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1.
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.

2.
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
3.
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.

4.
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
5.
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.

6.
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
7.
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.

8.
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
9.
ISA Trans ; 2024 May 09.
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.

10.
ACS Omega ; 9(12): 14187-14197, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38559977

ABSTRACT

In this work, a novel polydopamine/reduced graphene oxide (PDA/rGO) nanofiltration membrane was prepared to efficiently and stably remove radioactive strontium ions under an alkaline environment. Through the incorporation of PDA and thermal reduction treatment, not only has the interlayer spacing of graphene oxide (GO) nanosheets been appropriately regulated but also an improved antiswelling property has been achieved. The dosage of GO, reaction time with PDA, mass ratio of PDA to GO, and thermal treatment temperature have been optimized to achieve a high-performance PDA/rGO membrane. The resultant PDA/rGO composite membrane has exhibited excellent long-term stability at pH 11 and maintains a steady strontium rejection of over 90%. Moreover, the separation mechanism of the PDA/rGO membrane has been systematically investigated and determined to be a synergistic effect of charge repulsion and size exclusion. Results have indicated that PDA/rGO could be considered as a promising candidate for the separation of Sr2+ ions from nuclear industry wastewater.

11.
Adv Mater ; : e2402325, 2024 Apr 17.
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.

12.
Plant Cell ; 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38581430

ABSTRACT

Lateral branches are important components of shoot architecture and directly affect crop yield and production cost. Although sporadic studies have implicated abscisic acid (ABA) biosynthesis in axillary bud outgrowth, the function of ABA catabolism and its upstream regulators in shoot branching remain elusive. Here, we showed that the MADS-box transcription factor AGAMOUS-LIKE 16 (CsAGL16) is a positive regulator of axillary bud outgrowth in cucumber (Cucumis sativus). Functional disruption of CsAGL16 led to reduced bud outgrowth, whereas overexpression of CsAGL16 resulted in enhanced branching. CsAGL16 directly binds to the promoter of the ABA 8'-hydroxylase gene CsCYP707A4 and promotes its expression. Loss of CsCYP707A4 function inhibited axillary bud outgrowth and increased ABA levels. Elevated expression of CsCYP707A4 or treatment with an ABA biosynthesis inhibitor largely rescued the Csagl16 mutant phenotype. Moreover, cucumber General Regulatory Factor 1 (CsGRF1) interacts with CsAGL16 and antagonizes CsAGL16-mediated CsCYP707A4 activation. Disruption of CsGRF1 resulted in elongated branches and decreased ABA levels in the axillary buds. The Csagl16 Csgrf1 double mutant exhibited a branching phenotype resembling that of the Csagl16 single mutant. Therefore, our data suggest that the CsAGL16-CsGRF1 module regulates axillary bud outgrowth via CsCYP707A4-mediated ABA catabolism in cucumber. Our findings provide a strategy to manipulate ABA levels in axillary buds during crop breeding to produce desirable branching phenotypes.

13.
Acta Cardiol ; : 1-9, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38661286

ABSTRACT

BACKGROUND: The optimal revascularization strategy for non-culprit vessels is still up for debate nowadays, particularly when it comes to individuals with different Killip classes. Therefore, the aim of our study was to investigate whether multivessel revascularization, as compared with infarct-related artery (IRA) alone revascularization, improves long-term prognosis in patients who have experienced an acute myocardial infarction (AMI) and have multivessel coronary artery disease (CAD). METHODS: A retrospective analysis was conducted on clinical data from 646 patients who presented with AMI and multivessel CAD at Beijing Chaoyang hospital between November 2014 and November 2020. Based on various revascularization strategies, patients were categorised into two groups: IRA-only revascularization (n = 416) and multivessel revascularization (n = 230). The primary endpoint was cardiovascular death. RESULTS: In the following 60.6 months (60.6 ± 23.9), the primary endpoint occurred in 3% of the multivessel revascularization group versus 9.6% in the IRA-only revascularization group (HR 0.284, CI 0.120-0.669, p = 0.002). For the Killip I-II patients (n = 533), the primary endpoint occurred in 2.6% of the multivessel revascularization group versus 9.5% in the IRA-only revascularization group (HR 0.236, CI 0.083-0.667, p = 0.003). For Killip III-IV patients (n = 113), there was no significance differences in the primary endpoint. After using the inverse probability weighted method, the benefit of complete revascularization was consistently observed. CONCLUSIONS: Multivessel revascularization significantly reduced the incidence of cardiovascular death for patients presenting with AMI and multivessel CAD, particularly for Killip I-II patients. There were no significant differences in the primary outcome across the groups of patients with Killip III-IV.

14.
J Mater Chem B ; 12(18): 4389-4397, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38623831

ABSTRACT

A robust and easily manufactured high-strength and long-term release hydrazone-based isoniazid acrylic (HIA) bone cement is reported. The mechanical strength of HIA bone cement is similar to that of normal polymethyl methacrylate (PMMA) bone cement, far surpassing that of traditional isoniazid-containing antibiotic-loaded bone cement (INH bone cement). Isoniazid is connected to the bone cement through bioorthogonal hydrazone chemistry, and it possesses release properties superior to those of INH bone cement, allowing for the sustained release of isoniazid for up to 12 weeks. In vivo and in vitro studies also indicate that HIA cement exhibits better biocompatibility than INH bone cement. The results of this study not only signify progress in the realm of antimicrobial bone cement for addressing bone tuberculosis but also enhance our capacity to create and comprehend high-performing antimicrobial bone cement.


Subject(s)
Bone Cements , Hydrazones , Isoniazid , Isoniazid/chemistry , Isoniazid/pharmacology , Bone Cements/chemistry , Animals , Hydrazones/chemistry , Hydrazones/pharmacology , Antitubercular Agents/chemistry , Antitubercular Agents/pharmacology , Antitubercular Agents/administration & dosage , Mice , Drug Liberation , Polymethyl Methacrylate/chemistry , Materials Testing , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
15.
Cell Mol Biol (Noisy-le-grand) ; 70(3): 187-191, 2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38650135

ABSTRACT

We attempted to evaluate clinical application value of high-frequency ultrasound (HFUS), fine needle aspiration cytology (FNAC), BRAF gene, and combination of HFUS, FNAC, and BRAF gene in diagnosing papillary thyroid microcarcinoma (PTMC). The 150 patients with thyroid minimal lesions who underwent HFUS, FNAC and BRAF gene testing before surgery in our hospital from June 2020 to December 2021 were selected as research subjects. Patients were divided into two groups based on postoperative pathological results. The consistency of diagnostic results of HFUS, FNAC, and BRAF gene and their combination with those of pathological examination, diagnostic efficacy of HFUS, FNAC and BRAF gene combined detection and individual detection for PTMC lymph node metastasis, and diagnostic value of HFUS, FNAC and BRAF gene combined detection and individual detection for PTMC lymph node metastasis received analysis and comparison. The consistency of diagnostic results of combined detection with pathological examination exhibited elevation relative to that of HFUS, FNAC and BRAF gene detection alone (P < 0.05). The negative predictive value, sensitivity and accuracy of combined detection exhibited elevation relative to individual detection (P < 0.05). The AUC of combined detection in diagnosing PTMC lymph node metastasis exhibited elevation relative to that of HFUS and BRAF gene alone (P < 0.05). HFUS combined with FNAC and BRAF genes possesses high diagnostic value, with high diagnostic sensitivity, specificity, and accuracy. Thus, combined detection for PTMC before surgery can accurately determine whether lymph node metastasis occurs, reduce occurrence of missed diagnosis and misdiagnosis, and thus improve diagnostic precision.


Subject(s)
Carcinoma, Papillary , Lymphatic Metastasis , Proto-Oncogene Proteins B-raf , Thyroid Neoplasms , Ultrasonography , Adult , Aged , Female , Humans , Male , Middle Aged , Biopsy, Fine-Needle/methods , Carcinoma, Papillary/genetics , Carcinoma, Papillary/pathology , Carcinoma, Papillary/diagnostic imaging , Proto-Oncogene Proteins B-raf/genetics , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/diagnostic imaging , Ultrasonography/methods
16.
Chem Biol Interact ; 395: 111016, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38670420

ABSTRACT

Acute kidney injury (AKI) is a common and serious global health problem with high risks of mortality and the development of chronic kidney diseases. Leonurine is a unique bioactive component from Leonurus japonicus Houtt. and exerts antioxidant, antiapoptotic or anti-inflammatory properties. This study aimed to explore the benefits of leonurine on AKI and the possible mechanisms involved, with a particular foc on the regulation of ferroptosis and endoplasmic reticulum (ER) stress. Our results showed that leonurine exhibited prominent protective effects against AKI, as evidenced by the amelioration of histopathological alterations and reduction of renal dysfunction. In addition, leonurine significantly suppressed ferroptosis in AKI both in vivo and in vitro by effectively restoring ultrastructural abnormalities in mitochondria, decreasing ASCL4 and 4-HNE levels, scavenging reactive oxygen species (ROS), as well as increasing GPX4 and GSH levels. In parallel, leonurine also markedly mitigated ER stress via down-regulating PERK, eIF-2α, ATF4, CHOP and CHAC1. Further studies suggested that ER stress was closely involved in erastin-induced ferroptosis, and leonurine protected tubular epithelial cells in vitro by inhibiting ER stress-associated ferroptosis via regulating ATF4/CHOP/ASCL4 signalling pathway. Mechanistically, ATF4 silencing in vitro regulated CHOP and ACSL4 expressions, ultimately weakening both ER stress and ferroptosis. Notably, analyses of single-cell RNA sequencing data revealed that ATF4, CHOP and ASCL4 in renal tubular cells were all abnormally upregulated in patients with AKI compared to healthy controls, suggesting their contributions to the pathogenesis of AKI. Altogether, these findings suggest that leonurine alleviates AKI by inhibiting ER stress-associated ferroptosis via regulating ATF4/CHOP/ASCL4 signalling pathway, thus providing novel mechanisms for AKI treatment.


Subject(s)
Activating Transcription Factor 4 , Acute Kidney Injury , Endoplasmic Reticulum Stress , Ferroptosis , Gallic Acid , Signal Transduction , Transcription Factor CHOP , Ferroptosis/drug effects , Acute Kidney Injury/drug therapy , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Activating Transcription Factor 4/metabolism , Endoplasmic Reticulum Stress/drug effects , Animals , Transcription Factor CHOP/metabolism , Gallic Acid/analogs & derivatives , Gallic Acid/pharmacology , Gallic Acid/therapeutic use , Mice , Signal Transduction/drug effects , Male , Mice, Inbred C57BL , Humans , Reactive Oxygen Species/metabolism , Protective Agents/pharmacology
17.
Urolithiasis ; 52(1): 63, 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38613670

ABSTRACT

This study aims to elucidate the mechanism and potential of Rhizoma alismatis polysaccharides (RAPs) in preventing oxidative damage to human renal proximal tubule epithelial cells. The experimental approach involved incubating HK-2 cells with 100 nm calcium oxalate monohydrate for 24 h to establish a cellular injury model. Protection was provided by RAPs with varying carboxyl group contents: 3.57%, 7.79%, 10.84%, and 15.33%. The safeguarding effect of RAPs was evaluated by analyzing relevant cellular biochemical indicators. Findings demonstrate that RAPs exhibit notable antioxidative properties. They effectively diminish the release of reactive oxygen species, lactate dehydrogenase, and malondialdehyde, a lipid oxidation byproduct. Moreover, RAPs enhance superoxide dismutase activity and mitochondrial membrane potential while attenuating the permeability of the mitochondrial permeability transition pore. Additionally, RAPs significantly reduce levels of inflammatory factors, including NLRP3, TNF-α, IL-6, and NO. This reduction corresponds to the inhibition of overproduced pro-inflammatory mediator nitric oxide and the caspase 3 enzyme, leading to a reduction in cellular apoptosis. RAPs also display the ability to suppress the expression of the HK-2 cell surface adhesion molecule CD44. The observed results collectively underscore the substantial anti-inflammatory and anti-apoptotic potential of all four RAPs. Moreover, their capacity to modulate the expression of cell surface adhesion molecules highlights their potential in inhibiting the formation of kidney stones. Notably, RAP3, boasting the highest carboxyl group content, emerges as the most potent agent in this regard.


Subject(s)
Calcium Oxalate , Kidney Calculi , Humans , Oxidative Stress , Inflammation/drug therapy , Epithelial Cells , Kidney Calculi/drug therapy , Kidney Calculi/prevention & control
18.
Arch Toxicol ; 98(6): 1937-1951, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38563870

ABSTRACT

The high incidence of colorectal cancer (CRC) is closely associated with environmental pollutant exposure. To identify potential intestinal carcinogens, we developed a cell transformation assay (CTA) using mouse adult stem cell-derived intestinal organoids (mASC-IOs) and assessed the transformation potential on 14 representative chemicals, including Cd, iPb, Cr-VI, iAs-III, Zn, Cu, PFOS, BPA, MEHP, AOM, DMH, MNNG, aspirin, and metformin. We optimized the experimental protocol based on cytotoxicity, amplification, and colony formation of chemical-treated mASC-IOs. In addition, we assessed the accuracy of in vitro study and the human tumor relevance through characterizing interdependence between cell-cell and cell-matrix adhesions, tumorigenicity, pathological feature of subcutaneous tumors, and CRC-related molecular signatures. Remarkably, the results of cell transformation in 14 chemicals showed a strong concordance with epidemiological findings (8/10) and in vivo mouse studies (12/14). In addition, we found that the increase in anchorage-independent growth was positively correlated with the tumorigenicity of tested chemicals. Through analyzing the dose-response relationship of anchorage-independent growth by benchmark dose (BMD) modeling, the potent intestinal carcinogens were identified, with their carcinogenic potency ranked from high to low as AOM, Cd, MEHP, Cr-VI, iAs-III, and DMH. Importantly, the activity of chemical-transformed mASC-IOs was associated with the degree of cellular differentiation of subcutaneous tumors, altered transcription of oncogenic genes, and activated pathways related to CRC development, including Apc, Trp53, Kras, Pik3ca, Smad4 genes, as well as WNT and BMP signaling pathways. Taken together, we successfully developed a mASC-IO-based CTA, which might serve as a potential alternative for intestinal carcinogenicity screening of chemicals.


Subject(s)
Carcinogenicity Tests , Cell Transformation, Neoplastic , Colorectal Neoplasms , Environmental Pollutants , Organoids , Animals , Cell Transformation, Neoplastic/chemically induced , Cell Transformation, Neoplastic/drug effects , Carcinogenicity Tests/methods , Organoids/drug effects , Organoids/pathology , Mice , Environmental Pollutants/toxicity , Colorectal Neoplasms/pathology , Colorectal Neoplasms/chemically induced , Humans , Carcinogens/toxicity , Intestines/drug effects , Intestines/pathology , Intestinal Neoplasms/chemically induced , Intestinal Neoplasms/pathology , Dose-Response Relationship, Drug
19.
J Agric Food Chem ; 72(17): 9906-9914, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38625103

ABSTRACT

Phlorizin (PHZ) is one of the main pharmacologically active ingredients in Lithocarpus polystachyus. We have previously shown that PHZ inhibits the replication of bovine viral diarrhea virus (BVDV), but the exact antiviral mechanism, especially in vivo, is still unknown. Here, we further confirm that PHZ has good protective effects in BVDV-infected mice. We analyzed BVDV-induced CD3+, CD4+, and CD8+ T cells among peripheral blood lymphocytes and found that PHZ significantly restored their percentage. Metagenomic analyses revealed that PHZ markedly improved the richness and diversity of intestinal microbiota and increased the abundance of potentially health-related microbes (families Lachnosipiraceae, Ruminococcaceae, and Oscillospiraceae). Specifically, the relative abundance of short chain fatty acid (SCFA)-producing bacteria, including Lachnospiraceae_UCG-006, unclassified_f_Ruminococcaceae, Oscillibacter, Intestinimonas, Blautia, and Lachnoclostridium increased significantly after PHZ treatment. Interestingly, BVDV-infected mice that received fecal microbiota from PHZ-treated mice (PHZ-FMT) had a significantly lower viral load in the duodenum and jejunum than untreated mice. Pathological lesions of duodenum and jejunum were also greatly reduced in the PHZ-FMT group, confirming a significant antiviral effect. These findings show that gut microbiota play an important role in PHZ's antiviral activity and suggest that their targeted intervention might be a promising endogenous strategy to prevent and control BVDV.


Subject(s)
Bacteria , Bovine Virus Diarrhea-Mucosal Disease , Diarrhea Viruses, Bovine Viral , Gastrointestinal Microbiome , Animals , Gastrointestinal Microbiome/drug effects , Mice , Cattle , Bacteria/classification , Bacteria/isolation & purification , Bacteria/genetics , Bacteria/drug effects , Diarrhea Viruses, Bovine Viral/drug effects , Antiviral Agents/pharmacology , Antiviral Agents/administration & dosage , Feces/microbiology , Feces/virology , Female , Mice, Inbred BALB C , Male
20.
Membranes (Basel) ; 14(3)2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38535284

ABSTRACT

The operation of coal-fired power plants generates a large amount of wastewater. With the issuance of increasingly strict drainage standards, the cost of wastewater treatment is increasing, and the need to reduce the cost of wastewater treatment is becoming increasingly urgent. Thus, based on the principles of reverse osmosis (RO) and mechanical vapor recompression (MVR) in wastewater treatment, the operational optimization of an RO-MVR joint system was studied in this work with the consideration of reducing the operating costs of wastewater treatment under given operational conditions. Firstly, based on the basic principles of RO and MVR, corresponding mechanism models were established and their accuracy was verified. Then, an economic model of the RO-MVR joint system was established, with the goal of minimizing the water production unit price and daily operating costs of the joint system for optimization analysis. Finally, we analyzed the cost and water production performance of the RO-MVR joint system before and after optimization under different operating conditions. The results show that this optimization based on the RO-MVR joint system will reduce the unit price of water production to 3.16 CNY/m3, with the daily operating costs being decreased by 22% compared to before optimization. This result helps to reduce the cost of zero-discharge wastewater treatment in coal-fired power plants.

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