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1.
mSystems ; : e0121023, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38747603

ABSTRACT

The clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) system widely occurs in prokaryotic organisms to recognize and destruct genetic invaders. Systematic collation and characterization of endogenous CRISPR-Cas systems are conducive to our understanding and potential utilization of this natural genetic machinery. In this study, we screened 39 complete and 692 incomplete genomes of myxobacteria using a combined strategy to dispose of the abridged genome information and revealed at least 19 CRISPR-Cas subtypes, which were distributed with a taxonomic difference and often lost stochastically in intraspecies strains. The cas genes in each subtype were evolutionarily clustered but deeply separated, while most of the CRISPRs were divided into four types based on the motif characteristics of repeat sequences. The spacers recorded in myxobacterial CRISPRs were in high G+C content, matching lots of phages, tiny amounts of plasmids, and, surprisingly, massive organismic genomes. We experimentally demonstrated the immune and self-target immune activities of three endogenous systems in Myxococcus xanthus DK1622 against artificial genetic invaders and revealed the microhomology-mediated end-joining mechanism for the immunity-induced DNA repair but not homology-directed repair. The panoramic view and immune activities imply potential omnipotent immune functions and applications of the endogenous CRISPR-Cas machinery. IMPORTANCE: Serving as an adaptive immune system, clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) empower prokaryotes to fend off the intrusion of external genetic materials. Myxobacteria are a collective of swarming Gram-stain-negative predatory bacteria distinguished by intricate multicellular social behavior. An in-depth analysis of their intrinsic CRISPR-Cas systems is beneficial for our understanding of the survival strategies employed by host cells within their environmental niches. Moreover, the experimental findings presented in this study not only suggest the robust immune functions of CRISPR-Cas in myxobacteria but also their potential applications.

2.
BMJ Open ; 14(4): e074188, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38684278

ABSTRACT

OBJECTIVES: To compare the efficacy and safety of seven Chinese patent medicines (CPMs) combined with conventional triple/quadruple therapy (T/Q) for Helicobacter pylori-positive peptic ulcers. DESIGN: A systematic review and network meta-analysis. DATA SOURCES: China National Knowledge Infrastructure, VIP database, Wanfang database, ScienceDirect, EBSCO, EMBASE, Web of Science, Cochrane Library and PubMed were searched through 1 June 2022. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) testing CPMs combined with T/Q for H. pylori-positive peptic ulcers were included. The CPMs included Anweiyang capsule, Jianweiyuyang tablets/capsule/granule, Jinghuaweikang capsule, Kangfuxin liquid, Puyuanhewei capsule, Weifuchun tablets/capsule and Weisu granule. At least one of the following outcome indicators was recorded: complete ulcer healing rate (CUHR), effective rate (ER), H. pylori eradication rate (HPER), rate of peptic ulcer recurrence (RPUR) and incidence of adverse reactions (IAR). DATA EXTRACTION AND SYNTHESIS: Two researchers independently conducted the study selection and extracted data for included studies. The risk of bias was assessed using the Cochrane risk of bias tool. A pairwise meta-analysis was performed using RevMan V.5.3. Network meta-analysis was performed using STATA/MP V.15.0. Confidence in the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation. RESULTS: A total of 36 RCTs involving 3620 patients were included. Compared with T/Q alone, Weisu+T/Q, Weifuchun+T/Q and Puyuanhewei+T/Q had the highest CUHR, ER and HPER, respectively. Weisu+T/Q and Jianweiyuyang+T/Q had the lowest RPUR and IAR, respectively. The cluster analysis results showed Jianweiyuyang+T/Q might be the best choice concerning efficacy and safety simultaneously, followed by Kangfuxin+T/Q. CONCLUSION: Among the combination therapies with the CPMs, Jianweiyuyang+T/Q might be the most favourable option for H. pylori-positive peptic ulcers, followed by Kangfuxin+T/Q. Considering the limited quantity and quality of the included RCTs, the results should be interpreted with caution. PROSPERO REGISTRATION NUMBER: CRD42022327687.


Subject(s)
Anti-Bacterial Agents , Drug Therapy, Combination , Drugs, Chinese Herbal , Helicobacter Infections , Helicobacter pylori , Network Meta-Analysis , Peptic Ulcer , Humans , Helicobacter Infections/drug therapy , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/adverse effects , Peptic Ulcer/drug therapy , Peptic Ulcer/microbiology , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/administration & dosage , Randomized Controlled Trials as Topic , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/adverse effects , Anti-Ulcer Agents/therapeutic use , Anti-Ulcer Agents/administration & dosage , Anti-Ulcer Agents/adverse effects , Treatment Outcome , Nonprescription Drugs/therapeutic use , Nonprescription Drugs/adverse effects
3.
J Pharm Anal ; 14(4): 100910, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38655398

ABSTRACT

Eclipta prostrata L. has been used in traditional medicine and known for its liver-protective properties for centuries. Wedelolactone (WEL) and demethylwedelolactone (DWEL) are the major coumarins found in E. prostrata L. However, the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease (NAFLD) still remains to be explored. Utilizing a well-established zebrafish model of thioacetamide (TAA)-induced liver injury, the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis. Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver. The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped, and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized. Based on spatial metabolomics and transcriptomics, we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL. Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD, and presents a "multi-omics" platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

4.
Anim Biosci ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38665088

ABSTRACT

Objective: Embryonic interferon-tau (IFNT) and progesterone affect expression of interferon-stimulated genes (ISGs), progesterone receptor (PGR) and progesterone-induced blocking factor (PIBF) in the ovine thyroid. Methods: Thyroids of ewes were sampled at day 16 of nonpregnancy, days 13, 16 and 25 of pregnancy, and RT-qPCR assay, western blot and immunohistochemistry were used to detect expression of ISGs, PGR and PIBF. Results: Free ISG15 protein was undetected, but ISG15 conjugated proteins upregulated at day 16 of pregnancy, and expression levels of ISG15 conjugated proteins, PGR isoform (70 kDa), PIBF, interferon-gamma-inducible protein 10 and myxovirusresistance protein 1 peaked, but expression level of signal transducer and activator of transcription 1 was the lowest at day 16 of pregnancy. In addition, the expression levels of PGR isoform (70 kDa) and STAT1 decreased, but levels of PGR isoform (43 kDa), 2',5'-oligoadenylate synthetase, IP-10 and MX1 increased at day 25 of pregnancy comparing with day 16 of the estrous cycle. Conclusion: Early pregnancy affects expression of ISGs, PGR and PIBF in maternal thyroid through IFNT and progesterone, which may regulate thyroid autoimmunity and thyroid hormone secretion in ewes.

5.
Nat Commun ; 15(1): 2525, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38514635

ABSTRACT

MicroRNAs (miRNAs) play fundamental roles in many developmental and physiological processes in eukaryotes. MiRNAs in plants generally regulate their targets via either mRNA cleavage or translation repression; however, which approach plays a major role and whether these two function modes can shift remains elusive. Here, we identify a miRNA, miR408-5p that regulates AUXIN/INDOLE ACETIC ACID 30 (IAA30), a critical repressor in the auxin pathway via switching action modes in rice. We find that miR408-5p usually inhibits IAA30 protein translation, but in a high auxin environment, it promotes the decay of IAA30 mRNA when it is overproduced. We further demonstrate that IDEAL PLANT ARCHITECTURE1 (IPA1), an SPL transcription factor regulated by miR156, mediates leaf inclination through association with miR408-5p precursor promoter. We finally show that the miR156-IPA1-miR408-5p-IAA30 module could be controlled by miR393, which silences auxin receptors. Together, our results define an alternative auxin transduction signaling pathway in rice that involves the switching of function modes by miR408-5p, which contributes to a better understanding of the action machinery as well as the cooperative network of miRNAs in plants.


Subject(s)
MicroRNAs , Oryza , Oryza/metabolism , Indoleacetic Acids/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Signal Transduction/genetics , RNA, Messenger/metabolism , Gene Expression Regulation, Plant
6.
Toxics ; 12(3)2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38535961

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent chronic liver disease worldwide. At the same time, the relationship between air pollution and the likelihood of developing NAFLD has been a subject of debate due to conflicting findings in previous observational research. Our objective was to examine the potential correlation between air pollutant levels and the risk of NAFLD in the European population by employing a two-sample Mendelian randomization (MR) analysis. The UK Biobank Consortium provided the summary statistics for various air pollution indicators (PM2.5, PM2.5 absorbance, PM2.5-10, PM10, NO2, and NOx). Additionally, information on NAFLD was obtained from three studies, including one derivation set and two validation sets. Heterogeneity, pleiotropy, and sensitivity analyses were performed under different MR frameworks, and instrumental variables associated with confounders (such as education, smoking, alcohol, and BMI) were detected by tools. In the derivation set, causal relationships between PM2.5, NO2, and NAFLD were observed in univariable Mendelian randomization (UVMR) (Odds Ratio (OR) = 1.99, 95% confidence interval (95% CI) = [1.22-3.22], p = 0.005; OR = 2.08, 95% CI = [1.27-3.40], p = 0.004, respectively). After adjustment for air pollutants or alcohol intake frequency in multivariable Mendelian randomization (MVMR), the above genetic correlations disappeared. In validation sets, the null associations remained in UVMR. Our findings from MR analysis using genetic data did not provide evidence for a causal association between air pollution and NAFLD in the European population. The associations observed in epidemiological studies could be partly attributed to confounders.

7.
Mol Cancer ; 23(1): 59, 2024 03 21.
Article in English | MEDLINE | ID: mdl-38515149

ABSTRACT

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific biomarkers related to circRNAs in the era of targeted therapies, however, remain obscure. METHODS: The whole transcriptome RNA sequencing and function experiments were conducted to identify candidate anlotinib-regulated circRNAs, whose mechanism was confirmed by molecular biology experiments. CircHAS2 was profiled in a library of patient-derived CRC organoids (n = 22) and patient-derived CRC tumors in mice. Furthermore, a prospective phase II clinical study of 14 advanced CRC patients with anlotinib-based therapy was commenced to verify drug sensitivity (ClinicalTrials.gov identifier: NCT05262335). RESULTS: Anlotinib inhibits tumor growth in vitro and in vivo by downregulating circHAS2. CircHAS2 modulates CCNE2 activation by acting as a sponge for miR-1244, and binding to USP10 to facilitate p53 nuclear export as well as degradation. In parallel, circHAS2 serves as a potent biomarker predictive of anlotinib sensitivity, both in patient-derived organoids and xenograft models. Moreover, the efficacy of anlotinib inclusion into the treatment regimen yields meaningful clinical responses in patients with high levels of circHAS2. Our findings offer a promising targeted strategy for approximately 52.9% of advanced CRC patients who have high circHAS2 levels. CONCLUSIONS: CircHAS2 promotes cell proliferation via the miR-1244/CCNE2 and USP10/p53/CCNE2 bidirectional axes. Patient-derived organoids and xenograft models are employed to validate the sensitivity to anlotinib. Furthermore, our preliminary Phase II clinical study, involving advanced CRC patients treated with anlotinib, confirmed circHAS2 as a potential sensitivity marker.


Subject(s)
Colorectal Neoplasms , Indoles , MicroRNAs , Quinolines , Humans , Animals , Mice , RNA, Circular/genetics , Tumor Suppressor Protein p53 , Prospective Studies , MicroRNAs/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Cell Proliferation/genetics , Biomarkers , Ubiquitin Thiolesterase/metabolism , Cyclins/metabolism
8.
Int J Cardiol ; 405: 131959, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38484803

ABSTRACT

BACKGROUND: Takotsubo cardiomyopathy (TCM) is classically associated with significant gender disparities, such that it is more prevalent in females, but the clinical outcomes are worse for male patients. The goal of this study was to assess contemporary gender disparities in clinical outcomes of TCM hospitalizations and to determine predictors of male in-hospital mortality. METHODS: This was a retrospective analysis involving adult hospitalizations for TCM in the U.S between 2016 and 2020. Multivariable Logistic regression was used to estimate Odds Ratio (OR) for in-hospital mortality between the two genders. Univariable Cox regression was performed to identify predictors associated with in-hospital mortality for male hospitalizations. All factors from the univariable analysis with p < 0.20 were included in a multivariable Cox regression model. RESULTS: A total of 199,920 patients with TCM were identified. Female patients with TCM had 50% lower risk of in-hospital mortality compared to male patients (Adjusted OR 0.50, 95% CI 0.46-0.55, p < 0.001). Older age, higher Charlson comorbidity index, history of intracranial hemorrhage, cardiac arrest, need for vasopressor agents, mechanical intubation, and cardiogenic shock without the use of temporary mechanical circulatory support (MCS) were associated with higher in-hospital male mortality. CONCLUSIONS: Although TCM is more prevalent among females, gender disparities exist in the clinical outcomes of TCM patients. Cardiac arrest and cardiogenic shock without the use of temporary MCS were found to be the most significant predictors of male in-hospital mortality. Cardiogenic shock with use of temporary MCS did not lead to higher male in-hospital mortality.


Subject(s)
Hospital Mortality , Takotsubo Cardiomyopathy , Humans , Takotsubo Cardiomyopathy/mortality , Takotsubo Cardiomyopathy/diagnosis , Male , Female , Hospital Mortality/trends , Retrospective Studies , Aged , Middle Aged , Sex Factors , Aged, 80 and over , Risk Factors , United States/epidemiology
9.
Environ Sci Pollut Res Int ; 31(13): 19764-19778, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38363505

ABSTRACT

The changes of soil moisture, salinity, and nutrients by halophyte colonization in high-salinity environment profoundly affect the assembly and structure of microbial communities. However, salt marshes in arid region have received little attention. This study was conducted in Lianhuachi Lake, a typical inland salt marsh wetland in China, to determine the physicochemical characteristics of salt crusts in [Kalidium cuspidatum (Ung.-Sternb.) Grub.] colonization areas and bulk soil, respectively, and to analyze the microbial community structure of salt crusts by high-throughput sequencing. Kalidium cuspidatum colonization significantly decreased total salinity, soil water content, and water-soluble ions of salt crusts and increased total carbon, total nitrogen, and total phosphorus content. At the same time, changes in physicochemical properties caused by Kalidium cuspidatum colonization affect the ecological processes of bacterial, fungal, and archaeal community assemblies in salt crusts. In addition, cross-kingdom network analysis showed that Kalidium cuspidatum colonization increased the complexity and stability of microbial networks in salt crust soils. Functional projections further showed that bacterial diversity had a potential driving effect on the nitrogen cycle function of salt crust. Our study further demonstrated the different ecological strategies of microorganisms for halophyte colonization in extreme environments and contributed to the understanding of restoration and management of salt marsh wetlands in arid region.


Subject(s)
Chenopodiaceae , Microbiota , Wetlands , Bacteria , Soil/chemistry , Water , Soil Microbiology
10.
Article in English | MEDLINE | ID: mdl-38409281

ABSTRACT

Children with ADHD show abnormal brain function and structure. Neuroimaging studies found that stimulant medications may improve brain structural abnormalities in children with ADHD. However, prior studies on this topic were conducted with relatively small sample sizes and wide age ranges and showed inconsistent results. In this cross-sectional study, we employed latent class analysis and linear mixed-effects models to estimate the impact of stimulant medications using demographic, clinical measures, and brain structure in a large and diverse sample of children aged 9-11 from the Adolescent Brain and Cognitive Development Study. We studied 273 children with low ADHD symptoms and received stimulant medication (Stim Low-ADHD), 1002 children with high ADHD symptoms and received no medications (No-Med ADHD), and 5378 typically developing controls (TDC). After controlling for the covariates, compared to Stim Low-ADHD and TDC, No-Med ADHD showed lower cortical thickness in the right insula (INS, d = 0.340, PFDR = 0.003) and subcortical volume in the left nucleus accumbens (NAc, d = 0.371, PFDR = 0.003), indicating that high ADHD symptoms were associated with structural abnormalities in these brain regions. In addition, there was no difference in brain structural measures between Stim Low-ADHD and TDC children, suggesting that the stimulant effects improved both ADHD symptoms and ADHD-associated brain structural abnormalities. These findings together suggested that children with ADHD appear to have structural abnormalities in brain regions associated with saliency and reward processing, and treatment with stimulant medications not only improve the ADHD symptoms but also normalized these brain structural abnormalities.

11.
Biotechnol J ; 19(2): e2300484, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38403446

ABSTRACT

BACKGROUND: Owing to the characteristics of easier access in vitro, low immunogenicity, and high plasticity, human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are considered as a promising cell-based drugs for clinical application. No internationally recognized technology exists to evaluate the pharmacokinetics and distribution of cell-based drugs in vivo. METHODS: We determined the human-specific gene sequence, Homo1, from differential fragments Homo sapiens mitochondrion and Rattus norvegicus mitochondrion. The expression of Homo1 was utilized to determine the distribution of UC-MSCs in the normal and diabetic nephropathy (DN) rats. RESULTS: We observed a significant correlation between the number of UC-MSCs and the expression level of Homo1. Following intravenous transplantation, the blood levels of UC-MSCs peaked at 30 min. A large amount of intravenously injected MSCs were trapped in the lungs, but the number of them decreased rapidly after 24 h. Additionally, the distribution of UC-MSCs in the kidneys of DN rats was significantly higher than that of normal rats. CONCLUSIONS: In this study, we establish a highly sensitive and specific Homo1-based real-time quantitative PCR method to quantify the distribution of human UC-MSCs in rats. The method provides guidelines for the safety research of cells in preclinical stages.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Humans , Rats , Animals , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cell Transplantation/methods , Umbilical Cord/metabolism
12.
Article in English | MEDLINE | ID: mdl-38417787

ABSTRACT

BACKGROUND: Preterm infants with low birthweight are at heightened risk of developmental sequelae, including neurological and cognitive dysfunction that can persist into adolescence or adulthood. In addition, preterm birth and low birthweight can provoke changes in endocrine and metabolic processes that likely impact brain health throughout development. However, few studies have examined associations among birthweight, pubertal endocrine process, long-term neurological and cognitive development. METHODS: We investigated the associations between birthweight and brain morphometry, cognitive function, and onset of adrenarche assessed 9 to 11 years later in 3571 preterm and full-term children using the Adolescent Brain Cognitive Development dataset. RESULTS: The preterm children showed lower birthweight and early adrenarche, as expected. Birthweight was positively associated with cognitive function (all︱Cohen's d︱> 0.154, P < 0.005), global brain volumes (all︱Cohen's d︱> 0.170, P < 0.008) and regional volumes in frontal, temporal, and parietal cortices in preterm and full-term children (all︱Cohen's d︱> 0.170, P < 0.0007); and cortical volume in the lateral orbitofrontal cortex (lOFC) partially mediated the effect of low birthweight on cognitive function in preterm children. In addition, adrenal score and cortical volume in the lOFC mediated the associations between birthweight and cognitive function only in preterm children. CONCLUSIONS: These findings highlight the impact of low birthweight on long-term brain structural and cognitive function development, and showed important associations with early onset of adrenarche during the puberty. This understanding may help with prevention and treatment.

13.
Protein Pept Lett ; 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38343045

ABSTRACT

BACKGROUND: Heat-labile uracil-DNA glycosylase (HL-UDG) is commonly employed to eliminate carry-over contamination in DNA amplifications. However, the prevailing HL-UDG is markedly inactivated at 50°C, rendering it unsuitable for specific one-step RT-qPCR protocols utilizing reverse transcriptase at an optimal temperature of 42°C. OBJECTIVE: This study aimed to explore novel HL-UDG with lower inactivation temperature and for recombinant expression. METHODS: The gene encoding an HL-UDG was cloned from the cold-water fish rainbow trout (Oncorhynchus mykiss) and expressed in Escherichia coli with high yield. The thermostability of the enzyme and other enzymatic characteristics were thoroughly examined. The novel HL-UDG was then applied for controlling carry-over contamination in one-step RT-qPCR. RESULTS: This recombinantly expressed truncated HL-UDG of rainbow trout (OmUDG) exhibited high amino acids similarity (84.1% identity) to recombinant Atlantic cod UDG (rcUDG) and was easily denatured at 40°C. The optimal pH of OmUDG was 8.0, and the optimal concentrations of both Na+ and K+ were 10 mM. Since its inactivation temperature was lower than that of rcUDG, the OmUDG could be used to eliminate carry-over contamination in one-step RT-qPCR with moderate reverse transcription temperature. CONCLUSION: We successfully identified and recombinantly expressed a novel HL-UDG with an inactivation temperature of 40°C. It is suitable for eliminating carry-over contamination in one-step RT-qPCR.

14.
Front Psychol ; 15: 1330024, 2024.
Article in English | MEDLINE | ID: mdl-38420165

ABSTRACT

Fairness plays a crucial role in children's social life and has garnered considerable attention. However, previous research and theories primarily examined the development of children's fairness behaviors in the conflict between self-interest motivation and fairness-complying motivation, neglecting the influence of advantage-seeking motivation. Moreover, despite the well-established role of gain/loss frame in human decision-making, it remains largely unclear whether the framing effect modulates fairness behaviors in children. It was hypothesized that children would exhibit advantage-seeking motivation resulting in more selfish behaviors in the loss context. To examine the hypothesis, we combined an adapted dictator game and computational modeling to investigate various motivations underlying fairness behaviors of children in both loss and gain contexts and to explore the developmental directions by contrasting children and adults. In addition, the current design enabled the dissociation between fairness knowledge and behaviors by asking participants to decide for themselves (the first-party role) or for others (the third-party role). This study recruited a total of 34 children (9-10 years, Mage = 9.82, SDage = 0.38, 16 females) and 31 college students (Mage = 19.81, SDage = 1.40, 17 females). The behavioral results indicated that children behaved more selfishly in first-party and more fairly in third-party than adults, without any significant framing effects. The computational results revealed that both children and adults exhibited aversion to advantageous and disadvantageous inequity in third-party. However, they showed distinct preferences for advantageous inequity in first-party, with advantage-seeking preferences among children and aversion to advantageous inequity among adults. These findings contribute to a deeper understanding of children's social preferences and their developmental directions.

15.
J Pharm Biomed Anal ; 242: 116030, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38382318

ABSTRACT

Liver's distinctive function renders it highly susceptible to diverse damage sources. Characterizing the metabolic profiles and spatial signatures in different liver injuries is imperative for early diagnosis and etiology-oriented treatment. In this comparative study, we conducted whole-body spatial metabolomics on zebrafish with liver injury induced by ethanol (EtOH), acetaminophen (APAP), and thioacetamide (TAA). The two specific levels, the whole-body and liver-specific metabolic profiles, as well as their regional distributions, were systematically mapped in situ by mass spectrometry imaging, which is distinct from conventional LC-MS and GC-MS methods. We found that liver injury regions exhibited more pronounced metabolic reprogramming than the entire organism, leading to significant alterations in eight fatty acids, three phospholipids, and four low-molecular-weight metabolites. More importantly, fatty acids as well as small molecule metabolites including glutamine, glutamate, taurine and malic acid displayed contrasting changes between alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). In addition, phospholipids, including Lyso PC (16:0) and Lyso PE (18:0), demonstrated notable down-regulation in all damaged liver, whereas PC (34:1) underwent upregulation. This study not only deepens insights into distinct potential biomarkers for liver injuries, but also underscores spatial metabolomics as a powerful tool to elucidate possible pathogenic mechanisms in other metabolic diseases.


Subject(s)
Non-alcoholic Fatty Liver Disease , Zebrafish , Animals , Zebrafish/metabolism , Liver/metabolism , Metabolomics/methods , Mass Spectrometry , Non-alcoholic Fatty Liver Disease/metabolism , Fatty Acids/metabolism , Phospholipids/metabolism
16.
Adv Sci (Weinh) ; 11(13): e2305212, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38263873

ABSTRACT

Platinum (Pt)-based chemotherapy is the main treatment for ovarian cancer (OC); however, most patients develop Pt resistance (Pt-R). This work shows that Pt-R OC cells increase intracellular cholesterol through uptake via the HDL receptor, scavenger receptor type B-1 (SR-B1). SR-B1 blockade using synthetic cholesterol-poor HDL-like nanoparticles (HDL NPs) diminished cholesterol uptake leading to cell death and inhibition of tumor growth. Reduced cholesterol accumulation in cancer cells induces lipid oxidative stress through the reduction of glutathione peroxidase 4 (GPx4) leading to ferroptosis. In turn, GPx4 depletion induces decreased cholesterol uptake through SR-B1 and re-sensitizes OC cells to Pt. Mechanistically, GPx4 knockdown causes lower expression of the histone acetyltransferase EP300, leading to reduced deposition of histone H3 lysine 27 acetylation (H3K27Ac) on the sterol regulatory element binding transcription factor 2 (SREBF2) promoter and suppressing expression of this key transcription factor involved in the regulation of cholesterol metabolism. SREBF2 downregulation leads to decreased SR-B1 expression and diminished cholesterol uptake. Thus, chemoresistance and cancer cell survival under high ROS burden obligates high GPx4 and SR-B1 expression through SREBF2. Targeting SR-B1 to modulate cholesterol uptake inhibits this axis and causes ferroptosis in vitro and in vivo in Pt-R OC.


Subject(s)
Nanoparticles , Ovarian Neoplasms , Humans , Female , Scavenger Receptors, Class B/metabolism , Cholesterol/metabolism , Transcription Factors/metabolism , Ovarian Neoplasms/drug therapy , Oxidation-Reduction
17.
Chem Commun (Camb) ; 60(12): 1567-1570, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38224451

ABSTRACT

A novel dual-outward contraction mechanism is applied to construct 2D hollow carbon superstructures (HCSs) via pyrolysis of hybrid ZIF superstructures. One outward contraction stress is offered by the in situ formed thin carbon shell, while another originates from the interconnected facets of ZIF polyhedra within the ZIF superstructure.

18.
J Environ Manage ; 351: 119892, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38176380

ABSTRACT

Mangrove is one of the most productive and sensitive ecosystems in the world. Due to the complexity and specificity of mangrove habitat, the development of mangrove is regulated by several factors. Species distribution models (SDMs) are effective tools to identify the potential habitats for establishing and regenerating the ecosystem. Such models usually include exclusively environmental factors. Nevertheless, recent studies have challenged this notion and highlight the importance of including biotic interactions. Both factors are necessary for a mechanistic understanding of the mangrove distribution in order to promote the protection and restoration of mangroves. Thus, we present a novel approach of combining environmental factors and interactions with salt marsh for projecting mangrove distributions at the global level and within latitudinal zones. To test the salt marsh interaction, we fit the MaxEnt model with two predicting sets: (1) environments only and (2) environments + salt marsh interaction index (SII). We found that both sets of models had good predictive ability, although the SII improved model performance slightly. Potential distribution areas of mangrove decrease with latitudes, and are controlled by biotic and abiotic factors. Temperature, precipitation and wind speed are generally critical at both global scale and ecotones along latitudes. SII is important on global scale, with a contribution of 5.9%, ranking 6th, and is particularly critical in the 10-30°S and 20-30°N zone. Interactions with salt marsh, including facilitation and competition, are shown to affect the distribution of mangroves at the zone of coastal ecotone, especially in the latitudinal range from 10° - 30°. The contribution of SII to mangrove distribution increases with latitudes due to the difference in the adaptive capacity of salt marsh plants and mangroves to environments. Totally, this study identified and quantified the effects of salt marsh on mangrove distribution by establishing the SII. The results not only facilitate to establish a more accurate mangrove distribution map, but also improve the efficiency of mangrove restoration by considering the salt marsh interaction in the mangrove management projects. In addition, the method of incorporating biotic interaction into SDMs through establish the biotic interaction index has contributed to the development of SDMs.


Subject(s)
Avicennia , Wetlands , Ecosystem , Climate Change , Temperature
19.
Small ; : e2308956, 2024 Jan 06.
Article in English | MEDLINE | ID: mdl-38183403

ABSTRACT

The present study proposes a novel engineering concept for the customization of functionality and construction of superstructure to fabricate 2D monolayered N-doped carbon superstructure electrocatalysts decorated with Co single atoms or Co2 P nanoparticles derived from 2D bimetallic ZnCo-ZIF superstructure precursors. The hierarchically porous carbon superstructure maximizes the exposure of accessible active sites, enhances electron/mass transport efficiency, and accelerates reaction kinetics simultaneously. Consequently, the Co single atoms embedded N-doped carbon superstructure (Co-NCS) exhibits remarkable catalytic activity toward oxygen reduction reaction, achieving a half-wave potential of 0.886 V versus RHE. Additionally, the Co2 P nanoparticles embedded N-doped carbon superstructure (Co2 P-NCS) demonstrates high activity for both oxygen evolution reaction and hydrogen evolution reaction, delivering low overpotentials of 292 mV at 10 mA cm-2 and 193 mV at 10 mA cm-2 respectively. Impressively, when employed in an assembled rechargeable Zn-air battery, the as-prepared 2D carbon superstructure electrocatalysts exhibit exceptional performance with a peak power density of 219 mW cm-2 and a minimal charge/discharge voltage gap of only 1.16 V at 100 mA cm-2 . Moreover, the cell voltage required to drive an overall water-splitting electrolyzer at a current density of 10 mA cm-2 is merely 1.69 V using these catalysts as electrodes.

20.
Psychol Med ; 54(2): 409-418, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37365781

ABSTRACT

BACKGROUND: Preterm birth is a global health problem and associated with increased risk of long-term developmental impairments, but findings on the adverse outcomes of prematurity have been inconsistent. METHODS: Data were obtained from the baseline session of the ongoing longitudinal Adolescent Brain and Cognitive Development (ABCD) Study. We identified 1706 preterm children and 1865 matched individuals as Control group and compared brain structure (MRI data), cognitive function and mental health symptoms. RESULTS: Results showed that preterm children had higher psychopathological risk and lower cognitive function scores compared to controls. Structural MRI analysis indicated that preterm children had higher cortical thickness in the medial orbitofrontal cortex, parahippocampal gyrus, temporal and occipital gyrus; smaller volumes in the temporal and parietal gyrus, cerebellum, insula and thalamus; and smaller fiber tract volumes in the fornix and parahippocampal-cingulum bundle. Partial correlation analyses showed that gestational age and birth weight were associated with ADHD symptoms, picvocab, flanker, reading, fluid cognition composite, crystallized cognition composite and total cognition composite scores, and measures of brain structure in regions involved with emotional regulation, attention and cognition. CONCLUSIONS: These findings suggest a complex interplay between psychopathological risk and cognitive deficits in preterm children that is associated with changes in regional brain volumes, cortical thickness, and structural connectivity among cortical and limbic brain regions critical for cognition and emotional well-being.


Subject(s)
Premature Birth , Child , Female , Adolescent , Infant, Newborn , Humans , Brain/pathology , Cognition/physiology , Infant, Premature , Longitudinal Studies , Magnetic Resonance Imaging/methods
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