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1.
Small ; : e2401831, 2024 May 11.
Article En | MEDLINE | ID: mdl-38733226

Quasi-2D perovskites have attracted much attention in perovskite photovoltaics due to their excellent stability. However, their photoelectric conversion efficiency (PCE) still lags 3D counterparts, particularly with high short-circuit current (JSC) loss. The quantum confinement effect is pointed out to be the sole reason, which introduces widened bandgap and poor exciton dissociation, and undermines the light capture and charge transport. Here, the gradient incorporation of formamidinium (FA) cations into quasi-2D perovskite is proposed to address this issue. It is observed that FA prefers to incorporate into the larger n value phases near the film surface compared to the smaller n value phases in the bulk, resulting in a narrow bandgap and gradient structure within the film. Through charge dynamic analysis using in situ light-dark Kelvin probe force microscopy and transient absorption spectroscopy, it is demonstrated that incorporating 10% FA significantly facilitates efficient charge transfer between low n-value phases in the bulk and high n-value nearby film surface, leading to reduced charge accumulation. Ultimately, the device based on (AA)2(MA0.9FA0.1)4Pb5I16, where AA represents n-amylamine renowned for its exceptional environmental stability as a bulky organic ligand, achieves an impressive power conversion efficiency (PCE) of 18.58% and demonstrates enhanced illumination and thermal stability.

3.
Front Microbiol ; 15: 1387222, 2024.
Article En | MEDLINE | ID: mdl-38741732

Abiotic stresses can increase the total fatty acid (TFA) and astaxanthin accumulation in microalgae. However, it remains unknown whether a unified signal transduction mechanism exists under different stresses. This study explored the link between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) and the accumulation of fatty acids and astaxanthin in Chromochloris zofingiensis under three abiotic stresses. Results showed significant increases in fatty acid, astaxanthin, and ROS levels under nitrogen deficiency, phosphorus deficiency, and high-salinity stress. The introduction of the NADPH oxidase inhibitor diphenyleneiodonium (DPI) decreased the content of these components. This underscores the pivotal role of NADPH oxidase-derived ROS in the accumulation of fatty acid and astaxanthin under abiotic stress. Analysis of transcriptomes across three conditions following DPI addition revealed 1,445 shared differentially expressed genes (DEGs). Enrichment analysis revealed that biotin, betalain, thiamine, and glucosinolate may be important in stress responses. The heatmap demonstrated that DPI notably suppressed gene expression in the fatty acid and carotenoid biosynthesis pathways. Our findings underscore the pivotal role of NADPH oxidase-derived ROS in the accumulation of fatty acid and astaxanthin under abiotic stresses.

4.
Front Immunol ; 15: 1382449, 2024.
Article En | MEDLINE | ID: mdl-38745657

Background: Acute Respiratory Distress Syndrome (ARDS) or its earlier stage Acute lung injury (ALI), is a worldwide health concern that jeopardizes human well-being. Currently, the treatment strategies to mitigate the incidence and mortality of ARDS are severely restricted. This limitation can be attributed, at least in part, to the substantial variations in immunity observed in individuals with this syndrome. Methods: Bulk and single cell RNA sequencing from ALI mice and single cell RNA sequencing from ARDS patients were analyzed. We utilized the Seurat program package in R and cellmarker 2.0 to cluster and annotate the data. The differential, enrichment, protein interaction, and cell-cell communication analysis were conducted. Results: The mice with ALI caused by pulmonary and extrapulmonary factors demonstrated differential expression including Clec4e, Retnlg, S100a9, Coro1a, and Lars2. We have determined that inflammatory factors have a greater significance in extrapulmonary ALI, while multiple pathways collaborate in the development of pulmonary ALI. Clustering analysis revealed significant heterogeneity in the relative abundance of immune cells in different ALI models. The autocrine action of neutrophils plays a crucial role in pulmonary ALI. Additionally, there was a significant increase in signaling intensity between B cells and M1 macrophages, NKT cells and M1 macrophages in extrapulmonary ALI. The CXCL, CSF3 and MIF, TGFß signaling pathways play a vital role in pulmonary and extrapulmonary ALI, respectively. Moreover, the analysis of human single-cell revealed DCs signaling to monocytes and neutrophils in COVID-19-associated ARDS is stronger compared to sepsis-related ARDS. In sepsis-related ARDS, CD8+ T and Th cells exhibit more prominent signaling to B-cell nucleated DCs. Meanwhile, both MIF and CXCL signaling pathways are specific to sepsis-related ARDS. Conclusion: This study has identified specific gene signatures and signaling pathways in animal models and human samples that facilitate the interaction between immune cells, which could be targeted therapeutically in ARDS patients of various etiologies.


Acute Lung Injury , Cell Communication , Gene Expression Profiling , Animals , Acute Lung Injury/genetics , Acute Lung Injury/immunology , Mice , Humans , Cell Communication/immunology , Transcriptome , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/genetics , Disease Models, Animal , Single-Cell Analysis , Mice, Inbred C57BL , Neutrophils/immunology , Neutrophils/metabolism , COVID-19/immunology , COVID-19/genetics , Signal Transduction , Male , Macrophages/immunology , Macrophages/metabolism
5.
Nat Methods ; 2024 May 14.
Article En | MEDLINE | ID: mdl-38744917

AlphaFold2 revolutionized structural biology with the ability to predict protein structures with exceptionally high accuracy. Its implementation, however, lacks the code and data required to train new models. These are necessary to (1) tackle new tasks, like protein-ligand complex structure prediction, (2) investigate the process by which the model learns and (3) assess the model's capacity to generalize to unseen regions of fold space. Here we report OpenFold, a fast, memory efficient and trainable implementation of AlphaFold2. We train OpenFold from scratch, matching the accuracy of AlphaFold2. Having established parity, we find that OpenFold is remarkably robust at generalizing even when the size and diversity of its training set is deliberately limited, including near-complete elisions of classes of secondary structure elements. By analyzing intermediate structures produced during training, we also gain insights into the hierarchical manner in which OpenFold learns to fold. In sum, our studies demonstrate the power and utility of OpenFold, which we believe will prove to be a crucial resource for the protein modeling community.

6.
Nature ; 2024 May 08.
Article En | MEDLINE | ID: mdl-38720082

Most chemistry and biology occurs in solution, in which conformational dynamics and complexation underlie behaviour and function. Single-molecule techniques1 are uniquely suited to resolving molecular diversity and new label-free approaches are reshaping the power of single-molecule measurements. A label-free single-molecule method2-16 capable of revealing details of molecular conformation in solution17,18 would allow a new microscopic perspective of unprecedented detail. Here we use the enhanced light-molecule interactions in high-finesse fibre-based Fabry-Pérot microcavities19-21 to detect individual biomolecules as small as 1.2 kDa, a ten-amino-acid peptide, with signal-to-noise ratios (SNRs) >100, even as the molecules are unlabelled and freely diffusing in solution. Our method delivers 2D intensity and temporal profiles, enabling the distinction of subpopulations in mixed samples. Notably, we observe a linear relationship between passage time and molecular radius, unlocking the potential to gather crucial information about diffusion and solution-phase conformation. Furthermore, mixtures of biomolecule isomers of the same molecular weight and composition but different conformation can also be resolved. Detection is based on the creation of a new molecular velocity filter window and a dynamic thermal priming mechanism that make use of the interplay between optical and thermal dynamics22,23 and Pound-Drever-Hall (PDH) cavity locking24 to reveal molecular motion even while suppressing environmental noise. New in vitro ways of revealing molecular conformation, diversity and dynamics can find broad potential for applications in the life and chemical sciences.

7.
Exp Biol Med (Maywood) ; 249: 10104, 2024.
Article En | MEDLINE | ID: mdl-38708425

Seawater-drowning-induced acute lung injury (SD-ALI) is a life-threatening disorder characterized by increased alveolar-capillary permeability, an excessive inflammatory response, and refractory hypoxemia. Perfluorocarbons (PFCs) are biocompatible compounds that are chemically and biologically inert and lack toxicity as oxygen carriers, which could reduce lung injury in vitro and in vivo. The aim of our study was to explore whether the vaporization of PFCs could reduce the severity of SD-ALI in canines and investigate the underlying mechanisms. Eighteen beagle dogs were randomly divided into three groups: the seawater drowning (SW), perfluorocarbon (PFC), and control groups. The dogs in the SW group were intratracheally administered seawater to establish the animal model. The dogs in the PFC group were treated with vaporized PFCs. Probe-based confocal laser endomicroscopy (pCLE) was performed at 3 h. The blood gas, volume air index (VAI), pathological changes, and wet-to-dry (W/D) lung tissue ratios were assessed. The expression of heme oxygenase-1 (HO-1), nuclear respiratory factor-1 (NRF1), and NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasomes was determined by means of quantitative real-time polymerase chain reaction (qRT-PCR) and immunological histological chemistry. The SW group showed higher lung injury scores and W/D ratios, and lower VAI compared to the control group, and treatment with PFCs could reverse the change of lung injury score, W/D ratio and VAI. PFCs deactivated NLRP3 inflammasomes and reduced the release of caspase-1, interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) by enhancing the expression of HO-1 and NRF1. Our results suggest that the vaporization of PFCs could attenuate SD-ALI by deactivating NLRP3 inflammasomes via the HO-1/NRF1 pathway.


Acute Lung Injury , Fluorocarbons , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Animals , Fluorocarbons/pharmacology , Dogs , Acute Lung Injury/metabolism , Acute Lung Injury/drug therapy , Acute Lung Injury/pathology , Inflammasomes/metabolism , Inflammasomes/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Seawater , Male , Drowning/metabolism , Disease Models, Animal , Lung/pathology , Lung/metabolism , Lung/drug effects
8.
Angew Chem Int Ed Engl ; : e202404528, 2024 May 09.
Article En | MEDLINE | ID: mdl-38722260

Natural photoactive systems have evolved to harness broad-spectrum light from solar radiation for critical functions such as light perception and photosynthetic energy conversion. Molecular photoswitches, which undergo structural changes upon light absorption, are artificial photoactive tools widely used for developing photoresponsive systems and converting light energy. However, photoswitches generally need to be activated by light of specific narrow wavelength ranges for effective photoconversion, which limits their ability to directly work under sunlight and to efficiently harvest solar energy. Here, focusing on azo-switches-the most extensively studied photoswitches, we demonstrate effective solar E→Zphotoisomerization with photoconversions exceeding 80% under unfiltered sunlight. These sunlight-driven azo-switches are developed by rendering the absorption of E isomers overwhelmingly stronger than that of Z isomers across a broad ultraviolet to visible spectrum. This unusual type of spectral profile is realized by a simple yet highly adjustable molecular design strategy, enabling the fine-tuning of spectral window that extends light absorption beyond 600 nm. Notably, back-photoconversion can be achieved without impairing the forward solar isomerization, resulting in unique light-reversible solar switches. Such exceptional solar chemistry of photoswitches provides unprecedented opportunities for developing sustainable light-driven systems and efficient solar energy technologies.

9.
Am J Chin Med ; : 1-21, 2024 May 08.
Article En | MEDLINE | ID: mdl-38716621

The formation of fibrotic tissue, characterized by the excessive accumulation of extracellular matrix (ECM) components such as collagen and fibronectin, is a normal and crucial stage of tissue repair in all organs. The over-synthesis, deposition, and remodeling of ECM components lead to organ dysfunction, posing a significant medical burden. Berberine, an isoquinoline alkaloid, is commonly used in the treatment of gastrointestinal diseases. With the deepening of scientific research, it has been gradually discovered that berberine also plays an important role in fibrotic diseases. In this review, we systematically introduce the effective role of berberine in fibrosis-related diseases. Specifically, this paper aims to provide a comprehensive review of the therapeutic role of berberine in treating fibrosis in organs such as the heart, liver, lungs, and kidneys. By summarizing its various pathways and mechanisms of action, including the inhibition of the transforming growth factor-[Formula: see text]/Smad signaling pathway, PI3K/Akt signaling pathway, MAPK signaling pathway, RhoA/ROCK signaling, and mTOR/p70S6K signaling pathway, as well as its activation of the Nrf2-ARE signaling pathway, AMPK signaling pathway, phosphorylated Smad 2/3 and Smad 7, and other signaling pathways, this review offers additional evidence to support the treatment of fibrotic diseases.

10.
Article En | MEDLINE | ID: mdl-38695865

A novel Gram-staining-positive actinobacterium with antimicrobial activity, designated CFH 90308T, was isolated from the sediment of a salt lake in Yuncheng, Shanxi, south-western China. The isolate exhibited the highest 16S rRNA gene sequence similarities to Microbacterium yannicii G72T, Microbacterium hominis NBRC 15708T and Microbacterium xylanilyticum S3-ET (98.5, 98.4 and 98.2 %, respectively), and formed a separate clade with M. xylanilyticum S3-ET in phylogenetic trees. The strain grew at 15-40 ºC, pH 6.0-8.0 and could tolerate NaCl up to a concentration of 15 % (w/v). The whole genome of strain CFH 90308T consisted of 4.33 Mbp and the DNA G+C content was 69.6 mol%. The acyl type of the peptidoglycan was glycolyl and the whole-cell sugars were galactose and mannose. The cell-wall peptidoglycan mainly contained alanine, glycine and lysine. The menaquinones of strain CFH 90308T were MK-12, MK-13 and MK-11. Strain CFH 90308T contained anteiso-C15:0, anteiso-C17:0, iso-C16:0 and iso-C15:0 as the predominant fatty acids. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between CFH 90308T and the other species of the genus Microbacterium were found to be low (ANIb <81.3 %, dDDH <25.6 %). The secondary metabolite produced by strain CFH 90308T showed antibacterial activities against Bacillus subtilis, Pseudomonas syringae, Aeromonas hydrophila and methicillin-resistant Staphylococcus aureus. Based on genotypic, phenotypic and chemotaxonomic results, the isolate is considered to represent a novel species of the genus Microbacterium, for which the name Microbacterium salsuginis sp. nov. is proposed. The type strain is CFH 90308T (=DSM 105964T=KCTC 49052T).


Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Geologic Sediments , Microbacterium , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Vitamin K 2 , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , China , Vitamin K 2/analogs & derivatives , Geologic Sediments/microbiology , Peptidoglycan , Lakes/microbiology , Nucleic Acid Hybridization , Sodium Chloride/metabolism , Genome, Bacterial
11.
Sci Rep ; 14(1): 10776, 2024 05 11.
Article En | MEDLINE | ID: mdl-38734750

The age, creatinine, and ejection fraction (ACEF) score has been accepted as a predictor of poor outcome in elective operations. This study aimed to investigate the predictive value of ACEF score in acute type A aortic dissection (AAAD) patients after total arch replacement. A total of 227 AAAD patients from July 2021 and June 2022 were enrolled and divided into Tertiles 1 (ACEF ≤ 0.73), Tertiles 2 (0.73 < ACEF ≤ 0.95), and Tertiles 3 (ACEF > 0.95). Using inverse probability processing weighting (IPTW) to balance the baseline characteristics and compare the outcomes. Cox logistic regression was used to further evaluate the survival prediction ability of ACEF score. The in-hospital mortality was 9.8%. After IPTW, in the baseline characteristics reached an equilibrium, a higher ACEF score before operation still associated with higher in-hospital mortality. After 1 year follow-up, 184 patients (90.6%) survival. Multivariable analysis revealed that ACEF score (adjusted hazard ratio 1.68; 95% confidence interval 1.34-4.91; p = 0.036) and binary ACEF score (adjusted HR 2.26; 95% CI 1.82-6.20; p < 0.001) was independently associated with 1-year survival. In addition, net reclassification improvement (NRI) and integrated differentiation improvement (IDI) verified that the ACEF score and binary ACEF score is an accurate predictive tool in clinical settings. In conclusions, ACEF score could be considered as a useful tool to risk stratification in patients with AAAD before operation in daily clinical work.


Aortic Dissection , Creatinine , Hospital Mortality , Humans , Female , Male , Aortic Dissection/surgery , Aortic Dissection/mortality , Middle Aged , Creatinine/blood , Aged , Stroke Volume , Age Factors , Prognosis , Predictive Value of Tests , Aorta, Thoracic/surgery , Retrospective Studies , Aortic Aneurysm, Thoracic/surgery , Aortic Aneurysm, Thoracic/mortality
13.
Exp Eye Res ; 242: 109889, 2024 May.
Article En | MEDLINE | ID: mdl-38593971

Dry age-related macular degeneration (AMD) is a prevalent clinical condition that leads to permanent damage to central vision and poses a significant threat to patients' visual health. Although the pathogenesis of dry AMD remains unclear, there is consensus on the role of retinal pigment epithelium (RPE) damage. Oxidative stress and chronic inflammation are major contributors to RPE cell damage, and the NOD-like receptor thermoprotein structural domain-associated protein 3 (NLRP3) inflammasome mediates the inflammatory response leading to apoptosis in RPE cells. Furthermore, lipofuscin accumulation results in oxidative stress, NLRP3 activation, and the development of vitelliform lesions, a hallmark of dry AMD, all of which may contribute to RPE dysfunction. The process of autophagy, involving the encapsulation, recognition, and transport of accumulated proteins and dead cells to the lysosome for degradation, is recognized as a significant pathway for cellular self-protection and homeostasis maintenance. Recently, RPE cell autophagy has been discovered to be closely linked to the development of macular degeneration, positioning autophagy as a cutting-edge research area in the realm of dry AMD. In this review, we present an overview of how lipofuscin, oxidative stress, and the NLRP3 inflammasome damage the RPE through their respective causal mechanisms. We summarized the connection between autophagy, oxidative stress, and NLRP3 inflammatory cytokines. Our findings suggest that targeting autophagy improves RPE function and sustains visual health, offering new perspectives for understanding the pathogenesis and clinical management of dry AMD.


Autophagy , Oxidative Stress , Retinal Pigment Epithelium , Humans , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/pathology , Autophagy/physiology , Oxidative Stress/physiology , Inflammasomes/metabolism , Lipofuscin/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Geographic Atrophy/metabolism , Geographic Atrophy/pathology
14.
Materials (Basel) ; 17(7)2024 Mar 27.
Article En | MEDLINE | ID: mdl-38612047

The phase segregation of wide-bandgap perovskite is detrimental to a device's performance. We find that Sodium Benzenesulfonate (SBS) can improve the interface passivation of PTAA, thus addressing the poor wettability issue of poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine](PTAA). This improvement helps mitigate interface defects caused by poor contact between the perovskite and PTAA, reducing non-radiative recombination. Additionally, enhanced interface contact improves the crystallinity of the perovskite, leading to higher-quality perovskite films. By synergistically controlling the crystallization and trap passivation to reduce the phase segregation, SBS-modified perovskite solar cells (PSCs) achieved a power conversion efficiency (PCE) of 20.27%, with an open-circuit voltage (Voc) of 1.18 V, short-circuit current density (Jsc) of 20.93 mA cm-2, and fill factor (FF) of 82.31%.

15.
J Appl Toxicol ; 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38644760

Prolonged exposure to environments with high concentrations of crystalline silica (CS) can lead to silicosis. Macrophages play a crucial role in the pathogenesis of silicosis. In the process of silicosis, silica (SiO2) invades alveolar macrophages (AMs) and induces mitophagy which usually exists in three states: normal, excessive, and/or deficiency. Different mitophagy states lead to corresponding toxic responses, including successful macrophage repair, injury, necrosis, apoptosis, and even pulmonary fibrosis. This is a complex process accompanied by various cytokines. Unfortunately, the details have not been fully systematically summarized. Therefore, it is necessary to elucidate the role of macrophage mitophagy in SiO2-induced pulmonary fibrosis by systematic analysis on the literature reports. In this review, we first summarized the current data on the macrophage mitophagy in the development of SiO2-induced pulmonary fibrosis. Then, we introduce the molecular mechanism on how SiO2-induced mitophagy causes pulmonary fibrosis. Finally, we focus on introducing new therapies based on newly developed mitophagy-inducing strategies. We conclude that macrophage mitophagy plays a multifaceted role in the progression of SiO2-induced pulmonary fibrosis, and reprogramming the macrophage mitophagy state accordingly may be a potential means of preventing and treating pulmonary fibrosis.

16.
Nat Struct Mol Biol ; 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38658622

The PIWI-interacting RNA (piRNA) pathway is an adaptive defense system wherein piRNAs guide PIWI family Argonaute proteins to recognize and silence ever-evolving selfish genetic elements and ensure genome integrity. Driven by this intensive host-pathogen arms race, the piRNA pathway and its targeted transposons have coevolved rapidly in a species-specific manner, but how the piRNA pathway adapts specifically to target silencing in mammals remains elusive. Here, we show that mouse MILI and human HILI piRNA-induced silencing complexes (piRISCs) bind and cleave targets more efficiently than their invertebrate counterparts from the sponge Ephydatia fluviatilis. The inherent functional differences comport with structural features identified by cryo-EM studies of piRISCs. In the absence of target, MILI and HILI piRISCs adopt a wider nucleic-acid-binding channel and display an extended prearranged piRNA seed as compared with EfPiwi piRISC, consistent with their ability to capture targets more efficiently than EfPiwi piRISC. In the presence of target, the seed gate-which enforces seed-target fidelity in microRNA RISC-adopts a relaxed state in mammalian piRISC, revealing how MILI and HILI tolerate seed-target mismatches to broaden the target spectrum. A vertebrate-specific lysine distorts the piRNA seed, shifting the trajectory of the piRNA-target duplex out of the central cleft and toward the PAZ lobe. Functional analyses reveal that this lysine promotes target binding and cleavage. Our study therefore provides a molecular basis for the piRNA targeting mechanism in mice and humans, and suggests that mammalian piRNA machinery can achieve broad target silencing using a limited supply of piRNA species.

17.
J Ethnopharmacol ; 328: 118109, 2024 Jun 28.
Article En | MEDLINE | ID: mdl-38570147

ETHNOPHARMACOLOGICAL RELEVANCE: The Dryopteris crassirhizoma Nakai., a commonly used herb, is known as "Guan Zhong" in China, "Oshida" in Japan and "Gwanjung" in Korea. It has long been used for parasitic infestation, hemorrhages and epidemic influenza. AIM OF THE REVIEW: The present paper aims to provide an up-to-date review at the advancements of the investigations on the traditional use, phytochemistry, pharmacological activity, toxicology and pharmacokinetics of D. crassirhizoma. Besides, possible trends, therapeutic potentials, and perspectives for future research of this plant are also briefly discussed. MATERIALS AND METHODS: Relevant information on traditional use, phytochemistry, pharmacological activity, toxicology and pharmacokinetics of D. crassirhizoma was collected through published materials and electronic databases, including the Chinese Pharmacopoeia, Flora of China, Web of Science, PubMed, Baidu Scholar, Google Scholar, and China National Knowledge Infrastructure. 109 papers included in the article and we determined that no major information was missing after many checks. All authors participated in the review process for this article and all research paper are from authoritative published materials and electronic databases. RESULTS: 130 chemical components, among which phloroglucinols are the predominant groups, have been isolated and identified from D. crassirhizoma. D. crassirhizoma with its bioactive compounds is possessed of extensive biological activities, including anti-parasite, anti-microbial, anti-viral, anti-cancer, anti-inflammatory, anti-oxidant, anti-diabetic, bone protective, immunomodulatory, anti-platelet and anti-hyperuricemia activity. Besides, D. crassirhizoma has special toxicology and pharmacokinetics characterization. CONCLUSIONS: D. crassirhizoma is a traditional Chinese medicine having a long history of application. This review mainly summarized the different chemical components extract from D. crassirhizoma and various reported pharmacological effects. Besides, the toxicology and pharmacokinetics of D. crassirhizoma also be analysed in this review. However, the chemical components of D. crassirhizoma are understudied and require further research to expand its medicinal potential, and it is urgent to design a new extraction scheme, so that the active ingredients can be obtained at a lower cost.


Botany , Drugs, Chinese Herbal , Dryopteris , Phytochemicals/therapeutic use , Phytochemicals/toxicity , Phytotherapy , Medicine, Chinese Traditional , Ethnopharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/toxicity , Plant Extracts/therapeutic use , Plant Extracts/toxicity
18.
J Clin Invest ; 134(8)2024 Apr 15.
Article En | MEDLINE | ID: mdl-38618952

N6-Methyladenosine (m6A) is the most abundant posttranscriptional modification, and its contribution to cancer evolution has recently been appreciated. Renal cancer is the most common adult genitourinary cancer, approximately 85% of which is accounted for by the clear cell renal cell carcinoma (ccRCC) subtype characterized by VHL loss. However, it is unclear whether VHL loss in ccRCC affects m6A patterns. In this study, we demonstrate that VHL binds and promotes METTL3/METTL14 complex formation while VHL depletion suppresses m6A modification, which is distinctive from its canonical E3 ligase role. m6A RNA immunoprecipitation sequencing (RIP-Seq) coupled with RNA-Seq allows us to identify a selection of genes whose expression may be regulated by VHL-m6A signaling. Specifically, PIK3R3 is identified to be a critical gene whose mRNA stability is regulated by VHL in a m6A-dependent but HIF-independent manner. Functionally, PIK3R3 depletion promotes renal cancer cell growth and orthotopic tumor growth while its overexpression leads to decreased tumorigenesis. Mechanistically, the VHL-m6A-regulated PIK3R3 suppresses tumor growth by restraining PI3K/AKT activity. Taken together, we propose a mechanism by which VHL regulates m6A through modulation of METTL3/METTL14 complex formation, thereby promoting PIK3R3 mRNA stability and protein levels that are critical for regulating ccRCC tumorigenesis.


Adenine , Carcinoma, Renal Cell , Kidney Neoplasms , Adult , Humans , Carcinogenesis/genetics , Carcinoma, Renal Cell/genetics , Cell Transformation, Neoplastic , Gene Expression , Kidney Neoplasms/genetics , Methyltransferases/genetics , Phosphatidylinositol 3-Kinases/genetics
19.
Biotechnol Biofuels Bioprod ; 17(1): 50, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38566214

BACKGROUND: Autophagy is a crucial process of cellular self-destruction and component reutilization that can affect the accumulation of total fatty acids (TFAs) and carotenoids in microalgae. The regulatory effects of autophagy process in a docosahexaenoic acid (DHA) and carotenoids simultaneously producing microalga, Crypthecodinium sp. SUN, has not been studied. Thus, the autophagy inhibitor (3-methyladenine (MA)) and activator (rapamycin) were used to regulate autophagy in Crypthecodinium sp. SUN. RESULTS: The inhibition of autophagy by 3-MA was verified by transmission electron microscopy, with fewer autophagy vacuoles observed. Besides, 3-MA reduced the glucose absorption and intracellular acetyl-CoA level, which resulting in the decrease of TFA and DHA levels by 15.83 and 26.73% respectively; Surprisingly, 3-MA increased intracellular reactive oxygen species level but decreased the carotenoids level. Comparative transcriptome analysis showed that the downregulation of the glycolysis, pentose phosphate pathway and tricarboxylic acid cycle may underlie the decrease of acetyl-CoA, NADPH and ATP supply for fatty acid biosynthesis; the downregulation of PSY and HMGCR may underlie the decreased carotenoids level. In addition, the class I PI3K-AKT signaling pathway may be crucial for the regulation of carbon and energy metabolism. At last, rapamycin was used to activate autophagy, which significantly enhanced the cell growth and TFA level and eventually resulted in 1.70-fold increase in DHA content. CONCLUSIONS: Our findings indicate the mechanisms of autophagy in Crypthecodinium sp. SUN and highlight a way to manipulate cell metabolism by regulating autophagy. Overall, this study provides valuable insights to guide further research on autophagy-regulated TFA and carotenoids accumulation in Crypthecodinium sp. SUN.

20.
Appl Opt ; 63(8): 1952-1960, 2024 Mar 10.
Article En | MEDLINE | ID: mdl-38568634

The relative attitude estimation between chasers and uncooperative targets is an important prerequisite for executing in orbit service (OOS) tasks. Only by efficiently obtaining relative pose parameters can chasers design close-range rendezvous trajectories close to uncooperative targets. The focus of this article is on active systems, such as TOF cameras or LIDAR. This paper proposes an attitude estimation scheme to obtain relative attitude parameters between uncooperative targets. This scheme utilizes LIDAR to obtain three-dimensional point clouds of non-cooperative targets, extracts key points and simplifies the number of point clouds through joint farthest point sampling and point cloud feature analysis, and then uses point fast feature histograms (FPFHs) and robust iterative closest point algorithms to achieve point cloud registration between every two frames. Finally, a filtering framework was designed, whose scheme is an extended Kalman filter designed for updating measurements of relative position, velocity, attitude, and angular velocity estimation. The experimental results show that this method can effectively achieve point cloud registration for close range rotation and translation motion, and can estimate the motion state of the target.

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