ABSTRACT
Remyelination failure in diseases like multiple sclerosis (MS) was thought to involve suppressed maturation of oligodendrocyte precursors; however, oligodendrocytes are present in MS lesions yet lack myelin production. We found that oligodendrocytes in the lesions are epigenetically silenced. Developing a transgenic reporter labeling differentiated oligodendrocytes for phenotypic screening, we identified a small-molecule epigenetic-silencing-inhibitor (ESI1) that enhances myelin production and ensheathment. ESI1 promotes remyelination in animal models of demyelination and enables de novo myelinogenesis on regenerated CNS axons. ESI1 treatment lengthened myelin sheaths in human iPSC-derived organoids and augmented (re)myelination in aged mice while reversing age-related cognitive decline. Multi-omics revealed that ESI1 induces an active chromatin landscape that activates myelinogenic pathways and reprograms metabolism. Notably, ESI1 triggered nuclear condensate formation of master lipid-metabolic regulators SREBP1/2, concentrating transcriptional co-activators to drive lipid/cholesterol biosynthesis. Our study highlights the potential of targeting epigenetic silencing to enable CNS myelin regeneration in demyelinating diseases and aging.
Subject(s)
Epigenesis, Genetic , Myelin Sheath , Oligodendroglia , Remyelination , Animals , Myelin Sheath/metabolism , Humans , Mice , Remyelination/drug effects , Oligodendroglia/metabolism , Central Nervous System/metabolism , Mice, Inbred C57BL , Rejuvenation , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/drug effects , Sterol Regulatory Element Binding Protein 1/metabolism , Organoids/metabolism , Organoids/drug effects , Demyelinating Diseases/metabolism , Demyelinating Diseases/genetics , Cell Differentiation/drug effects , Small Molecule Libraries/pharmacology , Male , Regeneration/drug effects , Multiple Sclerosis/metabolism , Multiple Sclerosis/genetics , Multiple Sclerosis/drug therapy , Multiple Sclerosis/pathologyABSTRACT
Our previous study confirmed that umbilical cord mesenchymal stem cells-exosomes (ucMSC-Ex) inhibit apoptosis of pancreatic acinar cells to exert protective effects. However, the relationship between apoptosis and autophagy in traumatic pancreatitis (TP) has rarely been reported. We dissected the transcriptomics after pancreatic trauma and ucMSC-Ex therapy by high-throughput sequencing. Additionally, we used rapamycin and MHY1485 to regulate mTOR. HE, inflammatory factors and pancreatic enzymatic assays were used to comprehensively determine the local versus systemic injury level, fluorescence staining and electron microscopy were used to detect the effect of autophagy, and observe the expression levels of autophagy-related markers at the gene and protein levels. High-throughput sequencing identified that autophagy played a crucial role in the pathophysiological process of TP and ucMSC-Ex therapy. The results of electron microscopy, immunofluorescence staining, polymerase chain reaction and western blot suggested that therapeutic effect of ucMSC-Ex was mediated by activation of autophagy in pancreatic acinar cells through inhibition of mTOR. ucMSC-Ex can attenuate pancreas injury by inhibiting mTOR to regulate acinar cell autophagy after TP. Future studies will build on the comprehensive sequencing of RNA carried by ucMSC-Ex to predict and verify specific non-coding RNA.
Subject(s)
Exosomes , Mesenchymal Stem Cells , Pancreatitis , Humans , Exosomes/metabolism , Mesenchymal Stem Cells/metabolism , Umbilical Cord , TOR Serine-Threonine Kinases/metabolism , Pancreatitis/metabolism , Autophagy/genetics , ApoptosisABSTRACT
PURPOSE: Dynamic total-body imaging enables new perspectives to investigate the potential relationship between the central and peripheral regions. Employing uEXPLORER dynamic [11C]CFT PET/CT imaging with voxel-wise simplified reference tissue model (SRTM) kinetic modeling and semi-quantitative measures, we explored how the correlation pattern between nigrostriatal and digestive regions differed between the healthy participants as controls (HC) and patients with Parkinson's disease (PD). METHODS: Eleven participants (six HCs and five PDs) underwent 75-min dynamic [11C]CFT scans on a total-body PET/CT scanner (uEXPLORER, United Imaging Healthcare) were retrospectively enrolled. Time activity curves for four nigrostriatal nuclei (caudate, putamen, pallidum, and substantia nigra) and three digestive organs (pancreas, stomach, and duodenum) were obtained. Total-body parametric images of relative transporter rate constant (R1) and distribution volume ratio (DVR) were generated using the SRTM with occipital lobe as the reference tissue and a linear regression with spatial-constraint algorithm. Standardized uptake value ratio (SUVR) at early (1-3 min, SUVREP) and late (60-75 min, SUVRLP) phases were calculated as the semi-quantitative substitutes for R1 and DVR, respectively. RESULTS: Significant differences in estimates between the HC and PD groups were identified in DVR and SUVRLP of putamen (DVR: 4.82 ± 1.58 vs. 2.58 ± 0.53; SUVRLP: 4.65 ± 1.36 vs. 2.84 ± 0.67; for HC and PD, respectively, both p < 0.05) and SUVREP of stomach (1.12 ± 0.27 vs. 2.27 ± 0.65 for HC and PD, respectively; p < 0.01). In the HC group, negative correlations were observed between stomach and substantia nigra in both the R1 and SUVREP values (r=-0.83, p < 0.05 for R1; r=-0.94, p < 0.01 for SUVREP). Positive correlations were identified between pancreas and putamen in both DVR and SUVRLP values (r = 0.94, p < 0.01 for DVR; r = 1.00, p < 0.001 for SUVRLP). By contrast, in the PD group, no correlations were found between the aforementioned target nigrostriatal and digestive areas. CONCLUSIONS: The parametric images of R1 and DVR generated from the SRTM model, along with SUVREP and SUVRLP, were proposed to quantify dynamic total-body [11C]CFT PET/CT in HC and PD groups. The distinction in correlation patterns of nigrostriatal and digestive regions between HC and PD groups identified by R1 and DVR, or SUVRs, may provide new insights into the disease mechanism.
Subject(s)
Parkinson Disease , Positron Emission Tomography Computed Tomography , Humans , Parkinson Disease/diagnostic imaging , Parkinson Disease/metabolism , Male , Positron Emission Tomography Computed Tomography/methods , Female , Middle Aged , Aged , Substantia Nigra/diagnostic imaging , Substantia Nigra/metabolism , Tetrabenazine/analogs & derivatives , Tetrabenazine/pharmacokinetics , Whole Body Imaging/methods , Case-Control Studies , Carbon RadioisotopesABSTRACT
Exploring materials that balance the second harmonic generation (SHG) effect and laser-induced damage threshold (LIDT) is the frontier of nonlinear optical (NLO) crystal research at present. In this work, the NLO property of anhydrous aluminum iodate is extensively explored and discussed first. It exhibits a strong SHG intensity of 18.3 × KH2PO4 (KDP) and a high-powder LIDT of 1.4 × KDP at 1064 nm. Combining experimental and theoretical studies at the atomic level and electronic levels, it is found that the cations in the structure are replaced by cations with small radius and high valence, enabling the production of materials with large SHG responses. Unbonded and antibonding orbitals play a crucial positive role in the SHG response of the structure, whereas bonding orbitals produce a large negative contribution. This provides a scarce example of materials in which bonding orbitals make significant negative contributions.
ABSTRACT
African swine fever (ASF) is an infectious disease caused by ASF virus (ASFV), which is characterized by high infectivity, rapid onset of disease, and a high mortality rate. Outbreaks of ASFV have caused great economic losses to the global pig industry, and there is a need to develop safe and effective vaccines. In this study, two recombinant pseudorabies virus (PRV) strains, rGXGG-2016-ΔgI/ΔgE-EP364R and rGXGG-2016-ΔgI/ΔgE-B119L, expressing the EP364R and B119L protein, respectively, of ASFV, were constructed by homologous recombination technology. Western blotting and immunofluorescence analysis showed that these foreign proteins were expressed in cells infected with the recombinant strains. The strains showed good genetic stability and proliferative characteristics for 20 passages in BHK-21 cells. Both of these strains were immunogenic in mice, inducing the production of specific antibodies against the expressed ASFV proteins while providing protection against lethal challenge with PRV. Thus, the recombinant strains rGXGG-2016-ΔgI/ΔgE-EP364R and rGXGG-2016-ΔgI/ΔgE-B119L could be used as candidate vaccines for both ASFV and PRV. In addition, our study identifies two potential target genes for the development of safe and efficient ASFV vaccines, provides a reference for the construction of bivalent ASFV and PRV vaccines, and demonstrates the feasibility of developing a live ASFV vector vaccine.
Subject(s)
African Swine Fever Virus , African Swine Fever , Herpesvirus 1, Suid , Animals , Mice , Swine , African Swine Fever Virus/genetics , Herpesvirus 1, Suid/genetics , African Swine Fever/prevention & control , Vaccines, Attenuated , ImmunityABSTRACT
BACKGROUND AND OBJECTIVE: Nicotine metabolic ratio (NMR) has been associated with nicotine metabolism and smoking characteristics. However, there are few studies on the potential association between NMR and smoking cessation efficacy in smokers with chronic obstructive pulmonary disease (COPD) in China or elsewhere. METHODS: This study was a stratified block randomized controlled trial for smoking cessation in Chinese smokers with COPD. NMR was used as a stratification factor; slow metabolizers were defined as those with NMR <0.31, and normal metabolizers as those with NMR ≥0.31. Participants were randomly assigned to the varenicline or bupropion group. Follow-up visits were conducted at 1, 2, 4, 6, 9, 12 and 24 weeks. RESULTS: Two hundred twenty-four participants were recruited and analysed from February 2019 to June 2022. In normal metabolizers, the 9-12 weeks continuous abstinence rate of varenicline (43.1%) was higher than in bupropion (23.5%) (OR = 2.47, 95% CI 1.05-5.78, p = 0.038). There was no significant difference in abstinence rates between treatment groups in slow metabolizers (54.1% vs. 45.9%, OR = 1.39, 95% CI 0.68-2.83, p = 0.366). For slow metabolizers, the total score of side effects in the varenicline group was significantly higher than the bupropion group (p = 0.048), while there was no significant difference in side effects between groups for normal metabolizers (p = 0.360). CONCLUSION: Varenicline showed better efficacy than bupropion in normal metabolizers, and bupropion showed equivalent efficacy in slow metabolizers with less side effects. According to our study, NMR provides a better justification for both scientific research and tailoring optimal pharmacotherapy for smoking cessation among smokers in COPD.
Subject(s)
Bupropion , Nicotine , Pulmonary Disease, Chronic Obstructive , Smoking Cessation Agents , Smoking Cessation , Varenicline , Humans , Varenicline/therapeutic use , Bupropion/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/metabolism , Male , Female , Smoking Cessation/methods , Middle Aged , Smoking Cessation Agents/therapeutic use , Treatment Outcome , Aged , China/epidemiology , SmokersABSTRACT
Objective: This study aimed to assess the impact of combined moxibustion therapy and Gua sha on enhancing functional independence, reducing fall risk, and alleviating pain in patients undergoing post-rehabilitation for multiple cerebral infarctions. Methods: In a prospective clinical trial, 67 patients diagnosed with multiple cerebral infarctions (age range: 40 to 93 years) were enrolled. Baseline health characteristics included a median hospital stay of 10 days, prevalent medical conditions such as hypertension (64.18%), and various comorbidities like spondylosis (17.91%) and heart disease (14.93%). Patients received moxibustion treatment daily for 20-30 minutes on specific acupoints of the upper and lower extremities. Additionally, Gua sha therapy targeting the the head, back, chest, abdomen, and selected acupoints was administered twice a week with an interval of 3 to 4 days. Assessments included Barthel Index (BI) for functional independence, Morse Fall Scale (MFS) for fall risk, and Visual Analogue Scale (VAS) for pain intensity before and after the intervention. Results: After one week of rehabilitation, significant improvements were observed in the patient's functional independence, as indicated by a median BI score of 100 (IQR: 95-100), compared to the pre-rehabilitation median score of 95 (IQR: 90-100). The MFS score also showed a significant decrease after rehabilitation, with a median score of 35 (IQR: 35-45) compared to the pre-rehabilitation median score of 45 (IQR: 35-45). Additionally, pain intensity significantly decreased, with a median VAS score of 0 (range: 0-2) after rehabilitation, compared to the pre-rehabilitation median score of 0 (range: 0-3). Conclusion: Combined moxibustion therapy and Gua sha demonstrated positive effects on functional independence, fall risk reduction, and pain alleviation in post-rehabilitation for multiple cerebral infarctions. These findings suggest the potential of moxibustion and Gua sha as complementary interventions in stroke rehabilitation. The observed improvements in functional independence, fall risk, and pain underscore the potential benefits of these therapies for patients with multiple cerebral infarctions. Further exploration could delve into long-term effects, larger-scale trials, and mechanistic studies to elucidate the underlying pathways of efficacy.
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Diminished testosterone levels have been documented as a key factor in numerous male health disorders. Both human and animal studies have consistently demonstrated that cadmium (Cd), a pervasive environmental heavy metal, results in decreased testosterone levels. However, the exact mechanism through which Cd interferes with testosterone synthesis remains incompletely elucidated. This research sought to examine the impact of cellular senescence on Cd-suppressed testosterone synthesis. We also investigated the related m6A modification mechanism. The results demonstrated that Cd (100â¯mg/L) led to a decrease in testosterone levels, along with downregulated expression of testosterone synthase in C57BL/6â¯N male mice. Furthermore, Cd significantly increased ß-galactosidase staining intensity, senescence-related proteins, and senescence-related secretory phenotypes in mouse testicular Leydig cells. Subsequent investigations revealed that Cd decreased the mRNA and protein levels of NAD-dependent deacetylase Sirtuin-1 (SIRT1) in Leydig cells. Mechanistically, mice treated with resveratrol (50â¯mg/kg), a specific SIRT1 activator, mitigated Leydig cell senescence and reversed Cd-reduced testosterone levels in mouse testes. These effects were also restored by SIRT1 overexpression in Leydig cells. Additionally, we found that Cd increased the level of methyltransferase enzyme METTL3 and Sirt1 m6A modification in Leydig cells. Mettl3 siRNA effectively restored Cd-enhanced Sirt1 m6A level and reversed Cd-downregulated Sirt1 mRNA expression in Leydig cells. Overall, our findings suggest that Cd exposure inhibits testosterone synthesis via Sirt1 m6A modification-mediated senescence in mouse testes. These results offer an experimental basis for investigating the causes and potential treatments of hypotestosteronemia induced by environmental factors.
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OBJECTIVES: To evaluate the incidence rate of Duchenne muscular dystrophy (DMD) in the male newborns in the Ningxia region and establish a critical threshold for screening DMD in newborns to distinguish between the normal population and affected individuals. METHODS: A total of 10 000 male newborns were screened using immunofluorescence analysis of creatine kinase isoenzyme concentrations in heel spot dried blood specimens. Newborns with the concentrations higher than the critical threshold were recalled for serum creatine kinase measurements. Genetic testing was performed to confirm diagnosis in cases showing abnormalities. RESULTS: Among the screened 10 000 male newborns, two were confirmed to have DMD through genetic testing, resulting in a preliminary estimated incidence rate of 1/5 000 for male newborns in the Ningxia region. The critical threshold for creatine kinase isoenzyme concentration in newborns in this region was determined to be 468.57 ng/mL. CONCLUSIONS: Screening for DMD in newborns is feasible in the Ningxia region. Early screening, diagnosis, and treatment of DMD can improve the quality of life for affected individuals and help families make informed decisions regarding further pregnancies.
Subject(s)
Muscular Dystrophy, Duchenne , Humans , Male , Infant, Newborn , Muscular Dystrophy, Duchenne/diagnosis , Muscular Dystrophy, Duchenne/genetics , Isoenzymes , Quality of Life , Neonatal Screening/methods , Creatine KinaseSubject(s)
Incidental Findings , Intranuclear Inclusion Bodies , Meningeal Neoplasms , Meningioma , White Matter , tau Proteins , Aged , Female , Humans , Cerebellum/diagnostic imaging , Cerebellum/metabolism , Cerebellum/pathology , Intranuclear Inclusion Bodies/metabolism , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/metabolism , Meningioma/diagnostic imaging , Meningioma/metabolism , Meningioma/pathology , Neurodegenerative Diseases/diagnostic imaging , Neurodegenerative Diseases/metabolism , tau Proteins/metabolism , White Matter/diagnostic imaging , White Matter/metabolism , White Matter/pathologyABSTRACT
Iodate crystal materials are some of the important candidates for mid-infrared nonlinear optical (NLO) crystals. Almost all the structures and NLO properties of monometallic iodates have been studied, except for a few difficult to synthesize crystalline phases. In this work, crystalline Cr(IO3)3 was synthesized and its optical properties were studied. Cr(IO3)3 has a strong powder second-harmonic generation (SHG) effect (1.3 × AgGaS2) and a large birefringence (0.24) at 2100 nm. Theoretical calculations indicate that the 3d orbital of Cr3+ is strongly involved in the SHG process, and the contribution of the metal cation centered unit CrO6 to the SHG response is much greater than that of the non-metal cation centered unit IO3. This study provides a new case among the few NLO materials in which the SHG response is dominated by metal cation centered groups.
ABSTRACT
Glaucoma is a common and complex neurodegenerative disease characterized by progressive loss of retinal ganglion cells (RGCs) and axons. Currently, there is no effective method to address the cause of RGCs degeneration. However, studies on neuroprotective strategies for optic neuropathy have increased in recent years. Cell replacement and neuroprotection are major strategies for treating glaucoma and optic neuropathy. Regenerative medicine research into the repair of optic nerve damage using stem cells has received considerable attention. Stem cells possess the potential for multidirectional differentiation abilities and are capable of producing RGC-friendly microenvironments through paracrine effects. This article reviews a thorough researches of recent advances and approaches in stem cell repair of optic nerve injury, raising the controversies and unresolved issues surrounding the future of stem cells.
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Chromatin-remodeling protein BRG1/SMARCA4 is pivotal for establishing oligodendrocyte (OL) lineage identity. However, its functions for oligodendrocyte-precursor cell (OPC) differentiation within the postnatal brain and during remyelination remain elusive. Here, we demonstrate that Brg1 loss profoundly impairs OPC differentiation in the brain with a comparatively lesser effect in the spinal cord. Moreover, BRG1 is critical for OPC remyelination after injury. Integrative transcriptomic/genomic profiling reveals that BRG1 exhibits a dual role by promoting OPC differentiation networks while repressing OL-inhibitory cues and proneuronal programs. Furthermore, we find that BRG1 interacts with EED/PRC2 polycomb-repressive-complexes to enhance H3K27me3-mediated repression at gene loci associated with OL-differentiation inhibition and neurogenesis. Notably, BRG1 depletion decreases H3K27me3 deposition, leading to the upregulation of BMP/WNT signaling and proneurogenic genes, which suppresses OL programs. Thus, our findings reveal a hitherto unexplored spatiotemporal-specific role of BRG1 for OPC differentiation in the developing CNS and underscore a new insight into BRG1/PRC2-mediated epigenetic regulation that promotes and safeguards OL lineage commitment and differentiation.
Subject(s)
Cell Differentiation , DNA Helicases , Oligodendroglia , Polycomb Repressive Complex 2 , Animals , Mice , DNA Helicases/metabolism , DNA Helicases/genetics , Epigenesis, Genetic , Histones/metabolism , Histones/genetics , Mice, Inbred C57BL , Neurogenesis/genetics , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Oligodendrocyte Precursor Cells/metabolism , Oligodendroglia/metabolism , Polycomb Repressive Complex 2/metabolism , Polycomb Repressive Complex 2/genetics , Remyelination , Transcription Factors/metabolism , Transcription Factors/geneticsABSTRACT
Hemiboea pterocaulis is a unique species only found in Guilin, Guangxi, China. In this study, we sequenced and assembled the complete chloroplast genome of H. pterocaulis and revealed its phylogenetic relationship with other Hemiboea species. The chloroplast genome sequence of H. pterocaulis is 153,159 bp in length and comprises a large single-copy (LSC) region of 84,178 bp, a small single-copy (SSC) region of 18,087 bp, and a pair of inverted repeat (IR) regions, each with a length of 25,447 bp. It has a total GC content of 37.6% and encodes 132 genes, including 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic relationships based on the complete chloroplast genome sequences of Hemiboea taxa indicate that H. pterocaulis is most closely related to H. suiyangensis, indicating that H. pterocaulis is an independent species and is separated from the H. subcapitata complex. These results provide valuable insights into the phylogeny, species divergence, and delimitation of the Hemiboea genus.
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Semiaquilegia danxiashanensis is currently known only from the type locality, Danxia Mountain, characterized by its spectacular red sandstone cliffscape. In this study, we assembled the complete chloroplast genome sequence of S. danxiashanensis and inferred its phylogenetic relationships. Total length of the chloroplast genome was 160,548 bp, with an overall GC content of 39%. The chloroplast genome had typical quadripartite structure and contained one LSC region (89,882 bp) and one SSC region (17,386 bp), which were separated by two IRs regions (26,640 bp, respectively). It comprised 133 genes, including 84 protein coding genes, 41 tRNA genes and eight rRNA genes. The maximum likelihood phylogenetic analysis indicated that S. danxiashanensis was sister to S. adoxoides; meanwhile, Semiaquilegia was closely related to both Urophysa and Aquilegia in Ranunculaceae. This study sheds light on the evolutionary history of Semiaquilegia and provides preliminary data for future comparative analysis of chloroplast genomes.
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Perovskite light-emitting diodes (PeLEDs) have garnered significant attention due to their outstanding optoelectronic properties. However, investigating carrier transport and recombination behavior during device operation poses persistent challenges. In this study, we explore the impact of additive and interface engineering on device performance using transient electroluminescence (TREL). Polyethylene glycol (PEG) induces the formation of square-faceted nanocrystals with a homogeneous size distribution and extended fluorescence lifetime. Consequently, these PeLEDs exhibit remarkable stability. Additionally, employing an electron transport layer of 2,4,6-tris[3-(diphenylphosphino)phenyl]-1,3,5-triazine (PO-T2T), which has a better match to the energy bands of the perovskite layer and a higher carrier mobility, allows for lower turn-on voltage and faster response but also suffers from a short decay time and poor stability. Moreover, low-temperature TREL characterization shows that the carrier mobility is also significantly suppressed with decreasing temperature, which reduces the transient response speed.
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BACKGROUND: Depression is a chronic psychiatric disorder related to diminished dopaminergic neurotransmission. Deep brain stimulation (DBS) has shown effectiveness in treating patients with treatment-refractory depression (TRD). This study aimed to evaluate the effect of DBS on dopamine D2 receptor binding in patients with TRD. METHODS: Six patients with TRD were treated with bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS were recruited. Ultra-high sensitivity [11C]raclopride dynamic total-body positron emission tomography (PET) imaging was used to assess the brain D2 receptor binding. Each patient underwent a [11C]raclopride PET scan for 60-min under DBS OFF and DBS ON, respectively. A simplified reference tissue model was used to generate parametric images of binding potential (BPND) with the cerebellum as reference tissue. RESULTS: Depression and anxiety symptoms improved after 3-6 months of DBS treatment. Compared with two-day-nonstimulated conditions, one-day BNST-NAc DBS decreased [11C]raclopride BPND in the amygdala (15.9 %, p < 0.01), caudate nucleus (15.4 %, p < 0.0001) and substantia nigra (10.8 %, p < 0.01). LIMITATIONS: This study was limited to the small sample size and lack of a healthy control group. CONCLUSIONS: Chronic BNST-NAc DBS improved depression and anxiety symptoms, and short-term stimulation decreased D2 receptor binding in the amygdala, caudate nucleus, and substantia nigra. The findings suggest that DBS relieves depression and anxiety symptoms possibly by regulating the dopaminergic system.
Subject(s)
Deep Brain Stimulation , Depressive Disorder, Treatment-Resistant , Nucleus Accumbens , Positron-Emission Tomography , Raclopride , Receptors, Dopamine D2 , Humans , Receptors, Dopamine D2/metabolism , Deep Brain Stimulation/methods , Male , Female , Middle Aged , Depressive Disorder, Treatment-Resistant/therapy , Depressive Disorder, Treatment-Resistant/metabolism , Depressive Disorder, Treatment-Resistant/diagnostic imaging , Nucleus Accumbens/metabolism , Nucleus Accumbens/diagnostic imaging , Adult , Septal Nuclei/metabolism , Septal Nuclei/diagnostic imaging , Brain/metabolism , Brain/diagnostic imaging , Treatment OutcomeABSTRACT
Boehmeria is a taxonomically challenging group within the nettle family (Urticaceae). The polyphyly of the genus has been proposed by previous studies with respect to five genera (Debregeasia, Cypholophus, Sarcochlamys, Archiboehmeria, and Astrothalamus). Extensive homoplasy of morphological characters has made generic delimitation problematic. Previous studies in other plant groups suggest that plastome structural variations have the potential to provide characters useful in reconstructing evolutionary relationships. We aimed to test this across Boehmeria and its allied genera by mapping plastome structural variations onto a resolved strongly supported phylogeny. In doing so, we expanded the sampling of the plastome to include Cypholophus, Sarcochlamys, Archiboehmeria, and Astrothalamus for the first time. The results of our phylogenomic analyses provide strong support for Sarcochlamys as being more closely related to Leucosyke puya than to Boehmeria and for the clustering of Boehmeria s.l. into four subclades. The sizes of the plastomes in Boehmeria s.l. ranged from 142,627 bp to 170,958 bp. The plastomes recovered a typical quadripartite structure comprising 127~146 genes. We observe several obvious structural variations across the taxa such as gene loss and multiple gene duplication, inverted repeat (IR) contraction and wide expansions, and inversions. Moreover, we recover a trend for these variations that the early clades were relatively conserved in evolution, whereas the later diverging clades were variable. We propose that the structural variations documented may be linked to the adaptation of Boehmeria s.l. to a wide range of habitats, from moist broadleaf forests in Asia to xeric shrublands and deserts in Africa. This study confirms that variation in plastome gene loss/duplication, IR contraction/expansion, and inversions can provide evidence useful for the reconstruction of evolutionary relationships.
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Purpose: In recent years, exosomes have been proved to be used to treat many diseases. However, due to the lack of uniform quality control standards for exosomes, the safety of exosomes is still a problem to be solved, especially now more and more exosomes are used in clinical trials, and its non-clinical safety evaluation is particularly important. However, there is no safety evaluation standard for exosomes at present. Therefore, this study will refer to the evaluation criteria of therapeutic biological products, adopt non-human primates to evaluate the non-clinical safety of human umbilical cord mesenchymal stem cell exosomes from the general pharmacology and immunotoxicity, aiming at establishing a safety evaluation system of exosomes and providing reference for the clinical application of exosomes in the future. Methods: 3.85 × 1012 exosomes derived from human umbilical cord mesenchymal stem cells were injected into cynomolgus monkeys intravenously. The changes of general clinical conditions, hematology, immunoglobulin, Th1/Th2 cytokines, T lymphocytes and B lymphocytes, and immune organs were observed before and within 14 days after injection. Results: The results showed that exosomes did not have obvious pathological effects on the general clinical conditions, blood, coagulation function, organ coefficient, immunoglobulin, Th1/Th2 cytokines, lymphocytes, major organs, and major immune organs (spleen, thymus, bone marrow) of cynomolgus monkeys. However, the number of granulocyte-macrophage colonies in exosomes group was significantly higher than that in control group. Conclusion: To sum up, the general pharmacological results and immunotoxicity results showed that the injection of 3.85 × 1012 exosomes may have no obvious adverse reactions to cynomolgus monkeys. This dose of exosomes is relatively safe for treatment, which provides basis research for non-clinical safety evaluation of exosomes and provides reliable research basis for future clinical application of exosomes.
Subject(s)
Exosomes , Macaca fascicularis , Mesenchymal Stem Cells , Umbilical Cord , Animals , Exosomes/chemistry , Mesenchymal Stem Cells/cytology , Humans , Umbilical Cord/cytology , Male , Female , Cytokines/metabolismABSTRACT
BACKGROUND: The prevalence of cigarette smoking among women is significantly different from that of men, however, cigarette use by women is little known. The study aims to describe cigarette use prevalence and patterns among Chinese females by age and province. METHODS: This study was based on the 2018 China Health Literacy Survey (2018 CHLS), a nationally representative cross-sectional study, and our analysis included 43,319 female participants aged 20-69 with valid data. The prevalence of cigarette use was estimated overall by sociodemographic factors and weighted based on the census population data. The logistic regression model was conducted to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the risk factors associated with cigarette use and dependency. RESULTS: In China, the estimated female current cigarette use prevalence was 1.85%, with over half of the population suffering from tobacco dependence (7.34 million). Jilin Province has the highest cigarette prevalence among women (10.59%), while Fujian Province has the lowest (0.27%). Participants over 60 years old (aOR=1.61, 95%CI=1.20-2.14), single (aOR=1.54, 95%CI=1.07-2.21), with primary education (aOR=1.93, 95%CI=1.47-2.52) were more likely to smoke. The age of smoking initiation among women intergenerational advanced, and compared to the cigarette users without tobacco dependence, those who have tobacco dependence start smoking earlier in all age groups (25.69 years vs. 19.36 years, p<0.001). CONCLUSIONS: The cigarette use prevalence among Chinese women was 1.85%, and there are significant differences among provinces. We noted a trend of women initiating smoking at increasingly younger ages, particularly among those with tobacco dependence.