matrix (ECM) is a new strategy to modulate the cell microenvironment to improve implant integrity and longevity. However, the biomimicking ECM suffers from low sensitivity to pathological change and low efficiency to restore the physiological state in vivo. To overcome these problems, reactive oxygen species (ROS) and K+ dual-responsive micro-/nanofibers that encapsulate ascorbic acid-2-glucoside (AA-2G) are fabricated on an elastomer substrate with electrospinning to mimic the ECM. The strategy is based on the fact that ROS and K+ dual responsiveness enhance the sensitivity of the ECM to pathological changes and delivery of AA-2G from the ECM to cell membrane promotes reactivating Na/K-ATPase and shifting cellular diseased conditions to the normal state. We demonstrate that the ROS and K+-responsive tripolymer of poly(ethylene glycol)diacrylate, 1,2-ethanedithiol, and 4-nitrobenzo-18-crown-6-ether (PEGDA-EDT-BCAm) are synthesized successfully; the ECM composed of acylated poly(caprolactone)/PEGDA-EDT-BCAm/AA-2G micro-/nanofibers is prepared through reactive electrospinning; the ECM is sensitive to ROS and K+ concentration in the microenvironment to release AA-2G, which targets the membrane to remove the excessive ROS and reactivate Na/K-ATPase; as a result, the ECM reduces oxidative stress and restores the extracellular physiological state both in vitro and in vivo. This work provides basic principles to design an implant that can adjust the extracellular microenvironment while avoiding pathogenicity to improve implant integrity and longevity in vivo.

Co-Delivery of Curcumin and Paclitaxel by "Core-Shell" Targeting Amphiphilic Copolymer to Reverse Resistance in the Treatment of Ovarian Cancer.

BACKGROUND: Ovarian cancer is a common malignancy in the female reproductive system with a high mortality rate. The most important reason is multidrug resistance (MDR) of cancer chemotherapy. To reduce side effects, reverse resistance and improve efficacy for the treatment of ovarian cancer, a "core-shell" polymeric nanoparticle-mediated curcumin and paclitaxel co-delivery platform was designed. METHODS: Nuclear magnetic resonance confirmed the successful grafting of polyethylenimine (PEI) and stearic acid (SA) (PEI-SA), which is designed as a mother core for transport carrier. Then, PEI-SA was modified with hyaluronic acid (HA) and physicochemical properties were examined. To understand the regulatory mechanism of resistance and measure the anti-tumor efficacy of the treatments, cytotoxicity assay, cellular uptake, P-glycoprotein (P-gp) expression and migration experiment of ovarian cancer cells were performed. In addition, adverse reactions of nanoformulation to the reproductive system were examined. RESULTS: HA-modified drug-loaded PEI-SA had a narrow size of about 189 nm in diameters, and the particle size was suitable for endocytosis. The nanocarrier could target specifically to CD44 receptor on the ovarian cancer cell membrane. Co-delivery of curcumin and paclitaxel by the nanocarriers exerts synergistic anti-ovarian cancer effects on chemosensitive human ovarian cancer cells (SKOV3) and multi-drug resistant variant (SKOV3-TR30) in vitro, and it also shows a good anti-tumor effect in ovarian tumor-bearing nude mice. The mechanism of reversing drug resistance may be that the nanoparticles inhibit the efflux of P-gp, inhibit the migration of tumor cells, and curcumin synergistically reverses the resistance of PTX to increase antitumor activity. It is worth noting that the treatment did not cause significant toxicity to the uterus and ovaries with the observation of macroscopic and microscopic. CONCLUSION: This special structure of targeting nanoparticles co-delivery with the curcumin and paclitaxel can increase the anti-tumor efficacy without increasing the adverse reactions as a promising strategy for therapy ovarian cancer.

Novel pathogenic RECQL4 variants in Chinese patients with Rothmund-Thomson syndrome.

BACKGROUND: Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder mainly characterized by cutaneous poikiloderma, sparse hair, short stature and skeletal defects. Deleterious mutations in the RecQ-like DNA helicase type 4 (RECQL4) gene have been detected in approximately two-thirds of RTS cases. METHODS: Three Chinese patients from two unrelated families were enrolled for clinical evaluation. Targeted next-generation sequencing (NGS) using a custom panel consisting of 705 short-stature-related genes was performed for the probands. Variants detected by NGS were confirmed by Sanger sequencing and examined in family members. RESULTS: The probands presented with characteristic features of severe growth delay, poikiloderma mostly on the face, buttocks and extremities, sparse or absent hair, eyelashes, and eyebrows, forearm reduction defects, small hands with hypoplasia of the middle phalanx (little finger) in one of the probands, epicanthus, hypertelorism, and dental abnormalities. In addition, novel auricle features and other rare facial features, including narrow palpebral fissure, depressed nasal bridge, and small chin were exhibited. Four novel RECQL4 variants were identified, including three pathogenic frameshift variants, c.1724_1725delAC, p.His575fs*7; c.2421dupT, p.Asp808*; c.1770_1807del, p.Pro591fs*2, and one likely pathogenic missense variant, c.691G>A, p.Gly231Ser. CONCLUSION: Our study expands the mutational spectrum of RECQL4 gene and reveals novel phenotypes observed in Chinese RTS patients.

Herpesviruses in etiopathogenesis of aggressive periodontitis: A meta-analysis based on case-control studies.

OBJECTIVE: Previous studies have found that herpesviruses are associated with aggressive periodontitis (AgP). However, these findings are controversial. This meta-analysis was aimed at clarifying the association between herpesviruses and AgP. METHODS: We identified eligible case-control studies evaluating the association between herpesviruses and AgP from PubMed and Embase databases in October 2015. Original data were extracted and quality assessment was done. Overall odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Random-effects model was determined. The stability was evaluated by sensitivity analysis. Finally, Egger's funnel plot was used to investigate the publication bias. RESULTS: Twelve case-control studies involving 322 patients and 342 controls were included in the present meta-analysis. The included case-control studies were assessed as high quality. The quantitative synthesis results for Epstein-Barr virus (EBV) showed significance (10 studies: p = 0.0008, OR = 6.11, 95% CI = 2.13-17.51); nevertheless, evidence of publication bias for EBV was considerable (EBV: Egger's test, p<0.001). Human cytomegalovirus (HCMV) and Herpes simplex virus type 1 (HSV-1) had significant association with AgP (12 studies for HCMV: p = 0.009, OR = 3.63, 95% CI = 2.15-6.13; 4 studies for HSV-1: p<0.001, OR = 19.19, 95% CI = 4.16-79.06). Sensitivity analyses showed the results yielded consistency, and no significant publication bias was observed for HCMV. The association between Herpes simplex virus type 2 (HSV-2) and AgP was inconclusive (2 studies: p = 0.20, OR = 3.46, 95% CI = 0.51-23.51). CONCLUSION: This meta-analysis suggests that HCMV and HSV-1 are significantly associated with AgP. However, due to the heterogeneity among studies these conclusions should be cautiously interpreted. There is insufficient evidence to draw any conclusion between EBV, HSV-2 and AgP based on the currently limited data.

Long Blood Residence and Large Tumor Uptake of Ruthenium Sulfide Nanoclusters for Highly Efficient Cancer Photothermal Therapy.

Transition metal sulfide (TMS) holds great potential in cancer photothermal therapy (PTT) because of the high absorbance in the near-infrared (NIR) region. The short blood circulation time and limited tumor accumulation of TMS-based photothermal agents, however, limit their applications. Herein, we design a novel TMS-based PTT agent, ruthenium sulfide-based nanoclusters (NCs), to overcome the current limitations. We firstly develop a simple method to prepare oleic acid coated ruthenium sulfide nanodots (OA-RuS1.7 NDs) and assemble them into water-soluble NCs via sequentially coating with denatured bovine serum albumin (dBSA) and poly(ethylene glycol) (PEG). The obtained PEG-dBSA-RuS1.7 NCs possess excellent photothermal conversion ability. More significantly, they exhibit enhanced blood circulation time and tumor-targeting efficiency in vivo compared with other TMS-based PTT nanoagents, which may be attributed to their appropriate hydrodynamic diameter (~70 nm) and an ideal charge (~0 mV). These characteristics help the PEG-dBSA-RuS1.7 NCs to escape the removal by the reticuloendothelial system (RES) and kidney. All these advantages enable the PEG-dBSA-RuS1.7 NCs to selectively concentrate in tumor sites and effectively ablate the cancer cells upon NIR irradiation.