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2.
Oral Dis ; 2024 May 19.
Article in English | MEDLINE | ID: mdl-38764349

ABSTRACT

OBJECTIVES: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) exhibit varying degrees of halitosis. The author speculated that small intestinal bacterial overgrowth (SIBO) might lead to MASLD and subsequent extra-oral halitosis and aimed to test this hypothesis. METHODS: This retrospective cross-sectional study reviewed 885 extra-oral halitosis patients. Halitosis and exhaled dimethyl sulfide (DMS) were measured by organoleptic score (OLS) (0-5) and OralChroma, respectively. SIBO and MASLD were diagnosed by hydrogen breath test and Fibroscan combined with cardiometabolic criteria. RESULTS: In this study, 133/885 (15.05%) of the halitosis patients otherwise healthy had MASLD, while 87/133 (65.41%) of the MASLD patients were SIBO-positive. No significant differences were observed in physical parameters such as age, serum biochemical parameters such as lipids, or Fibroscan parameters between the SIBO-positive and SIBO-negative patients. However, the OLS was 4 (interquartile range: 3-4) and exhaled DMS level was 56 (43-75) parts per billion (ppb) in the SIBO-positive patients, significantly greater than 2 (2-3) and 43 (25-51) ppb in the SIBO-negative patients (both p < 0.001). Exhaled hydrogen levels positively correlated with the OLS and exhaled DMS levels (r = 0.774, r = 0.740, both p < 0.001). CONCLUSION: MASLD can cause halitosis by SIBO.

3.
PLoS Negl Trop Dis ; 18(5): e0012086, 2024 May.
Article in English | MEDLINE | ID: mdl-38739636

ABSTRACT

INTRODUCTION: Neglected tropical diseases (NTDs) mainly affect underprivileged populations, potentially resulting in catastrophic health spending (CHS) and impoverishment from out-of-pocket (OOP) costs. This systematic review aimed to summarize the financial hardship caused by NTDs. METHODS: We searched PubMed, EMBASE, EconLit, OpenGrey, and EBSCO Open Dissertations, for articles reporting financial hardship caused by NTDs from database inception to January 1, 2023. We summarized the study findings and methodological characteristics. Meta-analyses were performed to pool the prevalence of CHS. Heterogeneity was evaluated using the I2 statistic. RESULTS: Ten out of 1,768 studies were included, assessing CHS (n = 10) and impoverishment (n = 1) among 2,761 patients with six NTDs (Buruli ulcer, chikungunya, dengue, visceral leishmaniasis, leprosy, and lymphatic filariasis). CHS was defined differently across studies. Prevalence of CHS due to OOP costs was relatively low among patients with leprosy (0.0-11.0%), dengue (12.5%), and lymphatic filariasis (0.0-23.0%), and relatively high among patients with Buruli ulcers (45.6%). Prevalence of CHS varied widely among patients with chikungunya (11.9-99.3%) and visceral leishmaniasis (24.6-91.8%). Meta-analysis showed that the pooled prevalence of CHS due to OOP costs of visceral leishmaniasis was 73% (95% CI; 65-80%, n = 2, I2 = 0.00%). Costs of visceral leishmaniasis impoverished 20-26% of the 61 households investigated, depending on the costs captured. The reported costs did not capture the financial burden hidden by the abandonment of seeking healthcare. CONCLUSION: NTDs lead to a substantial number of households facing financial hardship. However, financial hardship caused by NTDs was not comprehensively evaluated in the literature. To develop evidence-informed strategies to minimize the financial hardship caused by NTDs, studies should evaluate the factors contributing to financial hardship across household characteristics, disease stages, and treatment-seeking behaviors.


Subject(s)
Neglected Diseases , Tropical Medicine , Neglected Diseases/economics , Neglected Diseases/epidemiology , Humans , Tropical Medicine/economics , Health Expenditures/statistics & numerical data , Financial Stress/epidemiology , Leprosy/economics , Leprosy/epidemiology , Poverty , Cost of Illness , Elephantiasis, Filarial/economics , Elephantiasis, Filarial/epidemiology
4.
J Am Chem Soc ; 146(20): 13886-13893, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38739909

ABSTRACT

Guest-induced (crystal-to-crystal) transformation, i.e., periodic flexibility, is a typical feature of molecule-based crystalline porous materials, but its role for adsorptive separation is controversial. On the other hand, aperiodic flexibility is rarely studied. This work reports a pair of isomeric Cu(I) triazolate frameworks, namely, α-[Cu(fetz)] (MAF-2Fa) and ß-[Cu(fetz)] (MAF-2Fb), which show typical periodic and aperiodic flexibility for CO chemical adsorption, respectively. Quantitative mixture breakthrough experiments show that, while MAF-2Fa exhibits high adsorption capacity at high pressures but negligible adsorption below the threshold pressure and with leakage concentrations of 3-8%, MAF-2Fb exhibits relatively low adsorption capacity at high pressures but no leakage (residual CO concentration <1 ppb). Tandem connection of MAF-2Fa and MAF-2Fb can combine their advantages of high CO adsorption capacities at high and low pressures, respectively. MAF-2Fa and MAF-2Fb can both keep the separation performances unchanged at high relative humidities, but only MAF-2Fb shows a unique coadsorption behavior at a relative humidity of 82%, which can be used to improve purification performances.

5.
Dig Liver Dis ; 2024 May 11.
Article in English | MEDLINE | ID: mdl-38735796

ABSTRACT

BACKGROUND AND AIMS: TGF-ß1 induces epithelial-mesenchymal transition (EMT) and leads to intestinal fibrosis in ulcerative colitis (UC). We aimed to investigate the expression of transcribed ultraconserved region uc.290 in chronic UC and its role in intestinal fibrosis. METHODS: Colon specimens were taken from thirty chronic active UC, chronic inactive UC and healthy controls respectively. Modified Mayo score, expressions of uc.290, TGF-ß1, EMT biomarkers (Vimentin, α-SMA and E-cadherin) and intestinal fibrosis biomarker (collagen Ⅲ) in colon biopsy specimens were determined in human. Expressions of TGF-ß1, EMT biomarkers and collagen Ⅲ were determined in uc.290 overexpressed or silenced epithelial colon cells (HT29). RESULTS: Uc.290, TGF-ß1 and collagen Ⅲ were overexpressed, and EMT was prominent in chronic active UC. Uc.290 level had a positive correlation with modified Mayo score in chronic active UC. TGF-ß1 and collagen Ⅲ were overexpressed, and EMT was prominent in uc.290 overexpressed HT29 cells. CONCLUSIONS: Uc.290 was overexpressed in chronic active UC and might promote intestinal fibrosis by TGF-ß1/EMT/collagen Ⅲ pathway.

6.
Int J Biol Macromol ; 269(Pt 2): 132179, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38723817

ABSTRACT

BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disorder, marked by the degeneration of dopamine (DA) neurons in the substantia nigra (SN). Current evidence strongly suggests that neuroinflammation, primarily mediated by microglia, contributes to PD pathogenesis. Triggering receptor expressed on myeloid cells 2 (TREM2) might serve as a promising therapeutic target for PD due to its ability to suppress neuroinflammation. Dihydroquercetin (DHQ) is an important natural dihydroflavone and confers apparent anti-inflammatory, antioxidant and anti-fibrotic effects. Recently, DHQ-mediated neuroprotection was exhibited. However, the specific mechanisms of its neuroprotective effects remain incompletely elucidated. METHODS: In this study, rat models were utilized to induce damage to DA neurons using lipopolysaccharide (LPS) and 6-hydroxydopamine (6-OHDA) to assess the impacts of DHQ on the loss of DA neurons. Furthermore, DA neuronal MN9D cells and microglial BV2 cells were employed to investigate the function of TREM2 in DHQ-mediated DA neuroprotection. Finally, TREM2 knockout mice were used to investigate whether the neuroprotective effects mediated by DHQ through a mechanism dependent on TREM2. RESULTS: The main findings demonstrated that DHQ effectively protected DA neurons against neurotoxicity induced by LPS and 6-OHDA and inhibited microglia-elicited neuroinflammation. Meanwhile, DHQ promoted microglial TREM2 signaling activation. Notably, DHQ failed to reduce inflammatory cytokines release and further present neuroprotection from DA neurotoxicity upon TREM2 silencing. Similarly, DHQ didn't exert DA neuroprotection in TREM2 knockout mice. CONCLUSIONS: These findings suggest that DHQ exerted DA neuroprotection by regulating microglia TREM2 activation.


Subject(s)
Dopaminergic Neurons , Membrane Glycoproteins , Microglia , Neuroprotective Agents , Quercetin , Receptors, Immunologic , Animals , Quercetin/pharmacology , Quercetin/analogs & derivatives , Receptors, Immunologic/metabolism , Membrane Glycoproteins/metabolism , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Rats , Neuroprotective Agents/pharmacology , Microglia/drug effects , Microglia/metabolism , Mice , Male , Lipopolysaccharides , Mice, Knockout , Oxidopamine , Rats, Sprague-Dawley , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Cell Line
8.
Huan Jing Ke Xue ; 45(5): 2613-2621, 2024 May 08.
Article in Chinese | MEDLINE | ID: mdl-38629525

ABSTRACT

This study selected five typical types of chemical industry volatile organic compounds (VOCs) emission characteristics in China for analysis. The results from 70 source samples showed that alkanes were the dominant VOCs category from synthetic material industry sources, petrochemical industry sources, and coating industry sources (accounting for 43%, 63%, and 68%, respectively); olefins were the main VOCs category from the daily supplies chemical industry (46%); and halogenated hydrocarbons were the dominate VOCs category from specialty chemicals industry account source emissions (43%). Additionally, the machine learning method was applied in this study to analyze the marker components of the above industries. The results showed that decane and tetrahydrofuran were the source markers of the synthetic material industry; n-butanol and toluene were the markers of the daily supplies industry source; 1,2,3-trimethylbenzene and 1,3,5-trimethylbenzene were the markers of the petrochemical industry source; propylene and 3-methyl pentane were the source markers of the coating industry; and P-Xylene and cumene were the markers of the specialty chemicals industry source. The maximum incremental reactivity method (MIR) was used to estimate the ozone formation potential (OFP) of different VOCs-sources. The calculation results showed that when considering per unit TVOCs concentration emissions, the contribution to the ozone generation potential was in the order of the daily supplies chemical industry, specialty chemical industry, petrochemical industry, synthetic material industry, and coating industry. Therefore, we suggest that more attention should be paid to the key active species emitted by various industry sources rather than only the total amount of VOCs emissions in future ozone prevention and control efforts.

10.
J Photochem Photobiol B ; 254: 112893, 2024 May.
Article in English | MEDLINE | ID: mdl-38531303

ABSTRACT

An aromatic ring-containing compound with a wide range of biological activities, 9-methylacridine (AD-9-Me) is a precursor for the synthesis of various drugs. However, its photoactivation properties and mechanism of damage as a photo activator against Aedes aegypti are unknown. The toxic effects of AD-9-Me on Aedes aegypti mosquitoes were determined under light and non-light conditions. The results showed that the toxicity of AD-9-Me to mosquito larvae was significantly higher than that of the dark treatment after 24 h of light exposure; AD-9-Me was mainly distributed in the midgut of larvae, after 24 h of treatment, it can cause an increase in calcium ion concentration, reactive oxygen species (ROS) eruption and ROS accumulation by blocking the ROS elimination pathway in midgut cells. This in turn caused an increase in protein carbonyl and malondialdehyde (MDA) content, a decrease in mitochondrial membrane potential (MMP), a disruption of the barrier function of midgut tissues, a significant decrease in midgut weight and chitin content, which induced the up-regulation of AeDronc, AeCaspase8 and AeCaspase7 genes, leading to apoptotic cell death. In this study, we confirmed that AD-9-Me has photoactivation activity and mainly acts on the midgut of mosquito larvae, which can generate a large amount of ROS in the cells of the midgut and induce apoptosis to occur, resulting in the disruption of the function of the tissues of mosquito larvae, accelerating the death and delaying the development of the mosquito larvae.


Subject(s)
Aedes , Animals , Reactive Oxygen Species/metabolism , Larva , Mitochondria/metabolism , Apoptosis
11.
J Environ Manage ; 356: 120612, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38537465

ABSTRACT

In this study, we synthesized a high removal efficiency catalyst using biochar-supported nanoscale zero-valent iron and g-C3N4, denoted as g-C3N4/nZVI@SBC, to activate persulfate (PS) for the degradation of total petroleum hydrocarbon (TPH) in groundwater. We characterized the morphology and physiochemical properties of g-C3N4/nZVI@SBC with scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), BET surface area analysis, and X-ray photoelectron spectroscopy (XPS). To assess the performance of the g-C3N4/nZVI@SBC catalyst, we investigated various reaction parameters, such as the mass ratio of g-C3N4 to nZVI@SBC, PS concentration, initial pH, initial TPH concentration, and the presence of coexisting ions in the system. The results from batch experiments and repeated use trials indicate that g-C3N4/nZVI@SBC exhibited both excellent catalytic activation capability and impressive durability, making it a promising choice for TPH degradation. Specifically, when the PS concentration reached 1 mM, the catalyst dosage was 0.3 g/L, and the g-C3N4 to nZVI@SBC mass ratio was 2, we achieved a remarkable TPH removal efficiency of 93.8%. Through electron paramagnetic resonance (EPR) testing and quenching experiments, we identified sulfate radicals, hydroxyl radicals, and superoxide radicals as the primary active substance involved in the TPH degradation process. Moreover, the g-C3N4/nZVI@SBC composite proved highly effective for in-situ TPH removal from groundwater and displayed an 86% removal rate, making it a valuable candidate for applications in permeable reactive barriers (PRB) aimed at enhancing environmental remediation. In summary, by skillfully utilizing g-C3N4/nZVI@SBC, this study has made notable advancements in synthesis and characterization, presenting a feasible and innovative approach to addressing TPH pollution in groundwater.


Subject(s)
Groundwater , Water Pollutants, Chemical , Water Pollutants, Chemical/chemistry , Iron/chemistry , Microscopy, Electron, Scanning , Hydrocarbons , Groundwater/chemistry
12.
World J Clin Cases ; 12(7): 1215-1226, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38524522

ABSTRACT

BACKGROUND: Although the etiology of nonalcoholic fatty liver disease (NAFLD) has not been thoroughly understood, the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been highlighted by accumulating evidence. AIM: To evaluate the causal relationships between five anthropometric indicators and NAFLD employing Mendelian randomization (MR) design. METHODS: The Anthropometric Consortium provided genetic exposure data for five anthropometric indicators, including hip circumference (HC), waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI), and body fat percentage (BF). Genetic outcome data for NAFLD were obtained from the United Kingdom Biobank and FinnGen Consortium. Genome-wide significant single nucleotide polymorphisms were chosen as instrumental variables. Univariable MR (UVMR) and multivariable MR (MVMR) designs with analytical approaches, including inverse variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode methods, were used to assess the causal relationships between anthropometric indicators and NAFLD. RESULTS: Causal relationships were revealed by UVMR, indicating that a higher risk of NAFLD was associated with a per-unit increase in WC [IVW: odds ratio (OR) = 2.67, 95%CI: 1.42-5.02, P = 2.25 × 10-3], and BF was causally associated with an increased risk of NAFLD (WM: OR = 2.23, 95%CI: 1.07-4.66, P = 0.033). The presence of causal effects of WC on the decreased risk of NAFLD was supported by MVMR after adjusting for BMI and smoking. However, no causal association between BF and NAFLD was observed. In addition, other causal relationships of HC, WHR (BMI adjusted), and BMI with the risk of NAFLD were not retained after FDR correction. CONCLUSION: This study establishes a causal relationship, indicating that an increase in WC is associated with a higher risk of NAFLD. This demonstrates that a suitable decrease in WC is advantageous for preventing NAFLD.

13.
Sci Rep ; 14(1): 6583, 2024 03 19.
Article in English | MEDLINE | ID: mdl-38503873

ABSTRACT

We collected thyroid-related hormone index levels, sleep duration, and other basic characteristics of the population with depression from the NHANES 2009-2012 cycles and evaluated the association of Thyroid-Stimulating Hormone Index (TSHI) with sleep duration in the euthyroid population with depression via different analysis methods. We found that the association between TSHI and sleep duration was only found in patients with depression degree < Moderate (score: 1-14) rather than > Moderate group. Among the populations with degree < Moderate (N = 1918), only 4 indexes (parametric Thyroid Feedback Quantile Index, PTFQI, Thyrotroph Thyroxine Resistance Index, TT4RI, Thyroid-Stimulating Hormone TSH, and TSHI) reflecting the sensitivity to thyroid hormones were related to the sleep duration, with a significant non-linear relationship after adjusting for potential confounders (all P < 0.05). Trend analysis indicated that with the level increase of these 4 indexes, the sleep duration increased (all P for trend < 0.001). Further, we found that TSHI was relatively more important among the 4 indexes. Sum up, sensitivity to thyroid hormones is associated with sleep duration in the euthyroid population with depression degree lower than Moderate. Poor sensitivity referred to a longer sleep duration.


Subject(s)
Depression , Sleep Duration , Humans , Nutrition Surveys , Thyroid Hormones , Thyroxine , Thyrotropin
14.
Nature ; 628(8009): 887-893, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38538796

ABSTRACT

Efficient termination is required for robust gene transcription. Eukaryotic organisms use a conserved exoribonuclease-mediated mechanism to terminate the mRNA transcription by RNA polymerase II (Pol II)1-5. Here we report two cryogenic electron microscopy structures of Saccharomyces cerevisiae Pol II pre-termination transcription complexes bound to the 5'-to-3' exoribonuclease Rat1 and its partner Rai1. Our structures show that Rat1 displaces the elongation factor Spt5 to dock at the Pol II stalk domain. Rat1 shields the RNA exit channel of Pol II, guides the nascent RNA towards its active centre and stacks three nucleotides at the 5' terminus of the nascent RNA. The structures further show that Rat1 rotates towards Pol II as it shortens RNA. Our results provide the structural mechanism for the Rat1-mediated termination of mRNA transcription by Pol II in yeast and the exoribonuclease-mediated termination of mRNA transcription in other eukaryotes.


Subject(s)
Cryoelectron Microscopy , Exoribonucleases , RNA Polymerase II , RNA, Messenger , Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae , Transcription Termination, Genetic , Exoribonucleases/chemistry , Exoribonucleases/metabolism , Exoribonucleases/ultrastructure , Models, Molecular , Protein Binding , RNA Polymerase II/chemistry , RNA Polymerase II/metabolism , RNA Polymerase II/ultrastructure , RNA, Messenger/biosynthesis , RNA, Messenger/chemistry , RNA, Messenger/genetics , RNA, Messenger/ultrastructure , RNA-Binding Proteins/chemistry , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/ultrastructure , Saccharomyces cerevisiae/chemistry , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/ultrastructure , Saccharomyces cerevisiae Proteins/chemistry , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae Proteins/ultrastructure , Transcriptional Elongation Factors/chemistry , Transcriptional Elongation Factors/metabolism , Transcriptional Elongation Factors/ultrastructure , Chromosomal Proteins, Non-Histone/chemistry , Chromosomal Proteins, Non-Histone/metabolism , Chromosomal Proteins, Non-Histone/ultrastructure , Protein Domains , RNA, Fungal/biosynthesis , RNA, Fungal/chemistry , RNA, Fungal/genetics , RNA, Fungal/ultrastructure
15.
Blood Cancer Discov ; 5(3): 180-201, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38442309

ABSTRACT

In many cancers, mortality is associated with the emergence of relapse with multidrug resistance (MDR). Thus far, the investigation of cancer relapse mechanisms has largely focused on acquired genetic mutations. Using acute myeloid leukemia (AML) patient-derived xenografts (PDX), we systematically elucidated a basis of MDR and identified drug sensitivity in relapsed AML. We derived pharmacologic sensitivity for 22 AML PDX models using dynamic BH3 profiling (DBP), together with genomics and transcriptomics. Using in vivo acquired resistant PDXs, we found that resistance to unrelated, narrowly targeted agents in distinct PDXs was accompanied by broad resistance to drugs with disparate mechanisms. Moreover, baseline mitochondrial apoptotic priming was consistently reduced regardless of the class of drug-inducing selection. By applying DBP, we identified drugs showing effective in vivo activity in resistant models. This study implies evasion of apoptosis drives drug resistance and demonstrates the feasibility of the DBP approach to identify active drugs for patients with relapsed AML. SIGNIFICANCE: Acquired resistance to targeted therapy remains challenging in AML. We found that reduction in mitochondrial priming and common transcriptomic signatures was a conserved mechanism of acquired resistance across different drug classes in vivo. Drugs active in vivo can be identified even in the multidrug resistant state by DBP.


Subject(s)
Apoptosis , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Leukemia, Myeloid, Acute , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/genetics , Humans , Apoptosis/drug effects , Animals , Mice , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Drug Resistance, Multiple/genetics , Drug Resistance, Multiple/drug effects , Xenograft Model Antitumor Assays , Granulocyte Precursor Cells/drug effects , Granulocyte Precursor Cells/pathology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use
16.
Chem Sci ; 15(10): 3661-3669, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38455005

ABSTRACT

Ferroelastic materials have gained widespread attention as promising candidates for mechanical switches, shape memory, and information processing. Their phase-transition mechanisms usually originate from conventional order-disorder and/or displacive types, while those involving dynamic coordination bonds are still scarce. Herein, based on a strategic molecular design of organic cations, we report three new polar hybrid crystals with a generic formula of AA'RbBiCl6 (A = A' = Me3SO+ for 1; A = Me3SO+ and A' = Me4N+ for 2; A = A' = Me3NNH2+ for 3). Their A-site cations link to the [RbBiCl6]n2n- inorganic framework with lon topology through Rb-O/N coordination bonds, while their significantly different interactions between A'-site cations and inorganic frameworks provide distinct phase-transition behaviour. In detail, the strongly coordinative A'-site Me3SO+ cations prevent 1 from a structural phase transition, while coordinatively free A'-site Me4N+ cations trigger a conventional order-disorder ferroelastic transition at 247 K in 2, accompanied by a latent heat of 0.63 J g-1 and a usual "high → low" second-harmonic-generation (SHG) switch. Interestingly, the A'-site Me3NNH2+ cations in 3 reveal unusual dynamic coordination bonds, driving a high-temperature ferroelastic transition at 369 K with a large latent heat of 18.34 J g-1 and an unusual "low → high" SHG-switching behaviour. This work provides an effective molecular assembly strategy to establish dynamic coordination bonds in a new type of host-guest model and opens an avenue for designing advanced ferroelastic multifunctional materials.

17.
World J Gastrointest Surg ; 16(2): 481-490, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38463353

ABSTRACT

BACKGROUND: Individuals with refractory ascites in the context of liver cirrhosis typically face an adverse prognosis. The transjugular intrahepatic portosystemic shunt (TIPS) is an efficacious intervention, but there is a lack of reliable tools for postoperative prognosis assessment. Previously utilized clinical biochemical markers, such as the serum albumin concentration (Alb), sodium (Na+) concentration, and serum creatinine (Scr), have limited predictive value. Therefore, the quest for novel, specific biomarkers to evaluate the post-TIPS prognosis in patients with liver cirrhosis and refractory ascites holds significant practical importance. AIM: To investigate the associations between the Child-Pugh score, model for end-stage liver disease (MELD) score, and serum cystatin C (Cys C) level and post-TIPS prognosis in patients with liver cirrhosis and refractory ascites. METHODS: A retrospective analysis was conducted on 75 patients with liver cirrhosis and refractory ascites who underwent TIPS at our institution from August 2019 to August 2021. These patients were followed up regularly for two years, and the death toll was meticulously documented. The patients were allocated into a survival group (n = 45 patients) or a deceased group (n = 30 patients) based on their prognosis status. The clinical data of the two groups were collected, and Child-Pugh scores and MELD scores were calculated for analysis. Spearman correlation analysis was carried out to evaluate the correlation of prognosis with Child-Pugh grade, MELD score, and Cys C level. Additionally, a multiple-factor analysis utilizing the Cox proportional hazard model was used to identify independent risk factors affecting the post-TIPS prognosis of patients with liver cirrhosis and refractory ascites. The receiver operating characteristic curve (ROC) ascertained the predictive value of the Cys C concentration, Child-Pugh grade, and MELD score for the prognosis of liver cirrhosis with refractory ascites in post-TIPS patients. RESULTS: During a 2-year follow-up period, among 75 patients with liver cirrhosis and refractory ascites who underwent TIPS treatment, 30 patients (40.00%) passed away. The deceased cohort exhibited heightened aspartate aminotransferase, alanine aminotransferase, total bilirubin, Scr, prothrombin time, Cys C, international normalized ratio, Child-Pugh, and MELD scores compared to those of the survival cohort, while Alb and Na+ levels were attenuated in the deceased group (P < 0.05). Spearman analysis revealed moderate to high positive correlations between prognosis and Child-Pugh score, MELD score, and Cys C level (r = 0.709, 0.749, 0.671, P < 0.05). Multivariate analysis using the Cox proportional hazard model demonstrated that the independent risk factors for post-TIPS prognosis in patients with liver cirrhosis and refractory ascites were Cys C (HR = 3.802; 95%CI: 1.313-11.015), Child-Pugh (HR = 3.030; 95%CI: 1.858-4.943), and MELD (HR = 1.222; 95%CI: 1.073-1.393) scores. ROC analysis confirmed that, compared to those of the classic prognostic models for Child-Pugh and MELD scores, the predictive accuracy of Cys C for post-TIPS prognosis in patients with liver cirrhosis and refractory ascites was slightly lower. This analysis yielded sensitivity and specificity values of 83.33% and 82.22%, respectively. The area under the curve value at this juncture was 0.883, with an optimal cutoff value set at 1.95 mg/L. CONCLUSION: Monitoring the serum Cys C concentration is valuable for assessing the post-TIPS prognosis in patients with liver cirrhosis and refractory ascites. Predictive models based on serum Cys C levels, as opposed to Scr levels, are more beneficial for evaluating the condition and prognosis of patients with ascites due to cirrhosis.

18.
Cell ; 187(5): 1127-1144.e21, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38428393

ABSTRACT

Chloroplasts are green plastids in the cytoplasm of eukaryotic algae and plants responsible for photosynthesis. The plastid-encoded RNA polymerase (PEP) plays an essential role during chloroplast biogenesis from proplastids and functions as the predominant RNA polymerase in mature chloroplasts. The PEP-centered transcription apparatus comprises a bacterial-origin PEP core and more than a dozen eukaryotic-origin PEP-associated proteins (PAPs) encoded in the nucleus. Here, we determined the cryo-EM structures of Nicotiana tabacum (tobacco) PEP-PAP apoenzyme and PEP-PAP transcription elongation complexes at near-atomic resolutions. Our data show the PEP core adopts a typical fold as bacterial RNAP. Fifteen PAPs bind at the periphery of the PEP core, facilitate assembling the PEP-PAP supercomplex, protect the complex from oxidation damage, and likely couple gene transcription with RNA processing. Our results report the high-resolution architecture of the chloroplast transcription apparatus and provide the structural basis for the mechanistic and functional study of transcription regulation in chloroplasts.


Subject(s)
DNA-Directed RNA Polymerases , Plastids , Chloroplasts/metabolism , Cryoelectron Microscopy , DNA-Directed RNA Polymerases/genetics , Nicotiana/genetics , Photosynthesis , Plastids/enzymology
19.
World J Clin Oncol ; 15(1): 145-158, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38292666

ABSTRACT

BACKGROUND: Emerging research suggests that microRNAs (miRNAs) play an important role in the development of hepatocellular carcinoma (HCC). A comprehensive analysis of recent research concerning miRNAs in HCC development could provide researchers with a valuable reference for further studies. AIM: To make a comprehensive analysis of recent studies concerning miRNAs in HCC. METHODS: All relevant publications were retrieved from the Web of Science Core Collection database. Bibliometrix software, VOSviewer software and CiteSpace software were used to visually analyze the distribution by time, countries, institutions, journals, and authors, as well as the keywords, burst keywords and thematic map. RESULTS: A total of 9426 publications on this topic were found worldwide. According to the keywords analysis, we found that the studies of miRNAs focused on their expression level, effects, and mechanisms on the biological behaviour of HCC. Keywords bursting analysis showed that in the early years (2013-2017), "microRNA expression", "gene expression", "expression profile", "functional polymorphism", "circulating microRNA", "susceptibility" and "mir 21" started to attract attention. In the latest phase (2018-2022), the hot topics turned to "sorafenib resistance", "tumor microenvironment" and so on. CONCLUSION: This study provides a comprehensive overview of the role of miRNAs in HCC development based on bibliometric analysis. The hotspots in this field focus on miRNAs expression level, effects, and mechanisms on the biological behavior of HCC. The frontiers turned to sorafenib resistance, tumor microenvironment and so on.

20.
J Breath Res ; 18(2)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38266272

ABSTRACT

Characteristics of extra-oral halitosis induced by functional constipation (FC) have never been revealed. To address this, this prospective cohort was conducted with 100 FC patients, who were divided into a halitosis group and a negative group. Organoleptic score (OLS) ⩾ 2 in nose breath was diagnosed as extra-oral halitosis. Concentration of overall volatile sulfur compounds (VSCs) measured by Halimeter, concentration of hydrogen sulfide (HS), methanethiol (MT), dimethyl sulfide (DMS) and their total amount measured by OralChroma in nose breath was recorded asC-VSC,C-HS,C-MT,C-DMS andC-sum respectively. We found that 82% (82/100) of the FC patients had extra-oral halitosis. However, only 12.5% (3/82) and 1.22% (1/82) of halitosis group were correctly diagnosed with the current diagnostic threshold ofC-VSC ⩾ 110 parts per billion (ppb) and ⩾150 ppb.C-VSC,C-DMS andC-sum were significantly higher in the halitosis group compared to the negative group (allP< 0.001), with ratios of about 2.2 times, 3.1 times and 2.1 times respectively.C-HS andC-MT were low and not significantly different between the groups. Positive correlations were observed among OLS,C-VSC,C-DMS andC-sum. The area under curve of receiver operating characteristics ofC-VSC, C-DMS andC-sum for predicting FC-induced halitosis was 0.909, 0.9073 and 0.962 respectively, with the threshold values of ⩾36 ppb, ⩾52 ppb and ⩾75 ppb respectively. Therefore, we conclude that: (1) DMS is the primary contributor to FC-induced extra-oral halitosis. (2) OLS, Halimeter and OralChroma are consistent in detecting FC-induced extra-oral halitosis. (3) The diagnostic threshold for Halimeter should be adjusted toC-VSC ⩾ 36 ppb and the diagnostic threshold for OralChroma should be set asC-DMS ⩾ 52 ppb for diagnosing FC-induced extra-oral halitosis.


Subject(s)
Halitosis , Hydrogen Sulfide , Sulfhydryl Compounds , Humans , Halitosis/diagnosis , Halitosis/etiology , Prospective Studies , Breath Tests , Sulfides , Sulfur Compounds/adverse effects
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