ABSTRACT
Background: Vital pulp therapy (VPT) is considered a conservative treatment for preserving pulp viability in caries and trauma-induced pulpitis. However, Mineral trioxide aggregate (MTA) as the most frequently used repair material, exhibits limited efficacy under inflammatory conditions. This study introduces an innovative nanocomposite hydrogel, tailored to simultaneously target anti-inflammation and dentin mineralization, aiming to efficiently preserve vital pulp tissue. Methods: The L-(CaP-ZnP)/SA nanocomposite hydrogel was designed by combining L-Arginine modified calcium phosphate/zinc phosphate nanoparticles (L-(CaP-ZnP) NPs) with sodium alginate (SA), and was characterized with TEM, SEM, FTIR, EDX, ICP-AES, and Zeta potential. In vitro, we evaluated the cytotoxicity and anti-inflammatory properties. Human dental pulp stem cells (hDPSCs) were cultured with lipopolysaccharide (LPS) to induce an inflammatory response, and the cell odontogenic differentiation was measured and possible signaling pathways were explored by alkaline phosphatase (ALP)/alizarin red S (ARS) staining, qRT-PCR, immunofluorescence staining, and Western blotting, respectively. In vivo, a pulpitis model was utilized to explore the potential of the L-(CaP-ZnP)/SA nanocomposite hydrogel in controlling pulp inflammation and enhancing dentin mineralization by Hematoxylin and eosin (HE) staining and immunohistochemistry staining. Results: In vitro experiments revealed that the nanocomposite hydrogel was synthesized successfully and presented desirable biocompatibility. Under inflammatory conditions, compared to MTA, the L-(CaP-ZnP)/SA nanocomposite hydrogel demonstrated superior anti-inflammatory and pro-odontogenesis effects. Furthermore, the nanocomposite hydrogel significantly augmented p38 phosphorylation, implicating the involvement of the p38 signaling pathway in pulp repair. Significantly, in a rat pulpitis model, the L-(CaP-ZnP)/SA nanocomposite hydrogel downregulated inflammatory markers while upregulating mineralization-related markers, thereby stimulating the formation of robust reparative dentin. Conclusion: The L-(CaP-ZnP)/SA nanocomposite hydrogel with good biocompatibility efficiently promoted inflammation resolution and enhanced dentin mineralization by activating p38 signal pathway, as a pulp-capping material, offering a promising and advanced solution for treatment of pulpitis.
Subject(s)
Alginates , Anti-Inflammatory Agents , Dental Pulp , Hydrogels , Nanocomposites , Dental Pulp/cytology , Dental Pulp/drug effects , Humans , Hydrogels/chemistry , Hydrogels/pharmacology , Nanocomposites/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Alginates/chemistry , Alginates/pharmacology , Pulpitis/therapy , Stem Cells/drug effects , Stem Cells/cytology , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Silicates/chemistry , Silicates/pharmacology , Rats , Cell Differentiation/drug effects , Calcium Compounds/chemistry , Calcium Compounds/pharmacology , Cells, Cultured , Aluminum Compounds/chemistry , Aluminum Compounds/pharmacology , Arginine/chemistry , Arginine/pharmacology , Rats, Sprague-Dawley , Drug Combinations , Male , Oxides/chemistry , Oxides/pharmacologyABSTRACT
The unsatisfactory oxygen reduction reaction (ORR) kinetics caused by the inherent lean-oxygen marine environment brings low power density for metal-dissolved oxygen seawater batteries (SWBs). In this study, we propose a seawater/electrode interfacial engineering strategy by constructing a hydrophobic coating to realize enhanced mass transfer of dissolved oxygen for the fully immersed cathode of SWBs. Accumulation of dissolved oxygen from seawater to the catalyst is particularly beneficial for improving the ORR performance under lean-oxygen conditions. As a result, SWB assembled with a hydrophobic cathode achieved a power density of up to 2.32 mW cm-2 and sustained discharge at 1.3 V for 250 h. Remarkably, even in environments with an oxygen concentration of 4 mg L-1, it can operate at a voltage approximately 100 mV higher than that of an unmodified SWB. The introduction of a hydrophobic interface enhances the discharge voltage and power of SWBs by improving interfacial oxygen mass transfer, providing new insights into improving the underwater ORR performance for practical SWBs.
ABSTRACT
The present study investigated the effects of temperature on growth performance, slaughtering traits, meat quality and antioxidant function of Pekin ducks from 21-42 d of age. Single factor analysis of variance was used in this experiment, 144 21 d-old Pekin ducks were randomly allotted to 4 environmentally controlled chambers: T20 (20°C), T23 (23°C), T26 (26°C) and T29 (29°C), with 3 replicates in each group (12 ducks in each replicate), the relative humidity of all groups is 74%. During the 21-day trial period, feed and water were freely available. At 42 d, the BW (body weight) and ADG (average daily gain) of T26 were significantly lower than T20 (p < 0.05), and the T29 was significantly lower than T20 and T23 (p < 0.05). The ADFI (average daily feed intake) of T26 and T29 were significantly lower than T20 and T23 (p < 0.05). Compared to the T29, the T20 showed a significant increase oblique body length and chest width, and both the keel length and thigh muscle weight significantly increased in both the T20 and T23, while the pectoral muscle weight increased significantly in other groups (p < 0.05). The cooking loss of the T29 was the lowest (p < 0.05). The T-AOC (total antioxidant capacity) of T29 was significantly higher than the other groups (p < 0.05), the SOD (superoxide dismutase) in the T29 was significantly higher than the T23 and T26 (p < 0.05). In conditions of 74% relative humidity, the BW and ADFI of Pekin ducks significantly decrease when the environmental temperature exceeds 26°C, and the development of body size and muscle weight follows this pattern. The growth development and serum redox state of Pekin ducks are more ideal and stable at temperatures of 20°C and 23°C.
ABSTRACT
Oral ulcers can significantly reduce the life quality of patients and even lead to malignant transformations. Local treatments using topical agents are often ineffective because of the wet and dynamic environment of the oral cavity. Current clinical treatments for oral ulcers, such as corticosteroids, have limitations and side effects for long-term usage. Here, we develop adhesive hydrogel patches (AHPs) that effectively promote the healing of oral ulcers in a rat model. The AHPs are comprised of the quaternary ammonium salt of chitosan, aldehyde-functionalized hyaluronic acid, and a tridentate complex of protocatechualdehyde and Fe3+ (PF). The AHPs exhibit tunable mechanical properties, self-healing ability, and wet adhesion on the oral mucosa. Through controlling the formula of the AHPs, PF released from the AHPs in a temporal manner. We further show that the AHPs have good biocompatibility and the capability to heal oral ulcers rapidly. Both in vitro and in vivo experiments indicate that the PF released from AHPs facilitated ulcer healing by suppressing inflammation, promoting macrophage polarization, enhancing cell proliferation, and inducing epithelial-mesenchymal transition involving inflammation, proliferation, and maturation stages. This study provides insights into the healing of oral ulcers and presents an effective therapeutic biomaterial for the treatment of oral ulcers. STATEMENT OF SIGNIFICANCE: By addressing the challenges associated with current clinical treatments for oral ulcers, the development of adhesive hydrogel patches (AHPs) presents an effective approach. These AHPs possess unique properties, such as tunable mechanical characteristics, self-healing ability, and strong adhesion to the mucosa. Through controlled release of protocatechualdehyde-Fe3+ complex, the AHPs facilitate the healing process by suppressing inflammation, promoting cell proliferation, and inducing epithelial-mesenchymal transition. The study not only provides valuable insights into the healing mechanisms of oral ulcers but also introduces a promising therapeutic biomaterial. This work holds significant scientific interest and demonstrates the potential to greatly improve the treatment outcomes and quality of life for individuals suffering from oral ulcers.
Subject(s)
Benzaldehydes , Catechols , Hydrogels , Oral Ulcer , Humans , Rats , Animals , Hydrogels/pharmacology , Adhesives , Quality of Life , Biocompatible Materials , Inflammation , Anti-Bacterial Agents/pharmacologyABSTRACT
Mouth ulcers, a highly prevalent ailment affecting the oral mucosa, leading to pain and discomfort, significantly impacting the patient's daily life. The development of innovative approaches for oral ulcer treatment is of great importance. Moreover, a deeper and more comprehensive understanding of mouth ulcers will facilitate the development of innovative therapeutic strategies. The oral environment possesses distinct traits as it serves as the gateway to the digestive and respiratory systems. The permeability of various epithelial layers can influence drug absorption. Moreover, oral mucosal injuries exhibit distinct healing patterns compared to cutaneous lesions, influenced by various inherent and extrinsic factors. Furthermore, the moist and dynamic oral environment, influenced by saliva and daily physiological functions like chewing and speaking, presents additional challenges in local therapy. Also, suitable mucosal adhesion materials are crucial to alleviate pain and promote healing process. To this end, the review comprehensively examines the anatomical and structural aspects of the oral cavity, elucidates the healing mechanisms of oral ulcers, explores the factors contributing to scar-free healing in the oral mucosa, and investigates the application of mucosal adhesive materials as drug delivery systems. This endeavor seeks to offer novel insights and perspectives for the treatment of oral ulcers.
ABSTRACT
Most navigation aids for visually impaired individuals require users to pay close attention and actively understand the instructions or feedback of guidance, which impose considerable cognitive loads in long-term usage. To tackle the issue, this study proposes a cognitive burden-free electronic travel aid for individuals with visual impairments. Utilizing human instinctive compliance in response to external force, we introduce the "Aerial Guide Dog", a helium balloon aerostat drone designed for indoor guidance, which leverages gentle tugs in real time for directional guidance, ensuring a seamless and intuitive guiding experience. The introduced Aerial Guide Dog has been evaluated in terms of directional guidance and path following in the pilot study, focusing on assessing its accuracy in orientation and the overall performance in navigation. Preliminary results show that the Aerial Guide Dog, utilizing Ultra-Wideband (UWB) spatial positioning and Measurement Unit (IMU) angle sensors, consistently maintained minimal deviation from the targeting direction and designated path, while imposing negligible cognitive burdens on users while completing the guidance tasks.
Subject(s)
Aircraft , Service Animals , Animals , Dogs , Humans , Pilot Projects , Electronics , CognitionABSTRACT
This study aimed to investigate the effects of different humidity levels on the growth performance, slaughter performance, and meat quality of Pekin ducks through the artificial control of humidity, and to identify the suitable environmental humidity for Pekin duck growth. A completely randomized single-factor design was employed, selecting 144 newly hatched male Pekin ducks with healthy and similar BW (body weight) (60.92 g ± 4.38). These ducks were randomly assigned to four groups (A (RH (relative humidity) = 60%), B (RH = 67%), C (RH = 74%), D (RH = 81%)), with 12 ducks and 3 replicates in each group. The ducks were raised in a climate-controlled room for 42 days with ad libitum access to feed and water. BW and feed intake were measured every 3 days, and slaughter performance and meat quality were assessed at 42 days. There was no significant difference in the ADG (average daily gain) from 1 to 21 days (p > 0.05). The ADFI (average daily feed intake) of Group D was significantly lower than that of Groups A, B, and C (p < 0.05), with no significant differences between Groups A, B, and C (p > 0.05). At 42 days, the BW, ADG, and ADFI of Groups A and C were significantly higher than those of Group D (p < 0.05), with no significant differences among Groups A, B, and C (p > 0.05). Group C had a significantly higher breast muscle weight, breast muscle ratio, liver weight, and liver index than Groups B and D (p < 0.05), with no significant differences between Groups A, B, and D (p > 0.05). The meat shear force in Group C was significantly lower than that in Groups A, B, and D (p < 0.05). The L* (brightness) of Group C was significantly lower than that of Group A (p < 0.05), and the a* (redness) value of Group C was significantly higher than that of Groups A and B (p < 0.05), with no significant difference compared to Group D (p > 0.05). Group B had a significantly higher cooking loss than Groups A, C, and D (p < 0.05), with no significant differences among Groups A, C, and D (p > 0.05). Under 26 °C conditions, Pekin ducks perform best in terms of the production performance and feed efficiency, with high-quality meat, especially when reared at 74% humidity.
ABSTRACT
Rad51 maintains genome integrity, whereas Rad52 causes non-canonical homologous recombination leading to gross chromosomal rearrangements (GCRs). Here we find that fission yeast Srr1/Ber1 and Skb1/PRMT5 promote GCRs at centromeres. Genetic and physical analyses show that srr1 and skb1 mutations reduce isochromosome formation mediated by centromere inverted repeats. srr1 increases DNA damage sensitivity in rad51 cells but does not abolish checkpoint response, suggesting that Srr1 promotes Rad51-independent DNA repair. srr1 and rad52 additively, while skb1 and rad52 epistatically reduce GCRs. Unlike srr1 or rad52, skb1 does not increase damage sensitivity. Skb1 regulates cell morphology and cell cycle with Slf1 and Pom1, respectively, but neither Slf1 nor Pom1 causes GCRs. Mutating conserved residues in the arginine methyltransferase domain of Skb1 greatly reduces GCRs. These results suggest that, through arginine methylation, Skb1 forms aberrant DNA structures leading to Rad52-dependent GCRs. This study has uncovered roles for Srr1 and Skb1 in GCRs at centromeres.
Subject(s)
Isochromosomes , Schizosaccharomyces pombe Proteins , Schizosaccharomyces , Humans , Schizosaccharomyces/genetics , Schizosaccharomyces/metabolism , Centromere/genetics , Centromere/metabolism , Schizosaccharomyces pombe Proteins/genetics , Schizosaccharomyces pombe Proteins/metabolism , Homologous Recombination , Protein-Arginine N-Methyltransferases/metabolism , Protein Kinases/genetics , Methyltransferases/genetics , RNA-Binding Proteins/metabolismABSTRACT
The aim of the current study was to improve temperature-monitoring precision using multiecho proton resonance frequency shift-based thermometry with view-sharing acceleration for MR-guided laser interstitial thermal therapy (MRgLITT) on a 0.5-T low-field MR system. Both precision and speed of the temperature measurement for clinical MRgLITT treatments suffer at low field, due to reduced image signal-to-noise ratio (SNR), decreased temperature-induced phase changes, and limited RF receiver channels. In this work, a bipolar multiecho gradient-recalled echo sequence with a temperature-to-noise ratio optimal weighted echo combination is applied to improve the temperature precision. A view-sharing-based approach is utilized to accelerate signal acquisitions while preserving image SNRs. The method was evaluated using ex vivo (pork and pig brain) LITT heating experiments and in vivo (human brain) nonheating experiments on a high-performance 0.5-T scanner. In terms of results, (1) after echo combination, multiecho thermometry (i.e., ~7.5-40.5 ms, 7 TEs) provides ~1.5-1.9 times higher temperature precision than the no echo combination case (i.e., TE7 = 40.5 ms) within the same readout bandwidth. Additionally, echo registration is necessary for the bipolar multiecho sequence; (2) for a threefold acceleration, the view-sharing approach with variable-density subsampling shows around 1.8 times lower temperature errors than the GRAPPA method. Particularly for view-sharing, variable-density subsampling performs better than Interleave subsampling; and (3) ex vivo heating and in vivo nonheating experiments demonstrated that the temperature accuracy was less than 0.5 ° C and that the temperature precision was less than 0.6 ° C using the proposed 0.5-T thermometry. It was concluded that view-sharing accelerated multiecho thermometry is a practical temperature measurement approach for MRgLITT at 0.5 T.
Subject(s)
Thermometry , Humans , Animals , Swine , Temperature , Phantoms, Imaging , Thermometry/methods , Magnetic Resonance Imaging/methods , LasersABSTRACT
BACKGROUND: The accumulation of fat in ducks is the main cause of low feed efficiency and metabolic diseases in ducks. Retinoic acid X receptor alpha (RXRA) is a member of the nuclear receptor superfamily involved in lipid, glucose, energy, and hormone metabolism. The effect of the RXRA gene on lipid metabolism in duck preadipocytes (DPACs) and the relationship between SNPs and the feed efficiency traits of ducks are unclear. METHODS: qRT-PCR and Western blotting analyses were used to detect changes in mRNA and protein in cells. Intracellular triglycerides (TGs) were detected using an ELISA kit. A general linear model analysis was used to determine the association between RXRA SNPs and feed efficiency. RESULTS: The duck RXRA gene was highly expressed on the fourth day of DPAC differentiation. The RXRA gene increased the content of fat and TG in DPACs and promoted the expression of cell differentiation genes; g.5,952,667 correlated with average daily feed intake (ADFI), residual feed intake (RFI), and feed conversion ratio (FCR). CONCLUSIONS: Duck RXRA can accelerate fat accumulation, and the polymorphism of the RXRA gene is closely related to feed efficiency, which provides basic data for breeding high feed efficiency ducks.
ABSTRACT
BACKGROUND: Studies focused on pregnant women with congenital heart disease (CHD)-associated pulmonary hypertension (PH) are scarce and limited by small sample sizes and single-center design. This study sought to describe the pregnancy outcomes in women with CHD with and without PH. METHODS: Outcomes for pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. PH was diagnosed on the basis of echocardiogram or catheterization. The incidence of maternal death, cardiac complications, and obstetric and offspring complications was compared for women with CHD and no PH, mild, and moderate-to-severe PH. RESULTS: A total of 2220 pregnant women with CHD had completed pregnancies. PH associated with CHD was identified in 729 women, including 398 with mild PH (right ventricle to right atrium gradient 30-50 mm Hg) and 331 with moderate-to-severe PH (right ventricle to right atrium gradient >50 mm Hg). Maternal mortality occurred in 1 (0.1%), 0, and 19 (5.7%) women with CHD and no, mild, or moderate-to-severe PH, respectively. Of the 729 patients with PH, 619 (85%) had CHD-associated pulmonary arterial hypertension, and 110 (15%) had other forms of PH. Overall, patients with mild PH had better maternal outcomes than those with moderate-to-severe PH, including the incidence of maternal mortality or heart failure (7.8% versus 39.6%; P<0.001), other cardiac complications (9.0% versus 32.3%; P<0.001), and obstetric complications (5.3% versus 15.7%; P<0.001). Brain natriuretic peptide >100 ng/L (odds ratio, 1.9 [95% CI, 1.0-3.4], P=0.04) and New York Heart Association class III to IV (odds ratio, 2.9 [95% CI, 1.6-5.3], P<0.001) were independently associated with adverse maternal cardiac events in pregnancy with PH, whereas follow-up with a multidisciplinary team (odds ratio, 0.4 [95% CI, 0.2-0.6], P<0.001) and strict antenatal supervision (odds ratio, 0.5 [95% CI, 0.3-0.7], P=0.001) were protective. CONCLUSIONS: Women with CHD-associated mild PH appear to have better outcomes compared with women with CHD-associated moderate-to-severe PH, and with event rates similar for most outcomes with women with CHD and no PH. Multimodality risk assessment, including PH severity, brain natriuretic peptide level, and New York Heart Association class, may be useful in risk stratification in pregnancy with PH. Follow-up with a multidisciplinary team and strict antenatal supervision during pregnancy may also help to mitigate the risk of adverse maternal cardiac events.
Subject(s)
Heart Defects, Congenital , Hypertension, Pulmonary , Pregnancy Complications, Cardiovascular , Pulmonary Arterial Hypertension , Pregnancy , Female , Humans , Male , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/complications , Pregnant Women , Retrospective Studies , Natriuretic Peptide, Brain , Pregnancy Complications, Cardiovascular/diagnosis , Pregnancy Outcome , Heart Defects, Congenital/diagnosisABSTRACT
Retinoid X receptor alpha (RXRA) is a well-characterized factor that regulates lipid metabolism; however, the regulatory mechanism in muscle cells of poultry is still unknown. The overexpression and the knockdown of RXRA in myoblasts (CS2 cells), RT-PCR, and western blotting were used to detect the expression levels of genes and proteins related to PPAR-signaling pathways. Intracellular triglycerides (TGs), cholesterol (CHOL), and nonesterified free fatty acids (NEFAs) were detected by the Elisa kit. Fat droplets were stained with Oil Red O. The double-fluorescein reporter gene and chromatin immunoprecipitation (CHIP) were used to verify the relationship between RXRA and candidate target genes. The RXRA gene was highly expressed in duck breast muscle, and its mRNA and its protein were reduced during the differentiation of CS2 cells. The CS2 cells, with the overexpression of RXRA, showed reduced content in TGs, CHOL, NEFAs, and lipid droplets and upregulated the mRNA expression of CD36, ACSL1, and PPARG genes and the protein expression of CD36 and PPARG. The knockdown of RXRA expression in CS2 cells enhanced the content of TGs, CHOL, NEFAs, and lipid droplets and downregulated the mRNA and protein expression of CD36, ACLS1, ELOVL6, and PPARG. The overexpression of the RXRA gene, the activity of the double-luciferase reporter gene of the wild-type CD36 promoter was higher than that of the mutant type. RXRA bound to -860/-852 nt, -688/-680 nt, and -165/-157 nt at the promoter region of CD36. Moreover, the overexpression of CD36 in CS2 cells could suppress the content of TGs, CHOL, NEFAs, and lipid droplets, while the knockdown expression of CD36 increased the content of TGs, CHOL, NEFAs, and lipid droplets. In this study, the transcription factor, RXRA, inhibited the accumulation of TGs, CHOL, NEFAs, and fat droplets in CS2 cells by promoting CD36 expression.
Subject(s)
Ducks , Transcription Factors , Animals , Transcription Factors/metabolism , Ducks/genetics , Retinoid X Receptor alpha/metabolism , PPAR gamma/metabolism , Fatty Acids, Nonesterified , Lipid Metabolism/genetics , Triglycerides/metabolism , Cholesterol , Myoblasts/metabolism , RNA, Messenger/metabolism , CD36 Antigens/genetics , CD36 Antigens/metabolismABSTRACT
BACKGROUND: Malaria remains a serious threat to global public health. With poor efficacies of vaccines and the emergence of drug resistance, novel strategies to control malaria are urgently needed. RESULTS: We developed erythrocyte membrane-camouflaged nanoparticles loaded with artemether based on the growth characteristics of Plasmodium. The nanoparticles could capture the merozoites to inhibit them from repeatedly infecting normal erythrocytes, owing to the interactions between merozoites and heparin-like molecules on the erythrocyte membrane. Modification with a phosphatidylserine-targeting peptide (CLIPPKF) improved the drug accumulation in infected red blood cells (iRBCs) from the externalized phosphatidylserine induced by Plasmodium infection. In Plasmodium berghei ANKA strain (pbANKA)-infected C57BL/6 mice, the nanoparticles significantly attenuated Plasmodium-induced inflammation, apoptosis, and anemia. We observed reduced weight variation and prolonged survival time in pbANKA-challenged mice, and the nanoparticles showed good biocompatibility and negligible cytotoxicity. CONCLUSION: Erythrocyte membrane-camouflaged nanoparticles loaded with artemether were shown to provide safe and effective protection against Plasmodium infection.
Subject(s)
Malaria , Merozoites , Animals , Mice , Erythrocyte Membrane , Phosphatidylserines , Biomimetics , Mice, Inbred C57BL , Malaria/drug therapy , Malaria/prevention & control , Erythrocytes , Artemether/pharmacology , Plasmodium berghei , Plasmodium falciparumABSTRACT
PURPOSE: To combine a new two-stage N/2 ghost correction and an adapted L1-SPIRiT method for reconstruction of 7T highly accelerated whole-brain diffusion MRI (dMRI) using only autocalibration scans (ACS) without the need of additional single-band reference (SBref) scans. METHODS: The proposed ghost correction consisted of a 3-line reference approach in stage 1 and the reference-free entropy method in stage 2. The adapted L1-SPIRiT method was formulated within the 3D k-space framework. Its efficacy was examined by acquiring two dMRI data sets at 1.05-mm isotropic resolutions with a total acceleration of 6 or 9 (i.e., 2-fold or 3-fold slice and 3-fold in-plane acceleration). Diffusion analysis was performed to derive DTI metrics and estimate fiber orientation distribution functions (fODFs). The results were compared with those of 3D k-space GRAPPA using only ACS, all in reference to 3D k-space GRAPPA using both ACS and SBref (serving as a reference). RESULTS: The proposed ghost correction eliminated artifacts more robustly than conventional approaches. Our adapted L1-SPIRiT method outperformed 3D k-space GRAPPA when using only ACS, improving image quality to what was achievable with 3D k-space GRAPPA using both ACS and SBref scans. The improvement in image quality further resulted in an improvement in estimation performances for DTI and fODFs. CONCLUSION: The combination of our new ghost correction and adapted L1-SPIRiT method can reliably reconstruct 7T highly accelerated whole-brain dMRI without the need of SBref scans, increasing acquisition efficiency and reducing motion sensitivity.
Subject(s)
Algorithms , Image Processing, Computer-Assisted , Image Processing, Computer-Assisted/methods , Diffusion Magnetic Resonance Imaging , Brain/diagnostic imaging , Phantoms, Imaging , ArtifactsABSTRACT
Centromeres play essential roles in the faithful segregation of chromosomes. CENP-A, the centromere-specific histone H3 variant, and heterochromatin characterized by di- or tri-methylation of histone H3 9th lysine (H3K9) are the hallmarks of centromere chromatin. Contrary to the epigenetic marks, DNA sequences underlying the centromere region of chromosomes are not well conserved through evolution. However, centromeres consist of repetitive sequences in many eukaryotes, including animals, plants, and a subset of fungi, including fission yeast. Advances in long-read sequencing techniques have uncovered the complete sequence of human centromeres containing more than thousands of alpha satellite repeats and other types of repetitive sequences. Not only tandem but also inverted repeats are present at a centromere. DNA recombination between centromere repeats can result in gross chromosomal rearrangement (GCR), such as translocation and isochromosome formation. CENP-A chromatin and heterochromatin suppress the centromeric GCR. The key player of homologous recombination, Rad51, safeguards centromere integrity through conservative noncrossover recombination between centromere repeats. In contrast to Rad51-dependent recombination, Rad52-mediated single-strand annealing (SSA) and microhomology-mediated end-joining (MMEJ) lead to centromeric GCR. This review summarizes recent findings on the role of centromere and recombination proteins in maintaining centromere integrity and discusses how GCR occurs at centromeres.
Subject(s)
Heterochromatin , Histones , Animals , Humans , Histones/genetics , Centromere Protein A , Centromere/genetics , Chromosome Aberrations , ChromatinABSTRACT
Strontium-containing agents have been demonstrated to elicit both bone anabolic and antiosteoporotic effects, showing great potential for the treatment of bone loss. However, an increased incidence of strontium-induced side effects restricts their clinical applications. Herein, oxidized carbon nitride nanosheets (CN) are delicately used to incorporate Sr2+ for the first time to achieve high osteogenic efficacy. The lamellar structure and enriched nitrogen species of CN provide them with a high surface area-to-volume ratio and abundant anchoring sites for Sr2+ incorporation. Importantly, Sr2+-incorporated CN (CNS) could synergistically promote osteoblast differentiation and bone regeneration at a single, very low Sr2+ dose. Mechanically, CNS could activate the FAK/RhoA signaling pathway to modulate the intracellular tension that stimulates osteoblasts differentiation. The present study will provide a new paradigm to enhance the efficacy of osteogenic metal ions by using lamellar nanocarriers.
Subject(s)
Bone Regeneration , Strontium , Strontium/pharmacology , Osteogenesis , Bone and BonesABSTRACT
The influence of surface substance production on the freeze-drying survival of Lactobacillus casei and methods to control the surface substances during fermentation were studied. The bacteria were treated with hypertonicity combined with ultrasound, and the survival rate was determined. The optimal conditions for removing surface substance without harming the bacteria were 81 w/18 min. The surface substances provided a protective effect on the lyophilization of the bacteria without protectants. However, in the presence of protectants, excessive surface substances reduced the protective effect of the optimum protectant alginate to 39.69 ± 1.27%. Finally, the amount of surface substances and lyophilized survival rate of collected bacteria were determined by adding EDTA during fermentation and regulating fermentation conditions, such as the carbon source, carbon-to-nitrogen ratio, and pH. The highest survival rate was 85.79 ± 3.29%, which was achieved when the amount of surface substances was (2.82 ± 0.55) × 10-11 mg/CFU. Therefore, the production of surface substances by the bacteria could be reduced by modifying the fermentation stage, which has significance in the improvement of the lyophilization survival rate of L. casei and the number of live bacteria per unit mass of L. casei in the lyophilized preparation.
ABSTRACT
BACKGROUND: cerebral malaria (CM) is an important complication of malaria with a high mortality rate. Artesunate is recommended as the first-line artemisinin compound treatment for severe malaria. Due to the difficulty of obtaining brain tissue samples clinically, the use of animals to research host responses to CM parasite infections is necessary. Rodent malaria models allow for detailed time series studies of host responses in multiple organs. To date, studies on the transcriptome of severe malaria are only limited to the parasites in the peripheral blood of patients, and there is little data on the transcriptional changes in brain tissue in mice with CM treated with artesunate. METHOD AND RESULT: in this study, fresh tissue samples (three biological replicates per mouse) from the same area of the brain in each animal were collected from the uninfected, Plasmodium berghei ANKA-infected and artesunate-treated C57BL/6 mice, and then transcriptome research was performed by the RNA-seq technique. Differentially expressed genes (DEGs) included Il-21, Tnf, Il-6, Il-1ß, Il-10, Ifng, and Icam-1. Among which, Il-6, Il-10, Tnf-α and Il-1ß were further verified and validated via qRT-PCR and ELISA. This revealed that Il-1ß (p < 0.0001), Il-10 (p < 0.05) and Tnf-α (p < 0.05) were significantly up-regulated in the Pb ANKA-infected versus uninfected group, while Il-1ß (p < 0.0001) and Tnf-α (p < 0.05) were significantly down-regulated after artesunate treatment. All DEGs were closely related to the top 3 artesunate treatment pathways, including the JAK-STAT signaling pathway, apoptosis, and Toll-like receptor signaling pathway. CONCLUSION: the mechanism of improving the prognosis of cerebral malaria by artesunate may not only involve the killing of plasmodium but also the inhibition of a cytokine storm in the host. This study provides new insights into the molecular mechanism by which artesunate improves the prognosis of cerebral malaria.
Subject(s)
Antimalarials , Artemisinins , Malaria, Cerebral , Animals , Anti-Inflammatory Agents/therapeutic use , Antimalarials/pharmacology , Antimalarials/therapeutic use , Artemisinins/pharmacology , Artemisinins/therapeutic use , Artesunate/pharmacology , Artesunate/therapeutic use , Disease Models, Animal , Gene Expression Profiling , Intercellular Adhesion Molecule-1/therapeutic use , Interleukin-10/therapeutic use , Interleukin-6/therapeutic use , Lead/therapeutic use , Malaria, Cerebral/drug therapy , Malaria, Cerebral/genetics , Malaria, Cerebral/metabolism , Mice , Mice, Inbred C57BL , RNA-Seq , Toll-Like Receptors/therapeutic use , Tumor Necrosis Factor-alpha/therapeutic useABSTRACT
PURPOSE: To develop a 2D multi-echo passband balanced SSFP (bSSFP) sequence using an echo-train readout with a sequential phase-encoding order (sequential multi-echo bSSFP), and evaluate its performance in fast functional brain imaging at 7 T. METHODS: As images of sequential multi-echo bSSFP exhibit multiple ghosts due to periodic k-space modulations, a GRAPPA-based reconstruction method was proposed to eliminate ghosting artifacts. MRI experiments were performed to compare the image quality of multi-echo bSSFP and conventional single-echo bSSFP. Submillimeter-resolution fMRI using a checkerboard visual stimulus was conducted to compare the activation characteristics of multi-echo bSSFP, conventional single-echo bSSFP and standard gradient-echo EPI (GE-EPI). RESULTS: A higher mean structural similarity index was found between images of single-echo bSSFP and multi-echo bSSFP with a shorter echo train length (ETL). Multi-echo bSSFP (ETL = 3) showed higher temporal SNR (tSNR) values than GRAPPA-accelerated single-echo bSSFP (R = 2). In submillimeter-resolution fMRI experiments, multi-echo bSSFP (ETL = 3) approached the imaging speed of GRAPPA-accelerated single-echo bSSFP (R = 2), but without tSNR penalty and reduced activation due to acceleration. The median t-value and the number of significantly activated voxels were comparable between GE-EPI and multi-echo bSSFP (ETL = 3) that provides virtually distortion-free functional images and inherits the activation patterns of conventional bSSFP. CONCLUSION: Sequential multi-echo bSSFP (ETL = 3) is suitable for fast fMRI with submillimeter in-plane resolution, and offers an option to accelerate bSSFP imaging without tSNR penalty like parallel imaging.
Subject(s)
Echo-Planar Imaging , Magnetic Resonance Imaging , Artifacts , Brain/diagnostic imaging , Echo-Planar Imaging/methods , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methodsABSTRACT
This study was done to evaluate the effects of heat stress (HS) on production performance, redox status, small intestinal barrier-related parameters, cecal microbiota, and metabolome of indigenous broilers. A total of forty female indigenous broilers (56-day-old) were randomly and equally divided into normal treatment group (NT group, 21.3 ± 1.2°C, 24 h/day) and HS group (32.5 ± 1.4°C, 8 h/day) with five replicates of each for 4 weeks feeding trial. The results showed that the body weight gain (BWG) of broilers in HS group was lower than those in NT group during 3-4 weeks and 1-4 weeks (p < 0.05). The HS exposure increased the abdominal fat rate (p < 0.05) but decreased the thigh muscle rate (p < 0.01). Besides, broilers in HS group had higher drip loss of breast muscle than NT group (p < 0.01). Broilers exposed to HS had lower total antioxidant capacity (T-AOC) in serum and jejunum, activities of total superoxide dismutase (T-SOD) in the jejunum, glutathione peroxidase (GSH-Px) in the thigh muscle, duodenum, and jejunum; and catalase (CAT) in breast muscle, duodenum, and jejunum (p < 0.05). Whereas the malondialdehyde (MDA) contents in breast muscle, duodenum, and jejunum was elevated by HS exposure (p < 0.05). Moreover, the relative mRNA expression of Occludin and ZO-1 in the duodenum, Occludin, Claudin-1, Claudin-4, ZO-1, Mucin-2 in the jejunum, and the Claudin-4 and Mucin-2 in the ileum was down-regulated by HS exposure (p < 0.05). The 16S rRNA sequencing results showed that the HS group increased the relative abundance of Anaerovorax in the cecum at the genus level (p < 0.05). Cecal metabolomics analysis indicated 19 differential metabolites between the two groups (p < 0.10, VIP >1). The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the differential metabolites mainly enriched in 10 signaling pathways such as the Citrate cycle (TCA cycle) (p < 0.01). In summary, chronic HS exposure caused a decline of production performance, reduced antioxidant capacity, disrupted intestinal barrier function, and negatively affected cecal microbiota and metabolome in indigenous broilers.