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1.
Article in English | MEDLINE | ID: mdl-39358301

ABSTRACT

BACKGROUND: Per- and poly-fluoroalkyl substances (PFASs) are pervasive synthetic compounds, prompting investigations into their intricate interactions with lifestyle factors and health indicators because of their enduring environmental presence and bioaccumulation. This study aimed to explore the effects of the oxidative balance score (OBS) and PFAS on liver-related indices. METHODS: Twenty dietary and lifestyle factors were used to calculate the OBS. The serum concentrations of PFASs were measured, and their sum was calculated for analysis. The levels of liver markers were also evaluated. Linear regression models and interaction analyses were used to assess the associations between OBS, PFAS concentrations, and liver indices. RESULTS: The results revealed an inverse association between high OBS and perfluorooctane sulfonic acid concentration, as well as the sum of PFAS concentrations. OBS was positively associated with liver markers. The PFAS concentrations were positively associated with total bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. Interaction analyses revealed significant interactions between OBS and specific PFASs for alkaline phosphatase (interaction P < 0.05). Possible interactions were also found between OBS and specific PFASs for ALT, and AST levels (interaction P < 0.10). CONCLUSIONS: This study clarified the association between total PFAS and OBS. This association was significant mainly for diet-related OBS. PFAS and OBS are associated with liver-related indicators in the blood.


Subject(s)
Environmental Pollutants , Fluorocarbons , Liver , Nutrition Surveys , Humans , Fluorocarbons/blood , Male , Female , Liver/metabolism , Adult , Environmental Pollutants/blood , Middle Aged , Oxidative Stress/drug effects , Biomarkers/blood , Alkanesulfonic Acids/blood , Environmental Exposure/analysis , Young Adult , Aged
2.
Hypertens Res ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39363003

ABSTRACT

To examine the association of household fuel use with prehypertension regression among middle-aged and older people based on the China Health and Retirement Longitudinal Study (CHARLS), we included a total of 3501 participants with prehypertension at baseline, and they were followed up from 2011-2012 to 2015-2016 with information on blood pressure and household solid fuel use (heating and cooking fuels). Cox proportional hazards regression models were used to explore the hazard ratio (HR) and 95% confidence interval (CI) between fuel use and prehypertension regression. Additionally, we investigated the impact of switching fuels (2011-2013) on the regression to normotension during the 4-year follow-up. Linear regression was used to examine the effect of household fuel use on changes in blood pressure. Compared to solid fuel users, those who used clean fuel for heating at baseline had a positive effect on the regression of prehypertension (HR: 1.28, 95% CI: 1.08-1.53). Participants who used clean fuels for both heating and cooking had increased odds for the regression of prehypertension (HR: 1.32, 95% CI: 1.09-1.60). Compared to consistent solid fuel users, those who consistently used clean fuel for heating had a higher likelihood of transitioning from prehypertension to normotension (HR: 1.36, 95% CI: 1.06-1.73) and exhibited 2.45 mmHg lower systolic blood pressure. In conclusion, household clean fuel use for heating was positively associated with the regression of prehypertension to normotension. Furthermore, switching from solid fuel to clean fuel for heating could reduce the risk of prehypertension in Chinese middle-aged and older adults.

3.
J Sci Food Agric ; 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39364803

ABSTRACT

BACKGROUND: This study investigated the contribution of 11 polysaccharides (2%, w/w), including pectin (PC), κ-carrageenan (KC), ι-carrageenan (IC), gellan gum (GG), guar gum (GM), sodium alginate (SA), konjac gum (KG), gum arabic (GA), fucoidan (FC), locust bean gum (LBG), and curdlan (CD), to the gel and microstructural properties of Meretrix meretrix clam gel (MMG). RESULTS: The hardness, springiness and chewiness of MMG with KC, IC, GG, SA and FC addition increased by ~10%-250%, while PC, GM, KG and LBG groups decreased by ~0.6% to 69%. KC, IC, SA, GG and FC decreased the cooking loss rate (CLR) by 69.4% to 88.7% and correspondingly enhanced the water holding capacity (WHC) by 10.2% to 21.4%, which was accompanied by an increased bound water and immobilized water area and high hydrogen proton density. The addition of KC transformed the MMG microstructure from a loose network with large pores to a compact, dense network, reducing lacunarity by 57.9%. The primary intermolecular forces in MMG with the incorporation of KC, IC, GG, SA and FC were hydrophobic interactions and disulfide bonds, which increased by 32.8%-105.3% and 45.6%-114.5% than MMG alone, respectively. CONCLUSION: Collectively, KC, IC, GG, SA and FC could improve the gel properties of MMG and the strongest synergistic combination was found in the MMG/KC system. This study suggests that the incorporation of polysaccharides is a strategy with potential for modifying the gel properties of shellfish surimi products. © 2024 Society of Chemical Industry.

4.
Hemasphere ; 8(10): e70007, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39380843

ABSTRACT

Severe cytokine release syndrome (sCRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have limited the widespread use of chimeric antigen receptor T (CAR T)-cell therapy. We designed a novel anti-CD19 CAR (ssCART-19) with a small hairpin RNA (shRNA) element to silence the interleukin-6 (IL-6) gene, hypothesizing it could reduce sCRS and ICANS by alleviating monocyte activation and proinflammatory cytokine release. In a post hoc analysis of two clinical trials, we compared ssCART-19 with common CAR T-cells (cCART-19) in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Among 87 patients, 47 received ssCART-19 and 40 received cCART-19. Grade ≥3 CRS occurred in 14.89% (7/47) of the ssCART-19 group versus 37.5% (15/40) in the cCART-19 group (p = 0.036). ICANS occurred in 4.26% (2/47) of the ssCART-19 group (all grade 1) compared to 15% (2/40) of the cCART-19 group. Patients in the ssCART-19 group showed comparable rates of treatment response (calculated with rates of complete remission and incomplete hematological recovery) were 91.49% (43/47) for ssCART-19 and 85% (34/40) for cCART-19 (p = 0.999). With a median follow-up of 21.9 months, cumulative nonrelapse mortality was 10.4% for ssCART-19 and 13.6% for cCART-19 (p = 0.33). Median overall survival was 37.17 months for ssCART-19 and 32.93 months for cCART-19 (p = 0.40). Median progression-free survival was 24.17 months for ssCART-19 and 9.33 months for cCART-19 (p = 0.23). These data support the safety and efficacy of ssCART-19 for r/r B-ALL, suggesting its potential as a promising therapy.

5.
Clin Chem ; 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39383112

ABSTRACT

BACKGROUND: Early detection of the cell type changes underlying several genitourinary tract diseases largely remains an unmet clinical need, where existing assays, if available, lack the cellular resolution afforded by an invasive biopsy. While messenger RNA in urine could reflect the dynamic signal that facilitates early detection, current measurements primarily detect single genes and thus do not reflect the entire transcriptome and the underlying contributions of cell type-specific RNA. METHODS: We isolated and sequenced the cell-free RNA (cfRNA) and sediment RNA from human urine samples (n = 6 healthy controls and n = 12 kidney stone patients) and measured the urine metabolome. We analyzed the resulting urine transcriptomes by deconvolving the noninvasively measurable cell type contributions and comparing to plasma cfRNA and the measured urine metabolome. RESULTS: Urine transcriptome cell type deconvolution primarily yielded relative fractional contributions from genitourinary tract cell types in addition to cell types from high-turnover solid tissues beyond the genitourinary tract. Comparison to plasma cfRNA yielded enrichment of metabolic pathways and a distinct cell type spectrum. Integration of urine transcriptomic and metabolomic measurements yielded enrichment for metabolic pathways involved in amino acid metabolism and overlapped with metabolic subsystems associated with proximal tubule function. CONCLUSIONS: Noninvasive whole transcriptome measurements of human urine cfRNA and sediment RNA reflects signal from hard-to-biopsy tissues exhibiting low representation in blood plasma cfRNA liquid biopsy at cell type resolution and are enriched in signal from metabolic pathways measurable in the urine metabolome.

6.
Org Lett ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39361810

ABSTRACT

Herein, a photoinduced, Pd-catalyzed direct 1,2-carboamination of conjugated 1,3-dienes has been successfully achieved. Sequential regioselective C-C bond and enantioselective C-N bond formation allows rapid assembly of a wide range of value-added chiral allylic amines from readily available N-hydroxyphthalimide (NHP) esters and 1,3-dienes under mild conditions. This developed protocol further demonstrates the versatility and potency of the photoexcited Pd catalytic system with a bifunctional reagent in the streamlined difunctionalization of C═C bonds.

7.
Langmuir ; 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39390824

ABSTRACT

The limited active sites and faster photogenerated electron-hole pair recombination rate of g-C3N4 restrict its application in photocatalytic H2 production. Constructing heterojunctions has been shown to improve the spatial (directional) separation of photogenerated electrons and holes. However, due to interface mismatch in traditional heterojunction structures and a lack of precise electron transport channels, the photocatalytic efficiency is limited. Here, we developed a two-step calcination approach to create an Fe2N/g-C3N4 heterojunction linked by Fe-O bonds (named as Fe-OCN). The newly formed Fe-O bonds within the heterojunction can act as atomic-level interface electron transfer channels, directly transferring the photogenerated electrons of g-C3N4 to the reactive center Fe2N, significantly improving the charge transfer rate and utilization, thus promoting visible-light-driven photocatalytic H2 production. The optimal Fe-OCN achieved a H2 production rate of 5986.29 µmol g-1 h-1 under visible light, 13.44 times higher than that of the OCN due to efficient charge separation and transfer capabilities. This work provides a constructive reference for the design and synthesis of organic-inorganic heterojunction with chemically bonded interfaces, establishing quick electron transfer channels, and achieving targeted electron transfer.

8.
Abdom Radiol (NY) ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39225717

ABSTRACT

BACKGROUND: The expansion of function-preserving surgery became possible due to a more profound understanding of gastric cancer (GC), and T1N + or T2N + gastric cancer patients might be potential beneficiaries. However, ways to evaluate the possibility of function-preserving pylorus surgery are still unknown. METHODS: A total of 288 patients at Renji Hospital and 58 patients at Huadong Hospital, pathologically diagnosed with gastric cancer staging at T1 and T2 with tumors located in the upper two-thirds of the stomach, were retrospectively enrolled from March 2015 to October 2022. Tumor regions of interest (ROIs) were manually delineated on bi-phase CT images, and a nomogram was built and evaluated. RESULTS: The radiomic features distributed differently between positive and negative pLNm groups. Two radiomic signatures (RS1 and RS2) and one clinical signature were constructed. The radiomic signatures exhibited good performance for discriminating pLNm status in the test set. The three signatures were then combined into an integrated nomogram (IN). The IN showed good discrimination of pLNm in the Renji cohort (AUC 0.918) and the Huadong cohort (AUC 0.649). The verification models showed high values. CONCLUSION: For GC patients with T1 and T2 tumors located in the upper two-thirds of the stomach, a nomogram was successfully built for predicting pylorus lymph node metastasis, which would guide the surgical indication extension of conservative gastrectomies.

9.
Front Immunol ; 15: 1451212, 2024.
Article in English | MEDLINE | ID: mdl-39253077

ABSTRACT

Gonadal and gonosomal mosaicism describe phenomena in which a seemingly healthy individual carries a genetic variant in a subset of their gonadal tissue or gonadal and somatic tissue(s), respectively, with risk of transmitting the variant to their offspring. In families with one or more affected offspring, occurrence of the same apparently de novo variants can be an indicator of mosaicism in either parent. Panel-based deep sequencing has the capacity to detect low-level mosaic variants with coverage exceeding the typical limit of detection provided by current, readily available sequencing techniques. In this study, we report three families with more than one affected offspring with either confirmed or apparent parental gonosomal or gonadal mosaicism for PIK3CD pathogenic variants. Data from targeted deep sequencing was suggestive of low-level maternal gonosomal mosaicism in Family 1. Through this approach we did not detect pathogenic variants in PIK3CD from parental samples in Family 2 and Family 3. We conclude that mosaicism was likely confined to the maternal gonads in Family 2. Subsequent long-read genome sequencing in Family 3 showed that the paternal chromosome harbored the pathogenic variant in PIK3CD in both affected children, consistent with paternal gonadal mosaicism. Detection of parental mosaic variants enables accurate risk assessment, informs reproductive decision-making, and provides helpful context to inform clinical management in families with PIK3CD pathogenic variants.


Subject(s)
Class I Phosphatidylinositol 3-Kinases , High-Throughput Nucleotide Sequencing , Mosaicism , Pedigree , Humans , Female , Male , Class I Phosphatidylinositol 3-Kinases/genetics , Adult , Mutation , Genetic Predisposition to Disease , Child , Gonads
10.
Nat Sci Sleep ; 16: 1355-1364, 2024.
Article in English | MEDLINE | ID: mdl-39282469

ABSTRACT

Background: Sleep is critical in health problems including Parkinson's disease (PD). This study examined the association between sleep characteristics and the likelihood of prodromal PD. Methods: At baseline examination of the Heart and Brain Investigation in Taicang (HABIT) study, potential PD biomarkers were obtained for 8777 participants aged over 50 years, and the probability of prodromal PD was assessed based on the Chinese expert consensus and Movement Disorder Society (MDS) criteria. General and component sleep characteristics were evaluated by the Pittsburgh Sleep Quality Index (PSQI). Median regression was applied to examine the association between sleep and the probability of prodromal PD, adjusting for age, sex, education level, physical activity, obesity, fast plasma glucose, lipids, and hypertension. Results: Based on China criteria, a higher level of PSQI score was significantly associated with a higher probability of prodromal PD (ß = 0.02, 95% CI: 0.01-0.03) and a higher risk of having an increased probability of prodromal PD (OR = 1.04, 95% CI: 1.02-1.05). Compared to participants with good quality sleep, those with poor quality sleep had a 0.07% increased probability of prodromal PD (95% CI: 0.01-0.13) and a 19% increased risk of having a high prodromal PD probability (95% CI: 1.04-1.20). Similar associations between sleep quality and the probability of prodromal PD were also observed using the MDS criteria. Subjective sleep quality, sleep latency, habitual sleep efficiency, daytime dysfunction, and use of sleep medications were also associated with the probability of prodromal PD. Conclusion: Poor sleep quality was associated with a high probability of prodromal PD. Sleep may be helpful for understanding and intervention of prodromal PD.

11.
Front Pharmacol ; 15: 1437773, 2024.
Article in English | MEDLINE | ID: mdl-39246657

ABSTRACT

Introduction: Chlorogenic acid (CGA) has been identified to possess salient anti-inflammatory, antioxidant, and anticancer attributes. However, its application is limited by its instability and low bioavailability. Liposomes have been considered effective pharmaceutical delivery vehicles due to their ability to continuously release loaded drugs, improve drug stability, and display good biocompatibility. They can be easily modified by other small molecules to acquire additional biological functions. In this study, we developed and characterized folic acid-TPGS-modified chlorogenic acid liposome (FTCLP) and evaluated its anti-inflammatory activity. Methods: The successful encapsulation of CGA within FTCLP was confirmed through examination using electron microscopy, fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The in vitro release characteristics of FTCLP were evaluated using the dialysis bag membrane method. Meanwhile, a dextran sulfate sodium (DSS) -induced colitis model was employed to investigate the anti-inflammatory effect of FTCLP and its mechanism. Results: The FTCLP exhibited an encapsulation efficiency (EE) of 84.85 ± 1.20% and a drug loading (DL) of 11.67 ± 0.04%. The particle size of FTCLP was determined to be 150.63 ± 0.71 nm, with a polydispersity index (PDI) of 0.198 ± 0.02 and a zeta potential of 2.61 ± 0.38 mV. The in vitro release profile followed the Higuchi model, indicating sustained-release characteristics. The in vivo study demonstrated that FTCLP treatment was effective in improving the symptoms of DSS-induced inflammatory response, as evidenced by mitigation of weight loss, reduction in the disease activity index (DAI) score, restoration of colon length, and attenuation of colon tissue damage. Furthermore, the levels of pro-inflammatory cytokines, including interferon-gamma (INF-γ), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6), were markedly diminished in both the serum and colon tissue. FTCLP was also observed to suppress the expression of INF-γ, IL-1ß, IL-6, tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) p65, while concomitantly upregulating the expression of Janus kinase (JAK) and signal transducer and activator of transcription 3 (STAT3). Besides, the administration of FTCLP was found to result in an increase in the abundance of Lactobacillaceae and Peptostreptococcaceae, while decreasing the abundance of Bacteroidaceae, Rikenellaceae, and Helicobacteraceae. Conclusion: Following encapsulation of CGA within liposomes, FTCLP revealed favorable stability and sustained release properties, and enhanced the anti-inflammatory effects by modulating multiple inflammation-related biomarkers. FTCLP has the potential to be a safe and effective drug for targeted therapy of colitis.

12.
ACS Appl Mater Interfaces ; 16(38): 50054-50060, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39283756

ABSTRACT

The understanding of the interfacial processes is critically important for extending the practical application of ionic liquids, particularly for the role of interfacial water. In the electrochemical system based on ionic liquid electrolytes, small amounts of water at the interface generate a significant change in the electrochemical behaviors of ionic liquids. Therefore, the investigation on the interfacial behavior of water is highly desired in ionic liquids with different anions, water content, and hydrophilicity. Herein, based on the probe strategy, in situ surface enhanced Raman spectroscopy (SERS) combined with electrochemical control (EC-SERS) was developed to investigate the influence of hydrophilicity/hydrophobicity of ionic liquids on the interfacial water. The water-sensitive transformation reaction of 4,4'-dimercaptoazobenzene (DMAB) to para-aminothiophenol (PATP) was employed as a probe reaction for investigating the behavior of interfacial water. The changes of relative SERS intensities of DMAB to PATP served as an indication of the quantity variation of interfacial water. The results show that the transformation reaction efficiencies were critically dependent on the additional water contents, potential, and hydrophilicity of ionic liquids. With a very low molar fraction of additional water (Xw = 0.01), transformation efficiency of DMAB (the amount of interfacial water) followed the sequence of [BMIm]BF4 < [BMIm]PF6 < [BMIm]Tf2N. It was in agreement with the hydrophobicity order of the ionic liquids. With the increase in additional water content, the potential for the full transformation was positively moved, and the efficiency increased significantly. The stronger hydrophobicity allowed more water molecules to migrate to the interface, which was attributed to the difference in interactions between water and the anions of ionic liquids. It demonstrated that the small amount of water tended to gather at the interface in hydrophobic ionic liquids. Compared to traditional cyclic voltammetry, the EC-SERS technique combined with probe reactions is more sensitive to interfacial water. It is anticipated to develop as a promising tool for the investigating water-related issues at interfaces and to provide guidance to screen ionic liquids for practical application.

13.
Proc Natl Acad Sci U S A ; 121(40): e2405117121, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39312657

ABSTRACT

Cholinergic neurons in the basal forebrain play a crucial role in regulating adult hippocampal neurogenesis (AHN). However, the circuit and molecular mechanisms underlying cholinergic modulation of AHN, especially the initial stages of this process related to the generation of newborn progeny from quiescent radial neural stem cells (rNSCs), remain unclear. Here, we report that stimulation of the cholinergic circuits projected from the diagonal band of Broca (DB) to the dentate gyrus (DG) neurogenic niche promotes proliferation and morphological development of rNSCs, resulting in increased neural stem/progenitor pool and rNSCs with longer radial processes and larger busy heads. Interestingly, DG granule cells (GCs) are required for DB-DG cholinergic circuit-dependent modulation of proliferation and morphogenesis of rNSCs. Furthermore, single-nucleus RNA sequencing of DG reveals cell type-specific transcriptional changes in response to cholinergic circuit stimulation, with GCs (among all the DG niche cells) exhibiting the most extensive transcriptional changes. Our findings shed light on how the DB-DG cholinergic circuits orchestrate the key niche components to support neurogenic function and morphogenesis of rNSCs at the circuit and molecular levels.


Subject(s)
Cholinergic Neurons , Dentate Gyrus , Neural Stem Cells , Neurogenesis , Animals , Neural Stem Cells/metabolism , Neural Stem Cells/cytology , Dentate Gyrus/metabolism , Dentate Gyrus/cytology , Neurogenesis/physiology , Cholinergic Neurons/metabolism , Cholinergic Neurons/physiology , Mice , Cell Proliferation , Adult Stem Cells/metabolism , Adult Stem Cells/physiology , Adult Stem Cells/cytology , Morphogenesis , Stem Cell Niche/physiology , Male
14.
Chem Sci ; 15(31): 12264-12269, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39118606

ABSTRACT

Metal oxides are promising (photo)electrocatalysts for sustainable energy technologies due to their good activity and abundant resources. Their applications such as photocatalytic water splitting predominantly involve aqueous interfaces under electrochemical conditions, but in situ probing oxide-water interfaces is proven to be extremely challenging. Here, we present an electrochemical scanning tunneling microscopy (EC-STM) study on the rutile TiO2(110)-water interface, and by tuning surface redox chemistry with careful potential control we are able to obtain high quality images of interfacial structures with atomic details. It is interesting to find that the interfacial water exhibits an unexpected double-row pattern that has never been observed. This finding is confirmed by performing a large scale simulation of a stepped interface model enabled by machine learning accelerated molecular dynamics (MLMD) with ab initio accuracy. Furthermore, we show that this pattern is induced by the steps present on the surface, which can propagate across the terraces through interfacial hydrogen bonds. Our work demonstrates that by combining EC-STM and MLMD we can obtain new atomic details of interfacial structures that are valuable to understand the activity of oxides under realistic conditions.

15.
Autophagy ; : 1-18, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39189526

ABSTRACT

Severe fever with thrombocytopenia syndrome is an emerging viral hemorrhagic fever caused by a tick-borne bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), with a high case fatality. We previously found that SFTSV nucleoprotein (NP) induces macroautophagy/autophagy to facilitate virus replication. However, the role of NP in antagonizing host innate immunity remains unclear. Mitophagy, a selected form of autophagy, eliminates damaged mitochondria to maintain mitochondrial homeostasis. Here, we demonstrate that SFTSV NP triggers mitophagy to degrade MAVS (mitochondrial antiviral signaling protein), thereby blocking MAVS-mediated antiviral signaling to escape the host immune response. Mechanistically, SFTSV NP translocates to mitochondria by interacting with TUFM (Tu translation elongation factor, mitochondrial), and mediates mitochondrial sequestration into phagophores through interacting with LC3, thus inducing mitophagy. Notably, the N-terminal LC3-interacting region (LIR) motif of NP is essential for mitophagy induction. Collectively, our results demonstrated that SFTSV NP serves as a novel virulence factor, inducing TUFM-mediated mitophagy to degrade MAVS and evade the host immune response.Abbreviation: 3-MA: 3-methyladenine; ACTB: actin beta; co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole, dihydrochloride; DMSO: dimethyl sulfoxide; FCCP: carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone; GFP: green fluorescent protein; HTNV: Hantan virus; IAV: influenza A virus; IFN: interferon; LAMP1: lysosomal associated membraneprotein 1; LIR: LC3-interacting region; MAP1LC3B/LC3B: microtubule associatedprotein 1 light chain 3 beta; MAVS: mitochondrial antiviral signaling protein; Mdivi-1: mitochondrial division inhibitor 1; MOI: multiplicity of infection; MT-CO2/COXII: mitochondrially encoded cytochrome C oxidase II; NP: nucleoprotein; NSs: nonstructural proteins; poly(I:C): polyinosinic:polycytidylic acid; RIGI: RNA sensor RIG-I; RLR: RIGI-like receptor; SFTSV: severe fever withthrombocytopenia syndrome virus; TCID50: 50% tissue culture infectiousdose; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20:translocase of outer mitochondrial membrane 20; TUFM: Tu translation elongationfactor, mitochondrial.

16.
J Phys Chem A ; 128(35): 7429-7439, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39171886

ABSTRACT

2-Pentanone is a significant carbon-neutral fuel. To better understand 2-pentanone combustion, the CCSD(T)/CBS method was used to calculate the potential energy surfaces (PES) for H-abstraction, isomerization, and ß-scission reactions of 2-pentanone. Rate constants for the above reactions were calculated by the MESS employing conventional transition state theory (CTST) at 300-2000 K. The findings reveal adherence to the Evans-Polanyi principle in the H-abstraction reactions of 2-pentanone by H atoms. Specifically, the 2-site shows more competitive kinetics due to having the lowest energy barrier of 7.8 kcal/mol. The 4-position has the highest energy barrier, making the reaction difficult to occur. In the subsequent reactions, the breaking of C-H bonds is most competitive at low temperatures. In particular, the H transfer from INT1 to INT3 has a potential well height of 24.8 kcal/mol. The ß-scission reactions become the main pathway for the depletion of pentanone radicals with increasing temperature. This study significantly extends the kinetic parameters of 2-pentanone combustion over a wide range of temperatures and pressures, which is expected to contribute to the development of 2-pentanone combustion models.

17.
ACS Nano ; 18(36): 24770-24783, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39164631

ABSTRACT

Regulating the complex microenvironment after tooth extraction to promote alveolar bone regeneration is a pressing challenge for restorative dentistry. In this study, through modulating the mechanical properties of the cellular matrix, we guided various types of cells by self-organizing to form multicellular spheroids (MCSs) and hybridized MCSs with Prussian Blue nanoparticles (PBNPs) in the process. The constructed Prussian Blue nanohybridized multicellular spheroids (PBNPs@MCSs) with empowered antioxidant functions effectively reduced cell apoptosis under peroxidative conditions and exhibited enhanced ability to regulate the microenvironment and promote bone repair both in vitro and in vivo. In addition, the PBNPs@MCSs exhibited enhanced photoacoustic imaging ability to trace low doses of PBNPs. Therefore, the constructed PBNPs@MCSs based on the biomimetic hydrogel can be used as a form of an engraftment building block, with a greater potential for pro-bone repair application in the complex microenvironment of the oral cavity.


Subject(s)
Antioxidants , Bone Regeneration , Ferrocyanides , Nanoparticles , Photoacoustic Techniques , Spheroids, Cellular , Ferrocyanides/chemistry , Ferrocyanides/pharmacology , Animals , Bone Regeneration/drug effects , Antioxidants/pharmacology , Antioxidants/chemistry , Spheroids, Cellular/drug effects , Nanoparticles/chemistry , Mice , Humans , Tomography , Apoptosis/drug effects
18.
Anal Methods ; 16(35): 5954-5958, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39188154

ABSTRACT

Detecting H2 at low concentrations is important due to it being a major safety concern in practical applications. However, semiconductor chemiresistive gas sensors always suffer from high operating temperatures and power consumption, as well as a limited concentration detection range, which restricts their widespread use. Herein, we developed a 3D nanostructured gas sensor employing a Pd-nanocluster-decorated SnO2 nanotube array as the sensing layer. The sensor showed sensitive and selective properties for detecting low concentrations of H2 at room temperature, with a low limit of detection of 1.6 ppb. It also showed good long-term stability, as long as 100 days. Moreover, systematical characterizations were performed in conjunction with density functional theory (DFT) calculations to determine the ability of Pd/SnO2 junctions to improve the gas-sensing properties. The engineering of the nano-Schottky junction allows us to expand the library for designing low-power-consumption H2 sensors for widespread applications.

20.
Mol Cancer ; 23(1): 157, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095854

ABSTRACT

BACKGROUND: Tumor heterogeneity presents a formidable challenge in understanding the mechanisms driving tumor progression and metastasis. The heterogeneity of hepatocellular carcinoma (HCC) in cellular level is not clear. METHODS: Integration analysis of single-cell RNA sequencing data and spatial transcriptomics data was performed. Multiple methods were applied to investigate the subtype of HCC tumor cells. The functional characteristics, translation factors, clinical implications and microenvironment associations of different subtypes of tumor cells were analyzed. The interaction of subtype and fibroblasts were analyzed. RESULTS: We established a heterogeneity landscape of HCC malignant cells by integrated 52 single-cell RNA sequencing data and 5 spatial transcriptomics data. We identified three subtypes in tumor cells, including ARG1+ metabolism subtype (Metab-subtype), TOP2A+ proliferation phenotype (Prol-phenotype), and S100A6+ pro-metastatic subtype (EMT-subtype). Enrichment analysis found that the three subtypes harbored different features, that is metabolism, proliferating, and epithelial-mesenchymal transition. Trajectory analysis revealed that both Metab-subtype and EMT-subtype originated from the Prol-phenotype. Translation factor analysis found that EMT-subtype showed exclusive activation of SMAD3 and TGF-ß signaling pathway. HCC dominated by EMT-subtype cells harbored an unfavorable prognosis and a deserted microenvironment. We uncovered a positive loop between tumor cells and fibroblasts mediated by SPP1-CD44 and CCN2/TGF-ß-TGFBR1 interaction pairs. Inhibiting CCN2 disrupted the loop, mitigated the transformation to EMT-subtype, and suppressed metastasis. CONCLUSION: By establishing a heterogeneity landscape of malignant cells, we identified a three-subtype classification in HCC. Among them, S100A6+ tumor cells play a crucial role in metastasis. Targeting the feedback loop between tumor cells and fibroblasts is a promising anti-metastatic strategy.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Single-Cell Analysis , Tumor Microenvironment , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Humans , Gene Expression Regulation, Neoplastic , Epithelial-Mesenchymal Transition/genetics , Animals , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Fibroblasts/metabolism , Fibroblasts/pathology , Genetic Heterogeneity , Mice , Cell Line, Tumor , Prognosis , Gene Expression Profiling , Transcriptome , Computational Biology/methods , Neoplasm Metastasis
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