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1.
J Clin Neurosci ; 129: 110839, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39326345

RESUMO

BACKGROUND: Lumbar disc herniation (LDH) is common in aged human beings. This study is to investigate the prevalence of lumbar disc herniation (LDH) in different symptomatic populations attending outpatient clinics based on magnetic resonance imaging (MRI) studies, and to analyze the characteristics, distribution, and treatment strategies thereof. METHODS: Patients who visited our outpatient clinics between January 1, 2022, and December 31, 2022, with complaints of low back pain, either accompanied or unaccompanied by lower limb symptoms (radiating pain, numbness or muscle weakness), were included. All patients underwent comprehensive lumbar spine MRI examinations. The prevalence of LDH in different symptomatic populations, as well as the characteristics, distribution, and treatment strategies of disc herniation were analyzed. RESULTS: Among 8,161 individuals (3,411 males and 4,750 females), 4,496 were diagnosed with LDH, resulting in a prevalence of 55.1 %. Of these, 683 (15.2 %) individuals underwent surgical treatment. Among all patients, 3,529 exhibited only low back pain symptoms, 1,820 (51.6 %) were diagnosed with LDH, and 201 (11.0 %) received surgical treatment. Additionally, 2,673 patients with low back pain accompanied by lower limb symptoms were identified, with 1,608 individuals (82.1 %) diagnosed with LDH; 319 (19.8 %) underwent surgical treatment. Furthermore, 1,959 patients presented with lower limb symptoms only, 1,068 (54.5 %) were diagnosed with LDH, and 163 received surgical treatment (P < 0.001). The prevalence rate for males was 58.8 %, compared to females with 52.4 % (P < 0.01). The prevalence of LDH exhibited an initially increasing trend, later decreasing with advancing age. L4/5 and L5/S1 were the most commonly affected segments. CONCLUSION: LDH prevalence varies among patients with different symptoms, with a higher rate in those presenting with low back pain accompanied by lower limb symptoms. These symptomatic patients also exhibit a higher rate of surgical intervention.

2.
BMC Med ; 22(1): 397, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285414

RESUMO

BACKGROUND: The effects of anesthetics on liver and kidney functions after infantile living-related liver transplantation (LRLT) are unclear. This study aimed to investigate the effects of propofol-based total intravenous anesthesia (TIVA) or desflurane-based inhalation anesthesia on postoperative liver and kidney functions in infant recipients after LRLT and to evaluate hepatic ischemia-reperfusion injury (HIRI). METHODS: Seventy-six infants with congenital biliary atresia scheduled for LRLT were randomly divided into two anesthesia maintenance groups: group D with continuous inhalation of desflurane and group P with an infusion of propofol. The primary focus was to assess alterations of liver transaminase and serum creatinine (Scr) levels within the first 7 days after surgery. And the peak aminotransferase level within 72 h post-surgery was used as a surrogate marker for HIRI. RESULTS: There were no differences in preoperative hepatic and renal functions between the two groups. Upon the intensive care unit (ICU) arrival, the levels of aspartate aminotransferase (AST, P = 0.001) and alanine aminotransferase (ALT, P = 0.005) in group P were significantly lower than those in group D. These changes persisted until the fourth and sixth days after surgery. The peak AST and ALT levels within 72 h after surgery were also lower in group P than in group D (856 (552, 1221) vs. 1468 (732, 1969) U/L, P = 0.001 (95% CI: 161-777) and 517 (428, 704) vs. 730 (541, 1100) U/L, P = 0.006, (95% CI: 58-366), respectively). Patients in group P had lower levels of Scr upon the ICU arrival and on the first day after surgery, compared to group D (17.8 (15.2, 22.0) vs. 23.0 (20.8, 30.8) µmol/L, P < 0.001 (95% CI: 3.0-8.7) and 17.1 (14.9, 21.0) vs. 20.5 (16.5, 25.3) µmol/L, P = 0.02 (95% CI: 0.0-5.0) respectively). Moreover, the incidence of severe acute kidney injury was significantly lower in group P compared to that in group D (15.8% vs. 39.5%, P = 0.038). CONCLUSIONS: Propofol-based TIVA might improve liver and kidney functions after LRLT in infants and reduce the incidence of serious complications, which may be related to the reduction of HIRI. However, further biomarkers will be necessary to prove these associations.


Assuntos
Desflurano , Isoflurano , Rim , Transplante de Fígado , Fígado , Propofol , Humanos , Propofol/administração & dosagem , Propofol/efeitos adversos , Transplante de Fígado/efeitos adversos , Desflurano/administração & dosagem , Lactente , Masculino , Feminino , Isoflurano/análogos & derivados , Isoflurano/administração & dosagem , Isoflurano/efeitos adversos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/efeitos adversos , Doadores Vivos , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/efeitos adversos , Creatinina/sangue , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Testes de Função Hepática , Período Pós-Operatório , Testes de Função Renal , Atresia Biliar/cirurgia
3.
Mol Ther ; 32(10): 3580-3596, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39217416

RESUMO

Programmed death-ligand 1 (PD-L1) on tumor-derived small extracellular vesicles (sEVs) limits therapeutic effectiveness by interacting with the PD-1 receptor on host immune cells. Targeting the secretion of sEV PD-L1 has emerged as a promising strategy to enhance immunotherapy. However, the lack of small-molecule inhibitors poses a challenge for clinical translation. In this study, we developed a target and phenotype dual-driven high-throughput screening strategy that combined virtual screening with nanoflow-based experimental verification. We identified ibuprofen (IBP) as a novel inhibitor that effectively targeted sEV PD-L1 secretion. IBP disrupted the biogenesis and secretion of PD-L1+ sEVs in tumor cells by physically interacting with a critical regulator of sEV biogenesis, hepatocyte growth factor-regulated tyrosine kinase substrate. Notably, the mechanism of action of IBP is distinct from its commonly known targets, cyclooxygenases. Administration of IBP stimulated antitumor immunity and enhanced the efficacy of anti-PD-1 therapy in melanoma and oral squamous cell carcinoma mouse models. To address potential adverse effects, we further developed an IBP gel for topical application, which demonstrated remarkable therapeutic efficacy when combined with anti-PD-1 treatment. The discovery of this specific small inhibitor provides a promising avenue for establishing durable, systemic antitumor immunity.


Assuntos
Antígeno B7-H1 , Vesículas Extracelulares , Ensaios de Triagem em Larga Escala , Ibuprofeno , Imunoterapia , Animais , Camundongos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Humanos , Ensaios de Triagem em Larga Escala/métodos , Ibuprofeno/farmacologia , Imunoterapia/métodos , Linhagem Celular Tumoral , Vesículas Extracelulares/metabolismo , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/terapia , Modelos Animais de Doenças , Sinergismo Farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Rejuvenation Res ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39225159

RESUMO

Pathogenesis of vascular dementia (VD) is still unclear, there are currently no effective prevention and treatment methods. We applied Mendelian randomization (MR) using summary statistics from large-scale GWAS of metabolites and VD to reveal the causal effect of metabolites on the VD. One set of genetics instrument was used for analysis, derived from publicly available genetic summary data. Which was 32 single-nucleotide polymorphisms robustly associated with metabolites. Inverse-variance weighted, weighted median method, MR-Egger regression, and MR Pleiotropy RESidual Sum and Outlier test were used for MR analyses. Strong evidence for a positive effect of metabolites, which means N6-threonylcarbamoyladenosine (t6A) on VD was found in inverse-variance weighted (odds ratios [OR]: 0.667, 95% confidence interval [CI]: 0.548-0.812, p < 0.001), MR-Egger (OR: 0.647, 95% CI: 0.458-0.913, p = 0.019), and weighted median (OR: 0.650, 95% CI: 0.466-0.908, p = 0.012). The MR analysis indicated that metabolites (t6A) may be causally associated with a positive effect on VD.

5.
Hum Immunol ; 85(5): 110856, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39018711

RESUMO

INTRODUCTION: Previous studies have shown that inflammatory bowel disease (IBD) is associated with osteoporosis (OP) and bone mineral density (BMD), but the underlying genetic mechanisms are unclear. Our study wanted to explore the genetic and causal relationship between IBD and OP. MATERIALS AND METHODS: Based on large-scale genome-wide association summary statistics and individual-level datasets (i.e., the UK Biobank), this study performed linkage disequilibrium score regression (LDSC), pleiotropic analysis under the composite null hypothesis (PLACO), and Mendelian randomization (MR) analyses to explore the genetic association, the pleiotropic genes and the causal relationship between IBD and BMD. RESULTS: LDSC revealed significant genetic correlations between IBD and BMD (e.g., forearm BMD (rg = -0.3479, P = 0.019) and femoral neck BMD (rg = -0.1335, P = 0.0307). PLACO identified 14 overlapping pleiotropic loci, 1 shared risk gene (CDYL), and multiple shared pathways, revealing possible mechanisms for IBD and OP. MR analysis demonstrated a causal association between IBD and BMD. CONCLUSIONS: Our study indicates that IBD may increase the risk of OP and reveals a complex genetic mechanism linking IBD and the risk of osteoporosis, which has important implications for diagnosing and treating IBD and OP.


Assuntos
Densidade Óssea , Pleiotropia Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Doenças Inflamatórias Intestinais , Desequilíbrio de Ligação , Análise da Randomização Mendeliana , Osteoporose , Polimorfismo de Nucleotídeo Único , Humanos , Osteoporose/genética , Osteoporose/etiologia , Doenças Inflamatórias Intestinais/genética , Densidade Óssea/genética , Feminino , Masculino
6.
Thorac Cancer ; 15(24): 1805-1814, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39045786

RESUMO

BACKGROUND: Organophosphate flame retardants (OPFRs) are extensively distributed in our environment, prompting concerns about potential health hazards, including lung injuries resulting from OPFR exposure. METHODS: The present study recruited 125 lung cancer patients, assessing their exposure to 10 OPFR compounds through urine samples. The final analysis comprised 108 participants after excluding those lacking epidermal growth factor receptor (EGFR) status and those with chronic kidney disease. Demographic and clinical characteristics, as well as urinary OPFR concentrations, were compared based on OPFR detection. Spearman correlation was conducted to explore the relationship between OPFR compounds, while logistic regression was used to identify OPFR compounds associated with EGFR mutation. RESULTS: The study revealed widespread OPFR exposure among lung cancer patients, with an overall detection frequency of 99.07%. Tris(2-butoxyethyl) phosphate (TBEP) exhibited a strong correlation to its metabolite bis(2-butoxyethyl) phosphate (r = 0.88, p < 0.01). Patients with TBEP in their urine had higher percentage of wild-type EGFR and the detection of TBEP was associated with a reduced likelihood of mutant EGFR expression. CONCLUSIONS: OPFR exposure was prevalent in lung cancer patients, with TBEP detection identified as a factor with lower EGFR mutation expression. This study contributes to the understanding of OPFR exposure in lung cancer patients and underscores the significance of TBEP in evaluating EGFR mutation in this population.


Assuntos
Receptores ErbB , Retardadores de Chama , Neoplasias Pulmonares , Organofosfatos , Humanos , Masculino , Feminino , Neoplasias Pulmonares/genética , Receptores ErbB/genética , Pessoa de Meia-Idade , Idoso , Exposição Ambiental/efeitos adversos , Mutação , Adulto
8.
Clin Nucl Med ; 49(9): 895-896, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38934476

RESUMO

ABSTRACT: A 50-year-old woman was admitted due to a liver mass discovered by ultrasound in routine physical examination. MRI demonstrated a large hepatocellular carcinoma. It also discovered an abdominal mass simultaneously. 18 F-FDG PET/CT was performed for staging. PET/CT showed mixed and mild metabolism of the hepatic lesion and giant abdominopelvic mass, respectively. Hepatocellular carcinoma combined with a benign mass in abdominopelvic cavity from uterine was considered and finally proved pathologically. We present a rare case of woman with large liver cancer accompanied by giant uterine fibroid where 18 F-FDG PET/CT helped in making the right diagnosis.


Assuntos
Carcinoma Hepatocelular , Fluordesoxiglucose F18 , Leiomioma , Neoplasias Hepáticas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/complicações , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/complicações , Leiomioma/diagnóstico por imagem , Leiomioma/complicações , Tomografia Computadorizada por Raios X , Imagem Multimodal , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/complicações
9.
Front Endocrinol (Lausanne) ; 15: 1325320, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38836225

RESUMO

Background: Creatinine-cystatin C ratio (CCR) has been demonstrated as an objective marker of sarcopenia in clinical conditions but has not been evaluated as an osteoporosis marker in individuals with normal renal function. Methods: We selected 271,831 participants with normal renal function from UK Biobank cohort. Multivariable linear/logistic regression and Cox proportional hazards model were used to investigate the phenotypic relationship between CCR and osteoporosis in total subjects and gender-stratified subjects. Based on the genome-wide association study (GWAS) data, linkage disequilibrium regression (LDSC) and Mendelian randomization (MR) analysis were performed to reveal the shared genetic correlations and infer the causal effects, respectively. Results: Amongst total subjects and gender-stratified subjects, serum CCR was positively associated with eBMD after adjusting for potential risk factors (all P<0.05). The multivariable logistic regression model showed that the decrease in CCR was associated with a higher risk of osteoporosis/fracture in all models (all P<0.05). In the multivariable Cox regression analysis with adjustment for potential confounders, reduced CCR is associated with the incidence of osteoporosis and fracture in both total subjects and gender-stratified subjects (all P<0.05). A significant non-linear dose-response was observed between CCR and osteoporosis/fracture risk (P non-linearity < 0.05). LDSC found no significant shared genetic effects by them, but PLACO identified 42 pleiotropic SNPs shared by CCR and fracture (P<5×10-8). MR analyses indicated the causal effect from CCR to osteoporosis/fracture. Conclusions: Reduced CCR predicted increased risks of osteoporosis/fracture, and significant causal effects support their associations. These findings indicated that the muscle-origin serum CCR was a potential biomarker to assess the risks of osteoporosis and fracture.


Assuntos
Biomarcadores , Creatinina , Cistatina C , Análise da Randomização Mendeliana , Osteoporose , Humanos , Feminino , Masculino , Osteoporose/genética , Osteoporose/sangue , Osteoporose/epidemiologia , Pessoa de Meia-Idade , Biomarcadores/sangue , Creatinina/sangue , Cistatina C/sangue , Cistatina C/genética , Idoso , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Adulto , Densidade Óssea/genética , Fatores de Risco
12.
Macromol Rapid Commun ; 45(15): e2400163, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38690806

RESUMO

Synthesis of monomer-recyclable polyesters solely from CO2 and bulk olefins holds great potential in significantly reducing CO2 emissions and addressing the issue of plastic pollution. Due to the kinetic disadvantage of direct copolymerization of CO2 and bulk olefins compared to homopolymerization of bulk olefins, considerable research attention has been devoted to synthesis of polyester via the ring-opening polymerization (ROP) of a six-membered disubstituted lactone intermediate, 1,2-ethylidene-6-vinyl-tetrahydro-2H-pyran-2-one (𝜹-L), obtained from telomerization of CO2 and 1,3-butadiene. However, the conjugate olefin on the six-membered ring of 𝜹-L leads to serious Michael addition side reactions. Thus, the selective ROP of 𝜹-L, which can precisely control the repeating unit for the production of polyesters potentially amenable to efficient monomer recycling, remains an unresolved challenge. Herein, the first example of selective ROP of 𝜹-L is reported using a combination of organobase and N,N'-Bis[3,5-bis(trifluoromethyl)phenyl]urea as the catalytic system. Systematic modifications of the substituent of the urea show that the presence of electron-deficient 3,5-bis(trifluoromethyl)-phenyl groups is the key to the extraordinary selectivity of ring opening over Michael addition. Efficient monomer recovery of oligo(𝜹-L) is also achieved under mild catalytic conditions.


Assuntos
Butadienos , Dióxido de Carbono , Poliésteres , Polimerização , Butadienos/química , Poliésteres/química , Poliésteres/síntese química , Dióxido de Carbono/química , Estrutura Molecular , Catálise
13.
J Agric Food Chem ; 72(20): 11321-11330, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38714361

RESUMO

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a crucial target enzyme in albino herbicides. The inhibition of HPPD activity interferes with the synthesis of carotenoids, blocking photosynthesis and resulting in bleaching and necrosis. To develop herbicides with excellent activity, a series of 3-hydroxy-2-(6-substituted phenoxynicotinoyl)-2-cyclohexen-1-one derivatives were designed via active substructure combination. The title compounds were characterized via infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopies, and high-resolution mass spectrometry. The structure of compound III-17 was confirmed via single-crystal X-ray diffraction. Preliminary tests demonstrated that some compounds had good herbicidal activity. Crop safety tests revealed that compound III-29 was safer than the commercial herbicide mesotrione in wheat and peanuts. Moreover, the compound exhibited the highest inhibitory activity against Arabidopsis thaliana HPPD (AtHPPD), with a half-maximal inhibitory concentration of 0.19 µM, demonstrating superior activity compared with mesotrione (0.28 µM) in vitro. A three-dimensional quantitative structure-activity relationship study revealed that the introduction of smaller groups to the 5-position of cyclohexanedione and negative charges to the 3-position of the benzene ring enhanced the herbicidal activity. A molecular structure comparison demonstrated that compound III-29 was beneficial to plant absorption and conduction. Molecular docking and molecular dynamics simulations further verified the stability of the complex formed by compound III-29 and AtHPPD. Thus, this study may provide insights into the development of green and efficient herbicides.


Assuntos
4-Hidroxifenilpiruvato Dioxigenase , Arabidopsis , Desenho de Fármacos , Inibidores Enzimáticos , Herbicidas , 4-Hidroxifenilpiruvato Dioxigenase/antagonistas & inibidores , Arabidopsis/efeitos dos fármacos , Arabidopsis/enzimologia , Proteínas de Arabidopsis/antagonistas & inibidores , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Cicloexanonas/química , Cicloexanonas/farmacologia , Cicloexanonas/síntese química , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Herbicidas/síntese química , Herbicidas/farmacologia , Cetonas/síntese química , Cetonas/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Triticum/efeitos dos fármacos
14.
World J Psychiatry ; 14(5): 715-725, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38808090

RESUMO

BACKGROUND: Psychological distress, especially depression, associated with perianal fistulizing Crohn's disease (PFCD) is widespread and refractory. However, there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD. AIM: To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD. METHODS: The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff. Depressive symptoms, life quality, and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9, Inflammatory Bowel Disease Patient Quality of Life Questionnaire (IBDQ), and Inflammatory Bowel Disease (IBD) Fatigue Patient Self-assessment Scale. The basic demographic information, overall disease features, perianal clinical information, and laboratory inflammation indicators were also gathered. Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD. RESULTS: A total of 123 patients with PFCD were involved, and 56.91% were suffering from depression. According to multivariate logistic regression analysis, Perianal Disease Activity Index (PDAI) score [odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.50 to 0.95], IBDQ score (OR = 0.93, 95%CI: 0.88 to 0.97), modified Van Assche index (OR = 1.24, 95%CI: 1.01 to 1.53), and IBD Fatigue score (OR = 1.72, 95%CI: 1.23 to 2.42) were independent risk factors of depression-related prevalence among patients with PFCD (P < 0.05). Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index (ß value = 0.166, 95%CI: 0.02 to 0.31) and decreasing IBDQ score (ß value = -0.116, 95%CI: -0.14 to -0.09) were independently associated with the severity of depression (P < 0.05). CONCLUSION: Depressive symptoms in PFCD patients have significantly high prevalence. PDAI score, modified Van Assche index, quality of life, and fatigue severity were the main independent risk factors.

15.
Front Pharmacol ; 15: 1360972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650625

RESUMO

Ethnopharmacological relevance: As a representative classical prescription, Sijunzi decoction has powerful therapeutic effects on spleen-stomach qi insufficiency. Ulcerative colitis (UC) is a chronic, diffuse, and non-specifically inflammatory disorder, the etiology of which still remains unclear. In the traditional Chinese medicine (TCM) perspective, splenic asthenia is the primary cause of UC. Based on this, Sijunzi decoction has been extensively used in TCM clinical practice to alleviate UC in recent years. However, the pharmacological mechanism of Sijunzi decoction in modern medicine is still not completely clear, which limits its clinical application. Aim of the study: The purpose of this study was to investigate the Sijunzi decoction's curative effect on acute UC mice and probe into its potential pharmacological mechanism. Materials and methods: The UC mouse model was set up by freely ingesting a 3% dextran sulfate sodium (DSS) solution. The relieving role of Sijunzi decoction on UC in mice was analyzed by evaluating the changes in clinical parameters, colon morphology, histopathology, inflammatory factor content, intestinal epithelial barrier protein expression level, and gut microbiota balance state. Finally, multivariate statistical analysis was conducted to elucidate the relationship between inflammatory factors, intestinal epithelial barrier proteins, and gut microbiota. Results: First, the research findings revealed that Sijunzi decoction could visibly ease the clinical manifestation of UC, lower the DAI score, and attenuate colonic damage. Moreover, Sijunzi decoction could also significantly inhibit IL-6, IL-1ß, and TNF-α while increasing occludin and ZO-1 expression levels. Subsequently, further studies showed that Sijunzi decoction could remodel gut microbiota homeostasis. Sijunzi decoction was beneficial in regulating the levels of Alistipes, Akkermansia, Lachnospiraceae_NK4A136_group, and other bacteria. Finally, multivariate statistical analysis demonstrated that key gut microbes were closely associated with inflammatory factors and intestinal epithelial barrier proteins. Conclusion: Sijunzi decoction can significantly prevent and treat UC. Its mechanism is strongly associated with the improvement of inflammation and intestinal epithelial barrier damage by regulating the gut microbiota.

16.
Anal Chem ; 96(16): 6186-6194, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38594223

RESUMO

Solvatochromes have gained great attention because of their unique roles in monitoring biomolecular location, interaction, and dynamics. Particularly, solvatochromes presenting both red-shifting excitation and dual-band switchable emission are in great demand yet significantly difficult to come true. In this article, we disclose an aromatic alcohol-based pH-sensitive chromophore NIR-HBT that not only presents red-shifting excitation and solvent-dependent dual-band emission but also shows high photostability and excellent brightness. To the best of our knowledge, this is the first solvatochrome to simultaneously display these optical properties. Especially, in contrast to the reported dual-band solvatochromes whose solvatochromism is achieved by affecting their excited state behaviors, the solvatochromism of NIR-HBT is realized by modulating its ground state proton dissociation, which is a new solvatochromic mechanism that has not been reported. Furthermore, based on the dual-band solvatochromism of NIR-HBT and its intrinsic binding ability to GQs, near-infrared ratiometric detection of GQs is achieved. These results indicate that NIR-HBT is an attractive solvatochrome that can be used to develop near-infrared ratiometric biosensors for biological research. More broadly, the discovered solvatochromic mechanism can also open new horizons for exploring the solvatochrome.

17.
J Am Chem Soc ; 146(18): 12320-12323, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38597430

RESUMO

Recently, metal-mediated electrochemical conversion of nitrogen and hydrogen to ammonia (M-eNRRs) has been attracting intense research attention as a potential route for ammonia synthesis under ambient conditions. However, which metals should be used to mediate M-eNRRs remains unanswered. This work provides an extensive comparison of the energy consumption in the classical Haber Bosch (H-B) process and the M-eNRRs. The results indicate that when employing lithium and calcium, metals popularly used to mediate the M-eNRRs, the energy consumption is more than 10 times greater than that of the H-B process even assuming a 100% Faradaic efficiency and zero overpotentials. Only electrosynthesis with a cell voltage not exceeding 0.38 V might have the potential to rival the H-B process from an energetic perspective. A further analysis of other metals in the periodic table reveals that only some heavy metals, including In, Tl, Co, Ni, Ga, Mo, Sn, Pb, Fe, W, Ge, Re, Bi, Cu, Po, Tc, Ru, Rh, Ag, Hg, Pd, Ir, Pt, and Au, can potentially consume less energy than that of the H-B process purely from a thermodynamic standpoint, but whether they can activate N2 under ambient conditions is yet to be explored. This work shows the importance of performing thermodynamic analysis for the development of an innovative strategy to synthesize ammonia with the ultimate goal of replacing the H-B process on a large scale.

18.
Int J Rheum Dis ; 27(4): e15156, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38665050

RESUMO

OBJECTS: Previous studies have suggested a potential correlation between rheumatoid arthritis (RA) and biological aging, but the intricate connections and mechanisms remain elusive. METHODS: In our study, we focused on two specific measures of biological age (PhenoAge and BioAge), which are derived from clinical biomarkers. The residuals of these measures, when compared to chronological age, are defined as biological age accelerations (BAAs). Utilizing the extensive UK Biobank dataset along with various genetic datasets, we conducted a thorough assessment of the relationship between BAAs and RA at both the individual and aggregate levels. RESULTS: Our observational studies revealed positive correlations between the two BAAs and the risk of developing both RA and seropositive RA. Furthermore, the genetic risk score (GRS) for PhenoAgeAccel was associated with an increased risk of RA and seropositive RA. Linkage disequilibrium score regression (LDSC) analysis further supported these findings, revealing a positive genetic correlation between PhenoAgeAccel and RA. PLACO analysis identified 38 lead pleiotropic single nucleotide polymorphisms linked to 301 genes, providing valuable insights into the potential mechanisms connecting PhenoAgeAccel and RA. CONCLUSION: In summary, our study has successfully revealed a positive correlation between accelerated biological aging, as measured by BAAs, and the susceptibility to RA.


Assuntos
Envelhecimento , Artrite Reumatoide , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Humanos , Artrite Reumatoide/genética , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/diagnóstico , Fatores de Risco , Pessoa de Meia-Idade , Envelhecimento/genética , Feminino , Medição de Risco , Masculino , Fatores Etários , Fenótipo , Idoso , Desequilíbrio de Ligação , Adulto
19.
J Endocr Soc ; 8(5): bvae035, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38505562

RESUMO

Objective: This study aimed to determine if a combination of 2 abnormal lipid profiles revealed a stronger association with low bone mass than a single blood lipid abnormality alone. Methods: This study enrolled 1373 participants who had received a dual-energy x-ray absorptiometry scan from January 2016 to December 2016 in a medical center in southern Taiwan. Logistic regression was used to examine association between lipid profiles and osteopenia or osteoporosis after adjusting for covariates. Results: Compared to people with total cholesterol (TC) < 200 mg/dL, those with TC ≥ 240 mg/dL tended to have osteopenia or osteoporosis (OR 2.61; 95% CI, 1.44-4.71). Compared to people with low-density lipoprotein cholesterol (LDL-C) < 130 mg/dL, those with LDL-C ≥ 160 mg/dL tended to develop osteopenia or osteoporosis (OR 2.13; 95% CI, 1.21-3.74). The association of increased triglyceride and decreased bone mass was similar, although not statistically significant. Those with the combination of TG ≥ 200 mg/dL and TC ≥ 240 mg/dL had a stronger tendency to have osteopenia or osteoporosis (OR 3.51; 95% CI, 1.11-11.13) than people with only one blood lipid abnormality. Similarly, people with TG ≥ 200 mg/dL and LDL-C ≥ 160 mg/dL had a stronger tendency to have osteopenia or osteoporosis (OR 9.31; 95% CI, 1.15-75.42) than people with only one blood lipid abnormality, after adjustment for the same covariates. Conclusion: Blood levels of TC, LDL-C, and TG were associated with osteopenia or osteoporosis. Results indicate that individuals aged older than 50 years with abnormal lipid profiles should be urged to participate in a bone density survey to exclude osteopenia or osteoporosis.

20.
Chem Rev ; 124(6): 3590-3607, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38478849

RESUMO

Carbon dioxide (CO2) has long been recognized as an ideal C1 feedstock comonomer for producing sustainable materials because it is renewable, abundant, and cost-effective. However, activating CO2 presents a significant challenge because it is highly oxidized and stable. A CO2/butadiene-derived δ-valerolactone (EVP), generated via palladium-catalyzed telomerization between CO2 and butadiene, has emerged as an attractive intermediate for producing sustainable copolymers from CO2 and butadiene. Owing to the presence of two active carbon-carbon double bonds and a lactone unit, EVP serves as a versatile intermediate for creating sustainable copolymers with a CO2 content of up to 29 wt % (33 mol %). In this Review, advances in the synthesis of copolymers from CO2 and butadiene with divergent structures through various polymerization protocols have been summarized. Achievements made in homo- and copolymerization of EVP or its derivatives are comprehensively reviewed, while the postmodification of the obtained copolymers to access new polymers are also discussed. Meanwhile, potential applications of the obtained copolymers are also discussed. The literature references were sorted into sections based on polymerization strategies and mechanisms, facilitating readers in gaining a comprehensive view of the present chemistry landscape and inspiring innovative approaches to synthesizing novel CO2-derived copolymers.

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