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1.
Am J Hum Genet ; 110(3): 516-530, 2023 03 02.
Article in English | MEDLINE | ID: mdl-36796361

ABSTRACT

Primate-specific genes (PSGs) tend to be expressed in the brain and testis. This phenomenon is consistent with brain evolution in primates but is seemingly contradictory to the similarity of spermatogenesis among mammals. Here, using whole-exome sequencing, we identified deleterious variants of X-linked SSX1 in six unrelated men with asthenoteratozoospermia. SSX1 is a PSG expressed predominantly in the testis, and the SSX family evolutionarily expanded independently in rodents and primates. As the mouse model could not be used for studying SSX1, we used a non-human primate model and tree shrews, which are phylogenetically similar to primates, to knock down (KD) Ssx1 expression in the testes. Consistent with the phenotype observed in humans, both Ssx1-KD models exhibited a reduced sperm motility and abnormal sperm morphology. Further, RNA sequencing indicated that Ssx1 deficiency influenced multiple biological processes during spermatogenesis. Collectively, our experimental observations in humans and cynomolgus monkey and tree shrew models highlight the crucial role of SSX1 in spermatogenesis. Notably, three of the five couples who underwent intra-cytoplasmic sperm injection treatment achieved a successful pregnancy. This study provides important guidance for genetic counseling and clinical diagnosis and, significantly, describes the approaches for elucidating the functions of testis-enriched PSGs in spermatogenesis.


Subject(s)
Asthenozoospermia , Tupaia , Animals , Male , Macaca fascicularis , Primates , Semen , Sperm Motility , Tupaiidae
2.
J Biol Chem ; 300(7): 107415, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38815863

ABSTRACT

While deubiquitinase ATXN3 has been implicated as a potential oncogene in various types of human cancers, its role in colon adenocarcinoma remains understudied. Surprisingly, our findings demonstrate that ATXN3 exerts an antitumor effect in human colon cancers through potentiating Galectin-9-induced apoptosis. CRISPR-mediated ATXN3 deletion unexpectedly intensified colon cancer growth both in vitro and in xenograft colon cancers. At the molecular level, we identified ATXN3 as a bona fide deubiquitinase specifically targeting Galectin-9, as ATXN3 interacted with and inhibited Galectin-9 ubiquitination. Consequently, targeted ATXN3 ablation resulted in reduced Galectin-9 protein expression, thereby diminishing Galectin-9-induced colon cancer apoptosis and cell growth arrest. The ectopic expression of Galectin-9 fully reversed the growth of ATXN3-null colon cancer in mice. Furthermore, immunohistochemistry staining revealed a significant reduction in both ATXN3 and Galectin-9 protein expression, along with a positive correlation between them in human colon cancer. Our study identifies the first Galectin-9-specific deubiquitinase and unveils a tumor-suppressive role of ATXN3 in human colon cancer.

3.
Funct Integr Genomics ; 24(2): 67, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38528184

ABSTRACT

BACKGROUND: Although the events associated with alternative splicing (AS), alternative polyadenylation (APA) and alternative transcription initiation (ATI) can be identified by many approaches based on isoform sequencing (Iso-Seq), these analyses are generally independent of each other and the links between these events are still rarely mentioned. However, an interdependency analysis can be achieved because the transcriptional start site, splice sites and polyA site could be simultaneously included in a long, full-length read from Iso-Seq. RESULTS: We create ASAPA pipeline that enables streamlined analysis for a robust detection of potential links among AS, ATI and APA using Iso-Seq data. We tested this pipeline using Arabidopsis data and found some interesting results: some adjacent introns tend to be simultaneously spliced or retained; coupling between AS and ATI or APA is limited to the initial or terminal intron; and ATI and APA are potentially linked in some special cases. CONCLUSION: Our pipeline enables streamlined analysis for a robust detection of potential links among AS, ATI and APA using Iso-Seq data, which is conducive to a better understanding of transcription landscape generation.


Subject(s)
Alternative Splicing , Polyadenylation , Protein Isoforms/genetics , Computational Biology , High-Throughput Nucleotide Sequencing
4.
Glob Chang Biol ; 30(5): e17302, 2024 May.
Article in English | MEDLINE | ID: mdl-38699927

ABSTRACT

Climate-smart agriculture (CSA) supports the sustainability of crop production and food security, and benefiting soil carbon storage. Despite the critical importance of microorganisms in the carbon cycle, systematic investigations on the influence of CSA on soil microbial necromass carbon and its driving factors are still limited. We evaluated 472 observations from 73 peer-reviewed articles to show that, compared to conventional practice, CSA generally increased soil microbial necromass carbon concentrations by 18.24%. These benefits to soil microbial necromass carbon, as assessed by amino sugar biomarkers, are complex and influenced by a variety of soil, climatic, spatial, and biological factors. Changes in living microbial biomass are the most significant predictor of total, fungal, and bacterial necromass carbon affected by CSA; in 61.9%-67.3% of paired observations, the CSA measures simultaneously increased living microbial biomass and microbial necromass carbon. Land restoration and nutrient management therein largely promoted microbial necromass carbon storage, while cover crop has a minor effect. Additionally, the effects were directly influenced by elevation and mean annual temperature, and indirectly by soil texture and initial organic carbon content. In the optimal scenario, the potential global carbon accrual rate of CSA through microbial necromass is approximately 980 Mt C year-1, assuming organic amendment is included following conservation tillage and appropriate land restoration. In conclusion, our study suggests that increasing soil microbial necromass carbon through CSA provides a vital way of mitigating carbon loss. This emphasizes the invisible yet significant influence of soil microbial anabolic activity on global carbon dynamics.


Subject(s)
Agriculture , Carbon , Climate Change , Soil Microbiology , Soil , Agriculture/methods , Carbon/analysis , Carbon/metabolism , Soil/chemistry , Biomass , Carbon Cycle , Fungi , Bacteria/metabolism
5.
BMC Cancer ; 24(1): 156, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38291366

ABSTRACT

BACKGROUND: Lactate dehydrogenase (LDHs) is an enzyme involved in anaerobic glycolysis, including LDHA, LDHB, LDHC and LDHD. Given the regulatory role in the biological progression of certain tumors, we analyzed the role of LDHs in pan-cancers. METHODS: Cox regression, Kaplan-Meier curves, Receiver Operating Characteristic (ROC) curves, and correlation of clinical indicators in tumor patients were used to assess the prognostic significance of LDHs in pan-cancer. The TCGA, HPA, TIMER, UALCAN, TISIDB, and Cellminer databases were used to investigate the correlation between the expression of LDHs and immune subtypes, immune checkpoint genes, methylation levels, tumor mutational load, microsatellite instability, tumor-infiltrating immune cells and drug sensitivity. The cBioPortal database was also used to identify genomic abnormalities of LDHs in pan-cancer. A comprehensive assessment of the biological functions of LDHs was performed using GSEA. In vitro, HepG2 and Huh7 cells were transfected with LDHD siRNA and GFP-LDHD, the proliferation capacity of cells was examined using CCK-8, EdU, and colony formation assays; the migration and invasion of cells was detected by wound healing and transwell assays; western blotting was used to detect the levels of MMP-2, MMP-9, E-cadherin, N-cadherin and Akt phosphorylation. RESULTS: LDHs were differentially expressed in a variety of human tumor tissues. LDHs subtypes can act as pro-oncogenes or anti-oncogenes in different types of cancer and have an impact on the prognosis of patients with tumors by influencing their clinicopathological characteristics. LDHs were differentially expressed in tumor immune subtypes and molecular subtypes. In addition, LDHs expression correlated with immune checkpoint genes, tumor mutational load, and microsatellite instability. LDHD was identified to play an important role in the prognosis of HCC patients, according to a comprehensive analysis of LDHs in pan-cancer. In HepG2 and Huh7 cells, knockdown of LDHD promoted cell proliferation, migration, and invasion, promoted the protein expression levels of MMP-2, MMP-9, N-cadherin, and Akt phosphorylation, but inhibited the protein expression level of E-cadherin. In addition, LDHD overexpression showed the opposite changes. CONCLUSION: LDHs subtypes can be used as potential prognostic markers for certain cancers. Prognostic and immunotherapeutic analysis indicated that LDHD plays an important role in the prognosis of HCC patients. In vitro experiments revealed that LDHD can affect HCC proliferation, migration, and invasion by regulating MMPs expression and EMT via Akt signaling pathway, which provides a new perspective on the anti-cancer molecular mechanism of LDHD in HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Cadherins/genetics , Carcinoma, Hepatocellular/genetics , L-Lactate Dehydrogenase , Liver Neoplasms/genetics , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Microsatellite Instability , Prognosis , Proto-Oncogene Proteins c-akt
6.
Phys Chem Chem Phys ; 26(6): 4968-4974, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38230694

ABSTRACT

Based on the excellent piezoelectric properties of 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 (PMN-PT) single crystals, a hole-doped manganite film/PMN-PT heterostructure has been constructed to achieve electric-field and light co-control of physical properties. Here, we report the resistivity switching behavior of Eu0.7Sr0.3MnO3/PMN-PT(111) multiferroic heterostructures under different in-plane reading currents, temperatures, light stimuli and electric fields, and discuss the underlying coupling mechanisms of resistivity change. The transition from the electric-field induced lattice strain effect to polarization current effect can be controlled effectively by decreasing the in-plane reading current at room temperature. With the decrease of temperature, the interfacial charge effect dominates over the lattice strain effect due to the reduced charge carrier density. In addition, light stimulus can lead to the delocalization of eg carriers, and thus enhance the lattice strain effect and suppress the interfacial charge effect. This work helps to understand essential physics of magnetoelectric coupling and also provides a potential method to realize energy-efficient multi-field control of manganite thin films.

7.
Plant Cell Rep ; 43(2): 30, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38195770

ABSTRACT

KEY MESSAGE: Sucrose invertase activity is positively related to osmotic and salt stress resistance in peanut. Sucrose invertases (INVs) have important functions in plant growth and response to environmental stresses. However, their biological roles in peanut are still not fully revealed. In this research, we identified 42 AhINV genes in the peanut genome. They were highly conserved and clustered into three groups with 24 segmental duplication events occurred under purifying selection. Transcriptional expression analysis exhibited that they were all ubiquitously expressed, and most of them were up-regulated by osmotic and salt stresses, with AhINV09, AhINV23 and AhINV19 showed the most significant up-regulation. Further physiochemical analysis showed that the resistance of peanut to osmotic and salt stress was positively related to the high sugar content and sucrose invertase activity. Our results provided fundamental information on the structure and evolutionary relationship of INV gene family in peanut and gave theoretical guideline for further functional study of AhINV genes in response to abiotic stress.


Subject(s)
Arachis , Sugars , Arachis/genetics , beta-Fructofuranosidase/genetics , Salt Stress , Sucrose
8.
BMC Public Health ; 24(1): 1453, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816714

ABSTRACT

OBJECTIVES: This study aimed to examine the impact of pertussis on the global, regional, and national levels between 1990 and 2019. METHODS: Data on pertussis on a global scale from 1990 to 2019 were collected from the 2019 Global Burden of Disease Study. We performed a secondary analysis to report the global epidemiology and disease burden of pertussis. RESULTS: During the period spanning from 1990 to 2019, pertussis exhibited a steady global decline in the age-standardized incidence rate (ASIR), age-standardized disability-adjusted life years rate (ASYR), and age-standardized death rate (ASDR). Nevertheless, upon delving into an in-depth analysis of various regions, it was apparent that ASIR in southern sub-Saharan Africa, ASYR and ASDR in high-income North America, and ASDR in Western Europe and Australasia, were witnessing an upward trajectory. Moreover, a negative correlation was observed between the Socio­demographic Index (SDI) and burden inflicted by pertussis. Notably, the incidence of pertussis was comparatively lower in men than in women, with 0-4-year-olds emerging as the most profoundly affected demographic. CONCLUSION: The global pertussis burden decreased from 1990 to 2019. However, certain regions and countries faced an increasing disease burden. Therefore, urgent measures are required to alleviate the pertussis burden in these areas.


Subject(s)
Global Burden of Disease , Global Health , Whooping Cough , Humans , Whooping Cough/epidemiology , Male , Incidence , Infant , Child, Preschool , Female , Global Health/statistics & numerical data , Disability-Adjusted Life Years , Child , Infant, Newborn , Adolescent , Adult , Cost of Illness
9.
J Clin Lab Anal ; 38(8): e25025, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38563451

ABSTRACT

OBJECTIVE: This study aimed to indicate whether a declined plasma concentration of valproic acid (VPA) induced by co-administration of meropenem (MEPM) could affect the antiepileptic efficacy of VPA. METHODS: We retrospectively reviewed data of hospitalized patients who were diagnosed with status epilepticus or epilepsy between 2010 and 2019. Patients co-administered VPA and MEPM during hospitalization were screened and assigned to the exposure group, while those co-administerd VPA and other broad-spectrum antibiotics were allocated to the control group. RESULTS: The exposure group and control group included 50 and 11 patients, respectively. With a similar dosage of VPA, the plasma concentration of VPA significantly decreased during co-administration (24.6 ± 4.3 µg/mL) compared with that before co-administration (88.8 ± 13.6 µg/mL, p < 0.0001), and it was partly recovered with the termination of co-administration (39.8 ± 13.2 µg/mL, p = 0.163) in the exposure group. The inverse probability of treatment weighting estimated the treatment efficacy via changes in seizure frequency, seizure duration, and concomitant use of antiepileptic drugs, which were not significantly different between the exposure and control groups. In the exposure group, there was no significant differences in seizure frequency between the periods of before-during and before-after (p = 0.074 and 0.153, respectively). Seizure duration during VPA-MEPM co-administration was not significantly different from that before co-administration (p = 0.291). CONCLUSIONS: In this study, the reduced plasma concentration of VPA induced by the co-administration of MEPM did not affect the antiepileptic efficacy of VPA. This conclusion should be interpreted with caution, and more research is warranted. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000034567. Registered on 10 July 2020.


Subject(s)
Anticonvulsants , Epilepsy , Meropenem , Valproic Acid , Humans , Valproic Acid/blood , Valproic Acid/therapeutic use , Valproic Acid/administration & dosage , Anticonvulsants/blood , Anticonvulsants/therapeutic use , Meropenem/blood , Meropenem/administration & dosage , Male , Female , Middle Aged , Retrospective Studies , Adult , Aged , Epilepsy/drug therapy , Epilepsy/blood , Drug Interactions , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/administration & dosage , Treatment Outcome
10.
PLoS Genet ; 17(10): e1009862, 2021 10.
Article in English | MEDLINE | ID: mdl-34710100

ABSTRACT

ZBED6 (zinc finger BED domain containing protein 6) is a transcription factor unique to placental mammals and its interaction with the IGF2 (insulin-like growth factor 2) locus plays a prominent role in the regulation of postnatal skeletal muscle growth. Here, we generated lean Bama miniature pigs by generating ZBED6-knockout (ZBED6-/-) and investigated the mechanism underlying ZBED6 in growth of muscle and internal organs of placental mammals. ZBED6-/- pigs show markedly higher lean mass, lean mass rate, larger muscle fiber area and heavier internal organs (heart and liver) than wild-type (WT) pigs. The striking phenotypic changes of ZBED6-/- pigs coincided with remarkable upregulation of IGF2 mRNA and protein expression across three tissues (gastrocnemius muscle, longissimus dorsi, heart). Despite a significant increase in liver weight, ZBED6-/- pigs show comparable levels of IGF2 expression to those of WT controls. A mechanistic study revealed that elevated methylation in the liver abrogates ZBED6 binding at the IGF2 locus, explaining the unaltered hepatic IGF2 expression in ZBED6-/- pigs. These results indicate that a ZBED6-IGF2-independent regulatory pathway exists in the liver. Transcriptome analysis and ChIP-PCR revealed new ZBED6 target genes other than IGF2, including cyclin dependent kinase inhibitor 1A (CDKN1A) and tsukushi, small leucine rich proteoglycan (TSKU), that regulates growth of muscle and liver, respectively.


Subject(s)
Muscle, Skeletal/metabolism , Repressor Proteins/metabolism , Animals , Female , Gene Expression Regulation/physiology , Insulin-Like Growth Factor II/metabolism , Liver/metabolism , Male , Muscle Development/physiology , Muscle Fibers, Skeletal/metabolism , Placenta/metabolism , Pregnancy , Swine , Transcription Factors/metabolism , Transcriptome/physiology , Up-Regulation/physiology
11.
Mikrochim Acta ; 191(7): 436, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38954059

ABSTRACT

A fluorescence probe based on molecularly imprinted polymers on red emissive biomass-derived carbon dots (r-BCDs@MIPs) was developed to detect tyramine in fermented meat products. The red emissive biomass-derived carbon dots (r-BCDs) were synthesized by the one-step solvothermal method using discarded passion fruit shells as raw materials. The fluorescence emission peak of r-BCDs was at 670 nm, and the relative quantum yield (QY) was about 2.44%. Molecularly imprinted sensing materials were prepared with r-BCDs as fluorescent centers for the detection of trace tyramine, which showed a good linear response in the concentration range of tyramine from 1 to 40 µg L-1. The linear correlation coefficient was 0.9837, and the limit of detection was 0.77 µg L-1. The method was successfully applied to the determination of tyramine in fermented meat products, and the recovery was 87.17-106.02%. The reliability of the results was verified through high-performance liquid chromatography (HPLC). Furthermore, we combined the r-BCDs@MIPs with smartphone-assisted signal readout to achieve real-time detection of tyramine in real samples. Considering its simplicity and convenience, the method could be used as a rapid and low-cost promising platform with broad application prospects for on-site detection of trace tyramine with smartphone-assisted signal readout.


Subject(s)
Carbon , Fluorescent Dyes , Limit of Detection , Meat Products , Molecularly Imprinted Polymers , Quantum Dots , Smartphone , Tyramine , Tyramine/analysis , Tyramine/chemistry , Carbon/chemistry , Quantum Dots/chemistry , Meat Products/analysis , Fluorescent Dyes/chemistry , Molecularly Imprinted Polymers/chemistry , Spectrometry, Fluorescence/methods , Biomass , Fermentation
12.
Int J Mol Sci ; 25(9)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38731831

ABSTRACT

Small secreted peptides (SSPs) play important roles in regulating plants' growth and development in response to external stimulus, but the genes and functions of SSPs in many species are still unknown. Therefore, it is particularly significant to characterize and annotate SSP genes in plant genomes. As a widely used stock of pears, Pyrus betulifolia has strong resistance to biotic and abiotic stresses. In this study, we analyzed the SSPs genes in the genome of P. betulifolia according to their characteristics and homology. A total of 1195 SSP genes were identified, and most of them are signaling molecules. Among these, we identified a new SSP, subtilase peptide 3 (SUBPEP3), which derived from the PA region of preSUBPEP3, increasing the expression level under salt stress. Both adding synthetic peptide SUBPEP3 to the culture medium of pears and the overexpression of SUBPEP3 in tobacco can improve the salt tolerance of plants. In summary, we annotated the SSP genes in the P. betulifolia genome and identified a small secreted peptide SUBPEP3 that regulates the salt tolerance of P. betulifolia, which provides an important theoretical basis for further revealing the function of SSPs.


Subject(s)
Gene Expression Regulation, Plant , Plant Proteins , Pyrus , Salt Tolerance , Pyrus/genetics , Pyrus/metabolism , Salt Tolerance/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Salt Stress/genetics , Nicotiana/genetics , Nicotiana/metabolism , Amino Acid Sequence , Peptides/metabolism , Peptides/genetics , Stress, Physiological/genetics , Plants, Genetically Modified/genetics
13.
J Sci Food Agric ; 104(6): 3341-3351, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38092560

ABSTRACT

BACKGROUND: Metal ions commonly inevitably appear in food products and have adverse effects on high-internal-phase emulsions (HIPEs) foods, but conformational conversion of soybean protein isolate (SPI)/soybean soluble polysaccharide (SSPS) on the interface layer of HIPEs influenced by different metal ions has rarely been reported. RESULTS: Here, the conformational conversion of SPI/SSPS induced by Na+ , K+ , Ca2+ , Mg2+ and Fe3+ ions and its effects on HIPEs were investigated. After adding the ions to SPI and SPI/SSPS dispersions, the particle size and zeta potential results showed different degrees of flocculation; the zeta potential and Fourier transform infrared spectra indicated that SPI and SPI/SSPS changes in structure involve electrostatic interactions and hydrogen bonding. Moreover, Raman spectra showed that the content of ß-sheet of SPI/SSPS HIPEs increased with the addition of Ca2+ , Mg2+ and Fe3+ , suggesting that SPI molecules at the interface formed a more orderly structure. The ultraviolet and fluorescence results showed that the hydrophobic environment of tryptophan and tyrosine residues inside protein molecules played a vital role in the emulsifying stability of SPI. CONCLUSION: These findings suggested that the SPI/SSPS complexes for food applications were not susceptible to ions, thus ensuring complex stability, showing potential for commercial application in the production of emulsions. © 2023 Society of Chemical Industry.


Subject(s)
Glycine max , Soybean Proteins , Soybean Proteins/chemistry , Emulsions/chemistry , Polysaccharides/chemistry , Cations
14.
J Am Chem Soc ; 145(37): 20521-20529, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37672393

ABSTRACT

Chalcogens, especially tellurium (Te), as conversion-type cathodes possess promising prospects for zinc batteries (ZBs) with potential rich valence supply and high energy density. However, the conversion reaction of Te is normally restricted to the Te2-/Te0 redox with a low voltage plateau at ∼0.59 V (vs Zn2+/Zn) rather than the expected positive valence conversion of Te0 to Ten+, inhibiting the development of Te-based batteries toward high output voltage and energy density. Herein, the desired reversible Te2-/Te0/Te2+/Te4+ redox behavior with up to six-electron transfer was successfully activated by employing a highly concentrated Cl--containing electrolyte (Cl- as strong nucleophile) for the first time. Three flat discharge plateaus located at 1.24, 0.77, and 0.51 V, respectively, are attained with a total capacity of 802.7 mAh g-1. Furthermore, to improve the stability of Ten+ products and enhance the cycling stability, a modified ionic liquid (IL)-based electrolyte was fabricated, leading to a high-performance Zn∥Te battery with high areal capacity (7.13 mAh cm-2), high energy density (542 Wh kgTe-1 or 227 Wh Lcathdoe+anode-1), excellent cycling performance, and a low self-discharge rate based on 400 mAh-level pouch cell. The results enhance the understanding of tellurium chemistry in batteries, substantially promising a remarkable route for advanced ZBs.

15.
Lab Invest ; 103(11): 100226, 2023 11.
Article in English | MEDLINE | ID: mdl-37532224

ABSTRACT

Diabetic cataract (DC) is a common cause of visual loss in older diabetic subjects. Krüppel-like factor 5 (KLF5) plays an essential role in migration and the epithelial-mesenchymal transition (EMT) in diverse cells and is involved in oxidative stress. However, the effects of KLF5 on DC remain unknown. This study aimed to examine the biological function of KLF5 in DC and its underlying mechanism. The expression patterns of KLF5 were detected in vivo and in vitro. Then, KLF5 was knocked down in human lens epithelial cells (HLECs) to explore its functional roles and underlying mechanisms. Dual-luciferase reporter assay and chromatin immunoprecipitation analysis were used to detect whether KLF5 could bind the promoter of E3 ubiquitin ligase mouse double minute 2 (MDM2), a key regulator of EMT. Lastly, the regulation of KLF5 in the biological behaviors of HLECs via MDM2 was analyzed. We found a significant increase of KLF5 in the DC lens anterior capsular, diabetic rat lens, and high glucose (HG)-stimulated HLECs. Knockdown of KLF5 inhibited oxidative stress, inflammation, migration, and EMT of HG-stimulated HLECs. KLF5 silencing impeded MDM2 expression and restricted the activation of MARK1/FAK and NF-κB signaling pathways in HLECs under HG condition. Additionally, KLF5 was found to bind the MDM2 promoter and enhance the transcriptional activity of MDM2. The protective effects by silencing KLF5 on HG-cultured HLECs could be offset by MDM2 overexpression. We demonstrated that knockdown of KLF5 alleviated oxidative stress, migration, and EMT of HG-cultured HLECs by regulating MDM2, suggesting a potential therapeutic strategy for DC.


Subject(s)
Cataract , Diabetes Mellitus , Humans , Rats , Mice , Animals , Aged , Epithelial-Mesenchymal Transition , Cataract/metabolism , Oxidative Stress , Diabetes Mellitus/metabolism , Epithelial Cells/metabolism , Proto-Oncogene Proteins c-mdm2/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism
16.
New Phytol ; 238(3): 1115-1128, 2023 05.
Article in English | MEDLINE | ID: mdl-36751904

ABSTRACT

Numerous plant endogenous mRNAs move via phloem and thus affect the growth and development of long-distant organs. mRNAs are transported with RNA-binding proteins forming a ribonucleoprotein complex. However, it remains elusive how such RNP complex assembles and facilitates mRNA trafficking. Protease digestion and RNA immunoprecipitation were used to investigate the RNP assembly function of the complete Chaperonin Containing T-complex Polypeptide-1. In situ hybridization, hairy root transformation, microprojectile bombardment, and grafting experiments demonstrate the role of CCT complex in the transport of a PbWoxT1-PbPTB3 RNP complex in Pyrus betulaefolia. PbCCT5 silenced caused defective movement of GFP-PbPTB3 and GFP-PbWoxT1 from hairy roots to new leaves via the phloem. PbCCT5 is shown to interact with PbPTB3. PbCCT complex enhanced PbPTB3 stabilization and permitted assembly of PbWoxT1 and PbPTB3 into an RNP complex. Furthermore, silencing of individual CCT subunits inhibited the intercellular movement of GFP-PbPTB3 and long-distance trafficking of PbWoxT1 and PbPTB3 in grafted plants. Taken together, the CCT complex assembles PbPTB3 and PbWoxT1 into an RNP complex in the phloem in order to facilitate the long-distance trafficking of PbWoxT1 in P. betulaefolia. This study therefore provides important insights into the mechanism of RNP complex formation and transport.


Subject(s)
Pyrus , Chaperonin Containing TCP-1/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plants/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Plant/genetics , RNA, Plant/metabolism , Ribonucleoproteins/metabolism
17.
Mol Ecol ; 32(7): 1673-1684, 2023 04.
Article in English | MEDLINE | ID: mdl-36567644

ABSTRACT

Environmental pollution can result in poor sperm quality either directly or indirectly in birds. However, adaptive and compensatory sperm morphology changes and motility improvements have rapidly evolved in tree sparrows (Passer montanus) inhabiting polluted areas over the past 65 years. To identify the genetic underpinnings of the rapidly evolving sperm phenotype, we carried out population genomics and transcriptomics on tree sparrow populations in the two differently polluted places. We identified a gene encoding the serine/threonine protein kinase PIM1, which may drive rapid phenotypic evolution of sperm. An unprecedented and remarkable expansion of the PIM gene family, caused by tandem and segmental duplication of PIM1, was subsequently observed in the tree sparrow genome. Most PIM1 duplicates showed a testis-specific expression pattern, suggesting that their functions are related to male reproduction. Furthermore, the elevated expression level of PIM1 was consistent with our earlier findings of longer and faster swimming sperm in polluted sites, indicating an important role for duplicated PIM1 in facilitating the rapid evolution of sperm. Our results suggest that duplicated PIM1 provides sources of genetic variation that may enable the rapid evolution of sperm under environmental heavy metal pollution. The findings of this study indicated that duplicated genes can be targets of selection and predominant sources for rapid adaptation to environmental change and shed light on sperm evolution under pollution stress.


Subject(s)
Sparrows , Animals , Male , Sparrows/genetics , Genes, Duplicate , Semen , Environmental Pollution , Spermatozoa
18.
J Exp Bot ; 74(12): 3765-3780, 2023 06 27.
Article in English | MEDLINE | ID: mdl-36988239

ABSTRACT

PHYTOCHROME INTERACTING FACTORS (PIFs) integrate light and temperature signs to control plant growth and development. However, little is known about PIFs in crop plants such as cotton. Here, we identified 68 PIF proteins and their coding genes from an allotetraploid and three diploid ancestors. Cotton PIFs contain typical ACTIVEPHYA-BINDING (APA) and ACTIVE PHYB-BINDING (APB) motifs by which they bind to phytochrome phyA and phyB, respectively, and have a BASIC HELIX-LOOP-HELIX (bHLH) domain and a nuclear localization sequence necessary for bHLH-type transcription factors. Bioinformatics analysis showed that the promoter of each PIF gene contains multiple cis-acting elements and that the evolution of cotton genomes probably underwent loss, recombination, and tandem replication. Further observations indicated that the sensitivity of cotton PIF expression to high temperature was significantly different from that to low temperature. We found that allotetraploid Gossypium hirsutum PIF4a (GhPIF4a) was induced by high temperature. GhPIF4a promotes flowering in cotton and Arabidopsis and binds to the promoter of GhFT (G. hirsutum FLOWERING LOCUS T), and binding increased with increasing temperature. Our work identifies the evolutionary and structural characteristics and functions of PIF family members in cotton.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Phytochrome , Phytochrome/genetics , Phytochrome/metabolism , Gossypium/genetics , Gossypium/metabolism , Temperature , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Gene Expression Regulation, Plant
19.
Mol Cell Biochem ; 2023 Jul 12.
Article in English | MEDLINE | ID: mdl-37436654

ABSTRACT

Herein, we investigated the role of the m6A methylation enzyme METTL14 in regulating myocardial ischemia/reperfusion injury (IR/I) through the Akt/mTOR signaling pathway and related biological mechanisms. Enzyme-linked immunosorbent assay (ELISA) and fluorescence quantitative polymerase chain reaction (qPCR) were performed to detect the m6A mRNA and METTL3, METTL14, WTAP, and KIAA1429 levels in a mouse myocardial IR/I model. An oxygen-glucose deprivation/reperfusion (OGD/R) model was constructed by transfecting neonatal rat cardiomyocytes (NRCM) with METTL14-knockdown lentivirus. METTL14, Bax, and cleaved-caspase3 mRNA expression levels were detected using fluorescence qPCR. Apoptosis was detected using TUNEL staining. After the IR/I surgery following the adeno-associated virus injection, the METTL14 mRNA and apoptosis-related BAX/BCL2 protein expression was detected using fluorescence qPCR and western blotting, respectively. Degree of cell necrosis was detected using an LDH assay. The oxidative stress response of the myocardial tissue was detected, and IL-6 and IL-1ß serum levels were detected using ELISAs. The mice injected with METTL14-knockdown AAV9 adeno-associated virus underwent IR/I surgery after the injection of an Akt/mTOR pathway inhibitor (MK2206) into the myocardial layer. Elevated mRNA m6A modification and m6A methyltransferase METTL14 levels were observed in the IR/I-injured mouse heart tissues. METTL14 knockdown significantly inhibited the OGD/R- and IR/I-induced apoptosis and necrosis in cardiac myocytes, inhibited IR/I-induced oxidative stress and inflammatory factor secretion, and activated the Akt/ mTOR pathway in vitro and in vivo. Akt/mTOR pathway inhibition significantly attenuated the alleviating effect of METTL14 knockdown on myocardial IR/I injury-induced apoptosis. Knocking down m6A methylase METTL14 inhibits IR/I-induced myocardial apoptosis and necrosis, inhibits myocardial oxidative stress and secretion of inflammatory cytokines, and activates the Akt/mTOR signaling pathway. Hence, METTL14 regulated myocardial apoptosis and necrosis in mice with IR/I through the Akt/mTOR signaling pathway.

20.
J Fluoresc ; 33(3): 1111-1123, 2023 May.
Article in English | MEDLINE | ID: mdl-36580202

ABSTRACT

Amino- and sulfhydryl- functionalized biomass carbon dots (BCDs) were prepared by one-pot reverse microemulsion for specific recognition of ferric ions (Fe3+) and L-cysteine (L-Cys). Green grapefruit peel was used as the carbon source while aminosilane and mercaptosilane were used as N- and S-supplier. Following the adsorption of Fe3+ on the surfaces of BCDs-NH2 and BCDs-SH, the fluorescence responses was quenched step by step, while adding L-Cys to the BCDs-NH2/Fe3+ system restored the fluorescence. The BCDs-NH2 and BCDs-SH system exhibited extremely low limits of detection for Fe3+ of 3.2 and 3.0 nM, respectively, within a wide linear ranges of 0.006-200 µM and 0.004-200 µM, respectively. The BCDs-NH2/Fe3+ systems were used as an optosensor for L-Cys in the concentration ranges of 0.08-30 and 30-1000 µM with a detection limit of 65 nM. Developed BCDs-NH2 and BCDs-SH were able to respond to Fe3+ in water samples with satisfactory recoveries of 100.1%-103.1% and 94.6%-108.5%, respectively, and the BCDs-NH2/Fe3+ system was also able to respond to BCDs-NH2/Fe3+ in actual lake water samples with recoveries from 87.3% to 98.8%. Meanwhile, The BCDs-NH2 exhibited good photoluminescence and stability, and the with a fluorescence quantum yield was as high as 25%. This work demonstrates the feasibility of using such materials to remove hazardous ions from water and employing the resulting complexes for optosensing in a sustainable manner.


Subject(s)
Cysteine , Quantum Dots , Carbon , Biomass , Water , Ions
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