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1.
Nature ; 605(7910): 567-574, 2022 05.
Article in English | MEDLINE | ID: mdl-35477760

ABSTRACT

Proteasomal degradation of ubiquitylated proteins is tightly regulated at multiple levels1-3. A primary regulatory checkpoint is the removal of ubiquitin chains from substrates by the deubiquitylating enzyme ubiquitin-specific protease 14 (USP14), which reversibly binds the proteasome and confers the ability to edit and reject substrates. How USP14 is activated and regulates proteasome function remain unknown4-7. Here we present high-resolution cryo-electron microscopy structures of human USP14 in complex with the 26S proteasome in 13 distinct conformational states captured during degradation of polyubiquitylated proteins. Time-resolved cryo-electron microscopy analysis of the conformational continuum revealed two parallel pathways of proteasome state transitions induced by USP14, and captured transient conversion of substrate-engaged intermediates into substrate-inhibited intermediates. On the substrate-engaged pathway, ubiquitin-dependent activation of USP14 allosterically reprograms the conformational landscape of the AAA-ATPase motor and stimulates opening of the core particle gate8-10, enabling observation of a near-complete cycle of asymmetric ATP hydrolysis around the ATPase ring during processive substrate unfolding. Dynamic USP14-ATPase interactions decouple the ATPase activity from RPN11-catalysed deubiquitylation11-13 and kinetically introduce three regulatory checkpoints on the proteasome, at the steps of ubiquitin recognition, substrate translocation initiation and ubiquitin chain recycling. These findings provide insights into the complete functional cycle of the USP14-regulated proteasome and establish mechanistic foundations for the discovery of USP14-targeted therapies.


Subject(s)
Proteasome Endopeptidase Complex , Ubiquitin , Adenosine Triphosphatases/metabolism , Cryoelectron Microscopy , Humans , Molecular Conformation , Proteasome Endopeptidase Complex/metabolism , Ubiquitin/metabolism , Ubiquitin Thiolesterase/metabolism
2.
Proc Natl Acad Sci U S A ; 120(39): e2307899120, 2023 09 26.
Article in English | MEDLINE | ID: mdl-37733740

ABSTRACT

The human blood-brain barrier (BBB) comprises a single layer of brain microvascular endothelial cells (HBMECs) protecting the brain from bloodborne pathogens. Meningitis is among the most serious diseases, but the mechanisms by which major meningitis-causing bacterial pathogens cross the BBB to reach the brain remain poorly understood. We found that Streptococcus pneumoniae, group B Streptococcus, and neonatal meningitis Escherichia coli commonly exploit a unique vesicle fusion mechanism to hitchhike on transferrin receptor (TfR) transcytosis to cross the BBB and illustrated the details of this process in human BBB model in vitro and mouse model. Toll-like receptor signals emanating from bacteria-containing vesicles (BCVs) trigger K33-linked polyubiquitination at Lys168 and Lys181 of the innate immune regulator TRAF3 and then activate the formation of a protein complex containing the guanine nucleotide exchange factor RCC2, the small GTPase RalA and exocyst subcomplex I (SC I) on BCVs. The distinct function of SEC6 in SC I, interacting directly with RalA on BCVs and the SNARE protein SNAP23 on TfR vesicles, tethers these two vesicles and initiates the fusion. Our results reveal that innate immunity triggers a unique modification of TRAF3 and the formation of the HBMEC-specific protein complex on BCVs to authenticate the precise recognition and selection of TfR vesicles to fuse with and facilitate bacterial penetration of the BBB.


Subject(s)
Blood-Brain Barrier , Endothelial Cells , Humans , Animals , Mice , Infant, Newborn , TNF Receptor-Associated Factor 3 , Transcytosis , Bacteria , Receptors, Transferrin
3.
Development ; 149(14)2022 07 15.
Article in English | MEDLINE | ID: mdl-35781558

ABSTRACT

Formation of highly unique and complex facial structures is controlled by genetic programs that are responsible for the precise coordination of three-dimensional tissue morphogenesis. However, the underlying mechanisms governing these processes remain poorly understood. We combined mouse genetic and genomic approaches to define the mechanisms underlying normal and defective midfacial morphogenesis. Conditional inactivation of the Wnt secretion protein Wls in Pax3-expressing lineage cells disrupted frontonasal primordial patterning, cell survival and directional outgrowth, resulting in altered facial structures, including midfacial hypoplasia and midline facial clefts. Single-cell RNA sequencing revealed unique transcriptomic atlases of mesenchymal subpopulations in the midfacial primordia, which are disrupted in the conditional Wls mutants. Differentially expressed genes and cis-regulatory sequence analyses uncovered that Wls modulates and integrates a core gene regulatory network, consisting of key midfacial regulatory transcription factors (including Msx1, Pax3 and Pax7) and their downstream targets (including Wnt, Shh, Tgfß and retinoic acid signaling components), in a mesenchymal subpopulation of the medial nasal prominences that is responsible for midline facial formation and fusion. These results reveal fundamental mechanisms underlying mammalian midfacial morphogenesis and related defects at single-cell resolution.


Subject(s)
Gene Regulatory Networks , Transcriptome , Animals , Face , Mammals/genetics , Mice , Morphogenesis/genetics , Transcriptome/genetics , Wnt Proteins/metabolism
4.
Nature ; 565(7737): 49-55, 2019 01.
Article in English | MEDLINE | ID: mdl-30479383

ABSTRACT

The proteasome is an ATP-dependent, 2.5-megadalton molecular machine that is responsible for selective protein degradation in eukaryotic cells. Here we present cryo-electron microscopy structures of the substrate-engaged human proteasome in seven conformational states at 2.8-3.6 Å resolution, captured during breakdown of a polyubiquitylated protein. These structures illuminate a spatiotemporal continuum of dynamic substrate-proteasome interactions from ubiquitin recognition to substrate translocation, during which ATP hydrolysis sequentially navigates through all six ATPases. There are three principal modes of coordinated hydrolysis, featuring hydrolytic events in two oppositely positioned ATPases, in two adjacent ATPases and in one ATPase at a time. These hydrolytic modes regulate deubiquitylation, initiation of translocation and processive unfolding of substrates, respectively. Hydrolysis of ATP powers a hinge-like motion in each ATPase that regulates its substrate interaction. Synchronization of ATP binding, ADP release and ATP hydrolysis in three adjacent ATPases drives rigid-body rotations of substrate-bound ATPases that are propagated unidirectionally in the ATPase ring and unfold the substrate.


Subject(s)
Cryoelectron Microscopy , Proteasome Endopeptidase Complex/metabolism , Proteasome Endopeptidase Complex/ultrastructure , Adenosine Triphosphatases/metabolism , Adenosine Triphosphate/metabolism , Allosteric Regulation , Holoenzymes/chemistry , Holoenzymes/metabolism , Holoenzymes/ultrastructure , Humans , Hydrolysis , Models, Molecular , Proteasome Endopeptidase Complex/chemistry , Protein Conformation , Protein Structure, Quaternary , Protein Unfolding , Substrate Specificity , Ubiquitination
5.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Article in English | MEDLINE | ID: mdl-35064088

ABSTRACT

Sensing technology is under intense development to enable the Internet of everything and everyone in new and useful ways. Here we demonstrate a method of stretchable and self-powered temperature sensing. The basic sensing element consists of three layers: an electrolyte, a dielectric, and an electrode. The electrolyte/dielectric interface accumulates ions, and the dielectric/electrode interface accumulates electrons (in either excess or deficiency). The ions and electrons at the two interfaces are usually not charge-neutral, and this charge imbalance sets up an ionic cloud in the electrolyte. The design functions as a charged temperature-sensitive capacitor. When temperature changes, the ionic cloud changes thickness, and the electrode changes open-circuit voltage. We demonstrate high sensitivity (∼1 mV/K) and fast response (∼10 ms). Such temperature sensors can be made small, stable, and transparent. Depending on the arrangement of the electrolyte, dielectric, and electrode, we develop four designs for the temperature sensor. In addition, the temperature sensor has good linearity in the range of tens of Kelvin. We further show that the temperature sensors can be integrated into stretchable electronics and soft robots.

6.
Nat Methods ; 18(4): 369-373, 2021 04.
Article in English | MEDLINE | ID: mdl-33795876

ABSTRACT

We introduce an axial localization with repetitive optical selective exposure (ROSE-Z) method for super-resolution imaging. By using an asymmetric optical scheme to generate interference fringes, a <2 nm axial localization precision was achieved with only ~3,000 photons, which is an approximately sixfold improvement compared to previous astigmatism methods. Nanoscale three-dimensional and two-color imaging was demonstrated, illustrating how this method achieves superior performance and facilitates the investigation of cellular nanostructures.


Subject(s)
Imaging, Three-Dimensional/methods , Microscopy/methods , Photons
7.
Arch Biochem Biophys ; 761: 110153, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39271097

ABSTRACT

Myocardial infarction (MI) is the primary source of death in cardiovascular diseases. Myricitrin (MYR) is a phenolic compound known for its antioxidant properties. This study aimed to investigate the impact of MYR alone or combined with exercise on a rat model of MI and its underlying mechanism. Sprague-Dawley rats were randomized into 5 groups: sham-operated (Sham), MI-sedentary (MI-Sed), MI-exercise (MI-Ex), MI-sedentary + MYR (MI-Sed-MYR) and MI-exercise + MYR (MI-Ex-MYR). MI was induced through ligation of left anterior descending coronary artery. The treatment with exercise or MYR (30 mg/kg/d) gavage began one week after surgery, either individually or in combination. After 8 weeks, the rats were assessed for cardiac function. Myocardial injuries were estimated using triphenyltetrazolium chloride, sirius red and Masson staining. Changes in reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), apoptosis and Nrf2/HO-1 pathway were analyzed by ROS kit, JC-1 kit, TUNEL assay, Western blot and immunohistochemistry. Both MYR and exercise treatments improved cardiac function, reduced infarct size, suppressed collagen deposition, and decreased myocardial fibrosis. Additionally, both MYR and exercise treatments lowered ROS production induced by MI, restored ΔΨm, and attenuated oxidative stress and apoptosis in cardiomyocytes. Importantly, the combination of MYR and exercise showed greater efficacy compared to individual treatments. Mechanistically, the combined intervention activated the Nrf2/HO-1 signaling pathway. These findings suggest that the synergistic effect of MYR and exercise may offer a promising therapeutic approach for alleviating MI.

8.
Environ Sci Technol ; 58(41): 18167-18176, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39365373

ABSTRACT

While substantial amounts of antibiotics and pesticides are applied to maintain orchard yields, their influence on the dissemination and risk of antibiotic resisitome in the orchard food chain remains poorly understood. In this study, we characterized the bacterial and fungal communities and differentiated both antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) in the soil, Chinese bayberry (matured and fallen), and fruit fly gut, collected from five geographic locations. Our results showed that fruit fly guts and soils exhibit a higher abundance of ARGs and VFGs compared with bayberry fruits. We identified 112 shared ARGs and 75 shared VFGs, with aminoglycoside and adherence factor genes being among the most abundant. The co-occurrence network revealed some shared microbes, such as Bacillus and Candida, as potential hosts of ARGs, highlighting the vector risks for both above- and below-ground parts of the orchard food chain. Notably, the elevated levels of antibiotics and pesticide residues in orchard soils increase ARGs, mobile genetic elements (MGEs), and VFGs in the soil-bayberry-fruit fly food chain. Our study highlighted that agricultural management, including the overuse of antibiotics and pesticides, could be the key factor in accumulating resistomes in the orchard food chain.


Subject(s)
Anti-Bacterial Agents , Pesticides , Soil Microbiology , Animals , Food Chain , Soil/chemistry , Ecosystem , Drug Resistance, Microbial/genetics , Tephritidae
9.
Phys Chem Chem Phys ; 26(9): 7351-7362, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38375620

ABSTRACT

The C2H2 + OH reaction is an important acetylene oxidation pathway in the combustion process, as well as a typical multi-well and multi-channel reaction. Here, we report an accurate full-dimensional machine learning-based potential energy surface (PES) for the C2H2 + OH reaction at the UCCSD(T)-F12b/cc-pVTZ-F12 level, based on about 475 000 ab initio points. Extensive quasi-classical trajectory (QCT) calculations were performed on the newly developed PES to obtain detailed dynamic data and analyze reaction mechanisms. Below 1000 K, the C2H2 + OH reaction produces H + OCCH2 and CO + CH3. With increasing temperature, the product channels H2O + C2H and H + HCCOH are accessible and the former dominates above 1900 K. It is found that the formation of H2O + C2H is dominated by a direct reaction process, while other channels belong to the indirect mechanism involving long-lived intermediates along the reaction pathways. At low temperatures, the C2H2 + OH reaction behaves like an unimolecular reaction due to the unique PES topographic features, of which the dynamic features are similar to the decomposition of energy-rich complexes formed by C2H2 + OH collision. The classification of trajectories that undergo different reaction pathways to generate each product and their product energy distributions were also reported in this work. This dynamic information may provide a deep understanding of the C2H2 + OH reaction.

10.
J Phys Chem A ; 128(32): 6695-6702, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39109749

ABSTRACT

The C2H2 + OH reaction is a key elementary reaction in acetylene oxidation, and the products forming in different reaction channels, such as C2H and CH3 radicals, are also important for subsequent reaction processes in the combustion process. In this work, we investigated the dynamics of the C2H2 + OH reaction with specific vibrational mode excitations and analyzed the mode specificity based on quasi-classical trajectory calculations on a recently developed full-dimensional potential energy surface. It is found that exciting OH stretching mode can promote the production of H + OCCH2 and CO + CH3, while the excitation of C-H symmetric/antisymmetric stretching mode of C2H2 can facilitate the H2O + C2H channel. Based on the prediction of vibrationally adiabatic and sudden vector projection models, the mode specificity in the C2H2 + OH reaction can be attributed to the difference in the degree of coupling between the initial motion mode and the reaction coordinate of each reaction path, which ultimately leads to the changes in rate constants and the product branching ratios. These findings can offer theoretical insights to regulate the branching ratio of the multichannel C2H2 + OH reaction.

11.
J Phys Chem A ; 128(1): 225-234, 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38146005

ABSTRACT

This work reports six new full-dimensional adiabatic potential energy surfaces (PESs) of the N3 system (four 4A″ states and two 2A″ states) at the MRCI + Q/AVQZ level of theory that correlated to N2(X1Σg+) + N(4S), N2(X1Σg+) + N(2D), N2(A3Σu+) + N(4S), N2(B3Πg) + N(4S), N2(W3Δu) + N(4S), and N(4S) + N(4S) + N(4S) channels. The neural networks with a proper account of the nuclear permutation invariant symmetry of N3 were employed to fit the PESs based on about 4000 ab initio points. The accuracy of the PESs was validated by excellent agreement on the equilibrium bond length, vertical excitation energy, and dissociation energy with experimental values. Two possible mechanisms of the formation of N2(A) were found. One is that the collision occurs between N2(X) and N(4S) in the 14A″ state, followed by a nonadiabatic transition through the conical intersection with the 24A″ PES, resulting in the formation of the N2(A) + N(4S) product. The other takes place in the collision among three N(4S) atoms in the adiabatic 24A″ state, and then, N2(A) + N(4S) is formed. This is the first systematical research of the N3 system focusing on the formation of the excited states of N2 via both adiabatic and nonadiabatic pathways.

12.
BMC Pulm Med ; 24(1): 165, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38575884

ABSTRACT

BACKGROUND: Postoperative pneumonia is one of the common complications after video-assisted thoracoscopic surgery. There is no related study on the effect of lung isolation with different airway devices on postoperative pneumonia. Therefore, in this study, the propensity score matching method was used to retrospectively explore the effects of different lung isolation methods on postoperative pneumonia in patients undergoing video-assisted thoracoscopic surgery. METHODS: This is A single-center, retrospective, propensity score-matched study. The information of patients who underwent VATS in Weifang People 's Hospital from January 2020 to January 2021 was retrospectively included. The patients were divided into three groups according to the airway device used in thoracoscopic surgery: laryngeal mask combined with bronchial blocker group (LM + BB group), tracheal tube combined with bronchial blocker group (TT + BB group) and double-lumen endobronchial tube group (DLT group). The main outcome was the incidence of pneumonia within 7 days after surgery; the secondary outcome were hospitalization time and hospitalization expenses. Patients in the three groups were matched using propensity score matching (PSM) analysis. RESULTS: After propensity score matching analysis, there was no significant difference in the incidence of postoperative pneumonia and hospitalization time among the three groups (P > 0.05), but there was significant difference in hospitalization expenses among the three groups (P < 0.05). CONCLUSIONS: There was no significant difference in the effect of different intubation lung isolation methods on postoperative pneumonia in patients undergoing thoracoscopic surgery.


Subject(s)
Lung Neoplasms , Pneumonia , Humans , Thoracic Surgery, Video-Assisted/adverse effects , Thoracic Surgery, Video-Assisted/methods , Retrospective Studies , Propensity Score , Lung , Lung Neoplasms/surgery , Intubation, Intratracheal/methods , Pneumonia/epidemiology , Pneumonia/etiology
13.
J Dairy Sci ; 107(7): 4320-4332, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38460872

ABSTRACT

In this study, milk fat globule membrane (MFGM) ingredients enriched in polar lipids were prepared using membrane filtration, including microfiltration, diafiltration, and ultrafiltration from butter serum powder. Polar lipids (phospholipids, sterols, and gangliosides) in prepared MFGM ingredients were analyzed by 31P nuclear magnetic resonance spectroscopy, GC-MS, and ultra-performance liquid chromatography (UPLC)-MS/MS, respectively. The lipolysis degree and microstructure of MFGM ingredient and soybean lecithin (SL) emulsions during in vitro digestion were also analyzed. Microfiltration showed higher concentration efficiency than ultrafiltration, which increased by 2.16% and 2.73% in phospholipids, respectively. Moreover, diafiltration concentrated more polar lipids (6.39% of phospholipids) than microfiltration. Milk fat globule membrane ingredients had high levels of sphingomyelin (1.27%-1.36%) and ratio of GD3 to GM3 is 9.25- to 9.88-fold. The different lipolysis behaviors between MFGM ingredient emulsions and SL emulsions were correlated with their different polar lipid compositions. Phospholipids from both MFGM ingredients and SL could help maintain the initial structure during the gastric digestion. These results could provide a scientific basis for developing high-polar-lipids food, particularly infant formulas and special functional foods.


Subject(s)
Glycolipids , Glycoproteins , Lipid Droplets , Animals , Glycolipids/chemistry , Glycoproteins/analysis , Lipids/analysis , Digestion , Phospholipids , Emulsions
14.
BMC Med Educ ; 24(1): 1128, 2024 Oct 11.
Article in English | MEDLINE | ID: mdl-39390473

ABSTRACT

BACKGROUND: Few studies quantified the influence of the coronavirus disease 2019 (COVID-19) pandemic on medical teaching and scientific research activities in China. This is the first national study to investigate such topics from the viewpoint of physicians practicing obstetrics and gynecology in China. METHODS: This is a national questionnaire survey with online interviews for respondents. This two-stage, stratified, cluster sampling method was applied based on city categories (categories 1 to 3 correspond to < 10,000, 10,000 to 30,000, and > 30,000 beds, respectively), hospital levels (primary, secondary, and tertiary), and hospital types (general and specialized) in China among physicians practicing obstetrics and gynecology. Physicians documented notable alterations in both overall and specialized teaching and research engagements. Comparative analyses were conducted across diverse municipal and hospital attributes. RESULTS: Data were collected from a representative sample of 11,806 physicians from 779 hospitals across 157 cities and 31 provinces. Notably, except for online seminars, a minimum reduction of 20% in both overall and specialized teaching and research activities was observed among physicians. Up to 61.7% (95% confidence interval 59.3-64.0) of physicians reported either a complete termination or a > 50% decline in resident training. Compared with category 1 cities and primary hospitals, category 3 cities and tertiary hospitals experienced greater reductions in items of resident or graduate education, visiting scholar, clinical trials, and laboratory studies (adjusted p values < 0.05), coupled with notable increases in online seminar participation (adjusted p values of 0.002 and < 0.001, respectively). CONCLUSIONS: Amidst the COVID-19 pandemic in China, activities requiring direct, face-to-face communication were more affected in resource-rich cities and general hospitals compared to resource-limited areas and specialized hospitals. Residency training experienced the most significant decline. Conversely, participation in online seminars increased, providing additional opportunities for continuing medical education.


Subject(s)
COVID-19 , Gynecology , Obstetrics , Pandemics , SARS-CoV-2 , COVID-19/epidemiology , Humans , China/epidemiology , Gynecology/education , Obstetrics/education , Surveys and Questionnaires , Female , Biomedical Research , Pneumonia, Viral/epidemiology , Coronavirus Infections/epidemiology , Male , Betacoronavirus , Adult
15.
Int J Mol Sci ; 25(16)2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39201345

ABSTRACT

The ripening process of Chinese bayberries (Myrica rubra) is intricate, involving a multitude of molecular interactions. Here, we integrated transcriptomic and metabolomic analysis across three developmental stages of the Myrica rubra (M. rubra) to elucidate these processes. A differential gene expression analysis categorized the genes into four distinct groups based on their expression patterns. Gene ontology and pathway analyses highlighted processes such as cellular and metabolic processes, including protein and sucrose metabolism. A metabolomic analysis revealed significant variations in metabolite profiles, underscoring the dynamic interplay between genes and metabolites during ripening. Flavonoid biosynthesis and starch and sucrose metabolism were identified as key pathways, with specific genes and metabolites playing crucial roles. Our findings provide insights into the molecular mechanisms governing fruit ripening in M. rubra and offer potential targets for breeding strategies aimed at enhancing fruit quality.


Subject(s)
Fruit , Metabolomics , Myrica , Flavonoids/metabolism , Flavonoids/biosynthesis , Fruit/metabolism , Fruit/genetics , Fruit/growth & development , Gene Expression Profiling , Gene Expression Regulation, Plant , Metabolome , Metabolomics/methods , Myrica/genetics , Myrica/metabolism , Myrica/growth & development , Plant Proteins/genetics , Plant Proteins/metabolism , Transcriptome
16.
Molecules ; 29(9)2024 May 01.
Article in English | MEDLINE | ID: mdl-38731587

ABSTRACT

We aimed to obtain the optimal formula for human milk fat substitute (HMFS) through a combination of software and an evaluation model and further verify its practicability through an animal experiment. The results showed that a total of 33 fatty acid (FA) and 63 triglyceride (TAG) molecular species were detected in vegetable oils. Palmitic acid, oleic acid, linoleic acid, 18:1/16:0/18:1, 18:2/16:0/18:2, 18:1/18:1/18:1 and 18:1/18:2/18:1, were the main molecular species among the FAs and TAGs in the vegetable oils. Based on the HMFS evaluation model, the optimal mixed vegetable oil formula was blended with 21.3% palm oil, 2.8% linseed oil, 2.6% soybean oil, 29.9% rapeseed oil and 43.4% maize oil, with the highest score of 83.146. Moreover, there was no difference in the weight, blood routine indices or calcium and magnesium concentrations in the feces of the mice between the homemade mixed vegetable oil (HMVO) group and the commercial mixed vegetable oil (CMVO) group, while nervonic acid (C24:1) and octanoic acid (C8:0) were absorbed easily in the HMVO group. Therefore, these results demonstrate that the mixing of the different vegetable oils was feasible via a combination of computer software and an evaluation model and provided a new way to produce HMFS.


Subject(s)
Fat Substitutes , Fatty Acids , Milk, Human , Plant Oils , Software , Triglycerides , Humans , Animals , Plant Oils/chemistry , Fatty Acids/chemistry , Milk, Human/chemistry , Mice , Triglycerides/chemistry , Fat Substitutes/chemistry , Palm Oil/chemistry , Soybean Oil/chemistry , Linseed Oil/chemistry , Rapeseed Oil/chemistry , Corn Oil/chemistry , Caprylates/chemistry , Palmitic Acid/chemistry , Oleic Acid/chemistry
17.
Microb Ecol ; 87(1): 5, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38030815

ABSTRACT

Cholangiocarcinoma (CCA) is a serious health problem worldwide. The gut and bile microbiota have not been clearly characterized in patients with CCA, and better noninvasive diagnostic approaches for CCA need to be established. The aim of this study was to investigate the characteristics of the gut and bile microbiota in CCA patients. Forty-two CCA patients and 16 healthy normal controls (HNCs) were enrolled. DNA was extracted from fecal and bile samples and subjected to 16S rRNA gene analysis. We found that there were significant differences in the species diversity, structure, and composition of the microbial communities between the CCA group and the HNC grouAt the phylum level, compared with that in the HNC group, the relative abundance of Firmicutes and Actinobacteriota was significantly decreased in the CCA group, whereas Proteobacteria and Bacteroidota were significantly enriched. The Firmicutes/Bacteroidota (F/B) ratio significantly decreased in the CCA group compared to the HNC grouThe relative abundance of Klebsiella in the CCA group was significantly higher than that in the HNC group, while the relative abundance of Bifidobacterium was significantly decreased. The Bifidobacterium/Klebsiella (B/K) ratio was established as a novel biomarker and was found to be significantly decreased in the CCA group compared with the HNC grouOur findings provide evidence supporting the use of Klebsiella and Bifidobacterium as noninvasive intestinal microbiomarkers for improving the diagnosis of CCA.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Humans , Bifidobacterium/genetics , Klebsiella/genetics , RNA, Ribosomal, 16S/genetics , Bile , Firmicutes/genetics , Bacteroidetes/genetics , Feces/microbiology
18.
Environ Sci Technol ; 57(15): 6139-6149, 2023 04 18.
Article in English | MEDLINE | ID: mdl-37017313

ABSTRACT

Previous studies have reported the immunotoxicity of per- and polyfluoroalkyl substances (PFASs), but it remains a significant challenge to assess over 10,000 distinct PFASs registered in the distributed structure-searchable toxicity (DSSTox) database. We aim to reveal the mechanisms of immunotoxicity of different PFASs and hypothesize that PFAS immunotoxicity is dependent on the carbon chain length. Perfluorobutanesulfonic acid (PFBA), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) representing different carbon chain lengths (4-9) at environmentally relevant levels strongly reduced the host's antibacterial ability during the zebrafish's early-life stage. Innate and adaptive immunities were both suppressed after PFAS exposures, exhibiting a significant induction of macrophages and neutrophils and expression of immune-related genes and indicators. Interestingly, the PFAS-induced immunotoxic responses were positively correlated to the carbon chain length. Moreover, PFASs activated downstream genes of the toll-like receptor (TLR), uncovering a seminal role of TLR in PFAS immunomodulatory effects. Myeloid differentiation factor 88 (MyD88) morpholino knock-down experiments and MyD88 inhibitors alleviated the immunotoxicity of PFASs. Overall, the comparative results demonstrate differences in the immunotoxic responses of PFASs due to carbon chain length in zebrafish, providing new insights into the prediction and classification of PFASs mode of toxic action based on carbon chain length.


Subject(s)
Alkanesulfonic Acids , Fluorocarbons , Water Pollutants, Chemical , Animals , Zebrafish , Carbon , Myeloid Differentiation Factor 88 , Fluorocarbons/toxicity
19.
Phys Chem Chem Phys ; 25(29): 19788-19794, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37449776

ABSTRACT

Fluidic transport down to the nanometer scale is of great importance for a wide range of applications such as energy harvesting, seawater desalination, and water treatment and may help to understand many biological processes. In this work, we studied the interfacial friction of liquid water on a series of nanostructures through molecular dynamics (MD) simulations. Our results reveal that the friction coefficient of the water-solid interface cannot be described using a previously reported simple function of the free energy corrugation. Considering that the water-solid friction is firmly correlated with the microscopic water motion, we proposed a probability parameter P(d, t) to classify water motion modes on a surface. We demonstrate that this parameter can be used to accurately predict the water-solid friction by simply monitoring the water binding time on a nanosurface. More importantly, according to the relationship between P(d, t) and friction, we found that the friction coefficient can be used as an indicative criterion for quantitatively assessing hydrophobic or hydrophilic materials, where the borderline is roughly 2 × 105 N s m-3. That is if the water-solid friction is less than 2 × 105 N s m-3, the surface is considered hydrophobic. But if the friction is larger than this value, the surface is hydrophilic. The present findings could help to better understand fluidic transport at the nanoscale and guide the future design of functional materials, such as super-hydrophobic and super-hydrophilic surfaces by structure engineering.

20.
Environ Res ; 217: 114911, 2023 01 15.
Article in English | MEDLINE | ID: mdl-36427641

ABSTRACT

Nonthermal plasma (NTP) irradiation was employed to adjust the morphological structures and valence distribution of ferromanganese (Fe-Mn)-based binary hydro (oxide) to enhance the heterogeneous adsorption of uranyl ions. The output voltage and the liquid-plate distance played a more vital role among the NTP factors in the irradiation system in influencing the polyvalent Fe-Mn binary hydro (oxide) (poly-Fe-Mn). The formation of plates, flakes, and nanoscale nodules was specifically observed, which caused more pores and fractures in the poly-Fe-Mn binary hydro (oxide). The poly-Fe-Mn performed explicitly better in the adsorption of uranium ions in comparison with the counterpart of the Fe-Mn, which was appropriately fitted by the pseudofirst-order kinetic and Elovich models. Maximum equilibrium adsorption capacities of 663.92 and 923.45 mg/g were obtained for the Fe-Mn and poly-Fe-Mn binary hydro (oxides) toward U ions in the orthogonal design, respectively. The maximum monolayer adsorption capacity achieved by the fitting of the Langmuir model was 1091.10 mg/g. Both physisorption and chemisorption contributed to the heterogeneous process of the poly-Fe-Mn toward uranium ions. The employment of NTP irradiation changed the monolayer adsorption of the traditional Fe-Mn materials and diversified the reaction mechanisms between the interface of the Fe-Mn materials and uranium ions. The elements, including O, N, and U exhibited higher compatibility and overlapped in the samples. The highly effective capture of uranium ions from the solution by the poly-Fe-Mn binary hydro (oxide) was mainly related to the chemical deposition of O and N radicals.


Subject(s)
Uranium , Water Purification , Oxides/chemistry , Wastewater , Hydrogen-Ion Concentration , Adsorption , Ions , Kinetics
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