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2.
J Hazard Mater ; 476: 134979, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38905982

ABSTRACT

Spatially confined structure exhibits surprising physics and chemistry properties that significantly impact the thermodynamics and kinetics of oxidation reactions. Herein, porous carbons are rationally designed for tunable nanopore structures (micropores, 4.12 % ∼ 91.64 %) and diverse spatial confinement ability, as indicated by their differential enhancement performances in the Fenton oxidation. Porous carbons can alter the characteristics of the charge transport process for accelerating sustainable electron shuttle between hydrogen peroxide and iron species, and thus exhibit long-term performance (17 cycling tests). The positive spatial confinement for boosting Fenton oxidation (charge transport, mass transfer) occurs in nanochannels < 1 nm, while the diminished effect ranges of 1-1.5 nm, and the adverse effect ranges greater than 1.5 nm. The density functional theory calculation provides further support for certifying the promoted charge transport process and spatial confinement for hydroxyl radical inside the confined nanochannel structure (below 1 nm, especially) by the comparatively large electron cloud and the relatively negative adsorption energy, respectively. Coupling nanochannels with the Fenton oxidation greatly utilize hydrogen peroxide, due to spatial nanoconfinement and selective adsorption towards target contaminants. This strategy of deploying nanochannels in catalyst design can be applied for the elaborate construction of efficient nanostructured catalysts for environmental remediation.

3.
J Chem Phys ; 160(21)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38832747

ABSTRACT

The interplay between orientation transition and chiral self-assemblies of para-terphenyl (P3P) molecules on the Cd(0001) surface has been investigated using low temperature scanning tunneling microscopy and density functional theory calculations. Three distinct molecular orientations have been discerned from the self-assembled thin films of P3P. At the low coverage, flat-lying molecules appear in the homochiral domains with the incommensurate registry to the substrate. With the coverage increasing, the incoming molecules are incorporated into the first layer with edge-on orientation and form the self-assembled zigzag chains. The alternative arrangement of zigzag chains with opposite chirality leads to the formation of a c(4 × 2) superstructure, in which the tilted molecules exhibit orientational frustration and fuzzy noises. The analysis of the tunneling spectra reveals that the electronic structure of P3P layers is contingent upon the hybridization between the electronic states of P3P molecules and the Cd(0001) surface. These results provide important insights into the interplay between orientational transition and chiral assembly of P3P molecules on metal substrates.

4.
Mol Ther Methods Clin Dev ; 32(2): 101268, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38911286

ABSTRACT

Excessive cytosolic calcium accumulation contributes to muscle degeneration in Duchenne muscular dystrophy (DMD). Sarco/endoplasmic reticulum calcium ATPase (SERCA) is a sarcoplasmic reticulum (SR) calcium pump that actively transports calcium from the cytosol into the SR. We previously showed that adeno-associated virus (AAV)-mediated SERCA2a therapy reduced cytosolic calcium overload and improved muscle and heart function in the murine DMD model. Here, we tested whether AAV SERCA2a therapy could ameliorate muscle disease in the canine DMD model. 7.83 × 1013 vector genome particles of the AAV vector were injected into the extensor carpi ulnaris (ECU) muscles of four juvenile affected dogs. Contralateral ECU muscles received excipient. Three months later, we observed widespread transgene expression and significantly increased SERCA2a levels in the AAV-injected muscles. Treatment improved SR calcium uptake, significantly reduced calpain activity, significantly improved contractile kinetics, and significantly enhanced resistance to eccentric contraction-induced force loss. Nonetheless, muscle histology was not improved. To evaluate the safety of AAV SERCA2a therapy, we delivered the vector to the ECU muscle of adult normal dogs. We achieved strong transgene expression without altering muscle histology and function. Our results suggest that AAV SERCA2a therapy has the potential to improve muscle performance in a dystrophic large mammal.

5.
JAMA Netw Open ; 7(6): e2415310, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38861260

ABSTRACT

Importance: Peceleganan spray is a novel topical antimicrobial agent targeted for the treatment of skin wound infections. However, its efficacy and safety remain unclear. Objective: To assess the safety and efficacy of peceleganan spray for the treatment of wound infections. Design, Setting, and Participants: This multicenter, open-label, phase 3 randomized clinical trial recruited and followed up 570 adult patients diagnosed with secondary open wound infections from 37 hospitals in China from August 23, 2021, to July 16, 2022. Interventions: Patients were randomized to 2 groups with a 2:1 allocation. One group received treatment with 2% peceleganan spray (n = 381) and the other with 1% silver sulfadiazine (SSD) cream (n = 189). Main Outcomes and Measures: The primary efficacy outcome was the clinical efficacy rate (the number of patients fulfilling the criteria for efficacy of the number of patients receiving the treatment) on the first day following the end of treatment (day 8). The secondary outcomes included the clinical efficacy rate on day 5 and the bacterial clearance rate (cases achieving negative bacteria cultures after treatment of all cases with positive bacteria cultures before treatment) on days 5 and 8. The safety outcomes included patients' vital signs, physical examination results, electrocardiographic findings, blood test results, and adverse reactions. Results: Among the 570 patients randomized to 1 of the 2 groups, 375 (98.4%) in the 2% peceleganan treatment group and 183 (96.8%) in the 1% SSD control group completed the trial (n = 558). Of these, 361 (64.7%) were men, and the mean (SD) age was 48.6 (15.3) years. The demographic characteristics were similar between groups. On day 8, clinical efficacy was achieved by 339 patients (90.4%) in the treatment group and 144 (78.7%) in the control group (P < .001). On day 5, clinical efficacy was achieved by 222 patients (59.2%) in the treatment group and 90 (49.2%) in the control group (P = .03). On day 8, bacterial clearance was achieved by 80 of 334 patients (24.0%) in the treatment group and in 75 of 163 (46.0%) in the control group (P < .001). On day 5, bacterial clearance was achieved by 55 of 334 patients (16.5%) in the treatment group and 50 of 163 (30.7%) in the control group (P < .001). The adverse events related to the application of peceleganan spray and SSD cream were similar. Conclusions and Relevance: This randomized clinical trial found that peceleganan spray is a safe topical antimicrobial agent with a satisfactory clinical efficacy rate for the treatment of skin wound infections, while the effectiveness of bacterial clearance remains uncertain. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100047202.


Subject(s)
Wound Infection , Humans , Male , Female , Middle Aged , Adult , Wound Infection/drug therapy , Anti-Infective Agents, Local/therapeutic use , Anti-Infective Agents, Local/administration & dosage , China , Silver Sulfadiazine/therapeutic use , Silver Sulfadiazine/administration & dosage , Treatment Outcome , Aged , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage
6.
China CDC Wkly ; 6(23): 558-562, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38933662

ABSTRACT

What is already known about this topic?: Echinococcosis exhibits a global distribution. In China, the primary endemic area is the northwest region. In December 2023, we documented a case of echinococcosis in an individual lacking any travel or residential history in endemic regions. What is added by this report?: This is the first laboratory-confirmed case of hepatic echinococcosis reported in Guangdong Province, associated with the G7 genotype of Echinococcus granulosus (E. granulosus). The most probable mode of transmission is a local infection resulting from E. granulosus introduced from endemic regions. What are the implications for public health practice?: As the circulation of agricultural products increases, it is essential to enhance the quarantine and management of livestock from epidemic areas to prevent and control the spread of echinococcosis to non-epidemic regions.

7.
BMC Public Health ; 24(1): 1358, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769474

ABSTRACT

BACKGROUND: Understanding factors associated with antiretroviral treatment (ART) adherence is crucial for ART success among people living with HIV (PLHIV) in the "test and treat" era. Multiple psychosocial factors tend to coexist and have a syndemic effect on ART adherence. We aimed to explore factors associated with ART adherence and the syndemic effect of multiple psychosocial factors on ART adherence among PLHIV newly starting ART in Guangdong Province, China. METHODS: Newly diagnosed PLHIV from six cities in Guangdong Province were recruited between May 2018 and June 2019, and then followed up from May 2019 to August 2020. Baseline and follow-up data were collected from a questionnaire and the national HIV surveillance system, the follow-up data of which were analyzed in this study. A Center for Adherence Support Evaluation (CASE) index > 10 points was defined as optimal ART adherence, which was measured via participants' self-reported adherence during follow-up survey. Multivariable logistic regression was used to identify factors associated with ART adherence. Exploratory factor analysis (EFA) and multi-order latent variable structural equation modeling (SEM) were performed to explore the syndemic effect of multiple psychosocial factors on ART adherence. RESULTS: A total of 734 (68.53%) follow-up participants were finally included in this study among the 1071 baseline participants, of whom 91.28% (670/734) had self-reported optimal ART adherence. Unemployment (aOR = 1.75, 95%CI: 1.01-3.02), no medication reminder (aOR = 2.28, 95%CI: 1.09-4.74), low medication self-efficacy (aOR = 2.28, 95%CI: 1.27-4.10), low social cohesion (aOR = 1.82, 95%CI: 1.03-3.19), no social participation (aOR = 5.65, 95%CI: 1.71-18.63), and ART side effects (aOR = 0.46, 95%CI: 0.26-0.81) were barriers to optimal ART adherence. The EFA and second-order latent variable SEM showed a linear relationship (standardized coefficient = 0.43, P < 0.001) between ART adherence and the latent psychosocial (syndemic) factor, which consisted of the three latent factors of medication beliefs and self-efficacy (standardized coefficient = 0.65, P < 0.001), supportive environment (standardized coefficient = 0.50, P < 0.001), and negative emotions (standardized coefficient=-0.38, P < 0.01). The latent factors of medication beliefs and self-efficacy, supportive environment, and negative emotions explained 42.3%, 25.3%, and 14.1% of the variance in the latent psychosocial factor, respectively. CONCLUSIONS: About nine out of ten PLHIV on ART in Guangdong Province self-reported optimal ART adherence. However, more efforts should be made to address barriers to optimal ART adherence.


Subject(s)
HIV Infections , Medication Adherence , Humans , HIV Infections/drug therapy , HIV Infections/psychology , China/epidemiology , Male , Female , Adult , Cross-Sectional Studies , Medication Adherence/statistics & numerical data , Medication Adherence/psychology , Middle Aged , Anti-Retroviral Agents/therapeutic use , Surveys and Questionnaires , Anti-HIV Agents/therapeutic use , Young Adult
8.
Front Plant Sci ; 15: 1388586, 2024.
Article in English | MEDLINE | ID: mdl-38779069

ABSTRACT

Introduction: "Baizhi" is a famous herbal medicine in China, and it includes four landraces named as 'Hangbaizhi', 'Chuanbaizhi', 'Qibaizhi', and 'Yubaizhi'. Long-term artificial selection had caused serious degradation of these germplasms. Determining the wild progenitor of the landraces would be benefit for their breed improvements. Previous studies have suggested Angelica dahurica var. dahurica, A. dahurica var. formosana, or A. porphyrocaulis as potential candidates, but the conclusion remains uncertain, and their phylogenetic relationships are still in controversy. Methods: In this study, the genetic variation and phylogenetic analyses of these species and four landraces were conducted on the basis of both the nrITS and plastome datasets. Results: Genetic variation analysis showed that all 8 population of four landraces shared only one ITS haplotype, meanwhile extremely low variation occurred within 6 population at plastid genome level. Both datasets supported the four landraces might be originated from a single wild germplasm. Phylogenetic analyses with both datasets revealed largely consistent topology using Bayesian inference and Maximum likelihood methods. Samples of the four landraces and all wild A. dahurica var. dahurica formed a highly supported monophyletic clade, and then sister to the monophyly clade comprised by samples of A. porphyrocaulis, while four landraces were clustered into one clade, which further clustered with a mixed branches of A. porphyrocaulis and A. dahurica var. dahurica to form sister branches for plastid genomes. Furthermore, the monophyletic A. dahurica var. formosana was far distant from the A. dahurica var. dahurica-"Baizhi" clade in Angelica phylogeny. Such inferences was also supported by the evolutionary patterns of nrITS haplotype network and K2P genetic distances. The outcomes indicated A. dahurica var. dahurica is most likely the original plant of "Baizhi". Discussion: Considering of phylogenetic inference and evolutionary history, the species-level status of A. dahurica var. formosana should be accepted, and the taxonomic level and phylgenetic position of A. porphyrocaulis should be further confirmed. This study preliminarily determined the wild progenitor of "Baizhi" and clarified the phylogenetic relationships among A. dahurica var. dahurica, A. dahurica var. formosana and A. porphyrocaulis, which will provide scientific guidance for wild resources protections and improvement of "Baizhi".

9.
Microbiol Spectr ; 12(6): e0310323, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38647275

ABSTRACT

Tail fat deposition of Altay sheep not only increased the cost of feeding but also reduced the economic value of meat. Currently, because artificial tail removal and gene modification methods cannot solve this problem, it is maybe to consider reducing tail fat deposition from the path of intestinal microbiota and metabolite. We measured body weight and tail fat weight, collected the serum for hormone detection by enzyme-linked immunosorbent assay, and collected colon contents to 16S rRNA sequence and liquid chromotography with mass spectrometry detection to obtain colon microbiota and metabolite information, from 12 3-month-old and 6-month-old Altay sheep. Subsequently, we analyzed the correlation between colon microbiota and tail fat weight, hormones, and metabolites, respectively. We identified that the tail fat deposition of Altay sheep increased significantly with the increase of age and body weight, and the main microbiota that changed were Verrucomicrobia, Cyanobacteria, Akkermansia, Bacteroides, Phocaeicola, Escherichia-Shigella, and Clostridium_sensu_stricto_1. The results indicated that the diversities of metabolites in the colon contents of 3-months old and 6-months old were mainly reflected in phosphocholine (PC) and phosphatidylethanolamine (PE) in the lipid metabolism pathway. The correlations analyzed showed that Verrucomicrobia, Chlamydiae, Akkermansia, Ruminococcaceae_UCG-005, Bacteroides, and Phocaeicola were negatively correlated with tail fat deposition. Verrucomicrobia, Akkermansia, and Bacteroides were negatively correlated with growth hormone (GH). Verrucomicrobia was positively correlated with L-a-lysophosphatidylserine and PE(18:1(9Z)/0:0). Our results showed that tail fat deposition of Altay sheep was probably correlated with the abundance of Verrucomicrobia, Akkermansia, Bacteroides of colon microbiota, PC, PE of metabolites, and GH of serum. IMPORTANCE: Excessive tail fat deposition of Altay sheep caused great economic losses, and the current research results could not solve this problem well. Now, our research speculates that the tail fat deposition of Aletay sheep may be related to the abundance of Verrucomicrobia, Akkermansia, Bacteroides, metabolites phosphocholine, phosphatidylethanolamine, and growth hormone of serum. Further investigation of the interaction mechanism between these microbiota or metabolites and tail fat deposition is helpful in reducing tail fat deposition of Altay sheep and increasing the economic benefits of breeding farms.


Subject(s)
Bacteria , Colon , Gastrointestinal Microbiome , RNA, Ribosomal, 16S , Tail , Animals , Sheep/microbiology , Gastrointestinal Microbiome/physiology , Colon/microbiology , Colon/metabolism , Tail/microbiology , RNA, Ribosomal, 16S/genetics , Bacteria/classification , Bacteria/metabolism , Bacteria/isolation & purification , Bacteria/genetics , Phosphatidylethanolamines/metabolism , Adipose Tissue/metabolism , Lipid Metabolism , Phosphatidylcholines/metabolism
10.
PhytoKeys ; 239: 229-238, 2024.
Article in English | MEDLINE | ID: mdl-38559634

ABSTRACT

Phyllanthodendron can be readily morphologically distinguished from Glochidion, but recent molecular evidence showed that Phyllanthodendron is paraphyletic due to Glochidion being nested within it. In this study, a new species of the former Phyllanthodendron is described and illustrated as Glochidionyangchunense Z.Q. Song & Gang Yao from the limestone areas of South China. This is a peculiar new species and morphologically distinguished by its discoid flowers, T-shaped disc segments, and glabrous flowering branches. A key to Glochidionyangchunense and related species in China is provided here.

11.
Molecules ; 29(6)2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38542890

ABSTRACT

An unparalleled copper(I)-catalyzed synthesis of 1,3,4-oxadiazoles from tertiary amines in one step has been described. The one-pot reactions involving (N-isocyanimine)triphenylphosphorane, tertiary amines, and carboxylic acids resulted in the formation of 1,3,4-oxadiazoles in moderate to good yields through a consecutive oxidative Ugi/aza-Wittig reaction, enabling the direct functionalization of sp3 C-H bonds adjacent to the nitrogen atom. This method offered several notable advantages, including ligands-free, exceptional productivity and a high functional group tolerance. The preliminary biological evaluation demonstrated that compound 4f inhibited hepatoma cells efficiently, suggesting potentially broad applications of the approach for synthesis and medicinal chemistry.


Subject(s)
Copper , Organophosphorus Compounds , Oxadiazoles , Copper/chemistry , Oxadiazoles/chemistry , Amines/chemistry , Catalysis , Oxidative Stress
12.
Zootaxa ; 5406(2): 373-382, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38480147

ABSTRACT

A new species of the genus Suwallia Ricker, 1943, S. rostrata sp. nov., from Xizang of southwestern China is described, illustrated and compared with similar species. Alloperla kurentzovi Zhiltzova & Zapekina-Dulkeit, 1977, A. kurilensis Zhiltzova, 1978, A. teleckojensis mal, 1939 are reported for the first time from China. The diagnostic features of these species are illustrated with color images.


Subject(s)
Insecta , Neoptera , Animals , Animal Distribution , China
13.
Small ; : e2400449, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38488742

ABSTRACT

Materials with low intrinsic lattice thermal conductivity are crucial in the pursuit of high-performance thermoelectric (TE) materials. Here, the TE properties of PbBi2 Te4-x Sex (0 ≤ x ≤ 0.6) samples are systematically investigated for the first time. Doping with Se in PbBi2 Te4 can simultaneously reduce carrier concentration and increase carrier mobility. The Seebeck coefficient is significantly increased by doping with Se, based on the density functional theory calculation, it is shown to be due to the increased bandgap and electronic density of states. In addition, the lattice strain is enhanced due to the difference in the size of Se and Te atoms, and the multidimensional defects formed by Se doping, such as vacancies, dislocations, and grain boundaries, enhance the phonon scattering and reduce the lattice thermal conductivity by about 37%. Finally, by using Se doping to reduce carrier concentration and thermal conductivity, a large ZTmax = 0.56 (at 574K) is achieved for PbBi2 Te3.5 Se0.5 , which is around 64% larger than those of the PbBi2 Te4 pristine sample. This work not only demonstrates that PbBi2 Te4 is a potential medium temperature thermoelectric material, but also provides a reference for enhancing thermoelectric properties through defect and energy band engineering.

14.
BMC Genomics ; 25(1): 158, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38331736

ABSTRACT

BACKGROUND: Studies have confirmed that Infectious bovine rhinotracheitis virus (IBRV) infection induces mitochondrial damage. MicroRNAs (miRNAs) are a class of noncoding RNA molecules, which are involved in various biological processes and pathological changes associated with mitochondrial damage. It is currently unclear whether miRNAs participate in IBRV-induced mitochondrial damage in Madin-Darby bovine kidney (MDBK) cells. RESULTS: In the present study, we used high-throughput sequencing technology, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to screen for mitochondria-related miRNAs and messenger RNAs (mRNAs). In total, 279 differentially expressed miRNAs and 832 differentially expressed mRNAs were identified in 6 hours (IBRV1) versus 24 hours (IBRV2) after IBRV infection in MDBK cells. GO and KEGG enrichment analysis revealed that 42 differentially expressed mRNAs and 348 target genes of differentially expressed miRNAs were correlated with mitochondrial damage, and the miRNA-mitochondria-related target genes regulatory network was constructed to elucidate their potential regulatory relationships. Among the 10 differentially expressed miRNAs, 8 showed expression patterns consistent with the high-throughput sequencing results. Functional validation results showed that overexpression of miR-10a and miR-182 aggravated mitochondrial damage, while inhibition of miR-10a and miR-182 alleviated mitochondrial damage. CONCLUSIONS: This study not only revealed the expression changes of miRNAs and mRNAs in IBRV-infected MDBK cells, but also revealed possible biological regulatory relationship between them. MiR-10a and miR-182 may have the potential to be developed as biomarkers for the diagnosis and treatment of IBRV. Together, Together, these data and analyses provide additional insights into the roles of miRNA and mRNA in IBRV-induced mitochondria damage.


Subject(s)
Herpesvirus 1, Bovine , MicroRNAs , Animals , Cattle , MicroRNAs/genetics , MicroRNAs/metabolism , Herpesvirus 1, Bovine/genetics , Epithelial Cells/metabolism , Kidney/metabolism , Gene Regulatory Networks , RNA, Messenger/genetics , Gene Expression Profiling
15.
Ann Bot ; 133(5-6): 697-710, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38230804

ABSTRACT

BACKGROUND AND AIMS: The staghorn fern genus Platycerium is one of the most commonly grown ornamental ferns, and it evolved to occupy a typical pantropical intercontinental disjunction. However, species-level relationships in the genus have not been well resolved, and the spatiotemporal evolutionary history of the genus also needs to be explored. METHODS: Plastomes of all the 18 Platycerium species were newly sequenced. Using plastome data, we reconstructed the phylogenetic relationships among Polypodiaceae members with a focus on Platycerium species, and further conducted molecular dating and biogeographical analyses of the genus. KEY RESULTS: The present analyses yielded a robustly supported phylogenetic hypothesis of Platycerium. Molecular dating results showed that Platycerium split from its sister genus Hovenkampia ~35.2 million years ago (Ma) near the Eocene-Oligocene boundary and began to diverge ~26.3 Ma during the late Oligocene, while multiple speciation events within Platycerium occurred during the middle to late Miocene. Biogeographical analysis suggested that Platycerium originated in tropical Africa and then dispersed eastward to southeast Asia-Australasia and westward to neotropical areas. CONCLUSIONS: Our analyses using a plastid phylogenomic approach improved our understanding of the species-level relationships within Platycerium. The global climate changes of both the Late Oligocene Warming and the cooling following the mid-Miocene Climate Optimum may have promoted the speciation of Platycerium, and transoceanic long-distance dispersal is the most plausible explanation for the pantropical distribution of the genus today. Our study investigating the biogeographical history of Platycerium provides a case study not only for the formation of the pantropical intercontinental disjunction of this fern genus but also the 'out of Africa' origin of plant lineages.


Subject(s)
Phylogeny , Phylogeography , Plastids , Polypodiaceae , Polypodiaceae/genetics , Polypodiaceae/classification , Plastids/genetics , Biological Evolution , Africa , Ferns/genetics , Ferns/classification , Evolution, Molecular
16.
Sci Data ; 11(1): 55, 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38195564

ABSTRACT

Chinese motherwort (Leonurus japonicus), a member of Lamiaceae family, is a commonly used medicinal herb for treating obstetrical and gynecological diseases, producing over 280 officinal natural products. Due to limited genomic resources, little progress has been made in deciphering the biosynthetic pathway of valuable natural products in L. japonicus. Here, we de novo assembled the L. japonicus genome using high-coverage ONT long reads and Hi-C reads. The chromosome-level genome assembly contained ten chromosomes representing 99.29% of 489.34 Mb genomic sequence with a contig and scaffold N50 of 7.27 Mb and 50.86 Mb, respectively. Genome validations revealed BUSCO and LAI score of 99.2% and 21.99, respectively, suggesting high quality of genome assembly. Using transcriptomic data from various tissues, 22,531 protein-coding genes were annotated. Phylogenomic analysis of 13 angiosperm plants suggested L. japonicus had 58 expanded gene families functionally enriched in specialized metabolism such as diterpenoid biosynthesis. The genome assembly, annotation, and sequencing data provide resources for the elucidation of biosynthetic pathways behind natural products of pharmaceutical applications in L. japonicus.


Subject(s)
Genome, Plant , Leonurus , Biological Products , China , Gene Expression Profiling , Genomics , Leonurus/genetics
17.
J Med Chem ; 67(3): 2049-2065, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38284310

ABSTRACT

Human genetic evidence shows that PDE3B is associated with metabolic and dyslipidemia phenotypes. A number of PDE3 family selective inhibitors have been approved by the FDA for various indications; however, given the undesirable proarrhythmic effects in the heart, selectivity for PDE3B inhibition over closely related family members (such as PDE3A; 48% identity) is a critical consideration for development of PDE3B therapeutics. Selectivity for PDE3B over PDE3A may be achieved in a variety of ways, including properties intrinsic to the compound or tissue-selective targeting. The high (>95%) active site homology between PDE3A and B represents a massive obstacle for obtaining selectivity at the active site; however, utilization of libraries with high molecular diversity in high throughput screens may uncover selective chemical matter. Herein, we employed a DNA-encoded library screen to identify PDE3B-selective inhibitors and identified potent and selective boronic acid compounds bound at the active site.


Subject(s)
DNA , Heart , Humans , Catalytic Domain , Cyclic Nucleotide Phosphodiesterases, Type 3
18.
Acta Biochim Biophys Sin (Shanghai) ; 56(1): 54-61, 2024 01 25.
Article in English | MEDLINE | ID: mdl-38098360

ABSTRACT

Long noncoding RNAs (lncRNAs) are important regulators of bone metabolism. In this study, lncRNA microarray analysis was used to identify differentially expressed lncRNAs in differentiated osteoclasts. lncRNA-Gm5532 is highly expressed during osteoclast differentiation. lncRNA-Gm5532 knockdown impairs osteoclast formation and bone resorption. Mechanistic experiments show that lncRNA-Gm5532 functions as a competing endogenous RNA (ceRNA) and acts as a sponge for miR-125a-3p, which promotes TNF receptor-associated factor 6 (TRAF6) expression. miR-125a-3p mimics suppress osteoclast differentiation and TAK1/NF-κB/MAPK signaling. The miR-125a-3p inhibitor reverses the negative effects of siGm5532 on osteoclast differentiation. In summary, our study reveals that lncRNA-Gm5532 functions as an activator in osteoclast differentiation by targeting the miR-125a-3p/TRAF6 axis, making it a novel biomarker and potential therapeutic target for osteoporosis.


Subject(s)
Bone Resorption , MicroRNAs , RNA, Long Noncoding , Humans , MicroRNAs/metabolism , Osteoclasts/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , TNF Receptor-Associated Factor 6/genetics , TNF Receptor-Associated Factor 6/metabolism , Bone Resorption/genetics , Bone Resorption/metabolism
19.
J Chem Phys ; 159(21)2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38038204

ABSTRACT

We have studied the epitaxial growth of Si thin films on the Cd(0001) surface using low-temperature scanning tunneling microscopy. When deposited at low temperatures (100 K), Si atoms form dendritic islands with triangular shapes, indicating the existence of anisotropic edge diffusion in the process of Si film growth. After annealing to elevated temperatures, the triangular dendritic Si islands become hexagonal compact islands. Moreover, the 2D Si islands located on two different substrate terraces exhibit different heights due to the influence of quantum-well states in Cd(0001) films. Based on high-resolution scanning tunneling microscopy images, it is observed that the first, second, and third Si layers show the pseudomorphic 1 × 1 structure. In particular, the first and second layer islands reveal the opposite triangles, indicating the hexagonal close-packed stacking of Si atoms. These results provide important information for the growth of pristine Si films on metal substrates and the understanding of Si-metal interaction.

20.
Iran J Kidney Dis ; 17(6): 327-334, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38043110

ABSTRACT

\Introduction. Diabetes mellitus (DM) is one of the most common chronic diseases worldwide, and diabetic nephropathy (DN) is the most significant complication of DM, which is highly prevalent and difficult to cure. This research project aims to investigate the role and mechanism of Nucleoporin 160kDa (NUP160)-regulated autophagy in the pathogenesis of DN. METHODS: NUP160 levels in diabetic and non-diabetic kidney tissues were measured by Western blot, and the connection between NUP160 and renal function of DN patients was analyzed. The podocytes were divided into four groups, namely the standard group (culture medium: standard glucose solution), high glucose (HG) group (HG solution), HG+si-NUP160 group (HG solution+si-NUP160 transfection) and HG+si-NC group (HG solution+si-NUP 160 transfection) for the determination of apoptosis by flow cytometry and measurements of LC3B, Prostacyclin-62 (P62), Janus kinase 2 (JAK2) and Signal transducer and activator of transcription3 (STAT3) by Western blot. RESULTS: In DN patients, NUP160 decreased in podocytes and was inversely proportional to Blood urea nitrogen (BUN), Serum creatinine (Scr) and ß2-Microglobulin (ß2-MG) (P < .05). Compared with a standard group, the apoptosis rate, P62 level, and the ratios of phosphorylation-JAK2 (p-JAK2)/JAK2, phosphorylation-STAT3 (p-STAT3)/STAT3, and LC3B-Ⅱ/LC3B-Ⅰ elevated in the other three groups (P < .05). Apoptosis rate and P62 level, p-JAK2/JAK2 and p-STAT3/STAT3 ratios increased, and LC3B-Ⅱ/LC3B-Ⅰ ratio decreased in the HG+si-NUP160 group (P < .05), while those in HG+si-NC group showed no evident changes, compared with HG group (P > .05). CONCLUSION: NUP160 is downregulated in DN and can affect cellular autophagy through the activation of JAK2/STAT3 signaling pathway.  DOI: 10.52547/ijkd.7884.


Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Podocytes , Humans , Podocytes/metabolism , Podocytes/pathology , Signal Transduction , Glucose , Autophagy , Apoptosis , Nuclear Pore Complex Proteins/genetics , Nuclear Pore Complex Proteins/metabolism
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