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1.
Sci Total Environ ; 935: 173303, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38761948

ABSTRACT

Cadmium (Cd) and sulfamethoxazole (SMX) frequently coexist in farmlands, yet their synergistic toxicological impacts on terrestrial invertebrates remain unexplored. In this study, earthworms were exposed to artificial soils percolated with Cd (5 mg/kg), SMX (5 mg/kg) or combination of them for 7 days, followed by a 12-day elimination phase in uncontaminated soil. The uptake of Cd and SMX by the earthworms, along with their subcellular distribution, was meticulously analyzed. Additionally, a suite of biomarkers-including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and weight loss-were evaluated to assess the health status of the earthworms and the toxicological effects of the Cd and SMX mixture. Notably, the cotreatment with Cd and SMX resulted in a significantly higher weight loss in Eisenia fetida (41.25 %) compared to exposure to Cd alone (26.84 %). Moreover, the cotreatment group exhibited substantially higher concentrations of Cd in the total internal body, fraction C (cytosol), and fraction E (tissue fragments and cell membranes) in Eisenia fetida compared to Cd alone counterparts. The combined exposure also significantly elevated the SMX levels in the total body and fraction C compared with the SMX-only treated earthworms. Additionally, Eisenia fetida subjected to the combined treatment showed markedly increased activities of SOD, CAT, and MDA compared to those treated with Cd alone. The effect addition indices (EAIs), ranging from 1.00 to 2.23, unequivocally demonstrated a synergistic effect of the combined treatments. Interestingly, relocating the earthworms to clean soil did not mitigate the observed adverse effects. These findings underscore the increased risk posed by the Cd-SMX complex to terrestrial invertebrates in agricultural areas.

2.
CNS Neurosci Ther ; 30(5): e14778, 2024 May.
Article in English | MEDLINE | ID: mdl-38801174

ABSTRACT

AIMS: Synaptic vesicle protein 2A (SV2A) is a unique therapeutic target for pharmacoresistant epilepsy (PRE). As seizure-induced neuronal programmed death, parthanatos was rarely reported in PRE. Apoptosis-inducing factor (AIF), which has been implicated in parthanatos, shares a common cytoprotective function with SV2A. We aimed to investigate whether parthanatos participates in PRE and is mitigated by SV2A via AIF. METHODS: An intraperitoneal injection of lithium chloride-pilocarpine was used to establish an epileptic rat model, and phenytoin and phenobarbital sodium were utilized to select PRE and pharmacosensitive rats. The expression of SV2A was manipulated via lentivirus delivery into the hippocampus. Video surveillance was used to assess epileptic ethology. Biochemical tests were employed to test hippocampal tissues following a successful SV2A infection. Molecular dynamic calculations were used to simulate the interaction between SV2A and AIF. RESULTS: Parthanatos core index, PARP1, PAR, nuclear AIF and MIF, γ-H2AX, and TUNEL staining were all increased in PRE. SV2A is bound to AIF to form a stable complex, successfully inhibiting AIF and MIF nuclear translocation and parthanatos and consequently mitigating spontaneous recurrent seizures in PRE. Moreover, parthanatos deteriorated after the SV2A reduction. SIGNIFICANCE: SV2A protected hippocampal neurons and mitigated epileptic seizures by inhibiting parthanatos via binding to AIF in PRE.


Subject(s)
Apoptosis Inducing Factor , Disease Models, Animal , Drug Resistant Epilepsy , Membrane Glycoproteins , Nerve Tissue Proteins , Rats, Sprague-Dawley , Animals , Rats , Apoptosis Inducing Factor/metabolism , Male , Nerve Tissue Proteins/metabolism , Drug Resistant Epilepsy/metabolism , Drug Resistant Epilepsy/drug therapy , Membrane Glycoproteins/metabolism , Hippocampus/metabolism , Hippocampus/drug effects , Anticonvulsants/pharmacology
3.
Int J Pharm ; 657: 124189, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38701906

ABSTRACT

Amorphous solid dispersions (ASDs) represent an important approach for enhancing oral bioavailability for poorly water soluble compounds; however, assuring that these ASDs do not recrystallize to a significant extent during storage can be time-consuming. Therefore, various efforts have been undertaken to predict ASD crystallization levels with kinetic models. However, only limited success has been achieved due to limits on crystal content quantification methods and the complexity of crystallization kinetics. To increase the prediction accuracy, the accelerated stability assessment program (ASAP), employing isoconversion (time to hit a specification limit) and a modified Arrhenius approach, are employed here for predictive shelf-life modeling. In the current study, a model ASD was prepared by spray drying griseofulvin and HPMC-AS-LF. This ASD was stressed under a designed combinations of temperature, relative humidity and time with the conditions set to ensure stressing was carried out below the glass transition temperature (Tg) of the ASD. Crystal content quantification method by X-ray powder diffraction (XRPD) with sufficient sensitivity was developed and employed for stressed ASD. Crystallization modeling of the griseofulvin ASD using ASAPprime® demonstrated good agreement with long-term (40 °C/75 %RH) crystallinity levels and support the use of this type of accelerated stability studies for further improving ASD shelf-life prediction accuracy.


Subject(s)
Crystallization , Drug Stability , Griseofulvin , Griseofulvin/chemistry , Hypromellose Derivatives/chemistry , X-Ray Diffraction/methods , Solubility , Drug Compounding/methods , Chemistry, Pharmaceutical/methods , Temperature , Humidity
4.
Comp Biochem Physiol C Toxicol Pharmacol ; 283: 109941, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38810898

ABSTRACT

The chiral fungicide prothioconazole (PTZ) is extensively employed in agricultural practices, prompting serious concern due to its environmental impact. PTZ is prone to undergo metabolism, leading to the formation of chiral prothioconazole-desthio (dPTZ) in the environment. However, limited knowledge exists regarding its enantioselective behavior and toxicity towards invertebrate organisms in soil ecosystems. In this study, R-(-)- and S-(+)- PTZ enantiomers were individually synthesized, and their stereoselective toxicity effects on earthworms (E. foetida) were studied in artificial soil under environmentally relevant concentration exposures. The results showed a significant accumulation of dPTZ in earthworms, surpassing the levels of PTZ. Moreover, the concentration of S-(-)- dPTZ in earthworms was notably higher than that of R-(+)- dPTZ after exposure, reaching peak levels on day 14. Concurrently, oxidative stress induced by S-(+)- PTZ enantiomers in earthworms exhibited a substantial increase compared to R-(-)- enantiomers on day 14, indicating a higher ecological risk associated with the former in non-target organisms. Transcriptome analysis unveiled distinct impacts on earthworm physiology. S-(+)-PTZ exposure significantly affected energy metabolism, immune responses and digestive systems. In contrast, R-(-)-PTZ exposure influenced the synthesis of carbohydrates, proteins, and lipids. These insights contribute to understanding the complex interactions between PTZ enantiomers and soil-dwelling organisms, providing a scientific foundation for advancing the application of high efficiency, low toxicity PTZ monomer pesticides.

5.
Aging (Albany NY) ; 16(10): 8880-8897, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38761176

ABSTRACT

OBJECTIVE: This inquiry endeavors to delineate the influence of PDIA3 on tumor-associated macrophages within the realm of colorectal malignancies, whilst elucidating the intrinsic biochemical pathways. METHOD: Leveraging bioinformatics, we scrutinized the symbiosis between PDIA3, STAT3, and CD274. A xenograft model in immunodeficient murine served to assess PDIA3's impact on colorectal carcinogenesis. Further, Western blot analysis quantified the protein expression of PDIA3, p-STAT3, PD-1, XBP-1, assorted enzymes, and IL-6. Moreover, in vitro assays gauged SW480 cellular dynamics inclusive of migration, invasive potential, and proliferation. RESULTS: Bioinformatics exploration exposed PDIA3's elevated presence in diverse cancers, with a marked expression in colorectal cancer, as per TCGA and GEO repositories. Correlative studies showed PDIA3 positively aligning with STAT3 and CD274, the latter also associated with monocyte-derived macrophages. Comparative analysis of colorectal neoplasms and normal colon samples unveiled heightened levels of PDIA3 markers which, when overexpressed in SW480 cells, escalated tumorigenicity and oncogenic behaviors, with a noted decrease upon PD-1 monoclonal antibody intervention. CONCLUSIONS: PDIA3 augments the M2 polarization of tumor-associated macrophages via modulation of the STAT3/PD-1 cascade, thus invigorating the tumorous proliferation and dissemination in colorectal cancer. Such revelations position PDIA3 as an auspicious target for PD-1 blockade therapeutics, offering a promising foundation for rectifying colorectal carcinoma.


Subject(s)
Colorectal Neoplasms , Programmed Cell Death 1 Receptor , Protein Disulfide-Isomerases , STAT3 Transcription Factor , Signal Transduction , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/genetics , Humans , Animals , Mice , Protein Disulfide-Isomerases/metabolism , Protein Disulfide-Isomerases/genetics , Programmed Cell Death 1 Receptor/metabolism , Programmed Cell Death 1 Receptor/genetics , Cell Line, Tumor , Disease Progression , Tumor-Associated Macrophages/metabolism , Tumor-Associated Macrophages/immunology , Cell Proliferation , Macrophages/metabolism
6.
Sensors (Basel) ; 24(7)2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38610295

ABSTRACT

In recent years, hydroacoustic transducers made of PZT/epoxy composites have been extensively employed in underwater detection, communication, and recognition for their high energy conversion efficiency. Despite the ease with which these transducers can be formed into complex shapes, their lack of mechanical flexibility limits their versatility across various sizes of underwater vehicles. This study introduces a novel flexible piezoelectric composite hydroacoustic transducer (FPCHT) based on a 1-3 PZT-5A/silicone rubber composite and an island-bridge flexible electrode, which can break the limitations of existing hydroacoustic transducers that do not have flexibility. The finite element method is used to optimize the structural parameters of high-performance 1-3 FPC. A large-sized (187 mm × 47 mm × 5.12 mm) FPC is fabricated using an improved cutting-filling method and packaged into the FPCHT. Compared with the planar rigid PZT/epoxy composite hydroacoustic transducer (RPCHT) of the same size, the TVR (186.5 db) of the FPCHT has increased by about 7 dB, indicating that it has better acoustic radiation performance and electroacoustic conversion efficiency. Furthermore, its electroacoustic performance exhibits excellent stability under different bending states. Therefore, the FPCHT with high electroacoustic performance is an ideal substitute for the existing RPCHT and promotes the development of hydroacoustic transducers towards flexibility and portability.

7.
Signal Transduct Target Ther ; 9(1): 95, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38653979

ABSTRACT

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180-365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients' improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).


Subject(s)
Corneal Dystrophies, Hereditary , Cytochrome P450 Family 4 , Dependovirus , Genetic Therapy , Retinal Diseases , Humans , Male , Female , Middle Aged , Adult , Corneal Dystrophies, Hereditary/genetics , Corneal Dystrophies, Hereditary/therapy , Corneal Dystrophies, Hereditary/pathology , Dependovirus/genetics , Cytochrome P450 Family 4/genetics , Genetic Vectors/genetics , Visual Acuity
8.
Mol Neurobiol ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38676809

ABSTRACT

Secondary brain injury (SBI) is a noticeable contributor to the high mortality and morbidity rates associated with intracerebral hemorrhage (ICH), and effective treatment options remain limited. Cystatin C (CysC) emerges as a novel candidate for SBI intervention. The therapeutic effects and underlying mechanisms of CysC in mitigating SBI following ICH were explored in the current research. An in vivo ICH rat model was established by injecting autologous blood into the right caudate nucleus. Western blotting (WB) was utilized to assess the levels of CysC, cathepsin B (CTSB), and the NLRP3 inflammasome. Subsequently, the ICH rat model was treated with exogenous CysC supplementation or CysC knockdown plasmids. Various parameters, including Evans blue (EB) extravasation, brain water content, and neurological function in rats, were examined. RT-qPCR and WB were employed to determine the expression levels of CTSB and the NLRP3 inflammasome. The co-expression of CTSB, CysC, and NLRP3 inflammasome with GFAP, NeuN, and Iba1 was assessed through double-labeled immunofluorescence. The interaction between CysC and CTSB was investigated using double-labeled immunofluorescence and co-immunoprecipitation. The findings revealed an elevation of CysC expression level, particularly at 24 h after ICH. Exogenous CysC supplementation alleviated severe brain edema, neurological deficit scores, and EB extravasation induced by ICH. Conversely, CysC knockdown produced opposite effects. The expression levels of CTSB and the NLRP3 inflammasome were significantly risen following ICH, and exogenous CysC supplement attenuated their expression levels. Double-labeled immunofluorescence illustrated that CysC, CTSB, and the NLRP3 inflammasome were predominantly expressed in microglial cells, and the interaction between CysC and CTSB was evidenced. CysC exhibited potential in ameliorating SBI following ICH via effectively suppressing the activation of the NLRP3 inflammasome mediated by CTSB specifically in microglial cells. These findings underscore the prospective therapeutic efficacy of CysC in the treatment of ICH-induced complications.

9.
Dev Cell ; 59(11): 1396-1409.e5, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38569547

ABSTRACT

The ability of cells to perceive and respond to mechanical cues is essential for numerous biological activities. Emerging evidence indicates important contributions of organelles to cellular mechanosensitivity and mechanotransduction. However, whether and how the endoplasmic reticulum (ER) senses and reacts to mechanical forces remains elusive. To fill the knowledge gap, after developing a light-inducible ER-specific mechanostimulator (LIMER), we identify that mechanostimulation of ER elicits a transient, rapid efflux of Ca2+ from ER in monkey kidney COS-7 cells, which is dependent on the cation channels transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and polycystin-2 (PKD2) in an additive manner. This ER Ca2+ release can be repeatedly stimulated and tuned by varying the intensity and duration of force application. Moreover, ER-specific mechanostimulation inhibits ER-to-Golgi trafficking. Sustained mechanostimuli increase the levels of binding-immunoglobulin protein (BiP) expression and phosphorylated eIF2α, two markers for ER stress. Our results provide direct evidence for ER mechanosensitivity and tight mechanoregulation of ER functions, placing ER as an important player on the intricate map of cellular mechanotransduction.


Subject(s)
Calcium , Endoplasmic Reticulum , Mechanotransduction, Cellular , Optogenetics , TRPP Cation Channels , Animals , Endoplasmic Reticulum/metabolism , Chlorocebus aethiops , COS Cells , Optogenetics/methods , Calcium/metabolism , TRPP Cation Channels/metabolism , TRPP Cation Channels/genetics , TRPV Cation Channels/metabolism , TRPV Cation Channels/genetics , Golgi Apparatus/metabolism , Endoplasmic Reticulum Stress/physiology , Endoplasmic Reticulum Chaperone BiP/metabolism
10.
Phytomedicine ; 128: 155533, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38552433

ABSTRACT

BACKGROUND: Ferroptosis and mitochondria-mediated apoptosis are both involved in the pathogenesis of acute liver failure (ALF). Ferroptosis-produced reactive oxygen species (ROS) trigger the chain oxidation of polyunsaturated phospholipids and promote mitochondrial apoptosis. Dihydroquercetin (DHQ) also plays an important protective role against liver injury. PURPOSE: Here, we aimed to investigate the protective effects of DHQ on ALF. We also explored the underlying mechanism. METHODS: We established a Lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced ALF mouse model and tumor necrosis factor-α (TNF-α)/D-Gal-induced ALF LO2 cell model. 2',7'-Dichlorofluorescein diacetate (DCFH-DA) and Dihydroethidium (DHE) were used to detect total ROS levels. Lipid ROS was assessed using C11-BODIPY flow cytometry. Lipid peroxidative products levels were detected using MDA ELISA assay and 4-hydroxynonenal (4-HNE) immunohistochemistry. QRT-PCR and western blots were used to test mRNA and protein expression levels, respectively. Cell viability was evaluated with CCK8 assay, and apoptosis was analyzed using flow cytometry. RESULTS: DHQ treatment improved LPS/D-Gal-induced ALF, as well as TNF-α/D-Gal-induced reductions in LO2 viability and increased sirtuin 1 (SIRT1) expression. DHQ pretreatment also reduced the accumulation of ROS, reduced lipid peroxidation, elevated mitochondrial membrane potentials (ΔΨm), and decreased liver cell apoptosis both in vivo and in vitro. Additionally, the knockdown of SIRT1 and p53 activator (Tenovin-6) treatment reversed DHQ's inhibitory effects on ferroptosis and mitochondria-mediated apoptosis in vitro. DHQ enhanced p53 deacetylation by both up-regulating SIRT1 expression and directly bonding to SIRT1. We also found that Tenovin-6's stimulatory effects on ferroptosis and mitochondria-mediated apoptosis in the DHQ-treated LO2 ALF cell model were partially attenuated by overexpression of solute carrier family 7member 11 (SLC7A11), as well as by apoptotic protease activating factor 1 (Apaf-1) knockdown. CONCLUSION: Our results suggest that DHQ alleviated ALF by inhibiting both ferroptosis and mitochondria-mediated apoptosis by regulating the SIRT1/p53 axis. Thus, DHQ may serve as a novel therapy for ALF.


Subject(s)
Apoptosis , Ferroptosis , Liver Failure, Acute , Quercetin , Sirtuin 1 , Tumor Suppressor Protein p53 , Animals , Humans , Male , Mice , Apoptosis/drug effects , Cell Line , Disease Models, Animal , Ferroptosis/drug effects , Galactosamine , Lipid Peroxidation/drug effects , Lipopolysaccharides , Liver Failure, Acute/drug therapy , Liver Failure, Acute/chemically induced , Mice, Inbred C57BL , Mitochondria/drug effects , Mitochondria/metabolism , Quercetin/pharmacology , Quercetin/analogs & derivatives , Reactive Oxygen Species/metabolism , Sirtuin 1/metabolism , Tumor Necrosis Factor-alpha/metabolism , Tumor Suppressor Protein p53/metabolism
11.
Phys Rev Lett ; 132(7): 076903, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38427859

ABSTRACT

We report pump-probe measurements of a hydrogen molecule (H_{2}) in the tunnel junction of a scanning tunneling microscope coupled to ultrashort terahertz (THz) pulses. The coherent oscillation of the THz-induced dc tunneling current at a frequency of ∼0.5 THz fingerprints the absorption by H_{2} as a two-level system (TLS). Two components of the oscillatory signal are observed and point to both photon and field aspects of the THz pulses. A few loosely bound states with similar energies for the upper state of the TLS are evidenced by the coherent revival of oscillatory signal. Furthermore, the comparison of spectroscopic features of H_{2} with different tips provides an understanding of the TLS for H_{2}.

12.
J Hazard Mater ; 468: 133724, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38382336

ABSTRACT

In the present study, we pyrolyzed a waste tire at various temperatures under an N2 atmosphere and a water environment in an autoclave reactor to investigate the effect of water on tire degradation. The analysis involved a comparison of product distribution, char properties, oil composition, and the behavior of heteroatom elements (especially oxygen, nitrogen, and sulfur) under different atmospheres. Elemental analysis, functional-group identification, and chemical state analysis of sulfur were performed for chars. In addition, the chemical composition, elemental composition, and molecular weight of the produced oils were evaluated. The heavy fraction of oils, not detectable by gas chromatography-mass spectrometry (GC-MS), was analyzed through Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The findings revealed that high temperatures promoted oil cracking, resulting in the formation of light oils in both pyrolysis and hydrolysis processes. Compared to pyrolysis, hydrolysis generated a higher yield of low molecular-weight oil. Elevated hydrolysis temperatures promoted aromatization, yielding an oil with a low H/C ratio and a high double bond equivalent number. Consequently, the concentration of aromatics in the light fraction of oils generated from the hydrolysis process exceeded that in oils from the pyrolysis process. Temperature exhibited a limited impact on oil composition during the pyrolysis process. Hydrolysis promoted the release of heteroatom-containing compounds at low temperatures. During pyrolysis, nitrogen was gradually released from the solid phase, whereas nitrogen-containing compounds were released early during hydrolysis, with gas-phase nitrogen accounting for more than 50 wt% at 320 °C. A maximum D-limonene yield of 45.58% was obtained at 360 °C within 0 min of hydrolysis, with the potential conversion of D-limonene into aromatics at higher hydrolysis temperatures. These results contribute to the understanding of tire valorization via hydrolysis.

13.
Plant Commun ; 5(4): 100812, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38213028

ABSTRACT

The Green Revolution of the mid-20th century transformed agriculture worldwide and has resulted in environmental challenges. A new approach, the Second Green Revolution, seeks to enhance agricultural productivity while minimizing negative environmental impacts. Plant microbiomes play critical roles in plant growth and stress responses, and understanding plant-microbiome interactions is essential for developing sustainable agricultural practices that meet food security and safety challenges, which are among the United Nations Sustainable Development Goals. This review provides a comprehensive exploration of key deterministic processes crucial for developing microbiome management strategies, including the host effect, the facilitator effect, and microbe-microbe interactions. A hierarchical framework for plant microbiome modulation is proposed to bridge the gap between basic research and agricultural applications. This framework emphasizes three levels of modulation: single-strain, synthetic community, and in situ microbiome modulation. Overall, rational management of plant microbiomes has wide-ranging applications in agriculture and can potentially be a core technology for the Second Green Revolution.


Subject(s)
Microbiota , Plants , Agriculture/methods , Plant Development
14.
J Hazard Mater ; 465: 133354, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38154183

ABSTRACT

Whether eukaryotic organisms can evolve for higher heavy metal resistance in laboratory conditions remains unknown. In this study, we challenged a macrofungi, Pleurotus ostreatus, in a designed microbial evolution and growth arena (MEGA)-plate with an extreme Cd gradient. Within months, the wild-type strain developed 10 mutants, exhibiting a maximum three-fold increase in Cd tolerance and slower growth rates. Genomic sequencing and re-sequencing of the wild-type and ten mutant strains generated about 51 GB data, allowing a comprehensive comparative genomics analysis. As a result, a total of 2512 common single nucleotide polymorphisms, 70 inserts and deletes, 39 copy number variations and 21 structural variations were found in the 10 mutants. The mutant genes were primarily involved in substrate transport. In combination with transcriptome analysis, we discovered that the ten mutants had a distinct Cd-resistant mechanism compared to the wild-type strain. Genes involved in oxidation-reduction, ion transmembrane transport, and metal compartment/efflux are primarily responsible for the extreme Cd tolerance in the P. ostreatus mutants. Our findings contribute to the understanding of eukaryotic Cd resistance at the genome level and establish a foundation for developing bioremediation tools utilizing highly tolerant macrofungi.


Subject(s)
Cadmium , Metals, Heavy , DNA Copy Number Variations , Genomics , Gene Expression Profiling
15.
ACS Nano ; 17(22): 23144-23151, 2023 Nov 28.
Article in English | MEDLINE | ID: mdl-37955976

ABSTRACT

Pump-probe measurements by ultrashort THz pulses can be used to excite and follow the coherence dynamics in the time domain of single hydrogen molecules (H2) in the junction of a scanning tunneling microscope (STM). By tailoring the resonance frequency through the sample bias, we identified two spectral signatures of the interactions among multiple H2 molecules. First, the avoided level crossing featured by energy gaps ranging from 20 to 80 GHz was observed because of the level repulsion between two H2 molecules. Second, the tip can sense the signal of H2 outside the junction through the projective measurement on the H2 inside the junction, owing to the entangled states created through the interactions. A dipolar-type interaction was integrated into the tunneling two-level system model of H2, enabling accurate reproduction of the observed behaviors. Our results obtained by the quantum superposition microscope reveal the intricate quantum mechanical interplay among H2 molecules and additionally provide a 2D platform to investigate unresolved questions of amorphous materials.

16.
Adv Sci (Weinh) ; 10(35): e2303799, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37890465

ABSTRACT

Cardiac development involves large-scale rearrangements of the proteome. How the developing cardiac cells maintain the integrity of the proteome during the rapid lineage transition remains unclear. Here it is shown that proteotoxic stress visualized by the misfolded and/or aggregated proteins appears during early cardiac differentiation of human pluripotent stem cells and is resolved by activation of the PERK branch of unfolded protein response (UPR). PERK depletion increases misfolded and/or aggregated protein accumulation, leading to pluripotency exit defect and impaired mesendoderm specification of human pluripotent stem cells. Mechanistically, it is found that PERK safeguards mesendoderm specification through its conserved downstream effector ATF4, which subsequently activates a novel transcriptional target WARS1, to cope with the differentiation-induced proteotoxic stress. The results indicate that protein quality control represents a previously unrecognized core component of the cardiogenic regulatory network. Broadly, these findings provide a framework for understanding how UPR is integrated into the developmental program by activating the PERK-ATF4-WARS1 axis.


Subject(s)
Pluripotent Stem Cells , eIF-2 Kinase , Humans , eIF-2 Kinase/genetics , eIF-2 Kinase/metabolism , Pluripotent Stem Cells/metabolism , Proteome/metabolism , Proteostasis , Unfolded Protein Response
17.
Cell Mol Biol (Noisy-le-grand) ; 69(9): 130-135, 2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37807324

ABSTRACT

MicroRNAs (miRNAs) control liver diseases, but the role of microRNA-181a-5p in acute liver failure (ALF) is unclear. In this study, the ALF model was generated by injection of D-galactosamine (D-GalN) and lipopolysaccharide (LPS). The levels of miRNAs were assessed by microarray and qRT-PCR. The expression of caspase 3 was detected as the marker of cell apoptosis in ALF by immunohistochemistry and western blot. The targeting of microRNA-181a-5p on the high mobility group box 1 (HMGB1) was verified by dual luciferase assay. The impact of microRNA-181a-5p and HMGB1 was explored by flow cytometry. Results showed that microRNA-181a-5p was significantly down-regulated by D-GalN/LPS in vivo and in vitro, while the level of HMGB1 was up-regulated after the challenge. Furthermore, microRNA-181a-5p overexpression attenuated cell apoptosis in D-GalN/TNF-treated BNLCL2 cells. MicroRNA-181a-5p could directly target HMGB1 mRNA and repress its expressions, in further HMGB1 is involved in microRNA-181a-5p effect on cell apoptosis of ALF. In conclusion, these findings demonstrate that microRNA-181a-5p regulates hepatocyte apoptosis via HMGB1 in the development of ALF, which may provide potential therapeutic targets for ALF. However, the precise underlying mechanism that connects microRNA-181a-5p and HMGB1 remains to be explored.


Subject(s)
HMGB1 Protein , Liver Failure, Acute , MicroRNAs , Animals , Mice , Apoptosis/genetics , Galactosamine , HMGB1 Protein/genetics , HMGB1 Protein/metabolism , Lipopolysaccharides , Liver Failure, Acute/genetics , Liver Failure, Acute/metabolism , Microarray Analysis , MicroRNAs/genetics , MicroRNAs/metabolism
19.
RSC Adv ; 13(40): 28097-28103, 2023 Sep 18.
Article in English | MEDLINE | ID: mdl-37746342

ABSTRACT

Defects formed by halide ion escape and wettability of the perovskite absorber are essential limiting factors in achieving high performance of perovskite solar cells (PSCs). Herein, a series of ionic organic modulators are designed to contain halide anions to prevent defect formation and improve the surface tension of the perovskite absorber. It was found that the surface modulator containing Br anions is the most effective one due to its capability in bonding with the undercoordinated Pb2+ ions to reduce charge recombination. Moreover, this surface modulator effectively creates a suitable energy level between the perovskite and hole transport layer to promote carrier transfer. In addition, the surface modulator forms a chemisorbed capping layer on the perovskite surface to improve its hydrophobicity. As a result, the efficiency of PSCs based on surface modulators containing Br anion enhances to 23.32% from 21.08% of the control device. The efficiency of unencapsulated PSCs with a surface modulator retains 75.42% of its initial value under about 35% humidity stored in the air for 28 days, while the control device only maintained 44.49% of its initial efficiency. The excellent stability originates from the hydrophobic perovskite surface after capping the surface modulator.

20.
BMC Genomics ; 24(1): 493, 2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37641002

ABSTRACT

BACKGROUND: Chromatin-associated phase separation proteins establish various biomolecular condensates via liquid-liquid phase separation (LLPS), which regulates vital biological processes spatially and temporally. However, the widely used methods to characterize phase separation proteins are still based on low-throughput experiments, which consume time and could not be used to explore protein LLPS properties in bulk. RESULTS: By combining gradient 1,6-hexanediol (1,6-HD) elution and quantitative proteomics, we developed chromatin enriching hexanediol separation coupled with liquid chromatography-mass spectrometry (CHS-MS) to explore the LLPS properties of different chromatin-associated proteins (CAPs). First, we found that CAPs were enriched more effectively in the 1,6-HD treatment group than in the isotonic solution treatment group. Further analysis showed that the 1,6-HD treatment group could effectively enrich CAPs prone to LLPS. Finally, we compared the representative proteins eluted by different gradients of 1,6-HD and found that the representative proteins of the 2% 1,6-HD treatment group had the highest percentage of IDRs and LCDs, whereas the 10% 1,6-HD treatment group had the opposite trend. CONCLUSION: This study provides a convenient high-throughput experimental method called CHS-MS. This method can efficiently enrich proteins prone to LLPS and can be extended to explore LLPS properties of CAPs in different biological systems.


Subject(s)
Chromatin , Corneal Dystrophies, Hereditary , Humans , Chromatography, Liquid , Glycols
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