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1.
Front Vet Sci ; 11: 1389738, 2024.
Article in English | MEDLINE | ID: mdl-38974336

ABSTRACT

The experiment aimed to evaluate the effects of different ratios of Clostridium autoethanogenum protein (CAP) used in the diets on the growth performance, muscle quality, serum indexes, and mTOR pathway of white feather broilers. Four hundred and eighty 1-day-old Arbor Acres (AA) broilers, comprising equal numbers of males and females, were randomly assigned to one of four treatments, and each treatment consisted of 12 replicates of 10 birds. Four diets were formulated based on isoenergetic and isonitrogenous principles. The control group (CAP 0) did not receive any CAP, while the experimental groups received 2% (CAP 2), 3% (CAP 3), and 4% (CAP 4) of CAP for six weeks. Compared with the CAP0, (1) The feed conversion ratio (FCR) was lower (p < 0.05), and the leg muscle yield was higher (p < 0.05) in the CAP3 and CAP4; (2) The serum levels of TP, ALB, T-AOC, and SOD were improved in the CAP3 (p < 0.05); (3) The expression of Lipin-1 gene was down-regulated and AMPKɑ2, Akt, and 4E-BP1 genes were up-regulated in the experiment group (p < 0.05); (4) The inclusion of 3% CAP in the diet increased the levels of 4E-BP1, S6K1, Akt, and AMPKɑ2 phosphorylation by modulating the mTOR signaling pathway (p < 0.05). In conclusion, broiler diets containing 3% CAP can activate the mTOR signaling pathway to promote muscle synthesis and improve growth performance.

2.
Environ Manage ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867057

ABSTRACT

The development of renewable energy has become an important means for the world to cope with climate change, ensure energy security, and protect the ecological environment. Using the panel data of 30 provinces in China from 2013 to 2021, this study used the mediating effect model and the spatial Durbin model (SDM) to explore the mechanism and spatial effects of renewable energy development on China's regional carbon emission reduction. The results show that: (1) Renewable energy development can help to reduce carbon emission intensity. (2) The results of mechanism analysis show that renewable energy development reduces carbon intensity by improving energy structure, promoting industrial structure optimization, and industrial structure upgrading. (3) The development of renewable energy can not only reduce the local carbon intensity but also have a positive spillover effect on the carbon intensity of neighboring regions. (4) Further analysis shows that the long-term effect of renewable energy development on carbon emissions is greater than the short-term effect. At the same time, the heterogeneity analysis shows that compared with the Yellow River basin, the development of renewable energy has a significant carbon emission reduction effect in the Yangtze River Economic Belt region. Energy-rich areas fall into the "resource curse", which makes the carbon emission reduction effect of renewable energy development not significant. This paper has certain reference significance for promoting reasonable decomposition between regions and formulating renewable energy development policies.

3.
Pharmaceuticals (Basel) ; 17(6)2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38931471

ABSTRACT

Purpose: Adhesion between calcium oxalate crystals and renal tubular epithelial cells is a vital cause of renal stone formation; however, the drugs that inhibit crystal adhesion and the mechanism of inhibition have yet to be explored. Methods: The cell injury model was constructed using nano-COM crystals, and changes in oxidative stress levels, endoplasmic reticulum (ER) stress levels, downstream p38 MAPK protein expression, apoptosis, adhesion protein osteopontin expression, and cell-crystal adhesion were examined in the presence of Laminarin polysaccharide (DLP) and sulfated DLP (SDLP) under protected and unprotected conditions. Results: Both DLP and SDLP inhibited nano-COM damage to human kidney proximal tubular epithelial cell (HK-2), increased cell viability, decreased ROS levels, reduced the opening of mitochondrial membrane permeability transition pore, markedly reduced ER Ca2+ ion concentration and adhesion molecule OPN expression, down-regulated the expression of ER stress signature proteins including CHOP, Caspase 12, and p38 MAPK, and decreased the apoptosis rate of cells. SDLP has a better protective effect on cells than DLP. Conclusions: SDLP protects HK-2 cells from nano-COM crystal-induced apoptosis by reducing oxidative and ER stress levels and their downstream factors, thereby reducing crystal-cell adhesion interactions and the risks of kidney stone formation.

4.
Int J Prosthodont ; 0(0): 1-22, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38848506

ABSTRACT

OBJECTIVE: To investigate the effect of digital scanning combined with reverse engineering technology in the demonstration of full crown tooth preparation. METHODS: Thirty-one students were randomly divided into the two groups. The students in the control group carried out traditional demonstration by the use of eye-measurement methods. The students in the experimental group carried out improved demonstration by the use of digital intraoral scan with 3D measurement data. The students in both groups were provided with two resin teeth to conduct full crown tooth preparation on head model dental simulators. The teeth prepared before and after demonstration were scored by Chinese Stomatological Association Group Standards, with a total score of 100 points. Analysis of covariance was performed to comparatively analyze the scores related to the tooth surfaces, and convergence angle between two groups. RESULTS: Analysis of two prepared teeth (tooth #11 and #16) in two groups showed that there was a statistical significant difference in the mean score between the control group and experimental group (tooth #11, P = 0.0039) (tooth #16, P = 0.0120).The demonstration of the tooth #16 showed that there were statistical significant differences in the scores related to buccolingual surface (P = 0.0205) and proximal surface (P = 0.0023) between the control group and experimental group; There was a statistical significant difference in the score related to the convergence angle of buccolingual surface between the control group and experimental group (P = 0.0265). CONCLUSION: The digital methods can effectively improve the quality of tooth preparations and has a pedagogical advantage for posterior teeth, which present greater operational challenges.

5.
PLoS One ; 19(6): e0304852, 2024.
Article in English | MEDLINE | ID: mdl-38917120

ABSTRACT

BACKGROUND: Known for its strong diuretic properties, the perennial herbaceous plant Orthosiphon stamineus Benth. is believed to preserve the kidney disease. This study compared the boiling water extract with powdered Orthosiphon stamineus Benth. and used a highly sensitive and high resolution UHPLC-Q-Exactive-Orbitrap-HRMS technology to evaluate its chemical composition. RESULTS: Furthermore, by monitoring the absorption of prototype components in rat plasma following oral treatment, the beneficial ingredients of the Orthosiphon stamineus Benth. decoction was discovered. Approximately 92 substances underwent a preliminary identification utilizing relevant databases, relevant literature, and reference standards. As the compound differences between the powdered Orthosiphon stamineus Benth. and its water decoction were analyzed, it was found that boiling produced additional compounds, 48 of which were new. 45 blood absorption prototype components and 49 OS metabolites were discovered from rat serum, and a kidney tissue homogenate revealed an additional 28 prototype components. Early differences in the distribution of ferulic acid, cis 4 coumaric acid, and rosmarinic acid were shown using spatial metabolomics. It was elucidated that the renal cortex region is where rosmarinic acid largely acts, offering a theoretical foundation for further studies on the application of OS in the prevention and treatment of illness as well as the preservation of kidney function. SIGNIFICANCE: In this study, UHPLC-Q Exactive Orbitrap-HRMS was employed to discern OS's chemical composition, and a rapid, sensitive, and broad-coverage AFADESI-MSI method was developed to visualize the spatial distribution of compounds in tissues.


Subject(s)
Orthosiphon , Plant Extracts , Orthosiphon/chemistry , Animals , Chromatography, High Pressure Liquid/methods , Rats , Plant Extracts/chemistry , Male , Rats, Sprague-Dawley , Mass Spectrometry/methods , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Kidney/metabolism
6.
Nat Commun ; 15(1): 5332, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38909052

ABSTRACT

Veratramine and cyclopamine, two of the most representative members of the isosteroidal alkaloids, are valuable molecules in agricultural and medicinal chemistry. While plant extraction of these compounds suffers from uncertain supply, efficient chemical synthesis approaches are in high demand. Here, we present concise, divergent, and scalable syntheses of veratramine and cyclopamine with 11% and 6.2% overall yield, respectively, from inexpensive dehydro-epi-androsterone. Our synthesis readily provides gram quantities of both target natural products by utilizing a biomimetic rearrangement to form the C-nor-D-homo steroid core and a stereoselective reductive coupling/(bis-)cyclization sequence to establish the (E)/F-ring moiety.


Subject(s)
Veratrum Alkaloids , Veratrum Alkaloids/chemical synthesis , Veratrum Alkaloids/chemistry , Stereoisomerism , Cyclization , Biological Products/chemical synthesis , Biological Products/chemistry , Molecular Structure
7.
BMC Endocr Disord ; 24(1): 81, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38890674

ABSTRACT

PURPOSE: Previous studies have suggested that obesity defined by body mass index(BMI) is a protective factor for bone mineral density(BMD), but have overlooked the potential influence of different types of obesity. This study aims to evaluate the correlation between abdominal obesity index A Body Shape Index(ABSI) and adolescent bone density, and analyze the relationship between abdominal obesity and bone metabolism. METHODS: A total of 1557 adolescent participants were included in NHANES from 2007 to 2018. Calculate the ABSI using a specific formula that takes into account waist circumference and BMI. A weighted multiple linear regression model is used to evaluate the linear correlation between ABSI and BMD. Forest plots are used to analyze the correlations between subgroups, and cubic splines are limited to evaluate the nonlinear correlations and saturation effects between ABSI and BMD. RESULTS: After adjusting for confounding factors, there was a significant linear correlation (P < 0.01) between ABSI and femoral BMD, both as a continuous variable and an ordered categorical variable. The restrictive cubic spline curve indicates a significant nonlinear correlation and saturation effect between adolescent ABSI and BMD. CONCLUSION: Research has shown a significant negative correlation between ABSI and BMD at the four detection sites of the femur, and this correlation may vary slightly due to age, race, family income, and different detection sites. The research results indicate that compared to overall body weight, fat distribution and content may be more closely related to bone metabolism.


Subject(s)
Body Mass Index , Bone Density , Bone Development , Nutrition Surveys , Obesity, Abdominal , Humans , Adolescent , Obesity, Abdominal/complications , Male , Female , Bone Development/physiology , Cross-Sectional Studies , Child , Waist Circumference , Prognosis
8.
Hortic Res ; 11(6): uhae110, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38898960

ABSTRACT

Flowers and fruits are the reproductive organs in plants and play essential roles in natural beauty and the human diet. CLAVATA (CLV) signaling has been well characterized as regulating floral organ development by modulating shoot apical meristem (SAM) size; however, the signaling molecules downstream of the CLV pathway remain largely unknown in crops. Here, we found that functional disruption of CsCLV3 peptide and its receptor CsCLV1 both resulted in flowers with extra organs and stumpy fruits in cucumber. A heterotrimeric G protein α-subunit (CsGPA1) was shown to interact with CsCLV1. Csgpa1 mutant plants derived from gene editing displayed significantly increased floral organ numbers and shorter and wider fruits, a phenotype resembling that of Csclv mutants in cucumber. Moreover, the SAM size was enlarged and the longitudinal cell size of fruit was decreased in Csgpa1 mutants. The expression of the classical stem cell regulator WUSCHEL (WUS) was elevated in the SAM, while the expression of the fruit length stimulator CRABS CLAW (CRC) was reduced in the fruit of Csgpa1 mutants. Therefore, the Gα-subunit CsGPA1 protein interacts with CsCLV1 to inhibit floral organ numbers but promote fruit elongation, via repressing CsWUS expression and activating CsCRC transcription in cucumber. Our findings identified a new player in the CLV signaling pathway during flower and fruit development in dicots, increasing the number of target genes for precise manipulation of fruit shape during crop breeding.

9.
J Med Virol ; 96(6): e29757, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38899432

ABSTRACT

No effective treatments can ameliorate symptoms of long COVID patients. Our study assessed the safety and efficacy of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) in the treatment of long COVID patients. Ten long COVID patients were enrolled and received intravenous infusions of UC-MSCs on Days 0, 7, and 14. Adverse events and clinical symptoms were recorded, and chest-high-resolution CT (HRCT) images and laboratory parameters were analyzed. During UC-MSCs treatment and follow-up, we did not observe serious adverse events, the symptoms of long COVID patients were significantly relieved in a short time, especially sleep difficulty, depression or anxiety, memory issues, and so forth, and the lung lesions were also repaired. The routine laboratory parameters did not exhibit any significant abnormalities following UC-MSCs transplantation (UMSCT). The proportion of regulatory T cells gradually increased, but it was not statistically significant until 12 months. The proportion of naive B cells was elevated, while memory B cells, class-switched B-cells, and nonswitched B-cells decreased at 1 month after infusion. Additionally, we observed a transient elevation in circulating interleukin (IL)-6 after UMSCT, while tumor necrosis factor (TNF)-α, IL-17A, and IL-10 showed no significant changes. The levels of circulating immunoglobulin (Ig) M increased significantly at month 2, while IgA increased significantly at month 6. Furthermore, the SARS-CoV-2 IgG levels remained consistently high in all patients at Month 6, and there was no significant decrease during the subsequent 12-month follow-up. UMSCT was safe and tolerable in long COVID patients. It showed potential in alleviating long COVID symptoms and improving interstitial lung lesions.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Umbilical Cord , Humans , COVID-19/therapy , COVID-19/immunology , Mesenchymal Stem Cell Transplantation/methods , Male , Female , Middle Aged , Umbilical Cord/cytology , Mesenchymal Stem Cells , Aged , Treatment Outcome , Adult , SARS-CoV-2 , T-Lymphocytes, Regulatory/immunology , B-Lymphocytes/immunology , Interleukin-6/blood
10.
Res Sq ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38826349

ABSTRACT

The reversal of ubiquitination induced by members of the SidE effector family of Legionella pneumophila produces phosphoribosyl ubiquitin (PR-Ub) that is potentially detrimental to host cells. Here we show that the effector LnaB functions to transfer the AMP moiety from ATP to the phosphoryl moiety of PR-Ub to convert it into ADP-ribosylated ubiquitin (ADPR-Ub), which is further processed to ADP-ribose and functional ubiquitin by the (ADP-ribosyl)hydrolase MavL, thus maintaining ubiquitin homeostasis in infected cells. Upon being activated by Actin, LnaB also undergoes self-AMPylation on tyrosine residues. The activity of LnaB requires a motif consisting of Ser, His and Glu (S-HxxxE) present in a large family of toxins from diverse bacterial pathogens. Our study not only reveals intricate mechanisms for a pathogen to maintain ubiquitin homeostasis but also identifies a new family of enzymes capable of protein AMPylation, suggesting that this posttranslational modification is widely used in signaling during host-pathogen interactions.

11.
Article in English | MEDLINE | ID: mdl-38912570

ABSTRACT

INTRODUCTION: Osteoarthritis (OA) is a prevailing degenerative disease in elderly population and can lead to severe joint dysfunction. Studies have revealed various pharmacological activities of diosmetin, including the anti-OA efficacy. The present study further investigated its effect on interleukin (IL)-1ß-induced OA in chondrocytes. MATERIAL AND METHODS: Primary chondrocytes were isolated from young mice, stimulated with IL-1ß (10 ng/mL), and pretreated with diosmetin (10 and 20 µM) to conduct the in vitro assays. CCK-8 assay assessed the cytotoxicity of diosmetin whereas the levels of inflammatory factors (PGE2, nitrite, TNF-α, and IL-6) in homogenized cells were evaluated by ELISA. The levels of inflammatory cytokines, content of extracellular matrix (ECM), and signaling-related proteins (Nrf2, HO-1, and NF-κB p65) were assessed by western blotting. Expression of collagen II, p65, and Nrf2 in the chondrocytes was confirmed by immunofluorescence staining. The chondrocytes treated with IL-1ß and diosmetin were transfected with Nrf2 knockdown plasmid (si-Nrf2) to investigate the role of Nrf2. In vivo OA mouse model was induced by surgically destabilizing the medial meniscus (DMM). Safranin O staining was conducted to assess the OA severity in the knee-joint tissue. RESULTS: Diosmetin suppressed the expression of iNOS, COX-2, PGE2, nitrite, TNF-α, IL-6, MMP-13, and ADAMTS-5 induced by IL-1ß in chondrocytes. The expression of p-p65, p-IκBα, and nuclear p65 was decreased whereas that of Nrf2 and HO-1 increased by diosmetin treatment in IL-1ß-treated chondrocytes. Nrf2 knockdown by siRNA reversed the inhibitory effect of diosmetin on IL-1ß-induced degradation of ECM proteins and inflammatory factors in cultured chondrocytes. In the DMM-induced model of OA, diosmetin alleviated cartilage degeneration and decreased the Osteoarthritis Research Society International score. C: ONCLUSIONS: Diosmetin ameliorates expression of inflammation biomarkers and ECM macromolecules degradation in cultured murine chondrocytes via inactivation of NF-κB signaling by activating Nrf2/HO-1 signaling pathway.

12.
Bioprocess Biosyst Eng ; 47(7): 1017-1026, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38740635

ABSTRACT

The microalgae industry shows a promising future in the production of high-value products such as pigments, phycoerythrin, polyunsaturated fatty acids, and polysaccharides. It was found that polysaccharides have high biomedical value (such as antiviral, antibacterial, antitumor, antioxidative) and industrial application prospects (such as antioxidants). This study aimed to improve the polysaccharides accumulation of Porphyridium purpureum CoE1, which was effectuated by inorganic salt starvation strategy whilst supplying rich carbon dioxide. At a culturing temperature of 25 °C, the highest polysaccharide content (2.89 g/L) was achieved in 50% artificial seawater on the 12th day. This accounted for approximately 37.29% of the dry biomass, signifying a 25.3% increase in polysaccharide production compared to the culture in 100% artificial seawater. Subsequently, separation, purification and characterization of polysaccharides produced were conducted. Furthermore, the assessment of CO2 fixation capacity during the cultivation of P. purpureum CoE1 was conducted in a 10 L photobioreactor. This indicated that the strain exhibited an excellent CO2 fixation capacity of 1.66 g CO2/g biomass/d. This study proposed an efficient and feasible approach that not only increasing the yield of polysaccharides by P. purpureum CoE1, but also fixing CO2 with a high rate, which showed great potential in the microalgae industry and Bio-Energy with Carbon Capture and Storage.


Subject(s)
Carbon Dioxide , Polysaccharides , Porphyridium , Porphyridium/metabolism , Porphyridium/growth & development , Polysaccharides/metabolism , Carbon Dioxide/metabolism , Biomass , Microalgae/metabolism , Microalgae/growth & development , Photobioreactors
13.
ISA Trans ; 150: 322-337, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38796392

ABSTRACT

The relay feedback auto-tuning method, which was an early commercialized approach, has maintained its popularity due to its simplicity and robustness. However, the classical proportional integral derivative (PID) controller auto-tuning method often results in unacceptable overshoot, especially for integrating and higher-order processes. By integrating the TID controller with the relay feedback technique, we significantly enhance dynamic control performance without relying on prior knowledge of the system. However, the direct application of the classical auto-tuning method to the TID controller encounters challenges due to the additional fractional-order transfer function s-1n. Therefore, we have developed a fractional-order Ziegler-Nichols (FOZ-N) approach, specifically designed to adjust the parameters of the TID controller. The proposed FOZ-N method is fast, simple, and capable of achieving the desired performance. In contrast to the previous Ziegler-Nichols tuning method, the TID controller parameters Kt and Ki are determined to shift the critical point (-1/Ku,j0) to the FOZ-N point (-0.5,-j0.7) on the Nyquist curve, ensuring system robustness and dynamic performance. The impact of the fractional order parameter s-1n and ratio r is explored through time-domain analysis, where these parameters are determined to ensure optimal dynamic performance. Additionally, we provide a detailed tuning procedure along with a helpful example. To demonstrate the advantages of the proposed auto-tuning TID controller over the Ziegler-Nichols PID controller, Optimal PID controller, simple internal model control (SIMC) PID controller, and Ziegler-Nichols FOPID controller, we present a simulation illustration involving multiple different systems. To validate the practical outcomes of this paper, we present experimental results on the temperature control of a Peltier cell.

14.
Sci Data ; 11(1): 488, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38734729

ABSTRACT

Domesticated herbivores are an important agricultural resource that play a critical role in global food security, particularly as they can adapt to varied environments, including marginal lands. An understanding of the molecular basis of their biology would contribute to better management and sustainable production. Thus, we conducted transcriptome sequencing of 100 to 105 tissues from two females of each of seven species of herbivore (cattle, sheep, goats, sika deer, horses, donkeys, and rabbits) including two breeds of sheep. The quality of raw and trimmed reads was assessed in terms of base quality, GC content, duplication sequence rate, overrepresented k-mers, and quality score distribution with FastQC. The high-quality filtered RNA-seq raw reads were deposited in a public database which provides approximately 54 billion high-quality paired-end sequencing reads in total, with an average mapping rate of ~93.92%. Transcriptome databases represent valuable resources that can be used to study patterns of gene expression, and pathways that are related to key biological processes, including important economic traits in herbivores.


Subject(s)
Herbivory , Transcriptome , Animals , Cattle/genetics , Female , Rabbits/genetics , Databases, Genetic , Deer/genetics , Equidae/genetics , Goats/genetics , Horses/genetics , Sheep/genetics
15.
J Robot Surg ; 18(1): 219, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771389

ABSTRACT

An experimental validation of a robotic system for radioactive iodine-125 seed implantation (RISI) in tumor treatment was conducted using customized phantom models and animal models simulating liver and lung lesions. The robotic system, consisting of planning, navigation, and implantation modules, was employed to implant dummy radioactive seeds into the models. Fiducial markers were used for target localization. In phantom experiments across 40 cases, the mean errors between planned and actual seed positions were 0.98 ± 1.05 mm, 1.14 ± 0.62 mm, and 0.90 ± 1.05 mm in the x, y, and z directions, respectively. The x, y, and z directions correspond to the left-right, anterior-posterior, and superior-inferior anatomical planes. Silicone phantoms exhibiting significantly smaller x-axis errors compared to liver and lung phantoms (p < 0.05). Template assistance significantly reduced errors in all axes (p < 0.05). No significant dosimetric deviations were observed in parameters such as D90, V100, and V150 between plans and post-implant doses (p > 0.05). In animal experiments across 23 liver and lung cases, the mean implantation errors were 1.28 ± 0.77 mm, 1.66 ± 0.69 mm, and 1.86 ± 0.93 mm in the x, y, and z directions, slightly higher than in phantoms (p < 0.05), with no significant differences between liver and lung models. The dosimetric results closely matched planned values, confirming the accuracy of the robotic system for RISI, offering new possibilities in clinical tumor treatment.


Subject(s)
Iodine Radioisotopes , Lung Neoplasms , Phantoms, Imaging , Robotic Surgical Procedures , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/instrumentation , Iodine Radioisotopes/therapeutic use , Animals , Lung Neoplasms/radiotherapy , Brachytherapy/methods , Brachytherapy/instrumentation , Liver Neoplasms/radiotherapy , Humans , Fiducial Markers
16.
Chem Biodivers ; : e202400817, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775105

ABSTRACT

Four undescribed sesquiterpenes, atramacrolodes A-D (1-4), along with six known compounds 5-10 were isolated from the rhizome of Atractylodes macrocephala. Compound 3 possessed a new skeleton based on an unprecedented carton-carton connection. Their structures were determined by UV, IR, HRESIMS, NMR spectra, 13C NMR calculation with DP4+ analysis, and the comparison of experimental and calculated ECD spectra. Compounds 5 and 8 showed protective effects against paracetamol-induced liver cell injury.

17.
PLoS Pathog ; 20(5): e1011783, 2024 May.
Article in English | MEDLINE | ID: mdl-38739652

ABSTRACT

Legionella pneumophila strains harboring wild-type rpsL such as Lp02rpsLWT cannot replicate in mouse bone marrow-derived macrophages (BMDMs) due to induction of extensive lysosome damage and apoptosis. The bacterial factor directly responsible for inducing such cell death and the host factor involved in initiating the signaling cascade that leads to lysosome damage remain unknown. Similarly, host factors that may alleviate cell death induced by these bacterial strains have not yet been investigated. Using a genome-wide CRISPR/Cas9 screening, we identified Hmg20a and Nol9 as host factors important for restricting strain Lp02rpsLWT in BMDMs. Depletion of Hmg20a protects macrophages from infection-induced lysosomal damage and apoptosis, allowing productive bacterial replication. The restriction imposed by Hmg20a was mediated by repressing the expression of several endo-lysosomal proteins, including the small GTPase Rab7. We found that SUMOylated Rab7 is recruited to the bacterial phagosome via SulF, a Dot/Icm effector that harbors a SUMO-interacting motif (SIM). Moreover, overexpression of Rab7 rescues intracellular growth of strain Lp02rpsLWT in BMDMs. Our results establish that L. pneumophila exploits the lysosomal network for the biogenesis of its phagosome in BMDMs.


Subject(s)
Legionella pneumophila , Lysosomes , Macrophages , Phagosomes , rab GTP-Binding Proteins , rab7 GTP-Binding Proteins , Legionella pneumophila/metabolism , Legionella pneumophila/genetics , Animals , rab GTP-Binding Proteins/metabolism , Mice , Phagosomes/metabolism , Phagosomes/microbiology , Lysosomes/metabolism , Lysosomes/microbiology , Macrophages/microbiology , Macrophages/metabolism , Legionnaires' Disease/metabolism , Legionnaires' Disease/microbiology , Sumoylation , Mice, Inbred C57BL , Endosomes/metabolism , Endosomes/microbiology
18.
Nat Commun ; 15(1): 3890, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719850

ABSTRACT

Shigella flexneri is a Gram-negative bacterium causing severe bloody dysentery. Its pathogenesis is largely dictated by a plasmid-encoded type III secretion system (T3SS) and its associated effectors. Among these, the effector OspG has been shown to bind to the ubiquitin conjugation machinery (E2~Ub) to activate its kinase activity. However, the cellular targets of OspG remain elusive despite years of extensive efforts. Here we show by unbiased phosphoproteomics that a major target of OspG is CAND1, a regulatory protein controlling the assembly of cullin-RING ubiquitin ligases (CRLs). CAND1 phosphorylation weakens its interaction with cullins, which is expected to impact a large panel of CRL E3s. Indeed, global ubiquitome profiling reveals marked changes in the ubiquitination landscape when OspG is introduced. Notably, OspG promotes ubiquitination of a class of cytoskeletal proteins called septins, thereby inhibiting formation of cage-like structures encircling cytosolic bacteria. Overall, we demonstrate that pathogens have evolved an elaborate strategy to modulate host ubiquitin signaling to evade septin-cage entrapment.


Subject(s)
Bacterial Proteins , Septins , Shigella flexneri , Signal Transduction , Ubiquitin , Ubiquitination , Shigella flexneri/metabolism , Shigella flexneri/pathogenicity , Septins/metabolism , Septins/genetics , Humans , Ubiquitin/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Phosphorylation , Host-Pathogen Interactions , HeLa Cells , Cullin Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , HEK293 Cells , Dysentery, Bacillary/microbiology , Dysentery, Bacillary/metabolism
19.
J Am Chem Soc ; 146(20): 14036-14047, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38725301

ABSTRACT

The use of nickel-rich layered materials as cathodes can boost the energy density of lithium batteries. However, developing a safe and long-term stable nickel-rich layered cathode is challenging primarily due to the release of lattice oxygen from the cathode during cycling, especially at high voltages, which will cause a series of adverse effects, leading to battery failure and thermal runaway. Surface coating is often considered effective in capturing active oxygen species; however, its process is rather complicated, and it is difficult to maintain intact on the cathode with large volume changes during cycling. Here, we propose an in situ construction of a multifunctional cathode/electrolyte interphase (CEI), which is easy to prepare, repairable, and, most importantly, capable of continuously capturing active oxygen species during the entire life span. This unique protective mechanism notably improves the cycling stability of Li||LiNi0.8Co0.1Mn0.1O2 (NCM811) cells at rigorous working conditions, including ultrahigh voltage (4.8 V), high temperature (60 °C), and fast charging (10 C). An industrial 1 A h graphite||NCM811 pouch cell achieved stable operation of 600 cycles with a capacity retention of 79.6% at 4.4 V, exhibiting great potential for practical use. This work provides insightful guidance for constructing a multifunctional CEI to bypass limitations associated with high-voltage operations of nickel-rich layered cathodes.

20.
Adv Mater ; 36(27): e2402325, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38631673

ABSTRACT

Perovskite quantum dot-based light-emitting diodes (QLEDs) have been considered a promising display technology due to their wide color gamut for authentic color expression. Currently, the external quantum efficiency (EQE) for state-of-the-art blue perovskite QLEDs is about 15%, which still lags behind its green and red counterparts (>25%) and blue film-based LEDs. Here, blue perovskite QLEDs that achieve an EQE of 23.5% at 490 nm is presented, to the best knowledge, which is the highest value reported among blue perovskite-based LED fields. This impressive efficiency is achieved through a combination of quantum dot (QD) passivation and optimal device design. First, blue mixed halide perovskite CsPbCl3- xBrx QDs passivated by trifluoroacetate exhibit excellent exciton recombination behavior with a photoluminescence quantum yield of 84% due to reducing uncoordinated Pb surface defects. Furthermore, the device is designed by introducing a mixed hole-transport layer (M-HTL) to increase hole injection and transportation capacity and improve carrier balance. It is further found that M-HTL can decrease carrier leakage and increase radiative recombination in the device, evidenced by the visual electroluminescence spectrum at 2.0 V. The work breaks through the EQE gap of 20% for blue perovskite-based QLEDs and significantly promotes their commercialization process.

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