Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 4.617
Filter
1.
BMC Cardiovasc Disord ; 24(1): 321, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918704

ABSTRACT

BACKGROUND: Catheter ablation and antiarrhythmic drug therapy are utilized for rhythm control in atrial fibrillation (AF), but their comparative effectiveness, especially with contemporary treatment modalities, remains undefined. We conducted a systematic review and meta-analysis contrasting current ablation techniques against antiarrhythmic medications for AF. METHODS: We searched PubMed, SCOPUS, Cochrane CENTRAL, and Web of Science until November 2023 for randomized trials comparing AF catheter ablation with antiarrhythmics, against antiarrhythmic drug therapy alone, reporting outcomes for > 6 months. Four investigators extracted data and appraised risk of bias (ROB) with ROB 2 tool. Meta-analyses estimated pooled efficacy and safety outcomes using R software. RESULTS: Twelve trials (n = 3977) met the inclusion criteria. Catheter ablation was associated with lower AF recurrence (relative risk (RR) = 0.44, 95%CI (0.33, 0.59), P ˂ 0.0001) and hospitalizations (RR = 0.44, 95%CI (0.23, 0.82), P = 0.009) than antiarrhythmic medications. Catheter ablation also improved the physical quality of life component score (assessed by a 36-item Short Form survey) by 7.61 points (95%CI -0.70-15.92, P = 0.07); but, due to high heterogeneity, it was not statistically significant. Ablation was significantly associated with higher procedural-related complications [RR = 15.70, 95%CI (4.53, 54.38), P < 0.0001] and cardiac tamponade [RR = 9.22, 95%CI (2.16, 39.40), P = 0.0027]. All-cause mortality was similar between the two groups. CONCLUSIONS: For symptomatic AF, upfront catheter ablation reduces arrhythmia and hospitalizations better than continued medical therapy alone, albeit with moderately more adverse events. Careful patient selection and risk-benefit assessment are warranted regarding the timing of ablation.


Subject(s)
Anti-Arrhythmia Agents , Atrial Fibrillation , Catheter Ablation , Recurrence , Humans , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Atrial Fibrillation/physiopathology , Atrial Fibrillation/drug therapy , Atrial Fibrillation/mortality , Atrial Fibrillation/therapy , Catheter Ablation/adverse effects , Anti-Arrhythmia Agents/therapeutic use , Anti-Arrhythmia Agents/adverse effects , Treatment Outcome , Risk Factors , Middle Aged , Female , Male , Heart Rate/drug effects , Aged , Quality of Life , Time Factors , Risk Assessment , Randomized Controlled Trials as Topic
2.
Respir Res ; 25(1): 259, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38915033

ABSTRACT

BACKGROUND: Management of PE has become streamlined with the implementation of PE Response Teams (PERT). Race, ethnicity and insurance status are known to influence the outcomes of patients with acute PE. However, whether the implementation of PERT-based care mitigates these racial and ethnic disparities remains unknown. Our aim was to assess the association of race, ethnicity and insurance with outcomes for patients with acute PE managed by PERT. METHODS: We performed a retrospective chart review of 290 patients with acute PE, who were admitted to one of three urban teaching hospitals in the Mount Sinai Health System (New York, NY) from January 2021 to October 2023. A propensity score-weighted analysis was performed to explore the association of race, ethnicity and insurance status with overall outcomes. RESULTS: Median age of included patients was 65.5 years and 149 (51.4%) were female. White, Black and Asian patients constituted 56.2% (163), 39.6% (115) and 3.5% [10] of the cohort respectively. Patients of Hispanic or Latino ethnicity accounted for 8.3% [24] of the sample. The 30-day rates of mortality, major bleeding and 30-day re-admission were 10.3%, 2.1% and 12.8% respectively. Black patients had higher odds of major bleeding (odds ratio [OR]: 1.445; p < 0.0001) when compared to White patients. Patients of Hispanic or Latino ethnicity had lower odds of receiving catheter-directed thrombolysis (OR: 0.966; p = 0.0003) and catheter-directed or surgical embolectomy (OR: 0.906; p < 0.0001) when compared to non-Hispanic/Latino patients. Uninsured patients had higher odds of receiving systemic thrombolysis (OR: 1.034; p = 0.0008) and catheter-directed thrombolysis (OR: 1.059; p < 0.0001), and lower odds of receiving catheter-directed or surgical embolectomy (OR: 0.956; p = 0.015) when compared to insured patients, although the odds of 30-day mortality and 30-day major bleeding were not significantly different. CONCLUSION: Within a cohort of PE patients managed by PERT, there were significant associations between race, ethnicity and overall outcomes. Hispanic or Latino ethnicity and uninsured status were associated with lower odds of receiving catheter-directed or surgical embolectomy. These results suggest that disparities related to ethnicity and insurance status persist despite PERT-based care of patients with acute PE.


Subject(s)
Ethnicity , Insurance Coverage , Pulmonary Embolism , Humans , Female , Male , Retrospective Studies , Aged , Middle Aged , Pulmonary Embolism/ethnology , Pulmonary Embolism/therapy , Insurance Coverage/statistics & numerical data , Treatment Outcome , Acute Disease , Healthcare Disparities/ethnology , Racial Groups , Aged, 80 and over
3.
J Org Chem ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38917372

ABSTRACT

A novel methodology for the synthesis of nitrones via palladium-catalyzed redox cross-coupling of nitro compounds and alcohols is established. The protocol is a mild, convenient, ligand-free, and scalable synthesis method that can be compatible with various nitro compounds and alcohols. Nitrone is a significant multifunctional platform synthon which can be synthesized directly and efficiently via this tactic from commercially available and cheap raw materials.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 819-824, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38926973

ABSTRACT

OBJECTIVE: To analyze the DTA (DNMT3A, TET2, ASXL1) mutations in patients with myeloproliferative neoplasms (MPN), and preliminarily explore their correlation with thromboembolism. METHODS: Clinical characteristics of 62 patients diagnosed de novo MPN at Central Hospital Affiliated to Shandong First Medical University from September 2016 to September 2022 were retrospectively analyzed. Next-generation sequencing was used to detect 35 MPN-related genes, and the DTA mutations in MPN patients and their relationship with thromboembolic events were analyzed. RESULTS: 75.8% (47/62) of the patients presented pathogenic non-driver mutations, and the mean number of pathogenic non-driver mutations per patient was 1.08. Among them, the most frequently mutated non-driver genes were TET2 (38.7%, 24/62), DNMT3A (9.7%, 6/62) and ASXL1 (6.5%, 4/62). The presence of DTA gene mutations was 50% (31/62) in the total MPN patients, and mainly accompanied by driver mutations. The mutation rate of DTA in patients aged ≥60 years was significantly higher than that in patients <60 years old (P =0.039). The incidence of thromboembolism in patients with DTA mutation was 58.1% (18/31), which was significantly higher than that in patients without DTA mutation (19.4%, 6/31) (P =0.002). The TET2 gene mutation rate in MPN patients with thromboembolism was 66.7% (16/24), which was significantly higher than that in patients without thromboembolism (21.1%, 8/38) (P =0.00). CONCLUSION: Patients with MPN have a higher incidence of DTA mutations, which are mainly accompanied by driver gene mutations. The incidence of thromboembolism in MPN patients with DTA mutations is higher than that in patients without DTA mutations. Especially, the elderly (≥60 years) essential thrombocythemia(ET) and polycythemia vera(PV) patients with TET2 mutation should be vigilant for thromboembolic events.


Subject(s)
DNA Methyltransferase 3A , DNA-Binding Proteins , Dioxygenases , Mutation , Myeloproliferative Disorders , Proto-Oncogene Proteins , Repressor Proteins , Thromboembolism , Humans , Middle Aged , Myeloproliferative Disorders/genetics , Myeloproliferative Disorders/complications , Thromboembolism/genetics , Retrospective Studies , Proto-Oncogene Proteins/genetics , DNA-Binding Proteins/genetics , Repressor Proteins/genetics , DNA (Cytosine-5-)-Methyltransferases/genetics , Male , Female , High-Throughput Nucleotide Sequencing
5.
J Med Chem ; 67(12): 9776-9788, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38837951

ABSTRACT

Type II kinase inhibitors bind in the "DFG-out" kinase conformation and are generally considered to be more potent and selective than type I inhibitors, which target a DFG-in conformation. Nine type II inhibitors are currently clinically approved, with more undergoing clinical development. Resistance-conferring secondary mutations emerged with the first series of type II inhibitors, most commonly at residues within the kinase activation loop and at the "gatekeeper" position. Recently, new inhibitors have been developed to overcome such mutations; however, mutations activating other pathways (and/or other targets) have subsequently emerged on occasion. Here, we systematically summarize the secondary mutations that confer resistance to type II inhibitors, the structural basis for resistance, newer inhibitors designed to overcome resistance, as well as the challenges and opportunities for the development of new inhibitors to overcome secondary kinase domain mutations.


Subject(s)
Mutation , Protein Kinase Inhibitors , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Humans , Animals
6.
Poult Sci ; 103(8): 103891, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38878746

ABSTRACT

Mercuric chloride (HgCl2) is a nephrotoxic contaminant that is widely present in the environment. Selenium (Se) can effectively antagonize the biological toxicity caused by heavy metals. Here, in vivo and in vitro models of Se antagonism to HgCl2-induced nephrotoxicity in chickens were established, with the aim of exploring the specific mechanism. Morphological observation and kidney function analysis showed that Se alleviated HgCl2-induced kidney tissue injury and cytotoxicity. The results showed that ferroptosis was the primary mechanism for the toxicity of HgCl2, as indicated by iron overload and lipid peroxidation. On the one hand, Se significantly prevented HgCl2-induced iron overload. On the other hand, Se alleviated the intracellular reactive oxygen species (ROS) levels caused by HgCl2. Subsequently, we focused on the sources of ROS during HgCl2-induced ferroptosis. Mechanically, Se reduced ROS overproduction induced by HgCl2 through mitochondrial calcium uniporter (MCU)/mitochondrial calcium uptake 1 (MICU1)-mediated mitochondrial calcium ion (Ca2+) overload. Furthermore, a dual luciferase reporter assay demonstrated that MICU1 was the direct target of miR-202-5p. Overall, Se represses miR-202-5p/MICU1 axis to attenuate HgCl2-induced kidney ferroptosis.

7.
Sci Rep ; 14(1): 13939, 2024 06 17.
Article in English | MEDLINE | ID: mdl-38886444

ABSTRACT

Feed efficiency (FE) is essential for pig production, has been reported to be partially explained by gut microbiota. Despite an extensive body of research literature to this topic, studies regarding the regulation of feed efficiency by gut microbiota remain fragmented and mostly confined to disorganized or semi-structured unrestricted texts. Meanwhile, structured databases for microbiota analysis are available, yet they often lack a comprehensive understanding of the associated biological processes. Therefore, we have devised an approach to construct a comprehensive knowledge graph by combining unstructured textual intelligence with structured database information and applied it to investigate the relationship between pig gut microbes and FE. Firstly, we created the pgmReading knowledge base and the domain ontology of pig gut microbiota by annotating, extracting, and integrating semantic information from 157 scientific publications. Secondly, we created the pgmPubtator by utilizing PubTator to expand the semantic information related to microbiota. Thirdly, we created the pgmDatabase by mapping and combining the ADDAGMA, gutMGene, and KEGG databases based on the ontology. These three knowledge bases were integrated to form the Pig Gut Microbial Knowledge Graph (PGMKG). Additionally, we created five biological query cases to validate the performance of PGMKG. These cases not only allow us to identify microbes with the most significant impact on FE but also provide insights into the metabolites produced by these microbes and the associated metabolic pathways. This study introduces PGMKG, mapping key microbes in pig feed efficiency and guiding microbiota-targeted optimization.


Subject(s)
Animal Feed , Gastrointestinal Microbiome , Animals , Swine , Knowledge Bases , Databases, Factual
8.
Animals (Basel) ; 14(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38891682

ABSTRACT

Crytosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi are important diarrheal pathogens with a global distribution that threatens the health of humans and animals. Despite cattle being potential transmission hosts of these protozoans, the associated risks to public health have been neglected. In the present study, a total of 1155 cattle fecal samples were collected from 13 administrative regions of Heilongjiang Province. The prevalence of Cryptosporidium spp., G. duodenalis, and E. bieneusi were 5.5% (64/1155; 95% CI: 4.2-6.9), 3.8% (44/1155; 95% CI: 2.7-4.9), and 6.5% (75/1155; 95% CI: 5.1-7.9), respectively. Among these positive fecal samples, five Cryptosporidium species (C. andersoni, C. bovis, C. ryanae, C. parvum, and C. occultus), two G. duodenalis assemblages (E and A), and eight E. bieneusi genotypes (BEB4, BEB6, BEB8, J, I, CHS7, CHS8, and COS-I) were identified. Phylogenetic analysis showed that all eight genotypes of E. bieneusi identified in the present study belonged to group 2. It is worth noting that some species/genotypes of these intestinal protozoans are zoonotic, suggesting a risk of zoonotic disease transmission in endemic areas. The findings expanded our understanding of the genetic composition and zoonotic potential of Cryptosporidium spp., G. duodenalis, and E. bieneusi in cattle in Heilongjiang Province.

9.
Science ; 384(6701): eadk5382, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38870290

ABSTRACT

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.


Subject(s)
ATP-Dependent Proteases , Artemisinins , Cholesterol Side-Chain Cleavage Enzyme , Mitochondrial Proteins , Polycystic Ovary Syndrome , Animals , Female , Humans , Mice , Rats , Androgens/metabolism , Artemisinins/therapeutic use , Artemisinins/pharmacology , Cholesterol Side-Chain Cleavage Enzyme/metabolism , Cholesterol Side-Chain Cleavage Enzyme/genetics , Disease Models, Animal , Hyperandrogenism/drug therapy , Hyperandrogenism/metabolism , Mitochondrial Proteins/metabolism , Mitochondrial Proteins/genetics , Ovary/drug effects , Ovary/metabolism , Polycystic Ovary Syndrome/drug therapy , Proteolysis , Mice, Inbred C57BL , Young Adult , Adult , Rats, Sprague-Dawley , ATP-Dependent Proteases/genetics , ATP-Dependent Proteases/metabolism
10.
Sci China Life Sci ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38902450

ABSTRACT

Energy status is linked to the production of reactive oxygen species (ROS) in macrophages, which is elevated in obesity. However, it is unclear how ROS production is upregulated in macrophages in response to energy overload for mediating the development of obesity. Here, we show that the Rab-GTPase activating protein (RabGAP) TBC1D1, a substrate of the energy sensor AMP-activated protein kinase (AMPK), is a critical regulator of macrophage ROS production and consequent adipose inflammation for obesity development. TBC1D1 deletion decreases, whereas an energy overload-mimetic non-phosphorylatable TBC1D1S231A mutation increases, ROS production and M1-like polarization in macrophages. Mechanistically, TBC1D1 and its downstream target Rab8a form an energy-responsive complex with NOX2 for ROS generation. Transplantation of TBC1D1S231A bone marrow aggravates diet-induced obesity whereas treatment with an ultra-stable TtSOD for removal of ROS selectively in macrophages alleviates both TBC1D1S231A mutation- and diet-induced obesity. Our findings therefore have implications for drug discovery to combat obesity.

11.
Org Lett ; 26(23): 4857-4862, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38838191

ABSTRACT

The efficient construction of π-conjugated polycyclic heteroarenes represents a significant task in the field of functional materials. A one-step oxidative tandem cyclization of aromatic acids with (benzo)thiophenes was developed to access planar sulfur-containing polycyclic heteroarenes. This protocol undergoes intermolecular cross-dehydrogenative coupling followed by intramolecular Friedel-Crafts acylation and provides a facile pathway to planar polycyclic compounds from inexpensive reactants. The synthesized heteroarenes serving as lipid-droplet-targeted probes exhibit outstanding performance with favorable biocompatibility and photostability.

12.
Angew Chem Int Ed Engl ; : e202408551, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858167

ABSTRACT

Heat-activated second harmonic generation (SHG) switching materials are gaining interest for their ability to switch between SHG on and off states, offering potential in optoelectronic applications. The novel nonlinear optical (NLO) switch, (C5H6NO)+(CH3SO3)- (4-hydroxypyridinium methylsulfonate, 4HPMS), is a near-room-temperature thermal driven material with a strong SHG response (3.3 × KDP), making it one of the most potent heat-stimulated NLO switches. It offers excellent contrast of 13 and a high laser-induced damage threshold (2.5 × KDP), with reversibility > 5 cycles. At 73 °C, 4HPMS transitions from the noncentrosymmetric Pna21 room temperature phase (RTP) to the centrosymmetric P21/c phase, caused by the rotation of the (C5H6NO)+ and (CH3SO3)- due to partially thermal breaking of intermolecular hydrogen bonds. The reverse phase change exhibits a large 50 °C thermal hysteresis. Density functional theory (DFT) calculations show that (C5H6NO)+ primarily dictates both the SHG coefficient (dij) and birefringence (∆n(Zeiss) = 0.216 vs ∆n(cal.) = 0.202 at 546 nm; Δn(Immersion) = 0.210 vs ∆n(cal.) = 0.198 at 589.3 nm), while the band gap (Eg) is influenced synergistically by (C5H6NO)+ and (CH3SO3)-. Additionally, 4HPMS-RTP also exhibits mechanochromism upon grinding as well as an aggregation-enhanced emission in a mixture of acetone and water.

13.
Micromachines (Basel) ; 15(6)2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38930766

ABSTRACT

This study introduces a novel approach for fabricating vertically stacked mini-LED arrays, integrating InGaN yellow and blue epitaxial layers with a stress buffer layer to enhance optoelectronic characteristics and structural stability. This method significantly simplifies the LED design by reducing the need for RGB configurations, thus lowering costs and system complexity. Employing vertical stacking integration technology, the design achieves high-density, efficient white light production suitable for multifunctional applications, including automotive lighting and outdoor signage. Experimental results demonstrate the exceptional performance of the stacked yellow and blue mini-LEDs in terms of luminous efficiency, wavelength precision, and thermal stability. The study also explores the performance of these LEDs under varying temperature conditions and their long-term reliability, indicating that InGaN-based yellow LEDs offer superior performance over traditional AlGaInP yellow LEDs, particularly in high-temperature environments. This technology promises significant advancements in the design and application of lighting systems, with potential implications for both automotive and general illumination markets.

14.
BMC Anesthesiol ; 24(1): 200, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840092

ABSTRACT

BACKGROUND: The inhalational anesthetic isoflurane is commonly utilized in clinical practice, particularly in the field of pediatric anesthesia. Research has demonstrated its capacity to induce neuroinflammation and long-term behavioral disorders; however, the underlying mechanism remains unclear [1]. The cation-chloride cotransporters Na+-K+-2Cl--1 (NKCC1) and K+-2Cl--2 (KCC2) play a pivotal role in regulating neuronal responses to gamma-aminobutyric acid (GABA) [2]. Imbalances in NKCC1/KCC2 can disrupt GABA neurotransmission, potentially leading to neural circuit hyperexcitability and reduced inhibition following neonatal exposure to anesthesia [3]. Therefore, this study postulates that anesthetics have the potential to dysregulate NKCC1 and/or KCC2 during brain development. METHODS: We administered 1.5% isoflurane anesthesia to neonatal rats for a duration of 4 h at postnatal day 7 (PND7). Anxiety levels were assessed using the open field test at PND28, while cognitive function was evaluated using the Morris water maze test between PND31 and PND34. Protein levels of NKCC1, KCC2, BDNF, and phosphorylated ERK (P-ERK) in the hippocampus were measured through Western blotting analysis. Pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α were quantified using ELISA. RESULTS: We observed a decrease in locomotion trajectories within the central region and a significantly shorter total distance in the ISO group compared to CON pups, indicating that isoflurane induces anxiety-like behavior. In the Morris water maze (MWM) test, rats exposed to isoflurane exhibited prolonged escape latency onto the platform. Additionally, isoflurane administration resulted in reduced time spent crossing in the MWM experiment at PND34, suggesting long-term impairment of memory function. Furthermore, we found that isoflurane triggered activation of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α; downregulated KCC2/BDNF/P-ERK expression; and increased the NKCC1/KCC2 ratio in the hippocampus of PND7 rats. Bumetadine (NKCC1 specific inhibitors) reversed cognitive damage and effective disorder induced by isoflurane in neonatal rats by inhibiting TNF-α activation, normalizing IL-6 and IL-1ß levels, restoring KCC2 expression levels as well as BDNF and ERK signaling pathways. Based on these findings, it can be speculated that BDNF, P-ERK, IL-1ß, IL-6 and TNF - α may act downstream of the NKCC1/KCC2 pathway. CONCLUSIONS: Our findings provide evidence that isoflurane administration in neonatal rats leads to persistent cognitive deficits through dysregulation of the Cation-Chloride Cotransporters NKCC1 and KCC2, BDNF, p-ERK proteins, as well as neuroinflammatory processes.


Subject(s)
Anesthetics, Inhalation , Animals, Newborn , Isoflurane , K Cl- Cotransporters , Solute Carrier Family 12, Member 2 , Symporters , Animals , Isoflurane/pharmacology , Solute Carrier Family 12, Member 2/metabolism , Symporters/metabolism , Anesthetics, Inhalation/pharmacology , Anesthetics, Inhalation/adverse effects , Rats , Mice , Rats, Sprague-Dawley , Male , Neuroinflammatory Diseases/chemically induced , Neuroinflammatory Diseases/metabolism , Female , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/metabolism
15.
Int Endod J ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38888425

ABSTRACT

AIM: (i) To characterize Enterococcus faecalis biofilm formation pathways by semi-targeted metabolomics and targeted nitrogen panel analysis of strong (Ef63) and weak (Ef 64) biofilm forming E. faecalis clinical isolates and (ii) to validate the identified metabolic markers using targeted inhibitors. METHODOLOGY: Previous proteomics profiling of E. faecalis clinical isolates with strong and weak biofilm formation revealed that differences in metabolic activity levels of small molecule, nucleotide and nitrogen compound metabolic processes and biosynthetic pathways, cofactor metabolic process, cellular amino acid and derivative metabolic process and lyase activity were associated with differences in biofilm formation. Hence, semi-targeted analysis of Ef 63, Ef 64 and ATC control strain Ef 29212 was performed by selecting metabolites that were part of both the previously identified pathways and a curated library with confirmed physical and chemical identity, followed by confirmatory targeted nitrogen panel analysis. Significantly regulated metabolites (p < .05) were selected based on fold change cut-offs of 1.2 and 0.8 for upregulation and downregulation, respectively, and subjected to pathway enrichment analysis. The identified metabolites and pathways were validated by minimum biofilm inhibitory concentration (MBIC) and colony forming unit (CFU) assays with targeted inhibitors. RESULTS: Metabolomics analysis showed upregulation of betaine, hypoxanthine, glycerophosphorylcholine, tyrosine, inosine, allantoin and citrulline in Ef 63 w.r.t Ef 64 and Ef 29212, and thesemetabolites mapped to purinemetabolism, urea cycle and aspartate metabolism pathways. MBIC and CFU assays using compounds against selected metabolites and metabolic pathways, namely glutathione against hypoxanthine and hydroxylamine against aspartate metabolism showed inhibitory effects against E. faecalis biofilm formation. CONCLUSIONS: The study demonstrated the importance of oxidative stress inducers such as hypoxanthine and aspartate metabolism pathway in E. faecalis biofilm formation. Targeted therapeutics against these metabolic markers can reduce the healthcare burden associated with E. faecalis infections.

16.
Kidney Res Clin Pract ; 43(3): 263-273, 2024 May.
Article in English | MEDLINE | ID: mdl-38863384

ABSTRACT

With an increasing aging population, the mean age of patients with end-stage kidney disease (ESKD) is globally increasing. However, the current clinical status of elderly patients undergoing hemodialysis (HD) is rarely reported in Korea. The current study analyzed the clinical features and trends of older patients undergoing HD from the Korean Renal Data System (KORDS) database. The patients were divided into three groups according to age: <65 years (the young group), n = 50,591 (35.9%); 65-74 years (the younger-old group), n = 37,525 (26.6%); and ≥75 years (the older-old group), n = 52,856 (37.5%). The proportion of older-old group undergoing HD significantly increased in incidence and decreased in prevalence from 2013 to 2022. The median levels of hemoglobin, serum creatinine, albumin, calcium, phosphorus, and intact parathyroid hormone significantly decreased in the older-old group. The proportions of arteriovenous fistula creation and left forearm placement showed decreased trends with age. Although the utilization of low surface area dialyzers increased with age, the dialysis adequacy, including urea reduction ratio and Kt/V was within acceptable range in the older-old group on HD. Over the past 20 years, the mortality rate in the older-old group has increased, with cardiovascular diseases decreasing and infectious diseases increasing. The incidence of elderly patients undergoing HD has increased over time, but the high mortality of the older-old group needs to be solved. Therefore, it is imperative to develop holistic strategies based on age and individual needs for patients with ESKD.

17.
J Agric Food Chem ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38885170

ABSTRACT

Milk fat content is a critical indicator of milk quality. Exploring the key regulatory genes involved in milk fat synthesis is essential for enhancing milk fat content. STF-62247 (STF), a thiazolamide compound, has the potential to bind with ALG5 and upregulate lipid droplets in fat synthesis. However, the effect of STF on the process of milk fat synthesis and whether it acts through ALG5 remains unknown. In this study, the impact of ALG5 on milk fat synthesis and its underlying mechanism were investigated using bovine mammary epithelial cells (BMECs) and mouse models through real-time PCR, western blotting, Oil Red O staining, and triglyceride analysis. Experimental findings revealed a positive correlation between STF and ALG5 with the ability to synthesize milk fat. Silencing ALG5 led to decreased expression of FASN, SREBP1, and PPARγ in BMECs, as well as reduced phosphorylation levels in the PI3K/AKT/mTOR signaling pathway. Moreover, the phosphorylation levels of the PI3K/AKT/mTOR signaling pathway were restored when ALG5 silencing was followed by the addition of STF. These results suggest that STF regulates fatty acid synthesis in BMECs by affecting the PI3K/AKT/mTOR signaling pathway through ALG5. ALG5 is possibly a new factor in milk fat synthesis.

18.
Zhen Ci Yan Jiu ; 49(6): 618-624, 2024 Jun 25.
Article in English, Chinese | MEDLINE | ID: mdl-38897806

ABSTRACT

OBJECTIVES: To observe the clinical efficacy of acupuncture intervention at different time for patients with sudden hearing loss. METHODS: According to the timing of acupuncture intervention, 86 patients were divided into early exposure group (n=43) and late exposure group (n=43) . The early exposure group was given acupuncture treatment within 14 days of onset, and the late exposure group was given acupuncture treatment after 14 days of onset. After propensity score matching (PSM, a statistical matching technique for observational data) processing by using SPSS26.0 software, outcomes of 30 cases in the early exposure group and 30 cases in the late exposure group were analyzed. In addition to receiving basic treatment with drugs for vascular dilatation, thrombolysis, nourishing nerve, etc., all patients of the two groups were treated with neck acupuncture ("Neck Seven Meridian Lines" acupuncture), once every other day except Sundays, for a total of 12 time. Before, after the treatment and 3 months after the treatment, the total score of the Tinnitus Handicap Inventory (THI, 0, 2 and 4 points for each of the 25 items, total scores = 100 points) scale was used to evaluate the improvement of tinnitus symptoms caused by hearing loss. The clinical therapeutic effect was evaluated according to the efficacy grading criteria in the Guidelines for Diagnosis and Treatment of Sudden Deafness (2015) and the changes of pure tone audiometry curve. Multivariate Logistic regression was used to analyze the effect of factors that might influence efficacy before propensity score matching. RESULTS: The THI scores of patients in both groups decreased strikingly after the treatment and 3 months' follow-up (P<0.05). Compared with the same time-points of the late exposure group, the total THI scores of post-treatment and 3 months' follow-up were evidently lower in the early exposure group (P<0.05). The effective rate of the early exposure group (22/30, 80.00%) was significantly higher (P<0.05) than that of the late exposure group (16/30, 53.33%). The classification of sudden deafness and the application of traditional Chinese medicine in this study were not independent factors affecting the total effective rate. CONCLUSIONS: The time point of acupuncture intervention is an important factor affecting the effect on hearing and tinnitus disability of patients with sudden deafness. The earlier acupuncture treatment is accepted, the better the therapeutic effect is.


Subject(s)
Acupuncture Therapy , Hearing Loss, Sudden , Humans , Hearing Loss, Sudden/therapy , Male , Female , Middle Aged , Adult , Treatment Outcome , Aged , Time Factors , Acupuncture Points , Young Adult , Tinnitus/therapy
19.
Ultrasound Med Biol ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38897841

ABSTRACT

PURPOSE: A novel nomogram incorporating artificial intelligence (AI) and clinical features for enhanced ultrasound prediction of benign and malignant breast masses. MATERIALS AND METHODS: This study analyzed 340 breast masses identified through ultrasound in 308 patients. The masses were divided into training (n = 260) and validation (n = 80) groups. The AI-based analysis employed the Samsung Ultrasound AI system (S-detect). Univariate and multivariate analyses were conducted to construct nomograms using logistic regression. The AI-Nomogram was based solely on AI results, while the ClinAI- Nomogram incorporated additional clinical factors. Both nomograms underwent internal validation with 1000 bootstrap resamples and external validation using the independent validation group. Performance was evaluated by analyzing the area under the receiver operating characteristic (ROC) curve (AUC) and calibration curves. RESULTS: The ClinAI-Nomogram, which incorporates patient age, AI-based mass size, and AI-based diagnosis, outperformed an existing AI-Nomogram in differentiating benign from malignant breast masses. The ClinAI-Nomogram surpassed the AI-Nomogram in predicting malignancy with significantly higher AUC scores in both training (0.873, 95% CI: 0.830-0.917 vs. 0.792, 95% CI: 0.748-0.836; p = 0.016) and validation phases (0.847, 95% CI: 0.763-0.932 vs. 0.770, 95% CI: 0.709-0.833; p < 0.001). Calibration curves further revealed excellent agreement between the ClinAI-Nomogram's predicted probabilities and actual observed risks of malignancy. CONCLUSION: The ClinAI- Nomogram, combining AI alongside clinical data, significantly enhanced the differentiation of benign and malignant breast masses in clinical AI-facilitated ultrasound examinations.

20.
Inorg Chem ; 63(23): 10786-10797, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38772008

ABSTRACT

To date, developing crystalline proton-conductive metal-organic frameworks (MOFs) with an inherent excellent proton-conducting ability and structural stability has been a critical priority in addressing the technologies required for sustainable development and energy storage. Bearing this in mind, a multifunctional organic ligand, 3,4-dimethylthiophene[2,3-b]thiophene-2,5-dicarboxylic acid (H2DTD), was employed to generate two exceptionally stable three-dimensional porous Zr/Hf MOFs, [Zr6O4(OH)4(DTD)6]·5DMF·H2O (Zr-DTD) and [Hf6O4(OH)4(DTD)6]·4DMF·H2O (Hf-DTD), using solvothermal means. The presence of Zr6 or Hf6 nodes, strong Zr/Hf-O bonds, the electrical influence of the methyl group, and the steric effect of the thiophene unit all contribute to their structural stability throughout a wide pH range as well as in water. Their proton conductivity was fully examined at various relative humidities (RHs) and temperatures. Creating intricate and rich H-bonded networks between the guest water molecules, coordination solvent molecules, thiophene-S, -COOH, and -OH units within the framework assisted proton transfer. As a result, both MOFs manifest the maximum proton conductivity of 0.67 × 10-2 and 4.85 × 10-3 S·cm-1 under 98% RH/100 °C, making them the top-performing proton-conductive Zr/Hf-MOFs. Finally, by combining structural characteristics and activation energies, potential proton conduction pathways for the two MOFs were identified.

SELECTION OF CITATIONS
SEARCH DETAIL
...