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1.
EMBO Rep ; 25(7): 3116-3136, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38877169

ABSTRACT

A novel pangolin-origin MERS-like coronavirus (CoV), MjHKU4r-CoV-1, was recently identified. It is closely related to bat HKU4-CoV, and is infectious in human organs and transgenic mice. MjHKU4r-CoV-1 uses the dipeptidyl peptidase 4 (DPP4 or CD26) receptor for virus entry and has a broad host tropism. However, the molecular mechanism of its receptor binding and determinants of host range are not yet clear. Herein, we determine the structure of the MjHKU4r-CoV-1 spike (S) protein receptor-binding domain (RBD) complexed with human CD26 (hCD26) to reveal the basis for its receptor binding. Measuring binding capacity toward multiple animal receptors for MjHKU4r-CoV-1, mutagenesis analyses, and homology modeling highlight that residue sites 291, 292, 294, 295, 336, and 344 of CD26 are the crucial host range determinants for MjHKU4r-CoV-1. These results broaden our understanding of this potentially high-risk virus and will help us prepare for possible outbreaks in the future.


Subject(s)
Dipeptidyl Peptidase 4 , Host Specificity , Protein Binding , Receptors, Virus , Spike Glycoprotein, Coronavirus , Viral Tropism , Humans , Animals , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/chemistry , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl Peptidase 4/genetics , Receptors, Virus/metabolism , Receptors, Virus/genetics , Receptors, Virus/chemistry , Mice , Binding Sites , Virus Internalization , Models, Molecular , Protein Domains , Host Tropism
2.
Apoptosis ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886312

ABSTRACT

With global warming, extreme environmental heat is becoming a social issue of concern, which can cause adverse health results including heatstroke (HS). Severe heat stress is characterized by cell death of direct heat damage, excessive inflammatory responses, and coagulation disorders that can lead to multiple organ dysfunction (MODS) and even death. However, the significant pathophysiological mechanism and treatment of HS are still not fully clear. Various modes of cell death, including apoptosis, pyroptosis, ferroptosis, necroptosis and PANoptosis are involved in MODS induced by heatstroke. In this review, we summarized molecular mechanism, key transcriptional regulation as for HSF1, NRF2, NF-κB and PARP-1, and potential therapies of cell death resulting in CNS, liver, intestine, reproductive system and kidney injury induced by heat stress. Understanding the mechanism of cell death provides new targets to protect multi-organ function in HS.

3.
Chemphyschem ; : e202400227, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38808500

ABSTRACT

Directly transforming solar energy into chemical compounds via photocatalytic water splitting can continually producing hydrogen, regarded as one of the ultimate sustainable energy sources. The key point of achieving high photoelectrochemical (PEC) water splitting performance depends on the successful design and synthesis of high-efficient photocatalysts. However, the slow separation and fast recombination of photo generated charge carriers greatly limit the utilization of solar energy, resulting in low PEC water splitting efficiency. Recently, piezoelectric/pyroelectric effect assisted PEC water splitting brings new sight on improving charger separate and transfer behaviors. In this review, the recent advancements and state-of-the-art progress in piezoelectric/pyroelectric effect assisted PEC water splitting are summarized and discussed. Different types of photocatalysts are classified according to their chemical constitutions and the corresponding advantages of each type are also discussed. Furthermore, the progress of coupling piezoelectric effect and pyroelectric effect in one PEC water splitting system is also introduced. Finally, the prospects, critical challenges and promising strategies for the application of piezoelectric/pyroelectric materials in PEC water splitting are highlighted.

4.
Gastrointest Endosc ; 99(1): 91-99.e9, 2024 01.
Article in English | MEDLINE | ID: mdl-37536635

ABSTRACT

BACKGROUND AND AIMS: The efficacy and safety of colonoscopy performed by artificial intelligence (AI)-assisted novices remain unknown. The aim of this study was to compare the lesion detection capability of novices, AI-assisted novices, and experts. METHODS: This multicenter, randomized, noninferiority tandem study was conducted across 3 hospitals in China from May 1, 2022, to November 11, 2022. Eligible patients were randomized into 1 of 3 groups: the CN group (control novice group, withdrawal performed by a novice independently), the AN group (AI-assisted novice group, withdrawal performed by a novice with AI assistance), or the CE group (control expert group, withdrawal performed by an expert independently). Participants underwent a repeat colonoscopy conducted by an AI-assisted expert to evaluate the lesion miss rate and ensure lesion detection. The primary outcome was the adenoma miss rate (AMR). RESULTS: A total of 685 eligible patients were analyzed: 229 in the CN group, 227 in the AN group, and 229 in the CE group. Both AMR and polyp miss rate were lower in the AN group than in the CN group (18.82% vs 43.69% [P < .001] and 21.23% vs 35.38% [P < .001], respectively). The noninferiority margin was met between the AN and CE groups of both AMR and polyp miss rate (18.82% vs 26.97% [P = .202] and 21.23% vs 24.10% [P < .249]). CONCLUSIONS: AI-assisted colonoscopy lowered the AMR of novices, making them noninferior to experts. The withdrawal technique of new endoscopists can be enhanced by AI-assisted colonoscopy. (Clinical trial registration number: NCT05323279.).


Subject(s)
Adenoma , Colonic Polyps , Colorectal Neoplasms , Polyps , Humans , Artificial Intelligence , Prospective Studies , Colonoscopy/methods , Research Design , Adenoma/diagnosis , Adenoma/pathology , Colonic Polyps/diagnostic imaging , Colorectal Neoplasms/diagnosis
5.
Endoscopy ; 56(4): 260-270, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37827513

ABSTRACT

BACKGROUND: The choice of polypectomy device and surveillance intervals for colorectal polyps are primarily decided by polyp size. We developed a deep learning-based system (ENDOANGEL-CPS) to estimate colorectal polyp size in real time. METHODS: ENDOANGEL-CPS calculates polyp size by estimating the distance from the endoscope lens to the polyp using the parameters of the lens. The depth estimator network was developed on 7297 images from five virtually produced colon videos and tested on 730 images from seven virtual colon videos. The performance of the system was first evaluated in nine videos of a simulated colon with polyps attached, then tested in 157 real-world prospective videos from three hospitals, with the outcomes compared with that of nine endoscopists over 69 videos. Inappropriate surveillance recommendations caused by incorrect estimation of polyp size were also analyzed. RESULTS: The relative error of depth estimation was 11.3% (SD 6.0%) in successive virtual colon images. The concordance correlation coefficients (CCCs) between system estimation and ground truth were 0.89 and 0.93 in images of a simulated colon and multicenter videos of 157 polyps. The mean CCC of ENDOANGEL-CPS surpassed all endoscopists (0.89 vs. 0.41 [SD 0.29]; P<0.001). The relative accuracy of ENDOANGEL-CPS was significantly higher than that of endoscopists (89.9% vs. 54.7%; P<0.001). Regarding inappropriate surveillance recommendations, the system's error rate is also lower than that of endoscopists (1.5% vs. 16.6%; P<0.001). CONCLUSIONS: ENDOANGEL-CPS could potentially improve the accuracy of colorectal polyp size measurements and size-based surveillance intervals.


Subject(s)
Colonic Polyps , Colorectal Neoplasms , Deep Learning , Humans , Colonic Polyps/diagnostic imaging , Colonoscopy/methods , Colorectal Neoplasms/diagnostic imaging
6.
Nature ; 559(7713): 193-204, 2018 07.
Article in English | MEDLINE | ID: mdl-29995865

ABSTRACT

China has responded to a national land-system sustainability emergency via an integrated portfolio of large-scale programmes. Here we review 16 sustainability programmes, which invested US$378.5 billion (in 2015 US$), covered 623.9 million hectares of land and involved over 500 million people, mostly since 1998. We find overwhelmingly that the interventions improved the sustainability of China's rural land systems, but the impacts are nuanced and adverse outcomes have occurred. We identify some key characteristics of programme success, potential risks to their durability, and future research needs. We suggest directions for China and other nations as they progress towards the Sustainable Development Goals of the United Nations' Agenda 2030.


Subject(s)
Soil , Sustainable Development/trends , Agriculture , Biodiversity , China , Conservation of Natural Resources , Food Supply , Forests , Goals , Grassland , Sustainable Development/economics , Sustainable Development/legislation & jurisprudence , Time Factors , United Nations , Water
7.
J Chem Phys ; 160(24)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38916267

ABSTRACT

We report the free energy barriers for the elementary reactions in the 2e- and 4e- oxygen reduction reaction (ORR) steps on Au(100) in an alkaline solution. Due to the weak adsorption energy of O2 on Au(100), the barrier for the association channel is very low, and the 2e- pathway is clearly favored, while the barrier for the O-O dissociation channel is significantly higher at 0.5 eV. Above 0.7 V reversible hydrogen electrode (RHE), the association channel becomes thermodynamically unfavorable, which opens up the O-O dissociation channel, leading to the 4e- pathway. The low adsorption energy of oxygenated species on Au is now an advantage, and residue ORR current can be observed up to the 1.0-1.2 V region (RHE). In contrast, the O-O dissociation barrier on Au(111) is significantly higher, at close to 0.9 eV, due to coupling with surface reorganization, which explains the lower ORR activity on Au(111) than that on Au(100). In combination with the previously suggested outer sphere electron transfer to O2 for its initial adsorption, these results provide a consistent explanation for the features in the experimentally measured polarization curve for the alkaline ORR on Au(100) and demonstrate an ORR mechanism distinct from that on Pt(111). It also highlights the importance to consider the spin state of O2 in ORR and to understand the activation barriers, in addition to the adsorption energies, to account for the features observed in electrochemical measurements.

8.
J Environ Manage ; 356: 120617, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38537466

ABSTRACT

Residents' environmental attitudes (EAs) towards ecological restoration programs are vital for evaluating program effectiveness and promoting environmental management. However, most local studies have neglected the indirect environmental contextual influences on residents' EAs, and have omitted the regional variations in the environmental contextual influences. To investigate the multilevel factors affecting residents' EAs, we conducted a transect survey that included the eastern, middle, and western regions in northern China's drylands, where have experienced ecological restoration. Multilevel linear models (MLMs) were applied to analyse the direct and indirect impacts of environmental contexts and individual characteristics on rural residents' EAs. The results showed the environmental context can indirectly impact EAs by amplifying the influence of individual characteristics such as family structure and income on EAs. The EAs are influenced by different local environmental contexts among the east, middle and west of China's drylands. The humidity attitude was influenced by precipitation only in the highly arid western and middle regions, while precipitation attitude is strongly influenced by land surface temperature and humidity in eastern China's drylands. These findings hold important implications for understanding the cross-scale impact of environmental contexts on EAs in drylands.


Subject(s)
Attitude , Income , Humans , Rural Population , China
9.
J Environ Manage ; 353: 120168, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38278111

ABSTRACT

Arsenic (As)-immobilizing iron (Fe)-manganese (Mn) minerals (AFMM) represent potential As sinks in As-enriched groundwater environments. The process and mechanisms governing As bio-leaching from AFMM through interaction with reducing bacteria, however, remain poorly delineated. This study examined the transformation and release of As from AFMM with varying Mn/Fe molar ratios (0:1, 1:5, 1:3, and 1:1) in the presence of As(V)-reducing bacteria specifically Shewanella putrefaciens CN32. Notably, strain CN32 significantly facilitated the bio-reduction of As(V), Fe(III), and Mn(IV) in AFMM. In systems with Mn/Fe molar ratios of 1:5, 1:3, and 1:1, As bio-reduction decreased by 28%, 34%, and 47%, respectively, compared to the system with a 0:1 ratio. This Mn-induced inhibition of Fe/As bio-reduction was linked to several concurrent factors: preferential Mn bio-reduction, reoxidation of resultant Fe(II)/As(III) due to Mn components, and As adsorption onto emergent Fe precipitates. Both the reductive dissolution of AFMM and the bio-reduction of As(V) predominantly controlled As bio-release. Structural equation models indicated that reducing bacteria destabilize natural As sinks more through As reduction than through Mn(II) release, Fe reduction, or Fe(II) release. Systems with Mn/Fe molar ratios of 1:5, 1:3, and 1:1 showed a decrease in As bio-release by 24%, 41%, and 59%, respectively, relative to the 0:1 system. The observed suppression of As bioleaching was ascribed to both the inhibition of As/Fe bio-reduction by Mn components and the immobilization of As by freshly generated Fe precipitates. These insights into the constraining effect of Mn on the biotransformation and bioleaching of As from AFMM are crucial for grasping the long-term stability of natural As sinks in groundwater, and enhance strategies for in-situ As stabilization in As-afflicted aquifers through Nature-Based Solutions.


Subject(s)
Arsenic , Groundwater , Water Pollutants, Chemical , Manganese/analysis , Arsenic/chemistry , Ferric Compounds/chemistry , Minerals/chemistry , Groundwater/chemistry , Bacteria , Ferrous Compounds , Oxidation-Reduction , Water Pollutants, Chemical/chemistry
10.
Fish Physiol Biochem ; 50(1): 295-305, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38386263

ABSTRACT

Peroxisome proliferator-activated receptor ß (pparß) is a key gene-regulating lipid metabolism pathway, but its function in turbot remains unclear. In this study, the CDS of pparß was cloned from kidney for the first time. The CDS sequence length was 1533 bp encoding 510 amino acids. Structural analysis showed that the pparß protein contained a C4 zinc finger and HOLI domain, suggesting that the pparß gene of turbot has high homology with the PPAR gene of other species. The high expression patterns of pparß, acox, and cpt-1 at high temperatures, as shown through qPCR, indicated that high temperatures activated the transcriptional activity of pparß and increased the activity of the acox and cpt-1 genes. The expression of acox and cpt-1 was significantly inhibited when pparß was downregulated using RNAi technology and inhibitor treatments, suggesting that pparß positively regulated acox and cpt-1 expression at high temperatures and, thus, modulates lipid catabolism activity. These results demonstrate that pparß is involved in the regulation of lipid metabolism at high temperatures and expand a new perspective for studying the regulation of lipid metabolism in stress environments of teleost.


Subject(s)
Flatfishes , PPAR-beta , Animals , PPAR-beta/genetics , Flatfishes/genetics , Lipid Metabolism/genetics , Lipids , Heat-Shock Response
11.
Chin J Traumatol ; 27(1): 18-26, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37423838

ABSTRACT

PURPOSE: The incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway. METHODS: We established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant. RESULTS: Electroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F = 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F = 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F = 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F = 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F = 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F = 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression. CONCLUSIONS: CGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.


Subject(s)
Calcitonin Gene-Related Peptide , Heat Stroke , Isoquinolines , Sulfonamides , Animals , Rats , Apoptosis , Brain Injuries/metabolism , Brain Injuries/pathology , Calcitonin Gene-Related Peptide/pharmacology , Calcitonin Gene-Related Peptide/metabolism , Caspase 3 , Proto-Oncogene Proteins c-bcl-2 , Rats, Sprague-Dawley , Heat Stroke/metabolism , Heat Stroke/pathology
12.
Chin J Traumatol ; 27(2): 91-96, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37973473

ABSTRACT

PURPOSE: Minimal data exist on brain injury in patients with exertional heatstroke (EHS) in developing country. In this study, we explored the risk factors for brain injury induced by EHS 90-day after onset. METHODS: A retrospective cohort study of patients with EHS was conducted in the intensive care unit of the General Hospital of Southern Theater Command of PLA in China from April 2014 to June 2019. Patients were divided into non-brain injury (fully recovered) and brain injury groups (comprising deceased patients or those with neurological sequelae). The brain injury group was further subdivided into a death group and a sequela group for detailed analysis. General information, neurological performance and information on important organ injuries in the acute stage were recorded and analysed. Multivariable logistic regression was used to identify risk factors for brain injury after EHS and mortality risk factors for brain injury, and Kaplan-Meier survival curve was used to evaluate the effect of the neurological dysfunction on survival. RESULTS: Out of the 147 EHS patients, 117 were enrolled, of which 96 (82.1%) recovered, 13 (11.1%) died, and 8 (6.8%) experienced neurological sequelae. Statistically significant differences were found between non-brain injury and brain injury groups in age, hypotension, duration of consciousness disorders, time to drop core body temperature below 38.5°C, lymphocyte counts, platelet counts, procalcitonin, alanine aminotransferase, aspartate aminotransferase, creatinine, cystatin C, coagulation parameters, international normalized ratio, acute physiology and chronic health evaluation II scores, sequential organ failure assessment (SOFA) scores, and Glasgow coma scale scores (all p < 0.05). Multivariate logistic regression showed that age (OR = 1.090, 95% CI: 1.02 - 1.17, p = 0.008), time to drop core temperature (OR = 8.223, 95% CI: 2.30 - 29.40, p = 0.001), and SOFA scores (OR = 1.676, 95% CI: 1.29 - 2.18, p < 0.001) are independent risk factors for brain injury induced by EHS. The Kaplan-Meier curves suggest significantly prolonged survival (p < 0.001) in patients with early Glasgow coma scale score > 8 and duration of consciousness disorders ≤ 24 h. CONCLUSIONS: Advanced age, delayed cooling, and higher SOFA scores significantly increase the risk of brain injury post-EHS. These findings underscore the importance of rapid cooling and early assessment of organ failure to improve outcomes in EHS patients.


Subject(s)
Brain Injuries , Heat Stroke , Sepsis , Humans , Retrospective Studies , Consciousness Disorders , Disease Progression , Risk Factors , Intensive Care Units , Heat Stroke/complications , Prognosis , ROC Curve
13.
J Environ Sci (China) ; 146: 81-90, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38969464

ABSTRACT

Silver carp mediated biological control techniques are often advocated for controlling cyanobacteria blooms in eutrophic water, which are often enriched with arsenic (As). However, the transfer and fate of As during the biological control of cyanobacteria blooms by silver carp in As-rich eutrophic water remain unclear. Based on the simulated ecosystem experiment, the accumulation of As in silver carp and the transfer and fate of As in the water-algae-silver carp system during Microcystis aeruginosa blooms controlled by silver carp were investigated. Microcystis aeruginosa showed high tolerance to As(V). The accumulation of As in different tissues of silver carp was different, as follows: intestine > liver > gill > skin > muscle. After silver carp ingested As-rich Microcystis aeruginosa, As accumulation in the intestine, liver, gill, and skin of silver carp was enhanced under the action of digestion and skin contact. Compared with the system without algal, As accumulation in the intestine, liver, gill, and skin of silver carp increased by 1.1, 3.3, 3.3, and 9.6 times, respectively, after incubation for 30 days in the system with Microcystis aeruginosa, while the accumulation of As in the muscle was only slightly increased by 0.56 mg/kg. This work revealed the transfer and fate of As during algal control by silver carp, elucidated the accumulation mechanism of As in water-algae-silver carp system, enriched our understanding of As bioaccumulation and transformation in As-rich eutrophication water, and provided a scientific basis for assessing and predicting As migration and enrichment in water-algae-silver carp system.


Subject(s)
Arsenic , Carps , Eutrophication , Microcystis , Water Pollutants, Chemical , Microcystis/metabolism , Animals , Carps/metabolism , Arsenic/metabolism , Arsenic/analysis , Water Pollutants, Chemical/metabolism , Water Pollutants, Chemical/analysis , Environmental Monitoring
14.
Mol Carcinog ; 62(5): 628-640, 2023 05.
Article in English | MEDLINE | ID: mdl-36727616

ABSTRACT

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Currently, therapeutic modalities such as surgery, chemotherapy, radiotherapy, and immunotherapy are being used to treat HNSCC. However, the treatment outcomes of most patients are dismal because they are already in middle or advanced stage by the time of diagnosis and poorly responsive to treatments. It is therefore of great interest to clarify mechanisms that contribute to the metastasis of cells to identify possible targets for therapy. In this study, we identified the Na+ -coupled bicarbonate transporter, SLC4A7, play essential roles in the metastasis of HNSCC. Our results showed that the relative expression of SLC4A7 messenger RNA was highly expressed in HNSCCs samples from TCGA, and compared with precancerous cells of human oral mucosa (DOK), SLC4A7 was highly expressed in HNSCC cell lines. In vitro and in vivo experiments showed that dysregulation of SLC4A7 had minor influence on the proliferation of HNSCC but impacted HNSCC's migration and invasion. Meanwhile, SLC4A7 could promote epithelial-mesenchymal transition (EMT) in HNSCC. RNA-seq, KEGG pathway enrichment analysis and Western blot further revealed that downregulation of SLC4A7 in HNSCC cells inhibited the PI3K/AKT pathway. These findings were further validated via rescue experiments using a small molecule inhibitor of PI3K/mTOR (GDC-0980). Our findings suggest that SLC4A7 promotes EMT and metastasis of HNSCC through the PI3K/AKT/mTOR signaling pathway, which may be a valuable predictive biomarker and potential therapeutic target in HNSCC.


Subject(s)
Head and Neck Neoplasms , Proto-Oncogene Proteins c-akt , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Bicarbonates/metabolism , Epithelial-Mesenchymal Transition/genetics , Head and Neck Neoplasms/genetics , Signal Transduction , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Cell Line, Tumor , Cell Proliferation , Cell Movement/genetics , Sodium-Bicarbonate Symporters/genetics , Sodium-Bicarbonate Symporters/metabolism
15.
Microb Pathog ; 184: 106373, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37769855

ABSTRACT

BACKGROUND: Children with refractory constipation experience intense and persistent symptoms that greatly diminish their quality of life. However, the underlying pathophysiological mechanism responsible for this condition remains uncertain. Our objective was to evaluate characteristics of colonic motor patterns and interstitial cells of Cajal (ICCs) to refractory constipation children, as well as intestinal microbiota compositions. METHODS: Colonic manometry (CM) was conducted on a cohort of 30 patients with refractory constipation to assess colonic motility, and 7 of them underwent full-thickness colon biopsy specimens. Another 5 colonic specimens from nonconstipation patients were collected to identify the ICCs by immunohistochemistry. Fecal samples from 14 children diagnosed with refractory constipation and subjecting 28 age-matched healthy children to analysis using high-throughput sequencing of 16S rRNA. RESULTS: According to CM results, dividing 30 children with refractory constipation into 2 groups: normal group (n = 10) and dysmotility group (n = 20). Dysmotility subjects showed lower colonic motility. Antegrade propagating pressure waves, retrograde propagating pressure waves, and periodic colonic motor activity were common in normal subjects and rare in dysmotility subjects (32.7 ± 8.9 vs 20.7 ± 13.0/17 h, P < 0.05, 11.5 ± 2.3 vs 9.6 ± 2.3/17 h, P < 0.05, and 5.2 ± 8.9 vs 3.5 ± 6.8 cpm, P < 0.005, respectively), whereas periodic rectal motor activity was more common in dysmotility subjects (3.4 ± 4.8 vs 3.0 ± 3.1 cpm, P < 0.05). Dysmotility subjects exhibited a significantly greater number of preprandial simultaneous pressure waves compared to the normal subjects (32.3 ± 25.0 vs 23.6 ± 13.2/1 h, P < 0.005). Dysmotility subjects displayed a notable decrease in postprandial count of antegrade propagating pressure waves and high amplitude propagating pressure waves when compared to normal subjects (3.9 ± 2.9 vs 6.9 ± 3.5/1 h and 2.3 ± 1.5 vs 5.4 ± 2.9/1 h, respectively, P < 0.05). The number, distribution, and morphology of ICCs were markedly altered in refractory constipation compared children to the controls (P < 0.05). Children diagnosed with refractory constipation displayed a distinct dissimilarity in composition of their intestinal microbiota comparing with control group (P < 0.005). In genus level, Bacteroidetes represented 34.34% and 43.78% in the refractory constipation and control groups, respectively. Faecalibacterium accounted for 3.35% and 12.56%, respectively (P < 0.005). Furthermore, the relative abundances of Faecalibacterium (P < 0.005), Lachnospira (P < 0.05), and Haemophilus (P < 0.05) significantly decreased, whereas those of Parabacteroides (P < 0.05), Alistipes (P < 0.005), Prevotella_2 (P < 0.005), [Ruminococcus]_torques_group (P < 0.005), Barnesiella (P < 0.05), Ruminococcaceae_UCG-002 (P < 0.005), and Christensensenellaceae_R-7_group (P < 0.05) were markedly increased in children with refractory constipation. CONCLUSIONS: Dysmotility subjects showed lower colonic motility and an impaired postprandial colonic response. The decreased number and abnormal morphology of colonic ICCs may contribute to the pathogenesis of refractory constipation. Children with refractory constipation exhibited significant variations in microbiota composition across various taxonomic levels compared to the healthy control group. Our findings contribute valuable insights into pathophysiological mechanism underlying refractory constipation and provide evidence to support the exploration of novel therapeutic strategies for affected children.


Subject(s)
Gastrointestinal Microbiome , Interstitial Cells of Cajal , Humans , Child , Interstitial Cells of Cajal/pathology , Quality of Life , RNA, Ribosomal, 16S/genetics , Constipation/diagnosis , Constipation/pathology , Colon/pathology , Bacteroidetes
16.
Chemistry ; 29(64): e202301967, 2023 Nov 16.
Article in English | MEDLINE | ID: mdl-37608518

ABSTRACT

Pyroelectric materials in the field of photoelectrochemical (PEC) water splitting still face the problems of difficult low spontaneous polarization intensity and excessive carrier recombination. Based on the above problems, we altered the interaction between S-Nb-S in the [NbO]6-x -xS structure, and the constructed [NbO]6-x -xS structure achieved the regulation of charge density change and spontaneous polarization. The results show that under the stimulation of light and temperature fluctuations, the current density of the NS-4 photoanode is as high as 0.574 mA/cm2 at 1.23 VRHE , which is about 1.59 times higher than the pure NaNbO3 current density value, and the NS -4 photoanode achieves IPCE value of 16.08 %. The first-principles density-functional theory calculations (DFT) reveal the principle of the [NbO]6-x -xS structure for the suppression function of the carrier recombination and the improvement function of the pyroelectric effect. The analysis shows that the S-doping leads to the weakening of S-Nb-S interactions in the [NbO]6-x -xS structure, which improves the pyroelectric effect and suppresses the photo/pyro-generated carrier recombination, and effectively enhances the performance of the pyro-photo-electric synergistic water splitting system. This work promotes the development of pyroelectric materials in the field of photoelectrochemical water splitting.

17.
J Fluoresc ; 33(2): 653-661, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36480126

ABSTRACT

Accurate monitoring of intracellular pH in living cells is critical for developing a better understanding of cellular activities. In the current study, label-free carbon dots (p-CDs), which were fabricated using a straightforward one-pot solvothermal treatment of p-phenylenediamine and urea, were employed to create a new ratiometric pH nanosensor. Under single-wavelength excitation (λex = 500 nm), the p-CDs gave dual emission bands at 525 and 623 nm. The fluorescent intensity ratio (I525/I623) was linearly related to pH over the range 4.0 to 8.8 in buffer solutions, indicating that the ratiometric fluorescence nanoprobe may be useful for pH sensing. In pH measurements, the p-CDs also demonstrated outstanding selectivity, reversibility, and photostability. Owing to the advantages outlined above, the nanoprobe was used to monitor the pH of HeLa cells effectively. The label-free CD-based ratiometric nanoprobe features comparatively easy manufacturing and longer excitation and emission wavelengths than the majority of previously reported CD-based ratiometric pH sensors, which is ultimately beneficial for applications in biological imaging.


Subject(s)
Quantum Dots , Humans , HeLa Cells , Carbon , Fluorescent Dyes , Hydrogen-Ion Concentration
18.
Phys Chem Chem Phys ; 25(32): 21331-21335, 2023 Aug 16.
Article in English | MEDLINE | ID: mdl-37529872

ABSTRACT

The transverse magneto-optical Kerr effect (TMOKE) has attracted widespread scientific interest because of its potential applications in biosensor technology, data storage, optical isolation, and telecommunications. More conventional architectures, including prism-based metal/magnetic multilayers and nanoarrays that integrate plasmonic and magnetic materials, are commonly used to amplify TMOKE through the high-quality propagation of the surface plasmon resonance optical mode. However, the main disadvantages of these architectures are their large ohmic losses and radiation damping, resulting in a large optical spectrum linewidth, which hinders the sensing performance. Here, we use a theoretical approach to show that it is possible to employ a low-loss Fabry-Perot optical mode on a magneto-optical platform for TMOKE signal and gaseous sensing enhancement by means of a single CoFeB ferromagnetic film directly overlayed on an already industrial anodic aluminum oxide/aluminum template. The proposed strategy can therefore potentially be exploited for high-precision and low-loss magneto-optical sensors.

19.
BMC Pulm Med ; 23(1): 77, 2023 Mar 08.
Article in English | MEDLINE | ID: mdl-36890507

ABSTRACT

BACKGROUND: To determine the diagnostic accuracy of a nanopore sequencing assay of PCR products from a M. tuberculosis complex-specific region for testing of bronchoalveolar lavage fluid (BALF) samples or sputum samples from suspected pulmonary tuberculosis (PTB) patients and compare the results to results obtained for MGIT and Xpert assays. METHODS: Cases with suspected PTB (n = 55) were diagnosed from January 2019 to December 2021 based on results of nanopore sequencing, MGIT culture, and Xpert MTB/RIF testing of BALF and sputum samples collected during hospitalization. Diagnostic accuracies of assays were compared. RESULTS: Ultimately, data from 29 PTB patients and 26 non-PTB cases were analyzed. PTB diagnostic sensitivities of MGIT, Xpert MTB/RIF, and nanopore sequencing assays were 48.28%, 41.38%, and 75.86%, respectively, thus demonstrating that nanopore sequencing provided greater sensitivity than was provided by MGIT culture and Xpert assays (P < 0.05). PTB diagnostic specificities of the respective assays were 65.38%, 100%, and 80.77%, which corresponded with kappa coefficient (κ) values of 0.14, 0.40, and 0.56, respectively. These results indicate that nanopore sequencing provided superior overall performance as compared to Xpert and MGIT culture assays and provided significantly greater PTB diagnostic accuracy than Xpert and sensitivity comparable to that of the MGIT culture assay. CONCLUSION: Our findings suggest that improved detection of PTB in suspected cases was achieved using nanopore sequencing-based testing of BALF or sputum samples than was achieved using Xpert and MGIT culture-based assays, and nanopore sequencing results alone cannot be used to rule out PTB.


Subject(s)
Mycobacterium tuberculosis , Nanopore Sequencing , Tuberculosis, Pulmonary , Humans , Mycobacterium tuberculosis/genetics , Bronchoalveolar Lavage Fluid , Sensitivity and Specificity , Sputum , Tuberculosis, Pulmonary/diagnosis
20.
Eur Spine J ; 32(11): 3892-3905, 2023 11.
Article in English | MEDLINE | ID: mdl-37624438

ABSTRACT

BACKGROUND: Imminent new vertebral fracture (NVF) is highly prevalent after vertebral augmentation (VA). An accurate assessment of the imminent risk of NVF could help to develop prompt treatment strategies. PURPOSE: To develop and validate predictive models that integrated the radiomic features and clinical risk factors based on machine learning algorithms to evaluate the imminent risk of NVF. MATERIALS AND METHODS: In this retrospective study, a total of 168 patients with painful osteoporotic vertebral compression fractures treated with VA were evaluated. Radiomic features of L1 vertebrae based on lumbar T2-weighted images were obtained. Univariate and LASSO-regression analyses were applied to select the optimal features and construct radiomic signature. The radiomic signature and clinical signature were integrated to develop a predictive model by using machine learning algorithms including LR, RF, SVM, and XGBoost. Receiver operating characteristic curve and calibration curve analyses were used to evaluate the predictive performance of the models. RESULTS: The radiomic-XGBoost model with the highest AUC of 0.93 of the training cohort and 0.9 of the test cohort among the machine learning algorithms. The combined-XGBoost model with the best performance with an AUC of 0.9 in the training cohort and 0.9 in the test cohort. The radiomic-XGBoost model and combined-XGBoost model achieved better performance to assess the imminent risk of NVF than that of the clinical risk factors alone (p < 0.05). CONCLUSION: Radiomic and machine learning modeling based on T2W images of preoperative lumbar MRI had an excellent ability to evaluate the imminent risk of NVF after VA.


Subject(s)
Fractures, Compression , Spinal Fractures , Humans , Spinal Fractures/diagnostic imaging , Spinal Fractures/surgery , Fractures, Compression/diagnostic imaging , Fractures, Compression/surgery , Retrospective Studies , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Magnetic Resonance Imaging
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